We evaluated the immunogenicity persistence of different immunization regimens of freeze-dried human rabies vaccine (Vero cells) in the 10–60 years age group of the Chinese population. Based on phase III clinical trials of Vero cells, participants who completed the full course of immunization were continuously enrolled in four-dose trial, five-dose, and five-dose control groups. Venous blood samples were collected 12 months after completion of the full immunization for rabies virus-neutralizing antibody (RVNA) testing, and the antibody-positive rate and geometric mean concentration (GMC) were calculated. Analysis of variance was used to compare three groups. The four-dose trial, five-dose trial, and five-dose control groups included 200, 186, and 214 participants, respectively. Twelve months after full immunization, the overall RVNA-positive rates were 97.00%, 93.55%, and 94.86% in the four-dose trial, five-dose control, and five-dose trial groups, respectively. The post-immunization RVNA GMCs values were 2.50, 2.05, and 2.04 IU/mL, respectively, with no statistically significant differences between them. Twelve months after full immunization, the overall RVNA-positive rate remained high, demonstrating satisfactory immunogenicity persistence for both immunization regimens.

Data from the WHO and UNICEF Estimates of National Immunization Coverage (WUENIC) 2022 revision were analyzed to assess the status of routine immunization in the WHO African Region, disrupted by the COVID-19 pandemic. In 2022, the coverage with the first and third dose of diphtheria-tetanus-pertussis containing vaccine (DTP1 and DTP3 respectively) and with the first dose of measles-containing vaccine (MCV1), in the region, was estimated at 80%, 72% and 69%, respectively (all below the 2019 level). Only 13 of the 47 countries (28%) achieved the global target coverage of 90% or above with DTP3 in 2022. From 2019 to 2022, 28.7 million zero-dose were recorded (19.0% of target population). Ten countries of the region accounted for 80.3% of all zero-dose children including the four most populous countries (Nigeria, Ethiopia, Democratic Republic of the Congo, United Republic of Tanzania). Reported administrative coverage greater than WUENIC was found in 19 countries, highlighting routine immunization data quality issues. The WHO African region has not yet recovered from COVID-19 disruptions to routine immunization. It is critical for Governments to ensure that processes are in place to prioritize investments for restoring immunization services, catching-up on vaccination of zero-dose and un-der-vaccinated children and improving data quality.

Computed tomography (CT) is a widely employed imaging modality with diverse clinical applications in pediatric and adult populations, offering numerous advantages. Despite several alternatives to imaging modalities with ionising radiation, CT scans have demonstrated persistent global popularity, contributing to a substantial amount of effective radiation doses for patients. This exposure results in hazards, including stochastic effects that amplify the radiation-induced cancer risk proportionally to the radiation dose received. CT-related radiation comprises a substantial portion of cumulative effective doses within diagnostic radiology, specifically impacting younger patient cohorts undergoing repeated investigations for chronic diseases over time. Scientific literature over recent decades has explored various methods to mitigate radiation doses during medical imaging. One notable strategy involves implementing low-dose and ultralow-dose CT protocols, maintaining diagnostic efficacy in acute and non-acute medical and surgical conditions. Utilising innovative image reconstruction algorithms, such as iterative reconstruction and emerging deep-learning algorithms based on artificial intelligence, plays a pivotal role in achieving an approximately 80% reduction in patient radiation compared to standard doses. This review article discusses the significance of low-dose protocols across a spectrum of acute and chronic medical conditions affecting different body systems.

Background: Computed tomography examinations have produced high radiation doses to patients, especially the CT brain. This study aimed to optimize the radiation dose and image quality in adult CT brain protocol. Materials and Methods: Images were acquired by Catphan 700 phantom. Radiation doses were recorded as CTDIvol and dose length product (DLP). CT brain protocols were optimized by varying parameters such as kVp, mAs, signal-to-noise ratio (SNR) level, and Clearview iterative reconstruction (IR). Image quality were also evaluataion by The AutoQA Plus software. Results: CT Number accuracy and linearity had a robust positive correlation with the linear attenuation coefficient (µ) and showed more inaccurate CT numbers when using 80 kVp. MTF showed a higher value in 100 and 120 kVp protocols, while high contrast spatial resolution showed a higher value in 80 and 100 kVp protocols. Low contrast detectability and CNR tended to increase when using high mAs, SNR and Clearview IR protocol. Noise decreased when using a high radiation dose and a high percentage of Clearview IR. CTDIvol and DLP were increased with increasing kVp, mAs, and SNR levels, while the increasing percentage of Clearview did not affect the radiation dose. Conclusion: Optimized protocols, including radiation dose and image quality, should be evaluated to preserve diagnostic capability. The recommended parameter settings include kVp set between 100-120 kVp, mAs ranging from 200-300 mAs, SNR level within the range of 0.7-1.0, and an iterative reconstruction value of 30% Clearview to 60% or higher.

Polarimetry is used to determine the Stokes parameters of a laser beam. Once all four S0,1,2,3 parameters are determined, the state of polarisation is established. Upon reflection of a laser beam with the defined S polarisation state, the directly measured S parameters can be used to determine the optical properties of the surface, which modified the S-state upon reflection. Here, we demonstrate polarimetry for the determination of surface anisotropies related to birefringence and dichroism from different materials, which have a common feature of linear patterns of different alignments and scales. It is shown that polarimetry in the back-reflected light is complementary to ellipsometry and four-polarisation camera imaging.

This paper proposes a novel biologically inspired design for an insect-scale flapping robot. The proposed scheme employs two motors to drive four wings, mimicking the flapping motion of nat-ural four-winged insects. The vehicle incorporates two pairs of flapping wings to generate lift force, with a transmission mechanism featuring flexure hinges instead of pivot joints, resulting in reduced weight and volume. The flexure hinges also exhibit nonlinear stiffness to facilitate smooth wing motion. The vehicle is designed to be symmetrical in structure, with the wings of each section generating greater lift through the clap-and-fling mechanism. The final product weighs 6.2g, pos-sesses a wingspan of 17cm, a one-sided flapping wing angle of 103 degrees, and generates lift that exceeds its weight, attesting to its successful design.

While there is a coordinated effort around reaching zero dose children and closing existing equity gaps in immunization delivery, it’s important that there is agreement and clarity around how ‘zero dose status’ is defined and what is gained and lost by using different indicators for zero dose status. There are two popular approaches used in research, program design, and advocacy to define zero dose status: one uses a single vaccine to serve as a proxy for zero dose status, while another uses a subset of vaccines to identify children who have missed all routine vaccines. We provide a global analysis utilizing the most recent publicly available DHS and MICS data to compare the number, proportion, and profile of children 12 to 23 months who are ‘penta-zero dose’ (have not received the pentavalent vaccine), ‘truly’ zero dose (have not received the BCG, polio, pentavalent, and measles vaccines), and ‘misclassified’ zero dose children (those who are penta-zero dose but have received at least one other vaccine). Our analysis includes 194,829 observations from 82 low- and middle-income countries. Globally, 14.2% of children are penta-zero dose and 7.5% are truly zero dose, suggesting that 46.5% of penta-zero dose children have had at least one contact with the immunization system. While there are similarities in the profile of children that are penta-zero dose and truly zero dose, there are key differences between the proportion of key characteristics among truly zero dose and misclassified zero dose children, including access to maternal and child health services. By understanding the extent of connection zero dose children may have with the health and immunization system and contrasting it with how much the use of a more feasible definition of zero dose may underestimate the level of vulnerability in the zero dose population, we provide insights that can help immunization programs design strategies that better target the most disadvantaged populations. If the vulnerability profiles of the truly zero dose children are qualitatively different from that of the penta zero dose children, then failing to distinguish the truly zero dose populations, and how to optimally reach them, may lead to the development of misguided or inefficient strategies for vaccinating the most disadvantaged population of children.

The physiological process of iodine uptake in the thyroid is used for 131I treatment of thyroid diseases. Children are more sensitive to radiation compared to adults and may react differently to 131I exposure. The aims of this study were to evaluate the effects on thyroid protein expression in young and adult rats one year after 131I injection, and identify potential biomarkers related to 131I exposure, absorbed dose, and age. Twelve Sprague Dawley Rats (young and adults) were i.v. injected with 50 kBq or 500 kBq 131I and were killed twelve months later. Twelve untreated rats were used as age-matched controls. Quantitative proteomics, statistical analysis and evaluation of biological effects was performed. The effects of irradiation were most prominent in young rats. Protein biomarker candidates were proposed related to age, absorbed dose, thyroid function and cancer and a panel was proposed for 131I exposure. In conclusion, the proteome of rat thyroid was differentially regulated twelve months after low-intermediate dose exposure to 131I in both young and adult rats. Several biomarker candidates are proposed for 131I exposure, age, and many of them are known to be related to thyroid function or thyroid cancer. Further research on human samples are needed for validation.

Zero-dose children, or children who have not received any routine vaccination, are a priority population for global health policy makers as these children are at high risk of mortality from vaccine-preventable illnesses. We conducted a narrative review to identify potential interventions, both within and outside of the health sector, to reach zero-dose children. We reviewed peer-reviewed and grey literature and identified 59 relevant resources. Additionally, we interviewed six key informants to enhance synthesis of our findings. Data were organized into three priority settings: (1) urban slums, (2) remote or rural communities, and (3) conflict settings. We found that zero-dose children in the three-priority settings face differing barriers to vaccina-tion and, therefore, require context-specific interventions, such as leveraging slum health commit-tees for urban slums or integrating with existing humanitarian response services for conflict set-tings. Three predominant themes emerged for grouping the various interventions: (1) community engagement, (2) health systems strengthening and integration, and (3) technological innovations. The barriers to reaching zero-dose children are multifaceted and nuanced to each setting, there-fore, no one intervention is enough. Technological interventions especially must be coupled with community engagement and health systems strengthening efforts. Evaluations of the suggested interventions are needed to guide scale up, as the evidence-base around these interventions is rel-atively small.

We study the nonlinear absorptive and dispersive optical properties of molecular systems immersed in a thermal reservoir interacting with a Four-wave Mixing (FWM) signal. Residual spin-orbit Hamiltonians are considered in order to take into account the internal structure of the molecule. As system parameters in the dissipation processes, transverse and longitudinal relaxation times are considered for stochastic solute-solvent interaction processes. The intramolecular coupling effects on the optical responses are studied using a molecule model consisting of two coupled harmonic curves of electronic energies with displaced minima in nuclear energies and positions. In this study, it was considered the complete frequency space is considered through the pump-probe detuning, not restricting the derivations to only maximums of population oscillations. This approach opens the possibility of studying the behavior of optical responses, which is very useful in experimental design. Our results indicate the sensitivity of the optical responses to parameters of the molecular structure as well as to those derived from the photonic process of FWM signal generation.

This paper investigates the periodic and quasi-periodic orbits in the symmetric collinear four-body problem through a variational approach. In Section 3, we analyze the conditions under which homographic solutions minimize the action functional. We demonstrate that these solutions for four equal masses arranged in a linear configuration are indeed the minimizers of the action functional and compute the minimum value of the action functional for these solutions. Additionally, we employ numerical experiments using Poincaré sections to explore the existence and stability of periodic and quasi-periodic solutions within this dynamical system. Our results provide a deeper understanding of the variational principles in celestial mechanics and reveal complex dynamical behaviors that are crucial for further studies in multi-body problems. The findings have significant implications for theoretical research and practical applications in astrodynamics and space mission planning.

This paper has designed a four-channel wide dynamic microwave rectifier circuit for the shortcomings of uneven output voltage of each branch of the multi-channel rectification technology. A voltage-doubling rectifier circuit with identical structure was used in each branch. The four rectifier branches shared the same load at the output terminal, allowing the rectifier circuit to have an RF-DC conversion efficiency greater than 50% over the input power range from 12mW to 274mW, widened by 274% compared to a single channel. Not only the advantages of multi-channel technology with wide dynamics were retained, but also the output voltage was highly consistent and could be directly output in parallel without complex power electronics conversion.

This brief report presents a comparative analysis to examine differences in the mean dose of nitrate supplementation between studies with positive and negative results on exercise performance. Protocols of at least six days that had positive results used lower nitrate doses (~7.7 mmol), whereas those with negative results used higher doses (~10.2 mmol), showing a statistically significant difference (p < 0.05). These findings suggest long-term supplementation with higher doses (~10.2 mmol) may not improve exercise performance. Further research is essential to understand the underlying mechanisms.

This retrospective study aimed to evaluate the impact of radiation dose on the outcomes of stereotactic radiosurgery (SRS) for benign meningiomas and determine an optimal dosing strategy for balancing tumor control and treatment-related toxicity. Clinical data of 147 patients with 164 lesions treated between 2014 and 2022 were reviewed. Primary outcomes included progression-free survival (PFS), local control rate (LCR), and radiation-induced toxicity, with secondary outcomes focusing on LCR and radiation-induced peritumoral edema (PTE) in two dose groups (≥14 Gy and &lt;14 Gy). Results revealed a median follow-up duration of 47 months, with 1-year, 2-year, and 5-year PFS rates of 99.3%, 96.7%, and 93.8% respectively, and an overall LCR of 95.1%. Radiation-induced toxicity was observed in 24.5% of patients, primarily presenting mild symptoms. Notably, no significant difference in LCR was found between the two dose groups (P = 0.628), while Group 2 (&lt;14 Gy) exhibited significantly lower PTE (P = 0.039). The study concludes that SRS with a radiation dose &lt;14 Gy demonstrates comparable tumor control with reduced toxicity, advocating for consideration of such dosing to achieve a balance between therapeutic efficacy and safety.

