Wet and dry troughs over Southern Africa during early summer

The synoptic scale structure of troughs transiting southern Africa in October and November is examined. Cases are chosen on the basis of an upper trough being present over southern Africa, and a minimum horizontal and vertical temperature change. Wet and dry troughs are differentiated by the extent and amount of interior rainfall produced. Once selected, a spatial and temporal framework was used on surface, upper-level synoptic maps and radiosonde sections. Individual and composite time-height and spatial sections are analysed for anomalies of temperature, geopotentials, kinematic, vorticity and divergence fields, dewpoint, dewpoint depression, mixing ratio, dry and total static energy and, equivalent potential temperature. European Centre for Medium Range Forecast (ECMWF) maps of vertical motion are analysed and ECMWF data were exclusively used in the wet and dry case study. The essential features of wet troughs include a large amplitude upper westerly wave with a diffluent and northward displaced sub-tropical jet stream, slow movement, westward tilted trough in the vertical and a negative - positive dipole where a high is located south of the low pressure system. In comparison dry troughs are characterised by a small amplitude upper wave, rapid movement, no tilted trough in the vertical, and a stationary high-pressure system over the western interior. Radiosonde moisture variables, circulation anomalies and ECMWF fields of moisture flux give evidence in the wet cases of inflow from the north-east, in conjunction with a ridging anticyclone south of the continent. In dry cases the trajectory of flow is north-westerly and the supply of moisture is limited. In the ECMWF composite maps of vertical motion, lift is weak over the interior in dry cases consistent with a gentle slope in the divergence profile. For wet cases upward motions are intense and widespread over the interior consistent with a steep slope in the divergence profile, and compensated by descending motions over the adjacent oceans along 30° S band. Precipitation in wet events is a combination of dynamical forcing, prefrontal moisture and unstable lower troposphere. In dry events, precursor moist inflow is limited, weak instability and, a gentle slope in the divergence/convergence fields are not conducive to sustain lift

Volcanic Unrest and Pre-eruptive Processes: A Hazard and Risk Perspective

Volcanic unrest is complex and capable of producing multiple hazards that can be triggered by a number of different subsurface processes. Scientific interpretations of unrest data aim to better understand (i) the processes behind unrest and their associated surface signals, (ii) their future spatio-temporal evolution and (iii) their significance as precursors for future eruptive phenomena. In a societal context, additional preparatory or contingency actions might be needed because relationships between and among individuals and social groups will be perturbed and even changed in the presence of significant uncertainty. Here we analyse some key examples from three international and multidisciplinary projects (VUELCO, CASAVA and STREVA) where issues around the limits of volcanic knowledge impact on volcanic risk governance. We provide an overview of the regional and global context of volcanic unrest and highlight scientific and societal challenges with a geographical emphasis on the Caribbean and Latin America. We investigate why the forecasting of volcanic unrest evolution and the exploitability of unrest signals to forecast future eruptive behaviour and framing of response protocols is challenging, especially during protracted unrest. We explore limitations of current approaches to decision-making and provide suggestions for how future improvements can be made in the framework of holistic volcanic unrest risk governance. We investigate potential benefits arising from improved communication, and framing of warnings around decision-making timescales and hazard levels

Regionally acquired intestinal failure data suggest an underestimate in national service requirements

Objectives, setting and patients: With complete case referral for prolonged parenteral nutrition (PN) beyond term equivalent, serving a stable population of 1.25 million people, we describe the long-term outcome and survival of patients referred to an intestinal failure (IF) nutrition support team over the first 8 years of existence at a regional paediatric centre, and extrapolate to potential numbers of national home parenteral nutrition (HPN) cases and intestinal transplantation data. Design and outcome measures: Retrospective analysis detailing patient demographics, interventions, use of HPN, occurrence of intestinal failure-associated liver disease (IFALD), and outcomes of enteral adaptation, survival, and referral for and receipt of organ transplantation. Results: 23 patients were referred over 8 years, 20 being PN dependent within the neonatal period. Diagnoses included short bowel syndrome (SBS) (18), neuromuscular abnormalities (4) and congenital enterocyte disorder (1). 12 696 days of PN were delivered with 314 confirmed episodes of sepsis at a median of 12 episodes per patient. 144 central venous catheters (CVCs) were required at a median of four per patient. IFALD occurred in 17 (73%) patients, with 10 (44%) referred for transplant assessment. Thirteen (56%) children received HPN. Overall mortality was 44%. A significant predictor for survival in the SBS group was residual bowel >40 cm (82% vs 28%, p = 0.049). Conclusions: Survival for IF at 56% was lower than reported from non-UK supra-regional centres, and nationally collected data, possibly reflecting pre-selected referral populations. Data from regional centres with complete ascertainment may be important both when counselling parents and when planning regional and national HPN and IF specialist services

The Genesis 12–19 (G1219) Study: A Twin and Sibling Study of Gene–Environment Interplay and Adolescent Development in the UK

