Showing papers by "University of Louisville published in 2017"
Theo Vos1, Amanuel Alemu Abajobir, Kalkidan Hassen Abate2, Cristiana Abbafati3 +775 more•Institutions (305)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.
10,401 citations
Gregory A. Roth1, Catherine O. Johnson1, Amanuel Alemu Abajobir2, Foad Abd-Allah3 +170 more•Institutions (99)
TL;DR: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden, finding that CVDs remain a major cause of health loss for all regions of the world.
2,525 citations
University of California, Los Angeles1, University of Utah2, University of South Florida3, University of Helsinki4, Primary Children's Hospital5, University of Groningen6, Norfolk and Norwich University Hospital7, Lund University8, Netherlands Cancer Institute9, University of Michigan10, Wake Forest University11, Ohio State University12, Peter MacCallum Cancer Centre13, University of Zurich14, University of Padua15, Pennsylvania State University16, Saint Louis University17, Tom Baker Cancer Centre18, University of Washington19, University of Lausanne20, Guy's and St Thomas' NHS Foundation Trust21, University of Kiel22, Thomas Jefferson University23, Sunnybrook Research Institute24, Vanderbilt University25, University of Queensland26, Fox Chase Cancer Center27, Greenville Health System28, Stony Brook University29, University Health Network30, Memorial Sloan Kettering Cancer Center31, Roswell Park Cancer Institute32, Northwestern University33, University of Wisconsin-Madison34, Rush University Medical Center35, Tel Aviv Sourasky Medical Center36, Dartmouth College37, Johns Hopkins University38, University of Louisville39, University of Barcelona40, University of Sydney41
TL;DR: Immediate completion lymph‐node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma‐specific survival among patients with melanoma and sentinel‐node metastases.
Abstract: BackgroundSentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. MethodsIn an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. ResultsImmediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in t...
946 citations
National Institutes of Health1, University of California, Irvine2, University of Louisville3, Sheba Medical Center4, Istituto Superiore di Sanità5, University of North Carolina at Chapel Hill6, Universidad Miguel Hernández de Elche7, University of Parma8, University of Turin9, University of Chicago10, University of Massachusetts Amherst11, University of Missouri12
TL;DR: This review will examine changes to the incidence of obesity, T2D and non-alcoholic fatty liver disease (NAFLD), the contribution of genetics to these disorders and describe the role of the endocrine system in these metabolic disorders.
599 citations
TL;DR: This data indicates that pre-emptive surgery is a viable option for the treatment of deep vein thrombosis in women with pre-operative indications and this work’s results support this view.
Abstract: Disclosures outside the scope of this work: Dr. Minei receiv grant support from Irrespet Corp. AtoxBio. Dr. Laronga rec sation for lectures from Genomic Health Inc. and royalties Date. Dr. Jensen is a consultant and paid speaker for Ethico ceives honoraria from CareFusion for their Speaker’s Progr from Irrimax Corp. for consulting and Research Funding honoraria from Surgical Inc. for consultation. Dr. Itani for a multi-institutional study for Sanofi-Pastuer and the Committee Chair. Dr. Dellinger is on the Advisory B Melinta, and Therevance and a grant recipient from Moti trial of iclaprim vs. vancomycin for treatment of skin and so tions. The remaining authors declare no conflicts. Presented at the Surgical Infection Society, Palm Beach, FL
594 citations
TL;DR: In this trial involving patients with advanced heart failure who were ineligible for heart transplantation, a small, intrapericardial, centrifugal‐flow LVAD was found to be noninferior to an axial‐ flow LVAD with respect to survival free from disabling stroke or device removal for malfunction or failure.
Abstract: BackgroundMechanical circulatory support with a left ventricular assist device (LVAD) is an established treatment for patients with advanced heart failure. We compared a newer LVAD design (a small intrapericardial centrifugal-flow device) against existing technology (a commercially available axial-flow device) in patients with advanced heart failure who were ineligible for heart transplantation. MethodsWe conducted a multicenter randomized trial involving 446 patients who were assigned, in a 2:1 ratio, to the study (centrifugal-flow) device or the control (axial-flow) device. Adults who met contemporary criteria for LVAD implantation for permanent use were eligible to participate in the trial. The primary end point was survival at 2 years free from disabling stroke or device removal for malfunction or failure. The trial was powered to show noninferiority with a margin of 15 percentage points. ResultsThe intention-to treat-population included 297 participants assigned to the study device and 148 participan...