This study investigated the influence of nutrient inputs and their timing on saffron yield and quality. The study was conducted from 2016 to 2020 and involved the application of eight different fertilization treatments at various stages of saffron growth. These treatments included single doses in Autumn (A), Winter (W), and Spring (S); double doses in Winter-Spring (AW), Autumn-Spring (AS), and Winter-Spring (WS); and a triple dose in Autumn-Winter-Spring (AWS). A control group (C) received no fertilizer. A compound fertilizer with a 15-15-15 composition was applied across all treatments, with nitrogen (N) rates of 67.5 kg/ha for single doses (A, W, S), 135 kg/ha for double doses (AWF, ASF, WSF), and 202.5 kg/ha for the triple dose (AWSF). Similar rates were applied for phosphorus (P) and potassium (K). The findings demonstrated that fertilization generally enhanced saffron attributes. The triple dose treatment yielded the most effective results. The timing of fertilization also played a crucial role, as split applications during different growth stages led to higher production especially winter fertilization. However, spring fertilization had limited impact due to decreased plant activity and reduced nutrient absorption during that period. Although the yield increased, the qualitative aspects of saffron, including color (crocin), taste (picrocrocin), and aroma (safranal), were not significantly influenced by the fertilization treatments. Nevertheless, these attributes remained within the natural limits defined by ISO-3632, indicating that fertilization practices did not compromise saffron quality. Our study highlights the significance of nutrient inputs and their timing in optimizing saffron yield. It provides valuable insights for developing efficient fertilization programs to enhance saffron production while preserving its quality characteristics.

Fexuprazan is a potassium-competitive acid blocker approved for treating gastric acid-related diseases. Herein, we evaluated the pharmacokinetics (PKs) of single-dose and multiple-dose oral administration of fexuprazan 10 mg tablets in healthy subjects (Part 1) and investigated the bioequivalence between fexuprazan 10 mg and 40 mg tablets (Part 2). Part 1 comprised a single- and multiple-dose, 1-sequence, and 2-period design, and Part 2 comprised a single-dose, 2×2 crossover design. Eight and 23 subjects completed Parts 1 and 2, respectively. In Part 1, multiple doses accumulated twice as much as single doses. In Part 2, the geometric mean ratios [90% confidence intervals] for maximum plasma concentration (Cmax) and area under the concentration–time curve from zero to the time of the last quantifiable concentration (AUClast) of four fexuprazan 10 mg tablets to those of one fexuprazan 40 mg tablet were 1.0290 (0.9352–1.1321) and 1.0290 (0.9476–1.1174), respectively, which met bioequivalence criteria. Overall, favorable PK was observed after single and multiple administrations of one fexuprazan 10 mg tablet, and four fexuprazan 10 mg tablets were pharmacokinetically equivalent to one fexuprazan 40 mg tablet.

Introduction The outcome of radiotherapy (RT) for prostate cancer (PCA) depends on the delivered dose. While the evidence for dose-escalated RT up to 80 Gy is well established, there have been only few studies examining dose escalation above 80 Gy. We initiated the presented study to assess the safety of dose escalation up to 84 Gy. Patients and methods In our retrospective analysis, we included patients who received dose-escalated RT for PCA at our institution between 2016 and 2021. We evaluated acute genitourinary (GU) and gastrointestinal (GI) toxicity as well as late GU and GI toxicity. Results A total of 86 patients could be evaluated, of whom 24 patients had received 80 Gy and 62 patients had received 84 Gy (35 without pelvis- and 27 with pelvis-radiotherapy). Regarding acute toxicities, no adverse events > grade 2 occurred. 12.5% of patients treated with 80Gy, in 25.7% of patients treated with 84 Gy excluding pelvis, and in 51.9% of patients treated with 84Gy including pelvis suffered from Grade 2 GU acute toxicity (80 Gy versus 84 Gy: p=0.186; with pelvis versus without pelvis: p=0.032). Grade 2 GI toxicity occurred in 12.5% of patients irradiated with 80Gy, in 14.3% of patients treated with 84 Gy excluding pelvis, and in 12.9% of patients treated with 84Gy including pelvis (80 Gy versus 84 Gy: p=0.582; with pelvis versus without pelvis: p=0.510).GU late toxicity of grade ≥ 2 occurred in 4.2% of patients treated with 80 Gy, in 7.1% of patients treated with 84 Gy excluding pelvic RT, and in 18.2% of patients treated with 84 Gy including pelvic RT (logrank-test p=0.237). 8.3% of patients treated with 80 Gy, in 3.6% of patients treated with Gy excluding pelvic RT, and in 0% of patients treated with 84 Gy including pelvic RT suffered from GI late toxicity of grade ≥ 2(logrank-test p=0.358). Conclusion We were able to show that dose-escalated RT in PCA up to 84 Gy is feasible and safe without asubstantial increase in toxicity. Further follow up is needed to assess survival.

Background: Although metastatic GCT is highly curable with initial cisplatin-based chemotherapy (CT), 20-30% of patients relapse. Salvage CT options include conventional (CDCT) and high dose chemotherapy (HDCT), however definitive comparative data remains lacking. We aimed to characterize the contemporary practice patterns of salvage CT across Canada. Methods: We conducted a 30-question online survey for Canadian medical and hematological oncologists with experience in treating GCT, assessing treatment availability, patient selection, and management strategies used for relapsed GCT patients. Results: Respondents included 30 staff; from 18 cancer centers across provinces. The most common CDCT regimens used were TIP (64%) and VIP (25%). HDCT was available for (70%) in 13 centers. HDCT regimen used included carboplatin and etoposide for 2 cycles (76% in 7 centers), 3 cycles (6% in two centers), and the TICE protocol (11%, in 2 centers). “Bridging” CDCT was used by 65% respondents. Post HDCT treatments considered include surgical resection for residual disease (87.5%), maintenance etoposide (6.3%) and sur-veillance only (6.3%). Conclusions: HDCT is the most commonly used GCT salvage strategy in Canada. Significant differences exist in the treatment availability, selection and delivery of HDCT, highlighting the need for standardization of care for patients with relapsed testicular GCT.

In the European Union (EU), cannabidiol products require pre-marketing authorisation under the novel food regulation. Currently, 19 CBD applications are under assessment at the European Food Safety Authority (EFSA). During the initial assessment of the application files, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) located several knowledge gaps in their 07 June 2022 statement on safety of cannabidiol as a novel food that need to be addressed before the evaluation of CBD can be concluded. Namely, the effect of CBD on the liver, gastrointestinal tract, endocrine system, nervous system, psychological function, and reproductive system needs to be clarified. Nevertheless, the available literature allows a benchmark dose (BMD)-response modelling of several bioassays, resulting in a BMD lower confidence limit (BMDL) of 20 mg/kg bw/day for liver toxicity in rats. Human data in healthy volunteers found increases in the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in a study at 4.3 mg/kg bw/day, which was defined by EFSA NDA panel as a lowest observed adverse effect level (LOAEL). The EFSA NDA panel currently concluded that the safety of CBD as a novel food cannot be evaluated, leading to a so-called clock stop of the applications until the applicants provide the required data. Meanwhile, the authors suggest that CBD products still available as food supplements on the EU market despite the lack of authorisation must be considered as “unsafe”. Products exceeding a health-based guidance value of 10 mg/day must be considered as being “unfit for consumption” (Article 14(1) and (2) (b) of Regulation No 178/2002), while the ones in exceedance of the human LOAEL must be considered “injurious to health” (Article 14(1) and (2) (a) of Regulation No 178/2002).

G4v is a four-vector theory of gravitation proposed by Mead (2015, 2023a,b) which reinterprets several major results commonly celebrated for the tensor-based approach of General Relativity (GR). Here, we show that G4v obeys the correspondence principle, an important test of any relativistic theory. We derive the non-relativistic Lagrangian and Energy expressions at the limit of low speeds and potentials, complete with the correct terms for potential energy (something traditional Special Relativity is incapable of achieving). G4v could represent a new interpretation of the gravitational field with essentially the same mathematics as electromagnetism (Mead 2023a). It is also possible to interpret G4v as a very interesting (and useful) approximation of the Einstein field equations (Mead 2023b).

Background: Parathyroid imaging techniques are used in patients with biochemically confirmed primary hyperparathyroidism (pHPT) to detect the localization of enlarged parathyroid gland(s) (PTG) and thereby to allow more focused, unilateral or minimally invasive parathyreoidectomy (PTX), instead of classical bilateral neck exploration (BNE). Although the preferred sequence of imaging continues to evolve, ultrasonography (US) is usually the first line modality, followed by 99mTc sestamibi parathyroid scan (SPS). However, both tests may have suboptimal localizing accuracy with considerable rate of non-localized cases. Therefore, more accurate four-dimensional computed tomography scan (4D-CT) has been employed for PTG imaging. Currently, there is a paucity of data evaluating the utility of 4D-CT in low case-load settings. Aim: To evaluate the impact of PTG imaging, using 4D-CT in conjunction with it’s intraoperatively displayed results, on the outcomes of surgical PTX. Our primary outcome was sensitivity of 4D-CT in comparison to US and SPS for preoperative PTG adenoma localization. The secondary outcomes were the need for redo surgery and morbidity. Additionally, the characteristics of surgical PTX, i.e. operative time, number of removed parathyroid glands, and rate of simultaneous thyroid surgery, were assessed. Methods: A single-center retrospective analysis of surgically treated patients with pHPT from 01/2010 to 01/2021 was conducted. Evaluation of impact of the preoperative imaging modalities on the results of surgical treatment was carried out. Results: During the study period 290 PTX were performed, 45 cases were excluded due to surgery for secondary, tertiary or recurrent HPT, or due to use of alternative imaging techniques; the remaining 245 patients were included in the study. US was carried out for PTG imaging in 236 (96.3%), SPS in 93 (38.0%), and 4D-CT in 52 patients (21.2%). The use of 4D-CT was associated with a significantly higher rate of successful localization of enlarged PTG (49 cases, 94.2%) compared to US and SPS (74 cases, 31.4%, and 54 cases, 58.1%, respectively). We distinguished between three groups of patients based on preoperative imaging: 1) PTG lateralization via US or SPS in 106 (43.3%) cases, 2) precise localization of PTG via 4D-CT in 49 (20.0%) patients, and 3) in 90 cases (36.7%) PTG imaging failed to localize enlarged gland. The group of 4D-CT localization had significantly shorter operative time, lower rate of simultaneous thyroid resections, as well as lower rate of removal of ≥2 PTG, compared to the other groups. The 4D-CT imaging was also associated with the lowest perioperative morbidity and with the lowest median PTH in one month follow-up; however, compared to the other groups, these differences were statistically not significant. Implementation of 4D-CT (since 01/2018) decreased the need for redo surgery (from 11.5% to 7.3%), and significantly increased the annual case load of PTX at our institution (from 15.3 to 41.0), compared to the period before 4D-CT diagnostics. Conclusions: 4D-CT imaging enabled to precisely locate almost 95% of enlarged PTG in patients with pHPT. Accurate localization and intraoperatively displayed imaging results are useful guides for surgeons in making PTX a faster and safer procedure in a low volume center.

Capabilities of the Attenuated Total Reflection (ATR) at THz wavelengths for increased sub-surface depth characterisation of (bio-)materials is presented. The penetration depth of a THz evanescent wave in biological samples is dependent on the wavelength and temperature and can reach 0.1-0.5 mm depth due to strong refractive index change ∼0.4 of the ice-water transition; this is quite significant and important when studying biological samples. Technical challenges are discussed when using ATR for uneven, heterogeneous, high refractive index samples with possibility of frustrated total internal reflection (a breakdown of the ATR reflection-mode into transmission-mode). Local field enhancements at the interface are discussed with numerical/analytical examples. Maxwell’s scaling was used to model behaviour of absorber-scatterer inside materials at the interface with ATR prism for realistic complex refractive indices of bio-materials. Modality of ATR with polarisation analysis is proposed and its principle illustrated, opening an invitation for its experimental validation. The sensitivity of the polarised ATR mode to the refractive index between the sample and ATR prism is revealed. Design principles of polarisation active optical elements and spectral filters are outlined. The results and concepts are based on experiments carried out at the THz beamline of the Australian Synchrotron.

We theoretically investigate and optimize the performance of four-wave mixing (FWM) in microring resonators (MRRs) integrated with two-dimensional (2D) layered graphene oxide (GO) films. Owing to the interaction between the MRRs and the highly nonlinear GO films as well as to the resonant enhancement effect, the FWM efficiency in GO-coated MRRs can be significantly improved. Based on previous experiments, we perform detailed analysis for the influence of the GO film parameters and MRR coupling strength on the FWM conversion efficiency (CE) of the hybrid MRRs. By optimizing the device parameters to balance the trade-off between the Kerr nonlinearity and loss, we achieve a high CE enhancement of ~18.6 dB relative to the uncoated MRR, which is ~8.3 dB higher than previous experimental results. The influence of photo-thermal changes in the GO films as well as variations in the MRR parameters such as the ring radius and waveguide dispersion on the FWM performance is also discussed. These results highlight the significantly improved FWM performance that can be achieved in MRRs incorporating GO films

The calculation and visualization of the dose field in the decommissioning of nuclear facilities is one of the important functions of the decommissioning virtual simulation system, which can provide accurate and intuitive radiation field distribution and play an important role in determining the demolition plan and protecting personnel during the engineering implementation process. This article investigates the development of dose field calculation and visualization in the reactor decommissioning virtual simulation systems, and preliminarily proposes a technical plan suitable for the development of the decommissioning dose field calculation and visualization display programs for the first Heavy Water Research Reactor (HWRR) in China. Besides, the applicability of the selected scheme is analyzed, the functional requirement and development direction of the HWRR reactor decommissioning dose field calculation and visual display module are preliminarily determined. Furthermore, the reactor vessel of HWRR reactor is modeled and the dose field distribution was calculated and visualized. This research can provide technical support for the development of the decommissioning simulation system for the first HWRR reactor in China.

