Treatment of Tuberculous Meningitis and Its Complications in Adults.

PURPOSE OF REVIEW: Tuberculous meningitis (TBM) is a global health problem. In this review, we systematically evaluate the evidence for current and emerging antimicrobials, host-directed therapies and supportive managements. RECENT FINDINGS: Current antimicrobial regimes do not factor the differing ability of drugs to cross the blood-brain barrier. Rifampicin may be more effective at higher doses yet the most recent clinical trial failed to demonstrate survival benefit at 15 mg/kg/day. Dose finding studies suggest that higher doses still may be safe and more effective. Fluoroquinolones are currently listed as important second-line agents in drug-resistant TBM; however, a survival benefit as a first-line agent has yet to be shown. Linezolid may be a promising antimicrobial with good central nervous system penetrance. Dexamethasone reduces mortality in HIV-uninfected individuals yet evidence for its use in HIV co-infection is lacking. Aspirin has anti-inflammatory and anti-thrombotic properties. Small studies have demonstrated efficacy in reducing stroke but further research is required to better understand its effect on controlling the host inflammatory response. Discovery of genetic polymorphisms may direct individualized immune therapies and mediators of the innate immune response may provide targets for the development of novel therapies. There is at present no significant evidence base to guide management of hydrocephalus in HIV co-infection. Further clinical trial data is required to improve treatment outcomes in TBM in particularly in regard to the value of high-dose rifampicin, newer antimicrobials with improved central nervous system penetration and host-directed therapies. Supportive measures in particular the management of hydrocephalus in HIV co-infection should be an area for future research

Ion Pair-Directed Regiocontrol in Transition-Metal Catalysis: A Meta-Selective C-H Borylation of Aromatic Quaternary Ammonium Salts

The use of noncovalent interactions to direct transition-metal catalysis is a potentially powerful yet relatively underexplored strategy, with most investigations thus far focusing on using hydrogen bonds as the controlling element. We have developed an ion pair-directed approach to controlling regioselectivity in the iridium-catalyzed borylation of two classes of aromatic quaternary ammonium salts, leading to versatile meta-borylated products. By examining a range of substituted substrates, this provides complex, functionalized aromatic scaffolds amenable to rapid diversification and more broadly demonstrates the viability of ion-pairing for control of regiochemistry in transition-metal catalysis.Engineering and Physical Sciences Research Council and Pfizer (CASE studentship), AstraZeneca (AZ-Cambridge Ph.D. Program studentship), Royal Society (University Research Fellowship), Engineering and Physical Sciences Research Council and Engineering and Physical Sciences Research Council U.K. National Mass Spectrometry Facility (Swansea University

Matching structure and bargaining outcomes in buyer–seller networks

We examine the relationship between the matching structure of a bipartite (buyer-seller) network and the (expected) shares of the unit surplus that each connected pair in this network can create. We show that in different bargaining environments, these shares are closely related to the Gallai-Edmonds Structure Theorem. This theorem characterizes the structure of maximum matchings in an undirected graph. We show that the relationship between the (expected) shares and the tructure Theorem is not an artefact of a particular bargaining mechanism or trade centralization. However, this relationship does not necessarily generalize to non-bipartite networks or to networks with heterogeneous link values

The Precursors and Products of Justice Climates: Group Leader Antecedents and Employee Attitudinal Consequences

Drawing on the organizational justice, organizational climate, leadership and personality, and social comparison theory literatures, we develop hypotheses about the effects of leader personality on the development of three types of justice climates (e.g., procedural, interpersonal, and informational), and the moderating effects of these climates on individual level justice- attitude relationships. Largely consistent with the theoretically-derived hypotheses, the results showed that leader (a) agreeableness was positively related to procedural, interpersonal and informational justice climates, (b) conscientiousness was positively related to a procedural justice climate, and (c) neuroticism was negatively related to all three types of justice climates. Further, consistent with social comparison theory, multilevel data analyses revealed that the relationship between individual justice perceptions and job attitudes (e.g., job satisfaction, commitment) was moderated by justice climate such that the relationships were stronger when justice climate was high

Minsky machines and algorithmic problems

This is a survey of using Minsky machines to study algorithmic problems in semigroups, groups and other algebraic systems.Comment: 19 page

Retrograde semaphorin-plexin signalling drives homeostatic synaptic plasticity.

Homeostatic signalling systems ensure stable but flexible neural activity and animal behaviour. Presynaptic homeostatic plasticity is a conserved form of neuronal homeostatic signalling that is observed in organisms ranging from Drosophila to human. Defining the underlying molecular mechanisms of neuronal homeostatic signalling will be essential in order to establish clear connections to the causes and progression of neurological disease. During neural development, semaphorin-plexin signalling instructs axon guidance and neuronal morphogenesis. However, semaphorins and plexins are also expressed in the adult brain. Here we show that semaphorin 2b (Sema2b) is a target-derived signal that acts upon presynaptic plexin B (PlexB) receptors to mediate the retrograde, homeostatic control of presynaptic neurotransmitter release at the neuromuscular junction in Drosophila. Further, we show that Sema2b-PlexB signalling regulates presynaptic homeostatic plasticity through the cytoplasmic protein Mical and the oxoreductase-dependent control of presynaptic actin. We propose that semaphorin-plexin signalling is an essential platform for the stabilization of synaptic transmission throughout the developing and mature nervous system. These findings may be relevant to the aetiology and treatment of diverse neurological and psychiatric diseases that are characterized by altered or inappropriate neural function and behaviour

Exact Speedup Factors and Sub-Optimality for Non-Preemptive Scheduling

Fixed priority scheduling is used in many real-time systems; however, both preemptive and non-preemptive variants (FP-P and FP-NP) are known to be sub-optimal when compared to an optimal uniprocessor scheduling algorithm such as preemptive earliest deadline first (EDF-P). In this paper, we investigate the sub-optimality of fixed priority non-preemptive scheduling. Specifically, we derive the exact processor speed-up factor required to guarantee the feasibility under FP-NP (i.e. schedulability assuming an optimal priority assignment) of any task set that is feasible under EDF-P. As a consequence of this work, we also derive a lower bound on the sub-optimality of non-preemptive EDF (EDF-NP). As this lower bound matches a recently published upper bound for the same quantity, it closes the exact sub-optimality for EDF-NP. It is known that neither preemptive, nor non-preemptive fixed priority scheduling dominates the other, in other words, there are task sets that are feasible on a processor of unit speed under FP-P that are not feasible under FP-NP and vice-versa. Hence comparing these two algorithms, there are non-trivial speedup factors in both directions. We derive the exact speed-up factor required to guarantee the FP-NP feasibility of any FP-P feasible task set. Further, we derive the exact speed-up factor required to guarantee FP-P feasibility of any constrained-deadline FP-NP feasible task set

Molecular astronomy of cool stars and sub-stellar objects

The optical and infrared spectra of a wide variety of `cool' astronomical objects including the Sun, sunspots, K-, M- and S-type stars, carbon stars, brown dwarfs and extrasolar planets are reviewed. The review provides the necessary astronomical background for chemical physicists to understand and appreciate the unique molecular environments found in astronomy. The calculation of molecular opacities needed to simulate the observed spectral energy distributions is discussed