The p-value has long been the figurehead of statistical analysis in biology, but its position is under threat. p is now widely recognized as providing quite limited information about our data, and as ...being easily misinterpreted. Many biologists are aware of p's frailties, but less clear about how they might change the way they analyse their data in response. This article highlights and summarizes four broad statistical approaches that augment or replace the p-value, and that are relatively straightforward to apply. First, you can augment your p-value with information about how confident you are in it, how likely it is that you will get a similar p-value in a replicate study, or the probability that a statistically significant finding is in fact a false positive. Second, you can enhance the information provided by frequentist statistics with a focus on effect sizes and a quantified confidence that those effect sizes are accurate. Third, you can augment or substitute p-values with the Bayes factor to inform on the relative levels of evidence for the null and alternative hypotheses; this approach is particularly appropriate for studies where you wish to keep collecting data until clear evidence for or against your hypothesis has accrued. Finally, specifically where you are using multiple variables to predict an outcome through model building, Akaike information criteria can take the place of the p-value, providing quantified information on what model is best. Hopefully, this quick-and-easy guide to some simple yet powerful statistical options will support biologists in adopting new approaches where they feel that the p-value alone is not doing their data justice.
Inflammatory cytokines are commonly elevated in acute depression and are associated with resistance to monoaminergic treatment. To examine the potential role of cytokines in the pathogenesis and ...treatment of depression, we carried out a systematic review and meta-analysis of antidepressant activity of anti-cytokine treatment using clinical trials of chronic inflammatory conditions where depressive symptoms were measured as a secondary outcome. Systematic search of the PubMed, EMBASE, PsycINFO and Cochrane databases, search of reference lists and conference abstracts, followed by study selection process yielded 20 clinical trials. Random effect meta-analysis of seven randomised controlled trials (RCTs) involving 2370 participants showed a significant antidepressant effect of anti-cytokine treatment compared with placebo (standardised mean difference (SMD)=0.40, 95% confidence interval (CI), 0.22-0.59). Anti-tumour necrosis factor drugs were most commonly studied (five RCTs); SMD=0.33 (95% CI; 0.06-0.60). Separate meta-analyses of two RCTs of adjunctive treatment with anti-cytokine therapy and eight non-randomised and/or non-placebo studies yielded similar small-to-medium effect estimates favouring anti-cytokine therapy; SMD=0.19 (95% CI, 0.00-0.37) and 0.51 (95% CI, 0.34-0.67), respectively. Adalimumab, etanercept, infliximab and tocilizumab all showed statistically significant improvements in depressive symptoms. Meta-regression exploring predictors of response found that the antidepressant effect was associated with baseline symptom severity (P=0.018) but not with improvement in primary physical illness, sex, age or study duration. The findings indicate a potentially causal role for cytokines in depression and that cytokine modulators may be novel drugs for depression in chronically inflamed subjects. The field now requires RCTs of cytokine modulators using depression as the primary outcome in subjects with high inflammation who are free of other physical illnesses.
The energetic cost of locomotion can be a substantial proportion of an animal's daily energy budget and thus key to its ecology. Studies on myriad species have added to our knowledge about the ...general cost of animal movement, including the effects of variations in the environment such as terrain angle. However, further such studies might provide diminishing returns on the development of a deeper understanding of how animals trade-off the cost of movement with other energy costs, and other ecological currencies such as time. Here, I propose the 'individual energy landscape' as an approach to conceptualising the choices facing the optimising animal. In this Commentary, first I outline previous broad findings about animal walking and running locomotion, focusing in particular on the use of net cost of transport as a metric of comparison between species, and then considering the effects of environmental perturbations and other extrinsic factors on movement costs. I then introduce and explore the idea that these factors combine with the behaviour of the animal in seeking short-term optimality to create that animal's individual energy landscape - the result of the geographical landscape and environmental factors combined with the animal's selected trade-offs. Considering an animal's locomotion energy expenditure within this context enables hard-won empirical data on transport costs to be applied to questions about how an animal can and does move through its environment to maximise its fitness, and the relative importance, or otherwise, of locomotion energy economy.
Major histocompatibility complex (MHC) genes have been put forward as a model for studying how genetic diversity is maintained in wild populations. Pathogen-mediated selection (PMS) is believed to ...generate the extraordinary levels of MHC diversity observed. However, establishing the relative importance of the three proposed mechanisms of PMS (heterozygote advantage, rare-allele advantage and fluctuating selection) has proved extremely difficult. Studies have attempted to differentiate between mechanisms of PMS using two approaches: (i) comparing MHC diversity with that expected under neutrality and (ii) relating MHC diversity to pathogen regime. Here, we show that in many cases the same predictions arise from the different mechanisms under these approaches, and that most studies that have inferred one mechanism of selection have not fully considered the alternative explanations. We argue that, while it may be possible to demonstrate that particular mechanisms of PMS are occurring, resolving their relative importance within a system is probably impossible. A more realistic target is to continue to demonstrate when and where the different mechanisms of PMS occur, with the aim of determining their relative importance across systems. We put forward what we believe to be the most promising approaches that will allow us to progress towards achieving this.
Several studies have identified clinical, psychosocial, patient characteristic, and perioperative variables that are associated with persistent postsurgical pain; however, the relative effect of ...these variables has yet to be quantified. The aim of the study was to provide a systematic review and meta-analysis of predictor variables associated with persistent pain after total knee arthroplasty (TKA).
Included studies were required to measure predictor variables prior to or at the time of surgery, include a pain outcome measure at least 3 months post-TKA, and include a statistical analysis of the effect of the predictor variable(s) on the outcome measure. Counts were undertaken of the number of times each predictor was analysed and the number of times it was found to have a significant relationship with persistent pain. Separate meta-analyses were performed to determine the effect size of each predictor on persistent pain. Outcomes from studies implementing uni- and multivariable statistical models were analysed separately.
