Substance Use in Adolescents 10 Years After the World Trade Center Attacks in New York City

We examined prevalence of and factors associated with substance use 10 to 11 years post-9/11 among adolescents in the World Trade Center Health Registry. Logistic regression analyses showed that adolescents who witnessed a disturbing event on 9/11 were twice as likely to report ever drinking and almost three times as likely to have ever used marijuana. Among those ≥ years of age on 9/11, fear for personal safety on 9/11 was significantly associated with having ever smoked cigarettes, ever drank, and ever used marijuana. Intervention and education for adolescents particularly focused on substance use and coping strategies may be warranted after large-scale disasters

A Qualitative Examination of Health and Health Care Utilization after the September 11th Terror Attacks among World Trade Center Health Registry Enrollees

Background Many individuals who have 9/11-related physical and mental health symptoms do not use or are unaware of 9/11-related health care services despite extensive education and outreach efforts by the World Trade Center (WTC) Health Registry (the Registry) and various other organizations. This study sought to evaluate Registry enrollees’ perceptions of the relationship between physical and mental health outcomes and 9/11, as well as utilization of and barriers to 9/11-related health care services. Methods Six focus groups were conducted in January 2010 with diverse subgroups of enrollees, who were likely eligible for 9/11-related treatment services. The 48 participants were of differing race/ethnicities, ages, and boroughs of residence. Qualitative analysis of focus group transcripts was conducted using open coding and the identification of recurring themes. Results Participants described a variety of physical and mental symptoms and conditions, yet their knowledge and utilization of 9/11 health care services were low. Participants highlighted numerous barriers to accessing 9/11 services, including programmatic barriers (lack of program visibility and accessibility), personal barriers such as stigmatization and unfamiliarity with 9/11-related health problems and services, and a lack of referrals from their primary care providers. Moreover, many participants were reluctant to connect their symptoms to the events of 9/11 due to lack of knowledge, the amount of time that had elapsed since 9/11, and the attribution of current health symptoms to the aging process. Conclusions Knowledge of the barriers to 9/11-related health care has led to improvements in the Registry’s ability to refer eligible enrollees to appropriate treatment programs. These findings highlight areas for consideration in the implementation of the new federal WTC Health Program, now funded under the James Zadroga 9/11 Health and Compensation Act (PL 111-347), which includes provisions for outreach and education. Keywords: September 11, 2001, 9/11; World Trade Center Health Registry; Health care utilization; Barriers to care; Focus group

Trajectories of PTSD Among Lower Manhattan Residents and Area Workers Following the 2001 World Trade Center Disaster, 2003–2012

Group-based trajectory modeling was used to explore empirical trajectories of symptoms of posttraumatic stress disorder (PTSD) among 17,062 adult area residents/workers (nonrescue/recovery workers) enrolled in the World Trade Center (WTC) Health Registry using 3 administrations of the PTSD Checklist (PCL) over 9 years of observation. Six trajectories described PTSD over time: low-stable (48.9%), moderate-stable (28.3%), moderate-increasing (8.2%), high-stable (6.0%), high-decreasing (6.6 %), and very high-stable (2.0%). To examine factors associated with improving or worsening PTSD symptoms, groups with similar intercepts, but different trajectories were compared using bivariate analyses and logistic regression. The adjusted odds of being in the moderate-increasing relative to the moderate-stable group were significantly greater among enrollees reporting low social integration (OR = 2.18), WTC exposures (range = 1.34 to 1.53), job loss related to the September 11, 2001 disaster (OR = 1.41), or unmet mental health need/treatment (OR = 4.37). The odds of being in the high-stable relative to the high-decreasing group were significantly greater among enrollees reporting low social integration (OR = 2.23), WTC exposures (range = 1.39 to 1.45), or unmet mental health need/treatment (OR = 3.42). The influence of severe exposures, scarce personal/financial resources, and treatment barriers on PTSD trajectories suggest a need for early and ongoing PTSD screening postdisaster

Comparison of health outcomes among affiliated and lay disaster volunteers enrolled in the World Trade Center Health Registry

Background. Volunteers (non-professional rescue/recovery workers) are universally present at manmade and natural disasters and share experiences and exposures with victims. Little is known of their disaster-related health outcomes. Methods. We studied 4974 adult volunteers who completed the World Trade Center Health Registry 2006–07 survey to examine associations between volunteer type (affiliated vs. lay) and probable posttraumatic stress disorder (PTSD); new or worsening respiratory symptoms; post-9/11 first diagnosis of anxiety disorder, depression, and/or PTSD; and asthma or reactive airway dysfunction syndrome (RADS). Affiliated volunteers reported membership in a recognized organization. Lay volunteers reported no organizational affiliation and occupations unrelated to rescue/recovery work. Adjusted odds ratios (ORadj) were calculated using multinomial regression. Results. Lay volunteers were more likely than affiliated volunteers to have been present in lower Manhattan, experience the dust cloud, horrific events and injury on 9/11 and subsequently to report unmet healthcare needs. They had greater odds of early post-9/11 mental health diagnosis (ORadj 1.6; 95% CI: 1.4–2.0) and asthma/RADS (1.8; 1.2–2.7), chronic PTSD (2.2; 1.7–2.8), late-onset PTSD (1.9; 1.5–2.5), and new or worsening lower respiratory symptoms (2.0; 1.8–2.4). Conclusions. Lay volunteers' poorer health outcomes reflect earlier, more intense exposure to and lack of protection from physical and psychological hazards. There is a need to limit volunteers' exposures during and after disasters, as well as to provide timely screening and health care post-disaster

Nonfatal Injuries 1 Week After Hurricane Sandy — New York City Metropolitan Area, October 2012

On October 29, 2012, Hurricane Sandy (Sandy) made landfall in densely populated areas of New York, New Jersey, and Connecticut. Flooding affected 51 square miles (132 square kilometers) of New York City (NYC) and resulted in 43 deaths, many caused by drowning in the home, along with numerous storm-related injuries. Thousands of those affected were survivors of the World Trade Center (WTC) disaster of September 11, 2001 (9/11) who had previously enrolled in the WTC Health Registry (Registry) cohort study. To assess Sandy-related injuries and associated risk factors among those who lived in Hurricane Sandy-flooded areas and elsewhere, the NYC Department of Health and Mental Hygiene surveyed 8,870 WTC survivors, who had provided physical and mental health updates 8 to 16 months before Sandy. Approximately 10% of the respondents in flooded areas reported injuries in the first week after Sandy; nearly 75% of those had more than one injury. Injuries occurred during evacuation and clean-up/repair of damaged or destroyed homes. Hurricane preparation and precautionary messages emphasizing potential for injury hazards during both evacuation and clean-up or repair of damaged residences might help mitigate the occurrence and severity of injury after a hurricane

Association of the PHACTR1/EDN1 genetic locus with spontaneous coronary artery dissection

Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. Objectives: This study sought to test the association between the rs9349379 genotype and SCAD. Methods: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. Results: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. Conclusions: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre

A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts.

The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance energy transfer (FRET) biosensor mouse and its utility for monitoring real-time activity of RhoA in a variety of native tissues in vivo. We assess changes in RhoA activity during mechanosensing of osteocytes within the bone and during neutrophil migration. We also demonstrate spatiotemporal order of RhoA activity within crypt cells of the small intestine and during different stages of mammary gestation. Subsequently, we reveal co-option of RhoA activity in both invasive breast and pancreatic cancers, and we assess drug targeting in these disease settings, illustrating the potential for utilizing this mouse to study RhoA activity in vivo in real time