Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability.

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

Underestimation of spirometry if recommended testing guidance is not followed.

Background: Lung function measured at work is used to make important employment decisions. Improving its quality will reduce misclassification and allow more accurate longitudinal interpretation over time. Aims: To assess the amount by which lung function (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]) values will be underestimated if recommended spirometry testing guidance is not followed. Methods: Lung function was measured in a population of workers. Knowledge of the final reproducible FEV1 and FVC for each worker allowed estimation of the underestimates that would have occurred if less forced manoeuvres than recommended had been performed. Results: A total of 667 workers (661 males, mean age 43 years, range 18-66) participated. Among them, 560 (84%) achieved reproducible results for both FEV1 and FVC; 470 (84%) of these did so after three technically acceptable forced expiratory manoeuvres, a cumulative total of 533 after four, 548 after five, 557 after six, 559 after seven and 560 after eight blows. If only one (or first two) technically acceptable blow(s) had been performed, mean underestimates were calculated for FEV1 of 115.1 ml (35.4 ml) and for FVC of 143.4 ml (42.3 ml). Conclusions: In this study, reproducible spirometry was achievable in most workers. Not adhering to standards underestimates lung function by clinically significant amounts.

Post-traumatic stress disorder and cardiometabolic disease: improving causal inference to inform practice.

Post-traumatic stress disorder (PTSD) has been declared 'a life sentence' based on evidence that the disorder leads to a host of physical health problems. Some of the strongest empirical research - in terms of methodology and findings - has shown that PTSD predicts higher risk of cardiometabolic diseases, specifically cardiovascular disease (CVD) and type 2 diabetes (T2D). Despite mounting evidence, PTSD is not currently acknowledged as a risk factor by cardiovascular or endocrinological medicine. This view is unlikely to change absent compelling evidence that PTSD causally contributes to cardiometabolic disease. This review suggests that with developments in methods for epidemiological research and the rapidly expanding knowledge of the behavioral and biological effects of PTSD the field is poised to provide more definitive answers to questions of causality. First, we discuss methods to improve causal inference using the observational data most often used in studies of PTSD and health, with particular reference to issues of temporality and confounding. Second, we consider recent work linking PTSD with specific behaviors and biological processes, and evaluate whether these may plausibly serve as mechanisms by which PTSD leads to cardiometabolic disease. Third, we evaluate how looking more comprehensively into the PTSD phenotype provides insight into whether specific aspects of PTSD phenomenology are particularly relevant to cardiometabolic disease. Finally, we discuss new areas of research that are feasible and could enhance understanding of the PTSD-cardiometabolic relationship, such as testing whether treatment of PTSD can halt or even reverse the cardiometabolic risk factors causally related to CVD and T2D.

Post-traumatic stress disorder symptom duration and remission in relation to cardiovascular disease risk among a large cohort of women.

BACKGROUND: Prior studies suggest that post-traumatic stress disorder (PTSD) is associated with elevated cardiovascular disease (CVD) risk, but effects of duration and remission of PTSD symptoms have rarely been evaluated. METHOD: We examined the association of time-updated PTSD symptom severity, remission and duration with incident CVD risk (552 confirmed myocardial infarctions or strokes) over 20 years in 49 859 women in the Nurses' Health Study II. Among women who reported trauma on the Brief Trauma Questionnaire, PTSD symptoms, assessed by a screener, were classified by symptom severity and chronicity: (a) no symptoms, (b) 1-3 ongoing, (c) 4-5 ongoing, (d) 6-7 ongoing, (e) 1-3 remitted, (f) 4-7 remitted symptoms. Inverse probability weighting was used to estimate marginal structural logistic regression models, adjusting for time-varying and time-invariant confounders. RESULTS: Compared with women with no trauma exposure, women with trauma/no PTSD [odds ratio (OR) 1.30, 95% confidence interval (CI) 1.03-1.65] and women with trauma/6-7 symptoms (OR 1.69, 95% CI 1.08-2.63) had elevated risk of CVD; women with remitted symptoms did not have elevated CVD risk. Among women exposed to trauma, every 5 additional years of PTSD symptomology was associated with 9% higher CVD incidence compared with women with trauma/no PTSD. CONCLUSIONS: The findings suggest that alleviating PTSD symptoms shortly after onset may attenuate CVD risk.

