Longitudinal symptoms of post-traumatic stress disorder (PTSD) are often characterized by heterogeneous trajectories, which may have unique pre-, peri- and post-trauma risk and protective factors. To ...date, however, no study has evaluated the nature and determinants of predominant trajectories of PTSD symptoms in World Trade Center (WTC) responders.
A total of 10835 WTC responders, including 4035 professional police responders and 6800 non-traditional responders (e.g. construction workers) who participated in the WTC Health Program (WTC-HP), were evaluated an average of 3, 6 and 8 years after the WTC attacks.
Among police responders, longitudinal PTSD symptoms were best characterized by four classes, with the majority (77.8%) in a resistant/resilient trajectory and the remainder exhibiting chronic (5.3%), recovering (8.4%) or delayed-onset (8.5%) symptom trajectories. Among non-traditional responders, a six-class solution was optimal, with fewer responders in a resistant/resilient trajectory (58.0%) and the remainder exhibiting recovering (12.3%), severe chronic (9.5%), subsyndromal increasing (7.3%), delayed-onset (6.7%) and moderate chronic (6.2%) trajectories. Prior psychiatric history, Hispanic ethnicity, severity of WTC exposure and WTC-related medical conditions were most strongly associated with symptomatic trajectories of PTSD symptoms in both groups of responders, whereas greater education and family and work support while working at the WTC site were protective against several of these trajectories.
Trajectories of PTSD symptoms in WTC responders are heterogeneous and associated uniquely with pre-, peri- and post-trauma risk and protective factors. Police responders were more likely than non-traditional responders to exhibit a resistant/resilient trajectory. These results underscore the importance of prevention, screening and treatment efforts that target high-risk disaster responders, particularly those with prior psychiatric history, high levels of trauma exposure and work-related medical morbidities.
Abstract
We analyse the velocity dispersion properties of 472 z ∼ 0.9 star-forming galaxies observed as part of the KMOS Redshift One Spectroscopic Survey (KROSS). The majority of this sample is ...rotationally dominated (83 ± 5 per cent with vC/σ0 > 1) but also dynamically hot and highly turbulent. After correcting for beam smearing effects, the median intrinsic velocity dispersion for the final sample is σ0 = 43.2 ± 0.8 km s−1 with a rotational velocity to dispersion ratio of vC/σ0 = 2.6 ± 0.1. To explore the relationship between velocity dispersion, stellar mass, star formation rate, and redshift, we combine KROSS with data from the SAMI survey (z ∼ 0.05) and an intermediate redshift MUSE sample (z ∼ 0.5). Whilst there is, at most, a weak trend between velocity dispersion and stellar mass, at fixed mass there is a strong increase with redshift. At all redshifts, galaxies appear to follow the same weak trend of increasing velocity dispersion with star formation rate. Our results are consistent with an evolution of galaxy dynamics driven by discs that are more gas rich, and increasingly gravitationally unstable, as a function of increasing redshift. Finally, we test two analytic models that predict turbulence is driven by either gravitational instabilities or stellar feedback. Both provide an adequate description of the data, and further observations are required to rule out either model.
Higher latitude, lower ultraviolet exposure, and lower serum 25-hydroxyvitamin D (25OHD) correlate with higher multiple sclerosis (MS) prevalence, relapse rate, and mortality. We therefore evaluated ...the effects of high-dose vitamin D2 (D2) in MS.
Adults with clinically active relapsing-remitting MS (RRMS) were randomized to 6 months' double-blind placebo-controlled high-dose vitamin D2, 6,000 IU capsules, dose adjusted empirically aiming for a serum 25OHD 130-175 nM. All received daily low-dose (1,000 IU) D2 to prevent deficiency. Brain MRIs were performed at baseline, 4, 5, and 6 months. Primary endpoints were the cumulative number of new gadolinium-enhancing lesions and change in the total volume of T2 lesions. Secondary endpoints were Expanded Disability Status Scale (EDSS) score and relapses.
Twenty-three people were randomized, of whom 19 were on established interferon or glatiramer acetate (Copaxone) treatment. Median 25OHD rose from 54 to 69 nM (low-dose D2) vs 59 to 120 nM (high-dose D2) (p = 0.002). No significant treatment differences were detected in the primary MRI endpoints. Exit EDSS, after adjustment for entry EDSS, was higher following high-dose D2 than following low-dose D2 (p = 0.05). There were 4 relapses with high-dose D2 vs none with low-dose D2 (p = 0.04).
We did not find a therapeutic advantage in RRMS for high-dose D2 over low-dose D2 supplementation.
This study provides Class I evidence that high-dose vitamin D2 (targeting 25OHD 130-175 nM), compared to low-dose supplementation (1,000 IU/d), was not effective in reducing MRI lesions in patients with RRMS.