Thirty-two studies involving almost 30 000 patients were included in the review. Preoperative pain was the predictor that most commonly demonstrated a significant relationship with persistent pain across uni- and multivariable analyses. In the meta-analyses of data from univariate models, the largest effect sizes were found for: other pain sites, catastrophizing, and depression. For data from multivariate models, significant effects were evident for: catastrophizing, preoperative pain, mental health, and comorbidities.
Catastrophizing, mental health, preoperative knee pain, and pain at other sites are the strongest independent predictors of persistent pain after TKA.
Disruption of foetal development by prenatal maternal infection is consistent with a neurodevelopmental model of schizophrenia. Whether specific prenatal infections are involved, their timing and the ...mechanisms of any effect are all unknown. We addressed these questions through a systematic review of population-based studies.
Electronic and manual searches and rigorous quality assessment yielded 21 studies that included an objective assessment of individual-level prenatal maternal infection and standardized psychotic diagnoses in adult offspring. Methodological differences between studies necessitated a descriptive review.
Results for prenatal maternal non-specific bacterial, respiratory or genital and reproductive infection differed between studies, which reported up to a two- to fivefold increased risk of schizophrenia. Evidence for herpes simplex virus type 2 (HSV-2) and Toxoplasma gondii was mixed; some studies reported up to a doubling of schizophrenia risk. Prenatal HSV-1 or cytomegalovirus (CMV) infections were not associated with increased risk. Exposure to influenza or other infections during early pregnancy may be more harmful than later exposure. Increased proinflammatory cytokines during pregnancy were also associated with risk. Prenatal infection was associated with structural and functional brain abnormalities relevant to schizophrenia.
Prenatal exposure to a range of infections and inflammatory responses may be associated with risk of adult schizophrenia. Larger samples, mediation and animal models should be used to investigate whether there is a 'sensitive period' during development, and the effects of prenatal infections on neurodevelopment. Inclusion of genetic and immunological information should help to elucidate to what extent genetic vulnerability to schizophrenia may be explained by vulnerability to infection.
It is a well-known and widely lamented fact that men outnumber women in a number of fields in STEM (science, technology, engineering and maths). The most commonly discussed explanations for the ...gender gaps are discrimination and socialization, and the most common policy prescriptions target those ostensible causes. However, a great deal of evidence in the behavioural sciences suggests that discrimination and socialization are only part of the story. The purpose of this paper is to highlight other aspects of the story: aspects that are commonly overlooked or downplayed. More precisely, the paper has two main aims. The first is to examine the evidence that factors other than workplace discrimination contribute to the gender gaps in STEM. These include relatively large average sex differences in career and lifestyle preferences, and relatively small average differences in cognitive aptitudes – some favouring males, others favouring females – which are associated with progressively larger differences the further above the average one looks. The second aim is to examine the evidence suggesting that these sex differences are not purely a product of social factors but also have a substantial biological (i.e. inherited) component. A more complete picture of the causes of the unequal sex ratios in STEM may productively inform policy discussions.
Summary
Sialic acids are nine‐carbon‐backbone sugars that occupy outermost positions on vertebrate cells and secreted sialoglycoproteins. These negatively charged hydrophilic carbohydrates have a ...variety of biological, biophysical and immunological functions. Mucosal surfaces and secretions of the mouth, airway, gut and vagina are especially sialoglycan‐rich. Given their prominent positions and important functions, a variety of microbial strategies have targeted host sialic acids for adherence, mimicry and/or degradation. Here we review the roles of bacterial sialidases (neuraminidases) during colonization and pathogenesis of mammalian mucosal surfaces. Evidence is presented to support the myriad roles of mucosal sialoglycans in protecting the host from bacterial infection. In opposition, many bacteria hydrolyse sialic acids during associations with the gastrointestinal, oral, respiratory and reproductive tracts. Sialidases promote bacterial survival in mucosal niche environments in several ways, including: (i) nutritional benefits of sialic acid catabolism, (ii) unmasking of cryptic host ligands used for adherence, (iii) participation in biofilm formation and (iv) modulation of immune function. Bacterial sialidases are among the best‐studied enzymes involved in pathogenesis and may also drive commensal and/or symbiotic host associations. Future studies should continue to define host substrates of bacterial sialidases and the mechanisms of theirpathologic, commensal and symbiotic interactions with the mammalian host.
The GALAH survey: scientific motivation De Silva, G. M; Freeman, K. C; Bland-Hawthorn, J ...
Monthly notices of the Royal Astronomical Society,
05/2015, Letnik:
449, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The Galactic Archaeology with HERMES (GALAH) survey is a large high-resolution spectroscopic survey using the newly commissioned High Efficiency and Resolution Multi-Element Spectrograph (HERMES) on ...the Anglo-Australian Telescope. The HERMES spectrograph provides high-resolution (R ∼ 28 000) spectra in four passbands for 392 stars simultaneously over a 2 deg field of view. The goal of the survey is to unravel the formation and evolutionary history of the Milky Way, using fossil remnants of ancient star formation events which have been disrupted and are now dispersed throughout the Galaxy. Chemical tagging seeks to identify such dispersed remnants solely from their common and unique chemical signatures; these groups are unidentifiable from their spatial, photometric or kinematic properties. To carry out chemical tagging, the GALAH survey will acquire spectra for a million stars down to V ∼ 14. The HERMES spectra of FGK stars contain absorption lines from 29 elements including light proton-capture elements, α-elements, odd-Z elements, iron-peak elements and n-capture elements from the light and heavy s-process and the r-process. This paper describes the motivation and planned execution of the GALAH survey, and presents some results on the first-light performance of HERMES.
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