The total ionizing dose (TID) effect significantly impacts the electrical parameters of fully depleted silicon on insulator (FDSOI) devices and even invalidates the on-off function of devices. At present, most of the irradiation research on the circuit level is focused on the single event effect, and the research on the total ionizing dose effect is very little. Therefore, this study mainly analyzes the influence of TID effects on a CMOS inverter circuit based on 22 nm FDSOI transistors. First, we constructed and calibrated an N-type FDSOI metal-oxide semiconductor (NMOS) structure and P-type FDSOI metal-oxide semiconductor (PMOS) structure. The transfer characteristics and trapped charge distribution of these devices were studied under different irradiation doses. Next, we studied the TID effect on an inverter circuit composed of these two MOS transistors. The simulation results show that when the radiation dose is 400 krad (Si), the logic threshold drift of the inverter is approximately 0.052 V. These results help further investigate the impact on integrated circuits in the irradiation environment.

Background: Manoka Health District (MHD), an enclaved archipelago district in Cameroon, is home to about 1,732 under-2 children. Over 90% of these children have not received a single dose of any vaccine. In this paper, we explored the reasons for the high proportion of zero-dose children in this district so as to generate information that policymakers can use to develop context-specific interventions to boast coverage for routine immunization (RI) in this remote fishing island Methodology: We collected qualitative data via key informant interviews (KII) and focused group discussions (FGD) and analyzed it using thematic analysis. Participants for KII were selected using purposive sampling, and a snowballing approach helped to recruit an intermixed population of locals and immigrants for FGDs. Results: MHD is a hard-to-reach zone with a lone health facility that lack a functional cold chain equipment to cover the 47 islets of the district. Diurnal floods, long distance, sea turbulence, infrastructural and resource constraints, and immigrant population without residence permits hinders optimal childhood vaccination. Insufficient community health workers and lack of proper community engagement with feedback loops hamper effective communication and vaccine uptake during campaigns and outreaches. The reasons for vaccination hesitancy included hospital-based vaccination preference over home-based vaccination, fear of post-vaccination fever, rumors, repeated postponement of the vaccination schedules, and refusal by some ethnic group leaders. Conclusion: This study revealed context-specific reasons for zero-dose childhood vaccination status in MHD. These findings should be leveraged to design tailored interventions to raise RI in MHD and similar under-vaccinated communities. Keywords: zero-dose, childhood vaccination, missed communities, Cameroon

Imidazoline derivatives, such as xylometazoline, naphazoline, tetryzoline, tramazoline or oxymetazoline play an important pharmacological role as nasal drops in the symptomatic treatment of rhinitis. When comparing the toxicological data of these substances, it is noticeable that Oxymetazoline has an LD₅₀ value which is two orders of magnitude lower than all other imidazoline derivatives. Thus, ten vials of commercially available oxymetazoline nasal drops already contain a lethal amount. An explanation for this unusually high toxicity has not yet been found.

Background: We considered a problem of inference in epidemiology when cumulative exposure is the true dose metric for disease, but investigators are only able to measure its duration on each subject. Methods: We undertook theoretical analysis of the problem in the context of a continuous response caused by cumulative exposure, when duration and intensity of exposure follow log-normal distributions, such that analysis by linear regression is natural. We present a Bayesian method to adjust duration-only analysis to incorporate partial knowledge about the relationship between duration and intensity of exposure and illustrate this method in the context of association of smoking and lung function. Results: We derive equations that (a) describe under what circumstances bias arises when duration of exposure is used as a proxy of cumulative exposure, (b) quantify the degree of such bias and loss of precision, and (c) describe how knowledge about relationship of duration and intensity of exposure can be used to recover an estimate of the effect of cumulative exposure when only duration was observed on every subject. Conclusions: Under our assumptions, when duration and intensity of exposure are either independent or positively correlated, we can be more confident in qualitatively interpreting the direction of effects that arise from use of duration of exposure per se. To make reliable inference about the magnitude of effect of cumulative exposure on the outcome, we can use external information on the relationship between duration and intensity of exposure even if intensity of exposure is not available at the individual level.

Michele Ruggieri (1543-1607) was the first Westerner officially approved to reside in China. He promoted Chinese and Western cultural exchange, and he was especially noted for facilitating dialogue between Confucianism and Catholicism. His writings had an important impact in both China and Europe. During his sojourn preaching in China, Ruggieri not only wrote the Tianzhu shilu-- the first catechism written in Chinese--but he was also the first Westerner to translate the Four Books into western language and introduce them to Europe. Based on Ruggieri’s two translations of the Four Books--one translation into Spanish, and one into Latin--this article analyses Ruggieri’s views of Confucius. In his translations, Ruggieri identified Confucius as a philosopher and a shengren, or saint, and he highlighted the status of Confucius in the Four Books. After the analysis of the Confucian concepts, this article discusses Ruggieri’s translations implied that despite showing the rational aspects of Confucianism, the religiousness was still in Confucianism. After Ruggieri, other Jesuits who came to China gradually turned to emphasize the rational aspects of Confucianism.

Layered 2D graphene oxide (GO) films are integrated with silicon nitride (SiN) waveguides to experimentally demonstrate an enhanced Kerr nonlinearity via four-wave mixing (FWM). Owing to the strong light–matter interaction between the SiN waveguides and the highly nonlinear GO films, the FWM performance of the hybrid waveguides is significantly improved. SiN waveguides with both uniformly coated and patterned GO films are fabricated based on a transfer-free, layer-by-layer GO coating method together with standard photolithography and lift-off processes, yielding precise control of the film thickness, placement and coating length. Detailed FWM measurements are carried out for the fabricated devices with different numbers of GO layers and at different pump powers. By optimizing the trade-off between the nonlinearity and loss, we obtain a significant improvement in the FWM conversion efficiency of ≈7.3 dB for a uniformly coated device with 1 layer of GO and ≈9.1 dB for a patterned device with 5 layers of GO. We also obtain a significant increase in FWM bandwidth for the patterned devices. A detailed analysis of the influence of pattern length and position on the FWM performance is performed. Based on the FWM measurements, the dependence of GO’s third-order nonlinearity on layer number and pump power is also extracted, revealing interesting physical insights about the 2D layered GO films. Finally, we obtain an enhancement in the effective nonlinear parameter of the hybrid waveguides by over a factor of 100. These results verify the enhanced nonlinear optical performance of SiN waveguides achievable by incorporating 2D layered GO films.

InGaN/GaN samples grown on c-plane sapphire substrate with different In concentrations by metal organic chemical vapor deposition are demonstrated. The subsequent capping GaN layer growth opens a possibility for dislocation reduction due to the lateral strain relaxation in growth geometry. We present the further growth optimization and innovative characterization of InGaN layers overgrown on different structures with varying In concentrations. The photoelectrical and optical properties of the InGaN layers with or without capping GaN layer were investigated by time-resolved picosecond transient grating and temperature dependence photoluminescence. We note a 10-fold increase in carrier lifetime in the InGaN layers when the sample structure changes from PIN to single InGaN layer.

Tunneled central venous catheters (CVC) are mainly considered as rescue vascular access option in dialysis but still used in about one quarter of prevalent patients worldwide as being associated with poor performances and higher risks. Study design. In this retrospective single-center study, we aimed to report on clinical performances achieved with high-flow tunneled CVC (DualCath, DCath) and compared it with arteriovenous accesses (AVAs; AV fistula, AV graft, Thomas Shunt) in a hospital-based dialysis unit. Methods. Sixty-eight stage 5 chronic kidney disease dialysis dependent patients (CKD5D) receiving high volume hemodiafiltration were followed-up for 30 months. The study consisted of two phases: baseline cross-sectional and longitudinal follow-up of key performance indicators. Clinical performances consisting of effective blood flow and blood volume, recirculation, urea and ionic Kt/V and total Kt, ultrafiltration volume and percent reduction of ß2-M were measured monthly as part of quality control in our unit. Results. At baseline, effective blood flow with DCath was close to 400 ml/min, similar to AVAs. Recirculation with DCath (7%, 6-13%) was higher than AVAs. Diffusive dialysis dose delivered with DCath (spKt and eKt/V) and convective dialysis dose achieved with DCath were slightly lower than AVAs, but still much higher than recommended by guidelines. Percent reduction of ß2-M achieved with DCath was also 4 to 10% lower than AVAs. On longitudinal follow-up, main clinical performance indicators of DCath (total Kt and total ultrafiltration volume, L/session) were maintained very stable over time and close to those achieved with AVAs. Conclusions. As shown in this study, high-flow DualCath tunneled two single lumen silicone catheters may be used to deliver high volume hemodiafiltration in a reliable and consistent manner without compromising clinical performances. These results rely from the specific design of the two silicone cannulas and the strict adherence to best catheter practices.

Hyper-radiosensitivity (HRS) is the increased sensitivity to low doses of ionizing radiation observed in most cell lines. We previously demonstrated that HRS is permanently abolished in cells irradiated at a low dose rate (LDR), in a mechanism dependent on transforming growth factor β3 (TGF-β3). In this study, we aimed to elucidate the activation and receptor binding of TGF-β3 in this mechanism. T-47D cells were pre-treated with inhibitors of potential receptors and activators of TGF-β3, along with addition of small extracellular vesicles (sEVs) from LDR primed cells, before their radiosensitivity was assessed by the clonogenic assay. The protein content of sEVs from LDR primed cells was analyzed with mass spectrometry. Our results show that sEVs contain TGF-β3 regardless of priming status, but only sEVs from LDR primed cells remove HRS in reporter cells. Inhibition of the matrix metalloproteinase (MMP) family prevents removal of HRS, suggesting an MMP-dependent activation of TGF-β3 in the LDR primed cells. We demonstrate a functional interaction between TGF-β3 and activin receptor like kinase 1 (ALK1), by showing that TGF-β3 removes HRS through ALK1 binding, independent of ALK5 and TGF-βRII. These results are an important contribution to a more comprehensive understanding of the mechanism behind TGF-β3 mediated removal of HRS.

The calculation of effective doses is crucial in many medical and radiation fields, in order to ensure safety and compliance with regulatory limits. Traditionally, Monte Carlo codes using detailed human body computational phantoms have been used for such calculations. Monte Carlo dose calculations can be time-consuming and require expertise in different processes when building the computational phantom and dose calculations. This study employs various machine learning (ML) algorithms to predict the organ doses and effective dose conversion coefficients (DCCs) for different anthropomorphic phantoms. A comprehensive data set comprising neutron energy bins, organ labels, masses, and densities is compiled from Monte Carlo studies, and is used to train and evaluate the supervised ML models. This study includes a broad range of phantoms, including those from the International Commission of Radiation Protection (ICRP-110, ICRP-116 phantom), the Visible-Human Project (VIP-man phantom), and the Medical Internal Radiation Dose Committee (MIRD-Phantom), with row data prepared using numerical data and organ categorical labeled data. Extreme gradient boosting (XGB), gradient boosting (GB), and the random forest-based Extra Trees regressor are employed to assess the performance of the ML models against published ICRP neutron DCC values using the mean square error, mean absolute error, and R² metrics. The results demonstrate that the ML predictions significantly vary in lower energy ranges and vary less in higher neutron energy ranges, while showing good agreement with ICRP values at mid-range energies. Moreover, the categorical data models align closely with the reference doses, suggesting the potential of ML in predicting effective doses for custom phantoms based on regional populations, such as the Saudi voxel-based model. This study paves the way for efficient dose prediction using ML, particularly in scenarios requiring rapid results without extensive computational resources or expertise. The findings also indicate potential improvements in data representation and the inclusion of larger data sets to refine model accuracy and prevent overfitting. Thus, ML methods can serve as valuable techniques for the continued development of personalized dosimetry.

Vaccination has proven to be one of the most effective strategies against the COVID 19 pandemic. Several studies have evaluated and confirmed its effectiveness in different populations, particularly in reducing severe outcomes such as hospitalization and death. However, the potential of vaccination to protect against infection itself has been overlooked. The aim of this study was to determine the effectiveness of the booster dose in a sample of Colombian patients during the fourth wave of COVID-19 pandemic, which was associated with the emergence and predominance of the Omicron variant. A cross-sectional study was conducted on individuals who underwent RT-PCR testing for COVID-19 detection in a dedicated laboratory in Bogotá, Colombia, between December 30th 2021 and February 7th 2022. A total of 1,468 subjects were included in the study. The comparison between fully vaccinated individuals with a booster dose and those without the booster dose revealed a 28% reduction in the odds of infection (OR = 0.719 CI 0.531 - 0.971). Age (OR = 1,009 CI 1,001 - 1,018) and low economic status (OR= 1,812 CI 1,416- 2,319) were associated with an increased risk of infection.These findings suggest the need for booster vaccination in the general population to improve the prevention rates of SARS-CoV-2 infection and mitigate severe outcomes.

The virtually complete loss of intestinal worms, known as helminths, from Western society has resulted in elimination of a range of helminth-induced morbidities. Unfortunately, that loss has also led to inflammation-associated deficiencies in immune function, ultimately contributing to widespread pandemics of allergies, autoimmunity, and neuropsychiatric disorders. Several socio-medical studies have examined the effects of intentional reworming, or self-treatment with helminths, on a variety of inflammation-related disorders. In this study, the latest results from ongoing socio-medical studies are described. The results point toward two important factors that appear to be overlooked in some if not most clinical trials. Specifically, (a) the method of preparation of the helminth can have a profound effect on its therapeutic efficacy, and (b) variation between individuals in the effective therapeutic dosage apparently covers a 10-fold range, regardless of the helminth used. These results highlight current limits in our understanding of the biology of both hosts and helminths, and suggest that information from self-treatment may be critical for clinical evaluation of the benefits and limits of helminth therapy.

