OBJECTIVE:The aim of the study was to declare a call to action to improve mental health in the workplace.
METHODS:We convened a public health summit and assembled an Advisory Council consisting of ...experts in the field of occupational health and safety, workplace wellness, and public policy to offer recommendations for action steps to improve health and well-being of workers.
RESULTS:The Advisory Council narrowed the list of ideas to four priority projects.
CONCLUSIONS:The recommendations for action include developing a mental health in the workplace (1) “how to” guide, (2) scorecard, (3) recognition program, and (4) executive training.
The Palomar Transient Factory (PTF) is a multiepochal robotic survey of the northern sky that acquires data for the scientific study of transient and variable astrophysical phenomena. The camera and ...telescope provide for wide-field imaging in optical bands. In the five years of operation since first light on 2008 December 13, images taken with Mould-R and SDSS-g′ camera filters have been routinely acquired on a nightly basis (weather permitting), and two different Hα filters were installed in 2011 May (656 and 663 nm). The PTF image-processing and data-archival program at the Infrared Processing and Analysis Center (IPAC) is tailored to receive and reduce the data, and, from it, generate and preserve astrometrically and photometrically calibrated images, extracted source catalogs, and co-added reference images. Relational databases have been deployed to track these products in operations and the data archive. The fully automated system has benefited by lessons learned from past IPAC projects and comprises advantageous features that are potentially incorporable into other ground-based observatories. Both off-the-shelf and in-house software have been utilized for economy and rapid development. The PTF data archive is curated by the NASA/IPAC Infrared Science Archive (IRSA). A state-of-the-art custom Web interface has been deployed for downloading the raw images, processed images, and source catalogs from IRSA. Access to PTF data products is currently limited to an initial public data release (M81, M44, M42, SDSS Stripe 82, and the Kepler Survey Field). It is the intent of the PTF collaboration to release the full PTF data archive when sufficient funding becomes available.
Long-lasting, latently infected resting CD4
T cells are the greatest obstacle to obtaining a cure for HIV infection, as these cells can persist despite decades of treatment with antiretroviral ...therapy (ART). Estimates indicate that more than 70 years of continuous, fully suppressive ART are needed to eliminate the HIV reservoir
. Alternatively, induction of HIV from its latent state could accelerate the decrease in the reservoir, thus reducing the time to eradication. Previous attempts to reactivate latent HIV in preclinical animal models and in clinical trials have measured HIV induction in the peripheral blood with minimal focus on tissue reservoirs and have had limited effect
. Here we show that activation of the non-canonical NF-κB signalling pathway by AZD5582 results in the induction of HIV and SIV RNA expression in the blood and tissues of ART-suppressed bone-marrow-liver-thymus (BLT) humanized mice and rhesus macaques infected with HIV and SIV, respectively. Analysis of resting CD4
T cells from tissues after AZD5582 treatment revealed increased SIV RNA expression in the lymph nodes of macaques and robust induction of HIV in almost all tissues analysed in humanized mice, including the lymph nodes, thymus, bone marrow, liver and lung. This promising approach to latency reversal-in combination with appropriate tools for systemic clearance of persistent HIV infection-greatly increases opportunities for HIV eradication.
The Palomar Transient Factory (PTF) is a fully-automated, wide-field survey aimed at a systematic exploration of the optical transient sky. The transient survey is performed using a new 8.1 square ...degree camera installed on the 48 inch Samuel Oschin telescope at Palomar Observatory; colors and light curves for detected transients are obtained with the automated Palomar 60 inch telescope. PTF uses 80% of the 1.2 m and 50% of the 1.5 m telescope time. With an exposure of 60 s the survey reaches a depth of
m
g
′
≈ 21.3
m
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′
≈
21.3
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m
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≈ 20.6
m
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≈
20.6
(5σ, median seeing). Four major experiments are planned for the five-year project: (1) a 5 day cadence supernova search; (2) a rapid transient search with cadences between 90 s and 1 day; (3) a search for eclipsing binaries and transiting planets in Orion; and (4) a 3π sr deep H-alpha survey. PTF provides automatic, real-time transient classification and follow-up, as well as a database including every source detected in each frame. This paper summarizes the PTF project, including several months of on-sky performance tests of the new survey camera, the observing plans, and the data reduction strategy. We conclude by detailing the first 51 PTF optical transient detections, found in commissioning data.
