Wearing the Label of Mental Illness: Community-Based Participatory Action Research of Mental Illness Stigma

Stigma remains an impediment to seeking and receiving the requisite care for mental illness. To enhance a local National Alliance for Mental Illness (NAMI) affiliate’s understanding of community members’ perceptions of mental illness and its associated stigma, a community-based participatory action research study was conducted. The study addressed the following research question: how do community members understand and experience the stigma associated with mental illness? Twenty-two participant-researchers wore mental illness labeled T-shirts around the local community, recorded their observations and reflections of this experience and recruited twenty-two community members for semi-structured interviews about mental illness stigma. Domain analysis of the interviews revealed community members’ understandings of (1) sources of stigma, (2) impacts of stigma, (3) conceptualizations of stigma and (4) pathways to change stigma. Findings were presented to members of the local NAMI affiliate as well as other community members. Practical implications, specific to the community of interest, are discussed

SARS-CoV-2 Infections and ACE2: Clinical Outcomes Linked With Increased Morbidity and Mortality in Individuals With Diabetes

Individuals with diabetes suffering from coronavirus disease 2019 (COVID-19) exhibit increased morbidity and mortality compared with individuals without diabetes. In this Perspective, we critically evaluate and argue that this is due to a dysregulated renin-angiotensin system (RAS). Previously, we have shown that loss of angiotensin-I converting enzyme 2 (ACE2) promotes the ACE/angiotensin-II (Ang-II)/angiotensin type 1 receptor (AT1R) axis, a deleterious arm of RAS, unleashing its detrimental effects in diabetes. As suggested by the recent reports regarding the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), upon entry into the host, this virus binds to the extracellular domain of ACE2 in nasal, lung, and gut epithelial cells through its spike glycoprotein subunit S1. We put forth the hypothesis that during this process, reduced ACE2 could result in clinical deterioration in COVID-19 patients with diabetes via aggravating Ang-II–dependent pathways and partly driving not only lung but also bone marrow and gastrointestinal pathology. In addition to systemic RAS, the pathophysiological response of the local RAS within the intestinal epithelium involves mechanisms distinct from that of RAS in the lung; however, both lung and gut are impacted by diabetes-induced bone marrow dysfunction. Careful targeting of the systemic and tissue RAS may optimize clinical outcomes in subjects with diabetes infected with SARS-CoV-2.This study was supported by National Institutes of Health grants R01EY025383, R01EY012601, R01EY028858, and R01EY028037 to M.B.G. A.G.O. was supported in part by R01NS10241

High-frequency climate variability in the Holocene from a coastal-dome ice core in east-central Greenland

An ice core drilled on the Renland ice cap in east-central Greenland contains a continuous climate record dating through the last glacial period. The Renland record is valuable because the coastal environment is more likely to reflect regional sea surface conditions compared to inland Greenland ice cores that capture synoptic variability. Here we present the δ¹⁸O water isotope record for the Holocene, in which decadal-scale climate information is retained for the last 8 kyr, while the annual water isotope signal is preserved throughout the last 2.6 kyr. To investigate regional climate information preserved in the water isotope record, we apply spectral analysis techniques to a 300-year moving window to determine the mean strength of varying frequency bands through time. We find that the strength of 15–20-year δ¹⁸O variability exhibits a millennial-scale signal in line with the well-known Bond events. Comparison to other North Atlantic proxy records suggests that the 15–20-year variability may reflect fluctuating sea surface conditions throughout the Holocene, driven by changes in the strength of the Atlantic Meridional Overturning Circulation. Additional analysis of the seasonal signal over the last 2.6 kyr reveals that the winter δ¹⁸O signal has experienced a decreasing trend, while the summer signal has predominantly remained stable. The winter trend may correspond to an increase in Arctic sea ice cover, which is driven by a decrease in total annual insolation, and is also likely influenced by regional climate variables such as atmospheric and oceanic circulation. In the context of anthropogenic climate change, the winter trend may have important implications for feedback processes as sea ice retreats in the Arctic

High-frequency climate variability in the Holocene from a coastal-dome ice core in east-central Greenland

An ice core drilled on the Renland ice cap in east-central Greenland contains a continuous climate record dating through the last glacial period. The Renland record is valuable because the coastal environment is more likely to reflect regional sea surface conditions compared to inland Greenland ice cores that capture synoptic variability. Here we present the δ¹⁸O water isotope record for the Holocene, in which decadal-scale climate information is retained for the last 8 kyr, while the annual water isotope signal is preserved throughout the last 2.6 kyr. To investigate regional climate information preserved in the water isotope record, we apply spectral analysis techniques to a 300-year moving window to determine the mean strength of varying frequency bands through time. We find that the strength of 15–20-year δ¹⁸O variability exhibits a millennial-scale signal in line with the well-known Bond events. Comparison to other North Atlantic proxy records suggests that the 15–20-year variability may reflect fluctuating sea surface conditions throughout the Holocene, driven by changes in the strength of the Atlantic Meridional Overturning Circulation. Additional analysis of the seasonal signal over the last 2.6 kyr reveals that the winter δ¹⁸O signal has experienced a decreasing trend, while the summer signal has predominantly remained stable. The winter trend may correspond to an increase in Arctic sea ice cover, which is driven by a decrease in total annual insolation, and is also likely influenced by regional climate variables such as atmospheric and oceanic circulation. In the context of anthropogenic climate change, the winter trend may have important implications for feedback processes as sea ice retreats in the Arctic

A Double-Blind, Placebo-Controlled, Randomized, Clinical Trial of the TLR-3 Agonist Rintatolimod in Severe Cases of Chronic Fatigue Syndrome

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a severely debilitating disease of unknown pathogenesis consisting of a variety of symptoms including severe fatigue. The objective of the study was to examine the efficacy and safety of a TLR-3 agonist, rintatolimod (Poly I: C(12)U), in patients with debilitating CFS/ME. METHODS AND FINDINGS: A Phase III prospective, double-blind, randomized, placebo-controlled trial comparing twice weekly IV rintatolimod versus placebo was conducted in 234 subjects with long-standing, debilitating CFS/ME at 12 sites. The primary endpoint was the intra-patient change from baseline at Week 40 in exercise tolerance (ET). Secondary endpoints included concomitant drug usage, the Karnofsky Performance Score (KPS), Activities of Daily Living (ADL), and Vitality Score (SF 36). Subjects receiving rintatolimod for 40 weeks improved intra-patient placebo-adjusted ET 21.3% (p = 0.047) from baseline in an intention-to-treat analysis. Correction for subjects with reduced dosing compliance increased placebo-adjusted ET improvement to 28% (p = 0.022). The improvement observed represents approximately twice the minimum considered medically significant by regulatory agencies. The rintatolimod cohort vs. placebo also reduced dependence on drugs commonly used by patients in an attempt to alleviate the symptoms of CFS/ME (p = 0.048). Placebo subjects crossed-over to receive rintatolimod demonstrated an intra-patient improvement in ET performance at 24 weeks of 39% (p = 0.04). Rintatolimod at 400 mg twice weekly was generally well-tolerated. CONCLUSIONS/SIGNIFICANCE: Rintatolimod produced objective improvement in ET and a reduction in CFS/ME related concomitant medication usage as well as other secondary outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00215800

Long-term follow-up of breast cancer survivors with post-mastectomy pain syndrome

Post-mastectomy pain syndrome (PMPS) is a recognised complication of breast surgery although little is known about the long-term outcome of this chronic pain condition. In 1996, Smith et al identified a prevalence rate of PMPS of 43% among 408 women in the Grampian Region, Northeast Scotland. The aim of this study was to assess long-term outcome at 7–12 years postoperatively in this cohort of women, to describe the natural history of PMPS and impact of pain upon quality of life. Chronic pain and quality of life were assessed using the McGill Pain Questionnaire (MPQ) and Short Form-36 (SF-36). Of 175 women reporting PMPS in 1996, 138 were eligible for questionnaire follow-up in 2002. Mean time since surgery was 9 years (s.d. 1.8 years). A response rate of 82% (113 out of 138) was achieved; 59 out of 113 (52%) women reported continued PMPS and 54 out of 113 (48%) women reported their PMPS had resolved since the previous survey in 1996. Quality of life scores were significantly lower in women with persistent PMPS compared to those women whose pain had resolved. However, for women with persistent PMPS, SF-36 scores had improved over time. Risk factors for persistent PMPS included younger age and heavier weight. This study found that, of women reporting PMPS in 1996, half of those surveyed in 2002 continued to experience PMPS at a mean of 9 years after surgery

Absolute Calibration of the Radio Astronomy Flux Density Scale from 22 to 43 GHz using Planck

The Planck mission detected hundreds of extragalactic radio sources at frequencies from 28 to 857 GHz. Since Planck's calibration is absolute, based on the satellite's annual motion around the Sun, and since its beams are well-characterized at the sub-percent levels, Planck's flux density measurements are absolute to percent-level accuracy. We have made coordinated Planck, VLA and ATCA observations of ~60 strong, unresolved sources in order to compare Planck's absolute calibration to that used by these two interferometers at 22, 28 and 43 GHz. The flux densities of the sources used to calibrate the VLA observations are taken from Perley and Butler (2013), which is fundamentally based on models of the planet Mars calibrated via WMAP observations. The flux densities of the sources used to calibrate the ATCA observations are based on models of the planet Uranus. Despite the scatter introduced by the variability of many of the sources, the three flux density scales are determined to agree to 1-2% accuracy. <P /