Extensive hydrogen supersaturations in the western South Atlantic Ocean suggest substantial underestimation of nitrogen fixation

The nitrogen cycle is fundamental to Earth's biogeochemistry. Yet major uncertainties of quantification remain, particularly regarding the global oceanic nitrogen fixation rate. Hydrogen is produced during nitrogen fixation and will become supersaturated in surface waters if there is net release from diazotrophs. Ocean surveys of hydrogen supersaturation thus have the potential to illustrate the spatial and temporal distribution of nitrogen fixation, and to guide the far more onerous but quantitative methods for measuring it. Here we present the first transect of high resolution measurements of hydrogen supersaturations in surface waters along a meridional 10,000 km cruise track through the Atlantic. We compare measured saturations with published measurements of nitrogen fixation rates and also with model-derived values. If the primary source of excess hydrogen is nitrogen fixation and has a hydrogen release ratio similar to Trichodesmium, our hydrogen measurements would point to similar rates of fixation in the North and South Atlantic, roughly consistent with modelled fixation rates but not with measured rates, which are lower in the south. Possible explanations would include any substantial nitrogen fixation by newly discovered diazotrophs, particularly any having a hydrogen release ratio similar to or exceeding that of Trichodesmium; under-sampling of nitrogen fixation south of the equator related to excessive focus on Trichodesmium; and methodological shortcomings of nitrogen fixation techniques that cause a bias towards colonial diazotrophs relative to unicellular forms. Alternatively our data are affected by an unknown hydrogen source that is greater in the southern half of the cruise track than the northern

Strategies to Reduce Non-Ventilator-Associated Hospital-Acquired Pneumonia: A Systematic Review

Background Point prevalence studies identify that pneumonia is the most common healthcare associated infection. However, non-ventilator associated healthcare associated pneumonia (NV-HAP) is both underreported and understudied. Most research conducted to date, focuses on ventilator associated pneumonia. We conducted a systematic review, to provide the latest evidence for strategies to reduce NV-HAP and describe the methodological approaches used. Methods We performed a systematic search to identify research exploring and evaluating NV-HAP preventive measures in hospitals and aged-care facilities. The electronic database Medline was searched, for peer-reviewed articles published between 1st January 1998 and 31st August 2018. An assessment of the study quality and risk of bias of included articles was conducted using the Newcastle–Ottawa Scale. Results The literature search yielded 1551 articles, with 15 articles meeting the inclusion criteria. The majority of strategies for NV-HAP prevention focussed on oral care (n = 9). Three studies evaluated a form of physical activity, such as passive movements, two studies used dysphagia screening and management; and another study evaluated prophylactic antibiotics. Most studies (n = 12) were conducted in a hospital setting. Six of the fifteen studies were randomised controlled trials. Conclusion There was considerable heterogeneity in the included studies, including the type of intervention, study design, methods and definitions used to diagnose the NV-HAP. To date, interventions to reduce NV-HAP appear to be based broadly on the themes of improving oral care, increased mobility or movement and dysphagia management

Protective effects of β-Funaltrexamine against LPS-induced CCL2 expression and behavioral deficits

Background: Inflammation is present in both neurological and peripheral disorders. Specifically, inflammation is one of the common factors in diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), mood disorders which include anxiety and depression, and even inflammatory bowel disease (IBD). Thus, exploring potential treatments geared toward the assessment of inflammation is crucial to the continuation of treatment development. One pharmacological agent researched for its antiinflammatory effects is β-funaltrexamine (β-FNA), a selective mu-opioid receptor antagonist. Preclinical studies using in vitro human astroglial cells showed that β-FNA inhibited inflammatory signaling, NF-κB signaling, and chemokine expression in a mechanism unrelated to MOR. Also, β-funaltrexamines neuroprotective effects were discovered in a preclinical model of lipopolysaccharide (LPS)-induced neuroinflammation and sickness-like behavior when administered before LPS.Methods: This study determines the effects of β-FNA (50 mg/kg, i.p.) on LPS-induced (0.83 mg/kg, i.p.) sickness-like behavior using a 10 min open field test, and anxiety-like behavior, using a 5 min elevated plus maze in male and female C57BL/6J. It also assesses the effects on LPS-induced neuro and peripheral inflammation when β-FNA is administered immediately or 10 h post-LPS. Tissue collected included whole brain, hippocampus, prefrontal cortex, cerebellum/brain stem, spleen, liver, small intestine, large intestine, and plasma.Results and Conclusions: Levels of inflammatory chemokine Monocyte Chemoattractant Protein-1 (MCP1, also known as CCL2) was measured using an enzyme-linked immunosorbent assay (ELISA). Two-way analysis of variance revealed that at 24 hours, LPS increased chemokines, and β-FNA treatment was protective depending on the dosing schedule and had region-specific effects. Also, to our knowledge, this is the first time β-FNAs effect on female mice has been assessed. Differential effects of β-FNA were found between the whole brain vs. brain regions, central vs. peripheral, and sexes. This study provides insight into the inflammatory protection offered by β-FNA in both the central and peripheral systems and further knowledge of the potential therapeutic options for inflammatory disorders

