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Early life adversity (ELA) has been associated with inflammation and immunosenescence, as well as hyporeactivity of the HPA axis. Because the immune system and the HPA axis are tightly intertwined around the glucocorticoid receptor (GR), we examined peripheral GR functionality in the EpiPath cohort among participants who either had been exposed to ELA (separation from parents and/or institutionalization followed by adoption; n = 40) or had been reared by their biological parents (n = 72).
Expression of the strict GR target genes FKBP5 and GILZ as well as total and 1F and 1H GR transcripts were similar between groups. Furthermore, there were no differences in GR sensitivity, examined by the effects of dexamethasone on IL6 production in LPS-stimulated whole blood. Although we did not find differences in methylation at the GR 1F exon or promoter region, we identified a region of the GR 1H promoter (CpG 1-9) that showed lower methylation levels in ELA.
Our results suggest that peripheral GR signaling was unperturbed in our cohort and the observed immune phenotype does not appear to be secondary to an altered GR response to the perturbed HPA axis and glucocorticoid (GC) profile, although we are limited in our measures of GR activity and time points.
An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care.
We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities.
We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend “mitochondrial cocktails” for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority.
While Canadian physicians’ views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols.
On October 7, 2016, Hurricane Matthew traveled along the coasts of Florida, Georgia, and South Carolina causing flooding and power outages. The Georgia Department of Public Health (DPH) developed the Web-based Responder Safety, Tracking, and Resilience (R-STaR) system to monitor the health and safety of public health responders and to inform disaster response planning for Hurricane Matthew. Using R-STaR, responders (n = 126) were e-mailed a daily survey while deployed to document injuries or harmful exposures and a post-deployment survey on their post-deployment health and satisfaction with using R-STaR. DPH epidemiologists contacted responders reporting injuries or exposures to determine the need for medical care. Frequencies were tabulated for quantitative survey responses, and qualitative data were summarized into key themes. Five percent (6/126) of responders reported injuries, and 81% (43/53) found R-STaR easy to use. Suggestions for R-STaR improvement included improving accessibility using mobile platforms and conducting pre-event training of responders on R-STaR. Lessons learned from R-STaR development and evaluation can inform the development and improvement of responder health surveillance systems at other local and state health departments and disaster and emergency response agencies. (Disaster Med Public Health Preparedness. 2019;13:74–81).
Non-suicidal self-injury (NSSI) prospectively predicts suicidal thoughts and behaviors in civilian populations. Despite high rates of suicide among US military members, little is known about the prevalence and course of NSSI, or how NSSI relates to suicidal thoughts and behaviors, in military personnel.
We conducted secondary analyses of two representative surveys of active-duty soldiers (N = 21 449) and newly enlisted soldiers (N = 38 507) from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS).
The lifetime prevalence of NSSI is 6.3% (1.2% 12-month prevalence) in active-duty soldiers and 7.9% (1.3% 12-month prevalence) in new soldiers. Demographic risk factors for lifetime NSSI include female sex, younger age, non-Hispanic white ethnicity, never having married, and lower educational attainment. The association of NSSI with temporally primary internalizing and externalizing disorders varies by service history (new v. active-duty soldiers) and gender (men v. women). In both active-duty and new soldiers, NSSI is associated with increased odds of subsequent onset of suicidal ideation [adjusted odds ratio (OR) = 1.66–1.81] and suicide attempts (adjusted OR = 2.02–2.43), although not with the transition from ideation to attempt (adjusted OR = 0.92–1.36). Soldiers with a history of NSSI are more likely to have made multiple suicide attempts, compared with soldiers without NSSI.
NSSI is prevalent among US Army soldiers and is associated with significantly increased odds of later suicidal thoughts and behaviors, even after NSSI has resolved. Suicide risk assessments in military populations should screen for history of NSSI.