Liver radioembolization is a treatment option for unresectable liver cancers, performed by infusion of 90Y or 166Ho loaded spheres in the hepatic artery. As tumoral cells are mainly perfused via the liver artery unlike hepatic lobules, a twofold tumor to normal liver dose ratio is commonly obtained. To improve tumoral cells killing while preserving lobules, co-infusion of arterial vasoconstrictor has been proposed but with limited success: the hepatic arterial buffer response (HABR) and hepatic vascular escape mechanism hamper the arterioles vasoconstriction. The proposed project aims to take benefit of the HABR by co-infusing a mesenteric arterial vasodilator: the portal flow enhancement inducing the vasoconstriction of the intra sinusoids arterioles barely impacting liver tumors that are mainly fed by novel and anarchic external arterioles. Animal studies were reviewed and dopexamine was identified as a promising safe candidate reducing by 4 the hepatic lobules arterial flow. A clinical trial design is proposed. A four to sixfold improvement of the tumoral to normal tissue dose ratio is expected, pushing the therapy towards a real curative intention, especially in HCC where ultra-selective spheres delivery is often not possible.

The new WHO Environmental Noise Guidelines for the European Region have recommendations for limiting noise exposure associated with adverse health effects. The limits are said to be based on a systematic review of existing evidence. This paper gives a systematic assessment of the presented evidence with respect to aircraft noise annoyance and demonstrates that the new guidelines are based on an arbitrary selection of existing studies comprising an imperfect and faulty set of data not representative for the general airport population.

Pipelines extend thousands of kilometers to transport and distribute oil and gas. Given the challenges often faced with corrosion, fatigue, and other issues on steel pipes, the demand for glass fiber reinforced plastics (GFRP) pipes is increasing in the oil and gas gathering and transmission systems. However, the medium transported through these pipelines contains multiple acid gases such as CO2 and H2S, as well as ions including Cl-、Ca2+、Mg2+、SO42-、CO32- and HCO3-. These substances can cause a series of problems, such as aging, debonding, delamination, and fracture. In this study, a series of aging damage experiments were conducted on V-shaped GFRP pipes with depths of 2mm and 5mm. The aging and failure of GFRP were studied under the combined effects of external force and acidic solution using acoustic emission (AE) techniques. It was found that the acidic aging solution promoted matrix damage, fiber/matrix desorption, and delamination damage in GFRP pipes over a short period. However, the overall aging effect was relatively weak. Based on the experimental data, the SSA-LSSVM algorithm was proposed and applied to the damage pattern recognition of GFRP. An average recognition rate of up to 90% was achieved, indicating that this method is highly suitable for analyzing AE signals related to GFRP damage.

In a motor-controlled hydraulic cylinder (MCC), the two chambers of the cylinder are directly connected to single or multiple fixed-displacement hydraulic pumps driven by electric servo motors. In contrast to a valve-controlled cylinder, an MCC does not have valve throttling, resulting in an improved system energy efficiency. Among various MCC topologies, the two-motor-two-pump (2M2P) MCC distinguishes itself through several notable advantages, including precise cylinder pressure control and eliminating mode switch oscillations. Nevertheless, there are remaining challenges in fully realizing its operations across four quadrants and establishing an effective load-holding function within these operations. This study bridges this gap by implementing a 2M2P MCC prototype on a laboratory knuckle boom crane, enabling operation across all four quadrants. Experimental results indicate that position tracking errors remain within ±2.5 mm across three cases. Furthermore, smooth intersection of cylinder bore side and rod side pressures is observed during transitions between quadrants. In conclusion, the proposed 2M2P MCC demonstrates seamless operation throughout all quadrants, with the load-holding function smoothly activating and deactivating in all four quadrants.

Let BT4l denotes a subclass of bounded turning functions connected with a four-leaf-type domain. The goal of the study is to probe into coefficients of |b6|, |b7|, |b8|, the bounds of the logarithmic coefficients and the third-order determinants of H3,1, H3,2, H3,3 for functions in this class.

This paper presents a theory on graph topological structure and graph coloring, proving that for any N-order graph structure (with a topological structure similar to ), the maximum number of colors required for coloring is less than or equal to . The Four Color Theorem is just one special case of this theory, with the maximum structure size for a four-color graph being a 4-order structure graph, hence requiring only a maximum of 4 colors for coloring.

The type III receptor tyrosine kinase FLT3 is a pivotal kinase for hematopoietic progenitor cell regulation, with significant implications in acute myeloid leukemia (AML) through mutations like internal tandem duplication (ITD). This study delves into the structural intricacies of FLT3, the roles of activation loop mutants, and their interaction with tyrosine kinase inhibitors. Coupled with this, the research leverages molecular contrastive learning and protein language modeling to examine interactions between small molecule inhibitors and FLT3 activation loop mutants. Utilizing the ConPLex platform, over 5.7 million unique FLT3 activation loop mutants-small molecule pairs were analyzed. The binding free energies of three inhibitors were assessed, and cellular apoptotic responses were evaluated under drug treatments. Notably, the introduction of the Xepto50 scoring system provides a nuanced metric for drug efficacy. The findings underscore the modulation of molecular interactions and cellular responses by Y842 mutations in FLT3-KD, highlighting the need for tailored therapeutic approaches in FLT3-ITD-related malignancies.

Unsmooth reversing is one of the most common faults in the four-way reversing valve of air conditioning system, and the airflow in the valve chamber and the shape of the slider of the reversing valve are the main factors in unsmooth reversing. In order to study the influence of the airflow in the chamber and the slider shape on the reversing process, the fluid flow in the valve chamber of a four-way reversing valve is obtained using computational fluid dynamics (CFD) simulations, and the influence of slider structure on slider thrust and resistance of the four-way reversing valve is analyzed. Four-way reversing valves with no-cutting, straight-cutting and arc-cutting sliders are employed to evaluate the reversing characteristics. A pressure measuring device for a four-way reversing valve chamber is designed, which is performed to test the chamber pressure of three different types of sliders of four-way reversing valves. The maximum error of experimental tests and simulations is within 5% of engineering tolerance, so as to verify the reliability of numerical simulation. The results indicate that the chamber pressure and resistance-thrust ratio with the cutting slider are reduced, which is beneficial to the reversing of the four-way reversing valve. Compared with the straight cutting structure, the arc cutting slider four-way reversing valve has a more stable reversing process and better comprehensive reversing performance. The results can provide a theoretical basis for engineers to improve the performance of four-way reversing valves.

We report photon-phonon atomic coherence (cascade- and nested-dressing) interaction from various phase transitions of Eu3+: BiPO4 crystal. Such atomic coherence spectral interaction evolves from out of phase fluorescence to in-phase spontaneous four-wave mixing (SFWM) by changing the time gate. The dressing dip switch and three dressing dips of SFWM result from strong photon-phonon destructive cross- and self-interaction for hexagonal phase, respectively. The more phonon dressing result in destructive interaction, while less phonon dressing result in constructive interaction of atomic coherences. The experimental measurements of photon-phonon interaction agree with theoretical simulations. Based on our results, we proposed a model for an optical transistor (as an amplifier and switch).

Nisin, an antibacterial compound produced by Lactococcus lactis strains, has been approved by the US Food and Drug Administration to be used as a safe food additive to control the growth of undesirable pathogenic bacteria. Nisin is commonly described as a pH-dependent primary metabolite, since its production depends on growth and culture pH evolution. However, the relationship between bacteriocin synthesis and the consumption of the limiting nutrient has not been described until now. Therefore, this study aimed to develop a competitive four-dimensional Lotka Volterra-like equation to describe the relationships between culture pH, limiting nutrient (total nitrogen: TN) consumption and production of biomass (X) and nisin (BT) in four series of batch fermentation with L. lactis CECT 539 in diluted whey (DW)-based media. The developed four-dimensional LV-like equation (with a unique set of parameters) could not be used to describe all cultures belonging to each fermentation series. However, the four-dimensional LV-like equation described accurately each individual culture, providing a good description of the relationships between pH, TN, X and BT, higher values for R2 and F-ratios, lower values (&lt; 10%) for the mean relative percentage deviation modulus, with bias and accuracy factor values approximately equal to one.

An adaptive control technique has been implemented for DSTATCOM for power quality enhancement in three phase four wires(3P4W) distribution system. The reference source currents are extracted from active components of load current for each phase by using this technique. It has also been used for load balancing, harmonic suppression, power factor improvement and reactive power compensation in distribution system. The adaptive control technique has been tested at varying load in steady state and dynamic conditions. This technique is developed using MATLAB/Simulink and source side harmonics are mitigated under different load conditions which are acceptable in accordance with IEEE standard.

Abstract: Epidemiological, experimental, and ecological data have indicated the controversial effect of in utero chronic low dose rate (100 mGy) dose radiation exposure. Our main goal of this study was to examine if different low dose rates of chronic pre- or/and post-natal radiation exposure with accumulative high doses could induce hippocampal cellular, mRNA, and miRNA changes leading to neuropsychiatric disorders. The comprehensive mouse phenotypic traits, organ weight pathological, blood mRNA and miRNA changes were also studied. Using different approaches including SmithKline, Harwell, Imperial College, Royal Hospital, Phenotype Assessment (SHIRPA), neurobehavioral tests, pathological examination, immunohistochemistry, mRNA and miRNA sequencing, and real-time quantitative polymerase chain reaction ( qRT-PCR) validation, we found that in prenatally irradiated (100 mGy/d for 18 days with an accumulative dose of 1.8 Gy) 1-year-old mice, no cellular changes including neurogenesis, mature neurons and glial cells in the hilus of the dentate gyrus and development of cognitive impairment, neuropsychiatric disorders occurred. However, a significant reduction in body weight and mass index (BMI) was indicated by the SHIRPA test. A reduced exploratory behavior was shown by an open field test. Organ weight measurement showed a significant reduction of the testes, kidneys, heart, liver, and epididymides although no abnormal changes from pathological examination. mRNA and miRNA sequencing and qRT-PCR validation revealed the upregulation of Rubcnl, Abhd14b and downregulation of Hspa1b, P4ha1, and Banp genes in both hippocampus and blood of mice prenatally irradiated with 100 mGy/d. Meanwhile, downregulation of miR-448-3p, miR1298-5p in the hippocampus, miR-320-3p, miR-423-5p, miR-486b-5p, miR-486b-3p, miR-423-3p, miR-652-3p, miR-324-3p, miR-181b-5p, miR-let-7b and miR-6904-5p in the blood was induced. The target scan revealed that Rubcnl is one of the miR-181b-5p targets in the blood. We, therefore, concluded that prenatal chronic irradiation with a low dose rate of 100 mGy/d and accumulative dose of 1.8Gy or below may not induce significant adverse health effects on the offspring. Further study of different low dose rate radiation exposure with accumulative high doses may provide threshold doses for authorities or regulators to set new radiation safety guidelines to replace those extrapolated from acute high dose/dose rate irradiation to reduce unnecessary emergency evacuation or expanding once a nuclear accident or leakage occurs.

ABSTRACT Objectives: Typical Diagnostic Reference Levels (DRL) in terms of Computed Tomography Dose Index (CTDI) and patient dose in terms of Effective Dose (ED ) and Size Specific Dose Estimate (SSDE) were estimated in Computed Tomography (CT) guided biopsy procedures. Materials and Methods: A total of 226 CT biopsy procedures - Iliac bone, liver, lung, mediastinum and para-aortic tissue - were retrospectively analyzed and Typical DRL extracted based on ICRP 135 instructions. Results: For helical mode acquisitions, DRLs in terms of CTDIvol were 9.7 mGy for Iliac bone, 8.9 mGy for liver, 8.8 mGy for lung, 7.9 mGy for mediastinal mass and 9 mGy for para-aortic lymph nodes biopsy procedures. For biopsy acquisitions, DRL values were 7.3 mGy, 7.7 mGy, 5.6 mGy, 5.6 mGy and 7.4 mGy respectively. Also, SSDE median values ranged from 7.6 mGy to 10 mGy for biopsy acquisitions and 11,3 mGy to 12,6 mGy for helical acquisitions, as well as the median values for effective dose ranged from 1.6 mSv to 5,7 mSv for biopsy scans and 3.9 to 9.3 mSv for helical scans. Conclusions: The use of DLR as an optimization tool for CT-guided biopsy procedures revealed that helical scans across the entire anatomical region greatly affect radiation dose compared to biopsy acquisitions.

Background: External beam radiation therapy requires a sophisticated and laborious planning procedure. To improve the efficiency and quality of the planning procedure, machine learning predictions of the dose distributions have been introduced to speed up the planning procedure and to serve as quality assurance. The most recent dose prediction models are based on deep learning U-Nets that give good approximations of the dose in 3D almost instantly. It is our purpose to train a 3D dose prediction for glioblastoma VMAT treatment and test its robustness and sensitivity for the purpose of quality assurance of automatic contouring. Methods: From a cohort of 125 glioblastoma (GBM) patients, VMAT plans were created according to a clinical protocol. The initial model was trained on a concatenated 3D U-Net. A total of 60 cases were used for training, 15 for validation and 20 for testing. The prediction model was tested for sensitivity to dose changes according to realistic contour variations. Additionally, the model was tested for robustness by exposing it to a worst-case test set containing out-of-distribution cases.Results: The initially trained prediction model had a dose score of 0.94 Gy and a mean DVH score for all structures of 1.95 Gy. In terms of sensitivity, the model was able to predict the dose changes that occurred due to the contour variations with a mean error of 1.38 Gy.Conclusions: We obtained a 3D VMAT dose prediction model for GBM with limited data, providing good sensitivity to realistic contour variations. We tested and improved the model's robustness, by targeted updating the training set, making it a useful technique for dose awareness in the contouring evaluation and quality assurance.

