Showing papers by "University of Colorado Denver published in 2010"
Harvard University1, Vanderbilt University2, Netherlands Cancer Institute3, University of Colorado Denver4, Institut Gustave Roussy5, University of Duisburg-Essen6, University of Mannheim7, University of Utah8, VU University Amsterdam9, Mount Sinai Hospital10, Washington University in St. Louis11, University Hospital Southampton NHS Foundation Trust12, University of Paris13, Technische Universität München14, Loyola University Chicago15, Memorial Sloan Kettering Cancer Center16, University of South Florida17, Medarex18, Bristol-Myers Squibb19
TL;DR: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.
Abstract: Background An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab — which blocks cytotoxic T-lymphocyte–associated antigen 4 to potentiate an antitumor T-cell response — administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. Methods A total of 676 HLA-A*0201–positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. Results The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P = 0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P = 0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Conclusions Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)
13,081 citations
Medical University of Vienna1, Boston University2, Arthritis Research UK3, Johns Hopkins University4, University of California, San Francisco5, Humboldt University of Berlin6, University of Toronto7, National Jewish Health8, Brigham and Women's Hospital9, Paris Descartes University10, University of Leeds11, Catholic University of the Sacred Heart12, Erasmus University Rotterdam13, University of Colorado Denver14, Leiden University15, University of California, San Diego16, University of Massachusetts Medical School17, University of Michigan18, University of Washington19, McGill University Health Centre20, University of Pittsburgh21, Ministry of Health (New Zealand)22, New York University23, University of Manchester24, University of Amsterdam25, University of Kansas26, Women's College Hospital27
TL;DR: This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features.
Abstract: Objective The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classifi cation criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classifi cation criteria for RA. Methods A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated infl ammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/ or erosive disease—this being the appropriate current paradigm underlying the disease construct ‘RA’. Results In the new criteria set, classifi cation as ‘defi nite RA’ is based on the confi rmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0–5), serological abnormality (range 0–3), elevated acute-phase response (range 0–1) and symptom duration (two levels; range 0–1). Conclusion This new classifi cation system redefi nes the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defi ning the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct ‘RA’.
7,120 citations
Medical University of Vienna1, Boston University2, Arthritis Research UK3, Johns Hopkins University4, University of California, San Francisco5, Charité6, University of Toronto7, National Jewish Health8, Harvard University9, University of Paris10, University of Leeds11, Catholic University of the Sacred Heart12, Erasmus University Rotterdam13, University of Colorado Denver14, Leiden University15, University of California, San Diego16, University of Massachusetts Medical School17, University of Michigan18, University of Washington19, McGill University20, University of Pittsburgh21, Ministry of Health (New Zealand)22, New York University23, University of Manchester24, University of Amsterdam25
TL;DR: This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features.
Abstract: Objective The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. Methods A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease—this being the appropriate current paradigm underlying the disease construct ‘RA’. Results In the new criteria set, classification as ‘definite RA’ is based on the confirmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0–5), serological abnormality (range 0–3), elevated acute-phase response (range 0–1) and symptom duration (two levels; range 0–1). Conclusion This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct ‘RA’.
5,964 citations
University of Colorado Denver1, University of California, San Francisco2, Asociación Civil Impacta Salud y Educación3, Oswaldo Cruz Foundation4, Chiang Mai University5, Federal University of Rio de Janeiro6, University of Cape Town7, Brown University8, University of São Paulo9, National Institutes of Health10
TL;DR: Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects and Detectable blood levels strongly correlated with the prophylactic effect.
Abstract: The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at en rollment, and 100 became infected during follow-up (36 in the FTC–TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P = 0.005). In the FTC–TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC–TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P = 0.57). Conclusions Oral FTC–TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foun dation; ClinicalTrials.gov number, NCT00458393.)
4,247 citations
University of Edinburgh1, Public Health Foundation of India2, University of Warwick3, Kenya Medical Research Institute4, University of Liverpool5, University of the Witwatersrand6, Alaska Native Tribal Health Consortium7, Johns Hopkins University8, International Military Sports Council9, University of Barcelona10, Dartmouth College11, Padjadjaran University12, University of Colorado Denver13, University of Split14
TL;DR: Mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b, and the development of novel prevention and treatment strategies should be accelerated as a priority.
