Obesity is observationally associated with altered risk of many female reproductive conditions. These include polycystic ovary syndrome (PCOS), abnormal uterine bleeding, endometriosis, infertility, ...and pregnancy-related disorders. However, the roles and mechanisms of obesity in the aetiology of reproductive disorders remain unclear. Thus, we aimed to estimate observational and genetically predicted causal associations between obesity, metabolic hormones, and female reproductive disorders.
Logistic regression, generalised additive models, and Mendelian randomisation (MR) (2-sample, non-linear, and multivariable) were applied to obesity and reproductive disease data on up to 257,193 women of European ancestry in UK Biobank and publicly available genome-wide association studies (GWASs). Body mass index (BMI), waist-to-hip ratio (WHR), and WHR adjusted for BMI were observationally (odds ratios ORs = 1.02-1.87 per 1-SD increase in obesity trait) and genetically (ORs = 1.06-2.09) associated with uterine fibroids (UF), PCOS, heavy menstrual bleeding (HMB), and pre-eclampsia. Genetically predicted visceral adipose tissue (VAT) mass was associated with the development of HMB (OR 95% CI per 1-kg increase in predicted VAT mass = 1.32 1.06-1.64, P = 0.0130), PCOS (OR 95% CI = 1.15 1.08-1.23, P = 3.24 × 10-05), and pre-eclampsia (OR 95% CI = 3.08 1.98-4.79, P = 6.65 × 10-07). Increased waist circumference posed a higher genetic risk (ORs = 1.16-1.93) for the development of these disorders and UF than did increased hip circumference (ORs = 1.06-1.10). Leptin, fasting insulin, and insulin resistance each mediated between 20% and 50% of the total genetically predicted association of obesity with pre-eclampsia. Reproductive conditions clustered based on shared genetic components of their aetiological relationships with obesity. This study was limited in power by the low prevalence of female reproductive conditions among women in the UK Biobank, with little information on pre-diagnostic anthropometric traits, and by the susceptibility of MR estimates to genetic pleiotropy.
We found that common indices of overall and central obesity were associated with increased risks of reproductive disorders to heterogenous extents in a systematic, large-scale genetics-based analysis of the aetiological relationships between obesity and female reproductive conditions. Our results suggest the utility of exploring the mechanisms mediating the causal associations of overweight and obesity with gynaecological health to identify targets for disease prevention and treatment.
Endometriosis Zondervan, Krina T; Becker, Christian M; Missmer, Stacey A
The New England journal of medicine,
03/2020, Volume:
382, Issue:
13
Journal Article
Peer reviewed
About 10% of reproductive-age women have endometriosis. Symptoms can include severe pain, dysmenorrhea, dyspareunia, dysuria, infertility, and fatigue. The pathogenesis is unclear. Hormonal therapy ...controls symptoms in some women; others require surgery, which may not be effective.
Objective To assess patient response rates to medical therapies used to treat endometriosis-associated pain. Design A systematic review with the use of Medline and Embase. Setting Not applicable. ...Patient(s) Women receiving medical therapy to treat endometriosis. Interventions(s) None. Main Outcome Measure(s) The proportions of patients who: experienced no reduction in endometriosis-associated pain symptoms; had pain symptoms remaining at the end of the treatment period; had pain recurrence after treatment cessation; experienced an increase or no change in disease score during the study; were satisfied with treatment; and discontinued therapy owing to adverse events or lack of efficacy. The change in pain symptom severity experienced during and after treatment, as measured on the visual analog scale, was also assessed. Result(s) In total, 58 articles describing 125 treatment arms met the inclusion criteria. Data for the response of endometriosis-associated pain symptoms to treatment were presented in only 29 articles. The median proportions of women with no reduction in pain were 11%–19%; at the end of treatment, 5%–59% had pain remaining; and after follow-up, 17%–34% had experienced recurrence of pain symptoms after treatment cessation. After median study durations of 2–24 months, the median discontinuation rates due to adverse events or lack of efficacy were 5%–16%. Conclusion(s) Few studies of medical therapies for endometriosis report outcomes that are relevant to patients, and many women gain only limited or intermittent benefit from treatment.
Marketing researchers are increasingly taking advantage of the instrumental variable (IV)-free Gaussian copula approach. They use this method to identify and correct endogeneity when estimating ...regression models with non-experimental data. The Gaussian copula approach's original presentation and performance demonstration via a series of simulation studies focused primarily on regression models without intercept. However, marketing and other disciplines' researchers mainly use regression models with intercept. This research expands our knowledge of the Gaussian copula approach to regression models with intercept and to multilevel models. The results of our simulation studies reveal a fundamental bias and concerns about statistical power at smaller sample sizes and when the approach's primary assumptions are not fully met. This key finding opposes the method's potential advantages and raises concerns about its appropriate use in prior studies. As a remedy, we derive boundary conditions and guidelines that contribute to the Gaussian copula approach's proper use. Thereby, this research contributes to ensuring the validity of results and conclusions of empirical research applying the Gaussian copula approach.
