Psi4 is an ab initio electronic structure program providing methods such as Hartree–Fock, density functional theory, configuration interaction, and coupled-cluster theory. The 1.1 release represents ...a major update meant to automate complex tasks, such as geometry optimization using complete-basis-set extrapolation or focal-point methods. Conversion of the top-level code to a Python module means that Psi4 can now be used in complex workflows alongside other Python tools. Several new features have been added with the aid of libraries providing easy access to techniques such as density fitting, Cholesky decomposition, and Laplace denominators. The build system has been completely rewritten to simplify interoperability with independent, reusable software components for quantum chemistry. Finally, a wide range of new theoretical methods and analyses have been added to the code base, including functional-group and open-shell symmetry adapted perturbation theory, density-fitted coupled cluster with frozen natural orbitals, orbital-optimized perturbation and coupled-cluster methods (e.g., OO-MP2 and OO-LCCD), density-fitted multiconfigurational self-consistent field, density cumulant functional theory, algebraic-diagrammatic construction excited states, improvements to the geometry optimizer, and the “X2C” approach to relativistic corrections, among many other improvements.
Mendelian randomisation (MR) studies allow a better understanding of the causal effects of modifiable exposures on health outcomes, but the published evidence is often hampered by inadequate ...reporting. Reporting guidelines help authors effectively communicate all critical information about what was done and what was found. STROBE-MR (strengthening the reporting of observational studies in epidemiology using mendelian randomisation) assists authors in reporting their MR research clearly and transparently. Adopting STROBE-MR should help readers, reviewers, and journal editors evaluate the quality of published MR studies. This article explains the 20 items of the STROBE-MR checklist, along with their meaning and rationale, using terms defined in a glossary. Examples of transparent reporting are used for each item to illustrate best practices.
Background Severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome is a recently recognized syndrome caused by mutations in the desmoglein 1 gene (DSG1) . To date, only 3 families ...have been reported. Objective We studied a new case of SAM syndrome known to have no mutations in DSG1 to detail the clinical, histopathologic, immunofluorescent, and ultrastructural phenotype and to identify the underlying molecular mechanisms in this rare genodermatosis. Methods Histopathologic, electron microscopy, and immunofluorescent studies were performed. Whole-exome sequencing data were interrogated for mutations in desmosomal and other skin structural genes, followed by Sanger sequencing of candidate genes in the patient and his parents. Results No mutations were identified in DSG1 ; however, a novel de novo heterozygous missense c.1757A>C mutation in the desmoplakin gene (DSP) was identified in the patient, predicting the amino acid substitution p.His586Pro in the desmoplakin polypeptide. Conclusions SAM syndrome can be caused by mutations in both DSG1 and DSP . Knowledge of this genetic heterogeneity is important for both analysis of patients and genetic counseling of families. This condition and these observations reinforce the importance of heritable skin barrier defects, in this case desmosomal proteins, in the pathogenesis of atopic disease.
IMPORTANCE: Clinical decisions are ideally based on evidence generated from multiple randomized controlled trials (RCTs) evaluating clinical outcomes, but historically, few clinical guideline ...recommendations have been based entirely on this type of evidence. OBJECTIVE: To determine the class and level of evidence (LOE) supporting current major cardiovascular society guideline recommendations, and changes in LOE over time. DATA SOURCES: Current American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology (ESC) clinical guideline documents (2008-2018), as identified on cardiovascular society websites, and immediate predecessors to these guideline documents (1999-2014), as referenced in current guideline documents. STUDY SELECTION: Comprehensive guideline documents including recommendations organized by class and LOE. DATA EXTRACTION AND SYNTHESIS: The number of recommendations and the distribution of LOE (A supported by data from multiple RCTs or a single, large RCT, B supported by data from observational studies or a single RCT, and C supported by expert opinion only) were determined for each guideline document. MAIN OUTCOMES AND MEASURES: The proportion of guideline recommendations supported by evidence from multiple RCTs (LOE A). RESULTS: Across 26 current ACC/AHA guidelines (2930 recommendations; median, 121 recommendations per guideline 25th-75th percentiles, 76-155), 248 recommendations (8.5%) were classified as LOE A, 1465 (50.0%) as LOE B, and 1217 (41.5%) as LOE C. The median proportion of LOE A recommendations was 7.9% (25th-75th percentiles, 0.9%-15.2%). Across 25 current ESC guideline documents (3399 recommendations; median, 130 recommendations per guideline 25th-75th percentiles, 111-154), 484 recommendations (14.2%) were classified as LOE A, 1053 (31.0%) as LOE B, and 1862 (54.8%) as LOE C. When comparing current guidelines with prior versions, the proportion of recommendations that were LOE A did not increase in either ACC/AHA (median, 9.0% current vs 11.7% prior) or ESC guidelines (median, 15.1% current vs 17.6% prior). CONCLUSIONS AND RELEVANCE: Among recommendations in major cardiovascular society guidelines, only a small percentage were supported by evidence from multiple RCTs or a single, large RCT. This pattern does not appear to have meaningfully improved from 2008 to 2018.
