Dense overflow into a large silled embayment: Tidal modulation, fronts and basin modes

A dense bottom overflow into a 100-km scale silled embayment has been observed for a 70-day period using a coherent array of current meters and thermistor chains. As the internal Rossby radius is less than the width of the bay, the overflow is controlled by rotational dynamics. The flow is strongly modulated by the tide at diurnal, semi-diurnal and fortnightly periods. This causes a series of cold temperature fronts, associated with separate overflow events, to pass through the mooring array. The overflow is also modulated at periods of 2–3 days. This appears to be associated with the interaction of the density current with bottom-trapped waves, or possibly with interior basin modes. It appears that the forcing of the oscillation is associated with the wind, which also contains a 3-d signal

Measurements of shoaling internal waves and turbulence in an estuary

Author Posting. © American Geophysical Union, 2013. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 118 (2013): 273–286, doi:10.1029/2012JC008154.The shoaling of horizontally propagating internal waves may represent an important source of mixing and transport in estuaries and coastal seas. Including such effects in numerical models demands improvements in the understanding of several aspects of the energetics, especially those relating to turbulence generation, and observations are needed to build this understanding. To address some of these issues in the estuarine context, we undertook an intensive field program for 10 days in the summer of 2008 in the St. Lawrence Estuary. The sampling involved shore-based photogrammetry, ship-based surveys, and an array of moorings in the shoaling region that held both conventional and turbulence-resolving sensors. The measurements shed light on many aspects of the wave shoaling process. Wave arrivals were generally phase-locked with the M2 tide, providing hints about far-field forcing. In the deeper part of the study domain, the waves propagated according to the predictions of linear theory. In intermediate-depth waters, the waves traversed the field site perpendicularly to isobaths, a pattern that continued as the waves transformed nonlinearly. Acoustic Doppler velocimeters permitted inference of the turbulent energetics, and two main features were studied. First, during a period of shoaling internal waves, turbulence dissipation rates exceeded values associated with tidal shear by an order of magnitude. Second, the evolving spectral signatures associated with a particular wave-shoaling event suggest that the turbulence is at least partly locally generated. Overall, the results of this study suggest that parameterizations of wave-induced mixing could employ relatively simple dynamics in deep water, but may have to handle a wide suite of turbulence generation and transport mechanisms in inshore regions.The work was supported by the Killam Foundation, the Natural Sciences and Engineering Research Council of Canada, the Canadian Foundation for Innovation, the Canadian Foundation for Climate and Atmospheric Sciences, and the Canadian Department of Fisheries and Oceans.2013-07-3

Vertical structure of surface gravity waves propagating over a sloping sea bed: theory and field measurements

[1] Theoretical predictions of the vertical structure of wave motion over a sloping seabed are compared with field observations close to the bed in the nearshore zone. Of particular interest is the effect of the local slope on the magnitude and phase of the vertical velocity. Field measurements of near-bed velocity profiles on a 2°bed slope were obtained using a coherent Doppler profiler. The surface elevation was measured by a colocated, upward looking, acoustic sounder. Results are presented from two intervals of different wave energy levels during a storm event: for wave height/water depth ratios smaller than 0.3 and for Ursell numbers smaller than 0.6. The local comparisons of magnitude and phase between the vertical velocity and surface elevation measurements are in good agreement with linear theory for a sloping bed, but differ greatly from that for a horizontal bottom, especially in the lower water column. The sloping bottom, however, has little effect on the horizontal velocity. Linear theory appears to adequately describe the transfer function between the surface elevation and the near-bed velocities, not only at the peak frequencies but also at their harmonics. However, in relatively shallow water the local transformations of free and forced waves at the harmonic frequencies are indistinguishable in the lower water column. Therefore, given surface elevation measurements at a particular location (which reflect the integrated effects of nonlinearities associated with wave shoaling), the vertical structure of the third moments of velocity fields estimated from linear theory is in reasonable agreement with the observations. Both theory and observations show that the skewness and asymmetry of the vertical velocity are subject to significant bottom slope effects, whereas those of horizontal velocity are not. Citation: Zou, Q., A. E. Hay, and A. J. Bowen, Vertical structure of surface gravity waves propagating over a sloping seabed: Theory and field measurements

Traumatic brain injury rehabilitation: an overview of systematic reviews of intervention effectiveness. A pre-published protocol