β-Funaltrexamine protects against lipopolysaccharide-induced neuroinflammation and behavioral impairment

Background: One of the commonalities present in a multitude of neurological disorders is inflammation. For this reason, targeting inflammation has emerged as a viable option for the potential treatment of neurological disorders. Previous work indicated that beta-funaltrexamine (β-FNA), a selective mu-opioid receptor (MOR) antagonist, not only inhibited inflammatory signaling in vitro in human astroglial cells but also inhibited lipopolysaccharide (LPS)-induced neuroinflammation and sickness-like behavior in mice when administered post-LPS immediately.Methods: The present study explores the extent to which β-FNA is protective when treatment occurs 10 hours after LPS administration. Male and female C57BL/6J mice were administered LPS (0.83 mg/kg, i.p.) followed by treatment with β-FNA (50 mg/kg, i.p.) immediately or 10h post-LPS. Sickness-like and anxiety-like behavior was assessed using a 10-min open-field test and a 5-min elevated plus-maze test followed by the collection of the whole brain, hippocampus, frontal cortex, cerebellum/brain stem, and plasma. Levels of inflammatory chemokines/cytokines(interferon γ-induced protein, CXCL10; monocyte chemotactic protein 1, CCL2; interleukin-6, IL-6; interleukin-1β, IL-1β, and Tumor Necrosis Factor Alpha, TNF-α) in tissues were measured using an enzyme-linked immunosorbent assay.Results: Two-way analysis of variance revealed that at 24 hours, LPS increased chemokines and cytokines, and β-FNA treatment was protective depending on the dosing schedule and had region-specific effects. β-FNA inhibited levels of CXCL10 in the hippocampus, frontal cortex, cerebellum/brain stem, and plasma, and more so in males. CCL2 had differential effects between males and females in the frontal cortex, cerebellum/brain stem, and plasma. β-FNA treatment also varied in IL-6, IL-1β, and TNF-α in a region-specific and sex-specific manner. Sickness-like behavior and anxiety-like behavior also differentiated between males and females.Conclusions: This study indicates that LPS-induced neuroinflammation was differentially affected by βFNA treatment across different brain regions. This shows that the treatment might have a regional effect more than a global one. Sex differences between males and females showed differential effects in the timing of treatment, tissue, and in some cases, even in their response to the LPS-induced stimulation. Further examination of β-FNA’s anti-inflammatory and neuroprotective actions is still necessary

Drift dynamics in microbial communities and the effective community size

The structure and diversity of all open microbial communities are shaped by individual births, deaths, speciation and immigration events; the precise timings of these events are unknowable and unpredictable. This randomness is manifest as ecological drift in the population dynamics, the importance of which has been a source of debate for decades. There are theoretical reasons to suppose that drift would be imperceptible in large microbial communities, but this is at odds with circumstantial evidence that effects can be seen even in huge, complex communities. To resolve this dichotomy we need to observe dynamics in simple systems where key parameters, like migration, birth and death rates can be directly measured. We monitored the dynamics in the abundance of two genetically modified strains of Escherichia coli, with tuneable growth characteristics, that were mixed and continually fed into 10 identical chemostats. We demonstrated that the effects of demographic (non‐environmental) stochasticity are very apparent in the dynamics. However, they do not conform to the most parsimonious and commonly applied mathematical models, where each stochastic event is independent. For these simple models to reproduce the observed dynamics we need to invoke an “effective community size”, which is smaller than the census community size

Clinical Significance of Bronchodilator Responsiveness Evaluated by Forced Vital Capacity in COPD: SPIROMICS Cohort Analysis.

