Plasmodium vivax transmission in Africa

Malaria in sub-Saharan Africa has historically been almost exclusively attributed to Plasmodium falciparum (Pf). Current diagnostic and surveillance systems in much of sub-Saharan Africa are not designed to identify or report non-Pf human malaria infections accurately, resulting in a dearth of routine epidemiological data about their significance. The high prevalence of Duffy negativity provided a rationale for excluding the possibility of Plasmodium vivax (Pv) transmission. However, review of varied evidence sources including traveller infections, community prevalence surveys, local clinical case reports, entomological and serological studies contradicts this viewpoint. Here, these data reports are weighted in a unified framework to reflect the strength of evidence of indigenous Pv transmission in terms of diagnostic specificity, size of individual reports and corroboration between evidence sources. Direct evidence was reported from 21 of the 47 malaria-endemic countries studied, while 42 countries were attributed with infections of visiting travellers. Overall, moderate to conclusive evidence of transmission was available from 18 countries, distributed across all parts of the continent. Approximately 86.6 million Duffy positive hosts were at risk of infection in Africa in 2015. Analysis of the mechanisms sustaining Pv transmission across this continent of low frequency of susceptible hosts found that reports of Pv prevalence were consistent with transmission being potentially limited to Duffy positive populations. Finally, reports of apparent Duffy-independent transmission are discussed. While Pv is evidently not a major malaria parasite across most of sub-Saharan Africa, the evidence presented here highlights its widespread low-level endemicity. An increased awareness of Pv as a potential malaria parasite, coupled with policy shifts towards species-specific diagnostics and reporting, will allow a robust assessment of the public health significance of Pv, as well as the other neglected non-Pf parasites, which are currently invisible to most public health authorities in Africa, but which can cause severe clinical illness and require specific control intervention

Evaluating a Measure of Social Health Derived from Two Mental Health Recovery Measures: The California Quality of Life (CA-QOL) and Mental Health Statistics Improvement Program Consumer Survey (MHSIP)

Social health is important to measure when assessing outcomes in community mental health. Our objective was to validate social health scales using items from two broader commonly used measures that assess mental health outcomes. Participants were 609 adults receiving psychological treatment services. Items were identified from the California Quality of Life (CA-QOL) and Mental Health Statistics Improvement Program (MHSIP) outcome measures by their conceptual correspondence with social health and compared to the Social Functioning Questionnaire (SFQ) using correlational analyses. Pearson correlations for the identified CA-QOL and MSHIP items with the SFQ ranged from .42 to .62, and the identified scale scores produced Pearson correlation coefficients of .56, .70, and, .70 with the SFQ. Concurrent validity with social health was supported for the identified scales. The current inclusion of these assessment tools allows community mental health programs to include social health in their assessments

Evidence-based guidelines for treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology

The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment.The use of medication is integrated with a coherent approach to psychoeducation and behaviour change

Dysregulation of the Norepinephrine Transporter Sustains Cortical Hypodopaminergia and Schizophrenia-Like Behaviors in Neuronal Rictor Null Mice

A novel animal model highlights the link between Akt dysfunction, reduced cortical dopamine function, norepinephrine transporters, and schizophrenia-like behaviors

Drug Discovery Using Chemical Systems Biology: Identification of the Protein-Ligand Binding Network To Explain the Side Effects of CETP Inhibitors

Systematic identification of protein-drug interaction networks is crucial to correlate complex modes of drug action to clinical indications. We introduce a novel computational strategy to identify protein-ligand binding profiles on a genome-wide scale and apply it to elucidating the molecular mechanisms associated with the adverse drug effects of Cholesteryl Ester Transfer Protein (CETP) inhibitors. CETP inhibitors are a new class of preventive therapies for the treatment of cardiovascular disease. However, clinical studies indicated that one CETP inhibitor, Torcetrapib, has deadly off-target effects as a result of hypertension, and hence it has been withdrawn from phase III clinical trials. We have identified a panel of off-targets for Torcetrapib and other CETP inhibitors from the human structural genome and map those targets to biological pathways via the literature. The predicted protein-ligand network is consistent with experimental results from multiple sources and reveals that the side-effect of CETP inhibitors is modulated through the combinatorial control of multiple interconnected pathways. Given that combinatorial control is a common phenomenon observed in many biological processes, our findings suggest that adverse drug effects might be minimized by fine-tuning multiple off-target interactions using single or multiple therapies. This work extends the scope of chemogenomics approaches and exemplifies the role that systems biology has in the future of drug discovery

Evidence for electron Landau damping in space plasma turbulence

How turbulent energy is dissipated in weakly collisional space and astrophysical plasmas is a major open question. Here, we present the application of a field-particle correlation technique to directly measure the transfer of energy between the turbulent electromagnetic field and electrons in the Earth's magnetosheath, the region of solar wind downstream of the Earth's bow shock. The measurement of the secular energy transfer from the parallel electric field as a function of electron velocity shows a signature consistent with Landau damping. This signature is coherent over time, close to the predicted resonant velocity, similar to that seen in kinetic Alfven turbulence simulations, and disappears under phase randomisation. This suggests that electron Landau damping could play a significant role in turbulent plasma heating, and that the technique is a valuable tool for determining the particle energisation processes operating in space and astrophysical plasmas.STFC Ernest Rutherford Fellowship [ST/N003748/2]; NASA HSR grant [NNX16AM23G]; NSF CAREER Award [AGS-1054061]; NASA HGI grant [80NSSC18K0643]; NASA MMS GI grant [80NSSC18K1371]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]