The Dynamics of Observed Lee Waves over the Snæfellsnes Peninsula in Iceland

On 20 October 2016, aircraft observations documented a significant train of lee waves above and downstream of the Snæfellsnes Peninsula on the west coast of Iceland. Simulations of this event with the Weather Research and Forecasting (WRF) Model provide an excellent representation of the observed structure of these mountain waves. The orographic features producing these waves are characterized by the isolated Snæfellsjökull volcano near the tip of the peninsula and a fairly uniform ridge along its spine. Sensitivity simulations with the WRF Model document that the observed wave train consists of a superposition of the waves produced individually by these two dominant orographic features. This behavior is consistent with idealized simulations of a flow over an isolated 3D mountain and over a 2D ridge, which reproduce the essential behavior of the observed waves and those captured in the WRF simulations. Linear analytic analysis confirms the importance of a strong inversion at the top on the boundary layer in promoting significant wave activity extending far downstream of the terrain. However, analysis of the forced and resonant modes for a two-layer atmosphere with a capping inversion suggest that this wave train may not be produced by resonant modes whose energy is trapped beneath the inversion. Rather, these appear to be vertically propagating modes with very small vertical group velocity that can persist far downstream of the mountain. These vertically propagating waves potentially provide a mechanism for producing near-resonant waves farther aloft due to interactions with a stable layer in the midtroposphere

Profound and Sustained Reduction in Chlamydia trachomatis in The Gambia: A Five-Year Longitudinal Study of Trachoma Endemic Communities

Trachoma is the most common infectious cause of blindness worldwide. Mass antibiotic treatment with azithromycin is used to control ocular Chlamydia trachomatis infection. There is uncertainty over how frequently and for how long treatment is needed, particularly in low prevalence settings. This study examines the effect of a single round of treatment on clinical disease and infection in a cluster of trachoma endemic Gambian villages over a five-year period. These villages had good water supplies and sanitation improved part way through the study. We found treatment was followed by a marked decline in infection prevalence (by PCR) to less than 1%. The decline in prevalence of active disease in children was less marked. Several villages had a prevalence of active trachoma in 1 to 9 year old children of greater than 10% during the follow-up period, mostly in the absence of detectable infection. The implication of this study is that a single, high coverage mass treatment may be sufficient to control C. trachomatis infection in a low prevalence setting, particularly when combined with environmental measures to limit transmission. However, relying on clinical signs to guide treatment decisions is likely to lead to significant amounts of over treatment where current guidelines are implemented

Cortical thickness, surface area and volume measures in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy

OBJECTIVE Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are neurodegenerative diseases that can be difficult to distinguish clinically. The objective of the current study was to use surface-based analysis techniques to assess cortical thickness, surface area and grey matter volume to identify unique morphological patterns of cortical atrophy in PD, MSA and PSP and to relate these patterns of change to disease duration and clinical features. METHODS High resolution 3D T1-weighted MRI volumes were acquired from 14 PD patients, 18 MSA, 14 PSP and 19 healthy control participants. Cortical thickness, surface area and volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.1.0). Measures of disease severity and duration were assessed for correlation with cortical morphometric changes in each clinical group. RESULTS Results show that in PSP, widespread cortical thinning and volume loss occurs within the frontal lobe, particularly the superior frontal gyrus. In addition, PSP patients also displayed increased surface area in the pericalcarine. In comparison, PD and MSA did not display significant changes in cortical morphology. CONCLUSION These results demonstrate that patients with clinically established PSP exhibit distinct patterns of cortical atrophy, particularly affecting the frontal lobe. These results could be used in the future to develop a useful clinical application of MRI to distinguish PSP patients from PD and MSA patients

Genetic variation for tuber mineral concentrations in accessions of the Commonwealth Potato Collection

The variation in tuber mineral concentrations amongst accessions of wild tuber-bearing Solanum species in the Commonwealth Potato Collection (CPC) was evaluated under greenhouse conditions. Selected CPC accessions, representing the eco-geographical distribution of wild potatoes, were grown to maturity in peat-based compost under controlled conditions. Tubers from five plants of each accession were harvested, bulked and their mineral composition analysed. Among the germplasm investigated, there was a greater range in tuber concentrations of some elements of nutritional significance to both plants and animals, such as (Ca, Fe and Zn; 6.7, 3.6, and 4.5-fold respectively) than others, such as (K, P and S; all <3-fold). Significant positive correlations were found between mean altitude of the species' range and tuber P, K, Cu and Mg concentrations. The amount of diversity observed in the CPC collection indicates the existence of wide differences in tuber mineral accumulation among different potato accessions. This might be useful in breeding for nutritional improvement of potato tubers

Pathogenesis of progressive scarring trachoma in Ethiopia and Tanzania and its implications for disease control: two cohort studies.

