Outdoor recreational activity experiences improve psychological wellbeing of military veterans with post-traumatic stress disorder: Positive findings from a pilot study and a randomised controlled trial

Exposure to the natural environment is increasingly considered to benefit psychological health. Recent reports in the literature also suggest that outdoor exposure that includes recreational pursuits such as surfing or fishing coupled with opportunities for social interaction with peers may be beneficial to Armed Forces Veterans experiencing Post-Traumatic Stress Disorder (PTSD). Two studies were conducted to evaluate this possibility. In particular, these studies aimed to test the hypothesis that a brief group outdoor activity would decrease participants’ symptoms as assessed by established measures of PTSD, depression, anxiety and perceived stress, and increase participants’ sense of general social functioning and psychological growth. Experiment one employed a repeated measures design in which UK men and women military veterans with PTSD (N = 30) participated in a group outdoor activity (angling, equine care, or archery and falconry combined). Psychological measures were taken at 2 weeks prior, 2 weeks post, and at 4 month follow up. We obtained a significant within participant main effect indicating significant reduction in PTSD symptoms. Experiment two was a waitlist controlled randomised experiment employing an angling experience (N = 18) and 2 week follow up. In experiment 2 the predicted interaction of Group (Experimental vs. Waitlist Control) X Time (2 weeks pre vs. 2 weeks post) was obtained indicating that the experience resulted in significant reduction in PTSD symptoms relative to waitlist controls. The effect size was large. Additional analyses confirmed that the observed effects might also be considered clinically significant and reliable. In sum, peer outdoor experiences are beneficial and offer potential to complement existing provision for military veterans with Post Traumatic Stress Disorder

Design and rationale of FINE-REAL: A prospective study of finerenone in clinical practice

AIMS: Contemporary patterns of care of patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D) and the adoption of finerenone are not known. The FINE-REAL study (NCT05348733) is a prospective observational study in patients with CKD and T2D to provide insights into the use of the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone in clinical practice. METHODS: FINE-REAL is an international, prospective, multicenter, single-arm study enrolling approximately 5500 adults with CKD and T2D in an estimated 200 sites across 22 countries. The study is anticipated to be ongoing until 2027. RESULTS: The primary objective is to describe treatment patterns in patients with CKD and T2D treated with finerenone in routine clinical practice. Secondary objectives include assessment of safety with finerenone. Other endpoints include characterization of healthcare resource utilization and occurrence of newly diagnosed diabetic retinopathy or its progression from baseline in patients with existing disease. A biobank is being organized for future explorative analyses with inclusion of participants from the United States. CONCLUSIONS: FINE-REAL is the first prospective observational study with a nonsteroidal MRA in a population with CKD and T2D and is expected to provide meaningful insights into the treatment of CKD associated with T2D. FINE-REAL will inform decision-making with respect to initiation of finerenone in patients with CKD and T2D

Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia

BACKGROUND: Most patients with familial primary pulmonary hypertension have defects in the gene for bone morphogenetic protein receptor II (BMPR2), a member of the transforming growth factor beta (TGF-beta) superfamily of receptors. Because patients with hereditary hemorrhagic telangiectasia may have lung disease that is indistinguishable from primary pulmonary hypertension, we investigated the genetic basis of lung disease in these patients. METHODS: We evaluated members of five kindreds plus one individual patient with hereditary hemorrhagic telangiectasia and identified 10 cases of pulmonary hypertension. In the two largest families, we used microsatellite markers to test for linkage to genes encoding TGF-beta-receptor proteins, including endoglin and activin-receptor-like kinase 1 (ALK1), and BMPR2. In subjects with hereditary hemorrhagic telangiectasia and pulmonary hypertension, we also scanned ALK1 and BMPR2 for mutations. RESULTS: We identified suggestive linkage of pulmonary hypertension with hereditary hemorrhagic telangiectasia on chromosome 12q13, a region that includes ALK1. We identified amino acid changes in activin-receptor-like kinase 1 that were inherited in subjects who had a disorder with clinical and histologic features indistinguishable from those of primary pulmonary hypertension. Immunohistochemical analysis in four subjects and one control showed pulmonary vascular endothelial expression of activin-receptor-like kinase 1 in normal and diseased pulmonary arteries. CONCLUSIONS: Pulmonary hypertension in association with hereditary hemorrhagic telangiectasia can involve mutations in ALK1. These mutations are associated with diverse effects, including the vascular dilatation characteristic of hereditary hemorrhagic telangiectasia and the occlusion of small pulmonary arteries that is typical of primary pulmonary hypertension