Geographic variation in hybridization and ecological differentiation between three syntopic, morphologically similar species of montane lizards.

To understand factors shaping species boundaries in closely related taxa, a powerful approach is to compare levels of genetic admixture at multiple points of contact and determine how this relates to intrinsic and extrinsic factors, such as genetic, morphological and ecological differentiation. In the Australian Alps, the threatened alpine bog skink Pseudemoia cryodroma co-occurs with two morphologically and ecologically similar congeners, P. entrecasteauxii and P. pagenstecheri, and all three species are suspected to hybridize. We predicted that the frequency of hybridization should be negatively correlated with genetic divergence, morphological differentiation and microhabitat separation. We tested this hypothesis using a mitochondrial locus, 13 microsatellite loci, morphological and microhabitat data and compared results across three geographically isolated sites. Despite strong genetic structure between species, we detected hybridization between all species pairs, including evidence of backcrossed individuals at the two sites where all three species are syntopic. Hybridization frequencies were not consistently associated with genetic, morphological or ecological differentiation. Furthermore, P. entrecasteauxii and P. pagenstecheri only hybridized at the two sites where they are syntopic with P. cryodroma, but not at the largest site where P. cryodroma was not recorded, suggesting that P. cryodroma may serve as a bridging species. This study reveals the complex dynamics within a three species hybrid zone and provides a baseline for assessing the impact of climate change and anthropogenic habitat modification on future hybridization frequencies.

Post-traumatic stress disorder symptoms and risk of hypertension over 22 years in a large cohort of younger and middle-aged women.

BACKGROUND: Post-traumatic stress disorder (PTSD) has been linked to hypertension, but most research on PTSD and hypertension is cross-sectional, and potential mediators have not been clearly identified. Moreover, PTSD is twice as common in women as in men, but understanding of the PTSD-hypertension relationship in women is limited. We examined trauma exposure and PTSD symptoms in relation to incident hypertension over 22 years in 47 514 civilian women in the Nurses' Health Study II. METHOD: We used proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for new-onset hypertension (N = 15 837). RESULTS: PTSD symptoms assessed with a screen were modestly associated with incident hypertension in a dose-response fashion after adjusting for potential confounders. Compared to women with no trauma exposure, women with 6-7 PTSD symptoms had the highest risk of developing hypertension (HR 1.20, 95% CI 1.12-1.30), followed by women with 4-5 symptoms (HR 1.17, 95% CI 1.10-1.25), women with 1-3 symptoms (HR 1.12, 95% CI 1.06-1.18), and trauma-exposed women with no symptoms (HR 1.04, 95% CI 1.00-1.09). Findings were maintained, although attenuated, adjusting for hypertension-relevant medications, medical risk factors, and health behaviors. Higher body mass index and antidepressant use accounted for 30% and 21% of the PTSD symptom-hypertension association, respectively. CONCLUSIONS: Screening for hypertension and reducing unhealthy lifestyle factors, particularly obesity, in women with PTSD may hold promise for offsetting cardiovascular risk.

Occupational chronic obstructive pulmonary disease: a standard of care.