Background. Metronidazole treats obligate anaerobic bacterial and protozoal infections, with an elimination half-life of around eight hours. The long elimination half-life, the favorable ratio of steady-state serum levels to minimum inhibitory concentration, and the presence of active metabolites lead to consideration of metronidazole use at 12-hour dosage intervals. This systematic review aimed to compare the clinical outcomes of twice-daily and thrice-daily metronidazole dosing. Methods. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. PubMed, Scopus, Science Direct, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials to systematically identify all relevant studies published up to June 16, 2023. Results. The final analysis included two published retrospective cohort studies; a single site (n = 200) and a multisite study (n = 85) of ‘good’ quality, as measured by the Newcastle-Ottawa scale. The reported baseline characteristics of the 8-hour and 12-hour dosing groups were comparable, and neither study identified significant differences in primary and secondary clinical outcomes. Meta-analysis of the need to escalate antibiotic therapy also showed no statistically significant differences using the Mantel-Haenszel fixed-effect method (95% CI: 47.6% lower to 6.4 times higher risk, p = 0.342) and inverse-variance method (RR: 1.87, 95% CI: 0.52-6.65, p = 0.336). Conclusions. Dosing metronidazole every 12 hours is as effective as every 8-hour dosing for anaerobic infections. Healthcare systems may consider the adoption of every 12-hour metronidazole dosing with continued evaluation of patient outcomes.

Rivaroxaban and aspirin are commonly used antithrombotic agents that are used in combination for the prevention of coronary artery disease (CAD) and atherothrombotic events in adult patients after an acute coronary syndrome (ACS) with elevated cardiac biomarkers, or with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) in high-risk patients. The recommended dosage is 2.5 mg Rivaroxaban twice daily with 75–100 mg aspirin daily. This study aimed to develop a fixed-dose combination tablet of rivaroxaban (2.5 mg) and aspirin (50 mg) to decrease the patient's pill burden and enhance medication adherence. The product formula was developed based on compatibility studies among the active ingredients and the active ingredients' compatibility studies. The formula and the manufacturing procedure were chosen based on the risk assessment for each active substance, wet granulation with both actives intragranular was found to have faster dissolution than direct mix formulae. Furthermore, a validated reverse-phase HPLC stability indicator method was developed to detect APIs and their possible degradants in the formula.

Abstract: Using adjuvants to optimize and increase the efficacy of herbicides is an acceptable manner to reduce herbicides undesirable impact on the environment in sustainable agriculture. In this study, it was demonstrated that the application of 0.1% of the non-ionic surfactant (NIS, Contact) and 0.5 L ha-1 of a crop oil concentrate (COC, Renol) did not improve the efficacy of rimsulfuron on Amaranthus retroflexus. In contrast, the same treatments enhanced performance and rainfastnes of rimsulfuron in Chenopodium album in pot expriments. Increasing non-ionic surfactant concentration to 1 L ha-1 increased rimsulfuron performance around 11-fold for Amaranthus retroflexus compared to around 3-fold for Chenopodium album. The same treatment, also reduced the rainfastness of rimsulfuron on Amaranthus retroflexus while improving the rainfastness of rimsulfuron on Chenopodium album. Measured ED50 and ED90 values of rimsulfuron indicated that the addition of the 0.2 L ha-1 of NIS improved the recommended (60 g ai. ha-1) and the reduced (30 g ai. ha-1) of rimsulfurom in field. The highest potato yield measured (60 tons per ha) when 60 g ai. ha-1 rimsulfuron was applied at three stages (S1, S4, and S7) without using a NIS; not significant differences were measured when the same dose of rimsulfuron was applied at the three (S1, S4, and S7) and two (S1, S4) stages with NIS.

Background: Primary central nervous system lymphomas (PCNSLs) are sensitive to chemotherapy. Standard treatment is high-dose methotrexate (MTX)-based chemotherapy. There are no reports of successful treatment of acute uric acid nephropathy with rasburicase after MTX administration in PCNSL. Case presentation: A 54-year-old man with a history of gout presented with character change and memory loss. MRI showed a large, enhancing mass spanning the bilateral frontal lobes and right temporal lobe. After endoscopic biopsy, MTX, procarbazine and vincristine (MPV) regimen was initiated for treatment of PCNSL. After initiation of chemotherapy, the patient suffered from a gout attack and blood examination revealed acute renal failure (ARF) and hyperuricemia. The considered causes of ARF included MTX toxicity and acute urid acid nephropathy. Since a good response to chemotherapy was observed, the latter was assumed. After improvement of renal function, MTX was resumed, initiating rasburicase for control of hyperuricemia. A complete response was obtained after induction chemotherapy. Hyperuricemia was controlled with rasburicase and renal function was preserved. Conclusions: Acute uric acid nephropathy should be considered when ARF occurs after initiation of MTX in PCNSL. For newly diagnosed PCNSL patients with large tumors or hyperuricemia, upfront usage of rasburicase should be considered to prevent it.

The COVID-19 pandemic caused an unprecedented effect on national radiological investigations. Since the World Health Organization officially declared the COVID-19 as a global pandemic, health policies have been rapidly organized to limit the spread of the virus and decrease the risk of exposure. These restrictions, in combination with home-stay arrangements and the onset of economic recession. As a result of public policies, financial difficulties and patient fear, many radiology departments have suffered a significant reduction in diagnostic examinations with important implications for their economic stability. The aim of this work is to evaluate the economic impact of the COVID-19 pandemic in the Radiology Department of an infectious disease hospital.

Increasing genetic diversity in crop plants has been used for chemical mutagenesis. Through the application of various mutagenic agents, over 430 new varieties have been derived as rice mutants (Oryza sativa L.) Chemical mutagens such as ethyl methane sulphonate (EMS), diepoxybutane derivative (DEB), sodium azide, and gamma ray, x-ray, and quick neutron irradiation have been commonly used to induce a large number of functional variations in rice and others crops. Among chemical mutagens, ethyl methane sulfonate (EMS) is the alkylating agent most widely used in plants because it induces nucleotide substitutions to be extremely frequent, as detected in various genomes. In this study, seeds of potential genotype of the popular variety, (Oryza sativa L. Super Basmati variety) were treated with EMS at concentrations of 0.25%, 0.50%, 0.75%, 1% and 1.5%. Various measurements on the M1 generation determined EMS sensitivity. As concentration of applied EMS increased, will decrease in germination, shoot length, root length, plant height, productive tillers, Panicle Length, Total Spikelet, sterile spikelet and fertility under field conditions were observed in M1 generation as compared to the non-treatment control. Emergence, shoot length, root length, plant height, productive tillers, Panicle Length, Total Spikelet, sterile spikelet and fertility also decreased with increases in EMS mutagenesis in an approximately linear fashion. The LD₅₀ values were observed based on growth reduction of seedlings after EMS treatment with 0.25% and 0.50% on the rice variety (Oryza sativa L. spp.).

Local anaesthetic agents suppress action potentials in excitable tissues by blocking voltage-gated sodium channels. In doing so they inhibit the depolarisation of nociceptive nerve fibres and so prevent the transmission of pain impulses. UK legislation allows HCPC-registered Podiatrists with POM-A annotation access to six local anaesthetic drugs and two of these with the addition of adrenaline. The use of local anaesthetia has transformed the treatment of nail pathology by Podiatrists. In the UK, the drug of choice in podiatric practice is 3% mepivacaine hydrochloride: it is a good choice of drug for digital anaesthesia. This paper will review the chemistry, pharmacology and dose calculation of mepivacaine, and challenge some of the orthodoxy over the rigid calculation of maximum safe dosages.

Purpose: Novel coronavirus disease (COVID-19) is the current global concern. Radiotherapy (RT), commonly employed in cancer management, has been considered one of the potential treatments for COVID-19 pneumonia. Here, we present the final report of the pilot trial evaluating the efficacy and safety of low-dose whole-lung irradiation (LD-WLI) in patients with COVID-19 pneumonia. Methods and Materials: We enrolled patients with moderate COVID-19 pneumonia who were older than 60 years. Participants were treated with LD-WLI in a single fraction of 0.5 or 1.0Gy along with the national protocol of COVID-19. The primary endpoints were improvement of SpO₂, the number of hospital/ICU stay days, and the number of intubations after RT and the secondary endpoints were alterations of the c-reactive peptide, interleukin-6, ferritin, procalcitonin, and D-dimer. The response rate (RR) was defined as a rise in SpO₂ upon RT with rising or constant trend in the next two days, and clinical recovery (CR) included patients who were discharged from the hospital or acquired SpO₂ ≥93% on room air. Results: Between 21 May 2020 and 2 July 2020, ten patients were enrolled. The median age was 75 years, 80% were male, and 80% had comorbidities. The first five patients received a single 0.5Gy-WLI, and others received 1.0Gy. Patients were followed for 2-14 days (median 5.5 days). Following one day, nine patients experienced an improvement in SpO₂. Five patients were discharged (median 6^th day, range 2^nd-14^th day), and four patients died (median 7^th day, range 3^rd-10^th day). Overall, the RR and CR were 60.0% and 55.5%, respectively. The RR and CR rates of 0.5- and 1.0Gy group were 80% vs 40% and 75% vs 40%, respectively. No acute radiation-induced toxicity was recorded. Conclusions: LD-WLI with a single 0.5Gy fraction seems to be a more appropriate dose to warrant further evaluation in a large-scale, randomized trial.

This study aims to evaluate the patient’s dose exposure from Computed Tomography Pulmonary Angiography (CTPA) examination and to estimates the cancer risk induced from the examinations based on the patient’s size. One hundred patients were recruited, and data information was collected retrospectively. A multi-detector (MDCT) (Philips Brilliance 128, USA) scanner were utilized for the CTPA examination, and dose data were obtained from the system. The effective diameter of each subjects’ image was measured for the Size-specific dose estimates (SSDEs). All subjects divided into Group 1 (19 – 25 cm), Group 2 (25-28 cm) and Group 3 (28-38 cm), where the association between gender were analysed. Effective dose (E), SSDE, organ dose and cancer risk of each group were evaluated and compared statistically using independent t-test and one-way ANOVA. The range of mean CTDI_vol, DLP and E values were (6.44 – 17.42 mGy), (239 – 631 mGy), (5.19 – 13.90 mSv), respectively. In respective with the patient’s effective diameter, the mean SSDE value for Group 1, Group 2 and Group 3 were 9.93 ± 3.89 mGy, 13.70 ± 9.04 mGy and 22.29 ± 7.35 mGy. The organ dose and cancer risk attained for breast, lung and liver were 17.05 ± 10.40 mGy (194 per one million procedure), 17.55 ± 10.86 mGy (192 per one million procedure) and 15.04 ± 9.75 mGy (53 per one million procedure), respectively. Lung and breast with more massive patient’s effective diameter received the highest dose exposure which increases the probability of the cancer risk. CTDI_vol was found to be underestimated, and SSDE provides more accurate in describing the radiation dose and cancer risk. Body effective diameter found to be significant on the estimation except for gender. Therefore, it is essential to apply optimised protocols in order to reduce patient’s exposure during CTPA examination.

This work is devoted to the construction and study of commutative gates for a two-qubit quantum system. Using four-dimensional algebra developed by the Kazakh mathematician Abenov M.M. all groups of commutative gates have been constructed, and among all states of a two-qubit quantum system, unitary states with which a specific gate is connected have been identified. An explicit type of gate is described that transfers a quantum system from one unitary state to another unitary state. The proposed approach opens up new possibilities for the design of quantum algorithms not only for two-qubit quantum systems, but also for $n$-qubit quantum systems.

Owing to the advantages of cost-effectiveness, compactness, and the avoidance of complicated camera synchronization, single-camera three-dimensional (3D) digital image correlation (DIC) techniques have gained increasing attention for deformation measurement of materials and structures. In the traditional single-camera 3D-DIC system, the left and right view images can be recorded by a single camera using a diffraction grating, a bi-prism or a set of planar mirrors. To further improve the measurement accuracy of single-camera 3D-DIC, this paper introduces a single-camera four-view imaging technique by installing a pyramidal prism in front of the camera. The 3D reconstruction of the measured points before and after deformation is realized with eight governing equations induced by four views, and the strong geometric constraints of four views can help to improve the measurement accuracy. A static experiment, a rigid body translation experiment and a four-point bending experiment show that the proposed single-camera 3D-DIC method can achieve higher measurement accuracy than the dual-view single-camera 3D-DIC techniques and has advantages in reducing both random error and systematic error.

Guessing effects frequently occur in testing data in educational or psychological applications. Different item response models have been proposed to handle guessing effects in dichotomous test items. However, it has been pointed out in the literature that the oftenemployed three-parameter logistic model poses implausible assumptions regarding the guessing process. The four-parameter guessing model has been proposed as an alternative to circumvent these conceptual issues. In this article, the four-parameter guessing model is compared with alternative item response models for handling guessing effects through a simulation study and an empirical example. It turned out that model selection for item response models should be rather based on the AIC than the BIC. However, the RMSD item fit statistic used with typical cutoff values was found to be ineffective in detecting misspecified item response models. Furthermore, sufficiently large sample sizes are required for sufficiently precise item parameter estimation. Moreover, it is argued that the criterion of statistical model fit should not be the sole criterion of model choice. The item response model used in operational practice should be valid with respect to the meaning of the ability variable and the underlying model assumptions. In this sense, the four-parameter guessing model could be the model of choice in educational large-scale assessment studies.

