Dynamic and mass transfer phenomena of spherical capped bubbles

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Frequency of <i>KLK3 </i>gene deletions in the general population

Background One of the kallikrein genes ( KLK3) encodes prostate-specific antigen, a key biomarker for prostate cancer. A number of factors, both genetic and non-genetic, determine variation of serum prostate-specific antigen concentrations in the population. We have recently found three KLK3 deletions in individuals with very low prostate-specific antigen concentrations, suggesting a link between abnormally reduced KLK3 expression and deletions of KLK3. Here, we aim to determine the frequency of kallikrein gene 3 deletions in the general population. Methods The frequency of KLK3 deletions in the general population was estimated from the 1958 Birth Cohort sample ( n = 3815) using amplification ratiometry control system. In silico analyses using PennCNV were carried out in the same cohort and in NBS-WTCCC2 in order to provide an independent estimation of the frequency of KLK3 deletions in the general population. Results Amplification ratiometry control system results from the 1958 cohort indicated a frequency of KLK3 deletions of 0.81% (3.98% following a less stringent calling criterion). From in silico analyses, we found that potential deletions harbouring the KLK3 gene occurred at rates of 2.13% (1958 Cohort, n = 2867) and 0.99% (NBS-WTCCC2, n = 2737), respectively. These results are in good agreement with our in vitro experiments. All deletions found were in heterozygosis. Conclusions We conclude that a number of individuals from the general population present KLK3 deletions in heterozygosis. Further studies are required in order to know if interpretation of low serum prostate-specific antigen concentrations in individuals with KLK3 deletions may offer false-negative assurances with consequences for prostate cancer screening, diagnosis and monitoring. </jats:sec

Integrating true multilingual capabilities into an Institutional Repository : Building the World Health Organization's Institutional Repository for Information Sharing

Introduction In a global context, how do we facilitate the dissemination and access if the material in a repository is primarily searchable and retrievable in only in one or two languages? It has been observed that there is much research and public health guidelines that goes unknown to large numbers of researchers, health workers and to the general public when they are only able to access in one language or another. How do we promote integration of various information sources in an international organization with 147 country offices, six regional offices and one headquarters, and with material being published in 6 official languages and 53 non-official languages? Research ethics should start considering, at design stage, the outreach of methods used and results obtained beyond the boundaries of the research language. Access to information in as many languages as possible should become a major component of any accessibilityrelated debate

Integrating true multilingual capabilities into an Institutional Repository : Building the World Health Organization's Institutional Repository for Information Sharing

Introduction In a global context, how do we facilitate the dissemination and access if the material in a repository is primarily searchable and retrievable in only in one or two languages? It has been observed that there is much research and public health guidelines that goes unknown to large numbers of researchers, health workers and to the general public when they are only able to access in one language or another. How do we promote integration of various information sources in an international organization with 147 country offices, six regional offices and one headquarters, and with material being published in 6 official languages and 53 non-official languages? Research ethics should start considering, at design stage, the outreach of methods used and results obtained beyond the boundaries of the research language. Access to information in as many languages as possible should become a major component of any accessibilityrelated debate

Genetic Structure and Extinction of the Woolly Mammoth, Mammuthus primigenius

SummaryThe interval since circa 50 Ka has been a period of significant species extinctions among the large mammal fauna. However, the relative roles of an increasing human presence and a synchronous series of complex environmental changes in these extinctions have yet to be fully resolved [1]. Recent analyses of fossil material from Beringia have clarified our understanding of the spatiotemporal pattern of Late Pleistocene extinctions, identifying periods of population turnover well before the last glacial maximum (LGM: circa 21 Ka) or subsequent human expansion [2–4]. To examine the role of pre-LGM population changes in shaping the genetic structure of an extinct species, we analyzed the mitochondrial DNA of woolly mammoths in western Beringia and across its range. We identify genetic signatures of a range expansion of mammoths, from eastern to western Beringia, after the last interglacial (circa 125 Ka), and then an extended period during which demographic inference indicates no population-size increase. The most marked change in diversity at this time is the loss of one of two major mitochondrial lineages

Passive transfer and rate of decay of maternal antibody against African horse sickness virus in South African throughbred foals

REASONS FOR PERFORMING STUDY : African horse sickness is an insect transmitted, non-contagious disease of equids caused by African horse sickness virus (AHSV). Mortality can exceed 90% in fully susceptible horse populations. A live-attenuated (modified-live) cell culture-adapted (MLV) polyvalent AHSV vaccine is widely used to control AHS in endemic areas in southern Africa. Field studies detailing antibody responses of vaccinated horses are lacking. OBJECTIVES : To determine antibody titres to the 9 known serotypes of AHSV in a cohort of brood mares that were regularly vaccinated with the MLV AHSV vaccine, and to measure the passive transfer and rate of decay of maternal antibody to the individual virus serotypes in foals. METHODS : Serum was collected from 15 mares before foaling and from their foals after foaling and monthly thereafter for 6 months. Antibody titres to each of the 9 AHSV serotypes were determined by serum-virus neutralisation assay. RESULTS : There was marked variation in the antibody response of the mares to individual AHSV serotypes even after repeated vaccination, with consistently higher titre responses to some virus serotypes. Similarly, duration of maternally-derived antibodies in foals differed among serotypes. CONCLUSIONS : Data from this study confirm variation of the neutralising antibody response of individual mares to repeated vaccination with polyvalent AHSV vaccine. Virus strains of individual AHSV serotypes included in the vaccine may vary in their inherent immunogenicity. Passivelyacquired maternal antibodies to AHSV vary markedly among foals born to vaccinated mares, with further variation in the duration of passive immunity to individual AHSV serotypes. POTENTIAL RELEVANCE : These data are relevant to the effective utilization of live-attenuated AHSV vaccines in endemic regions, and potentially to the use of vaccines in response to future incursions of AHSV into previously free regions. Further studies involving a larger population will be required to determine the optimal time for vaccinating foals.Racing South Africa and the Equine Research Centre, University of Pretoria.http://www.evj.co.uk/journals/hb2013ab201