Background
The immunopathology of autoimmune seronegative myasthenia gravis (SN MG) is poorly understood. Our objective was to determine immune profiles associated with a diagnosis of SN MG.
Methods
...We performed high‐dimensional flow cytometry on blood samples from SN MG patients (N = 68), healthy controls (N = 46), and acetylcholine receptor antibody (AChR+) MG patients (N = 27). We compared 12 immune cell subsets in SN MG to controls using logistic modeling via a discovery‐replication design. An exploratory analysis fit a multinomial model comparing AChR+ MG and controls to SN MG.
Results
An increase in CD19+CD20−CD38hi plasmablast frequencies was associated with lower odds of being a SN MG case in both the discovery and replication analyses (discovery P‐value = .0003, replication P‐value = .0021). Interleukin (IL) ‐21 producing helper T cell frequencies were associated with a diagnosis of AChR+ MG (P = .004).
Conclusions
Reduced plasmablast frequencies are strongly associated with a SN MG diagnosis and may be a useful diagnostic biomarker in the future.
See Editorial on pages 439–441 in this issue.
Advanced measures of cardiac function are increasingly important to clinical assessment due to their superior diagnostic and predictive capabilities. Cine DENSE cardiovascular magnetic resonance ...(CMR) is ideal for quantifying advanced measures of cardiac function based on its high spatial resolution and streamlined post-processing. While many studies have utilized cine DENSE in both humans and small-animal models, the inter-test and inter-observer reproducibility for quantification of advanced cardiac function in mice has not been evaluated. This represents a critical knowledge gap for both understanding the capabilities of this technique and for the design of future experiments. We hypothesized that cine DENSE CMR would show excellent inter-test and inter-observer reproducibility for advanced measures of left ventricular (LV) function in mice.
Five normal mice (C57BL/6) and four mice with depressed cardiac function (diet-induced obesity) were imaged twice, two days apart, on a 7T ClinScan MR system. Images were acquired with 15-20 frames per cardiac cycle in three short-axis (basal, mid, apical) and two long-axis orientations (4-chamber and 2-chamber). LV strain, twist, torsion, and measures of synchrony were quantified. Images from both days were analyzed by one observer to quantify inter-test reproducibility, while inter-observer reproducibility was assessed by a second observer's analysis of day-1 images. The coefficient of variation (CoV) was used to quantify reproducibility.
LV strains and torsion were highly reproducible on both inter-observer and inter-test bases with CoVs ≤ 15%, and inter-observer reproducibility was generally better than inter-test reproducibility. However, end-systolic twist angles showed much higher variance, likely due to the sensitivity of slice location within the sharp longitudinal gradient in twist angle. Measures of synchrony including the circumferential (CURE) and radial (RURE) uniformity of strain indices, showed excellent reproducibility with CoVs of 1% and 3%, respectively. Finally, peak measures (e.g., strains) were generally more reproducible than the corresponding rates of change (e.g., strain rate).
Cine DENSE CMR is a highly reproducible technique for quantification of advanced measures of left ventricular cardiac function in mice including strains, torsion and measures of synchrony. However, myocardial twist angles are not reproducible and future studies should instead report torsion.
Obesity is a risk factor for cardiovascular disease. There is evidence of impaired left ventricular (LV) function associated with obesity, which may relate to cardiovascular mortality, but some ...studies have reported no dysfunction. Ventricular function data are generally acquired under resting conditions, which could mask subtle differences and potentially contribute to these contradictory findings. Furthermore, abnormal ventricular mechanics (strains, strain rates, and torsion) may manifest prior to global changes in cardiac function (i.e., ejection fraction) and may therefore represent more sensitive markers of cardiovascular disease. This study evaluated LV mechanics under both resting and stress conditions with the hypothesis that the LV mechanical dysfunction associated with obesity is exacerbated with stress and manifested at earlier stages of disease compared to baseline.