Background/Objectives: Encouraging results reported of Platelet-Rich Plasma (PRP) treatment for knee osteoarthritis (KOA). The present retrospective study reports the efficacy and safety of a high dose of neutrophile and red blood cell-depleted PRP to treat 212 patients with KOA. Methods: 212 consecutive patients diagnosed with Kellgren-Lawrence (KL) grading 1-3 KOA chronic knee pain for at least 1 year were treated with 3 injections at 15-day intervals with a high dose of neutrophil-depleted PRP (4 billion platelets). Clinical outcomes were retrospectively recorded as a percentage of responders at 3,6, and 12-month follow-up, following the OMERACT-OARSI criteria. Pain through VAS score and WOMAC score have also been recorded. Results: 4ml of PRP containing 4X109 platelets were obtained by single spin centrifugation and injected intra-articular into each patient with no pre-activation. The overall responder rate of patients responding to OMERACT-OARSI criteria at 3,6,12 months was 68.9%, 72,7% and 70,6%. There was a significant improvement in VAS and WOMAC scores at 3-, 6- and 12-month follow-up compared to the pre-treatment value (p&lt; 0.01). The lowest VAS score was observed at 6 months overall and in all three-grade KL groups. KL2 groups showed the best results regarding pain reduction and WOMAC score at 6 months (p&lt; 0.01). Conclusions: a high dose of neutrophil-depleted PRP is an effective treatment for KL1-3 KOA. It provides symptomatic relief, can potentially reduce disease progression, and has sustained effects for up to 12 months.

The Hepatitis B virus, chronically infects over 240 million persons worldwide. The Hepatitis B vaccine is 90% effective in preventing perinatal transmission if the first dose is given within the first 24 hours of life followed by a minimum of 2 subsequent doses. In October 2021, Antigua and Barbuda, through it’s only public hospital - the Sir Lester Bird Medical Centre, instituted a hospital based Hepatitis B vaccine birth dose policy. Timely birth dose coverage was 72% and total birth dose coverage 81%. 10.5% of parents refused the hepatitis b – birth dose, of which 76% either felt uncomfortable or preferred to wait. 100% of babies born before arrival received timely vaccine administration, likewise 100% of Hepatitis B exposed babies were vaccinated, with 83% of them receiving the Hepatitis B Immunoglobulin. A maternal Hepatitis B surface antigen result was available for 90.4% of mothers. Barriers to timely birth dose administration included vaccination hesitancy, gaps in healthcare worker knowledge, and the consistent supply of Hepatitis B vaccine. Instituting a quality improvement team, health information system, robust educational efforts, and addressing barriers will make achieving the WHO programmatic targets of eliminating mother to child transmission of hepatitis B by 2030 possible.

To determine the impacts of metabolizable energy levels on the performance indices of geese and to forecast the ideal range of dietary metabolizable energy levels, this study was carried out. Literature on the effects of dietary metabolized energy level on the performance of geese was searched from CNKI, Wanfang, VIP, PubMed, Web of Science, and ScienceDirect databases from January 1, 2000, to December 31, 2022. A dose-response meta-analysis was performed by STATA (14.0), data were calculated by the robust error meta-regression model (REMR), and nonlinear dose-effect curves were plotted by the restricted cubic spline method (RCS). 29 papers were chosen from the 1,475 literatures that fit the criteria and were included in the dose-response meta-analysis. There were 6,079 geese included in the sample. The following production performance indices included average daily gain (ADG), average daily feed intake (ADFI), feed-to-gain ratio (F/G), dressed percentage, percentage of half-eviscerated yield, percentage of eviscerated yield, percentage of breast muscle, percentage of leg muscle and percentage of abdominal fat. The Egger test assessed publication bias, while sensitivity analysis was used to examine the heterogeneity. The verified results are consistent and reliable. The results indicated that for each group, the optimal dietary metabolizable energy level was about 13 to 13.5MJ/kg for medium-sized geese aged 0 to 4 weeks, 12 to 13MJ/kg for medium-sized geese aged above 5 weeks, 12.5 to 13MJ/kg for small-sized geese aged 0 to 4 weeks, and 13 to 13.5MJ/kg for mall-sized geese over 5 weeks of age. Future research should be conducted on related diets of large-sized geese, small-sized geese, and higher metabolizable energy levels.

We present here seven new zircon (U-Th)/He (ZHe) ages and three new zircon fission track ages (ZFT) analyzed from an age-elevation profile (Machu Picchu, Peru). ZFT data present older ages in comparison with the other thermochronological data, whereas the ZHe data interestingly present similar ages than the ones obtained with apatite (U-Th)/He (AHe). It has been proposed that He retention in zircon is linked to the damage dose, with an evolution of the closure-temperature from low values associated to low α-dose (<1016 α/g), subsequently increasing before decreasing again at very high α-dose (>1018 α /g). Studies have been focused on the He diffusion behavior at high α-dose, but little is known at low dose. We propose that the ZHe closure temperature at α-dose ranging from 0.6×1015 to 4×1016 α/g is in the range of ~60-80°C. This value is lower than the one proposed in the current damage model ZRDAAM and demonstrates that the ZHe and AHe methods could have similar closure temperatures at low α-dose (i.e. similar ages). These new data strengthen our previous geological conclusions and even highlight an about twice more important cooling rate than the one deduced from AHe and apatite fission-track data alone registered at Machu Picchu.

Background: Asthma is ranked 16th among the leading causes of years lived with disability and 28th among the leading causes of disease in the world. Metered dose inhaler remains the principal route for drug administration and it has greater advantages over systemic treatment. In routine use, however, a vast majority of patients make inhalation errors. Suboptimal inhaler technique worsens health outcomes, with poor disease control, and increases the risk of hospitalization. This study aimed to assess practice metered-dose inhalation techniques and associated factors among asthmatic patients at Debre Markos comprehensive specialized hospital, East Gojjam, Amhara region, Ethiopia. Methods: Prospective cross-sectional study was conducted from July 15 to August 30/ 2020. Data were collected through a semi-structured questioner. The data was analyzed using SPSS version 25. Associations between dependent and independent variables were assessed by using binary and multiple logistic regressions. P-values less than 0.05 were considered to be statistically significant in all cases. Results presented in tables, figures, numbers, and percentages. Result: A total of 166 patients had involved in the study, of which 52.4% were females. One hundred eleven (66.9%) of participants had good knowledge of asthma and inhalational techniques with the rest of them had poor knowledge. One hundred eight (65.1%) patients had effective practice on metered-dose inhaler use techniques. Participant's knowledge regarding asthma and meter dose inhaler and marital status has a significant association with their practice of metered-dose inhaler techniques with P-value 0.001 and 0.006 respectively. Conclusion: In this study, most participants are suffering from asthma for a long duration and they have repeated exacerbation. Around two-thirds of patients had good knowledge regarding asthma and meter dose inhaler and practice on metered-dose inhaler techniques. Participants who had poor knowledge and who were unmarried had poor practice on tech metered-dose inhaler techniques. Health education and counseling services should be consistently provided to the clients regarding the proper steps of inhalers use.

Background: Superspreading events are important drivers of the SARS-CoV-2 pandemic. By analyzing two outbreaks associated with choir rehearsals in March 2020, we demonstrate the risk of indoor, long-range (LR) transmission and singing, to help prevent similar outbreaks. Methods: We conducted two retrospective cohort studies and obtained demographic, clinical, laboratory and contact data, performed SARS-CoV-2 serology, whole genome sequencing (WGS), calculated LR transmission probabilities, measured particle emissions of selected choir members, and calculated particle air concentrations and inhalation doses.Results: We included 65 (84%) and 42 (100%) members of choirs 1 and 2, respectively. WGS confirmed strain identity in both choirs and the primary case of choir 1 (transmitting presymptomatically). Particle emission rate when singing was 7 times higher compared to talking. In choir 1, the median concentration of primary cases’ emitted particles was 8 times higher, exposure at least 30 minutes longer and room volume smaller than in choir 2, resulting in markedly different estimated probabilities for LR transmission (median: 89% vs. 18%, 95%CI: 80-95% vs. 6-36%). Observed AR in choir 1 (89%) was significantly higher than in choir 2 (24%). According to a risk model, first transmission in choir 1 occurred likely after 7 minutes of singing. The number of inhaled particles emitted by an infectious case, sufficient to infect 50% of exposed, was calculated to 1039-2883 particles (95%CI).Conclusions: Even in large rooms, singing of an infectious person may lead to secondary infections through LR exposure within minutes. Given the potential for presymptomatic infectiousness, greatest caution is required wherever aerosols can accumulate.

Chemotherapy is a standard therapeutic option for triple-negative breast cancer (TNBC); however, its effectiveness is often compromised by drug-related toxicity and resistance development. Herein, we aimed to evaluate whether an improved antineoplastic effect could be achieved in vitro and in vivo in TNBC by combining dovitinib, a multi-kinase inhibitor, with calcitriol, a natural anti-cancer hormone. In vitro, cell proliferation and cell-cycle distribution were studied by sulforhodamine B-assays and flow cytometry. In vivo, dovitinib/calcitriol effects on tumor growth, angiogenesis and endothelium activation were evaluated in xenografted mice by caliper measures, Itgb3-immunohistochemistry and 99mTc-RGD2-tumor uptake. The drug combination elicited a synergistically improved antiproliferative effect in TNBC-derived cells, which allowed a 7-fold dovitinib dose-reduction. Mechanistically, the co-treatment induced cell death and accumulation in S and G2/M phases, while inhibited tumor growth to a greater extent than each compound alone. Tumor uptake of 99mTc-RGD2 was reduced by dovitinib, suggesting angiogenesis inhibition, which was corroborated by decreased endothelial cell growth and tumor vessel density. In summary, calcitriol synergized dovitinib anticancer effects in vitro and in vivo, allowing for a significant dose-reduction of dovitinib, while maintaining its antiproliferative potency. Our results suggest the beneficial convergence of independent antitumor mechanisms of dovitinib and calcitriol to inhibit TNBC-tumor growth.

DNA vaccines are stable, safe, cost effective to produce and relatively quick and easy to manufacture. However, to date DNA vaccines have shown relatively poor immunogenicity in humans despite promising preclinical results. Consequently, a number of different approaches have been investigated to improve the immunogenicity of DNA vaccines. These include the use of improved delivery methods, adjuvants, stronger promoters and enhancer elements to increase antigen expression, and codon optimization of the gene of interest. This review describes the creation and use of a DNA vaccine vector containing a porcine circovirus (PCV-1) enhancer element that significantly increases recombinant antigen expression and immunogenicity and allows for dose sparing. A 172bp region containing the PCV-1 capsid protein promoter (Pcap) and a smaller element (PC; 70 bp) within this were found to be equally effective. DNA vaccines containing the Pcap region expressing various HIV-1 antigens were found to be highly immunogenic in mice, rabbits and macaques, at 4 to 10-fold lower doses than normally used and to be highly effective in heterologous prime-boost regimens. By lowering the amount of DNA used for immunization, safety concerns over injecting large amounts of DNA into humans can be overcome.

The correspondence between classical and quaternion quantum equations, permits considering the universe (vacuum) as an ideal elastic solid. Elementary particles would have to be standing or soliton-like waves. Tension induced by the compression and twisting of the elastic medium would increase the energy density, consequently generate a gravity forcing and affect the wave speed. Consequently the gravity could be described by an index of refraction. Theory was created by combining the Cauchy model of the elastic continuum with the Planck-Kleinert crystal hypothesis. The quaternion-imaginary Lagrange’an, the quaternion motion equation and the quaternionic oscillator allowed deriving: - The Schrödinger equation from the functional integral, which identifies the quaternion-imaginary quantum Hamiltonian. - The 2nd order wave equation system describing both the bosons and the gravity in terms of quaternionic Poisson equation. - The first order quaternionic wave equation system. - The family of the second order wave equation systems describing both the particles and the generated quaternionic force-fields (four-potentials). - The fundamental Planck and gravity constants. - The quaternionic continuity equation in an ideal elastic solid.

We report enhanced nonlinear optics in complementary metal-oxide-semiconductor (CMOS) compatible photonic platforms through the use of layered two-dimensional (2D) graphene oxide (GO) films. We integrate GO films with silicon-on-insulator nanowires (SOI), high index doped silica glass (Hydex) and silicon nitride (SiN) waveguides and ring resonators, to demonstrate an enhanced optical nonlinearity including Kerr nonlinearity and four-wave mixing (FWM). The GO films are integrated using a large-area, transfer-free, layer-by-layer method while the film placement and size are controlled by photolithography. In SOI nanowires we observe a dramatic enhancement in both the Kerr nonlinearity and nonlinear figure of merit (FOM) due to the highly nonlinear GO films. Self-phase modulation (SPM) measurements show significant spectral broadening enhancement for SOI nanowires coated with patterned films of GO. The dependence of GO’s Kerr nonlinearity on layer number and pulse energy shows trends of the layered GO films from 2D to quasi bulk-like behavior. The nonlinear parameter of GO coated SOI nanowires is increased 16 folds, with the nonlinear FOM increasing over 20 times to FOM > 5. We also observe an improved FWM efficiency in SiN waveguides integrated with 2D layered GO films. FWM measurements for samples with different numbers of GO layers and at different pump powers are performed, achieving up to ≈7.3 dB conversion efficiency (CE) enhancement for a uniformly coated device with 1 layer of GO and ≈9.1 dB for a patterned device with 5 layers of GO. These results reveal the strong potential of GO films to improve the nonlinear optics of silicon, Hydex and SiN photonic devices.

With our long experience in the field of unification of gravity and quantum mechanics, we understood that, when mass of any elementary is extremely small/negligible compared to macroscopic bodies, highly curved microscopic space-time can be addressed with large gravitational constants and magnitude of elementary gravitational constant seems to increase with decreasing mass and increasing interaction range. In our earlier publications, we proposed that, 1) There exist three atomic gravitational constants associated with electroweak, strong and electromagnetic interactions; 2) There exists a strong interaction elementary charge in such a way that, it's squared ratio with normal elementary charge is close to inverse of the strong coupling constant; and 3) Considering a fermion-boson mass ratio of 2.27, quarks can be split into quark fermions and quark bosons. Further, we noticed that, electroweak field seems to be operated by a primordial massive fermion of rest energy 584.725 GeV and hadron masses seem to be generated by a new hadronic fermion of rest energy 103.4 GeV. In this context, starting from lepton rest masses to stellar masses, we have developed many interesting and workable relations. With further study, a workable model of final unification can be developed.