INTRODUCTION. Many authors are in favour of using systematic reviews as a method for evidence synthesis in rehabilitation and the last decade has introduced several guidelines to help with their implementation in rehabilitation contexts. At present, however, there is little clear information about the quantity and quality of systematic reviews on TBI rehabilitation interventions. AIM. We aim to conduct an overview of systematic reviews published on TBI rehabilitation interventions in order to summarise the current state of evidence in this area of clinical practice. In addition to providing information on strength of evidence for intervention effectiveness, our goal is to research and summarise two additional domains: reviews’ characteristics and evidence gaps. METHODS. We will carry out a comprehensive search of the Cochrane Library database (including Database of Abstracts and Reviews of Effectiveness) MEDLINE, CINAHL, EMBASE, Epistemonikos, PDQ-evidence, and PubMed to find relevant systematic reviews. We also will make efforts to identify ongoing reviews by searching for protocols in the Cochrane Library database and in PROSPERO. We are not going to search grey literature. We will use Covidence (https://www.covidence.org/home) to manage review selection. Two review team members will independently select the reviews to be included to the overview. A third researcher will be consulted for resolving disagreements. We will use Knack software (https://www.knack.com/), to extract data on review characteristics and review findings. We will include the systematic reviews on the adult TBI population (regardless of severity, stage of recovery, or other aspects of clinical presentation), any kind of rehabilitation interventions (regardless of setting, uni- or multidisciplinarity etc) to describe review characteristics. From those systematic reviews the ones with comparisons with no treatment, placebo or sham treatment, and usual care; and with outcomes such as quality of life, activity and participation – as per International Classification of Functioning, Disability & Health –residential status, family burden, and adverse effects will provide basis for intervention effectiveness analysis. We will assess the quality of reporting with updated PRISMA (Transparent Reporting of Systematic Reviews and Meta-Analysis) by making a judgement of “yes/no/unclear” without further descriptions. We will assess the methodological quality of included reviews with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) instrument. SYNTHESIS. We will provide a report on the characteristics of all included reviews using simple statistical analyses and narrative accounts and the main summary of results based on intervention effectiveness. Also, we aim to present conclusions specific to each intervention in terms of the current evidence base: statistical and/or narrative descriptions of effects and the evidence quality, relevant contextual factors, population, rehabilitation setting, and comparisons researched. We will not perform meta-analysis. In order to example gaps in the current evidence of TBI rehabilitation, we will separately summarise the information on ICF categorizations covered with low or very-low quality evidence or no evidence at all from existing systematic reviews. CONCLUSIONS. To support knowledge translation, we will organise the overview of reviews’ findings as comprehensive evidence maps

Interplay between chromophore binding and domain assembly by the B₁₂-dependent photoreceptor protein, CarH.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-05-01, epub 2021-05-05Publication status: PublishedFunder: Biotechnology and Biological Sciences Research Council; Grant(s): BB/L002655/1, BB/L016486/1, BB/M011208/1Organisms across the natural world respond to their environment through the action of photoreceptor proteins. The vitamin B12-dependent photoreceptor, CarH, is a bacterial transcriptional regulator that controls the biosynthesis of carotenoids to protect against photo-oxidative stress. The binding of B12 to CarH monomers in the dark results in the formation of a homo-tetramer that complexes with DNA; B12 photochemistry results in tetramer dissociation, releasing DNA for transcription. Although the details of the response of CarH to light are beginning to emerge, the biophysical mechanism of B12-binding in the dark and how this drives domain assembly is poorly understood. Here - using a combination of molecular dynamics simulations, native ion mobility mass spectrometry and time-resolved spectroscopy - we reveal a complex picture that varies depending on the availability of B12. When B12 is in excess, its binding drives structural changes in CarH monomers that result in the formation of head-to-tail dimers. The structural changes that accompany these steps mean that they are rate-limiting. The dimers then rapidly combine to form tetramers. Strikingly, when B12 is scarcer, as is likely in nature, tetramers with native-like structures can form without a B12 complement to each monomer, with only one apparently required per head-to-tail dimer. We thus show how a bulky chromophore such as B12 shapes protein/protein interactions and in turn function, and how a protein can adapt to a sub-optimal availability of resources. This nuanced picture should help guide the engineering of B12-dependent photoreceptors as light-activated tools for biomedical applications

Vectorial capacity and vector control: reconsidering sensitivity to parameters for malaria elimination

