65 research outputs found
National identity predicts public health support during a global pandemic
Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.publishedVersio
Mapping and characterization of structural variation in 17,795 human genomes
A key goal of whole-genome sequencing for studies of human genetics is to interrogate all forms of variation, including single-nucleotide variants, small insertion or deletion (indel) variants and structural variants. However, tools and resources for the study of structural variants have lagged behind those for smaller variants. Here we used a scalable pipeline1 to map and characterize structural variants in 17,795 deeply sequenced human genomes. We publicly release site-frequency data to create the largest, to our knowledge, whole-genome-sequencing-based structural variant resource so far. On average, individuals carry 2.9 rare structural variants that alter coding regions; these variants affect the dosage or structure of 4.2 genes and account for 4.0–11.2% of rare high-impact coding alleles. Using a computational model, we estimate that structural variants account for 17.2% of rare alleles genome-wide, with predicted deleterious effects that are equivalent to loss-of-function coding alleles; approximately 90% of such structural variants are noncoding deletions (mean 19.1 per genome). We report 158,991 ultra-rare structural variants and show that 2% of individuals carry ultra-rare megabase-scale structural variants, nearly half of which are balanced or complex rearrangements. Finally, we infer the dosage sensitivity of genes and noncoding elements, and reveal trends that relate to element class and conservation. This work will help to guide the analysis and interpretation of structural variants in the era of whole-genome sequencing
Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility
Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn's disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.Cellular mechanisms in basic and clinical gastroenterology and hepatolog
Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease
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Clonazepam Open Clinical Treatment Trial for Myofascial Syndrome Associated Chronic Pain
Objective. A number of case reports and nonplacebo controlled studies have documented the efficacy of clonazepam (Klonopin) in the treatment of a number of chronic pain syndromes including lancinating and neuropathic/deafferentation pain. There are, however, no data on the efficacy of clonazepam for chronic pain (CP) associated with myofascial pain syndrome (MFPS). Therefore, we wish to report the results of an open clinical treatment trial of clonazepam for CP associated with MFPS.
Design. Forty‐six patients with chronic pain (PWCP) and a diagnosis of MFPS were recruited into a clonazepam pain treatment open clinical trial. At entrance and completion of the study the patients completed a 10‐cm visual analog scale (VAS) requesting them to rate their pain over the last 24 hours. Clonazepam was titrated upwards from 0.5 mg per day, at 0.5 mg increments, every 2 days. These patients rated their perceived pain relief daily on a 3‐point rating scale: none, partial, total. Once a patient claimed partial pain relief clonazepam increases were stopped. Patients who complained of intolerable side effects before partial pain relief were withdrawn from the study. For a subgroup of patients claiming partial pain relief, clonazepam serum levels were determined. Because of the reported efficacy of clonazepam for neuropathic/deafferentation type of pain, patients with this diagnosis were withdrawn from the partial response group. Statistical analyses were performed on this remaining patient group with myofascial pain syndrome without a secondary diagnosis of neuropathic/deafferentation pain and partially responsive to clonazepam. Descriptive statistics were calculated for this group. Drop in pain level from entrance to partial response was tested for statistical significance via t test. In addition, 17 independent variables such as presence of trigger points, presence of burning pain etc, were utilized in a regression analysis, with drop in pain level as the dependent variable. A Pearson correlation analysis was first performed in order to determine which of the independent variables significantly correlated with decrease in pain level. Independent variables having a Pearson r of .3687 or greater were selected for the regression procedure.
Setting. Multidisciplinary pain facility.
Patients. Patients with chronic pain with a diagnosis of MFPS and without neuropathic/deafferentation pain.
Results. Of the 46 patients entered into the study, 9 were not titrated to partial pain relief because of intolerable sedation and 9 had a diagnosis of neuropathic/deafferentation pain. For the remaining group (n = 28), mean drop in VAS pain level from beginning of the study to partial response was 2.78 (SD = 1.94). This was statistically significant (t = 5.49, P < .001). Mean clonazepam dosage to reach partial response was 2.41 (SD = 1.62) mg/day and the mean dosage per kilogram body weight per day was 0.04 (SD = 0.03) mg. Mean clonazepam serum level was 30.58 (SD = 24.53) μg/L. Decrease in pain level was associated with the presence of the following independent variables: trigger points (r = .451); range of motion restriction (r = .653); non anatomical sensory abnormalities (r = .370); chronic low back pain (r = .451); and burning pain (r = .482). In the regression analysis, restricted range of motion and presence of burning pain accounted for 42% and 16% of the variance respectfully.
Conclusion. Clonazepam may have an antinociceptive effect for pain associated with myofascial pain syndrome
Cause-effect relationships and partially defined Boolean functions
This paper investigates the use of Boolean techniques in a systematic study of cause-effect relationships. The model uses partially defined Boolean functions. Procedures are provided to extrapolate from limited observations, concise and meaningful theories to explain the effect under study, and to prevent (or provoke) its occurrenc
Rejection of the name Borreliella and all proposed species comb. nov. placed therein
Rejection (nomen rejiciendum) of the name Borreliella and all new combinations therein is being requested on grounds of risk to human health and patient safety (Principle 1, subprinciple 2 and Rule 56a) and violation to aim for stability of names, to avoid useless creation of names (Principle 1, subprinciple 1 and 3) and that names should not be changed without sufficient reason (Principle 9 of the International Code of Nomenclature of Prokaryotes)
Stellated cuboctahedron of Fe<sup>III</sup>
The solvothermal reaction of FeCl2 ⋅ 4H2O and H4TBC[4] in a basic dmf/EtOH solution affords an [FeIII18] Keplerate conforming to a stellated cuboctahedron. Magnetic and heat capacity measurements reveal spin frustration effects arising from the high symmetry. A crossover between inverse and direct magnetocaloric effects is observed at ~10 K for applied-field changes lower than 3 T.</p
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