BACKGROUND: Consistent evidence from population studies report that 10-15% of the total burden of chronic obstructive pulmonary disease (COPD) is associated with workplace exposures. This proportion of COPD could be eliminated if harmful workplace exposures were controlled adequately. AIMS: To produce a standard of care for clinicians, occupational health professionals, employers and employees on the identification and management of occupational COPD. METHODS: A systematic literature review was used to identify published data on the prevention, identification and management of occupational COPD. Scottish Intercollegiate Guidance Network grading and the Royal College of General Practitioner three star grading system were used to grade the evidence. RESULTS: There are a number of specific workplace exposures that are established causes of COPD. Taking an occupational history in patients or workers with possible or established COPD will identify these. Reduction in exposure to vapours, gases, dusts and fumes at work is likely to be the most effective method for reducing occupational COPD. Identification of workers with rapidly declining lung function, irrespective of their specific exposure, is important. Individuals can be identified at work by accurate annual measures of lung function. CONCLUSIONS: Early identification of cases with COPD is important so that causality can be considered and action taken to reduce causative exposures thereby preventing further harm to the individual and other workers who may be similarly exposed. This can be achieved using a combination of a respiratory questionnaire, accurate lung function measurements and control of exposures in the workplace.

Maladaptive health factors as potential mediators for the association between posttraumatic stress disorder and cardiovascular disease: A sex-stratified analysis in the U.S. adult population.

OBJECTIVES: This study examined sex differences for health risk factors as potential mediators in the association between posttraumatic stress disorder (PTSD) and cardiovascular disease (CVD). METHODS: Secondary data from the 2012-2013 National Epidemiological Survey on Alcohol and Related Conditions Wave 3 was used. This cross-sectional survey contains a nationally representative sample of 36,309 U.S. adults (nfemales = 20,447, Mage = 47.16, 95% CI = [46.74, 47,57]; nmales = 15,682, Mage = 45.88, 95% CI = [45.42, 46.34]). Natural effect models and logistic regression analyses were conducted to evaluate health risk factors (smoking, substance use, low physical activity, high body mass index [BMI], binge eating, and multiple health risk factors) as potential mediators for the PTSD-CVD relationship in females and males. RESULTS: High BMI (indirect AOR = 1.05, 95% CI = [1.02, 1.07]) and substance use (indirect AOR = 0.93, 95% CI = [0.88, 0.98], p = 0.005) were potential mediators in females and males respectively. Binge eating, smoking, and low physical activity were not mediators in either sex. The number of health risk factors was also a potential mediator in females (indirect AOR = 1.12, 95% CI = [1.07, 1.19], p = <0.001) though not males (indirect AOR = 1.09, 95% CI = [1.00, 1.19], p = .059). CONCLUSIONS: The results inform prevention strategies, such as screening for health risk factors to mitigate the adverse effect of PTSD on CVD risk. Findings also inform important directions for future longitudinal research to establish causal pathways.

Type D personality is not associated with coronary heart disease risk in a North American sample of retirement-aged adults.

BACKGROUND: Type D personality is associated with recurrent coronary heart disease (CHD) risk but there is limited and inconsistent evidence regarding incident risk among persons free of clinical CHD. PURPOSE: We examined the association between Type D personality and coronary heart disease (CHD) risk in apparently healthy adults. We also explored the association of these traits with waist circumference, body mass index (BMI), and inhibited physician consultation behavior. METHODS: Cross-sectional study of North American retirement-aged residents (N = 303). The primary outcome variable was a modified 10-year absolute CHD risk score from the Framingham Heart Study. Secondary outcomes included adiposity and a 5-item measure of patient/provider interaction inhibition. We regressed CHD risk on negative affect (NA), social inhibition (SI), and the NAxSI interaction (i.e., the Type D personality) and repeated these analyses for adiposity and for patient/provider interaction inhibition. We also contrasted CHD risk across Type D and non-Type D categories. RESULTS: None of the personality variables were associated with CHD risk for the whole sample (regression coefficients from −0.11 to .10, Ps > 0.29) or in gender-specific analyses. For adiposity, NA was positively associated and SI was negatively associated with BMI in women (Ps < 0.05), but there were no other personality associations. Patient/provider interaction inhibition was associated with SI (P < 0.001) but not NA or the NAxSI interaction (P = 0.42). The contrast between Type D and non-Type D personality revealed no differences in CHD risk (P = 0.93). CONCLUSIONS: Neither Type D nor its constituent NA and SI traits were associated with absolute incident CHD risk in retirement-aged adults free of reported CHD. Optimal analytic practices and attention to patient/provider interaction behavior will improve our understanding of the association between Type D personality traits and health.

Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification.

Methylenetetrahydrofolate reductase (MTHFR) catalyses the reduction of methylenetetrahydrofolate to methyltetrahydrofolate, a cofactor for homocysteine methylation to methionine. MTHFR deficiency, an autosomal recessive disorder, results in homocysteinemia. Using degenerate oligonucleotides based on porcine peptide sequence data, we isolated a 90-bp cDNA by PCR from pig liver RNA. This cDNA was used to isolate a human cDNA, the predicted amino acid sequence of which shows strong homology to porcine MTHFR and to bacterial metF genes. The human gene has been localized to chromosome 1p36.3. Two mutations were identified in MTHFR-deficient patients: a missense mutation (Arg to Gln), in a residue conserved in bacterial enzymes, and a nonsense mutation (Arg to Ter).

Geriatric Services Hub - A Collaborative Frailty Management Model between The Hospital and Community Providers.

BACKGROUND: Frailty is an important geriatric syndrome especially with ageing populations. Frailty can be managed or even reversed with community-based interventions delivered by a multi-disciplinary team. Innovation is required to find community frailty models that can deliver cost-effective and feasible care to each local context. OBJECTIVES: We share pilot data from our Geriatric Service Hub (GSH) which is a novel frailty care model in Singapore that identifies and manages frailty in the community, supported by a hospital-based multi-disciplinary team. METHODS: We describe in detail our GSH model and its implementation. We performed a retrospective data analysis on patient characteristics, uptake, prevalence of frailty and sarcopenia and referral rates for multi-component interventions. RESULTS: A total of 152 persons attended between January 2020 to May 2021. Majority (59.9%) were female and mean age was 81.0 ± 7.1 years old. One-fifth (21.1%) of persons live alone. Mean Charlson Co-morbidity Index was 5.2 ± 1.8. Based on the clinical frailty risk scale (CFS), 31.6% were vulnerable, 51.3% were mildly frail and 12.5% were moderately frail. Based on SARC-F screening, 45.3% were identified to be sarcopenic whilst 56.9% had a high concern about falling using the Falls-Efficacy Scale-International. BMD scans were done for 41.4% of participants, of which 58.7% were started on osteoporosis treatment. In terms of referrals to allied health professionals, 87.5% were referred for physiotherapy, 71.1% for occupational therapy and 50.7% to dieticians. CONCLUSION: The GSH programme demonstrates a new local model of partnering with community service providers to bring comprehensive population level frailty screening and interventions to pre-frail and frail older adults. Our study found high rates of frailty, sarcopenia and fear of falling in community-dwelling older adults who were not presently known to geriatric care services.

Comparison of three assays for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in SurePath Pap samples and the role of pre- and postcytology testing.

Chlamydia trachomatis and Neisseria gonorrhoeae are common causes of sexually transmitted infections, and there is interest in screening SurePath liquid-based Pap (L-Pap) samples with Aptima Combo 2 (AC2), Amplicor (AMP), and ProbeTec ET (PT) assays. SurePath L-Pap samples and a cervical swab (CS) were collected from 394 women attending health clinics in Hamilton and Toronto, ON, Canada. L-Pap samples were tested with the three assays prior to being processed for cytology, and the CS sample was tested with AC2. The prevalence of C. trachomatis was 8.9%, and that of N. gonorrhoeae was 1.5%. By using the positives from CS testing, as well as CS negatives corresponding to L-Pap samples that tested positive in 2 of 3 assays, the sensitivities of AC2, AMP, and PT for C. trachomatis in precytology samples were calculated to be 97.1% (34 of 35 positive samples were detected), 91.4% (32 of 35 were detected), and 77.1% (27 of 35 were detected), respectively. Six women were infected with N. gonorrhoeae. After cytology processing, the results of testing the remaining liquid in the L-Pap vial and the cell-enriched fraction for C. trachomatis by AC2 showed positive agreements of 98.9% (kappa [k], 0.93) and 98.7% (k, 0.92), respectively, with the results of testing precytology L-Pap samples. Although all testing showed high specificity, testing for C. trachomatis by AC2 was significantly more sensitive than testing by PT for SurePath samples (P = 0.02). Newer versions of AMP (Cobas 4800) and PT (Q(x) with XTR technology) need published evaluations for detecting C. trachomatis and N. gonorrhoeae in L-Pap samples. C. trachomatis testing can be performed with similar results on pre- and postcytology SurePath samples.

