During the past 50 years, there have been marked improvement in the social and legal environment of sexual minorities in the United States. Minority stress theory predicts that health of sexual ...minorities is predicated on the social environment. As the social environment improves, exposure to stress would decline and health outcomes would improve. We assessed how stress, identity, connectedness with the LGBT community, and psychological distress and suicide behavior varied across three distinct cohorts of sexual minority people in the United States. Using a national probability sample recruited in 2016 and 2017, we assessed three a priori defined cohorts of sexual minorities we labeled the pride (born 1956-1963), visibility (born 1974-1981), and equality (born 1990-1997) cohorts. We found significant and impressive cohort differences in coming out milestones, with members of the younger cohort coming out much earlier than members of the two older cohorts. But we found no signs that the improved social environment attenuated their exposure to minority stressors-both distal stressors, such as violence and discrimination, and proximal stressors, such as internalized homophobia and expectations of rejection. Psychological distress and suicide behavior also were not improved, and indeed were worse for the younger than the older cohorts. These findings suggest that changes in the social environment had limited impact on stress processes and mental health for sexual minority people. They speak to the endurance of cultural ideologies such as homophobia and heterosexism and accompanying rejection of and violence toward sexual minorities.
This systematic umbrella review examines and updates the evidence on the relationship between physical activity (PA) and blood pressure (BP) presented in the 2008 Physical Activity Guidelines ...Advisory Committee Scientific Report.
We performed a systematic review to identify systematic reviews and meta-analyses involving adults with normal BP, prehypertension, and hypertension published from 2006 to February 2018.
In total, 17 meta-analyses and one systematic review with 594,129 adults ≥18 yr qualified. Strong evidence demonstrates: 1) an inverse dose-response relationship between PA and incident hypertension among adults with normal BP; 2) PA reduces the risk of cardiovascular disease (CVD) progression among adults with hypertension; 3) PA reduces BP among adults with normal BP, prehypertension, and hypertension; and 4) the magnitude of the BP response to PA varies by resting BP, with greater benefits among adults with prehypertension than normal BP. Moderate evidence indicates the relationship between resting BP and the magnitude of benefit does not vary by PA type among adults with normal BP, prehypertension, and hypertension. Limited evidence suggests the magnitude of the BP response to PA varies by resting BP among adults with hypertension. Insufficient evidence is available to determine if factors such as sex, age, race/ethnicity, socioeconomic status, and weight status or the frequency, intensity, time, and duration of PA influence the associations between PA and BP.
Future research is needed that adheres to standard BP measurement protocols and classification schemes to better understand the influence of PA on the risk of comorbid conditions, health-related quality of life, and CVD progression and mortality; the interactive effects between PA and antihypertensive medication use; and the immediate BP-lowering benefits of PA.
Light plays a critical role in the regulation of numerous aspects of physiology and behaviour, including the entrainment of circadian rhythms and the regulation of sleep. These responses involve ...melanopsin (OPN4)-expressing photosensitive retinal ganglion cells (pRGCs) in addition to rods and cones. Nocturnal light exposure in rodents has been shown to result in rapid sleep induction, in which melanopsin plays a key role. However, studies have also shown that light exposure can result in elevated corticosterone, a response that is not compatible with sleep. To investigate these contradictory findings and to dissect the relative contribution of pRGCs and rods/cones, we assessed the effects of light of different wavelengths on behaviourally defined sleep. Here, we show that blue light (470 nm) causes behavioural arousal, elevating corticosterone and delaying sleep onset. By contrast, green light (530 nm) produces rapid sleep induction. Compared to wildtype mice, these responses are altered in melanopsin-deficient mice (Opn4-/-), resulting in enhanced sleep in response to blue light but delayed sleep induction in response to green or white light. We go on to show that blue light evokes higher Fos induction in the SCN compared to the sleep-promoting ventrolateral preoptic area (VLPO), whereas green light produced greater responses in the VLPO. Collectively, our data demonstrates that nocturnal light exposure can have either an arousal- or sleep-promoting effect, and that these responses are melanopsin-mediated via different neural pathways with different spectral sensitivities. These findings raise important questions relating to how artificial light may alter behaviour in both the work and domestic setting.
In the past 2 decades, sonoelastography has been progressively used as a tool to help evaluate soft-tissue elasticity and add to information obtained with conventional gray-scale and Doppler ...ultrasonographic techniques. Recently introduced on clinical scanners, shear-wave elastography (SWE) is considered to be more objective, quantitative, and reproducible than compression sonoelastography with increasing applications to the musculoskeletal system. SWE uses an acoustic radiation force pulse sequence to generate shear waves, which propagate perpendicular to the ultrasound beam, causing transient displacements. The distribution of shear-wave velocities at each pixel is directly related to the shear modulus, an absolute measure of the tissue's elastic properties. Shear-wave images are automatically coregistered with standard B-mode images to provide quantitative color elastograms with anatomic specificity. Shear waves propagate faster through stiffer contracted tissue, as well as along the long axis of tendon and muscle. SWE has a promising role in determining the severity of disease and treatment follow-up of various musculoskeletal tissues including tendons, muscles, nerves, and ligaments. This article describes the basic ultrasound physics of SWE and its applications in the evaluation of various traumatic and pathologic conditions of the musculoskeletal system.