IMPORTANCE: Mendelian randomization (MR) studies use genetic variation associated with modifiable exposures to assess their possible causal relationship with outcomes and aim to reduce potential bias ...from confounding and reverse causation. OBJECTIVE: To develop the STROBE-MR Statement as a stand-alone extension to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guideline for the reporting of MR studies. DESIGN, SETTING, AND PARTICIPANTS: The development of the STROBE-MR Statement followed the Enhancing the Quality and Transparency of Health Research (EQUATOR) framework guidance and used the STROBE Statement as a starting point to draft a checklist tailored to MR studies. The project was initiated in 2018 by reviewing the literature on the reporting of instrumental variable and MR studies. A group of 17 experts, including MR methodologists, MR study design users, developers of previous reporting guidelines, and journal editors, participated in a workshop in May 2019 to define the scope of the Statement and draft the checklist. The draft checklist was published as a preprint in July 2019 and discussed on the preprint platform, in social media, and at the 4th Mendelian Randomization Conference. The checklist was then revised based on comments, further refined through 2020, and finalized in July 2021. FINDINGS: The STROBE-MR checklist is organized into 6 sections (Title and Abstract, Introduction, Methods, Results, Discussion, and Other Information) and includes 20 main items and 30 subitems. It covers both 1-sample and 2-sample MR studies that assess 1 or multiple exposures and outcomes, and addresses MR studies that follow a genome-wide association study and are reported in the same article. The checklist asks authors to justify why MR is a helpful method to address the study question and state prespecified causal hypotheses. The measurement, quality, and selection of genetic variants must be described and attempts to assess validity of MR-specific assumptions should be well reported. An item on data sharing includes reporting when the data and statistical code required to replicate the analyses can be accessed. CONCLUSIONS AND RELEVANCE: STROBE-MR provides guidelines for reporting MR studies. Improved reporting of these studies could facilitate their evaluation by editors, peer reviewers, researchers, clinicians, and other readers, and enhance the interpretation of their results.
Summary Background Despite a recent resurgence in the incidence of bovine tuberculosis in UK cattle herds, no associated rise in the number of cases in man has been noted. Disease due to human ...Mycobacterium bovis infection usually occurs in older patients, in whom drinking unpasteurised milk in the past is the probable source of infection. Person-to-person transmission is very rare. Methods After identification of two epidemiologically-linked cases of human M bovis infection through routine laboratory and surveillance activities, all patients identified with M bovis infection in the Midlands from 2001–05 (n=20) were assessed by DNA fingerprinting (MIRU-VNTR and spoligotyping), with additional interviews for patients with a clustered strain. Findings A cluster of six cases was identified. All clustered cases were young and UK-born; five patients had pulmonary disease, and one patient died due to M bovis meningitis, with four patients possessing factors predisposing to tuberculosis. All patients had common social links through visits to bars in two different areas. With the exception of the first case, there was an absence of zoonotic links or consumption of unpasteurised dairy products, suggesting that person-to-person transmission had occurred. Interpretation This report of several instances of M bovis transmission between people in a modern urban setting emphasises the need to maintain control measures for human and bovine tuberculosis. Transmission and subsequent disease was probably due to a combination of host and environmental factors. Prospective surveillance and DNA fingerprinting identified the cluster, enabling health protection teams to set up control measures and prevent further transmission.