Abstract
BACKGROUND
Endometriosis is a chronic gynaecological disorder that affects 2–10% of women of reproductive age. The aetiology of endometriosis is largely under-explored, yet abnormalities in ...the immune system have been suggested to explain the origin of ectopic endometrial tissues, and an association between endometriosis and autoimmune diseases has been proposed. Evaluation of current evidence investigating the association between endometriosis and autoimmune diseases from population-based studies will facilitate our understanding of the causes and consequences of endometriosis and provide a reference for better healthcare practices population-wide.
OBJECTIVE AND RATIONALE
The aim of this study was to systematically review the literature on population-based studies investigating an association between endometriosis and autoimmune diseases and to conduct a meta-analysis of combinable results to investigate the extent and robustness of evidence.
SEARCH METHODS
Four electronic databases were searched (MEDLINE, Embase, Web of Science, and CINAHL) from each database inception date until 7 April 2018. Search terms included a combination of database-specific controlled vocabulary terms and free-text terms relating to ‘endometriosis’ and ‘autoimmune diseases’. Study inclusion criteria focused on peer-reviewed published articles that reported an association between endometriosis and autoimmune diseases, excluding case reports/series, review papers, meta-analyses, organizational guidelines, editorial letters, expert opinions, and conference abstracts. Quality assessment of included studies was performed based on GRADE criteria. Key information of eligible studies was abstracted into a standard form. Meta-analysis was performed for autoimmune diseases with combinable study results from at least three studies investigating an association with endometriosis. For cross-sectional studies and case–control studies, raw data from each study were documented to calculate a Mantel–Haenszel odds ratio with 95% CIs. For cohort studies, an inverse variance probability weighted model was used to pool study results to calculate a rate ratio (a hazard ratio or a standardized incidence rate) with 95% CIs.
OUTCOMES
A total of 26 published population-based cross-sectional, case–control, and cohort studies that investigated the association between endometriosis and autoimmune diseases met all eligible criteria and were included in the review. The studies quantified an association between endometriosis and several autoimmune diseases, including systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS), rheumatoid arthritis (RA), autoimmune thyroid disorder, coeliac disease (CLD), multiple sclerosis (MS), inflammatory bowel disease (IBD), and Addison’s disease. However, the quality of the evidence was generally poor due to the high risk of bias in the majority of the chosen study designs and statistical analyses. Only 5 of the 26 studies could provide high-quality evidence, and among these, 4 supported a statistically significant association between endometriosis and at least 1 autoimmune disease: SLE, SS, RA, CLD, MS, or IBD.
WIDER IMPLICATIONS
The observed associations between endometriosis and autoimmune diseases suggest that clinicians need to be aware of the potential coexistence of endometriosis and autoimmune diseases when either is diagnosed. Scientists interested in research studies on endometriosis or autoimmune diseases should consider the likelihood of comorbidity when studying these two types of health conditions. Well-designed large prospective cohort studies with confounding control and mediation quantification, as well as genetic and biological studies, are needed to generate further insights into whether endometriosis is a risk factor for, or a consequence of, autoimmune diseases, and whether these two types of disorders share pathophysiological mechanisms even if they arise independently. Such insights may offer opportunities for the development of novel non-hormonal medications such as immuno-modulators or repurposing of existing immunomodulatory therapies for endometriosis.
Mixture regression models are an important method for uncovering unobserved heterogeneity. A fundamental challenge in their application relates to the identification of the appropriate number of ...segments to retain from the data. Prior research has provided several simulation studies that compare the performance of different segment retention criteria. Although collinearity between the predictor variables is a common phenomenon in regression models, its effect on the performance of these criteria has not been analyzed thus far. We address this gap in research by examining the performance of segment retention criteria in mixture regression models characterized by systematically increased collinearity levels. The results have fundamental implications and provide guidance for using mixture regression models in empirical (marketing) studies.
Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we ...perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endometriosis cases and 191,596 controls. In addition to replicating previously reported loci, we identify five novel loci significantly associated with endometriosis risk (P<5 × 10
), implicating genes involved in sex steroid hormone pathways (FN1, CCDC170, ESR1, SYNE1 and FSHB). Conditional analysis identified five secondary association signals, including two at the ESR1 locus, resulting in 19 independent single nucleotide polymorphisms (SNPs) robustly associated with endometriosis, which together explain up to 5.19% of variance in endometriosis. These results highlight novel variants in or near specific genes with important roles in sex steroid hormone signalling and function, and offer unique opportunities for more targeted functional research efforts.