2,317 citations
TL;DR: The cTAKES annotations are the foundation for methods and modules for higher-level semantic processing of clinical free-text, and its components, specifically trained for the clinical domain, create rich linguistic and semantic annotations.
1,748 citations
TL;DR: The benefits of physical training are discussed, along with recommendations for varying activities, PA-associated blood glucose management, diabetes prevention, gestational diabetes mellitus, and safe and effective practices for PA with diabetes-related complications.
Abstract: Although physical activity (PA) is a key element in the prevention and management of type 2 diabetes, many with this chronic disease do not become or remain regularly active. High-quality studies establishing the importance of exercise and fitness in diabetes were lacking until recently, but it is now well established that participation in regular PA improves blood glucose control and can prevent or delay type 2 diabetes, along with positively affecting lipids, blood pressure, cardiovascular events, mortality, and quality of life. Structured interventions combining PA and modest weight loss have been shown to lower type 2 diabetes risk by up to 58% in high-risk populations. Most benefits of PA on diabetes management are realized through acute and chronic improvements in insulin action, accomplished with both aerobic and resistance training. The benefits of physical training are discussed, along with recommendations for varying activities, PA-associated blood glucose management, diabetes prevention, gestational diabetes mellitus, and safe and effective practices for PA with diabetes-related complications.
1,635 citations
University of Virginia1, University of Chicago2, University of Texas MD Anderson Cancer Center3, Thomas Jefferson University4, Wake Forest University5, University of Colorado Denver6, Stanford University7, Memorial Sloan Kettering Cancer Center8, Orlando Regional Medical Center9, University of Texas Southwestern Medical Center10, University of Toronto11, University of Rochester12, University of Utah13, Johns Hopkins University14, University of Wisconsin-Madison15, Vrije Universiteit Brussel16, Fox Chase Cancer Center17, Duke University18
TL;DR: The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality.
Abstract: Task Group 101 of the AAPM has prepared this report for medical physicists, clinicians, and therapists in order to outline the best practice guidelines for the external-beam radiation therapy technique referred to as stereotactic body radiation therapy (SBRT). The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality. Information is provided for establishing a SBRT program, including protocols, equipment, resources, and QA procedures. Additionally, suggestions for developing consistent documentation for prescribing, reporting, and recording SBRT treatment delivery is provided.
1,586 citations
TL;DR: A consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society as discussed by the authors reviewed the state of science concerning the association between diabetes and cancer incidence or prognosis.
Abstract: Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and treatments. This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning 1) the association between diabetes and cancer incidence or prognosis; 2) risk factors common to both diabetes and cancer; 3) possible biologic links between diabetes and cancer risk; and 4) whether diabetes treatments influence the risk of cancer or cancer prognosis. In addition, key unanswered questions for future research are posed.
1,546 citations
TL;DR: This work identified key predictors of survival based on the patient's most recent evaluation and formulated a contemporary prognostic equation that may allow the individualization and optimization of therapeutic strategies.
Abstract: Background— Factors that determine survival in pulmonary arterial hypertension (PAH) drive clinical management. A quantitative survival prediction tool has not been established for research or clinical use. Methods and Results— Data from 2716 patients with PAH enrolled consecutively in the US Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) were analyzed to assess predictors of 1-year survival. We identified independent prognosticators of survival and derived a multivariable, weighted risk formula for clinical use. One-year survival from the date of enrollment was 91.0% (95% confidence interval [CI], 89.9 to 92.1). In a multivariable analysis with Cox proportional hazards, variables independently associated with increased mortality included pulmonary vascular resistance >32 Wood units (hazard ratio [HR], 4.1; 95% CI, 2.0 to 8.3), PAH associated with portal hypertension (HR, 3.6; 95% CI, 2.4 to 5.4), modified New York Heart Association/World Health Organization functional class IV (HR, 3.1; 95% CI, 2.2 to 4.4), men >60 years of age (HR, 2.2; 95% CI, 1.6 to 3.0), and family history of PAH (HR, 2.2; 95% CI, 1.2 to 4.0). Renal insufficiency, PAH associated with connective tissue disease, functional class III, mean right atrial pressure, resting systolic blood pressure and heart rate, 6-minute walk distance, brain natriuretic peptide, percent predicted carbon monoxide diffusing capacity, and pericardial effusion on echocardiogram all predicted mortality. Based on these multivariable analyses, a prognostic equation was derived and validated by bootstrapping technique. Conclusions— We identified key predictors of survival based on the patient’s most recent evaluation and formulated a contemporary prognostic equation. Use of this tool may allow the individualization and optimization of therapeutic strategies. Serial follow-up and reassessment are warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214.