BACKGROUND: Trachoma causes blindness through a conjunctival scarring process initiated by ocular Chlamydia trachomatis infection; however, the rates, drivers and pathophysiological determinants are poorly understood. We investigated progressive scarring and its relationship to conjunctival infection, inflammation and transcript levels of cytokines and fibrogenic factors. METHODOLOGY/PRINCIPAL FINDINGS: We recruited two cohorts, one each in Ethiopia and Tanzania, of individuals with established trachomatous conjunctival scarring. They were followed six-monthly for two years, with clinical examinations and conjunctival swab sample collection. Progressive scarring cases were identified by comparing baseline and two-year photographs, and compared to individuals without progression. Samples were tested for C. trachomatis by PCR and transcript levels of S100A7, IL1B, IL13, IL17A, CXCL5, CTGF, SPARCL1, CEACAM5, MMP7, MMP9 and CD83 were estimated by quantitative RT-PCR. Progressive scarring was found in 135/585 (23.1%) of Ethiopian participants and 173/577 (30.0%) of Tanzanian participants. There was a strong relationship between progressive scarring and increasing inflammatory episodes (Ethiopia: OR 5.93, 95%CI 3.31-10.6, p<0.0001. Tanzania: OR 5.76, 95%CI 2.60-12.7, p<0.0001). No episodes of C. trachomatis infection were detected in the Ethiopian cohort and only 5 episodes in the Tanzanian cohort. Clinical inflammation, but not scarring progression, was associated with increased expression of S100A7, IL1B, IL17A, CXCL5, CTGF, CEACAM5, MMP7, CD83 and reduced SPARCL1. CONCLUSIONS/SIGNIFICANCE: Scarring progressed in the absence of detectable C. trachomatis, which raises uncertainty about the primary drivers of late-stage trachoma. Chronic conjunctival inflammation appears to be central and is associated with enriched expression of pro-inflammatory factors and altered expression of extracellular matrix regulators. Host determinants of scarring progression appear more complex and subtle than the features of inflammation. Overall this indicates a potential role for anti-inflammatory interventions to interrupt progression and the need for trichiasis disease surveillance and surgery long after chlamydial infection has been controlled at community level

Evaluation of biases present in the cohort multiple randomised controlled trial design: a simulation study

Background The cohort multiple randomised controlled trial (cmRCT) design provides an opportunity to incorporate the benefits of randomisation within clinical practice; thus reducing costs, integrating electronic healthcare records, and improving external validity. This study aims to address a key concern of the cmRCT design: refusal to treatment is only present in the intervention arm, and this may lead to bias and reduce statistical power. Methods We used simulation studies to assess the effect of this refusal, both random and related to event risk, on bias of the effect estimator and statistical power. A series of simulations were undertaken that represent a cmRCT trial with time-to-event endpoint. Intention-to-treat (ITT), per protocol (PP), and instrumental variable (IV) analysis methods, two stage predictor substitution and two stage residual inclusion, were compared for various refusal scenarios. Results We found the IV methods provide a less biased estimator for the causal effect when refusal is present in the intervention arm, with the two stage residual inclusion method performing best with regards to minimum bias and sufficient power. We demonstrate that sample sizes should be adapted based on expected and actual refusal rates in order to be sufficiently powered for IV analysis. Conclusion We recommend running both an IV and ITT analyses in an individually randomised cmRCT as it is expected that the effect size of interest, or the effect we would observe in clinical practice, would lie somewhere between that estimated with ITT and IV analyses. The optimum (in terms of bias and power) instrumental variable method was the two stage residual inclusion method. We recommend using adaptive power calculations, updating them as refusal rates are collected in the trial recruitment phase in order to be sufficiently powered for IV analysis

Risk Factors for Ocular Infection with Chlamydia trachomatis in Children 6 Months following Mass Treatment in Tanzania