The characterization of thin-film solar cells is of huge importance for obtaining high open-circuit voltage and low recombination rates from the interfaces or within the bulk of the main materials. Among the many electrical characterization techniques, the two- and four-wire probe using the Cascade instrument is of interest since the resistance of the wires, and the electrical contacts can be excluded by the additional two wires in 4-wire probe configuration. In this paper, both two and four-point probes configuration are employed to characterize the CIGS chalcogenide thin-film solar cells. The two-wire probe has been used to measure the current-voltage characteristics of the cell which results in a huge internal resistance. Therefore, the four-wire connection is also used to eliminate the lead resistance to enhance the characterization’s accuracy. The load resistance in the two-wire probe diminishes the photogenerated current density at smaller voltage ranges. In contrast, the proposed four-wire probe collects more current at higher voltages due to enhanced carrier collection efficiency from contact electrodes. The current conduction mechanism is also identified at every voltage region represented by the value of the ideality factor of that voltage region. It is observed that a long time given to the charge collection results in increased current density at a higher voltage. According to the results and device characteristics, a novel double-diode model is suggested to extract the saturation current density, shunt and series resistances and the ideality factor of the cells. These cells are shown to be efficient in terms of low recombination at the interfaces and with lower series resistance as the quality of the materials is in its most possible conductive form. The measured internal resistance and saturation current density and ideality factor of the two measurement configuration is measured and compared.

The switched inertance hydraulic system (SIHS) is a novel high-bandwidth and energy-efficient digital device which can adjust or control flow and pressure by a means that does not rely on throttling the flow and dissipation of power. An SIHS can provide an efficient step-up or step-down of pressure or flow rate by using a digital control signal. In this article, analytical models of an SIHS in a four-port high-speed switching valve configuration are proposed, and the system dynamics and performance are investigated theoretically and experimentally. The flow responses, system characteristics and power consumption can be predicted effectively and accurately by using the proposed models, which were validated by comparing with experiments and with numerical simulation. The four-port configuration is compared with the three-port configuration, and it is concluded that the former one is less efficient for valves of the same size, but provides a bi-direction control capability. As bi-direction control is a common requirement, this constitutes an important contribution to the development of efficient digital hydraulics.

The reasons for the circular sense of human color perception generated by two sorts of color opponent neurons and three cone types are not well understood. Here we use geometrical analysis to examine the hypothesis that opponency, the recursive nature of color perception, and trichromacy arise as the most efficient ways of distinguishing spectrally different points on a plane using a minimum of color classes and receptor types.

This paper is concerned with a hydraulic cylinder directly controlled by a variable speed fixed displacement pump. The considered configuration is referred to as a one-motor-one-pump (1M1P) motor-controlled hydraulic cylinder (MCC). A 1M1P MCC with a hydraulically driven passive load-holding function enabled by controlled system pressures is proposed. The proposed load-holding functionality works if there is a standstill command, a loss of power supply, or a hose rupture. Additionally, this paper conducts a comprehensive analysis of the proposed system's operation and load-holding function across four quadrants. Simulation results demonstrate the four-quadrant operation and good load-holding performance under the aforementioned scenarios. In conclusion, the proposed 1M1P MCC can be successfully used on practical applications characterized by overrunning loads and four quadrant operation.

We report the use of four-layer graphene (4LG) as a highly reliable transparent conductive electrode (TCE) for polymer-dispersed liquid crystal (PDLC)-based smart window devices. The adhesion between 4LG and the substrate was successfully improved through a water-induced interface-cleaning (WIIC) process. We compared the performance of a device with a WIIC-processed 4LG electrode with that of devices with a conventional Indium tin oxide (ITO) electrode and a 4LG electrode without a WIIC. With the application of the WIIC process, the PDLC smart window with a 4LG electrode exhibited reduced turn-on voltage and haze compared to 4LG without the WIIC process and characteristics comparable to those of the ITO electrode. Based on our observations, we conclude that 4LG with WIIC is a promising TCE for flexible smart windows.

Recently, cobalt iron boron (CoFeB) thin films have been widely investigated to apply to magnetic sensors, due to their high magnetic moment, anisotropy, and stability. However, most of these studies are conducted on rigid silicon substrates. For more diverse applications of magnetic sensors and angle sensors, it is important to explore the properties of ferromagnetic thin films grown on non-rigid deformable substrates. Here, using representative deformable substrates such as polyimide (PI), polyethylene naphthalate (PEN) and polydimethylsiloxane (PDMS) that can be bent or stretched, we report experimental comparison of in-plane magnetic field angle-dependent properties of the amorphous Ta/CoFeB/MgO/Ta thin film which is grown on those deformable substrates. We investigate effects of substrate roughness, tensile stress, characteristics of deformable substrates, and sputtering process on the change of magnetic properties like coercive field (Hc), remanence over saturation magnetization (Mr/Ms), and their biaxial characteristics. This work presents unconventional foundations for exploring deformable magnetic sensors capable of detecting magnetic field angle.

We compare several different measures of non-Gaussianity for two families of four-photon superpositions of the Fock states: even vacuum squeezed states and orthogonal-even coherent states.

Layered two-dimensional (2D) graphene oxide (GO) films are integrated with micro-ring resonators (MRRs) to experimentally demonstrate enhanced nonlinear optics in the form of four-wave mixing (FWM). Both uniformly coated and patterned GO films are integrated on CMOS-compatible doped silica MRRs using a large-area, transfer-free, layer-by-layer GO coating method together with photolithography and lift-off processes, yielding precise control of the film thickness, placement, and coating length. The high Kerr nonlinearity and low loss of the GO films combined with the strong light-matter interaction within the MRRs results in a significant improvement in the FWM efficiency in the hybrid MRRs. Detailed FWM measurements are performed at different pump powers and resonant wavelengths for the uniformly coated MRRs with 1−5 layers of GO as well as the patterned devices with 10−50 layers of GO. The experimental results show good agreement with theory, achieving up to ~7.6-dB enhancement in the FWM conversion efficiency (CE) for an MRR uniformly coated with 1 layer of GO and ~10.3-dB for a patterned device with 50 layers of GO. By fitting the measured CE as a function of pump power for devices with different numbers of GO layers, we also extract the dependence of GO’s third-order nonlinearity on layer number and pump power, revealing interesting physical insights about the evolution of the layered GO films from 2D monolayers to quasi bulk-like behavior. These results confirm the high nonlinear optical performance of integrated photonic resonators incorporated with 2D layered GO films.

To understand the mystery of final unification, in our earlier publications, we proposed that there exist three atomic gravitational constants associated with electroweak, strong and electromagnetic interactions. During cosmic evolution, if one is willing to give equal importance to Higgs boson and Planck mass in understanding the massive origin of elementary particles, then it seems quite logical to expect a common relation in between Planck scale and Electroweak scale. Based on these two points, we noticed that, electroweak field seems to be operated by a primordial massive fermion of rest energy 585 GeV. It can be considered as the zygote of all elementary particles and galactic dark matter. H-bar seems to be a characteristic outcome of unified electroweak gravity. Electron rest mass seems to be a characteristic outcome of electroweak and strong gravity. Proton rest mass seems to be a characteristic outcome of electroweak, strong and electromagnetic gravity. Recently observed 3.5 keV photon seems to be an outcome of annihilation of charged baby lepton of rest energy 1.75 keV. Interesting point to be noted is that, Schwarzschild radius of electron is 0.48 nanometer and it needs further investigation with respect to emerging nano-science and technology. Proceeding further, by considering electromagnetic and weak gravitational constants, neutron life time can be understood.

An investigation was made to determine the effects of tungsten surface coating on the coefficient of friction of sliding contact between lubricated steel surfaces. The four-ball test was modified, using a tungsten carbide ball bearing in the spindle to cause sliding contact onto three hard steel ball bearings coated with tungsten disulfide lamellar dry lubricant coating, with a coating of grease lubrication applied to the ball bearings. The coatings, loads, speed, and grease level was varied to best understand the impact of different conditions to the friction coefficient.

Cannabidiol (CBD), a non-psychotropic main component of the Cannabis plant, is approved as a drug in the European Union (EU) under the name “Epidyolex”. However, the approval process as a food ingredient under the Novel Food Regulation was paused by the European Food Safety Authority (EFSA) due to a lack of safety data. Nevertheless, there is a growing, unregulated market in which CBD is advertised with various health claims and different dosage instructions. Of particular concern is its toxic effect on the liver and possible reproductive toxicity in humans. Studies suitable for calculating a benchmark dose were identified from the available data. Animal studies yielded a Benchmark Dose Lower Confidence Limit (BMDL) of 43 mg/kg bw/day, which translates into a safe human dose of approximately 15 mg/day. Only a Lowest Observed Adverse Effect Level (LOAEL) of 4.3 mg/kg bw/day could be identified from the human data. This updated risk assessment confirmed the Health-based Guidance Value (HBGV) of 10 mg/day based on human LOAEL. Despite existing data gaps, preliminary regulation appears advisable as the current form of the gray CBD market is unacceptable from the standpoint of consumer safety and protection.

Abstract: Effectiveness of a Single Fixed Dose 3 mg Rasburicase for Prevention and Management of Hyperuricemia of Tumor Lysis Syndrome in adult Cancer Patients Background: Tumor lysis syndrome (TLS) is a potentially life-threatening complication associated with certain types of cancer. Rasburicase is an essential medicine required to prevent and treat the hyperuricemia associated with TLS. Due to a shortage of rasburicase during the COVID-19 pandemic, a fixed dose strategy of 3 mg rasburicase had been used in many adult cancer patients in our center. Objective: The objective of this study was to assess the effectiveness of a 3 mg fixed dose of rasburicase in preventing and managing hyperuricemia associated with TLS in adult cancer patients. Methods: We conducted a retrospective, observational cohort study between March 2020 and November 2022. The study included adult patients who received a fixed dose of 3 mg rasburicase. The primary outcome measure was the reduction in serum UA levels of

The purpose of this study was to determine the maximum tolerated dose (MTD) for stereotactic body radiation therapy (SBRT) in the treatment of non-metastatic prostate cancer. This study was a phase 1 dose escalation trial conducted in Japan. Patients with histologically proven prostate cancer without lymph node or distant metastasis were enrolled. The prescribed doses were 42.5, 45, or 47.5 Gy in five fractions. Dose-limiting toxicity (DLT) was defined as grade (G) 3+ gastrointestinal or genitourinary toxicity within 180 days after SBRT completion and a 6 plus 6 design was used as the method of dose escalation. A total of 16 patients were enrolled, with 6 in the 42.5 Gy group and 10 in the 45 Gy group. No DLT was observed in the 42.5 Gy group. In the 45 Gy group, one patient experienced G3 rectal hemorrhage, and another had G4 rectal perforation, leading to the determination of 42.5 Gy as the MTD. None of the patients experienced biochemical recurrence or death during the follow-up period. We concluded that SBRT for non-metastatic prostate cancer at 42.5 Gy in 5 fractions could be safely performed, but a total dose of 45 Gy increased severe toxicity.

(1) Background: “Zero-dose” (ZD) refers to a child not receiving any doses of the pentavalent (diphtheria-tetanus-pertussis-Haemophilus influenzae type b (Hib)-Hepatitis B) vaccine in the routine national immunization schedule. These children are vulnerable to vaccine-preventable diseases (VPDs), and are often already disadvantaged due to poverty, conflict, and lack of access to basic health services. The Luambo health district (HD) is one of the 26 HDs in the Kasai Central Province and has the largest number of ZD children. This study was conducted to examine the factors associated with ZD status in the Luambo HD; (2) Methods: We conducted a mixed study of children aged 12-23 months in the Luambo HD in the Kasai Central Province; (3) Results: A total of 445 children aged 12-23 months were included in the study, including 89 cases and 356 controls. Correlates of zero dose (ZD) status in children aged 12-23 months were mothers who were not receiving Antenatal Care (ANC), of not knowing any VPD, the fact of the children being born in Angola and the fact of the children being born at home. In addition, the perceptions of children’s parents influenced child immunization; (4) Conclusions: Missing ANC services during pregnancy leads to home delivery with consequences being lack of knowledge on childhood’s VPD and subsequently children not being vaccinated.

We aimed to investigate the clinical results following poor-quality embryo transfer and the parameters to foresee the prognosis. In this study, 2123 cycles that had day 3 and day 5 single-fresh embryo with a poor-quality embryo transfers and a good-quality embryo transfers were compared. The cycles according to transfer day were evaluated by conducting a subgroup analysis. The correlation between all the obtained demographic characteristics, controlled ovarian stimulation parameters and cycle results were analysed. Clinical pregnancy was established in 53 patients that underwent transfer in the poor-quality embryo group (14.9%). Of these patients, 36 had live birth (live birth rate per clinical pregnancy 67.9%). In cleavage-stage embryos, live birth rates per clinical pregnancy were higher in poor-quality blastocyst transfer. When analysing the factors affecting live births in poor-quality embryo group, as the total gonadotropin dose increases, the probability of live birth decreases, as in the probability of hCG positivity. In conclusion; although the probability of pregnant is low, when clinical pregnancy is established, there is a high chance of having a live birth after poor-quality embryo transfers. This could be regarded as an acceptable option in cycles when only poor-quality embryos were available.

