Mediational pathways of the impact of cigarette warning labels on quit attempts

OBJECTIVES: To test and develop, using structural equation modelling, a robust model of the mediational pathways through which health warning labels exert their influence on smokers’ subsequent quitting behaviour. METHODS: Data come from the International Tobacco Control Four-Country Survey, a longitudinal cohort study conducted in Australia, Canada, the UK, and the US. Waves 5–6 data (n=4988) were used to calibrate the hypothesized model of warning label impact on subsequent quit attempts via a set of policy-specific and general psychosocial mediators. The finalised model was validated using Waves 6–7 data (n=5065). RESULTS: As hypothesized, warning label salience was positively associated with thoughts about risks of smoking stimulated by the warnings (β=.58, p<.001), which in turn were positively related to increased worry about negative outcomes of smoking (β=.52, p<.001); increased worry in turn predicted stronger intention to quit (β=.39, p<.001) which was a strong predictor of subsequent quit attempts (β=.39, p<.001). This calibrated model was successfully replicated using Waves 6–7 data. CONCLUSIONS: Health warning labels seem to influence future quitting attempts primarily through their ability to stimulate thoughts about the risks of smoking, which in turn help to raise smoking-related health concerns, which lead to stronger intentions to quit, a known key predictor of future quit attempts for smokers. By making warning labels more salient and engaging, they should have a greater chance to change behaviour

The TBX21 transcription factor T-1993C polymorphism is associated with decreased IFN-γ and IL-4 production by primary human lymphocytes

T-bet is a transcription factor that drives the Th1 immune response primarily through promoting expression of the IFN-γ gene. Polymorphisms in the T-bet gene, TBX21, have been associated with immune-mediated diseases such as asthma and systemic sclerosis. We found that the TBX21 promoter polymorphism T-1993C is associated with a significant decrease in IL-4 and IFN-γ production by stimulated primary human lymphocytes from healthy participants

ILLUMINATING THE DARKEST GAMMA-RAY BURSTS WITH RADIO OBSERVATIONS

We present X-ray, optical, near-infrared (IR), and radio observations of gamma-ray bursts (GRBs) 110709B and 111215A, as well as optical and near-IR observations of their host galaxies. The combination of X-ray detections and deep optical/near-IR limits establish both bursts as "dark." Sub-arcsecond positions enabled by radio detections lead to robust host galaxy associations, with optical detections that indicate z ≾ 4 (110709B) and z ≈ 1.8-2.9 (111215A). We therefore conclude that both bursts are dark due to substantial rest-frame extinction. Using the radio and X-ray data for each burst we find that GRB 110709B requires A_V^(host) ≳ 5.3 mag and GRB 111215A requires A_V^(host) ≳ 8.5 mag (assuming z = 2). These are among the largest extinction values inferred for dark bursts to date. The two bursts also exhibit large neutral hydrogen column densities of N H, int ≳ 10^(22) cm^(–2) (z = 2) as inferred from their X-ray spectra, in agreement with the trend for dark GRBs. Moreover, the inferred values are in agreement with the Galactic A_V -N_H relation, unlike the bulk of the GRB population. Finally, we find that for both bursts the afterglow emission is best explained by a collimated outflow with a total beaming-corrected energy of E_γ + E_K ≈ (7-9) × 10^(51) erg (z = 2) expanding into a wind medium with a high density, Ṁ ≈ (6-20) x 10^(-5) M_☉ yr^(–1) (n ≈ 100-350 cm^(–3) at ≈ 10^(17) cm). While the energy release is typical of long GRBs, the inferred density may be indicative of larger mass-loss rates for GRB progenitors in dusty (and hence metal rich) environments. This study establishes the critical role of radio observations in demonstrating the origin and properties of dark GRBs. Observations with the JVLA and ALMA will provide a sample with sub-arcsecond positions and robust host associations that will help to shed light on obscured star formation and the role of metallicity in GRB progenitors

Antiferromagnetic ordering in a 90 K copper oxide superconductor

Using elastic neutron scattering, we evidence a commensurate antiferromagnetic Cu(2) order (AF) in the superconducting (SC) high-$\rm T_c$ cuprate $\rm YBa_2(Cu_{1-y}Co_y)_3O_{7+\delta}$ (y=0.013, $\rm T_c$=93 K). As in the Co-free system, the spin excitation spectrum is dominated by a magnetic resonance peak at 41 meV but with a reduced spectral weight. The substitution of Co thus leads to a state where AF and SC cohabit showing that the CuO$_2$ plane is a highly antiferromagnetically polarizable medium even for a sample where T$_c$ remains optimum.Comment: 3 figure

Psychological distress and quality of life in lung cancer: The role of health-related stigma, illness appraisals and social constraints