592 citations
University of Paris-Sud1, University of Louisville2, Pierre-and-Marie-Curie University3, University of Bonn4, University of Zurich5, University of Manchester6, University of Warwick7, Aix-Marseille University8, Karlsruhe Institute of Technology9, Wayne State University10, Niigata University11, Nara Women's University12, University of Cambridge13, Ludwig Maximilian University of Munich14, Chinese Academy of Sciences15, University of Bristol16, Jožef Stefan Institute17, Spanish National Research Council18, Imperial College London19, University of Milano-Bicocca20, CERN21, University of Victoria22, École Polytechnique Fédérale de Lausanne23, University of Cincinnati24, Budker Institute of Nuclear Physics25, Novosibirsk State University26, Fermilab27, KEK28, Graduate University for Advanced Studies29, University of Melbourne30, Indiana University31, University of Florida32, University of Ljubljana33
TL;DR: In this article, the authors report world averages of measurements of b-hadron, c-, c-, and tau-lepton properties obtained by the Heavy Flavor Averaging Group (HFAG) using results available through the end of 2011.
Abstract: This article reports world averages of measurements of b-hadron, c-hadron, and tau-lepton properties obtained by the Heavy Flavor Averaging Group (HFAG) using results available through the end of 2011. In some cases results available in the early part of 2012 are included. For the averaging, common input parameters used in the various analyses are adjusted (rescaled) to common values, and known correlations are taken into account. The averages include branching fractions, lifetimes, neutral meson mixing parameters, CP violation parameters, parameters of semileptonic decays and CKM matrix elements.
554 citations
University of Louisville1, Roswell Park Cancer Institute2, University of North Carolina at Chapel Hill3, Mayo Clinic4, University of Iowa5, University of California, Los Angeles6, University of Texas MD Anderson Cancer Center7, Icahn School of Medicine at Mount Sinai8, University of Tübingen9, Indiana University10, University of Kiel11, University of Paris12, Amgen13, University of Utah14, Rutgers University15
TL;DR: The study met its primary end point; the objective response rate was significantly higher with talimogene laherparepvec plus ipilimumab versus ipilitationab alone, indicating that the combination has greater antitumor activity without additional safety concerns versus ipILimumab.
Abstract: Purpose We evaluated the combination of talimogene laherparepvec plus ipilimumab versus ipilimumab alone in patients with advanced melanoma in a phase II study. To our knowledge, this was the first randomized trial to evaluate addition of an oncolytic virus to a checkpoint inhibitor. Methods Patients with unresectable stages IIIB to IV melanoma, with no more than one prior therapy if BRAF wild-type, no more than two prior therapies if BRAF mutant, measurable/injectable disease, and without symptomatic autoimmunity or clinically significant immunosuppression were randomly assigned 1:1 to receive talimogene laherparepvec plus ipilimumab or ipilimumab alone. Talimogene laherparepvec treatment began in week 1 (first dose, ≤ 4 mL × 106 plaque-forming units/mL; after 3 weeks, ≤ 4 mL × 108 plaque-forming units/mL every 2 weeks). Ipilimumab (3 mg/kg every 3 weeks; up to four doses) began week 1 in the ipilimumab alone arm and week 6 in the combination arm. The primary end point was objective response rate evaluated by investigators per immune-related response criteria. Results One hundred ninety-eight patients were randomly assigned to talimogene laherparepvec plus ipilimumab (n = 98), or ipilimumab alone (n = 100). Thirty-eight patients (39%) in the combination arm and 18 patients (18%) in the ipilimumab arm had an objective response (odds ratio, 2.9; 95% CI, 1.5 to 5.5; P = .002). Responses were not limited to injected lesions; visceral lesion decreases were observed in 52% of patients in the combination arm and 23% of patients in the ipilimumab arm. Frequently occurring adverse events (AEs) included fatigue (combination, 59%; ipilimumab alone, 42%), chills (combination, 53%; ipilimumab alone, 3%), and diarrhea (combination, 42%; ipilimumab alone, 35%). Incidence of grade ≥ 3 AEs was 45% and 35%, respectively. Three patients in the combination arm had fatal AEs; none were treatment related. Conclusion The study met its primary end point; the objective response rate was significantly higher with talimogene laherparepvec plus ipilimumab versus ipilimumab alone. These data indicate that the combination has greater antitumor activity without additional safety concerns versus ipilimumab.
445 citations
TL;DR: In this paper, the authors use the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to improve and expand the quantification of personal health-care access and quality for 195 countries and territories from 1990 to 2015.
427 citations
University of Louisville1, Max Planck Society2, University of Giessen3, Indiana University4, University of Bonn5, Karolinska Institutet6, International Centre for Genetic Engineering and Biotechnology7, University of Miami8, Johns Hopkins University School of Medicine9, Temple University10, Harvard University11, Cedars-Sinai Medical Center12, The Texas Heart Institute13, Cincinnati Children's Hospital Medical Center14
TL;DR: The intent here is to define areas of agreement and areas requiring further elucidation related to the regenerative potential of the myocardium itself and to formulate a consensus for many of the pertinent questions.