This work presents patient radiation dose data for pediatric interventional cardiology procedures in a large hospital in Colombia. The data collection period was from April 2020 to July 2022. The local DRLs were calculated as the 3rd quartile of patient dose data distributions for kerma area-product (Pka) values. The sample of collected clinical procedures (255) was divided into diagnostic and therapeutic procedures and grouped into five weight and five age bands. The Pka differences found between diagnostic and therapeutic procedures were statistically in all weight and age bands, except the group between 1-5 years. The local DRLs were 69 Gy/cm2 (< 5 kg), 3.44 Gy/cm2 (5-<15 kg), 8.87 Gy/cm2 (15-<30 kg), 10.51 Gy/cm2 (30-<50 kg) y 22.61 Gy/cm2 (50-<80 kg), respectively. In conclusion, from comparing our results with other existing DRL values, we are similar to other centers and scope to continue optimizing the radiation dose values. This will contribute to setting national diagnostic reference levels (DRLs) for Colombia in the near future.

The papaya mealybug Paracoccus marginatus is an invasive, polyphagous pest and poses a quarantine threat to tropical and subtropical countries. Infested commodity internationally should be undergoing phytosanitary treatment, while irradiation is recommended to replace methyl bromide fumigation. Dose-response tests were conducted on the 2-, 4-, and 6-d-old eggs and gravid females of P. marginatus using the X-ray radiation doses of 15–105 Gy with an interval of 15 Gy, respectively. Radiotolerance was compared using fiducial overlapping and lethal dose ratio (LDR) test, resulting in insignificant difference except for LDR test at LD90 (leading 90% mortality at 95% confidence level (CL)); the estimated dose for 99.9968% mortality at 95% CL was 176.5–185.2 Gy, which was validated in the confirmatory tests using gamma irradiation because gammy and X-rays have equal biological effect on pests. Therefore, a total of estimating 60,386 gravid females of papaya mealybug irradiated with 146.8–185.0 Gy resulted in no F1 nymphs developing. Eggs can therefore be used as an alternative to gravid females for dose-response tests; the recommended minimum dose for phytosanitary treatment of P. marginatus on infested commodity is 185 Gy, with treatment efficacy ≥ 99.9950% at 95% CL.

Angiogenesis is new blood vessel formation from existing vessels and is a critical first step in tissue repair following chronic disturbances in healing and degenerative tissues. Chronic pathoanatomic tissues are characterized by a high number of inflammatory cells, overexpression of inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1), the presence of mast cells, T cells, reactive oxygen species, and matrix metalloproteinases, and a decreased angiogenic capacity. Multiple studies have demonstrated that autologous orthobiological cellular preparations (e.g., platelet-rich plasma [PRP]) im-prove tissue repair and regenerate tissues. There are many PRP devices on the market. Unfortunately, they differ greatly in platelet numbers, cellular composition, and bioformulation. PRP is a platelet concentrate consisting of a high concentration of platelets with or without certain leukocytes, platelet-derived growth factors (PGFs), cytokines, molecules, and signaling cells. Several PRP products have immunomodulatory capacities that can influence resident cells in a diseased microenvironment, inducing tissue repair or re-generation. Generally, PRP is a blood-derived product, regardless of its platelet number and bioformulation, and the literature indicates both positive and negative patient treatment outcomes. Strangely, the literature does not designate specific PRP preparation qualifications that can potentially contribute to tissue re-pair. Moreover, the literature scarcely addresses the impact of platelets and leukocytes in PRP on (neo)angiogenesis other than a general one-size-fits-all statement that “PRP has angiogenic capabilities.” Here, we review the cellular composition of all PRP constituents, including leukocytes, and describe the importance of platelet dosing and bioformulation strategies in orthobiological applications to initiate angiogenic pathways that re-establish microvasculature networks, facilitating the supply of oxygen and nutrients to impaired tissues.

The combination of non-steroidal anti-inflammatory drugs (NSAIDs) with non-opioid analgesics is common in clinical practice for the treatment of acute pain conditions like post-operative and post-traumatic pain. Besides that, and despite the very satisfactory results achieved by oral analgesics, parenteral analgesia is a key tool in the treatment of painful conditions when the enteral routes are not convenient. The parenteral ready-to-use fixed-dose combinations of NSAIDs with non-opioid analgesics like paracetamol or metamizole could play a central role in the treatment of painful conditions since they are able to gather into only one formulation the advantages of multimodal and parenteral analgesia. Surprisingly, only very recently a parenteral ready-to-use fixed-dose combination of Ibuprofen/Paracetamol was launched to the market. This review aims to review the current availability of NSAID-based Parenteral Fixed-dose combinations with paracetamol and metamizole in the European and American markets, and how the combination of such drugs could play a central role in a multimodal analgesia strategy. Also, it is explored how the parenteral formulations of NSAIDs, paracetamol, and metamizole could serve as starting elements for the development of new parenteral ready-to-use fixed-dose combinations. With this review, we concluded that, despite the well-recognized utility of combining NSAIDs with non-opioid analgesics, there are in the literature several randomized clinical trial studies unable to demonstrate clear advantages concerning their efficacy and safety. In the future, it is deemed necessary to perform clinical trials specifically designed to assess the efficacy and safety of these fixed-dose formulations to generate solid evidence of their clinical advantages.

Polybrominated diphenyl ethers (PBDE) are a group of flame retardants used in a variety of artificial materials. Despite phasing out in most industrial countries, they persist in the environment and human tissues due to their persistence, lipophilicity, and bioaccumulation. Populational and experimental studies demonstrate male reproductive toxicity of PBDEs including increased incidence of genital malformations (hypospadias and cryptorchidism), altered weight of testes and other reproductive tissues, altered testes histology and transcriptome, decreased sperm production and sperm quality, altered epigenetic regulation of developmental genes in spermatozoa and altered secretion of reproductive hormones. A broad range of mechanistic hypotheses of PBDE reproductive toxicity has been suggested. Among these hypotheses, oxidative stress, disruption of estrogenic signaling, and mitochondria disruption are affected by PBDE concentrations much higher, than concentrations found in human tissues, making them unlikely links between exposures and adverse reproductive outcomes in the general population. Robust evidence suggests that at environmentally relevant doses, PBDEs and their metabolites may affect male reproductive health via mechanisms including AR antagonism and the disruption of a complex network of metabolic signaling.

The main aspects of material research: material synthesis, material structure, and material properties, are interrelated. Acquiring atomic structure information of electron beam sensitive materials by electron microscope, such as porous zeolites, organic-inorganic hybrid perovskites, metal-organic frameworks, is an important and challenging task. The difficulties in characterization of the structures will inevitably limit the optimization of their synthesis methods and further improve their performance. The emergence of integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM), a STEM characterization technique capable of obtaining images with high signal-to-noise ratio under lower doses, has made great breakthroughs in the atomic structure characterization of these materials. This article reviews the developments and applications of iDPC-STEM in electron beam sensitive materials, and provides an outlook on its capabilities and development.

To resolve the controversial issues of UV-light-initiatedcornealcollagen cross-linking (CXL) by theoretical formulas and measured clinical outcomes. The controversial issues are addressed and resolved by analytical formulas including: the validation of Bunsen Roscoe law (BRL), the cutoff light intensity, the minimum corneal thickness, the demarcation line depth, the role of oxygen riboflavin (RF) concentration. The overall CXL efficacy is governed by UV-A light intensity, dose, exposure time, mode of exposure (pulsed or CW), riboflavin concentration, diffusion and drops pre-operation and interoperation administration, concentration of oxygen in the stromal tissue (pre-op and inter-op), and environmental conditions. The length of the riboflavin presoaking time and viscosity of the riboflavin film also affect the crosslink depth. Analytic formulas are derived for the scaling laws for type-I and type-II efficacy, given by the square-root of light intensity, and light dose, respectively. The controversial issues of CXL may be partially resolved via analytic formulas, and compared with measurements. The scaling laws of type-I and type-II efficacy are different and given by analytic formulas. Our formulas also predict the maximum light intensity and the minimum corneal thickness, which are consistent with measurements.

The major stress-inducible Hsp70 (HSPA1A) is overexpressed in the cytosol of many highly aggressive tumor cells including glioblastoma multiforme and presented on their plasma membrane. Depending on its intracellular or membrane localization, Hsp70 either promotes tumor growth or serves as a target for NK cells. The kinetics of the membrane Hsp70 (mHsp70) density on human glioma cells (U87) was studied after different irradiation doses to define the optimal therapeutic window for Hsp70-targeting NK cells. To maintain the cells in the exponential growth phase during a cultivation period of 7 days different initial cell counts were seeded. Although cytosolic Hsp70 levels remained unchanged on days 4 and 7 after a sublethal irradiation with 2 Gy, 4 Gy and 6 Gy, a dose of 2 Gy resulted in an upregulated mHsp70 density in U87 cells which peaks on day 4 and starts to decline on day 7. Higher radiation doses (4 Gy, 6 Gy) resulted in an earlier and more rapid onset of the mHsp70 expression on days 2 and 1, respectively, followed by a decline on day 5. Membrane Hsp70 levels are higher in G2/M than in G1, however, an irradiation-induced cell cycle arrest on days 4 and 7, was not associated with an increase in the mHsp70 density. Extracellular Hsp70 concentrations increased significantly compared to sham (0 Gy) irradiated cells on days 4 and 7 but not on day 1. Functionally, elevated mHsp70 densities were associated with a significantly better lysis by Hsp70-targeting NK cells. In summary, the kinetics of changes in the mHsp70 density upon irradiation on tumor cells is time- and dose-dependent.

There is a lack of data comparing sugammadex with anticholinesterase for the quality of anaesthesia recovery, especially following a single bolus dose of rocuronium. Thus, we evaluated the influence of reversal with sugammadex or neostigmine on post-operative quality of recovery by using the Post-operative Quality Recovery Scale (PQRS). A total of 86 patients undergoing trans-pars plana vitrectomy (TPPV) under general anaesthesia were intubated following a single bolus dose of rocuronium (0.6 mg/kg). At the end of surgery, patients were received either neostigmine or sugammadex. The quality of recovery was assessed using the PQRS at 15 minutes and 40 minutes after surgery, and on post-operative day 1. The recovery rate in the physiological domain was higher in the sugammadex group at 15 minutes after surgery (P = 0.02). Though there were no significant differences in the overall cognitive recovery domain, patients in the sugammadex group could recall more numbers in reverse order. However, there were no significant differences between the groups in the other domains of the PQRS. The use of sugammadex may increase the quality of the post-operative physiological recovery at early post-operative periods compared with neostigmine use following a single bolus dose of rocuronium in patients undergoing TPPV with general anaesthesia.

The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults (aged 60-75 years) received a single administration of 100, 150 or 200 mg/kg body weight of tyrosine. For comparison, 17 young adults (aged 18-35 years) received a dose of 150 mg/kg body weight of tyrosine. Tyrosine plasma concentrations were determined before and 90, 120, 150, 180, 210 and 240 minutes after tyrosine intake. Working memory was assessed using the N-back task at 90 minutes after tyrosine administration. Older adults showed a dose-dependent increase in plasma tyrosine concentrations (p<.001), and the plasma response was higher than for young adults with the same dose (p<.001). Load-dependent working memory performance decreased with higher doses of tyrosine (p=.048), especially in older adults with greater dose-dependent plasma tyrosine responses (p=.035). Our results show an age-related increase in plasma tyrosine response, which was associated with a dose-dependent decline in cognitive functioning in older adults.

We review some recent developments about strongly interacting relativistic Fermi theories in three spacetime dimensions. These models realize the asymptotic safety scenario and are used to describe the low-energy properties of Dirac materials in condensed matter physics. We begin with a general discussion of the symmetries of multi-flavor Fermi systems in arbitrary dimensions. Then we review known results about the critical flavor number $N_\mathrm{crit}$ of Thirring models in three dimensions. Only models with flavor number below $N_\mathrm{crit}$ show a phase transition from a symmetry-broken strong-coupling phase to a symmetric weak-coupling phase. Recent simulations with chiral fermions show that $N_\mathrm{crit}$ is smaller than previously extracted with various non-perturbative methods. Our simulations with chiral SLAC fermions reveal that for four-component flavors $N_\mathrm{crit}=0.80(4)$. This means that all reducible Thirring models with $\Nr=1,2,3,\dots$ show no phase transition with order parameter. Instead we discover footprints of phase transitions without order parameter. These new transitions are probably smooth and could be used to relate the lattice Thirring models to Thirring models in the continuum. For a single irreducible flavor, we provide previously unpublished values for the critical couplings and critical exponents.

Locally advanced rectal cancer requires multimodal treatment. Radiotherapy is being explored for intensification to improve rates of pathological complete responses (ypCR-rates) that correlates with better outcomes. This study reports a comparison between standard versus escalated dose in preoperative scenario. YpCR-rates, toxicity, postoperative complications, disease-free and overall survival at 5 years have been described. From 2012 to 2019, 99 patients were analyzed retrospectively: standard arm (mean 47.5Gy) vs. dose-escalated arm (mean 54.3Gy). All patients were treated with 3DRT in 25 fractions, concomitantly capecitabine and surgery performed according to total mesorectal excision principles in both arms. YpCR was reported by “College of American Pathologist grades”; gastrointestinal (GI) and genitourinary (GU) toxicity using the “Common Terminology Criteria for Adverse Events” (CTCAE 4.0). YpCR-rates were higher in the dose-escalated group (25% vs. 10.64%; p = 0.07) with a lower rate of non-treatment response (61.36% vs. 38.64%; p = 0.11). No statistical differences between arms were found in terms of oncological outcomes, all postoperative complications (p = 0.15), second surgeries (p = 0.62), or deaths (p = 0.62). CTCAE acute-GI and GU toxicity were grade I or II in both arms. Our study shows that the dose-escalated scheme is safer and obtains higher ypCR-rates.