Introduction: Deep vein thrombosis (DVT) can lead to significant morbidity and mortality if not diagnosed and treated promptly. Currently, few methods aside from venous duplex scanning can rule out DVT in patients presenting to the Emergency Department (ED). Current screening tools, including the use of the subjective Wells score, frequently leads to unnecessary investigations and anticoagulation. In this study, we sought to determine whether two-site compression point-of-care ultrasound (POCUS) combined with a negative age-adjusted D-dimer test can accurately rule out DVT in ED patients irrespective of the modified Wells score. Methods: This is a single-center, prospective observational study in the ED of the Jewish General Hospital in Montreal. We are recruiting a convenience sample of patients presenting to the ED with symptoms suggestive of DVT. All enrolled patients are risk-stratified using the modified Wells criteria for DVT, then undergo two-site compression POCUS, and testing for age-adjusted D-dimer. Patients with DVT unlikely according to modified Wells score, negative POCUS and negative age-adjusted D-dimer are discharged home and receive a three-month phone follow-up. Patients with DVT likely according to modified Wells score, a positive POCUS or a positive age-adjusted D-dimer, will undergo a venous duplex scan. A true negative DVT is defined as either a negative venous duplex scan or a negative follow-up phone questionnaire for patients who were sent home without a venous duplex scan. Results: Of the 42 patients recruited thus far, the mean age is 56 years old and 42.8% are male. Twelve (28.6%) patients had DVT unlikely as per modified Wells score, negative POCUS and negative age-adjusted D-dimer and were discharged home. None of these patients developed a DVT on three-month follow-up. Thirty patients (71.4%) had either a DVT likely as per modified Wells score, a positive POCUS or a positive age-adjusted D-dimer and underwent a venous duplex scan. Of those, six patients had a confirmed DVT (3 proximal & 3 distal). POCUS detected all proximal DVTs, while combined POCUS and age-adjusted D-dimer detected all proximal and distal DVTs. None of the patients with a negative POCUS and age-adjusted D-dimer were found to have a DVT. Conclusion: Two-site compression POCUS combined with a negative age-adjusted D-dimer test appears to accurately rule out DVT in ED patients without the need for follow-up duplex venous scan. Using this approach would alleviate the need to calculate the Wells score, and also reduce the need for radiology-performed duplex venous scan for many patients.
Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.
Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.
HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.
Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.
In response to the 2014 Ebola virus disease (EVD) outbreak in West Africa, the Georgia Department of Public Health developed the Infectious Disease Network (IDN) based on an EVD preparedness needs assessment of hospitals and Emergency Medical Services (EMS) providers. The network consists of 12 hospitals and 16 EMS providers with staff specially trained to provide a coordinated response and utilize appropriate personal protective equipment (PPE) for the transport or treatment of a suspected or confirmed serious communicable disease patient. To become a part of the network, each hospital and EMS provider had to demonstrate EVD capabilities in areas such as infection control, PPE, waste management, staffing and ongoing training, and patient transport and placement. To establish the network, the Georgia Department of Public Health provided training and equipment for EMS personnel, evaluated hospitals for EVD capabilities, structured communication flow, and defined responsibilities among partners. Since March 2015, the IDN has been used to transport, treat, and/or evaluate suspected or confirmed serious communicable disease cases while ensuring health care worker safety. Integrated infectious disease response systems among hospitals and EMS providers are critical to ensuring health care worker safety, and preventing or mitigating a serious communicable disease outbreak. (Disaster Med Public Health Preparedness. 2018;12:765-771)
Scientific observations of sea ice began more than a century ago, but detailed sea-ice models appeared only in the latter half of the last century. The high albedo of sea ice is critical for the Earth’s heat balance, and ice motion across the ocean’s surface transports fresh water and salt. The basic components in a complete sea-ice model must include vertical thermodynamics and horizontal dynamics, including a constitutive relation for the ice, advection and deformational processes. This overview surveys topics in sea-ice modeling from the global climate modeling perspective, emphasizing work that significantly advanced the state of the art and highlighting promising new developments.
