Anthropology, Brokerage and Collaboration in the development of a Tongan Public Psychiatry: Local Lessons for Global Mental Health

The Global Mental Health (GMH) movement has revitalised questions of the translatability of psychiatric concepts and the challenges of community engagement in countries where knowledge of the biomedical basis for psychiatric diagnosis is limited or challenged by local cultural codes. In Tonga, the local psychiatrist Dr Puloka has successfully established a publicly accessible psychiatry that has raised admission rates for serious mental illness and addressed some of the stigma attached to diagnosis. On the basis of historical analysis and ethnographic fieldwork with healers, doctors and patients since 1998, this article offers an ethnographic contextualization of the development and reception of three key interventions during the 1990s inspired by traditional healing and reliant on the translation of psychiatric terms and diagnosis. Dr Puloka’s use of medical anthropological and transcultural psychiatry research informed a community engaged brokerage between the implications of psychiatric nosologies and local needs. As such it reveals deficiencies in current polarised positions on the GMH project and offers suggestions to address current challenges of the Global Mental Health movement

Exploring the Conformational Landscape of Bioactive Small Molecules

By using a combination of classical Hamiltonian replica exchange with high-level quantum mechanical calculations on more than one hundred drug-like molecules, we explored here the energy cost associated with binding of drug-like molecules to target macromolecules. We found that, in general, the drug-like molecules present bound to proteins in the Protein Data Bank (PDB) can access easily the bioactive conformation and in fact for 73% of the studied molecules the bioactiveconformation is within 3kBT from the most-stable conformation in solution as determined by DFT/SCRF calculations. Cases with large differences between the most-stable and the bioactive conformations appear in ligands recognized by ionic contacts, or very large structures establishing many favorable interactions with the protein. There are also a few cases where we observed a non-negligible uncertainty related to the experimental structure deposited in PDB. Remarkably, the rough automatic force field used here provides reasonable estimates of the conformational ensemble of drugs in solution. The outlined protocol can be used to better estimate the cost of adopting the bioactive conformation

DNA structure directs positioning of the mitochondrial genome packaging protein Abf2p

The mitochondrial genome (mtDNA) is assembled into nucleo-protein structures termed nucleoids and maintained differently compared to nuclear DNA, the involved molecular basis remaining poorly understood. In yeast (Saccharomyces cerevisiae), mtDNA is a similar to 80 kbp linear molecule and Abf2p, a double HMG-box protein, packages and maintains it. The protein binds DNA in a non-sequence-specific manner, but displays a distinct 'phased-binding' at specific DNA sequences containing poly-adenine tracts (A-tracts). We present here two crystal structures of Abf2p in complex with mtDNA-derived fragments bearing A-tracts. Each HMG-box of Abf2p induces a 90. bend in the contacted DNA, causing an overall U-turn. Together with previous data, this suggests that U-turn formation is the universal mechanism underlying mtDNA compaction induced by HMG-box proteins. Combining this structural information with mutational, biophysical and computational analyses, we reveal a unique DNA binding mechanism for Abf2p where a characteristic N-terminal flag and helix are crucial for mtDNA maintenance. Additionally, we provide the molecular basis for A-tract mediated exclusion of Abf2p binding. Due to high prevalence of Atracts in yeast mtDNA, this has critical relevance for nucleoid architecture. Therefore, an unprecedented A-tract mediated protein positioning mechanism regulates DNA packaging proteins in the mitochondria, and in combination with DNA-bending and U-turn formation, governs mtDNA compaction

Survey of Infections Transmissible Between Baboons and Humans, Cape Town, South Africa

Baboons on South Africa’s Cape Peninsula come in frequent contact with humans. To determine potential health risks for both species, we screened 27 baboons from 5 troops for 10 infections. Most (56%) baboons had antibodies reactive or cross-reactive to human viruses. Spatial overlap between these species poses low but potential health risks

Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study.

Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice

Direct Air Capture based on ionic liquids: from molecular design to process assessment

Direct air capture is a key carbon dioxide removal technology to mitigate climate change and keep the global average temperature rise below 1.5-2 °C. This work addresses for the first time the use of ionic liquids for direct air capture connecting their material design by molecular simulation to process modelling. First, 26 different ionic liquids were designed through quantum chemical calculations and their isotherms were computed to identify those with a positive cyclic working capacity at conditions relevant for direct air capture. Then, the most promising ionic liquids were assessed via process simulations in Aspen Plus. A wide range of operating configurations were screened by modifying the key process variables: air velocity (1 – 3 m/s), solvent mass flow (5 – 50 t/h) and temperature (293 – 323 K), and regeneration pressure (0.1 – 1 bar) and temperature (373 – 393 K). Exergy, energy and productivity were computed to detect optimal operating conditions; moreover, a simplified economic analysis was carried out to highlight the major cost components. The direct air capture system based on [P66614][Im] exhibited the most exergy (5.44 – 16.73 MJ/kg) and energy (15.15 – 35.42 MJ/kg) efficiency for similar productivity (0.5 – 1.3 kg/(m3·h)) thanks to its enhanced cyclic capacity (0.6 – 0.3 mol/kg). The minimum exergy required by [P66614][Im]-based DAC process is slightly better than alkali scrubbing (6.21 MJ/kg) and in line with amine (5.59 MJ/kg) scrubbing. In addition, the assessed DAC process has a theoretical potential to operate in the range of 200 $/tCO2 under reasonable energy and plant expenses. We conclude this work providing guidelines to address future development of direct air capture technologies based on ionic liquids

Rapid evolution of virulence and drug resistance in the emerging zoonotic pathogen Streptococcus suis

Background: Streptococcus suis is a zoonotic pathogen that infects pigs and can occasionally cause serious infections in humans. S. suis infections occur sporadically in human Europe and North America, but a recent major outbreak has been described in China with high levels of mortality. The mechanisms of S. suis pathogenesis in humans and pigs are poorly understood. Methodology/Principal Findings: The sequencing of whole genomes of S. suis isolates provides opportunities to investigate the genetic basis of infection. Here we describe whole genome sequences of three S. suis strains from the same lineage: one from European pigs, and two from human cases from China and Vietnam. Comparative genomic analysis was used to investigate the variability of these strains. S. suis is phylogenetically distinct from other Streptococcus species for which genome sequences are currently available. Accordingly, ,40% of the ,2 Mb genome is unique in comparison to other Streptococcus species. Finer genomic comparisons within the species showed a high level of sequence conservation; virtually all of the genome is common to the S. suis strains. The only exceptions are three ,90 kb regions, present in the two isolates from humans, composed of integrative conjugative elements and transposons. Carried in these regions are coding sequences associated with drug resistance. In addition, small-scale sequence variation has generated pseudogenes in putative virulence and colonization factors. Conclusions/Significance: The genomic inventories of genetically related S. suis strains, isolated from distinct hosts and diseases, exhibit high levels of conservation. However, the genomes provide evidence that horizontal gene transfer has contributed to the evolution of drug resistance

The Pit & the Pendulum: Sex Offender Laws

For centuries the criminal justice system has struggled to define the methodology of and the justifications for social control of sexual behavior that does not conform to community mores. This poster compares and contrasts the historical and contemporary attempts in the United States, Canada, Belgium, the United Kingdom, and Germany to address the risk created by individuals who engage in behaviors broadly characterized as sexually deviant. Where available, we consider the rationale for sentencing, and the earliest attempts to bring “treatment” into the criminal dispositional formula for sexual based prosecution. We also consider the impact that the choice of societal response has on risk assessment and evaluation in the various systems, including where available, the assessment and commitment of juvenile offenders. The current practice of civil commitment for a person deemed to be a sexually violent predator (SVP) is discussed highlighting the U.S. Supreme Court decision in Kansas v. Hendricks. This practice will then be compared and contrasted with the approach of designating an offender as a Dangerous Offender (DO) or a Long-Term Offender (LTO) under the criminal law. We also highlight sex offender registries where applicable. This poster is intended as an overview of the law as it exists, and not as a defense or a critique of any specific model