Abstract: Cell therapy is an exciting option for repairing the injured heart, one that has attracted considerable interest over the past 15 years. Consensus exists that the injection/infusion or tissue-based implantation of various cell types may exert therapeutic effects,1–3 and there is general agreement that additional molecular, translational, and clinical studies are required to define the optimal cell source, method of delivery, and underlying mechanism(s) of action.
One of the remaining questions in this field pertains to cardiomyocyte turnover under normal and diseased conditions and its contribution to the beneficial effects of cell therapy. Although results published in the literature have not been consistent, we believe that the time is ripe to formulate a consensus for many of the pertinent questions.
It is important to emphasize that the focus of this consensus statement is on cardiomyocyte renewal; it is not on cell therapy in general. Although we touch on some aspects of therapeutic strategies based on delivery of exogenous cells, our intent here is to define areas of agreement and areas requiring further elucidation related to the regenerative potential of the myocardium itself.
We have included references to the scientific literature throughout the document. Although it is impossible for us to include all publications in this expansive field, representative studies that corroborate statements herein have been cited.
1. Definition of cardiomyocyte renewal.
In this consensus statement, the term cardiomyocyte renewal is defined as the ability to replace lost cardiomyocytes by new ones. It is distinct from the turnover of cardiac proteins or the generation of polyploid cardiomyocytes (ie, those harboring >2 sets of chromosomes), either by nuclear division giving rise to multinucleation or by duplication of DNA without nuclear division resulting in polyploid nuclei.
2. Naturally occurring cardiomyocyte renewal and proliferation.
1. During normal mammalian development
1. Growth of the heart during …
372 citations
Dartmouth College1, Duke University2, University of Texas Southwestern Medical Center3, National Institutes of Health4, University of Michigan5, University of Illinois at Chicago6, Columbia University7, Columbia University Medical Center8, University of Minnesota9, Anschutz Medical Campus10, Virginia Commonwealth University11, University of British Columbia12, University of Louisville13, Stanford University14, University of Massachusetts Medical School15, Albany Medical College16, University of California, Los Angeles17, Hofstra University18, New York University19, University of Dundee20, St. Jude Medical21, Emory University22, Centre for Addiction and Mental Health23, Toronto Western Hospital24
TL;DR: This study confirmed the safety and feasibility of subcallosal cingulate DBS as a treatment for treatment-resistant depression but did not show statistically significant antidepressant efficacy in a 6-month double-blind, sham-controlled trial.
TL;DR: It is shown that an electrochemically reduced SnO2 porous nanowire catalyst (Sn-pNWs) with a high density of grain boundaries (GBs) exhibits an energy conversion efficiency of CO2 -into-HCOOH higher than analogous catalysts.
Abstract: Electrochemical conversion of CO2 into energy-dense liquids, such as formic acid, is desirable as a hydrogen carrier and a chemical feedstock. SnOx is one of the few catalysts that reduce CO2 into formic acid with high selectivity but at high overpotential and low current density. We show that an electrochemically reduced SnO2 porous nanowire catalyst (Sn-pNWs) with a high density of grain boundaries (GBs) exhibits an energy conversion efficiency of CO2-into-HCOOH higher than analogous catalysts. HCOOH formation begins at lower overpotential (350 mV) and reaches a steady Faradaic efficiency of ca. 80 % at only −0.8 V vs. RHE. A comparison with commercial SnO2 nanoparticles confirms that the improved CO2 reduction performance of Sn-pNWs is due to the density of GBs within the porous structure, which introduce new catalytically active sites. Produced with a scalable plasma synthesis technology, the catalysts have potential for application in the CO2 conversion industry.
TL;DR: Limits on the coupling strength of A^{'} to e^{+}e^{-} in the mass range m_{A^{'}}≤8 GeV are set, which exclude the values of the A^' coupling suggested by thedark-photon interpretation of the muon (g-2)_{μ} anomaly, as well as a broad range of parameters for the dark-sector models.
Abstract: We search for single-photon events in 53 fb^{-1} of e^{+}e^{-} collision data collected with the BABAR detector at the PEP-II B-Factory. We look for events with a single high-energy photon and a large missing momentum and energy, consistent with production of a spin-1 particle A^{'} through the process e^{+}e^{-}→γA^{'}; A^{'}→invisible. Such particles, referred to as "dark photons," are motivated by theories applying a U(1) gauge symmetry to dark matter. We find no evidence for such processes and set 90% confidence level upper limits on the coupling strength of A^{'} to e^{+}e^{-} in the mass range m_{A^{'}}≤8 GeV. In particular, our limits exclude the values of the A^{'} coupling suggested by the dark-photon interpretation of the muon (g-2)_{μ} anomaly, as well as a broad range of parameters for the dark-sector models.
TL;DR: It is demonstrated that MVP-mediated selective sorting of tumour suppressor miRNA into exosomes promotes tumour progression and causes cell cycle G1 arrest and cell proliferation repression through targeting of Caprin1.
Abstract: Exosomes are emerging mediators of intercellular communication; whether the release of exosomes has an effect on the exosome donor cells in addition to the recipient cells has not been investigated to any extent. Here, we examine different exosomal miRNA expression profiles in primary mouse colon tumour, liver metastasis of colon cancer and naive colon tissues. In more advanced disease, higher levels of tumour suppressor miRNAs are encapsulated in the exosomes. miR-193a interacts with major vault protein (MVP). Knockout of MVP leads to miR-193a accumulation in the exosomal donor cells instead of exosomes, inhibiting tumour progression. Furthermore, miR-193a causes cell cycle G1 arrest and cell proliferation repression through targeting of Caprin1, which upregulates Ccnd2 and c-Myc. Human colon cancer patients with more advanced disease show higher levels of circulating exosomal miR-193a. In summary, our data demonstrate that MVP-mediated selective sorting of tumour suppressor miRNA into exosomes promotes tumour progression. Exosomes are involved in the development of metastasis but how their composition is regulated is not well known. Here the authors propose that major vault protein-dependent loading of miR-193a into exosomes could be a general mechanism by which cancer cells get rid of oncosuppressor miRNAs.
TL;DR: In this article, a search for new resonant and non-resonant high-mass phenomena in dielectron and dimuon fi nal states was conducted using 36 : 1 fb(-1) of proton-proton collision data.
Abstract: A search is conducted for new resonant and non-resonant high-mass phenomena in dielectron and dimuon fi nal states. The search uses 36 : 1 fb(-1) of proton-proton collision data, collected at root ...
TL;DR: In this article, milk-derived exosomes have been investigated for oral delivery of the chemotherapeutic drug paclitaxel (PAC) as an alternative to conventional i.p. therapy for improved efficacy and reduced toxicity.
University of Duisburg-Essen1, Memorial Sloan Kettering Cancer Center2, Harvard University3, University of Colorado Denver4, Aix-Marseille University5, Texas Oncology6, University of Michigan7, University of Louisville8, University of Paris-Sud9, University of Utah10, Bristol-Myers Squibb11, The Royal Marsden NHS Foundation Trust12, Cornell University13
TL;DR: Efficacy outcomes seemed similar between patients who discontinued nivolumab plus ipilimumab treatment because of AEs during the induction phase and those who did not discontinue because of aEs, suggesting that many patients may continue to derive benefit from combination therapy even after discontinuation.
Abstract: Purpose Approximately 40% of patients with advanced melanoma who received nivolumab combined with ipilimumab in clinical trials discontinued treatment because of adverse events (AEs). We conducted a retrospective analysis to assess the efficacy and safety of nivolumab plus ipilimumab in patients who discontinued treatment because of AEs. Methods Data were pooled from phase II and III trials of patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, every 3 weeks for four doses, followed by nivolumab monotherapy 3 mg/kg every 2 weeks (N = 409). Efficacy was assessed in all randomly assigned patients who discontinued because of AEs during the induction phase (n = 96) and in those who did not discontinue because of AEs (n = 233). Safety was assessed in treated patients who discontinued because of AEs (n = 176) at any time and in those who did not discontinue because of AEs (n = 231). Results At a minimum follow-up of 18 months, median progression-free survival was 8.4 months for patients who discontinued treatment because of AEs during the induction phase and 10.8 months for patients who did not discontinue because of AEs ( P = .97). Median overall survival had not been reached in either group ( P = .23). The objective response rate was 58.3% for patients who discontinued because of AEs during the induction phase and 50.2% for patients who did not discontinue. The vast majority of grade 3 or 4 AEs occurred during the induction phase, with most resolving after appropriate management. Conclusion Efficacy outcomes seemed similar between patients who discontinued nivolumab plus ipilimumab treatment because of AEs during the induction phase and those who did not discontinue because of AEs. Therefore, even after discontinuation, many patients may continue to derive benefit from combination therapy.
TL;DR: The estimated US burden of CAP is substantial, with >1.5 million unique adults being hospitalized annually, 100000 deaths occurring during hospitalization, and approximately 1 of 3 patients hospitalized with CAP dying within 1 year.
Abstract: Background Understanding the burden of community-acquired pneumonia (CAP) is critical to allocate resources for prevention, management, and research. The objectives of this study were to define incidence, epidemiology, and mortality of adult patients hospitalized with CAP in the city of Louisville, and to estimate burden of CAP in the US adult population. Methods This was a prospective population-based cohort study of adult residents in Louisville, Kentucky, from 1 June 2014 to 31 May 2016. Consecutive hospitalized patients with CAP were enrolled at all adult hospitals in Louisville. The annual population-based CAP incidence was calculated. Geospatial epidemiology was used to define ecological associations among CAP and income level, race, and age. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization. Results During the 2-year study, from a Louisville population of 587499 adults, 186384 hospitalizations occurred. A total of 7449 unique patients hospitalized with CAP were documented. The annual age-adjusted incidence was 649 patients hospitalized with CAP per 100000 adults (95% confidence interval, 628.2-669.8), corresponding to 1591825 annual adult CAP hospitalizations in the United States. Clusters of CAP cases were found in areas with low-income and black/African American populations. Mortality during hospitalization was 6.5%, corresponding to 102821 annual deaths in the United States. Mortality at 30 days, 6 months, and 1 year was 13.0%, 23.4%, and 30.6%, respectively. Conclusions The estimated US burden of CAP is substantial, with >1.5 million unique adults being hospitalized annually, 100000 deaths occurring during hospitalization, and approximately 1 of 3 patients hospitalized with CAP dying within 1 year.
Journal Article•
University of Louisville1, University of the Pacific (United States)2, University of Illinois at Chicago3, University of Texas Health Science Center at Houston4, University of Kentucky5, LSU Health Sciences Center New Orleans6, Florida State University7, New York University8, Hofstra University9, Lenox Hill Hospital10, NorthShore University HealthSystem11, University of Illinois at Urbana–Champaign12, Wright State University13, Illinois State University14, Icahn School of Medicine at Mount Sinai15, West Virginia University16, Geisinger Medical Center17, University of Oklahoma18, Stanford University19, University of Texas MD Anderson Cancer Center20, University of Wisconsin-Madison21, Harvard University22, University of Texas Medical Branch23, Johns Hopkins University24, Illinois Wesleyan University25, Mary Greeley Medical Center26
TL;DR: These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique.
Abstract: Background Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use. Objectives To provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique. Methods The methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ).Summary of Recommendations:i. Initial Steps of Opioid Therapy 1. Comprehensive assessment and documentation. (Evidence: Level I; Strength of Recommendation: Strong) 2. Screening for opioid abuse to identify opioid abusers. (Evidence: Level II-III; Strength of Recommendation: Moderate) 3. Utilization of prescription drug monitoring programs (PDMPs). (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 4. Utilization of urine drug testing (UDT). (Evidence: Level II; Strength of Recommendation: Moderate) 5. Establish appropriate physical diagnosis and psychological diagnosis if available. (Evidence: Level I; Strength of Recommendation: Strong) 6. Consider appropriate imaging, physical diagnosis, and psychological status to collaborate with subjective complaints. (Evidence: Level III; Strength of Recommendation: Moderate) 7. Establish medical necessity based on average moderate to severe (≥ 4 on a scale of 0 - 10) pain and/or disability. (Evidence: Level II; Strength of Recommendation: Moderate) 8. Stratify patients based on risk. (Evidence: Level I-II; Strength of Recommendation: Moderate) 9. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: Level I-II; Strength of Recommendation: Moderate) 10. Obtain a robust opioid agreement, which is followed by all parties. (Evidence: Level III; Strength of Recommendation: Moderate)ii. Assessment of Effectiveness of Long-Term Opioid Therapy 11. Initiate opioid therapy with low dose, short-acting drugs, with appropriate monitoring. (Evidence: Level II; Strength of Recommendation: Moderate) 12. Consider up to 40 morphine milligram equivalent (MME) as low dose, 41 to 90 MME as a moderate dose, and greater than 91 MME as high dose. (Evidence: Level II; Strength of Recommendation: Moderate) 13. Avoid long-acting opioids for the initiation of opioid therapy. (Evidence: Level I; Strength of Recommendation: Strong) 14. Recommend methadone only for use after failure of other opioid therapy and only by clinicians with specific training in its risks and uses, within FDA recommended doses. (Evidence: Level I; Strength of Recommendation: Strong) 15. Understand and educate the patients of the effectiveness and adverse consequences. (Evidence: Level I; Strength of Recommendation: Strong) 16. Similar effectiveness for long-acting and short-acting opioids with increased adverse consequences of long-acting opioids. (Evidence: Level I-II; Strength of recommendation: Moderate to strong) 17. Periodically assess pain relief and/or functional status improvement of ≥ 30% without adverse consequences. (Evidence: Level II; Strength of recommendation: Moderate) 18. Recommend long-acting or high dose opioids only in specific circumstances with severe intractable pain. (Evidence: Level I; Strength of Recommendation: Strong)iii. Monitoring for Adherence and Side Effects 19. Monitor for adherence, abuse, and noncompliance by UDT and PDMPs. (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 20. Monitor patients on methadone with an electrocardiogram periodically. (Evidence: Level I; Strength of Recommendation: Strong). 21. Monitor for side effects including constipation and manage them appropriately, including discontinuation of opioids when indicated. (Evidence: Level I; Strength of Recommendation: Strong)iv. Final Phase 22. May continue with monitoring with continued medical necessity, with appropriate outcomes. (Evidence: Level I-II; Strength of Recommendation: Moderate) 23. Discontinue opioid therapy for lack of response, adverse consequences, and abuse with rehabilitation. (Evidence: Level III; Strength of Recommendation: Moderate) CONCLUSIONS: These guidelines were developed based on comprehensive review of the literature, consensus among the panelists, in consonance with patient preferences, shared decision-making, and practice patterns with limited evidence, based on randomized controlled trials (RCTs) to improve pain and function in chronic non-cancer pain on a long-term basis. Consequently, chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function, independently or in conjunction with other modalities of treatments in low doses with appropriate adherence monitoring and understanding of adverse events.Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversionDisclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."
TL;DR: The most common approaches used for tuning mechanical properties of hydrogels including but are not limited to, interpenetrating polymer networks, nanocomposites, self-assembly techniques, and co-polymerization are discussed.
TL;DR: An understanding of how different domains of the environment, individually and collectively, affect CVD risk could lead to a better appraisal of CVD and aid in the development of new preventive and therapeutic strategies to limit the increasingly high global burden of heart disease and stroke.
Abstract: Many features of the environment have been found to exert an important influence on cardiovascular disease (CVD) risk, progression, and severity. Changes in the environment because of migration to different geographic locations, modifications in lifestyle choices, and shifts in social policies and cultural practices alter CVD risk, even in the absence of genetic changes. Nevertheless, the cumulative impact of the environment on CVD risk has been difficult to assess and the mechanisms by which some environment factors influence CVD remain obscure. Human environments are complex, and their natural, social, and personal domains are highly variable because of diversity in human ecosystems, evolutionary histories, social structures, and individual choices. Accumulating evidence supports the notion that ecological features such as the diurnal cycles of light and day, sunlight exposure, seasons, and geographic characteristics of the natural environment such as altitude, latitude, and greenspaces are important determinants of cardiovascular health and CVD risk. In highly developed societies, the influence of the natural environment is moderated by the physical characteristics of the social environments such as the built environment and pollution, as well as by socioeconomic status and social networks. These attributes of the social environment shape lifestyle choices that significantly modify CVD risk. An understanding of how different domains of the environment, individually and collectively, affect CVD risk could lead to a better appraisal of CVD and aid in the development of new preventive and therapeutic strategies to limit the increasingly high global burden of heart disease and stroke.
TL;DR: The results of these studies are building the case that urinary extracellular vesicles act as mediators of renal pathophysiology, and this Review focuses on primary data obtained from studies of human urine rather than on data from Studies of laboratory animals or cultured immortalized cells.
Abstract: Urine is a valuable diagnostic medium and, with the discovery of urinary extracellular vesicles, is viewed as a dynamic bioactive fluid. Extracellular vesicles are lipid-enclosed structures that can be classified into three categories: exosomes, microvesicles (or ectosomes) and apoptotic bodies. This classification is based on the mechanisms by which membrane vesicles are formed: fusion of multivesicular bodies with the plasma membranes (exosomes), budding of vesicles directly from the plasma membrane (microvesicles) or those shed from dying cells (apoptotic bodies). During their formation, urinary extracellular vesicles incorporate various cell-specific components (proteins, lipids and nucleic acids) that can be transferred to target cells. The rigour needed for comparative studies has fueled the search for optimal approaches for their isolation, purification, and characterization. RNA, the newest extracellular vesicle component to be discovered, has received substantial attention as an extracellular vesicle therapeutic, and compelling evidence suggests that ex vivo manipulation of microRNA composition may have uses in the treatment of kidney disorders. The results of these studies are building the case that urinary extracellular vesicles act as mediators of renal pathophysiology. As the field of extracellular vesicle studies is burgeoning, this Review focuses on primary data obtained from studies of human urine rather than on data from studies of laboratory animals or cultured immortalized cells.
TL;DR: This paper defines the Association of Standardized Patient Educators (ASPE) Standards of Best Practice (SOBP) for those working with human role players who interact with learners in a wide range of experiential learning and assessment contexts and describes five domains of best practice.
Abstract: In this paper, we define the Association of Standardized Patient Educators (ASPE) Standards of Best Practice (SOBP) for those working with human role players who interact with learners in a wide range of experiential learning and assessment contexts. These human role players are variously described by such terms as standardized/simulated patients or simulated participants (SP or SPs). ASPE is a global organization whose mission is to share advances in SP-based pedagogy, assessment, research, and scholarship as well as support the professional development of its members. The SOBP are intended to be used in conjunction with the International Nursing Association for Clinical Simulation and Learning (INACSL) Standards of Best Practice: SimulationSM, which address broader simulation practices. We begin by providing a rationale for the creation of the ASPE SOBP, noting that with the increasing use of simulation in healthcare training, it is incumbent on ASPE to establish SOBP that ensure the growth, integrity, and safe application of SP-based educational endeavors. We then describe the three and a half year process through which these standards were developed by a consensus of international experts in the field. Key terms used throughout the document are defined. Five underlying values inform the SOBP: safety, quality, professionalism, accountability, and collaboration. Finally, we describe five domains of best practice: safe work environment; case development; SP training for role portrayal, feedback, and completion of assessment instruments; program management; and professional development. Each domain is divided into principles with accompanying key practices that provide clear and practical guidelines for achieving desired outcomes and creating simulations that are safe for all stakeholders. Failure to follow the ASPE SOBP could compromise the safety of participants and the effectiveness of a simulation session. Care has been taken to make these guidelines precise yet flexible enough to address the diversity of varying contexts of SP practice. As a living document, these SOBP will be reviewed and modified periodically under the direction of the ASPE Standards of Practice Committee as SP methodology grows and adapts to evolving simulation practices.
TL;DR: AstroImageJ (AIJ) as discussed by the authors is a GUI-driven, public domain, Java-based, software package for general image processing traditionally used mainly in life sciences fields.
Abstract: ImageJ is a graphical user interface (GUI) driven, public domain, Java-based, software package for general image processing traditionally used mainly in life sciences fields. The image processing capabilities of ImageJ are useful and extendable to other scientific fields. Here we present AstroImageJ (AIJ), which provides an astronomy specific image display environment and tools for astronomy specific image calibration and data reduction. Although AIJ maintains the general purpose image processing capabilities of ImageJ, AIJ is streamlined for time-series differential photometry, light curve detrending and fitting, and light curve plotting, especially for applications requiring ultra-precise light curves (e.g., exoplanet transits). AIJ reads and writes standard Flexible Image Transport System (FITS) files, as well as other common image formats, provides FITS header viewing and editing, and is World Coordinate System aware, including an automated interface to the astrometry.net web portal for plate solving images. AIJ provides research grade image calibration and analysis tools with a GUI driven approach, and easily installed cross-platform compatibility. It enables new users, even at the level of undergraduate student, high school student, or amateur astronomer, to quickly start processing, modeling, and plotting astronomical image data with one tightly integrated software package.
TL;DR: Future studies of prophylactic HPV vaccines must demonstrate protection against six month type specific persistent infections, not actual cervical cancer precursor disease endpoints, such as cervical intraepithelial neoplasia grade 3 (CIN 3) or adenocarcinoma in situ (AIS).
TL;DR: The clinical and experimental evidence supporting the new paradigm of citrullinated epitopes recognized by anti-citrullination protein antibodies is discussed and the potential mechanisms involved in linking periodontitis to RA are presented.
Abstract: Rheumatoid arthritis (RA), an autoimmune disease that affects ∼1% of the human population, is driven by autoantibodies that target modified self-epitopes, whereas ∼11% of the global adult population are affected by severe chronic periodontitis, a disease in which the commensal microflora on the tooth surface is replaced by a dysbiotic consortium of bacteria that promote the chronic inflammatory destruction of periodontal tissue. Despite differences in aetiology, RA and periodontitis are similar in terms of pathogenesis; both diseases involve chronic inflammation fuelled by pro-inflammatory cytokines, connective tissue breakdown and bone erosion. The two diseases also share risk factors such as smoking and ageing, and have strong epidemiological, serological and clinical associations. In light of the ground-breaking discovery that Porphyromonas gingivalis, a pivotal periodontal pathogen, is the only human pathogen known to express peptidylarginine deiminase, an enzyme that generates citrullinated epitopes that are recognized by anti-citrullinated protein antibodies, a new paradigm is emerging. In this Review, the clinical and experimental evidence supporting this paradigm is discussed and the potential mechanisms involved in linking periodontitis to RA are presented.
