Swiss School of Archaeology in Greece
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Tracking in context: Variation in the effects of reforms in the age at tracking on educational mobility
No full textTreatment persistence and clinical outcomes in patients starting B cell depleting therapies within the Swiss MS Cohort.
No full textPersistence to B cell depleting therapies (BCDT) like ocrelizumab and rituximab may be higher compared with other disease-modifying therapies (DMT) in multiple sclerosis (MS). Clinical trials directly comparing these treatments are lacking.
To compare the risk of treatment discontinuation, relapse, and confirmed disability worsening in patients starting BCDT vs other DMT within real-world settings.
In a longitudinal cohort study, patients with relapsing MS starting BCDT (ocrelizumab/rituximab, n = 269) after enrolment into the Swiss MS Cohort (SMSC) were evaluated for treatment discontinuation, occurrence of relapses, and disability worsening in comparison with platform (n = 57) and oral (n = 454) DMT, or natalizumab (n = 73) using Cox regression with double robust adjustment for baseline covariates.
Patients starting BCDT were less likely to discontinue treatment than all other DMT combined (HR = 0.26, 95% CI = 0.18-0.36, p < .01), oral DMT (HR = 0.28, 95% CI = 0.20-0.39, p < .01) and natalizumab (HR = 0.35, 95% CI = 0.21-0.58, p < .01). BCDT were associated with lower risk of relapses as compared to oral DMT HR = 0.59, 95% CI = 0.39-0.88, p < .01), but not to natalizumab (HR = 0.90, 95% CI = 0.45-1.82, p = .778). Disability worsening was not significantly different between treatment groups.
We provide real-world evidence for patients being more persistent to BCDT than to other treatments, and better clinical outcomes may partly explain this
Evidence map of liver surgery: study protocol of a living systematic review.
No full textThe amount of scientific data on liver surgery is exploding. There is a critical unmet need to develop tools that will facilitate navigating the literature and offer easy, fast and accurate access to data with a high level of evidence. Evidence maps (EM) combining living systematic reviews (SR) and user-friendly synthesis with graphs and figures were developed for this purpose in other medical fields and showed promising results but remain yet unavailable in liver surgery. The present study protocol aims to generate an EM in liver surgery, gathering randomised clinical trials (RCT) and SR.
A systematic search will be conducted in the Cochrane Central Register of Controlled Trials, Web of Science, Embase and Medline to identify all RCT and SR concerning liver surgery. RCT and SR will be classified in research topics. Selected endpoints will be extracted and meta-analysed. Results will be freely available for patients, clinicians and researchers via a web-based evidence map platform. EM and meta-analyses (MA) will be updated at regular intervals.
Including publicly available data, this type of study design did not require ethical committee approval. EM displays the required properties to facilitate literature search and to get a rapid overview of the current evidence, an unavailable tool in liver surgery, to date. Generating such an aid may considerably help patients, clinicians and researchers in many aspects: accessing accurate data, helping in decision-making and identifying gaps in the field. On completion of the project, results will be published, freely available via www.evidencemap.surgery and permanently updated.
CRD42023489201 (https://www.crd.york.ac.uk/prospero/)
Subtilisin 6 From the Dermatophyte Trichophyton benhamiae Is a Marker of Infection but Not a Unique Virulence Factor.
No full textTrichophyton benhamiae is a common dermatophyte whose natural host is the guinea pig and which causes highly inflammatory skin lesions in humans. The subtilisin 6 (SUB6) of this fungus belongs to a family of 12 SUB genes. Its encoding gene, overexpressed in vivo but not in vitro, has been considered a potentially important virulence factor, but its role in pathogenesis remains to be elucidated.
The aim of this study was to assess the role of T. benhamiae SUB6 in virulence in a mouse skin infection model.
To assess the contribution of SUB6 to virulence, SUB6-deleted (ΔSUB6) and complemented strains were generated by genetic transformation. The pathogenicity of these strains was compared with that of the parental strain in vivo in mice, based on the evolution of skin symptoms, histopathological lesions and molecular analyses targeting the expression of host pro-inflammatory genes and fungal genes encoding subtilisins from the same family as SUB6.
The ΔSUB6 strain induced superficial skin signs and histopathological inflammatory lesions similar to those caused by the parental strain. Significant overexpression of the SUB1, SUB3, SUB8 and SUB10 genes in the tissues was observed regardless of the strain tested, with no difference between these strains, reflecting the absence of any compensatory mechanism among subtilisins.
SUB6 appears to be more of a marker of fungal infection than a virulence factor, at least acting alone
A primer on fixed-effects and fixed-effects panel modeling using R, Stata, and SPSS
No full textFixed-effects modeling is a powerful tool for estimating within-cluster associations in cross-sectional data and within-participant associations in longitudinal data. Although commonly used by other social scientists, this tool remains largely unknown to psychologists. To address this issue, we offer a pedagogical primer tailored for this audience, complete with R, Stata, and SPSS scripts. This primer is organized into three parts. In PART 1, we show how fixed-effects modeling applies to clustered cross-sectional data. We introduce the concepts of ‘cluster dummies’ and ‘demeaning,’ and provide scripts to estimate the within-school association between sports and depression in a fictional dataset. In PART 2, we show how fixed-effects modeling applies to longitudinal data, and provide scripts to estimate the within-participant association between sports and depression over time in a fictional four-wave dataset. In this part, we cover three additional topics. First, we explain how to calculate effect sizes and offer simulation-based sample size guidelines to detect within-participant effects of plausible magnitude with sufficient power. Second, we show how to test two possible interactions: between a time-invariant and a time-varying predictor, and between two time-varying predictors. Third, we introduce three relevant extensions: first-difference modeling (estimating changes from one wave to the next); time-distributed fixed-effects modeling (estimating changes before, during, and after an individual event); and within-between multilevel modeling (estimating both within- and between-participant associations). In PART 3, we discuss two limitations of fixed-effects modeling: time-varying confounders and reverse causation. We conclude with reflections on causality in nonexperimental data.</p
Enhanced TLR7-dependent production of type I interferon by pDCs underlies pandemic chilblains.