GIGYF1 loss of function is associated with clonal mosaicism and adverse metabolic health.

Funder: Department of HealthMosaic loss of chromosome Y (LOY) in leukocytes is the most common form of clonal mosaicism, caused by dysregulation in cell-cycle and DNA damage response pathways. Previous genetic studies have focussed on identifying common variants associated with LOY, which we now extend to rarer, protein-coding variation using exome sequences from 82,277 male UK Biobank participants. We find that loss of function of two genes-CHEK2 and GIGYF1-reach exome-wide significance. Rare alleles in GIGYF1 have not previously been implicated in any complex trait, but here loss-of-function carriers exhibit six-fold higher susceptibility to LOY (OR = 5.99 [3.04-11.81], p = 1.3 × 10-10). These same alleles are also associated with adverse metabolic health, including higher susceptibility to Type 2 Diabetes (OR = 6.10 [3.51-10.61], p = 1.8 × 10-12), 4 kg higher fat mass (p = 1.3 × 10-4), 2.32 nmol/L lower serum IGF1 levels (p = 1.5 × 10-4) and 4.5 kg lower handgrip strength (p = 4.7 × 10-7) consistent with proposed GIGYF1 enhancement of insulin and IGF-1 receptor signalling. These associations are mirrored by a common variant nearby associated with the expression of GIGYF1. Our observations highlight a potential direct connection between clonal mosaicism and metabolic health

Limits from the Hubble Space Telescope on a Point Source in SN 1987A

We observed supernova 1987A (SN 1987A) with the Space Telescope Imaging Spectrograph (STIS) on the Hubble Space Telescope (HST) in 1999 September, and again with the Advanced Camera for Surveys (ACS) on the HST in 2003 November. No point source is observed in the remnant. We obtain a limiting flux of F_opt < 1.6 x 10^{-14} ergs/s/cm^2 in the wavelength range 2900-9650 Angstroms for any continuum emitter at the center of the supernova remnant (SNR). It is likely that the SNR contains opaque dust that absorbs UV and optical emission, resulting in an attenuation of ~35% due to dust absorption in the SNR. Taking into account dust absorption in the remnant, we find a limit of L_opt < 8 x 10^{33} ergs/s. We compare this upper bound with empirical evidence from point sources in other supernova remnants, and with theoretical models for possible compact sources. Bright young pulsars such as Kes 75 or the Crab pulsar are excluded by optical and X-ray limits on SN 1987A. Of the young pulsars known to be associated with SNRs, those with ages < 5000 years are all too bright in X-rays to be compatible with the limits on SN 1987A. Examining theoretical models for accretion onto a compact object, we find that spherical accretion onto a neutron star is firmly ruled out, and that spherical accretion onto a black hole is possible only if there is a larger amount of dust absorption in the remnant than predicted. In the case of thin-disk accretion, our flux limit requires a small disk, no larger than 10^{10} cm, with an accretion rate no more than 0.3 times the Eddington accretion rate. Possible ways to hide a surviving compact object include the removal of all surrounding material at early times by a photon-driven wind, a small accretion disk, or very high levels of dust absorption in the remnant.Comment: 40 pages, 5 figures. AAStex. Accepted, ApJ 04/28/200

All-Optical Programmable Disaggregated Data Centre Network realized by FPGA-based Switch and Interface Card