ObjectiveBronchodilator responsiveness (BDR) is prevalent in COPD, but its clinical implications remain unclear. We explored the significance of BDR, defined by post-bronchodilator change in FEV1 (BDRFEV1) as a measure reflecting the change in flow and in FVC (BDRFVC) reflecting the change in volume.MethodsWe analyzed 2974 participants from a multicenter observational study designed to identify varying COPD phenotypes (SPIROMICS). We evaluated the association of BDR with baseline clinical characteristics, rate of prospective exacerbations and mortality using negative binomial regression and Cox proportional hazards models.ResultsA majority of COPD participants exhibited BDR (52.7%). BDRFEV1 occurred more often in earlier stages of COPD, while BDRFVC occurred more frequently in more advanced disease. When defined by increases in either FEV1 or FVC, BDR was associated with a self-reported history of asthma, but not with blood eosinophil counts. BDRFVC was more prevalent in subjects with greater emphysema and small airway disease on CT. In a univariate analysis, BDRFVC was associated with increased exacerbations and mortality, although no significance was found in a model adjusted for post-bronchodilator FEV1.ConclusionWith advanced airflow obstruction in COPD, BDRFVC is more prevalent in comparison to BDRFEV1 and correlates with the extent of emphysema and degree of small airway disease. Since these associations appear to be related to the impairment of FEV1, BDRFVC itself does not define a distinct phenotype nor can it be more predictive of outcomes, but it can offer additional insights into the pathophysiologic mechanism in advanced COPD.Clinical trials registrationClinicalTrials.gov: NCT01969344T4

Free text adversity statements as part of a contextualised admissions process:a qualitative analysis

Abstract Background Medical schools globally are encouraged to widen access and participation for students from less privileged backgrounds. Many strategies have been implemented to address this inequality, but much still needs to be done to ensure fair access for all. In the literature, adverse circumstances include financial issues, poor educational experience and lack of professional-status parents. In order to take account of adverse circumstances faced by applicants, The University of Dundee School of Medicine offers applicants the opportunity to report circumstances which may have resulted in disadvantage. Applicants do this by completing a free text statement, known as an ‘adversity statement’, in addition to the other application information. This study analysed adversity statements submitted by applicants during two admissions cycles. Analysis of content and theme was done to identify the information applicants wished to be taken into consideration, and what range of adverse circumstances individuals reported. Methods This study used a qualitative approach with thematic analysis to categorise the adversity statements. The data was initially analysed to create a coding framework which was then applied to the whole data set. Each coded segment was then analysed for heterogeneity and homogeneity, segments merged into generated themes, or to create sub-themes. Results The data set comprised a total of 384 adversity statements. These showed a wide range of detail involving family, personal health, education and living circumstances. Some circumstances, such as geographical location, have been identified and explored in previous research, while others, such as long term health conditions, have had less attention in the literature. The degree of impact, the length of statement and degree of detail, demonstrated wide variation between submissions. Conclusions This study adds to the debate on best practice in contextual admissions and raises awareness of the range of circumstances and impact applicants wish to be considered. The themes which emerged from the data included family, school, personal health, and geographical location issues. Descriptions of the degree of impact that an adverse circumstance had on educational or other attainment was found to vary substantially from statements indicating minor, impact through to circumstances stated as causing major impact

De novo assembly of the cattle reference genome with single-molecule sequencing.

BackgroundMajor advances in selection progress for cattle have been made following the introduction of genomic tools over the past 10-12 years. These tools depend upon the Bos taurus reference genome (UMD3.1.1), which was created using now-outdated technologies and is hindered by a variety of deficiencies and inaccuracies.ResultsWe present the new reference genome for cattle, ARS-UCD1.2, based on the same animal as the original to facilitate transfer and interpretation of results obtained from the earlier version, but applying a combination of modern technologies in a de novo assembly to increase continuity, accuracy, and completeness. The assembly includes 2.7 Gb and is >250× more continuous than the original assembly, with contig N50 >25 Mb and L50 of 32. We also greatly expanded supporting RNA-based data for annotation that identifies 30,396 total genes (21,039 protein coding). The new reference assembly is accessible in annotated form for public use.ConclusionsWe demonstrate that improved continuity of assembled sequence warrants the adoption of ARS-UCD1.2 as the new cattle reference genome and that increased assembly accuracy will benefit future research on this species