C57BL/6J mice were randomized to a high-fat or control diet (60 %, 10 % kcal from fat, respectively) for varying time intervals (n = 7 - 10 subjects per group per time point, 100 total; 4 - 55 weeks on diet). LV mechanics were quantified under baseline (resting) and/or stress conditions (40 μg/kg/min continuous infusion of dobutamine) using cine displacement encoding with stimulated echoes (DENSE) with 7.4 ms temporal resolution on a 7 T Bruker ClinScan. Peak strain, systolic strain rates, and torsion were quantified. A linear mixed model was used with Benjamini-Hochberg adjustments for multiple comparisons.
Reductions in LV peak longitudinal strain at baseline were first observed in the obese group after 42 weeks, with no differences in systolic strain rates or torsion. Conversely, reductions in longitudinal strain and circumferential and radial strain rates were seen under inotropic stress conditions after only 22 weeks on diet. Furthermore, stress cardiovascular magnetic resonance (CMR) evaluation revealed supranormal values of LV radial strain and torsion in the obese group early on diet, followed by later deficits.
Differences in left ventricular mechanics in obese mice are exacerbated under stress conditions. Stress CMR demonstrated a broader array of mechanical dysfunction and revealed these differences at earlier time points. Thus, it may be important to evaluate cardiac function in the setting of obesity under stress conditions to fully elucidate the presence of ventricular dysfunction.
Background: Germline mutations in the CDKN2A gene have been linked to melanoma incidence in many families with multiple cases of the disease. Previous studies of multiple-case families have indicated ...that the lifetime risk (i.e., penetrance) of melanoma in CDKN2A mutation carriers is very high, ranging from 58% in Europe to 91% in Australia by age 80 years. In this study, we examined lifetime melanoma risk among CDKN2A mutation carriers using carriers who were identified in a population-based study of melanoma. Methods: Probands for the study were incident case patients with either first or subsequent melanoma who were identified in nine geographic regions in Australia, Canada, the United States, and Italy. A total of 3626 probands (53% participation rate) with adequate DNA for analysis were recruited and genotyped for CDKN2A mutations. From the 3550 probands whose DNA could be amplified by polymerase chain reaction of CDKN2A exons 1α, 2, and 3 and surrounding regions, 65 mutation carriers were identified. Melanoma histories in first-degree relatives of these probands were used to calculate the lifetime risk in CDKN2A mutation carriers using the kin–cohort method. Results: The risk of melanoma in CDKN2A mutation carriers was approximately 14% (95% CI = 8% to 22%) by age 50 years, 24% (95% CI = 15% to 34%) by age 70 years, and 28% (95% CI = 18% to 40%) by age 80 years. Eighteen probands had three or more first-degree relatives with melanoma, but only one was a carrier of a CDKN2A mutation. Conclusions: CDKN2A mutation carriers in the general population have a much lower risk of melanoma than that suggested by estimates obtained from multiple-case families. The preponderance of familial clustering of melanoma occurs in families without identifiable mutations in CDKN2A.
The melanocortin-1-receptor (MC1R) gene regulates human pigmentation and is highly polymorphic in populations of European origins. The aims of this study were to evaluate the association between MC1R ...variants and the risk of non-melanoma skin cancer (NMSC), and to investigate whether risk estimates differed by phenotypic characteristics.
Data on 3527 NMSC cases and 9391 controls were gathered through the M-SKIP Project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. We calculated summary odds ratios (SOR) with random-effect models, and performed stratified analyses.
Subjects carrying at least one MC1R variant had an increased risk of NMSC overall, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC): SOR (95%CI) were 1.48 (1.24-1.76), 1.39 (1.15-1.69) and 1.61 (1.35-1.91), respectively. All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19-1.70) for V60L to 2.66 (1.06-6.65) for D84E variant. In stratified analysis, there was no consistent pattern of association between MC1R and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair.
Our pooled-analysis highlighted a role of MC1R variants in NMSC development and suggested an effect modification by red hair colour phenotype.
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