Objective: Health-related stigma is associated with negative psychological and quality of life outcomes in lung cancer patients. This study describes the impact of stigma on lung cancer patients\u27 psychological distress and quality of life and explores the role of social constraints and illness appraisal as mediators of effect. Methods: A self-administered cross-sectional survey examined psychological distress and quality of life in 151 people (59% response rate) diagnosed with lung cancer from Queensland and New South Wales. Health-related stigma, social constraints and illness appraisals were assessed as predictors of adjustment outcomes. Results: Forty-nine percent of patients reported elevated anxiety; 41% were depressed; and 51% had high global distress. Health-related stigma was significantly related to global psychological distress and quality of life with greater stigma and shame related to poorer outcomes. These effects were mediated by illness appraisals and social constraints. Conclusions: Health-related stigma appears to contribute to poorer adjustment by constraining interpersonal discussions about cancer and heightening feelings of threat. There is a need for the development and evaluation of interventions to ameliorate the negative effects of health-related stigma among lung cancer patients

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies

Schinzel-Giedion syndrome (SGS) is a rare developmental disorder characterized by multiple malformations, severe neurological alterations and increased risk of malignancy. SGS is caused by de novo germline mutations clustering to a 12bp hotspot in exon 4 of SETBP1. Mutations in this hotspot disrupt a degron, a signal for the regulation of protein degradation, and lead to the accumulation of SETBP1 protein. Overlapping SETBP1 hotspot mutations have been observed recurrently as somatic events in leukemia. We collected clinical information of 47 SGS patients (including 26 novel cases) with germline SETBP1 mutations and of four individuals with a milder phenotype caused by de novo germline mutations adjacent to the SETBP1 hotspot. Different mutations within and around the SETBP1 hotspot have varying effects on SETBP1 stability and protein levels in vitro and in in silico modeling. Substitutions in SETBP1 residue I871 result in a weak increase in protein levels and mutations affecting this residue are significantly more frequent in SGS than in leukemia. On the other hand, substitutions in residue D868 lead to the largest increase in protein levels. Individuals with germline mutations affecting D868 have enhanced cell proliferation in vitro and higher incidence of cancer compared to patients with other germline SETBP1 mutations. Our findings substantiate that, despite their overlap, somatic SETBP1 mutations driving malignancy are more disruptive to the degron than germline SETBP1 mutations causing SGS. Additionally, this suggests that the functional threshold for the development of cancer driven by the disruption of the SETBP1 degron is higher than for the alteration in prenatal development in SGS. Drawing on previous studies of somatic SETBP1 mutations in leukemia, our results reveal a genotype-phenotype correlation in germline SETBP1 mutations spanning a molecular, cellular and clinical phenotype

Clinical Endpoints for Evaluating Efficacy in COVID-19 Vaccine Trials

Several vaccine candidates to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19) have entered or will soon enter large-scale, phase 3, placebo-controlled randomized clinical trials. To facilitate harmonized evaluation and comparison of the efficacy of these vaccines, a general set of clinical endpoints is proposed, along with considerations to guide the selection of the primary endpoints on the basis of clinical and statistical reasoning. The plausibility that vaccine protection against symptomatic COVID-19 could be accompanied by a shift toward more SARS-CoV-2 infections that are asymptomatic is highlighted, as well as the potential implications of such a shift

A Deferred-Vaccination Design to Assess Durability of COVID-19 Vaccine Effect After the Placebo Group Is Vaccinated

Multiple candidate vaccines to prevent COVID-19 have entered large-scale phase 3 placebo-controlled randomized clinical trials, and several have demonstrated substantial short-term efficacy. At some point after demonstration of substantial efficacy, placebo recipients should be offered the efficacious vaccine from their trial, which will occur before longer-term efficacy and safety are known. The absence of a placebo group could compromise assessment of longer-term vaccine effects. However, by continuing follow-up after vaccination of the placebo group, this study shows that placebo-controlled vaccine efficacy can be mathematically derived by assuming that the benefit of vaccination over time has the same profile for the original vaccine recipients and the original placebo recipients after their vaccination. Although this derivation provides less precise estimates than would be obtained by a standard trial where the placebo group remains unvaccinated, this proposed approach allows estimation of longer-term effect, including durability of vaccine efficacy and whether the vaccine eventually becomes harmful for some. Deferred vaccination, if done open-label, may lead to riskier behavior in the unblinded original vaccine group, confounding estimates of long-term vaccine efficacy. Hence, deferred vaccination via blinded crossover, where the vaccine group receives placebo and vice versa, would be the preferred way to assess vaccine durability and potential delayed harm. Deferred vaccination allows placebo recipients timely access to the vaccine when it would no longer be proper to maintain them on placebo, yet still allows important insights about immunologic and clinical effectiveness over time