This fast car can move faster Ghasemy, Majid; Teeroovengadum, Viraiyan; Becker, Jan-Michael ...
Higher education,
12/2020, Volume:
80, Issue:
6
Journal Article
Peer reviewed
The relevance and prominence of the partial least squares structural equation modeling (PLS-SEM) method has recently increased in higher education research, especially in explanatory and predictive ...studies. We therefore first aim to assess previous PLS-SEM applications by providing a systematic review; second, we aim to highlight and summarize important guidelines for conducting a rigorous PLS-SEM analysis of the current state of results reporting in higher education journals. Specifically, this study focuses on empirical PLS-SEM applications in 14 major higher education journals indexed in the Thomson Reuters Web of Science and in the Elsevier-Scopus databases between 1999 and 2018. We initially identified 49 relevant papers published in 10 higher education journals. Based on these papers’ generally followed guidelines, we thereafter identified various issues related to data screening, model characteristics, measurement model evaluation, structural model evaluation, and the application of state-of-the-art PLS-SEM advanced methods requiring particular attention. Furthermore, we recommend recent guidelines to improve PLS-SEM applications and practices, besides providing specific suggestions regarding utilizing the method’s strength in terms of relevant higher education research questions. Our findings remind researchers, reviewers, and journal editors to remain vigilant, should help them avoid inaccuracies in future publications, and ensure rigor.
Caesarean section (C-section) is a life-saving procedure when medically indicated but unmet need and overuse can add to avoidable morbidity and mortality. It is not clear whether C-section has a ...negative impact on breastfeeding and there is limited data available on rates of C-section or breastfeeding from Northern Cyprus, an emerging region in Europe. This study aimed to investigate prevalence, trends and associations of C-section and breastfeeding in this population.
Using self-reported data from the representative Cyprus Women's Health Research (COHERE) Initiative, we used 2,836 first pregnancies to describe trends in C-section and breastfeeding between 1981 and 2017. Using modified Poisson regression, we examined the relationship between year of pregnancy and C-section and breastfeeding, as well as the association between C-section and breastfeeding prevalence and duration.
C-section prevalence in first pregnancies increased from 11.1% in 1981 to 72.5% in 2017 with a relative risk of 2.60 (95%CI; 2.14-2.15) of babies being delivered by C-section after 2005 compared to before 1995, after full adjustment for demographic and maternal medical and pregnancy related factors. Prevalence of ever breastfeeding remained steady throughout the years at 88.7% and there was no significant association between breastfeeding initiation and the year of pregnancy, or demographic and maternal medical and pregnancy related variables. After full adjustment, women who gave birth after 2005 were 1.24 (95%CI; 1.06-1.45) times more likely to breastfeed for >12 weeks compared to women who gave birth before 1995. There was no association between C-section and breastfeeding prevalence or length.
Prevalence of C-section in this population is much higher than WHO recommendations. Public awareness campaigns surrounding choice during pregnancy and change in legal framework to allow for midwife-led continuity models of birthing care should be implemented. Further research is required to understand the reasons and drivers behind this high rate.
PLS-SEM’s most wanted guidance Becker, Jan-Michael; Cheah, Jun-Hwa; Gholamzade, Rasoul ...
International journal of contemporary hospitality management,
01/2023, Volume:
35, Issue:
1
Journal Article
Peer reviewed
Open access
Purpose
Partial least squares structural equation modeling (PLS-SEM) has attracted much attention from both methodological and applied researchers in various disciplines – also in hospitality ...management research. As PLS-SEM is relatively new compared to other multivariate analysis techniques, there are still numerous open questions and uncertainties in its application. This study aims to address this important issue by offering guidance regarding its use in contexts with which researchers struggle.
Design/methodology/approach
The authors examine the most prominent questions and answers posed in a well-known PLS-SEM discussion forum. The authors do so by using a text analysis technique to identify the most salient topics.
Findings
The data analysis identifies three salient PLS-SEM topics (i.e. bootstrapping and significance testing, higher-order constructs and moderation).
Research limitations/implications
The results allow us to address the PLS-SEM community’s main methodological issues. The authors discuss each area separately and provide explanations and guidelines.
Practical implications
The guidelines on the most important PLS-SEM topics provide decision-making and application aids. In this way, the authors make a decisive contribution to clarifying ambiguities when applying the PLS-SEM method in hospitality management research and other disciplines.
Originality/value
There has as yet been no systematic analysis of this kind in the field of PLS-SEM; the authors, therefore, present the first research results. The findings and recommendations provide guidance for PLS-SEM applications in hospitality research and practice.
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