Abstract
Globally, there are millions of kilometres of drainage ditches which have the potential to emit the powerful greenhouse gas methane (CH
4
), but these emissions are not reported in budgets ...of inland waters or drained lands. Here, we synthesise data to show that ditches spanning a global latitudinal gradient and across different land uses emit large quantities of CH
4
to the atmosphere. Area-specific emissions are comparable to those from lakes, streams, reservoirs, and wetlands. While it is generally assumed that drainage negates terrestrial CH
4
emissions, we find that CH
4
emissions from ditches can, on average, offset ∼10% of this reduction. Using global areas of drained land we show that ditches contribute 3.5 Tg CH
4
yr
−1
(0.6–10.5 Tg CH
4
yr
−1
); equivalent to 0.2%–3% of global anthropogenic CH
4
emissions. A positive relationship between CH
4
emissions and temperature was found, and emissions were highest from eutrophic ditches. We advocate the inclusion of ditch emissions in national GHG inventories, as neglecting them can lead to incorrect conclusions concerning the impact of drainage-based land management on CH
4
budgets.
Summary Background Despite its common use in cancer treatment, radiotherapy has not yet entered the era of precision medicine, and there have been no approaches to adjust dose based on biological ...differences between or within tumours. We aimed to assess whether a patient-specific molecular signature of radiation sensitivity could be used to identify the optimum radiotherapy dose. Methods We used the gene-expression-based radiation-sensitivity index and the linear quadratic model to derive the genomic-adjusted radiation dose (GARD). A high GARD value predicts for high therapeutic effect for radiotherapy; which we postulate would relate to clinical outcome. Using data from the prospective, observational Total Cancer Care (TCC) protocol, we calculated GARD for primary tumours from 20 disease sites treated using standard radiotherapy doses for each disease type. We also used multivariable Cox modelling to assess whether GARD was independently associated with clinical outcome in five clinical cohorts: Erasmus Breast Cancer Cohort (n=263); Karolinska Breast Cancer Cohort (n=77); Moffitt Lung Cancer Cohort (n=60); Moffitt Pancreas Cancer Cohort (n=40); and The Cancer Genome Atlas Glioblastoma Patient Cohort (n=98). Findings We calculated GARD for 8271 tissue samples from the TCC cohort. There was a wide range of GARD values (range 1·66–172·4) across the TCC cohort despite assignment of uniform radiotherapy doses within disease types. Median GARD values were lowest for gliomas and sarcomas and highest for cervical cancer and oropharyngeal head and neck cancer. There was a wide range of GARD values within tumour type groups. GARD independently predicted clinical outcome in breast cancer, lung cancer, glioblastoma, and pancreatic cancer. In the Erasmus Breast Cancer Cohort, 5-year distant-metastasis-free survival was longer in patients with high GARD values than in those with low GARD values (hazard ratio 2·11, 95% 1·13–3·94, p=0·018). Interpretation A GARD-based clinical model could allow the individualisation of radiotherapy dose to tumour radiosensitivity and could provide a framework to design genomically-guided clinical trials in radiation oncology. Funding None.
ABSTRACT The COSMOS-Legacy survey is a 4.6 Ms Chandra program that has imaged 2.2 deg2 of the COSMOS field with an effective exposure of ks over the central 1.5 deg2 and of ks in the remaining area. ...The survey is the combination of 56 new observations obtained as an X-ray Visionary Project with the previous C-COSMOS survey. We describe the reduction and analysis of the new observations and the properties of 2273 point sources detected above a spurious probability of 2 × 10−5. We also present the updated properties of the C-COSMOS sources detected in the new data. The whole survey includes 4016 point sources (3814, 2920 and 2440 in the full, soft, and hard band). The limiting depths are 2.2 × 10−16, 1.5 × 10−15, and 8.9 × 10−16 in the 0.5-2, 2-10, and 0.5-10 keV bands, respectively. The observed fraction of obscured active galactic nuclei with a column density >1022 cm−2 from the hardness ratio (HR) is ∼50 %. Given the large sample we compute source number counts in the hard and soft bands, significantly reducing the uncertainties of 5%-10%. For the first time we compute number counts for obscured (HR > −0.2) and unobscured (HR < −0.2) sources and find significant differences between the two populations in the soft band. Due to the unprecedent large exposure, COSMOS-Legacy area is three times larger than surveys at similar depths and its depth is three times fainter than surveys covering similar areas. The area-flux region occupied by COSMOS-Legacy is likely to remain unsurpassed for years to come.