Indirect effects of the COVID-19 pandemic on paediatric healthcare use and severe disease: a retrospective national cohort study

OBJECTIVES: To determine the indirect consequences of the COVID-19 pandemic on paediatric healthcare utilisation and severe disease at a national level following lockdown on 23 March 2020. DESIGN: National retrospective cohort study. SETTING: Emergency childhood primary and secondary care providers across Scotland; two national paediatric intensive care units (PICUs); statutory death records. PARTICIPANTS: 273 455 unscheduled primary care attendances; 462 437 emergency department attendances; 54 076 emergency hospital admissions; 413 PICU unplanned emergency admissions requiring invasive mechanical ventilation; and 415 deaths during the lockdown study period and equivalent dates in previous years. MAIN OUTCOME MEASURES: Rates of emergency care consultations, attendances and admissions; clinical severity scores on presentation to PICU; rates and causes of childhood death. For all data sets, rates during the lockdown period were compared with mean or aggregated rates for the equivalent dates in 2016–2019. RESULTS: The rates of emergency presentations to primary and secondary care fell during lockdown in comparison to previous years. Emergency PICU admissions for children requiring invasive mechanical ventilation also fell as a proportion of cases for the entire population, with an OR of 0.52 for likelihood of admission during lockdown (95% CI 0.37 to 0.73), compared with the equivalent period in previous years. Clinical severity scores did not suggest children were presenting with more advanced disease. The greatest reduction in PICU admissions was for diseases of the respiratory system; those for injury, poisoning or other external causes were equivalent to previous years. Mortality during lockdown did not change significantly compared with 2016–2019. CONCLUSIONS: National lockdown led to a reduction in paediatric emergency care utilisation, without associated evidence of severe harm

Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study):a prospective, randomised, open-label, blinded-endpoint clinical trial

Background: Studies have suggested that evening dosing with antihypertensive therapy might have better outcomes than morning dosing. The Treatment in Morning versus Evening (TIME) study aimed to investigate whether evening dosing of usual antihypertensive medication improves major cardiovascular outcomes compared with morning dosing in patients with hypertension. Methods: The TIME study is a prospective, pragmatic, decentralised, parallel-group study in the UK, that recruited adults (aged ≥18 years) with hypertension and taking at least one antihypertensive medication. Eligible participants were randomly assigned (1:1), without restriction, stratification, or minimisation, to take all of their usual antihypertensive medications in either the morning (0600–1000 h) or in the evening (2000–0000 h). Participants were followed up for the composite primary endpoint of vascular death or hospitalisation for non-fatal myocardial infarction or non-fatal stroke. Endpoints were identified by participant report or record linkage to National Health Service datasets and were adjudicated by a committee masked to treatment allocation. The primary endpoint was assessed as the time to first occurrence of an event in the intention-to-treat population (ie, all participants randomly assigned to a treatment group). Safety was assessed in all participants who submitted at least one follow-up questionnaire. The study is registered with EudraCT (2011-001968-21) and ISRCTN (18157641), and is now complete. Findings: Between Dec 17, 2011, and June 5, 2018, 24 610 individuals were screened and 21 104 were randomly assigned to evening (n=10 503) or morning (n=10 601) dosing groups. Mean age at study entry was 65·1 years (SD 9·3); 12 136 (57·5%) participants were men; 8968 (42·5%) were women; 19 101 (90·5%) were White; 98 (0·5%) were Black, African, Caribbean, or Black British (ethnicity was not reported by 1637 [7·8%] participants); and 2725 (13·0%) had a previous cardiovascular disease. By the end of study follow-up (March 31, 2021), median follow-up was 5·2 years (IQR 4·9–5·7), and 529 (5·0%) of 10 503 participants assigned to evening treatment and 318 (3·0%) of 10 601 assigned to morning treatment had withdrawn from all follow-up. A primary endpoint event occurred in 362 (3·4%) participants assigned to evening treatment (0·69 events [95% CI 0·62–0·76] per 100 patient-years) and 390 (3·7%) assigned to morning treatment (0·72 events [95% CI 0·65–0·79] per 100 patient-years; unadjusted hazard ratio 0·95 [95% CI 0·83–1·10]; p=0·53). No safety concerns were identified. Interpretation: Evening dosing of usual antihypertensive medication was not different from morning dosing in terms of major cardiovascular outcomes. Patients can be advised that they can take their regular antihypertensive medications at a convenient time that minimises any undesirable effects. Funding: British Heart Foundation