Spatial Variability of Snow Chemistry of High Altitude Glaciers in the Peruvian Andes

Atmospheric contaminants become incorporated in glaciers through both wet and dry deposition. Some of this particulate matter can act as a source of contamination to glacial streams, leading to a concern for the chemical contamination to cause downstream toxicity to aquatic organisms and toxicity to people ingesting that water. Other portions of this particulate matter, including black carbon, can decrease the amount of light reflected off the snow, thereby contributing to increased rates of glacial melting. These issues are especially of concern to tropical glaciers, which are receding rapidly and are relied on heavily to provide drinking water in the dry season. A snow sampling campaign was conducted on the glaciers of seven mountains in the Cordillera Blanca mountain range in Peru during June-August, 2015 to determine concentrations of inorganic contaminants and black carbon in the upper layer of snow on high altitude glaciers (\u3e5000 m.a.s.l.). Elevation did not appear to be a factor in chemical concentrations, as there were no significant linear relationships with measured analytes and elevation, with the exception of Zn on one mountain sampled. Snow samples on two of the mountains had higher As and Pb concentrations than U.S. Environmental Protection Agency (USEPA) established water quality criteria for human health. Five metals (Al, Cd, Fe, Pb, and Zn) were found to exceed the USEPA aquatic life criteria in at least one sample. The highest concentrations of black carbon and metals were found closest to a local population center and lowest were found in areas furthest from anthropogenic influences. This study also provides supporting evidence that soil/dust is a contributing source of particulate matter but not the light absorbing fraction. An initial attempt at sourcing the particulate matter in these samples was made through an examination of analyte ratios, correlations, and principal components analysis. Multivariate analysis, including hierarchical clustering on principal components, could not explain categories based solely on concentrations of light absorbing particles or distance from the closest large city in the region. The sources of contaminants in the area appears to be complicated, and further studies would provide more insight into the source and spatial distribution of particulate matter on these tropical glaciers

Assessing the Effects of Chemical Mixtures using a Bayesian Network-Relative Risk Model (BN-RRM) Integrating Adverse Outcome Pathways (AOPs)

There are long-standing uncertainties about toxicity of chemical mixtures to populations. Laboratory toxicity tests have confirmed synergistic and antagonistic effects to individuals, but not to populations.We will conduct a regional scale ecological risk assessment by evaluating the effects chemical mixtures to populations with a new Bayesian Network- Relative Risk Model (BN-RRM) incorporating an Adverse Outcome Pathway (AOP). We started applying this new BN-RRM framework in a case study with organophosphate pesticide mixtures (diazinon, chlorpyrifos, and malathion). Acetylcholinesterase inhibition (AChE) was chosen the molecular initiating event and the Puget Sound Chinook salmon (Oncorhynchus tshawytscha) and Coho salmon (Oncorhynchus kisutch) Evolutionary Significant Units (ESU) were chosen as population endpoints. Dose-response equations will be generated from the mixtures, integrated into the new BN-RRM framework and then overall risk will be calculated for the populations. Preliminary results indicate that organophosphate pesticide mixtures act synergistically and impair olfactory function that lead to loss of antipredator, homing and reproductive behavior which lead to changes in population age structure and patch dynamics. Assessing mixtures through this new BN-RRM framework is an innovative method of predicting effects to populations. This research will demonstrate a probabilistic approach to synthesize the effects of mixtures and predict impacts to populations

Brief psychological therapies for anxiety and depression in primary care: meta-analysis and meta-regression

Psychological therapies provided in primary care are usually briefer than in secondary care. There has been no recent comprehensive review comparing their effectiveness for common mental health problems. We aimed to compare the effectiveness of different types of brief psychological therapy administered within primary care across and between anxiety, depressive and mixed disorders

Lower-Level Stimulus Features Strongly Influence Responses in the Fusiform Face Area

An intriguing region of human visual cortex (the fusiform face area; FFA) responds selectively to faces as a general higher-order stimulus category. However, the potential role of lower-order stimulus properties in FFA remains incompletely understood. To clarify those lower-level influences, we measured FFA responses to independent variation in 4 lower-level stimulus dimensions using standardized face stimuli and functional Magnetic Resonance Imaging (fMRI). These dimensions were size, position, contrast, and rotation in depth (viewpoint). We found that FFA responses were strongly influenced by variations in each of these image dimensions; that is, FFA responses were not “invariant” to any of them. Moreover, all FFA response functions were highly correlated with V1 responses (r = 0.95–0.99). As in V1, FFA responses could be accurately modeled as a combination of responses to 1) local contrast plus 2) the cortical magnification factor. In some measurements (e.g., face size or a combinations of multiple cues), the lower-level variations dominated the range of FFA responses. Manipulation of lower-level stimulus parameters could even change the category preference of FFA from “face selective” to “object selective.” Altogether, these results emphasize that a significant portion of the FFA response reflects lower-level visual responses

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Erratum: Corrigendum: Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution

International Chicken Genome Sequencing Consortium. The Original Article was published on 09 December 2004. Nature432, 695–716 (2004). In Table 5 of this Article, the last four values listed in the ‘Copy number’ column were incorrect. These should be: LTR elements, 30,000; DNA transposons, 20,000; simple repeats, 140,000; and satellites, 4,000. These errors do not affect any of the conclusions in our paper. Additional information. The online version of the original article can be found at 10.1038/nature0315