The Bacillus Calmette-Guérin (BCG) vaccine has been used for over one hundred years to protect against the most lethal infectious agent in human history, tuberculosis. Over four billion BCG doses have been given and, worldwide, most newborns receive BCG. A few countries, including the United States, did not adopt the WHO recommendation for routine use of BCG. Moreover, within the past several decades, most of Western Europe and Australia, having originally employed routine BCG, have discontinued its use. This review article articulates the impacts of those decisions. The associated consequences include increased tuberculosis, increased infections caused by non-tuberculous mycobacteria (NTM), increased autoimmune disease (autoimmune diabetes and multiple sclerosis) and increased neurodegenerative disease (Parkinson’s disease and Alzheimer’s disease). This review also offers an emerged zoonotic pathogen, Mycobacterium avium ss. paratuberculosis (MAP) as a mostly unrecognized NTM that may have a causal role in some, if not all, of these diseases. Current clinical trials with BCG for varied infectious, autoimmune and neurodegenerative diseases have brought this century-old vaccine to the fore due to its presumed immuno-modulating capacity. With its historic success and strong safety profile, the new and novel applications for BCG may lead to its universal use –putting the Western World back onto the road not taken.

The emergence of proteins in the prebiotic world was a watershed event at the origin of life. With their astonishing versatility, the protein enzymes catalyzed crucial biochemical reactions within protocells into more complex biomolecules in diverse metabolic pathways, whereas structural proteins provided strength and permeability in the cell membrane. Five major biochemical innovations followed in succession after availability of various kinds of protein molecules during decoding and translation of mRNAs. These are: (1) the modification of the phospholipid membrane into the plasma membrane; (2) the origin of primitive cytoplasm; (3) primitive gene regulation; (4) the beginnings of the virus world; and (5) the advent of DNA. The creative role of viruses during prebiotic synthesis led to the origin of the DNA world, when DNA replaced mRNA as the major genome of the protocells. With the advent of DNA, replication of information was entirely dissociated from its expression. Because DNA is much more stable than mRNA with more storage capacity, it is a superb archive for information systems in the form of base sequences. DNA progressively took over the replicative storage function of mRNA, leaving the latter for protein synthesis. Genetic information began to flow from DNA to mRNA to protein in a two-step process involving transcription and translation. In the biological stage, DNA replication was central to the binary fission of the first cell, orchestrated by the duplication of genomes and then the division of the parent cell into two identical daughter cells. With the onset of binary fission, the population of primitive cells grew rapidly in the hydrothermal vent environment, undergoing Darwinian evolution and diversification by mutation. The habitat of the earliest fossil record (≥ 3.5 Ga) from the Archean sedimentary rocks of Canada, Greenland, Australia, South Africa, and India offers a new window on the early radiation of microbial life. The development of anoxygenic and then oxygenic photosynthesis from early hyperthermophiles would have allowed life to escape the hydrothermal setting to the mesophilic global ocean.

The Van der Pol oscillator is a chaotic non-linear system. Small perturbations in initial conditions may result in wildly different trajectories. Because of its chaotic nature, controlling, or forcing, the behavior of a Van der Pol oscillator is difficult to achieve through traditional adaptive control methods. Connecting two Van der Pol oscillators together where the output of one oscillator, the driver, drives the behavior of its partner, the responder, is a proven technique for controlling the Van der Pol oscillator. Deterministic AI (DAI) is an adaptive feedback control method that leverages the known physics of the Van der Pol system to learn optimal system parameters for the forcing function. We assessed the performance of DAI employing three different online parameter estimation algorithms. Our evaluation criteria include mean absolute error (MAE) between the target trajectory and the response oscillator trajectory over time. RLS with exponential forgetting (RLS-EF) had the lowest MAE overall, with a 2.46% reduction in error. However, another method was notable. Least Mean Squares with normalized gradient adaptation (LMS-NG) had worse initial error in the first 10% of the simulation, but after that point had consistently better performance. We found that over the last 90% of the simulation, DAI with LMS-NG had a 48.7% reduction in MAE compared to feedforward alone.

The main objective of this communication is to describe the ‘Global Salt Cycle’. Giant salt accumulations are commonly found along continental margins of former rifts. The first stage in the accumulation process is saturation of newly formed oceanic crust with seawater. Final mobilisation and accumulation of the salts occurs during rifting, localised in the vicinity of relict subduction zones. Oceanic crust is created along the spreading ridges in the deep oceans of the Earth. It exchanges mass and energy with seawater in hydrothermal circulation cells that penetrate deep into the new and fractured crust. Water-rock interactions include the formation of hydrated and hydroxylated minerals, e.g., serpentinites and clay minerals. By incorporating hydroxyl groups and water in their crystal lattices, the salinity of remaining brines increases. Subduction of oceanic crust and serpentinised lithosphere transports water, hydrated minerals, and marine salts deep into the crust and mantle. Upon pressurisation and heating of the subducting slab, different parts of this water are expelled at different depths/temperatures. The resulting fluids will contain salts brought in with the slab, as well as new salts formed by water-rock interaction. The combination of elevated pressures and temperatures, water, salinity, and CO2, create permeability in the normally impermeable, peridotitic mantle, by altering the fluid-rock dihedral angles of mineral grains. This P/T-determined intergranular permeability allows ascent of saline fluids, under lithostatic pressure, within the mantle wedge, or the slab itself. The fluids produce a mechanically weakened and buoyant zone within the mantle wedge due to high pore pressure between mineral grains and reduced mantle density. During the lifetime of a subduction zone, a substantial accumulation of saline fluids within the mantle wedge and crust, is evident. Deep, fluid reservoirs accumulate between the subduction trench and the volcanic front. They may exist for hundreds of millions of years, even after the extinction of the subduction zone. Saline fluids may escape to the surface along deep faults, due to overfilling of available pores/fractures. Fluids within the mantle wedge may form rock melts or exist as supercritical, mineral rich fluids. The combination of reduced pressure due to rifting, and a saline and buoyant mantle, creates a mantle circulation that brings the accumulated, saline fluids, to crustal levels. Salts will therefore accumulate during initial stages of rifting as a result of massive fluid expulsion, phase change and boiling of mantle fluids. No extra energy is required to produce phase change and boiling. The result is formation of solid salts or dense brines/slurries invading fractured crustal rocks, or escaping to the surface/seabed. This process may take place both before and after the sea has invaded a continental rift.