This paper reports an FPGA-based switch and interface card (SIC) and its application scenario in an all-optical, programmable disaggregated data center network (DCN). Our novel SIC is designed and implemented to replace traditional optical network interface cards, plugged into the server directly, supporting optical packet switching (OPS)/optical circuit switching (OCS) or time division multiplexing (TDM)/wavelength division multiplexing (WDM) traffic on demand. Placing the SIC in each server/blade, we eliminate electronics from the top of rack (ToR) switch by pushing all the functionality on each blade while enabling direct intrarack blade-to-blade communication to deliver ultralow chip-to-chip latency. We demonstrate the disaggregated DCN architecture scenarios along with all-optical dimension-programmable N × M spectrum selective Switches (SSS) and an architecture-on-demand (AoD) optical backplane. OPS and OCS complement each other as do TDM and WDM, which can support variable traffic flows. A flat disaggregated DCN architecture is realized by connecting the optical ToR switches directly to either an optical top of cluster switch or the intracluster AoD optical backplane, while clusters are further interconnected to an intercluster AoD for scaling out

Human Gain-of-Function MC4R Variants Show Signaling Bias and Protect against Obesity.

The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor whose disruption causes obesity. We functionally characterized 61 MC4R variants identified in 0.5 million people from UK Biobank and examined their associations with body mass index (BMI) and obesity-related cardiometabolic diseases. We found that the maximal efficacy of β-arrestin recruitment to MC4R, rather than canonical Gαs-mediated cyclic adenosine-monophosphate production, explained 88% of the variance in the association of MC4R variants with BMI. While most MC4R variants caused loss of function, a subset caused gain of function; these variants were associated with significantly lower BMI and lower odds of obesity, type 2 diabetes, and coronary artery disease. Protective associations were driven by MC4R variants exhibiting signaling bias toward β-arrestin recruitment and increased mitogen-activated protein kinase pathway activation. Harnessing β-arrestin-biased MC4R signaling may represent an effective strategy for weight loss and the treatment of obesity-related cardiometabolic diseases

Vacuum Energy Density Fluctuations in Minkowski and Casimir States via Smeared Quantum Fields and Point Separation

We present calculations of the variance of fluctuations and of the mean of the energy momentum tensor of a massless scalar field for the Minkowski and Casimir vacua as a function of an intrinsic scale defined by a smeared field or by point separation. We point out that contrary to prior claims, the ratio of variance to mean-squared being of the order unity is not necessarily a good criterion for measuring the invalidity of semiclassical gravity. For the Casimir topology we obtain expressions for the variance to mean-squared ratio as a function of the intrinsic scale (defined by a smeared field) compared to the extrinsic scale (defined by the separation of the plates, or the periodicity of space). Our results make it possible to identify the spatial extent where negative energy density prevails which could be useful for studying quantum field effects in worm holes and baby universe, and for examining the design feasibility of real-life `time-machines'. For the Minkowski vacuum we find that the ratio of the variance to the mean-squared, calculated from the coincidence limit, is identical to the value of the Casimir case at the same limit for spatial point separation while identical to the value of a hot flat space result with a temporal point-separation. We analyze the origin of divergences in the fluctuations of the energy density and discuss choices in formulating a procedure for their removal, thus raising new questions into the uniqueness and even the very meaning of regularization of the energy momentum tensor for quantum fields in curved or even flat spacetimes when spacetime is viewed as having an extended structure.Comment: 41 pages, 2 figure

HST Spectroscopy of Spot 1 on the Circumstellar Ring of SN 1987A

We present ultraviolet and optical spectra of the first bright spot (PA = 29 degrees) on Supernova 1987A's equatorial circumstellar ring taken with the Space Telescope Imaging Spectrograph. We interpret this spot as the emission produced by radiative shocks that occur where the supernova blast wave strikes an inward protrusion of the ring. The observed line widths and intensity ratios indicate the presence of radiative shocks with velocities ranging from 100 to 250 km s^-1 entering dense (> 10^4 cm^-3) gas. These observations, and future observations of the development of the spectra and line profiles, provide a unique opportunity to study the hydrodynamics of radiative shocks.Comment: Accepted by ApJL on Aug. 3, 200