Trachoma control programs aim for high coverage of endemic communities with oral azithromycin to reduce the pool of infection with Chlamydia trachomatis. However, even with high coverage, infection is seen following treatment. In four communities in Tanzania, we followed every child aged under ten years from baseline through treatment to six months post-treatment. We determined who had infection at baseline and who still had or developed infection six months later. Coverage was over 95% in children in these communities, and infection in these children decreased by over 50% at six months. The study found that, at baseline, uninfected children who were treated had prevalence of infection at 6 months of 6%, but infected children who were treated had prevalence of infection of 22% at 6 months. Other risk factors for infection at 6 months included living in a household with other infected children, and living in a household with untreated children. Our data suggest that households with untreated children might be targeted for more intensive follow up to increase coverage and reduce subsequent infection in the community

Behavioral and molecular genetics of reading-related AM and FM detection thresholds

Auditory detection thresholds for certain frequencies of both amplitude modulated (AM) and frequency modulated (FM) dynamic auditory stimuli are associated with reading in typically developing and dyslexic readers. We present the first behavioral and molecular genetic characterization of these two auditory traits. Two extant extended family datasets were given reading tasks and psychoacoustic tasks to determine FM 2 Hz and AM 20 Hz sensitivity thresholds. Univariate heritabilities were significant for both AM (h2 = 0.20) and FM (h2 = 0.29). Bayesian posterior probability of linkage (PPL) analysis found loci for AM (12q, PPL = 81 %) and FM (10p, PPL = 32 %; 20q, PPL = 65 %). Bivariate heritability analyses revealed that FM is genetically correlated with reading, while AM was not. Bivariate PPL analysis indicates that FM loci (10p, 20q) are not also associated with reading

Therapeutic Efficacy of Potent Neutralizing HIV-1-Specific Monoclonal Antibodies in SHIV-Infected Rhesus Monkeys

HIV-1-specific monoclonal antibodies (mAbs) with extraordinary potency and breadth have recently been described. In humanized mice, combinations of mAbs have been shown to suppress viremia, but the therapeutic potential of these mAbs has not yet been evaluated in primates with an intact immune system. Here we show that administration of a cocktail of HIV-1-specific mAbs, as well as the single glycan-dependent mAb PGT121, resulted in a rapid and precipitous decline of plasma viremia to undetectable levels in rhesus monkeys chronically infected with the pathogenic virus SHIV-SF162P3. A single mAb infusion afforded up to a 3.1 log decline of plasma viral RNA in 7 days and also reduced proviral DNA in peripheral blood, gastrointestinal mucosa, and lymph nodes without the development of viral resistance. Moreover, following mAb administration, host Gag-specific T lymphocyte responses exhibited improved functionality. Virus rebounded in the majority of animals after a median of 56 days when serum mAb titers had declined to undetectable levels, although a subset of animals maintained long-term virologic control in the absence of further mAb infusions. These data demonstrate a profound therapeutic effect of potent neutralizing HIV-1-specific mAbs in SHIV-infected rhesus monkeys as well as an impact on host immune responses. Our findings strongly encourage the investigation of mAb therapy for HIV-1 in humans

Garden and landscape-scale correlates of moths of differing conservation status: significant effects of urbanization and habitat diversity

Moths are abundant and ubiquitous in vegetated terrestrial environments and are pollinators, important herbivores of wild plants, and food for birds, bats and rodents. In recent years, many once abundant and widespread species have shown sharp declines that have been cited by some as indicative of a widespread insect biodiversity crisis. Likely causes of these declines include agricultural intensification, light pollution, climate change, and urbanization; however, the real underlying cause(s) is still open to conjecture. We used data collected from the citizen science Garden Moth Scheme (GMS) to explore the spatial association between the abundance of 195 widespread British species of moth, and garden habitat and landscape features, to see if spatial habitat and landscape associations varied for species of differing conservation status. We found that associations with habitat and landscape composition were species-specific, but that there were consistent trends in species richness and total moth abundance. Gardens with more diverse and extensive microhabitats were associated with higher species richness and moth abundance; gardens near to the coast were associated with higher richness and moth abundance; and gardens in more urbanized locations were associated with lower species richness and moth abundance. The same trends were also found for species classified as increasing, declining and vulnerable under IUCN (World Conservation Union) criteria