Results are presented from EXOSAT observations of Seyfert type active galactic nuclei (AGN). The sample chosen for study are 48 hard X-ray selected Seyfert type AGN, including all 30 of the emission line AGN in the Piccinotti sample. Combining EXOSAT LE and ME data has allowed us to obtain broad band X-ray spectra over the range 0.1–10 keV. Spectra in the ∼ 2–10 keV range are found to be well described by a simple power-law. The distribution of spectral indices across the sample can be approximated by a Gaussian distribution of mean energy index ∝ = 0.70 with σ∝ = 0.17 although not all individual spectra are consistent with this mean at the 90% confidence level. EXOSAT has also revealed a substantial number of sources with complex soft X-ray spectra. These include spectra with a second spectral component at soft X-ray energies and sources with “leaky” absorbing columns. Evidence that soft excess components occur in at least 50% of Seyfert type AGN together with detection of rapid variability in the soft component provides quantitative support for an accretion disc model for AGN.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
Introduction: Undiagnosed deep vein thrombosis (DVT) can lead to significant morbidity and mortality, including death from DVT-associated massive pulmonary embolism (PE). While several validated clinical prediction rules, blood test and imaging modalities exist to investigate a potential DVT, there is currently a lack of rapid, accessible and reliable methods to exclude the possibility of DVT without resorting to formal venous duplex scanning. Currently, the use in the ED of a validated clinical prediction rule combined to either a high-sensitivity D-dimer test or ultrasonography of the lower extremities has a poor predictive value, as 75-90% of patients suspected of DVT have a negative formal venous duplex scan. Compression bedside ultrasound has however recently been shown to be a safe, rapid and accurate method for the diagnosis of proximal DVT in the emergency department with a high sensitivity and specificity (combined sensitivity and specificity of 96.1% and 96.8%, respectively1). Research question: In the present study, we will primarily assess whether two-site compression POCUS combined with a negative age-adjusted D-dimer test can accurately rule out DVT in ED patients regardless of the Wells criteria. Methods: This is a single-center, prospective, observational study carried out over one year in the Emergency Department of the Jewish General Hospital in Montreal, Quebec. We aim to enroll a convenience sample of 475 patients aged 18 years and older presenting to the ED with symptoms suggestive of a DVT. All enrolled patients will receive the standard of care required for a lower leg DVT presentation. After calculating Patients DVT risk using modified wells criteria, all patients will undergo POCUS for DVT followed by a D-dimer test. Based on their results, patients will either undergo formal duplex scanning, or will be discharged without further testing and receive a three-month phone follow-up. A true negative lower leg DVT will be defined as follows: (1) Negative follow-up phone questionnaire for patients who were sent home with no formal duplex venous scanning. (2) Negative formal duplex venous scanning for patients who were deemed likely to have lower leg DVT using the Wells score, with a negative D-dimer and POCUS. Age adjusted DVT was added to account for below knee DVT and avoid the need for patients to return for fellow up duplex study in 1 week. To estimate our technique’s sensitivity with a 4% margin of error with 95% confidence intervals, 92 confirmed DVT patients are needed. We expect to recruit a total 475 patients within one-year period at the JGH (95 DVT-positive patients and 380 DVT-negative patients). Impact: The use of compression bedside ultrasound with a negative age-adjusted D-dimer test to rule out DVT in the ED may accelerate the decision regarding patient disposition and significantly decrease the length of patient stay in the ED. In addition, it may help avoid unnecessary medical interventions and diagnostic tests, thus representing potential quality of care and cost-saving improvements as well.