Lie Markov models.

Recent work has discussed the importance of multiplicative closure for the Markov models used in phylogenetics. For continuous-time Markov chains, a sufficient condition for multiplicative closure of a model class is ensured by demanding that the set of rate-matrices belonging to the model class form a Lie algebra. It is the case that some well-known Markov models do form Lie algebras and we refer to such models as "Lie Markov models". However it is also the case that some other well-known Markov models unequivocally do not form Lie algebras (GTR being the most conspicuous example). In this paper, we will discuss how to generate Lie Markov models by demanding that the models have certain symmetries under nucleotide permutations. We show that the Lie Markov models include, and hence provide a unifying concept for, "group-based" and "equivariant" models. For each of two and four character states, the full list of Lie Markov models with maximal symmetry is presented and shown to include interesting examples that are neither group-based nor equivariant. We also argue that our scheme is pleasing in the context of applied phylogenetics, as, for a given symmetry of nucleotide substitution, it provides a natural hierarchy of models with increasing number of parameters. We also note that our methods are applicable to any application of continuous-time Markov chains beyond the initial motivations we take from phylogenetics.

The algebra of the general Markov model on phylogenetic trees and networks.

It is known that the Kimura 3ST model of sequence evolution on phylogenetic trees can be extended quite naturally to arbitrary split systems. However, this extension relies heavily on mathematical peculiarities of the associated Hadamard transformation, and providing an analogous augmentation of the general Markov model has thus far been elusive. In this paper, we rectify this shortcoming by showing how to extend the general Markov model on trees to include incompatible edges; and even further to more general network models. This is achieved by exploring the algebra of the generators of the continuous-time Markov chain together with the "splitting" operator that generates the branching process on phylogenetic trees. For simplicity, we proceed by discussing the two state case and then show that our results are easily extended to more states with little complication. Intriguingly, upon restriction of the two state general Markov model to the parameter space of the binary symmetric model, our extension is indistinguishable from the Hadamard approach only on trees; as soon as any incompatible splits are introduced the two approaches give rise to differing probability distributions with disparate structure. Through exploration of a simple example, we give an argument that our extension to more general networks has desirable properties that the previous approaches do not share. In particular, our construction allows for convergent evolution of previously divergent lineages; a property that is of significant interest for biological applications.

Advances in respiratory protective equipment: practical experiences of CleanSpace® HALO™ by healthcare workers.

BACKGROUND: Personal protective equipment (PPE) offers protection from infections and hazardous materials. Advances in technology have seen rapid improvement of respiratory PPEs but real-world evaluations are needed to understand whether newer devices offer greater usability and overcome common barriers to correct use. AIM: To survey the user experiences of a new PPE device, CleanSpace® HALO™, in comparison to existing masks and respirators to determine advantages and disadvantages. METHODS: Frontline healthcare workers of a large healthcare provider cluster in Singapore with practical experience of using respiratory PPE, including the CleanSpace® HALO™, were surveyed. Ease of communication, comfort, usability, ability to provide care, perceived effectiveness, barriers, and enablers to respiratory PPE use were investigated. FINDINGS: A total of 93 respondents were included in the analysis. CleanSpace® HALO™ was rated highly in terms of perceived safety (92%), comfort (40%), and ease of donning and doffing (53%). CleanSpace® HALO™ was less disruptive to patient care (8%), although the ability to communicate effectively remained an obstacle (22%). Respondents also noted the incomplete facial protection provided by CleanSpace® HALO™. CONCLUSION: Respiratory protective devices are integral to effective infection control protocols, but their usefulness is limited by their impact on care delivery and incorrect use. The CleanSpace® HALO™ demonstrated advantages over existing powered air purifying respirator devices but some issues remain. Future iterations must strive to overcome communication challenges and address common side-effects. Better education is also needed to improve user confidence with CleanSpace® HALO™.