Objectives This study sought to evaluate the safety and efficacy of the CoreValve transcatheter heart valve (THV) for the treatment of severe aortic stenosis in patients at extreme risk for surgery. ...Background Untreated severe aortic stenosis is a progressive disease with a poor prognosis. Transcatheter aortic valve replacement (TAVR) with a self-expanding bioprosthesis is a potentially effective therapy. Methods We performed a prospective, multicenter, nonrandomized investigation evaluating the safety and efficacy of self-expanding TAVR in patients with symptomatic severe aortic stenosis with prohibitive risks for surgery. The primary endpoint was a composite of all-cause mortality or major stroke at 12 months, which was compared with a pre-specified objective performance goal (OPG). Results A total of 41 sites in the United States recruited 506 patients, of whom 489 underwent attempted treatment with the CoreValve THV. The rate of all-cause mortality or major stroke at 12 months was 26.0% (upper 2-sided 95% confidence bound: 29.9%) versus 43.0% with the OPG (p < 0.0001). Individual 30-day and 12-month events included all-cause mortality (8.4% and 24.3%, respectively) and major stroke (2.3% and 4.3%, respectively). Procedural events at 30 days included life-threatening/disabling bleeding (12.7%), major vascular complications (8.2%), and need for permanent pacemaker placement (21.6%). The frequency of moderate or severe paravalvular aortic regurgitation was lower 12 months after self-expanding TAVR (4.2%) than at discharge (10.7%; p = 0.004 for paired analysis). Conclusions TAVR with a self-expanding bioprosthesis was safe and effective in patients with symptomatic severe aortic stenosis at prohibitive risk for surgical valve replacement. (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement; NCT01240902 )
Post-traumatic stress disorder (PTSD) in response to the World Trade Center (WTC) disaster of 11 September 2001 (9/11) is one of the most prevalent and persistent health conditions among both ...professional (e.g. police) and non-traditional (e.g. construction worker) WTC responders, even several years after 9/11. However, little is known about the dimensionality and natural course of WTC-related PTSD symptomatology in these populations.
Data were analysed from 10 835 WTC responders, including 4035 police and 6800 non-traditional responders who were evaluated as part of the WTC Health Program, a clinic network in the New York area established by the National Institute for Occupational Safety and Health. Confirmatory factor analyses (CFAs) were used to evaluate structural models of PTSD symptom dimensionality; and autoregressive cross-lagged (ARCL) panel regressions were used to examine the prospective interrelationships among PTSD symptom clusters at 3, 6 and 8 years after 9/11.
CFAs suggested that five stable symptom clusters best represent PTSD symptom dimensionality in both police and non-traditional WTC responders. This five-factor model was also invariant over time with respect to factor loadings and structural parameters, thereby demonstrating its longitudinal stability. ARCL panel regression analyses revealed that hyperarousal symptoms had a prominent role in predicting other symptom clusters of PTSD, with anxious arousal symptoms primarily driving re-experiencing symptoms, and dysphoric arousal symptoms primarily driving emotional numbing symptoms over time.
Results of this study suggest that disaster-related PTSD symptomatology in WTC responders is best represented by five symptom dimensions. Anxious arousal symptoms, which are characterized by hypervigilance and exaggerated startle, may primarily drive re-experiencing symptoms, while dysphoric arousal symptoms, which are characterized by sleep disturbance, irritability/anger and concentration difficulties, may primarily drive emotional numbing symptoms over time. These results underscore the importance of assessment, monitoring and early intervention of hyperarousal symptoms in WTC and other disaster responders.
Variation in venom composition is a ubiquitous phenomenon in snakes and occurs both interspecifically and intraspecifically. Venom variation can have severe outcomes for snakebite victims by ...rendering the specific antibodies found in antivenoms ineffective against heterologous toxins found in different venoms. The rapid evolutionary expansion of different toxin-encoding gene families in different snake lineages is widely perceived as the main cause of venom variation. However, this view is simplistic and disregards the understudied influence that processes acting on gene transcription and translation may have on the production of the venom proteome. Here, we assess the venom composition of six related viperid snakes and compare interspecific changes in the number of toxin genes, their transcription in the venom gland, and their translation into proteins secreted in venom. Our results reveal that multiple levels of regulation are responsible for generating variation in venom composition between related snake species. We demonstrate that differential levels of toxin transcription, translation, and their posttranslational modification have a substantial impact upon the resulting venom protein mixture. Notably, these processes act to varying extents on different toxin paralogs found in different snakes and are therefore likely to be as important as ancestral gene duplication events for generating compositionally distinct venom proteomes. Our results suggest that these processes may also contribute to altering the toxicity of snake venoms, and we demonstrate how this variability can undermine the treatment of a neglected tropical disease, snakebite.
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