Treatment of hypertension in rural Cambodia: results of a 6-year programme

This study was aimed to describe the outcomes of a hypertension treatment programme in two outpatient clinics in Cambodia. We determined proportions of patients who met the optimal targets for blood pressure (BP) control and assessed the evolution of mean systolic and diastolic BP (SBP/DBP) over time. Multivariate analyses were used to identify predictors of BP decrease and risk factors for LTFU. A total of 2858 patients were enrolled between March 2002 and June 2008 of whom 69.2% were female, 30.5% were aged >/=64years and 32.6% were diabetic. The median follow-up time was 600 days. By the end of 2008, 1642 (57.4%) were alive-in-care, 8 (0.3%) had died and 1208 (42.3%) were lost to follow-up. On admission, mean SBP and DBP were 162 and 94 mm Hg, respectively. Among the patients treated, a significant SBP reduction of 26.8 mm Hg (95% CI: 28.4-25.3) was observed at 6 months. Overall, 36.5% of patients reached the BP targets at 24 months. The number of young adults, non-overweight patients and non-diabetics reaching the BP targets was more. Older age (>64 years), uncontrolled DBP (>/=90 mm Hg) on last consultation and coming late for the last consultation were associated with LTFU, whereas non-diabetic patients were 1.5 times more likely to default than diabetics (95% CI: 1.3-1.7). Although the definite magnitude of the BP decrease due to antihypertension medication over time cannot be assessed definitely without a control group, our results suggest that BP reduction can be obtained with essential hypertension treatment in a large-scale programme in a resource-limited setting

Peri-conceptual and mid-pregnancy drinking:a cross-sectional assessment in two Scottish health board areas using a 7-day Retrospective Diary

Aims: The aim of this study was to evaluate the use of a 7-day Retrospective Diary to assess peri-conceptual and mid-pregnancy alcohol consumption. Background: Alcohol consumption among women has increased significantly and is of international concern. Heavy episodic (‘binge’) drinking is commonplace and is associated with unintended pregnancy. Pre-pregnancy drinking is strongly associated with continued drinking in pregnancy. Routine antenatal assessment of alcohol history and current drinking is variable; potentially harmful peri-conceptual drinking may be missed if a woman reports low or no drinking during pregnancy. Design: Cross-sectional study (n=510) in two Scottish health board areas. Methods: Face-to-face Retrospective Diary administration from February to June 2015 assessing alcohol consumption in peri-conceptual and mid-pregnancy periods. Women were recruited at the mid-pregnancy ultrasound clinic. Results: Of 510 women, 470 (92·0%) drank alcohol before their pregnancy; 187 (39·9%) drank every week. Retrospective assessment of peri-conceptual consumption identified heavy episodic drinking (more than six units on one occasion) in 52·2% (n=266); 19·6% (n=100) reported drinking more than 14 units per week, mostly at the weekend; ‘mixing’ of drinks was associated with significantly higher consumption. While consumption tailed off following pregnancy recognition, 5·5% (n=28) still exceeded the recommended daily two-unit limit in pregnancy. Multivariable logistic regression identified that women who ‘binged’ peri-conceptually were 3·2 times more likely to do this. Conclusion: Statistically significant peri-conceptual consumption levels suggest a substantial proportion of alcohol-exposed pregnancies before pregnancy recognition. Not taking a detailed alcohol history, including patterns of consumption, will result in under-detection of alcohol-exposed pregnancies. The Retrospective Diary offers practitioners a detailed way of enquiring about alcohol history for this population

From descriptive to predictive distribution models: a working example with Iberian amphibians and reptiles

BACKGROUND: Aim of the study was to identify the conditions under which spatial-environmental models can be used for the improved understanding of species distributions, under the explicit criterion of model predictive performance. I constructed distribution models for 17 amphibian and 21 reptile species in Portugal from atlas data and 13 selected ecological variables with stepwise logistic regression and a geographic information system. Models constructed for Portugal were extrapolated over Spain and tested against range maps and atlas data. RESULTS: Descriptive model precision ranged from 'fair' to 'very good' for 12 species showing a range border inside Portugal ('edge species', kappa (k) 0.35–0.89, average 0.57) and was at best 'moderate' for 26 species with a countrywide Portuguese distribution ('non-edge species', k = 0.03–0.54, average 0.29). The accuracy of the prediction for Spain was significantly related to the precision of the descriptive model for the group of edge species and not for the countrywide species. In the latter group data were consistently better captured with the single variable search-effort than by the panel of environmental data. CONCLUSION: Atlas data in presence-absence format are often inadequate to model the distribution of species if the considered area does not include part of the range border. Conversely, distribution models for edge-species, especially those displaying high precision, may help in the correct identification of parameters underlying the species range and assist with the informed choice of conservation measures

Adult Attention Deficit Hyperactivity Disorder and Violence in the Population of England: Does Comorbidity Matter?

