This study reveals a potential role for MAIT cells in patients with AS and is the first linking IL-7 to the elevated IL-17 profile in patients through the AS-associated risk gene IL7R.

Rat dams show natural variations in maternal care, licking and grooming (LG), that are associated with distinct behavioral and neural phenotypes in offspring. However, there has been limited research on the effects of differences in LG received by female pups and of variations in maternal care within the litter. Here, we investigated LG received by measuring active maternal care after pup retrieval of female offspring. We then examined locomotor activity, open field exploration, and restraint stress reactivity in adult female offspring. We also investigated the expression of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) and DNA methylation of the GR17 promoter in the hippocampus. High compared with low LG siblings and female offspring from high compared with low LG dams showed increased locomotor activity. High compared with low LG siblings also showed reduced anxiety behavior regardless of the overall level of LG received in the litter. Unexpectedly, both the lowest licked offspring from low LG litters and the highest licked offspring from high LG litters showed suppressed corticosterone (CORT) responses to stress. However, high LG offspring within litters also showed increased expression of the GR gene, which was negatively correlated with the CORT response to restraint. DNA methylation at 2 CpG sites within GR17 promoter was significantly higher in high LG offspring. These differences in the response to maternal care both within- and between-litters were distinct in part from previous reports of between litter effects, potentially a result of the sex studied or the methods used to observe maternal care.

Background Methodological studies – studies that evaluate the design, analysis or reporting of other research-related reports – play an important role in health research. They help to highlight issues in the conduct of research with the aim of improving health research methodology, and ultimately reducing research waste. Main body We provide an overview of some of the key aspects of methodological studies such as what they are, and when, how and why they are done. We adopt a “frequently asked questions” format to facilitate reading this paper and provide multiple examples to help guide researchers interested in conducting methodological studies. Some of the topics addressed include: is it necessary to publish a study protocol? How to select relevant research reports and databases for a methodological study? What approaches to data extraction and statistical analysis should be considered when conducting a methodological study? What are potential threats to validity and is there a way to appraise the quality of methodological studies? Conclusion Appropriate reflection and application of basic principles of epidemiology and biostatistics are required in the design and analysis of methodological studies. This paper provides an introduction for further discussion about the conduct of methodological studies.

Background Dietary recommendations and policies should be guided by rigorous systematic reviews. Reviews that are of poor methodological quality may be ineffective or misleading. Most of the evidence in nutrition comes from nonrandomized studies of nutritional exposures (usually referred to as nutritional epidemiology studies), but to date methodological evaluations of the quality of systematic reviews of such studies have been sparse and inconsistent. Objectives We aimed to investigate the quality of recently published systematic reviews and meta-analyses of nutritional epidemiology studies and to propose guidance addressing major limitations. Methods We searched MEDLINE (January 2018–August 2019), EMBASE (January 2018–August 2019), and the Cochrane Database of Systematic Reviews (January 2018–February 2019) for systematic reviews of nutritional epidemiology studies. We included a random sample of 150 reviews. Results Most reviews were published by authors from Asia (n = 49; 32.7%) or Europe (n = 43; 28.7%) and investigated foods or beverages (n = 60; 40.0%) and cancer morbidity and mortality (n = 54; 36%). Reviews often had important limitations: less than one-quarter (n = 30; 20.0%) reported preregistration of a protocol and almost one-third (n = 42; 28.0%) did not report a replicable search strategy. Suboptimal practices and errors in the synthesis of results were common: one-quarter of meta-analyses (n = 30; 26.1%) selected the meta-analytic model based on statistical indicators of heterogeneity and almost half of meta-analyses (n = 50; 43.5%) did not consider dose–response associations even when it was appropriate to do so. Only 16 (10.7%) reviews used an established system to evaluate the certainty of evidence. Conclusions Systematic reviews of nutritional epidemiology studies often have serious limitations. Authors can improve future reviews by involving statisticians, methodologists, and researchers with substantive knowledge in the specific area of nutrition being studied and using a rigorous and transparent system to evaluate the certainty of evidence.

