Bisphenol A in Thermal Paper Receipts: Taylor et al. Respond

We agree with Schwartz and Landrigan that there is a need for change in the regulatory system for chemicals used in products in the United States. Bisphenol A (BPA) is one of thousands of chemicals of concern, but it provides a striking example of what happens when there is no requirement for premarket testing

Perceptions towards the adoption of multi-risk factors cancer prevention educational tool among european union citizens: A multi-country qualitative study protocol

Background: Cancer is a major public health problem. Four million new cancer cases are diagnosed annually in Europe, of which around 40% could be prevented. The European Code Against Cancer (ECAC) is a health education tool to raise awareness about risk factors and evidence-based measures to prevent cancer. The ECAC 4th edition consists of 12 recommendations to reduce individuals’ cancer risk and related deaths. This study explores perceived barriers to adopting the cancer prevention actions recommended by the ECAC fourth edition in the European Union (EU). Methods: The COM-B model of behaviour change will be used as a framework for the design and analysis of the study since it identifies factors (capability, opportunity, motivation) that need to be present for any behaviour change to occur. A qualitative study using an exploratory research methodology was designed to obtain information from adults with no previous cancer diagnosis by employing in-depth semi-structured interviews. Participants are selected using a quota sampling strategy according to sex, age, and education level (18 profiles/country). Interviews will be conducted in participants’ native language by trained researchers. Afterward, a thematic content analysis will be conducted to identify common topics, followed by a critical analysis of their discourse. Discussion: This study will contribute to informing the fifth edition of the ECAC –currently under development; by providing insights on how EU citizens perceive the cancer prevention recommendations of the fourth edition and whether they can motivate them to change unhealthy behaviours. Additionally, the study will help to identify the main facilitators and barriers (perceived or already confronted) to adopt these cancer prevention recommendations so that this knowledge will contribute to updating the recommendations of the fifth edition of the ECAC

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Using mineral equilibria to estimate H2O activities in peridotites from the Western Gneiss Region of Norway

The Earth's mantle is an important reservoir of H2O, and even a small amount of H2O has a significant influence on the physical properties of mantle rocks. Estimating the amount of H2O in rocks from the Earth's mantle would, therefore, provide some insights into the physical properties of this volumetrically dominant portion of the Earth. The goal of this study is to use mineral equilibria to determine the activities of H2O (aH2O) in orogenic mantle peridotites from the Western Gneiss Region of Norway. An amphibole dehydration reaction yielded values of aH2O ranging from 0.1 to 0.4 for these samples. Values of fO2 of approximately 1 to 2 log units below the FMQ oxygen buffer were estimated from afO2-buffering reaction between olivine, orthopyroxene, and spinel for these same samples. These results demonstrate that the presence of amphibole in the mantle does not require elevated values of aH2O (i.e., aH2O 1) nor relatively oxidizing values offO2 (i.e., >FMQ). It is possible to estimate a minimum value of aH2O by characterizing fluid speciation in C-O-H system for a given value of oxygen fugacity fO2). Our results show that the estimates of aH2O obtained from the amphibole dehydration equilibrium are significantly lower than values of aH2O estimated from this combination of fO2 and C-O-H calculations. This suggests that fluid pressure (Pfluid) is less than lithostatic pressure (Plith) and, for metamorphic rocks, implies the absence of a free fluid phase. Fluid absent condition could be generated by amphibole growth during exhumation. If small amounts of H2O were added to these rocks, the formation of amphibole could yield low values of aH2O by consuming all available H2O. On the other hand, if the nominally anhydrous minerals (NAMs) contained significant H2O at conditions outside of the stability field of amphibole they might have served as a reservoir of H2O. In this case, NAMs could supply the OH necessary for amphibole growth once retrograde P-T conditions were consistent with amphibole stability. Thus, amphibole growth may effectively dehydrate coexisting NAMs and enhance the strength of rocks as long as the NAMs controlled the rheology of the rock