It is unclear whether the association between Attention Deficit/Hyperactivity Disorder (ADHD) and violence is explained by ADHD symptoms or co-existing psychopathology. We investigated associations of ADHD and its symptom domains of hyperactivity and inattention, among individuals reporting violence in the UK population. Methods We report data from the Adult Psychiatric Morbidity Survey (2007), a representative sample of the household population of England. A randomly selected sample of 7,369 completed the Adult Self-Report Scale for ADHD and the self-reported violence module, including repetition, injury, minor violence, victims and location of incidents. All models were weighted to account for non-response and carefully adjusted for demography and clinical predictors of violence: antisocial personality, substance misuse and anxiety disorders. Results ADHD was moderately associated with violence after adjustments (OR 1.75, p = .01). Hyperactivity, but not inattention was associated with several indicators of violence in the domestic context (OR 1.16, p = .03). Mild and moderate ADHD symptoms were significantly associated with violence repetition, but not severe ADHD where the association was explained by co-existing disorders. Stratified analyses further indicated that most violence reports are associated with co-occurring psychopathology. Conclusions The direct effect of ADHD on violence is only moderate at the population level, driven by hyperactivity, and involving intimate partners and close persons. Because violence associated with severe ADHD is explained by co-existing psychopathology, interventions should primarily target co-existing disorders

Quantifying Relative Diver Effects in Underwater Visual Censuses

Diver-based Underwater Visual Censuses (UVCs), particularly transect-based surveys, are key tools in the study of coral reef fish ecology. These techniques, however, have inherent problems that make it difficult to collect accurate numerical data. One of these problems is the diver effect (defined as the reaction of fish to a diver). Although widely recognised, its effects have yet to be quantified and the extent of taxonomic variation remains to be determined. We therefore examined relative diver effects on a reef fish assemblage on the Great Barrier Reef. Using common UVC methods, the recorded abundance of seven reef fish groups were significantly affected by the ongoing presence of SCUBA divers. Overall, the diver effect resulted in a 52% decrease in the mean number of individuals recorded, with declines of up to 70% in individual families. Although the diver effect appears to be a significant problem, UVCs remain a useful approach for quantifying spatial and temporal variation in relative fish abundances, especially if using methods that minimise the exposure of fishes to divers. Fixed distance transects using tapes or lines deployed by a second diver (or GPS-calibrated timed swims) would appear to maximise fish counts and minimise diver effects

Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing

Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution

Automated High-Content Live Animal Drug Screening Using C. elegans Expressing the Aggregation Prone Serpin α1-antitrypsin Z

The development of preclinical models amenable to live animal bioactive compound screening is an attractive approach to discovering effective pharmacological therapies for disorders caused by misfolded and aggregation-prone proteins. In general, however, live animal drug screening is labor and resource intensive, and has been hampered by the lack of robust assay designs and high throughput work-flows. Based on their small size, tissue transparency and ease of cultivation, the use of C. elegans should obviate many of the technical impediments associated with live animal drug screening. Moreover, their genetic tractability and accomplished record for providing insights into the molecular and cellular basis of human disease, should make C. elegans an ideal model system for in vivo drug discovery campaigns. The goal of this study was to determine whether C. elegans could be adapted to high-throughput and high-content drug screening strategies analogous to those developed for cell-based systems. Using transgenic animals expressing fluorescently-tagged proteins, we first developed a high-quality, high-throughput work-flow utilizing an automated fluorescence microscopy platform with integrated image acquisition and data analysis modules to qualitatively assess different biological processes including, growth, tissue development, cell viability and autophagy. We next adapted this technology to conduct a small molecule screen and identified compounds that altered the intracellular accumulation of the human aggregation prone mutant that causes liver disease in α1-antitrypsin deficiency. This study provides powerful validation for advancement in preclinical drug discovery campaigns by screening live C. elegans modeling α1-antitrypsin deficiency and other complex disease phenotypes on high-content imaging platforms

Tracking a Medically Important Spider: Climate Change, Ecological Niche Modeling, and the Brown Recluse (Loxosceles reclusa)

Most spiders use venom to paralyze their prey and are commonly feared for their potential to cause injury to humans. In North America, one species in particular, Loxosceles reclusa (brown recluse spider, Sicariidae), causes the majority of necrotic wounds induced by the Araneae. However, its distributional limitations are poorly understood and, as a result, medical professionals routinely misdiagnose brown recluse bites outside endemic areas, confusing putative spider bites for other serious conditions. To address the issue of brown recluse distribution, we employ ecological niche modeling to investigate the present and future distributional potential of this species. We delineate range boundaries and demonstrate that under future climate change scenarios, the spider's distribution may expand northward, invading previously unaffected regions of the USA. At present, the spider's range is centered in the USA, from Kansas east to Kentucky and from southern Iowa south to Louisiana. Newly influenced areas may include parts of Nebraska, Minnesota, Wisconsin, Michigan, South Dakota, Ohio, and Pennsylvania. These results illustrate a potential negative consequence of climate change on humans and will aid medical professionals in proper bite identification/treatment, potentially reducing bite misdiagnoses

Ecological commonalities among pelagic fishes: comparison of freshwater ciscoes and marine herring and sprat

Systematic comparisons of the ecology between functionally similar fish species from freshwater and marine aquatic systems are surprisingly rare. Here, we discuss commonalities and differences in evolutionary history, population genetics, reproduction and life history, ecological interactions, behavioural ecology and physiological ecology of temperate and Arctic freshwater coregonids (vendace and ciscoes, Coregonus spp.) and marine clupeids (herring, Clupea harengus, and sprat, Sprattus sprattus). We further elucidate potential effects of climate warming on these groups of fish based on the ecological features of coregonids and clupeids documented in the previous parts of the review. These freshwater and marine fishes share a surprisingly high number of similarities. Both groups are relatively short-lived, pelagic planktivorous fishes. The genetic differentiation of local populations is weak and seems to be in part correlated to an astonishing variability of spawning times. The discrete thermal window of each species influences habitat use, diel vertical migrations and supposedly also life history variations. Complex life cycles and preference for cool or cold water make all species vulnerable to the effects of global warming. It is suggested that future research on the functional interdependence between spawning time, life history characteristics, thermal windows and genetic differentiation may profit from a systematic comparison of the patterns found in either coregonids or clupeids