No full textOutbreaks of chilblains were reported during the COVID-19 pandemic. Given the essential role of type I interferon (I-IFN) in protective immunity against SARS-CoV-2 and the association of chilblains with inherited type I interferonopathies, we hypothesized that excessive I-IFN responses to SARS-CoV-2 might underlie the occurrence of chilblains in this context. We identified a transient I-IFN signature in chilblain lesions, accompanied by an acral infiltration of activated plasmacytoid dendritic cells (pDCs). Patients with chilblains were otherwise asymptomatic or had mild disease without seroconversion. Their leukocytes produced abnormally high levels of I-IFN upon TLR7 stimulation with agonists or ssRNA viruses-particularly SARS-CoV-2-but not with DNA agonists of TLR9 or the dsDNA virus HSV-1. Moreover, the patients' pDCs displayed cell-intrinsic hyperresponsiveness to TLR7 stimulation regardless of TLR7 levels. Inherited TLR7 or I-IFN deficiency confers a predisposition to life-threatening COVID-19. Conversely, our findings suggest that enhanced TLR7 activity in predisposed individuals could confer innate, pDC-mediated, sterilizing immunity to SARS-CoV-2 infection, with I-IFN-driven chilblains as a trade-off
Exploring the Promising Impact of Pulmonary Rehabilitation on Gait and Balance in Patients With COPD: A Systematic Review and Meta-Analysis.
No full textChronic obstructive pulmonary disease (COPD) is commonly associated with respiratory difficulties, but it also presents with musculoskeletal problems. The objective of this systematic review and meta-analysis was to evaluate the effects of pulmonary rehabilitation (PR) on balance and gait in patients with COPD.
We conducted a comprehensive search of 4 databases, including PubMed, Google Scholar, Science Direct, and Web of Science, from inception to November 2023. The review included studies reporting the association between COPD status and balance and gait using PR. Two independent reviewers examined the titles and abstracts, extracted the data using a standardized form, and assessed the risk of bias of the included articles.
A total of 14 studies with 320 patients in the study groups and 188 controls were included in the analysis. The risk of bias in the included studies was medium to high. The results showed that PR non-statistically significantly improved balance, as demonstrated by moderate effect sizes in the Timed Up and Go (standardized mean difference [SMD] = 0.1: 95% CI, -1.41 to 1.69) and Berg Balance Scale (SMD = -0.39: 95% CI, -1.30 to 0.53). However, the impact of PR on gait function was less clear, with mixed results. The study findings highlight the positive but non-significant effects of PR on balance in individuals with COPD. The results suggest that PR programs could include exercises that target balance improvement to enhance the overall quality of patients. However, further research is needed to determine the optimal duration and intensity of these exercises to achieve maximum benefits for patients with COPD
Metrics for diplomats: is mortality from non-communicable diseases increasing or decreasing?
No full textCross-national risk factors for childbirth-related PTSD: Findings from the INTERSECT study
No full textChildbirth-related post-traumatic stress disorder (CB-PTSD) is an underrecognized condition with consequences for mothers and infants. This study aimed to determine risk factors for CB-PTSD symptoms across countries within a stress-diathesis framework, focusing on antenatal, birth-related, and postpartum predictors.
The INTERSECT cross-sectional survey (April 2021-January 2024) included 11,302 women at 6-12 weeks postpartum. The study was carried out across maternity services in 31 countries. Outcomes were CB-PTSD diagnosis, symptom severity, and perceived traumatic birth, assessed with the City Birth Trauma Scale. Multiple risk factors were assessed, including preexisting vulnerability, pregnancy, birth, and infant-related factors. All models were adjusted for country-level variation as a random effect.
Models explained substantial variance across all outcomes (conditional R2 = 0.53-0.58). Negative birth experience was the strongest predictor (e.g. odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.80-0.84 for diagnosis). Ongoing maternal complications predicted both CB-PTSD diagnosis and symptoms (e.g. OR = 1.61, 95% CI = 1.41-1.84), and major infant complications were associated with CB-PTSD diagnosis (OR = 1.63, 95% CI = 1.29-2.07). Reports of perceived danger to self or infant (criterion A) were linked to higher CB-PTSD symptoms and traumatic birth ratings (e.g., β =0.25, 95% CI = 0.21-0.29). Other predictors reached significance but showed small effects.
Findings support a stress-diathesis framework, showing that while pre-existing vulnerabilities contribute, birth-related stressors exert the strongest influence. Trauma-informed maternity care should prioritize these factors, with attention to women's appraisals of birth