RSNA, 2017.
Abstract
We present long-term (2012–2022) optical monitoring of the candidate black hole X-ray binary Swift J1910.2–0546 with the Faulkes Telescopes and Las Cumbres Observatory network. Following its ...initial bright 2012 outburst, we find that the source displayed a series of at least seven quasi-periodic, high-amplitude (~3 mag) optical reflares in 2013, with a recurrence time increasing from ∼42 to ∼49 days. In 2014, the source experienced a mini outburst with two peaks in the optical. We also study the recent 2022 outburst of the source at optical wavelengths, and perform a comparative analysis with the earlier rebrightenings. A single X-ray detection and only two radio detections were obtained during the 2013 reflaring period, and only optical detections were acquired in 2014. During the reflaring in both 2013 and 2014, the source showed bluer-when-brighter behavior, having optical colors consistent with blackbody heating and cooling between 4500 and 9500 K, i.e., the temperature range in which hydrogen starts to ionize. Finally, we compare the flaring behavior of the source to rebrightening events in other X-ray binaries. We show that the repeated reflarings of Swift J1910.2–0546 are highly unusual, and propose that they arise from a sequence of repetitive heating and cooling front reflections traveling through the accretion disk.
Powerful relativistic jets are one of the main ways in which accreting black holes provide kinetic feedback to their surroundings. Jets launched from or redirected by the accretion flow that powers ...them are expected to be affected by the dynamics of the flow, which for accreting stellar-mass black holes has shown evidence for precession
due to frame-dragging effects that occur when the black-hole spin axis is misaligned with the orbital plane of its companion star
. Recently, theoretical simulations have suggested that the jets can exert an additional torque on the accretion flow
, although the interplay between the dynamics of the accretion flow and the launching of the jets is not yet understood. Here we report a rapidly changing jet orientation-on a time scale of minutes to hours-in the black-hole X-ray binary V404 Cygni, detected with very-long-baseline interferometry during the peak of its 2015 outburst. We show that this changing jet orientation can be modelled as the Lense-Thirring precession of a vertically extended slim disk that arises from the super-Eddington accretion rate
. Our findings suggest that the dynamics of the precessing inner accretion disk could play a role in either directly launching or redirecting the jets within the inner few hundred gravitational radii. Similar dynamics should be expected in any strongly accreting black hole whose spin is misaligned with the inflowing gas, both affecting the observational characteristics of the jets and distributing the black-hole feedback more uniformly over the surrounding environment
.
The selective TRK inhibitor larotrectinib was approved for paediatric and adult patients with advanced TRK fusion-positive solid tumours based on a primary analysis set of 55 patients. The aim of our ...analysis was to explore the efficacy and long-term safety of larotrectinib in a larger population of patients with TRK fusion-positive solid tumours.
Patients were enrolled and treated in a phase 1 adult, a phase 1/2 paediatric, or a phase 2 adolescent and adult trial. Some eligibility criteria differed between these studies. For this pooled analysis, eligible patients were aged 1 month or older, with a locally advanced or metastatic non-CNS primary, TRK fusion-positive solid tumour, who had received standard therapy previously if available. This analysis set includes the 55 patients on which approval of larotrectinib was based. Larotrectinib was administered orally (capsule or liquid formulation), on a continuous 28-day schedule, to adults mostly at a dose of 100 mg twice daily, and to paediatric patients mostly at a dose of 100 mg/m2 (maximum of 100 mg) twice daily. The primary endpoint was objective response as assessed by local investigators in an intention-to-treat analysis. Contributing trials are registered with ClinicalTrials.gov, NCT02122913 (active not recruiting), NCT02637687 (recruiting), and NCT02576431 (recruiting).
Between May 1, 2014, and Feb 19, 2019, 159 patients with TRK fusion-positive cancer were enrolled and treated with larotrectinib. Ages ranged from less than 1 month to 84 years. The proportion of patients with an objective response according to investigator assessment was 121 (79%, 95% CI 72–85) of 153 evaluable patients, with 24 (16%) having complete responses. In a safety population of 260 patients treated regardless of TRK fusion status, the most common grade 3 or 4 larotrectinib-related adverse events were increased alanine aminotransferase (eight 3% of 260 patients), anaemia (six, 2%), and decreased neutrophil count (five 2%). The most common larotrectinib-related serious adverse events were increased alanine aminotransferase (two <1% of 260 patients), increased aspartate aminotransferase (two <1%), and nausea (two <1%). No treatment-related deaths occurred.
These data confirm that TRK fusions define a unique molecular subgroup of advanced solid tumours for which larotrectinib is highly active. Safety data indicate that long-term administration of larotrectinib is feasible.
Bayer and Loxo Oncology.
The evolution of massive stars is influenced by the mass lost to stellar winds over their lifetimes. These winds limit the masses of the stellar remnants (such as black holes) that the stars ...ultimately produce. We used radio astrometry to refine the distance to the black hole x-ray binary Cygnus X-1, which we found to be Formula: see text kiloparsecs. When combined with archival optical data, this implies a black hole mass of 21.2 ± 2.2 solar masses, which is higher than previous measurements. The formation of such a high-mass black hole in a high-metallicity system (within the Milky Way) constrains wind mass loss from massive stars.
PDF