1,382 citations
National Heart Foundation of Australia1, University of Toronto2, Cleveland Clinic3, University of Chicago4, University of Alberta5, Inova Fairfax Hospital6, Ochsner Health System7, University of Alabama at Birmingham8, Newcastle upon Tyne Hospitals NHS Foundation Trust9, Ludwig Maximilian University of Munich10, Saint Barnabas Medical Center11, Duke University12, Primary Children's Hospital13, University of Pittsburgh14, University of Utah15, University of Maryland, Baltimore16, University of Vienna17, Stanford University18, University College London19, Washington University in St. Louis20, Loma Linda University21, University of A Coruña22, The Texas Heart Institute23, Katholieke Universiteit Leuven24, Northwestern University25, University of Wisconsin-Madison26, Yeshiva University27, Cincinnati Children's Hospital Medical Center28, University of Colorado Denver29, Drexel University30, University of Pennsylvania31, Mayo Clinic32, St Vincent Hospital33, Papworth Hospital34, Emory University35, Johns Hopkins University36
TL;DR: Institutional Affiliations Chair Costanzo MR: Midwest Heart Foundation, Lombard Illinois, USA Task Force 1 Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Starlings R: University of Chicago, Chicago, Illinois,USA; Chan M: university of Alberta, Edmonton, Alberta, Canada ; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA.
Abstract: Institutional Affiliations Chair Costanzo MR: Midwest Heart Foundation, Lombard Illinois, USA Task Force 1 Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Anderson A: University of Chicago, Chicago, Illinois, USA; Chan M: University of Alberta, Edmonton, Alberta, Canada; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA; Fedson S: University of Chicago, Chicago, Illinois, USA; Fisher P: Ochsner Clinic, New Orleans, Louisiana, USA; Gonzales-Stawinski G: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Martinelli L: Ospedale Niguarda, Milano, Italy; McGiffin D: University of Alabama, Birmingham, Alabama, USA; Parisi F: Ospedale Pediatrico Bambino Gesu, Rome, Italy; Smith J: Freeman Hospital, Newcastle upon Tyne, UK Task Force 2 Taylor D: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Meiser B: University of Munich/Grosshaden, Munich, Germany; Baran D: Newark Beth Israel Medical Center, Newark, New Jersey, USA; Carboni M: Duke University Medical Center, Durham, North Carolina, USA; Dengler T: University of Hidelberg, Heidelberg, Germany; Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, USA; Frigerio M: Ospedale Niguarda, Milano, Italy; Kfoury A: Intermountain Medical Center, Murray, Utah, USA; Kim D: University of Alberta, Edmonton, Alberta, Canada; Kobashigawa J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Shullo M: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Stehlik J: University of Utah, Salt Lake City, Utah, USA; Teuteberg J: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Uber P: University of Maryland, Baltimore, Maryland, USA; Zuckermann A: University of Vienna, Vienna, Austria. Task Force 3 Hunt S: Stanford University, Palo Alto, California, USA; Burch M: Great Ormond Street Hospital, London, UK; Bhat G: Advocate Christ Medical Center, Oak Lawn, Illinois, USA; Canter C: St. Louis Children Hospital, St. Louis, Missouri, USA; Chinnock R: Loma Linda University Children's Hospital, Loma Linda, California, USA; Crespo-Leiro M: Hospital Universitario A Coruna, La Coruna, Spain; Delgado R: Texas Heart Institute, Houston, Texas, USA; Dobbels F: Katholieke Universiteit Leuven, Leuven, Belgium; Grady K: Northwestern University, Chicago, Illlinois, USA; Kao W: University of Wisconsin, Madison Wisconsin, USA; Lamour J: Montefiore Medical Center, New York, New York, USA; Parry G: Freeman Hospital, Newcastle upon Tyne, UK; Patel J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Pini D: Istituto Clinico Humanitas, Rozzano, Italy; Pinney S: Mount Sinai Medical Center, New York, New York, USA; Towbin J: Cincinnati Children's Hospital, Cincinnati, Ohio, USA; Wolfel G: University of Colorado, Denver, Colorado, USA Independent Reviewers Delgado D: University of Toronto, Toronto, Ontario, Canada; Eisen H: Drexler University College of Medicine, Philadelphia, Pennsylvania, USA; Goldberg L: University of Pennsylvania, Philadelphia, Pennsylvania, USA; Hosenpud J: Mayo Clinic, Jacksonville, Florida, USA; Johnson M: University of Wisconsin, Madison, Wisconsin, USA; Keogh A: St Vincent Hospital, Sidney, New South Wales, Australia; Lewis C: Papworth Hospital Cambridge, UK; O'Connell J: St. Joseph Hospital, Atlanta, Georgia, USA; Rogers J: Duke University Medical Center, Durham, North Carolina, USA; Ross H: University of Toronto, Toronto, Ontario, Canada; Russell S: Johns Hopkins Hospital, Baltimore, Maryland, USA; Vanhaecke J: University Hospital Gasthuisberg, Leuven, Belgium.
University of Milan1, University of Siena2, Marche Polytechnic University3, Sapienza University of Rome4, University of Nantes5, University of Pécs6, Umeå University7, Newcastle University8, University of Greifswald9, Ludwig Maximilian University of Munich10, University of Paris11, Case Western Reserve University12, University of Zagreb13, University of Florida14, Indiana University15, Leeds General Infirmary16, University of Liège17, University of Groningen18, Tel Aviv University19, Medical University of Warsaw20, University of Colorado Denver21, Lille University of Science and Technology22, Erasmus University Rotterdam23, University of Iowa24
TL;DR: This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants.
Abstract: The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.
TL;DR: This educational activity is designed for all cardiovascular physicians and cardiac sonographers with erest and knowledge base in the field of echocardiography; in addition, reschers, clinicians, intensivists, and other medical professionals with a cardiac ultrasound will find this activity beneficial.
Abstract: n Society of Echocardiography designates this educational activity for of 15 AMA PRA Category 1 Credits Physicians should only claim credit te with the extent of their participation in the activity CCI recognize the ASE’s certificates and have agreed to honor the credit their registry requirements for sonographers n Society of Echocardiography is committed to ensuring that its educan and all sponsored educational programs are not influenced by the special y corporation or individual, and itsmandate is to retain only those authors ial interests can be effectively resolved to maintain the goals and educaty of the activity Although amonetary or professional affiliationwith a cors not necessarily influence an author’s presentation, the Essential Areas and e ACCME require that any relationships that could possibly conflict with al value of the activity be resolved prior to publication and disclosed to Disclosures of faculty and commercial support relationships, if any, dicated ience: is designed for all cardiovascular physicians and cardiac sonographers with erest and knowledge base in the field of echocardiography; in addition, reschers, clinicians, intensivists, and other medical professionals with a spein cardiac ultrasound will find this activity beneficial
TL;DR: Empirical evidence supports the efficacy of psychodynamic therapy and the perception that psychodynamic approaches lack empirical support does not accord with available scientific evidence and may reflect selective dissemination of research findings.
Abstract: Empirical evidence supports the efficacy of psychodynamic psychotherapy. Effect sizes for psychodynamic psychotherapy are as large as those reported for other therapies that have been actively promoted as "empirically supported" and "evidence based." Additionally, patients who receive psychodynamic therapy maintain therapeutic gains and appear to continue to improve after treatment ends. Finally, non-psychodynamic therapies may be effective in part because the more skilled practitioners utilize techniques that have long been central to psychodynamic theory and practice. The perception that psychodynamic approaches lack empirical support does not accord with available scientific evidence and may reflect selective dissemination of research findings. There is a belief in some quarters that psychodynamic concepts and treatments lack empirical support, or that scientific evidence shows that other forms of treatment are more effective. The belief appears to have taken on a life of its own. Academicians repeat it to one another, as do healthcare administrators, as do healthcare policy makers. With each repetition, its apparent credibility grows. At some point, there seems little need to question or revisit it because "everyone" knows it to be so. The scientific evidence tells a different story: considerable research supports the efficacy and effectiveness of psychodynamic psychotherapy. The discrepancy between perceptions and evidence may be due, in part, to biases in the dissemination of research findings. One potential source of bias is a lingering distaste in the mental health professions for past psychoanalytic arrogance and authority. In decades past, American psychoanalysis was dominated by a hierarchical medical establishment that denied training to non-MDs and adopted a dismissive stance toward research. This did not win friends in academic circles. When empirical findings emerged that supported non-psychodynamic treatments, many academicians greeted them enthusiastically and were eager to discuss and disseminate them. When empirical evidence supported psychodynamic concepts and treatments, it was often overlooked. This article brings together findings from several empirical literatures that bear on the efficacy of psychodynamic treatment. It will first outline the distinctive features of psychodynamic psychotherapy.
TL;DR: The focus of the present study was to define the human plasma lipidome and to establish novel analytical methodologies to quantify the large spectrum of plasma lipids and to quantitatively assessed the levels of over 500 distinct molecular species distributed among the main lipid categories.
American Foundation for Suicide Prevention1, San Francisco State University2, University of California, Los Angeles3, Pennsylvania State University4, University of Colorado Denver5, Columbia University6, University of Illinois at Chicago7, City University of New York8, University of Arizona9, University of California, San Francisco10, Drexel University11, University of Minnesota12, Fenway Health13, Yale University14, University of Pennsylvania15, Ben-Gurion University of the Negev16, University of Pittsburgh17, Howard Brown Health Center18, Kaiser Permanente19
TL;DR: This article is a culmination of a three-year effort by an expert panel to address the need for better understanding of suicidal behavior and suicide risk in sexual minority populations, and stimulate the development of needed prevention strategies, interventions and policy changes.
Abstract: Despite strong indications of elevated risk of suicidal behavior in lesbian, gay, bisexual, and transgender people, limited attention has been given to research, interventions or suicide prevention programs targeting these populations. This article is a culmination of a three-year effort by an expert panel to address the need for better understanding of suicidal behavior and suicide risk in sexual minority populations, and stimulate the development of needed prevention strategies, interventions and policy changes. This article summarizes existing research findings, and makes recommendations for addressing knowledge gaps and applying current knowledge to relevant areas of suicide prevention practice.
TL;DR: Compared with patients meeting the traditional hemodynamic definition of PAH, patients with a PCWP of 16 to 18 mm Hg were older, more obese, had a lower 6-min walk distance, and had a higher incidence of systemic hypertension, sleep apnea, renal insufficiency, and diabetes.
TL;DR: This review focuses on the parallels between epithelial plasticity/EMT in the mammary gland and other organs during development, and on a selection of developmental EMT regulators that are misexpressed specifically during breast cancer.
Abstract: From the earliest stages of embryonic development, cells of epithelial and mesenchymal origin contribute to the structure and function of developing organs. However, these phenotypes are not always permanent, and instead, under the appropriate conditions, epithelial and mesenchymal cells convert between these two phenotypes. These processes, termed Epithelial-Mesenchymal Transition (EMT), or the reverse Mesenchymal-Epithelial Transition (MET), are required for complex body patterning and morphogenesis. In addition, epithelial plasticity and the acquisition of invasive properties without the full commitment to a mesenchymal phenotype are critical in development, particularly during branching morphogenesis in the mammary gland. Recent work in cancer has identified an analogous plasticity of cellular phenotypes whereby epithelial cancer cells acquire mesenchymal features that permit escape from the primary tumor. Because local invasion is thought to be a necessary first step in metastatic dissemination, EMT and epithelial plasticity are hypothesized to contribute to tumor progression. Similarities between developmental and oncogenic EMT have led to the identification of common contributing pathways, suggesting that the reactivation of developmental pathways in breast and other cancers contributes to tumor progression. For example, developmental EMT regulators including Snail/Slug, Twist, Six1, and Cripto, along with developmental signaling pathways including TGF-β and Wnt/β-catenin, are misexpressed in breast cancer and correlate with poor clinical outcomes. This review focuses on the parallels between epithelial plasticity/EMT in the mammary gland and other organs during development, and on a selection of developmental EMT regulators that are misexpressed specifically during breast cancer.
TL;DR: The epidemiology of type 1 diabetes mellitus around the world and across the lifespan is described and data indicates that the incidence of T1D has been increasing by 2% to 5% worldwide and that the prevalence is approximately 1 in 300 in the United States by 18 years of age.
TL;DR: To update SCD population estimates by using recent U.S. Census and birth-cohort SCD prevalence for at-risk populations as available through the centralized reporting of universal newborn screening for hemoglobinopathies, with an effort to demonstrate the potential effect of early mortality.
Abstract: We have conducted a detailed investigation of the broadband spectral properties of the gamma-ray selected blazars of the Fermi LAT Bright AGN Sample (LBAS). By combining our accurately estimated Fermi gamma-ray spectra with Swift, radio, infra-red, optical, and other hard X-ray/gamma-ray data, collected within 3 months of the LBAS data taking period, we were able to assemble high-quality and quasi-simultaneous spectral energy distributions (SED) for 48 LBAS blazars. The SED of these gamma-ray sources is similar to that of blazars discovered at other wavelengths, clearly showing, in the usual log nu-log nu F-nu representation, the typical broadband spectral signatures normally attributed to a combination of low-energy synchrotron radiation followed by inverse Compton emission of one or more components. We have used these SED to characterize the peak intensity of both the low-and the high-energy components. The results have been used to derive empirical relationships that estimate the position of the two peaks from the broadband colors (i.e., the radio to optical, alpha(ro), and optical to X-ray, alpha(ox), spectral slopes) and from the gamma-ray spectral index. Our data show that the synchrotron peak frequency (nu(S)(peak)) is positioned between 10(12.5) and 10(14.5) Hz in broad-lined flat spectrum radio quasars (FSRQs) and between 10(13) and 10(17) Hz in featureless BL Lacertae objects. We find that the gamma-ray spectral slope is strongly correlated with the synchrotron peak energy and with the X-ray spectral index, as expected at first order in synchrotron-inverse Compton scenarios. However, simple homogeneous, one-zone, synchrotron self-Compton (SSC) models cannot explain most of our SED, especially in the case of FSRQs and low energy peaked (LBL) BL Lacs. More complex models involving external Compton radiation or multiple SSC components are required to reproduce the overall SED and the observed spectral variability. While more than 50% of known radio bright high energy peaked (HBL) BL Lacs are detected in the LBAS sample, only less than 13% of known bright FSRQs and LBL BL Lacs are included. This suggests that the latter sources, as a class, may be much fainter gamma-ray emitters than LBAS blazars, and could in fact radiate close to the expectations of simple SSC models. We categorized all our sources according to a new physical classification scheme based on the generally accepted paradigm for Active Galactic Nuclei and on the results of this SED study. Since the LAT detector is more sensitive to flat spectrum gamma-ray sources, the correlation between nu(S)(peak) and gamma-ray spectral index strongly favors the detection of high energy peaked blazars, thus explaining the Fermi overabundance of this type of sources compared to radio and EGRET samples. This selection effect is similar to that experienced in the soft X-ray band where HBL BL Lacs are the dominant type of blazars.
TL;DR: Recent observations reveal the ability of γδ T cells to rapidly produce cytokines that regulate pathogen clearance, inflammation and tissue homeostasis in response to tissue stress, and insights are provided into how they acquire these properties.
Abstract: Gammadelta T cells have several innate cell-like features that allow their early activation following recognition of conserved stress-induced ligands. Here we review recent observations revealing the ability of gammadelta T cells to rapidly produce cytokines that regulate pathogen clearance, inflammation and tissue homeostasis in response to tissue stress. These studies provide insights into how they acquire these properties, through both developmental programming in the thymus and functional polarization in the periphery. Innate features of gammadelta T cells underlie their non-redundant role in several physiopathological contexts and are therefore being exploited in the design of new immunotherapeutic approaches.
Washington University in St. Louis1, University of Illinois at Urbana–Champaign2, Uppsala University3, University of California, Los Angeles4, Wellcome Trust Sanger Institute5, University of Oxford6, Duke University7, University of Houston8, University of Kent9, University of Oviedo10, Weizmann Institute of Science11, Institute for Systems Biology12, Louisiana State University13, University of Colorado Denver14, University of Washington15, University of Sheffield16, University of Edinburgh17, Max Planck Society18, Free University of Berlin19, Harvard University20, Monsanto21
TL;DR: This work shows that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets and shows evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience.
Abstract: The zebra finch is an important model organism in several fields with unique relevance to human neuroscience. Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chicken-the only bird with a sequenced genome until now. Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes. We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage-specific gene family expansions, the number of long-terminal-repeat-based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour.
Beaumont Hospital1, Charité2, Veterans Health Administration3, University of Alberta4, University of Melbourne5, University of Colorado Denver6, University of Padua7, University College London8, University of Helsinki9, University of Groningen10, University of Western Ontario11, George Washington University12, University of California, San Diego13, Mayo Clinic14, University of Paris15, University of Siena16, Duke University17, University of Maryland, College Park18, Wrocław Medical University19
TL;DR: A consensus conference on cardio-renal syndromes (CRS) was held in Venice Italy, in September 2008 under the auspices of the Acute Dialysis Quality Initiative (ADQI).
Abstract: A consensus conference on cardio-renal syndromes (CRS) was held in Venice Italy, in September 2008 under the auspices of the Acute Dialysis Quality Initiative (ADQI). The following topics were matter of discussion after a systematic literature review and the appraisal of the best available evidence: definition/classification system; epidemiology; diagnostic criteria and biomarkers; prevention/protection strategies; management and therapy. The umbrella term CRS was used to identify a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. Different syndromes were identified and classified into five subtypes. Acute CRS (type 1): acute worsening of heart function (AHF–ACS) leading to kidney injury and/or dysfunction. Chronic cardio-renal syndrome (type 2): chronic abnormalities in heart function (CHF-CHD) leading to kidney injury and/or dysfunction. Acute reno-cardiac syndrome (type 3): acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. Chronic reno-cardiac syndrome (type 4): chronic kidney disease leading to heart injury, disease, and/or dysfunction. Secondary CRS (type 5): systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Consensus statements concerning epidemiology, diagnosis, prevention, and management strategies are discussed in the paper for each of the syndromes.
TL;DR: This document presents an updated version of the guideline for the management of bleeding following severe injury, which provides an evidence-based multidisciplinary approach to themanagement of critically injured bleeding trauma patients.
Abstract: Introduction: Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient, which when implemented may improve patient outcomes. Methods: The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document presents an updated version of the guideline published by the group in 2007. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature. Results: Key changes encompassed in this version of the guideline include new recommendations on coagulation support and monitoring and the appropriate use of local haemostatic measures, tourniquets, calcium and desmopressin in the bleeding trauma patient. The remaining recommendations have been reevaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies. Conclusions: This guideline provides an evidence-based multidisciplinary approach to the management of critically injured bleeding trauma patients.
TL;DR: It is hoped that this chapter will shed light on the major problems associated with DILI in regards to the pharmaceutical industry, drug regulatory agencies, physicians and pharmacists, and patients.
Abstract: Many drugs and environmental chemicals are capable of evoking some degree of liver injury. The liver represents a primary target for adverse drug reactions due to its central role in biotransformation and excretion of foreign compounds, its portal location within the circulation exposing it to a wide variety of substances, and its anatomic and physiologic structure. Drug-induced liver injury (DILI) remains the single most common adverse indication leading to drug candidate failure or withdrawal from the market. However, the absolute incidence of DILI is low, and this presents a challenge to mechanistic studies. DILI remains unpredictable making prevention very difficult. In this chapter, we focus on the current understanding of DILI. We begin with an overview regarding the significance and epidemiology of DILI and then examine the clinical presentation and susceptibility factors related to DILI. This is followed by a review of the current literature regarding the proposed pathogenesis of DILI, which involves the participation of a drug, or most often a reactive metabolite of the drug, that either directly affects cellular function or elicits an immune response. It is our hope that this chapter will shed light on the major problems associated with DILI in regards to the pharmaceutical industry, drug regulatory agencies, physicians and pharmacists, and patients.
Harvard University1, University of Southern California2, University of Arkansas for Medical Sciences3, University of Colorado Denver4, Boston Children's Hospital5, New York University6, University of California, Davis7, Columbia University Medical Center8, Baylor College of Medicine9, State University of New York System10, Columbia University11, University of Rochester Medical Center12, Mahidol University13, University of Medicine and Dentistry of New Jersey14, Cleveland Clinic15, New York Academy of Medicine16, Children's Memorial Hospital17, University of California, Los Angeles18
TL;DR: The consensus expert opinion of the panel was that individuals with ASDs deserve the same thoroughness and standard of care in the diagnostic workup and treatment of gastrointestinal concerns as should occur for patients without ASDs.
Abstract: Autism spectrum disorders (ASDs) are common and clinically heterogeneous neurodevelopmental disorders. Gastrointestinal disorders and associated symptoms are commonly reported in individuals with ASDs, but key issues such as the prevalence and best treatment of these conditions are incompletely understood. A central difficulty in recognizing and characterizing gastrointestinal dysfunction with ASDs is the communication difficulties experienced by many affected individuals. A multidisciplinary panel reviewed the medical literature with the aim of generating evidence-based recommendations for diagnostic evaluation and management of gastrointestinal problems in this patient population. The panel concluded that evidence-based recommendations are not yet available. The consensus expert opinion of the panel was that individuals with ASDs deserve the same thoroughness and standard of care in the diagnostic workup and treatment of gastrointestinal concerns as should occur for patients without ASDs. Care providers should be aware that problem behavior in patients with ASDs may be the primary or sole symptom of the underlying medical condition, including some gastrointestinal disorders. For these patients, integration of behavioral and medical care may be most beneficial. Priorities for future research are identified to advance our understanding and management of gastrointestinal disorders in persons with ASDs.
TL;DR: The genetic underpinnings of AA are defined, placing it within the context of shared pathways among autoimmune diseases, and implicating a novel disease mechanism, the upregulation of ULBP ligands, in triggering autoimmunity.
Abstract: Alopecia areata (AA) is among the most highly prevalent human autoimmune diseases, leading to disfiguring hair loss due to the collapse of immune privilege of the hair follicle and subsequent autoimmune attack. The genetic basis of AA is largely unknown. We undertook a genome-wide association study (GWAS) in a sample of 1,054 cases and 3,278 controls and identified 139 single nucleotide polymorphisms that are significantly associated with AA (P
TL;DR: IL-37 emerged as a natural suppressor of innate inflammatory and immune responses and protected from lipopolysaccharide-induced shock, and transgenic mice showed less cytokine suppression when endogenous Smad3 was depleted.
Abstract: The function of interleukin 37 (IL-37; formerly IL-1 family member 7) has remained elusive. Expression of IL-37 in macrophages or epithelial cells almost completely suppressed production of pro-inflammatory cytokines, whereas the abundance of these cytokines increased with silencing of endogenous IL-37 in human blood cells. Anti-inflammatory cytokines were unaffected. Mice with transgenic expression of IL-37 were protected from lipopolysaccharide-induced shock, and showed markedly improved lung and kidney function and reduced liver damage after treatment with lipopolysaccharide. Transgenic mice had lower concentrations of circulating and tissue cytokines (72-95% less) than wild-type mice and showed less dendritic cell activation. IL-37 interacted intracellularly with Smad3 and IL-37-expressing cells and transgenic mice showed less cytokine suppression when endogenous Smad3 was depleted. IL-37 thus emerges as a natural suppressor of innate inflammatory and immune responses.
TL;DR: Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient.
Abstract: Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to these guidelines and recommendations to be voluntary, with the ultimate determination regarding their application to be made by the physician in light of each patient’s individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed or endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice.