A wellcome change?

UK researchers are debating the merits of the new Wellcome Trust Investigator Awards. With concerns over public funding cuts for research, some question the timing of the charity's change in funding strategy.

Evaluating Primary Treatment for People with Advanced Glaucoma: Five-Year Results of the Treatment of Advanced Glaucoma Study.

PURPOSE: To determine whether primary trabeculectomy or medical treatment produces better outcomes in terms of quality of life (QoL), clinical effectiveness, and safety in patients with advanced glaucoma. DESIGN: Multicenter randomized controlled trial. PARTICIPANTS: Between June 3, 2014, and May 31, 2017, 453 adults with newly diagnosed advanced open-angle glaucoma in at least 1 eye (Hodapp classification) were recruited from 27 secondary care glaucoma departments in the United Kingdom. Two hundred twenty-seven were allocated to trabeculectomy, and 226 were allocated medical management. METHODS: Participants were randomized on a 1:1 basis to have either mitomycin C-augmented trabeculectomy or escalating medical management with intraocular pressure (IOP)-reducing drops as the primary intervention and were followed up for 5 years. MAIN OUTCOME MEASURES: The primary outcome was vision-specific QoL measured with the 25-item Visual Function Questionnaire (VFQ-25) at 5 years. Secondary outcomes were general health status, glaucoma-related QoL, clinical effectiveness (IOP, visual field, and visual acuity), and safety. RESULTS: At 5 years, the mean ± standard deviation VFQ-25 scores in the trabeculectomy and medication arms were 83.3 ± 15.5 and 81.3 ± 17.5, respectively, and the mean difference was 1.01 (95% confidence interval [CI], -1.99 to 4.00; P = 0.51). The mean IOPs were 12.07 ± 5.18 mmHg and 14.76 ± 4.14 mmHg, respectively, and the mean difference was -2.56 (95% CI, -3.80 to -1.32; P < 0.001). Glaucoma severity measured with visual field mean deviation were -14.30 ± 7.14 dB and -16.74 ± 6.78 dB, respectively, with a mean difference of 1.87 (95% CI, 0.87-2.87 dB; P < 0.001). Safety events occurred in 115 (52.2%) of patients in the trabeculectomy arm and 124 (57.9%) of patients in the medication arm (relative risk, 0.92; 95% CI, 0.72-1.19; P = 0.54). Serious adverse events were rare. CONCLUSIONS: At 5 years, the Treatment of Advanced Glaucoma Study demonstrated that primary trabeculectomy surgery is more effective in lowering IOP and preventing disease progression than primary medical treatment in patients with advanced disease and has a similar safety profile. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Photosynthetic capacity in middle-aged larch and spruce acclimates independently to experimental warming and elevated CO2.

Photosynthetic acclimation to both warming and elevated CO2 of boreal trees remains a key uncertainty in modelling the response of photosynthesis to future climates. We investigated the impact of increased growth temperature and elevated CO2 on photosynthetic capacity (Vcmax and Jmax) in mature trees of two North American boreal conifers, tamarack and black spruce. We show that Vcmax and Jmax at a standard temperature of 25°C did not change with warming, while Vcmax and Jmax at their thermal optima (Topt) and growth temperature (Tg) increased. Moreover, Vcmax and Jmax at either 25°C, Topt or Tg decreased with elevated CO2. The Jmax/Vcmax ratio decreased with warming when assessed at both Topt and Tg but did not significantly vary at 25°C. The Jmax/Vcmax increased with elevated CO2 at either reference temperature. We found no significant interaction between warming and elevated CO2 on all traits. If this lack of interaction between warming and elevated CO2 on the Vcmax, Jmax and Jmax/Vcmax ratio is a general trend, it would have significant implications for improving photosynthesis representation in vegetation models. However, future research is required to investigate the widespread nature of this response in a larger number of species and biomes.

Researchers find their Nemo.

With its genome almost fully sequenced, the zebrafish has gone from bit player to rising star among model organisms. Its lower maintenance costs and the ease of tissue imaging in live zebrafish are among the benefits that have cast this organism as an emerging player in disease research and drug screening.

Adverse childhood experiences, health risk factors, and significant problems with substances and behaviors among U.S. college students.

Adverse childhood experiences (ACEs) are often associated with higher rates of mental health issues and problematic behaviors within the U.S. college population. Therefore, the primary purpose of this study was to investigate the current associations among ACEs, six psychosocial risk factors for poor health (i.e., anxiety, depression, loneliness, negative urgency, positive urgency, and stress), and significant behavioral and substance problems in a large sample of college students (N = 1,993). Overall, 72.3% of participants reported one or more ACEs, with 21.7% reporting at least five of these experiences; the most prevalent ACE types were emotional abuse (51.7%) and parental mental illness (33.8%). Cumulative ACEs were positively associated with all health risk factors, rs = .07-.38, ps ≤ .001, and these ACE scores were most connected to student problems with alcohol, overeating, and sex, rs = .19-.22, ps < .001. Furthermore, using logistic regression, cumulative ACEs predicted which students were more likely to report behavioral problems, OR = 1.08, 95% CI [1.03, 1.14]; substance problems, OR = 1.16, 95% CI [1.07, 1.26]; and both types of problems, OR = 1.28, 95% CI [1.20, 1.36], relative to students without these problems. Aside from ACEs, higher anxiety was the only other risk factor all three problem types shared. Collectively, these findings highlight the differential impact of ACEs and other psychosocial risk factors on the susceptibility of college students to particular forms of maladaptive coping and suggest potential targets for intervention and prevention efforts in these areas.

Withdrawal catastrophizing scale: initial psychometric properties and implications for the study of opioid use disorder and hyperkatifeia.

Background: Discovery of modifiable factors influencing subjective withdrawal experience might advance opioid use disorder (OUD) research and precision treatment. This study explores one factor - withdrawal catastrophizing - a negative cognitive and emotional orientation toward withdrawal characterized by excessive fear, worry or inability to divert attention from withdrawal symptoms.Objectives: We define a novel concept - withdrawal catastrophizing - and present an initial evaluation of the Withdrawal Catastrophizing Scale (WCS).Methods: Prospective observational study (n = 122, 48.7% women). Factor structure (exploratory factor analysis) and internal consistency (Cronbach's α) were assessed. Predictive validity was tested via correlation between WCS and next-day subjective opiate withdrawal scale (SOWS) severity. The clinical salience of WCS was evaluated by correlation between WCS and withdrawal-motivated behaviors including risk taking, OUD maintenance, OUD treatment delay, history of leaving the hospital against medical advice and buprenorphine-precipitated withdrawal.Results: WCS was found to have a two-factor structure (distortion and despair), strong internal consistency (α = .901), and predictive validity - Greater withdrawal catastrophizing was associated with next-day SOWS (rs (99) = 0.237, p = .017). Withdrawal catastrophizing was also correlated with risk-taking behavior to relieve withdrawal (rs (119) = 0.357, p < .001); withdrawal-motivated OUD treatment avoidance (rs (119) = 0.421, p < .001), history of leaving the hospital against medical advice (rs (119) = 0.373, p < .001) and buprenorphine-precipitated withdrawal (rs (119) = 0.369, p < .001).Conclusion: This study provides first evidence of withdrawal catastrophizing as a clinically important phenomenon with implications for the future study and treatment of OUD.

Can Positive Play Deficits Explain the Associations Between Posttraumatic Stress Symptoms, Gambling Motives, and Problem Gambling? Results of a National U.S. Sample.

Past research has demonstrated a consistent connection between symptoms of posttraumatic stress disorder (PTSD) and problematic gambling in both general and clinical United States (U.S.) populations. Little is known, however, about the mediating role that responsible gambling practices related to positive play might have in the relationships between symptoms of PTSD, problem gambling (PG) severity, and different motives for gambling. Therefore, using mediation analysis, this study investigated these associations within a census-matched national sample of U.S. adults (N = 2,806). Results indicated PTSD symptoms and PG often co-occur in this population (r = .43, p < .01), and coping motives for gambling were the key mechanism connecting PTSD symptoms to PG severity rather than deficits in positive play practices or other gambling motives. Moreover, it was found that the average gambler who had sought treatment for gambling in the past not only had more severe PTSD symptoms and PG but also had the strongest gambling motives, the largest deficits in positive play, and was more likely to be younger than 50 years old. In this sample, approximately 1 in 10 people who gambled in the past year were classified as problem gamblers, 1 in 5 met criteria for a provisional PTSD diagnosis, and 1 in 33 sought out gambling treatment previously. These findings provide further evidence for the relationship between symptoms of posttraumatic stress and problematic gambling behaviors in the U.S. population and offer critical insights into the explanatory roles of coping motives and positive play practices in this connection.

Rare copy number variation in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10-8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q < 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further.

Down on the farm: Farm coronaviruses are a large reservoir for new spillover events into humans.

Until COVID-19, coronaviruses were largely overlooked by virologists. Yet, their abundance in mammalian species could cause new spillover events into humans.

Vaccines beyond antibodies: Spurred by pandemic research, are T-cell vaccines moving closer to reality?

Lessons learned from the vaccines against SARS-CoV-2 has encouraged research and vaccine development aimed at mustering strong T cell responses against the pathogen.

An Interventional Response Phenotyping Study in Chronic Low Back Pain: Protocol for a Mechanistic Randomized Controlled Trial.

Evidence-based treatments for chronic low back pain (cLBP) typically work well in only a fraction of patients, and at present there is little guidance regarding what treatment should be used in which patients. Our central hypothesis is that an interventional response phenotyping study can identify individuals with different underlying mechanisms for their pain who thus respond differentially to evidence-based treatments for cLBP. Thus, we will conduct a randomized controlled Sequential, Multiple Assessment, Randomized Trial (SMART) design study in cLBP with the following three aims. Aim 1: Perform an interventional response phenotyping study in a cohort of cLBP patients (n = 400), who will receive a sequence of interventions known to be effective in cLBP. For 4 weeks, all cLBP participants will receive a web-based pain self-management program as part of a run-in period, then individuals who report no or minimal improvement will be randomized to: a) mindfulness-based stress reduction, b) physical therapy and exercise, c) acupressure self-management, and d) duloxetine. After 8 weeks, individuals who remain symptomatic will be re-randomized to a different treatment for an additional 8 weeks. Using those data, we will identify the subsets of participants that respond to each treatment. In Aim 2, we will show that currently available, clinically derived measures, can predict differential responsiveness to the treatments. In Aim 3, a subset of participants will receive deeper phenotyping (n = 160), to identify new experimental measures that predict differential responsiveness to the treatments, as well as to infer mechanisms of action. Deep phenotyping will include functional neuroimaging, quantitative sensory testing, measures of inflammation, and measures of autonomic tone.

Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis.

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.

The second coming: The comeback of the live vaccines.

Live vaccines are gradually replaced by protein-based vaccines given the latter's better safety. But live vaccines seem to be more efficient via stimulation of the innate immune system.

Fast news or fake news?: The advantages and the pitfalls of rapid publication through pre-print servers during a pandemic.

Pre-print servers have helped to rapidly publish important information during the COVID-19 pandemic. The downside is the risk of spreading false information or fake news though.