The Genesis 12–19 (G1219) Study is an ongoing longitudinal study of a sample of UK twin pairs, non-twin sibling pairs, and their parents. G1219 was initially designed to examine the role of gene–environment interplay in adolescent depression. However, since then data have continued to be collected from both parents and their offspring into young adulthood. This has allowed for longitudinal analyses of depression and has enabled researchers to investigate multiple phenotypes and to ask questions about intermediate mechanisms. The study has primarily focused on emotional development, particularly depression and anxiety, which have been assessed at multiple levels of analysis (symptoms, cognitions, and relevant environmental experiences). G1219 has also included assessment of a broader range of psychological phenotypes ranging from antisocial behaviors and substance use to sleep difficulties, in addition to multiple aspects of the environment. DNA has also been collected. The first wave of data collection began in the year 1999 and the fifth wave of data collection will be complete before the end of 2012. In this article, we describe the sample, data collection, and measures used. We also summarize some of the key findings to date

Functional analysis of epilepsy-associated variants in STXBP1/Munc18-1 using humanised Caenorhabditis elegans

Objective: Genetic variants in STXBP1 , which encodes the conserved exocytosis protein Munc18‐1, are associated with a variety of infantile epilepsy syndromes. We aimed to develop an in vivo Caenorhabditis elegans model that could be used to test the pathogenicity of such variants in a cost‐effective manner. Methods: The CRISPR/Cas9 method was used to introduce a null mutation into the unc‐18 gene (the C. elegans orthologue of STXBP1 ), thereby creating a paralyzed worm strain. We subsequently rescued this strain with transgenes encoding the human STXBP1/Munc18‐1 protein (wild‐type and eight different epilepsy‐associated missense variants). The resulting humanized worm strains were then analyzed via behavioral, electrophysiological, and biochemical approaches. Results: Transgenic expression of wild‐type human STXBP1 protein fully rescued locomotion in both solid and liquid media to the same level as the standard wild‐type worm strain, Bristol N2. Six variant strains (E59K, V84D, C180Y, R292H, L341P, R551C) exhibited impaired locomotion, whereas two (P335L, R406H) were no different from worms expressing wild‐type STXBP1. Electrophysiological recordings revealed that all eight variant strains displayed less frequent and more irregular pharyngeal pumping in comparison to wild‐type STXBP1‐expressing strains. Four strains (V84D, C180Y, R292H, P335L) exhibited pentylenetetrazol‐induced convulsions in an acute assay of seizure‐like activity, in contrast to worms expressing wild‐type STXBP1. No differences were seen between wild‐type and variant STXBP1 strains in terms of mRNA abundance. However, STXBP1 protein levels were reduced to 20%‐30% of wild‐type in all variants, suggesting that the mutations result in STXBP1 protein instability. Significance: The approach described here is a cost‐effective in vivo method for establishing the pathogenicity of genetic variants in STXBP1 and potentially other conserved neuronal proteins. Furthermore, the humanized strains we created could potentially be used in the future for high‐throughput drug screens to identify novel therapeutics

Historical Trajectories of Disaster Risk in Dominica

The calamitous consequences of 2017 Hurricane Maria for the Caribbean island of Dominica highlighted the acute and increasing susceptibility of the region to disasters. Despite increasing international attention to disaster risk reduction, recovery from hazard events can be especially lengthy and difficult for small island developing states. In this article, we build on existing understandings of disaster risk as a physical and social condition, showing that historical processes are fundamental to understanding how conditions of risk emerge and persist over time. We take an integrated approach to analyzing the drivers of risk accumulation, using the example of Dominica, where processes set in motion during the colonial period have shaped the location of people and assets, the degree to which they might be harmed, the societal repercussions of that harm and the prospects for recovery. We focus on the underlying economic vulnerabilities and physical exposure to hazards created by agricultural, economic, and social practices, and successive disaster responses that have constrained recovery. Uncovering these historical drivers and persistent issues, elucidates lessons for pursuing a more resilient development trajectory, including through the promotion of economic restructuring and diversification, and land reform

Open urethroplasty versus endoscopic urethrotomy - clarifying the management of men with recurrent urethral stricture (the OPEN trial) : study protocol for a randomised controlled trial

Peer reviewedPublisher PD

Mailed Human Papillomavirus Self-Collection With Papanicolaou Test Referral for Infrequently Screened Women in the United States

Testing for high-risk human papillomavirus (HPV) infection using mailed, self-collected samples is a promising approach to increase screening in women who do not attend clinic screening at recommended intervals

Use of a targeted, computer/web-based guided self-help psychoeducation toolkit for distressing hallucinations (MUSE) in people with an at-risk mental state for psychosis: protocol for a randomised controlled feasibility trial

Individuals who access at-risk mental state (ARMS) services often have unusual sensory experiences and levels of distress that lead them to seek help. The Managing Unusual Sensory Experiences (MUSE) treatment is a brief symptom targeted intervention that draws on psychological explanations to help account for unusual experiences. Practitioners use formulation and behavioural experiments to support individuals to make sense of their experiences and enhance coping strategies. The primary objective of this feasibility trial is to resolve key uncertainties before a definitive trial and inform parameters of a future fully powered trial