Introduction: The Institute of Medicine (IOM) has recommended that high-quality, evidence-based guidelines be developed for emergency medical services (EMS). The National Association of EMS Physicians (NAEMSP) has outlined a strategy that will see this task fulfilled, consisting of multiple working groups focused on all aspects of guideline development and implementation. A first step, and our objective, was a cataloguing and appraisal of the current guidelines targeting EMS providers. Methods: A systematic search of the literature was conducted in MEDLINE (1175), EMBASE (519), PubMed (14), Trip (416), and guidelines.gov (64) through May 1, 2016. Two independent reviewers screened titles for relevance to prehospital care, and then abstracts for essential guideline features, including a systematic review, a grading system, and an association between level of evidence and strength of recommendation. All disagreements were moderated by a third party. Citations meeting inclusion criteria were appraised with the AGREE II tool, which looks at six different domains of guideline quality, containing a total of 23 items rated from 1 to 7. Each guideline was appraised by three separate reviewers, and composite scores were calculated by averaging the scaled domain totals. Results: After primary (kappa 97%) and secondary (kappa 93%) screening, 49 guidelines were retained for full review. Only three guidelines obtained a score of >90%, the topics of which included aeromedical transport, analgesia in trauma, and resuscitation of avalanche victims. Only two guidelines scored between 80% and 90%, the topics of which included stroke and pediatric seizure management. One guideline, splinting in an austere environment, scored between 70% and 80%. Nine guidelines scored between 60% and 70%, the topics of which included ischemic stroke, cardiovascular life support, hemorrhage control, intubation, triage, hypothermia, and fibrinolytic use. Of the remaining guidelines, 14 scored between 50% and 60%, and 20 obtained a score of <50%. Conclusion: There are few high-quality, evidence-based guidelines in EMS. Of those that are published, the majority fail to meet established quality measures. Although a lack of randomized controlled trials (RCTs) conducted in the prehospital field continues to limit guideline development, suboptimal methodology is also commonplace within the existing literature.
We describe the performance of the Boolardy Engineering Test Array, the prototype for the Australian Square Kilometre Array Pathfinder telescope. Boolardy Engineering Test Array is the first aperture synthesis radio telescope to use phased array feed technology, giving it the ability to electronically form up to nine dual-polarisation beams. We report the methods developed for forming and measuring the beams, and the adaptations that have been made to the traditional calibration and imaging procedures in order to allow BETA to function as a multi-beam aperture synthesis telescope. We describe the commissioning of the instrument and present details of Boolardy Engineering Test Array’s performance: sensitivity, beam characteristics, polarimetric properties, and image quality. We summarise the astronomical science that it has produced and draw lessons from operating Boolardy Engineering Test Array that will be relevant to the commissioning and operation of the final Australian Square Kilometre Array Path telescope.
Dairy cows grazing pasture and milked using automated milking systems (AMS) have lower milking frequencies than indoor fed cows milked using AMS. Therefore, milk recording intervals used for herd testing indoor fed cows may not be suitable for cows on pasture based farms. We hypothesised that accurate standardised 24 h estimates could be determined for AMS herds with milk recording intervals of less than the Gold Standard (48 hs), but that the optimum milk recording interval would depend on the herd average for milking frequency. The Gold Standard protocol was applied on five commercial dairy farms with AMS, between December 2011 and February 2013. From 12 milk recording test periods, involving 2211 cow-test days and 8049 cow milkings, standardised 24 h estimates for milk volume and milk composition were calculated for the Gold Standard protocol and compared with those collected during nine alternative sampling scenarios, including six shorter sampling periods and three in which a fixed number of milk samples per cow were collected. Results infer a 48 h milk recording protocol is unnecessarily long for collecting accurate estimates during milk recording on pasture based AMS farms. Collection of two milk samples only per cow was optimal in terms of high concordance correlation coefficients for milk volume and components and a low proportion of missed cow-test days. Further research is required to determine the effects of diurnal variations in milk composition on standardised 24 h estimates for milk volume and components, before a protocol based on a fixed number of samples could be considered. Based on the results of this study New Zealand have adopted a split protocol for herd testing based on the average milking frequency for the herd (NZ Herd Test Standard 8100:2015).