30 research outputs found

    Assessing the perceptions of a biostatistics and epidemiology module: Views of Year 2 medical students from a Malaysian university. A cross-sectional survey

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    Background In the era of evidence based medicine, biostatistics and epidemiology are considered as the main elements aiding the health professional to design a research study, understand the literature, and make decisions about patient care. The aim of the study is to explore students' perception about this subject because it plays an important role in determining educational outcome. Methods Data were collected from a self-administered questionnaire distributed among 164 Year 2 medical students. The 5-point Likert scale anchored by Strongly disagree = 1 and Strongly agree = 5 included 36 questions in four domains designed to assess the perception of a biostatistics and epidemiology module amongst students. Results 138 students with ages ranging from 20 to 24 years (Mean = 20.7; SD = 0.62) returned their responses to the questionnaire. This was a response rate of 84.14%. Of the 138 students, 80.7% realized the relevance of the subject to real health issues at the end of the module, while 89.8% believed the module focused on interpretation more than calculation. More than three quarters (78.1%) agreed that lack of practicing exercises was the cause for declining interest in the subject, while only 26.1% believed that lectures were not interesting. Another three quarters (75.4%) believed that there were too many lectures for one day of teaching activities, while 84.6% recommended practical sessions for designing research and data collection. Conclusions This study found that students perceived the relevance of biostatistics and epidemiology to real health issues. The major cause of poor interest in the subject was attributed to the short duration of the course, lack of practicing exercises, and the need for practical data collection sessions. Emphasis should be given to early introduction of projects for data collection and analysis

    Quantifying Relative Diver Effects in Underwater Visual Censuses

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    Diver-based Underwater Visual Censuses (UVCs), particularly transect-based surveys, are key tools in the study of coral reef fish ecology. These techniques, however, have inherent problems that make it difficult to collect accurate numerical data. One of these problems is the diver effect (defined as the reaction of fish to a diver). Although widely recognised, its effects have yet to be quantified and the extent of taxonomic variation remains to be determined. We therefore examined relative diver effects on a reef fish assemblage on the Great Barrier Reef. Using common UVC methods, the recorded abundance of seven reef fish groups were significantly affected by the ongoing presence of SCUBA divers. Overall, the diver effect resulted in a 52% decrease in the mean number of individuals recorded, with declines of up to 70% in individual families. Although the diver effect appears to be a significant problem, UVCs remain a useful approach for quantifying spatial and temporal variation in relative fish abundances, especially if using methods that minimise the exposure of fishes to divers. Fixed distance transects using tapes or lines deployed by a second diver (or GPS-calibrated timed swims) would appear to maximise fish counts and minimise diver effects

    Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study

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    BACKGROUND: This study undertakes a systematic and comprehensive analysis of brain gene expression profiles of immune/inflammation-related genes in aging and Alzheimer’s disease (AD). METHODS: In a well-powered microarray study of young (20 to 59 years), aged (60 to 99 years), and AD (74 to 95 years) cases, gene responses were assessed in the hippocampus, entorhinal cortex, superior frontal gyrus, and post-central gyrus. RESULTS: Several novel concepts emerge. First, immune/inflammation-related genes showed major changes in gene expression over the course of cognitively normal aging, with the extent of gene response far greater in aging than in AD. Of the 759 immune-related probesets interrogated on the microarray, approximately 40% were significantly altered in the SFG, PCG and HC with increasing age, with the majority upregulated (64 to 86%). In contrast, far fewer immune/inflammation genes were significantly changed in the transition to AD (approximately 6% of immune-related probesets), with gene responses primarily restricted to the SFG and HC. Second, relatively few significant changes in immune/inflammation genes were detected in the EC either in aging or AD, although many genes in the EC showed similar trends in responses as in the other brain regions. Third, immune/inflammation genes undergo gender-specific patterns of response in aging and AD, with the most pronounced differences emerging in aging. Finally, there was widespread upregulation of genes reflecting activation of microglia and perivascular macrophages in the aging brain, coupled with a downregulation of select factors (TOLLIP, fractalkine) that when present curtail microglial/macrophage activation. Notably, essentially all pathways of the innate immune system were upregulated in aging, including numerous complement components, genes involved in toll-like receptor signaling and inflammasome signaling, as well as genes coding for immunoglobulin (Fc) receptors and human leukocyte antigens I and II. CONCLUSIONS: Unexpectedly, the extent of innate immune gene upregulation in AD was modest relative to the robust response apparent in the aged brain, consistent with the emerging idea of a critical involvement of inflammation in the earliest stages, perhaps even in the preclinical stage, of AD. Ultimately, our data suggest that an important strategy to maintain cognitive health and resilience involves reducing chronic innate immune activation that should be initiated in late midlife

    Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.

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    BACKGROUND: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. METHODS: We present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 1010 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). FINDINGS: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4-74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3-85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59-0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3-91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0-69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18-55 years (GMR 2·32 [2·01-2·68]). INTERPRETATION: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose. FUNDING: UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

    Hypoxia: From molecular responses to ecosystem responses

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    Hypoxia affects thousands of km 2 of marine waters all over the world, and has caused mass mortality of marine animals, benthic defaunation and decline in fisheries production in many places. The severity, frequency occurrence and spatial scale of hypoxia have increased in the last few decades. Due to rapid human population growth and global warming, the problem of hypoxia is likely to become worse in the coming years. Molecular responses of marine animals to hypoxia are poorly known. In many animals, a haem protein probably serves as the cellular sensor for oxygen, and reactive oxygen species are generated as signaling molecules. In mammal and fish, a heterodimeric transcription factor, hypoxia-inducible factor 1 (HIF-1) has been identified. HIF-1 receives signals from the molecular oxygen senor through redox reactions and/or phosphorylation, and in turn, regulates the transcription of a number of hypoxia-inducible genes, including genes involved in erythropoiesis, angiogenesis and glycolysis. These molecular responses then cascade into a series of biochemical and physiological adjustments, enabling the animal to survive better under hypoxic conditions. Marine animals respond to hypoxia by first attempting to maintain oxygen delivery (e.g. increases in respiration rate, number of red blood cells, or oxygen binding capacity of hemoglobin), then by conserving energy (e.g. metabolic depression, down regulation of protein synthesis and down regulation/modification of certain regulatory enzymes). Upon exposure to prolonged hypoxia, animals must eventually resort to anaerobic respiration. Hypoxia reduces growth and feeding, which may eventually affect individual fitness. Effects of hypoxia on reproduction and development of marine animals, albeit important in affecting species survival, remain almost unknown. Many fish and marine organisms can detect, and actively avoid hypoxia. Some benthos may leave their burrows and move to sediment surface during hypoxia. These behaviorial changes may render the animals more vulnerable to predation. Hypoxia may eliminate sensitive species, thereby causing major changes in species composition of benthic, fish and phytoplankton communities. Decreases in species diversity and species richness are well documented, and changes in trophodynamics and functional groups have also been reported. Under hypoxic conditions, there is a general tendency for suspended feeders to be replaced by deposit feeders; demersal fish by pelagic fish; and macrobenthos by meiobenthos. Microflagellates and nanoplankton also tend to dominate in the phytoplankton community in hypoxic environments. Existing evidence suggest that recovery of benthic communities in temperate region take two to several years. Recovery however, appears to be much quicker in subtropical environments. In natural conditions, hypoxia is often associated with increases in ammonia, hydrogen sulphide and particulate organic materials. The inability to isolate effects of hypoxia from interactions of these compounding factors makes it difficult to attribute many of the observed ecological effects to hypoxia. © 2002 Elsevier Science Ltd. All rights reserved.link_to_subscribed_fulltex
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