IntroductionPilot and feasibility trials are conducted to determine feasibility or to collect information that would inform the design of a larger definitive trial. Clear progression criteria are required to determine if a definitive or main trial is feasible and how it should be designed. We sought to determine how often progression criteria are reported and the associated factors.MethodsWe conducted a methodological review of protocols for pilot randomised trials published in three journals that publish research protocols (BMJ Open, Trials, Pilot and Feasibility Studies), using a PubMed search (2013–2017). We extracted bibliometric information including the country in which the study was conducted, source of funding, type of intervention, use of a primary feasibility outcome, sample size reporting, and justification. We used generalised linear models to determine the factors associated with reporting progression criteria.ResultsOur search retrieved 276 articles, of which 49 were not eligible. We included 227 articles. Overall, 45/227 (19.8%; 95% confidence interval [CI] 14.8–25.6) reported progression criteria. Protocols published in more recent years were significantly associated with higher odds of reporting progression criteria (adjusted odds ratio [aOR] 1.40; 95% CI 1.03–1.92; p = 0.034). Pilot trials from Europe (aOR 0.19; 95% CI 0.08–0.48; p < 0.001) and the rest of the world (aOR 0.05; 95% CI 0.01–0.18; p < 0.003) compared to North America were significantly associated with lower odds of reporting progression criteria. Journal, source of funding, sample size, intervention type, and having a primary outcome related to feasibility were not significantly associated with reporting progression criteria.ConclusionProgression criteria are not often explicitly stated in protocols of pilot trials leaving room for varied interpretation of findings. The development of formal guidance for progression criteria in protocols of pilot trials is warranted.

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Background Observational studies provide important information about the effects of exposures that cannot be easily studied in clinical trials, such as nutritional exposures, but are subject to confounding. Investigators adjust for confounders by entering them as covariates in analytic models. Objective The aim of this study was to evaluate the reporting and credibility of methods for selection of covariates in nutritional epidemiology studies. Methods We sampled 150 nutritional epidemiology studies published in 2007/2008 and 2017/2018 from the top 5 high-impact nutrition and medical journals and extracted information on methods for selection of covariates. Results Most studies did not report selecting covariates a priori (94.0%) or criteria for selection of covariates (63.3%). There was general inconsistency in choice of covariates, even among studies investigating similar questions. One-third of studies did not acknowledge potential for residual confounding in their discussion. Conclusion Studies often do not report methods for selection of covariates, follow available guidance for selection of covariates, nor discuss potential for residual confounding.

Background Pilot trials often use quantitative data such as recruitment rate and retention rate to inform the design and feasibility of a larger trial. However, qualitative data such as patient, healthcare provider, and research staff perceptions of an intervention may also provide insights for a larger trial. Methods As part of a larger study investigating the reporting of progression criteria in pilot studies, we sought to determine how often pilot studies planned to use qualitative data to inform the design and feasibility of a larger trial and the factors associated with plans to use qualitative data. We searched for protocols of pilot studies of randomized trials in PubMed between 2013 and 2017. Results We included 227 articles. Only 92 (40.5%; 95% confidence interval [CI] 34.1–47.2) reported plans to collect qualitative data. The factors associated with collecting qualitative data were large studies (defined as sample size ≥ 60; adjusted odds ratio [aOR] 2.77; 95% CI 1.47–5.23; p = 0.002) and studies from Europe (aOR 3.86; 95% CI 1.68–8.88; p = 0.001) compared to North America and the rest of the world. Pilot trials with pharmacological interventions were less likely to plan to collect qualitative data (aOR 0.20; 95% CI 0.07–0.58; p = 0.003). Conclusions Qualitative data is not used enough in pilot trials. Large pilot trials, pilot trials from Europe, and pilot trials of non-pharmacological interventions are more likely to plan for qualitative data.