Evidence Gaps and Future Directionse208 Appendix 1 Author Relationships With Industry and Other Entities (Relevant)e238 Appendix 2 Reviewer Relationships With Industry and Other Entities ...(Comprehensive)e240 Preamble Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to improve cardiovascular health.In 2013, the National Heart, Lung, and Blood Institute (NHLBI) Advisory Council recommended that the NHLBI focus specifically on reviewing the highest-quality evidence and partner with other organizations to develop recommendations (P-1,P-2)....the ACC and AHA collaborated with the NHLBI and stakeholder and professional organizations to complete and publish 4 guidelines (on assessment of cardiovascular risk, lifestyle modifications to reduce cardiovascular risk, management of blood cholesterol in adults, and management of overweight and obesity in adults) to make them available to the widest possible constituency.Adherence to recommendations can be enhanced by shared decision making between clinicians and patients, with patient engagement in selecting interventions on the basis of individual values, preferences, and associated conditions and comorbidities.Methodology and Modernization The ACC/AHA Task Force on Clinical Practice Guidelines (Task Force) continuously reviews, updates, and modifies guideline methodology on the basis of published standards from organizations, including the Institute of Medicine (P-3,P-4), and on the basis of internal reevaluation.
Dopaminergic Network Differences in Human Impulsivity Buckholtz, Joshua W; Treadway, Michael T; Cowan, Ronald L ...
Science (American Association for the Advancement of Science),
07/2010, Letnik:
329, Številka:
5991
Journal Article
Recenzirano
Odprti dostop
Dopamine (DA) has long been implicated in impulsivity, but the precise mechanisms linking human variability in DA signaling to differences in impulsive traits remain largely unknown. By using a ...dual-scan positron emission tomography approach in healthy human volunteers with amphetamine and the D2/D3 ligand ¹⁸Ffallypride, we found that higher levels of trait impulsivity were predicted by diminished midbrain D2/D3 autoreceptor binding and greater amphetamine-induced DA release in the striatum, which was in turn associated with stimulant craving. Path analysis confirmed that the impact of decreased midbrain D2/D3 autoreceptor availability on trait impulsivity is mediated in part through its effect on stimulated striatal DA release.
CONTEXT The joint cardiovascular practice guidelines of the American College of Cardiology (ACC) and the American Heart Association (AHA) have become important documents for guiding cardiology ...practice and establishing benchmarks for quality of care. OBJECTIVE To describe the evolution of recommendations in ACC/AHA cardiovascular guidelines and the distribution of recommendations across classes of recommendations and levels of evidence. DATA SOURCES AND STUDY SELECTION Data from all ACC/AHA practice guidelines issued from 1984 to September 2008 were abstracted by personnel in the ACC Science and Quality Division. Fifty-three guidelines on 22 topics, including a total of 7196 recommendations, were abstracted. DATA EXTRACTION The number of recommendations and the distribution of classes of recommendation (I, II, and III) and levels of evidence (A, B, and C) were determined. The subset of guidelines that were current as of September 2008 was evaluated to describe changes in recommendations between the first and current versions as well as patterns in levels of evidence used in the current versions. RESULTS Among guidelines with at least 1 revision or update by September 2008, the number of recommendations increased from 1330 to 1973 (+48%) from the first to the current version, with the largest increase observed in use of class II recommendations. Considering the 16 current guidelines reporting levels of evidence, only 314 recommendations of 2711 total are classified as level of evidence A (median, 11%), whereas 1246 (median, 48%) are level of evidence C. Level of evidence significantly varies across categories of guidelines (disease, intervention, or diagnostic) and across individual guidelines. Recommendations with level of evidence A are mostly concentrated in class I, but only 245 of 1305 class I recommendations have level of evidence A (median, 19%). CONCLUSIONS Recommendations issued in current ACC/AHA clinical practice guidelines are largely developed from lower levels of evidence or expert opinion. The proportion of recommendations for which there is no conclusive evidence is also growing. These findings highlight the need to improve the process of writing guidelines and to expand the evidence base from which clinical practice guidelines are derived.
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