Development of a state wide tobacco treatment specialist training and certification programme for Massachusetts

OBJECTIVE: To describe the research conducted to structure and develop a statewide tobacco training and certification programme for tobacco treatment specialists (TTSs) in Massachusetts. DESIGN: Qualitative research strategies were used to obtain information on certification development and opinions regarding TTS training and certification from key informants. A role definition and validation study was then conducted to determine the core competencies for TTSs. A comprehensive training programme was developed, piloted, and finalised, and a certification programme was initiated. PARTICIPANTS: Key informants included: individuals involved in the development of their professional certification programmes; tobacco treatment providers from across Massachusetts; and national tobacco treatment experts. MAIN OUTCOME MEASURES: Participants\u27 opinions about the need for and structure of a training and certification programme for individuals specialising in the provision of moderate to intensive tobacco treatment; delineation of core competencies for TTSs, using the Agency for Health Care Policy and Research (now the Agency for Healthcare Research and Quality) clinical practice guideline as a foundation for the development of evidence based standards of practice for the treatment of nicotine dependence. RESULTS: The data support a comprehensive training and certification programme for TTSs in Massachusetts. Main concerns include the cost of obtaining certification, the potential to exclude uncertified healthcare professionals from delivering basic tobacco treatment, and the role of the TTS in the healthcare delivery system and the community. The training programme developed for Massachusetts was piloted, and the structure of a statewide training and certification programme for TTSs was finalised. CONCLUSIONS: The research provides support for the need and acceptance of a training and certification programme for TTSs in Massachusetts, and presents the challenges to be addressed. We demonstrated the feasibility of developing and implementing an evidence based training programme, and of initiating a statewide certification programme in Massachusetts. This work will add to a national dialogue on the development of a training and certification programme for tobacco treatment providers and encourage further research into the potential impact of statewide and national certification

The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that usually affects elderly people. It has a poor prognosis and there are limited therapies. Since epigenetic alterations are associated with IPF, histone deacetylase (HDAC) inhibitors offer a novel therapeutic strategy to address the unmet medical need. This study investigated the potential of romidepsin, an FDA-approved HDAC inhibitor, as an anti-fibrotic treatment and evaluated biomarkers of target engagement that may have utility in future clinical trials. The anti-fibrotic effects of romidepsin were evaluated both in vitro and in vivo together with any harmful effect on alveolar type II cells (ATII). Bronchoalveolar lavage fluid (BALF) from IPF or control donors was analyzed for the presence of lysyl oxidase (LOX). In parallel with an increase in histone acetylation, romidepsin potently inhibited fibroblast proliferation, myofibroblast differentiation and LOX expression. ATII cell numbers and their lamellar bodies were unaffected. In vivo, romidepsin inhibited bleomycin-induced pulmonary fibrosis in association with suppression of LOX expression. LOX was significantly elevated in BALF of IPF patients compared to controls. These data show the anti-fibrotic effects of romidepsin, supporting its potential use as novel treatment for IPF with LOX as a companion biomarker for evaluation of early on-target effects

A Longitudinal Study of Medicaid Coverage for Tobacco Dependence Treatments in Massachusetts and Associated Decreases in Hospitalizations for Cardiovascular Disease

Thomas Land and colleagues show that among Massachusetts Medicaid subscribers, use of a comprehensive tobacco cessation pharmacotherapy benefit was followed by a substantial decrease in claims for hospitalizations for acute myocardial infarction and acute coronary heart disease

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure)

"The committee elected to focus this document on the prevention of HF and on the diagnosis and management of chronic HF in the adult patient with normal or low LVEF. It specifically did not consider acute HF, which might merit a separate set of guidelines and is addressed in part in the ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (8) and the ACC/AHA 2003 Update of the Guidelines for the Management of Unstable Angina and Non-ST Elevation Myocardial Infarction (9). We have also excluded HF in children, both because the underlying causes of HF in children differ from those in adults and because none of the controlled trials of treatments for HF have included children. We have not considered the management of HF due to primary valvular disease [see ACC/AHA Guidelines on the Management of Patients With Valvular Heart Disease (10)] or congenital malformations, and we have not included recommendations for the treatment of specific myocardial disorders (e.g., hemochromatosis, sarcoidosis, or amyloidosis). These practice guidelines are intended to assist healthcare providers in clinical decision making by describing a range of generally acceptable approaches for the prevention, diagnosis, and management of HF. The guidelines attempt to define practices that meet the needs of most patients under most circumstances. However, the ultimate judgment regarding the care of a particular patient must be made by the healthcare provider in light of all of the circumstances that are relevant to that patient. These guidelines do not address cost-effectiveness from a societal perspective. The guidelines are not meant to assist policy makers faced with the necessity to make decisions regarding the allocation of finite healthcare resources. In fact, these guidelines assume no resource limitation. They do not provide policy makers with sufficient information to be able to choose wisely between options for resource allocation. The various therapeutic strategies described in this document can be viewed as a checklist to be considered for each patient in an attempt to individualize treatment for an evolving disease process. Every patient is unique, not only in terms of his or her cause and course of HF, but also in terms of his or her personal and cultural approach to the disease. Guidelines can only provide an outline for evidence-based decisions or recommendations for individual care; these guidelines are meant to provide that outline.

ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure)

"The committee elected to focus this document on the prevention of HF and on the diagnosis and management of chronic HF in the adult patient with normal or low LVEF. It specifically did not consider acute HF, which might merit a separate set of guidelines and is addressed in part in the ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (8) and the ACC/AHA 2003 Update of the Guidelines for the Management of Unstable Angina and Non-ST Elevation Myocardial Infarction (9). We have also excluded HF in children, both because the underlying causes of HF in children differ from those in adults and because none of the controlled trials of treatments for HF have included children. We have not considered the management of HF due to primary valvular disease [see ACC/AHA Guidelines on the Management of Patients With Valvular Heart Disease (10)] or congenital malformations, and we have not included recommendations for the treatment of specific myocardial disorders (e.g., hemochromatosis, sarcoidosis, or amyloidosis). These practice guidelines are intended to assist healthcare providers in clinical decision making by describing a range of generally acceptable approaches for the prevention, diagnosis, and management of HF. The guidelines attempt to define practices that meet the needs of most patients under most circumstances. However, the ultimate judgment regarding the care of a particular patient must be made by the healthcare provider in light of all of the circumstances that are relevant to that patient. These guidelines do not address cost-effectiveness from a societal perspective. The guidelines are not meant to assist policy makers faced with the necessity to make decisions regarding the allocation of finite healthcare resources. In fact, these guidelines assume no resource limitation. They do not provide policy makers with sufficient information to be able to choose wisely between options for resource allocation. The various therapeutic strategies described in this document can be viewed as a checklist to be considered for each patient in an attempt to individualize treatment for an evolving disease process. Every patient is unique, not only in terms of his or her cause and course of HF, but also in terms of his or her personal and cultural approach to the disease. Guidelines can only provide an outline for evidence-based decisions or recommendations for individual care; these guidelines are meant to provide that outline.

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe