Report of the Topical Group on Electroweak Precision Physics and Constraining New Physics for Snowmass 2021

The precise measurement of physics observables and the test of their consistency within the standard model (SM) are an invaluable approach, complemented by direct searches for new particles, to determine the existence of physics beyond the standard model (BSM). Studies of massive electroweak gauge bosons (W and Z bosons) are a promising target for indirect BSM searches, since the interactions of photons and gluons are strongly constrained by the unbroken gauge symmetries. They can be divided into two categories: (a) Fermion scattering processes mediated by s- or t-channel W/Z bosons, also known as electroweak precision measurements; and (b) multi-boson processes, which include production of two or more vector bosons in fermion-antifermion annihilation, as well as vector boson scattering (VBS) processes. The latter categories can test modifications of gauge-boson self-interactions, and the sensitivity is typically improved with increased collision energy. This report evaluates the achievable precision of a range of future experiments, which depend on the statistics of the collected data sample, the experimental and theoretical systematic uncertainties, and their correlations. In addition it presents a combined interpretation of these results, together with similar studies in the Higgs and top sector, in the Standard Model effective field theory (SMEFT) framework. This framework provides a model-independent prescription to put generic constraints on new physics and to study and combine large sets of experimental observables, assuming that the new physics scales are significantly higher than the EW scale.Comment: 55 pages; Report of the EF04 topical group for Snowmass 202

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Beyond Professional Licensure: A Statement of Principle on Culturally-Responsive Healthcare.

This work calls on healthcare institutions and organizations to move toward inclusive recognition and representation of healthcare practitioners whose credibility is established both inside and outside of professional licensure mechanisms. Despite professional licensure's advantages, this credentialing mechanism has in many cases served to reinforce unjust sociocultural power relations in relation to ethnicity and race, class and gender. To foster health equity and the delivery of culturally-responsive care, it is essential that mechanisms other than licensure be recognized as legitimate pathways for community accountability, safety and quality assurance. Such mechanisms include certification with non-statutory occupational bodies, as well as community-based recognition pathways such as those engaged for Community Health Workers (including Promotores de Salud) and Indigenous healing practitioners. Implementation of this vision will require interdisciplinary dialogue and reconciliation, constructive collaboration, and shared decision making between healthcare institutions and organizations, practitioners and the communities they serve

Neural correlates of metacognitive ability and of feeling confident: a large-scale fMRI study

One important aspect of metacognition is the ability to accurately evaluate one’s performance. People vary widely in their metacognitive ability and in general are too confident when evaluating their performance. This often leads to poor decision making with potentially disastrous consequences. To further our understanding of the neural underpinnings of these processes, this fMRI study investigated inter-individual differences in metacognitive ability and effects of trial-by-trial variation in subjective feelings of confidence when making metacognitive assessments. Participants (N = 308) evaluated their performance in a high-level social and cognitive reasoning task. The results showed that higher metacognitive accuracy was associated with a decrease in activation in the anterior medial prefrontal cortex, an area previously linked to metacognition on perception and memory. Moreover, the feeling of confidence about one’s choices was associated with an increase of activation in reward, memory and motor related areas including bilateral striatum and hippocampus, while less confidence was associated with activation in areas linked with negative affect and uncertainty, including dorsomedial prefrontal and bilateral orbitofrontal cortex. This might indicate that positive affect is related to higher confidence thereby biasing metacognitive decisions towards overconfidence. In support, behavioural analyses revealed that increased confidence was associated with lower metacognitive accuracy

Report of the Topical Group on Electroweak Precision Physics and Constraining New Physics for Snowmass 2021

The precise measurement of physics observables and the test of their consistency within the standard model (SM) are an invaluable approach, complemented by direct searches for new particles, to determine the existence of physics beyond the standard model (BSM). Studies of massive electroweak gauge bosons (W and Z bosons) are a promising target for indirect BSM searches, since the interactions of photons and gluons are strongly constrained by the unbroken gauge symmetries. They can be divided into two categories: (a) Fermion scattering processes mediated by s- or t-channel W/Z bosons, also known as electroweak precision measurements; and (b) multi-boson processes, which include production of two or more vector bosons in fermion-antifermion annihilation, as well as vector boson scattering (VBS) processes. The latter categories can test modifications of gauge-boson self-interactions, and the sensitivity is typically improved with increased collision energy. This report evaluates the achievable precision of a range of future experiments, which depend on the statistics of the collected data sample, the experimental and theoretical systematic uncertainties, and their correlations. In addition it presents a combined interpretation of these results, together with similar studies in the Higgs and top sector, in the Standard Model effective field theory (SMEFT) framework. This framework provides a model-independent prescription to put generic constraints on new physics and to study and combine large sets of experimental observables, assuming that the new physics scales are significantly higher than the EW scale