Work-related symptoms in nail salon technicians.

BACKGROUND: Nail salons are a rapidly expanding small business sector. Environmental health practitioners have raised concerns about potential health and safety issues. AIMS: To establish the extent of work-related health issues reported by nail salon technicians, their knowledge of health and safety regulations and of the products used. METHODS: Nail technicians completed a researcher-administered questionnaire, and responses were compared to those of non-exposed office-based control subjects. RESULTS: In all, 39 of 588 nail salons approached agreed to participate (7%), with all 71 (100%) of the available nail technicians within these salons completing study questionnaires. The majority of the nail technicians (99%) had received training that had included aspects of health and safety and most reported being aware of the Control of Substances Hazardous to Health regulations (59/70, 84%) and risk assessments (65/70, 93%). Compared to the control group, the nail technicians reported statistically significant increased levels of work-related neck (OR 5.0, 95% CI 1.6-15.6), shoulder (15.0, 3.1-71.8), wrist/hand (3.6, 1.2-10.7) and lower back problems (3.5, 1.0-12.5). Work-related nasal symptoms were also significantly more common in nail technicians (6.2, 1.3-30.7). CONCLUSIONS: This study demonstrated a higher prevalence of a range of musculoskeletal problems and respiratory symptoms reported by nail technicians compared to office-based controls. An ergonomic and exposure assessment of work practices in this industry is warranted to identify the working practices associated with these symptoms, in order to inform best practice, supplement industry and regulatory guidance and develop appropriate practical work-based training.

Phylogenetic estimation with partial likelihood tensors.

We present an alternative method for calculating likelihoods in molecular phylogenetics. Our method is based on partial likelihood tensors, which are generalizations of partial likelihood vectors, as used in Felsenstein's approach. Exploiting a lexicographic sorting and partial likelihood tensors, it is possible to obtain significant computational savings. We show this on a range of simulated data by enumerating all numerical calculations that are required by our method and the standard approach.

Demographic variables are associated with knowledge, attitudes, and preventive behaviors related to environmental tobacco smoke.

INTRODUCTION: Environmental tobacco smoke (ETS) is the third leading preventable cause of death in the United States. Few biopsychosocial studies have addressed knowledge of specific ETS health effects, attitudes toward ETS, and personal preventive efforts related to ETS. METHOD: We surveyed a diverse U.S. community sample of convenience (N = 328) in Flagstaff, Arizona, to examine the following: (a) Does ETS knowledge measured using two response formats, open-ended (OPEF) versus closed-ended (CLEF), result in differences in apparent knowledge? and (b) what are demographic predictors of ETS knowledge, attitudes, and preventive behaviors? RESULTS: Participants scored significantly higher on the ETS knowledge CLEF than OPEF. In regression analyses, predictors of ETS knowledge on the OPEF scale included ethnicity, age, and smoking status; the model predicting knowledge using the CLEF scale was not significant. Knowledge and smoking status, as measured on both the CLEF and the OPEF, were significant predictors of negative attitudes. Additional predictors of attitudes included income for the model using the OPEF and gender for the model using the CLEF. Predictors of preventive behaviors included attitudes and age (OPEF and CLEF models). DISCUSSION: Differences in apparent ETS knowledge of specific ETS health effects by varying response format suggest that open-ended surveys may be useful in identifying specific content areas to address in public health education efforts. Various demographic variables predicted ETS knowledge, attitudes, and preventive behaviors, highlighting specific populations to target in public health interventions relating to ETS, such as non-White and younger populations.