South London and Maudsley NHS Foundation Trust1, World Psychiatric Association2, University of Louisville3, Centre for Mental Health4, Queen Mary University of London5, Beth Israel Deaconess Medical Center6, Columbia University Medical Center7, University of Oxford8, Mayo Clinic9, Cayetano Heredia University10, The Chinese University of Hong Kong11, Wright State University12, Cardiff University13, Prince of Songkla University14, Pan American Health Organization15, Kowloon Hospital16, University of Antwerp17, University of Toronto18, Wellesley Institute19, University of Nottingham20, University of Western Australia21, University of New South Wales22, University of Western Sydney23, Beijing Forestry University24, Harvard University25, Ain Shams University26, Mental Health Services27, Monash University28, Royal College of Psychiatrists29, University of Pittsburgh30, University of Foggia31
TL;DR: The therapeutic relationship remains paramount, and psychiatrists will need to acquire the necessary communication skills and cultural awareness to work optimally as patient demographics change, and psychiatry faces major challenges.
TL;DR: In this article, the authors analyzed 990 police fatal shootings using data compiled by The Washington Post in 2015 and examined the data for evidence of implicit bias by using multivariate regression models that predict two indicators of threat perception failure: (1) whether the civilian was not attacking the officer(s) or other civilians just before being fatally shot and (2) whether a civilian was unarmed when fatally shot.
Abstract: Research Summary
We analyzed 990 police fatal shootings using data compiled by The Washington Post in 2015. After first providing a basic descriptive analysis of these shootings, we then examined the data for evidence of implicit bias by using multivariate regression models that predict two indicators of threat perception failure: (1) whether the civilian was not attacking the officer(s) or other civilians just before being fatally shot and (2) whether the civilian was unarmed when fatally shot. The results indicated civilians from “other” minority groups were significantly more likely than Whites to have not been attacking the officer(s) or other civilians and that Black civilians were more than twice as likely as White civilians to have been unarmed.
Policy Implications
We implore the U.S. government to move forward with its publication of a national police use-of-force database, including as much information about the officers involved as possible. We further suggest police departments use training programs and community activities to minimize implicit bias among their officers.
National University of Ireland, Galway1, Harvard University2, Wyss Institute for Biologically Inspired Engineering3, Technische Universität München4, Boston Children's Hospital5, University of Central Florida6, Royal College of Surgeons in Ireland7, University of California, Los Angeles8, University of Louisville9
TL;DR: A soft robotic sleeve that is implanted around the heart and actively compresses and twists to act as a cardiac ventricular assist device, which does not contact blood, obviating the need for anticoagulation therapy or blood thinners, and reduces complications with current Ventricular assist devices, such as clotting and infection.
Abstract: There is much interest in form-fitting, low-modulus, implantable devices or soft robots that can mimic or assist in complex biological functions such as the contraction of heart muscle. We present a soft robotic sleeve that is implanted around the heart and actively compresses and twists to act as a cardiac ventricular assist device. The sleeve does not contact blood, obviating the need for anticoagulation therapy or blood thinners, and reduces complications with current ventricular assist devices, such as clotting and infection. Our approach used a biologically inspired design to orient individual contracting elements or actuators in a layered helical and circumferential fashion, mimicking the orientation of the outer two muscle layers of the mammalian heart. The resulting implantable soft robot mimicked the form and function of the native heart, with a stiffness value of the same order of magnitude as that of the heart tissue. We demonstrated feasibility of this soft sleeve device for supporting heart function in a porcine model of acute heart failure. The soft robotic sleeve can be customized to patient-specific needs and may have the potential to act as a bridge to transplant for patients with heart failure.
11 Apr 2017
TL;DR: A review of the most significant recent studies in the field of phosphorene research and technology can be found in this article, where the authors focus on the synthesis and layer number determination, anisotropic properties, tuning of the band gap and related properties, strain engineering, and applications in electronics, thermoelectrics, and energy storage.
Abstract: Since its first fabrication by exfoliation in 2014, phosphorene has been the focus of rapidly expanding research activities. The number of phosphorene publications has been increasing at a rate exceeding that of other two-dimensional materials. This tremendous level of excitement arises from the unique properties of phosphorene, including its puckered layer structure. With its widely tunable band gap, strong in-plane anisotropy, and high carrier mobility, phosphorene is at the center of numerous fundamental studies and applications spanning from electronic, optoelectronic, and spintronic devices to sensors, actuators, and thermoelectrics to energy conversion, and storage devices. Here, we review the most significant recent studies in the field of phosphorene research and technology. Our focus is on the synthesis and layer number determination, anisotropic properties, tuning of the band gap and related properties, strain engineering, and applications in electronics, thermoelectrics, and energy storage. The current needs and likely future research directions for phosphorene are also discussed.