Background: Major gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria.Methods and Results: Using analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention.Conclusions: Reaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions.<br/

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

Accelerated waning of the humoral response to COVID-19 vaccines in obesity

Funding: EAVE II is funded by the Medical Research Council (MRC) (MC_PC_19075) with the support of BREATHE—The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20058) and National Core Studies–Immunity. Additional support was provided through Public Health Scotland, the Scottish Government Director-General Health and Social Care and the University of Edinburgh. The SCORPIO study was supported by the MRC (MR/W020564/1, a core award to J.E.T.; MC_UU_0025/12 and MR/T032413/1, awards to N.J.M.) and the Medical Research Foundation (MRF-057-0002-RG-THAV-C0798). Additional support was provided by NHS Blood and Transplant (WPA15-02 to N.J.M.), the Wellcome Trust (Institutional Strategic Support Fund 204845/Z/16/Z to N.J.M.), Addenbrooke’s Charitable Trust (900239 to N.J.M.) and the NIHR Cambridge Biomedical Research Centre and NIHR BioResource. M.A.L is supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (BBS/E/B/000C0427 and BBS/E/B/000C0428) and is a Lister Institute Fellow and an EMBO Young Investigator. I.M.H. is supported by a Cambridge Institute for Medical Research PhD studentship. H.J.S. is supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (109407), and a BBSRC institutional program grant (BBS/E/B/000C0433). I.S.F. is supported by the Wellcome Trust (207462/Z/17/Z), the Botnar Fondation, the Bernard Wolfe Health Neuroscience Endowment and an NIHR Senior Investigator Award.Obesity is associated with an increased risk of severe Coronavirus Disease 2019 (COVID-19) infection and mortality. COVID-19 vaccines reduce the risk of serious COVID-19 outcomes; however, their effectiveness in people with obesity is incompletely understood. We studied the relationship among body mass index (BMI), hospitalization and mortality due to COVID-19 among 3.6 million people in Scotland using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) surveillance platform. We found that vaccinated individuals with severe obesity (BMI > 40 kg/m2) were 76% more likely to experience hospitalization or death from COVID-19 (adjusted rate ratio of 1.76 (95% confidence interval (CI), 1.60–1.94). We also conducted a prospective longitudinal study of a cohort of 28 individuals with severe obesity compared to 41 control individuals with normal BMI (BMI 18.5–24.9 kg/m2). We found that 55% of individuals with severe obesity had unquantifiable titers of neutralizing antibody against authentic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus compared to 12% of individuals with normal BMI (P = 0.0003) 6 months after their second vaccine dose. Furthermore, we observed that, for individuals with severe obesity, at any given anti-spike and anti-receptor-binding domain (RBD) antibody level, neutralizing capacity was lower than that of individuals with a normal BMI. Neutralizing capacity was restored by a third dose of vaccine but again declined more rapidly in people with severe obesity. We demonstrate that waning of COVID-19 vaccine-induced humoral immunity is accelerated in individuals with severe obesity. As obesity is associated with increased hospitalization and mortality from breakthrough infections, our findings have implications for vaccine prioritization policies.Publisher PDFPeer reviewe

Civil society leadership in the struggle for AIDS treatment in South Africa and Uganda

Includes abstract.Includes bibliographical references.This thesis is an attempt to theorise and operationalise empirically the notion of ‘civil society leadership’ in Sub-Saharan Africa. ‘AIDS leadership,’ which is associated with the intergovernmental institutions charged with coordinating the global response to HIV/AIDS, is both under-theorised and highly context-specific. In this study I therefore opt for an inclusive framework that draws on a range of approaches, including the literature on ‘leadership’, institutions, social movements and the ‘network’ perspective on civil society mobilisation. This framework is employed in rich and detailed empirical descriptions (‘thick description’) of civil society mobilisation around AIDS, including contentious AIDS activism, in the key case studies of South Africa and Uganda. South Africa and Uganda are widely considered key examples of poor and good leadership (from national political leaders) respectively, while the Treatment Action Campaign (TAC) and The AIDS Support Organisation (TASO) are both seen as highly effective civil society movements. These descriptions emphasise ‘transnational networks of influence’ in which civil society leaders participated (and at times actively constructed) in order to mobilise both symbolic and material resources aimed at exerting influence at the transnational, national and local levels

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus