Showing papers by "University of Miami published in 2012"
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2010 aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex, using the Cause of Death Ensemble model.
11,809 citations
Daniel C. Koboldt1, Robert S. Fulton1, Michael D. McLellan1, Heather Schmidt1 +352 more•Institutions (35)
TL;DR: The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.
Abstract: We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.
9,355 citations
TL;DR: In this paper, the authors estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010.
9,324 citations
TL;DR: Prevalence and severity of health loss were weakly correlated and age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010, but population growth and ageing have increased YLD numbers and crude rates over the past two decades.
7,021 citations
TL;DR: The results for 1990 and 2010 supersede all previously published Global Burden of Disease results and highlight the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account.
6,861 citations
TL;DR: T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane.
Abstract: Background Trastuzumab emtansine (T-DM1) is an antibody–drug conjugate incorporating the human epidermal growth factor receptor 2 (HER2)–targeted antitumor properties of tras tuz u mab with the cytotoxic activity of the microtubule-inhibitory agent DM1. The antibody and the cytotoxic agent are conjugated by means of a stable linker. Methods We randomly assigned patients with HER2-positive advanced breast cancer, who had previously been treated with tras tuz u mab and a taxane, to T-DM1 or la pa ti nib plus cap e ci ta bine. The primary end points were progression-free survival (as assessed by independent review), overall survival, and safety. Secondary end points included progression-free survival (investigator-assessed), the objective response rate, and the time to symptom progression. Two interim analyses of overall survival were conducted. Results Among 991 randomly assigned patients, median progression-free survival as assessed by independent review was 9.6 months with T-DM1 versus 6.4 months with la pa ti nib plus cap e ci ta bine (hazard ratio for progression or death from any cause, 0.65; 95% confidence interval [CI], 0.55 to 0.77; P<0.001), and median overall survival at the second interim analysis crossed the stopping boundary for efficacy (30.9 months vs. 25.1 months; hazard ratio for death from any cause, 0.68; 95% CI, 0.55 to 0.85; P<0.001). The objective response rate was higher with T-DM1 (43.6%, vs. 30.8% with la pa ti nib plus cap e ci ta bine; P<0.001); results for all additional secondary end points favored T-DM1. Rates of adverse events of grade 3 or above were higher with la pati nib plus cap e ci ta bine than with T-DM1 (57% vs. 41%). The incidences of thrombocytopenia and increased serum aminotransferase levels were higher with T-DM1, whereas the incidences of diarrhea, nausea, vomiting, and palmar–plantar erythro dysesthesia were higher with la pa ti nib plus cap e ci ta bine. Conclusions T-DM1 significantly prolonged progression-free and overall survival with less toxicity than la pa ti nib plus cap e ci ta bine in patients with HER2-positive advanced breast cancer previously treated with tras tuz u mab and a taxane. (Funded by F. Hoffmann– La Roche/Genentech; EMILIA ClinicalTrials.gov number, NCT00829166.)
2,862 citations
TL;DR: Additive manufacturing processes take the information from a computer-aided design (CAD) file that is later converted to a stereolithography (STL) file as discussed by the authors.
Abstract: Additive manufacturing processes take the information from a computer-aided design (CAD) file that is later converted to a stereolithography (STL) file. In this process, the drawing made in the CAD software is approximated by triangles and sliced containing the information of each layer that is going to be printed. There is a discussion of the relevant additive manufacturing processes and their applications. The aerospace industry employs them because of the possibility of manufacturing lighter structures to reduce weight. Additive manufacturing is transforming the practice of medicine and making work easier for architects. In 2004, the Society of Manufacturing Engineers did a classification of the various technologies and there are at least four additional significant technologies in 2012. Studies are reviewed which were about the strength of products made in additive manufacturing processes. However, there is still a lot of work and research to be accomplished before additive manufacturing technologies become standard in the manufacturing industry because not every commonly used manufacturing material can be handled. The accuracy needs improvement to eliminate the necessity of a finishing process. The continuous and increasing growth experienced since the early days and the successful results up to the present time allow for optimism that additive manufacturing has a significant place in the future of manufacturing.
1,777 citations
Albert Einstein Institution1, Ewha Womans University2, University of Oxford3, Hungarian Academy of Sciences4, University of Savoy5, CERN6, Uppsala University7, Petersburg Nuclear Physics Institute8, King's College London9, Jagiellonian University10, École Normale Supérieure11, Pierre-and-Marie-Curie University12, Princeton University13, University of Copenhagen14, University of Lyon15, University of Miami16, Imperial College London17, Pennsylvania State University18, University of California, Santa Barbara19, Humboldt University of Berlin20, Utrecht University21, University of York22, Perimeter Institute for Theoretical Physics23
TL;DR: In this article, the authors present an overview of the achievements and the status of integrability in the context of the AdS/CFT correspondence as of the year 2010.
Abstract: This is the introductory chapter of a review collection on integrability in the context of the AdS/CFT correspondence. In the collection we present an overview of the achievements and the status of this subject as of the year 2010.
1,564 citations
TL;DR: In this article, the authors present a perioperative anticoagulation management for patients with thromboembolism and bleeding, which is based on risk assessment for risk assessment.
1,393 citations
University of Texas MD Anderson Cancer Center1, University of Washington2, Loyola University Chicago3, Mayo Clinic4, University of Miami5, University of British Columbia6, Wayne State University7, Washington University in St. Louis8, Georgetown University9, University of California, Los Angeles10, University of Alabama at Birmingham11, Memorial Sloan Kettering Cancer Center12, University of Cologne13, Seattle Genetics14, City of Hope National Medical Center15
TL;DR: The ADC brentuximab vedotin was associated with manageable toxicity and induced objective responses in 75% of patients with relapsed or refractory HL after autologous stem-cell transplantation (auto-SCT).
Abstract: Purpose Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. In phase I studies, brentuximab vedotin demonstrated significant activity with a favorable safety profile in patients with relapsed or refractory CD30-positive lymphomas. Patients and Methods In this multinational, open-label, phase II study, the efficacy and safety of brentuximab vedotin were evaluated in patients with relapsed or refractory Hodgkin’s lymphoma (HL) after autologous stem-cell transplantation (auto-SCT). Patients had histologically documented CD30-positive HL by central pathology review. A total of 102 patients were treated with brentuximab vedotin 1.8 mg/kg by intravenous infusion every 3 weeks. In the absence of disease progression or prohibitive toxicity, patients received a maximum of 16 cycles. The primary end point was the overall objective response rate (ORR) determined by an independent radiology review facility. Results The ORR was 75% with complete remission (CR) in 34% of patients. The median progression-free survival time for all patients was 5.6 months, and the median duration of response for those in CR was 20.5 months. After a median observation time of more than 1.5 years, 31 patients were alive and free of documented progressive disease. The most common treatment-related adverse events were peripheral sensory neuropathy, nausea, fatigue, neutropenia, and diarrhea. Conclusion The ADC brentuximab vedotin was associated with manageable toxicity and induced objective responses in 75% of patients with relapsed or refractory HL after auto-SCT. Durable CRs approaching 2 years were observed, supporting study in earlier lines of therapy. J Clin Oncol 30:2183-2189. © 2012 by American Society of Clinical Oncology
1,254 citations
TL;DR: By in vivo magnetic resonance spectroscopy, brain lactate concentrations in mutants were increased compared with controls, but were detectable only in mice exposed to volatile anaesthetics, which indicates that aerobic glycolysis products derived from oligodendrocytes are rapidly metabolized within white matter tracts.
Abstract: Oligodendrocytes, the myelin-forming glial cells of the central nervous system, maintain long-term axonal integrity. However, the underlying support mechanisms are not understood. Here we identify a metabolic component of axon-glia interactions by generating conditional Cox10 (protoheme IX farnesyltransferase) mutant mice, in which oligodendrocytes and Schwann cells fail to assemble stable mitochondrial cytochrome c oxidase (COX, also known as mitochondrial complex IV). In the peripheral nervous system, Cox10 conditional mutants exhibit severe neuropathy with dysmyelination, abnormal Remak bundles, muscle atrophy and paralysis. Notably, perturbing mitochondrial respiration did not cause glial cell death. In the adult central nervous system, we found no signs of demyelination, axonal degeneration or secondary inflammation. Unlike cultured oligodendrocytes, which are sensitive to COX inhibitors, post-myelination oligodendrocytes survive well in the absence of COX activity. More importantly, by in vivo magnetic resonance spectroscopy, brain lactate concentrations in mutants were increased compared with controls, but were detectable only in mice exposed to volatile anaesthetics. This indicates that aerobic glycolysis products derived from oligodendrocytes are rapidly metabolized within white matter tracts. Because myelinated axons can use lactate when energy-deprived, our findings suggest a model in which axon-glia metabolic coupling serves a physiological function.
Harvard University1, University of Queensland2, Johns Hopkins University3, ICF International4, Centre for Mental Health5, Boston University6, University of Sydney7, University of Melbourne8, Imperial College London9, University of New South Wales10, University of California, San Diego11, Emory University12, University of Pennsylvania13, Autonomous University of Barcelona14, University of London15, National Institutes of Health16, French Institute of Health and Medical Research17, Medical Research Council18, Auckland University of Technology19, Federal University of São Paulo20, National Institute of Population and Social Security Research21, Howard University22, Flinders University23, Erasmus University Rotterdam24, King's College London25, Karolinska Institutet26, University of California, San Francisco27, All India Institute of Medical Sciences28, Nova Southeastern University29, University of Miami30, Swansea University31, Tehran University of Medical Sciences32, Queen Mary University of London33, Allen Institute for Brain Science34, University of Cape Town35, Columbia University36, Watford General Hospital37, Centro Studi GISED38, University of Oxford39, Deakin University40, University of British Columbia41, University of Toronto42, Box Hill Hospital43, Vanderbilt University44, University of Washington45, Brandeis University46, University of Tokyo47, The Queen's Medical Center48, Norwegian University of Science and Technology49, China Medical Board50, University of Cambridge51, Royal Cornwall Hospital52, Cedars-Sinai Medical Center53, Shanghai Jiao Tong University54
TL;DR: In this paper, a comprehensive re-estimation of disability weights for the Global Burden of Disease Study 2010 through a large-scale empirical investigation in which judgments about health losses associated with many causes of disease and injury were elicited from the general public in diverse communities through a new, standardised approach.
TL;DR: In this article, a global-scale high-resolution (0.1°) mapping of sources based on Moderate Resolution Imaging Spectroradiometer (MODIS) Deep Blue estimates of dust optical depth in conjunction with other data sets including land use is presented.
Abstract: [1] Our understanding of the global dust cycle is limited by a dearth of information about dust sources, especially small-scale features which could account for a large fraction of global emissions. Here we present a global-scale high-resolution (0.1°) mapping of sources based on Moderate Resolution Imaging Spectroradiometer (MODIS) Deep Blue estimates of dust optical depth in conjunction with other data sets including land use. We ascribe dust sources to natural and anthropogenic (primarily agricultural) origins, calculate their respective contributions to emissions, and extensively compare these products against literature. Natural dust sources globally account for 75% of emissions; anthropogenic sources account for 25%. North Africa accounts for 55% of global dust emissions with only 8% being anthropogenic, mostly from the Sahel. Elsewhere, anthropogenic dust emissions can be much higher (75% in Australia). Hydrologic dust sources (e.g., ephemeral water bodies) account for 31% worldwide; 15% of them are natural while 85% are anthropogenic. Globally, 20% of emissions are from vegetated surfaces, primarily desert shrublands and agricultural lands. Since anthropogenic dust sources are associated with land use and ephemeral water bodies, both in turn linked to the hydrological cycle, their emissions are affected by climate variability. Such changes in dust emissions can impact climate, air quality, and human health. Improved dust emission estimates will require a better mapping of threshold wind velocities, vegetation dynamics, and surface conditions (soil moisture and land use) especially in the sensitive regions identified here, as well as improved ability to address small-scale convective processes producing dust via cold pool (haboob) events frequent in monsoon regimes.
TL;DR: In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions.
Abstract: Context Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared. Objective To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM. Design, Setting, and Patients A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up. Intervention Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites. Main Outcome Measures Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs). Efficacy assessments included 6-minute walk test, exercise peak VO 2 , Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index. Results Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%. The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46). At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10). Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO 2 max. Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P Conclusions In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions. In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling. Trial Registration clinicaltrials.gov Identifier: NCT01087996
TL;DR: The American Diabetes Association (ADA) convened a Consensus Development Conference on Diabetes and Older Adults (defined as those aged ≥ 65 years) in February 2012 as discussed by the authors, where a series of scientific presentations by experts in the field were independently developed.
Abstract: More than 25% of the U.S. population aged ≥65 years has diabetes (1), and the aging of the overall population is a significant driver of the diabetes epidemic. Although the burden of diabetes is often described in terms of its impact on working-age adults, diabetes in older adults is linked to higher mortality, reduced functional status, and increased risk of institutionalization (2). Older adults with diabetes are at substantial risk for both acute and chronic microvascular and cardiovascular complications of the disease.
Despite having the highest prevalence of diabetes of any age-group, older persons and/or those with multiple comorbidities have often been excluded from randomized controlled trials of treatments—and treatment targets—for diabetes and its associated conditions. Heterogeneity of health status of older adults (even within an age range) and the dearth of evidence from clinical trials present challenges to determining standard intervention strategies that fit all older adults. To address these issues, the American Diabetes Association (ADA) convened a Consensus Development Conference on Diabetes and Older Adults (defined as those aged ≥65 years) in February 2012. Following a series of scientific presentations by experts in the field, the writing group independently developed this consensus report to address the following questions:
1. What is the epidemiology and pathogenesis of diabetes in older adults?
2. What is the evidence for preventing and treating diabetes and its common comorbidities in older adults?
3. What current guidelines exist for treating diabetes in older adults?
4. What issues need to be considered in individualizing treatment recommendations for older adults?
5. What are consensus recommendations for treating older adults with or at risk for diabetes?
6. How can gaps in the evidence best be filled?
According to the most recent surveillance data, the prevalence of diabetes among U.S. adults aged ≥65 years varies from 22 to 33%, depending on the diagnostic criteria …
Abstract: The Yen–Mullins model, also known as the modified Yen model, specifies the predominant molecular and colloidal structure of asphaltenes in crude oils and laboratory solvents and consists of the following: The most probable asphaltene molecular weight is ∼750 g/mol, with the island molecular architecture dominant. At sufficient concentration, asphaltene molecules form nanoaggregates with an aggregation number less than 10. At higher concentrations, nanoaggregates form clusters again with small aggregation numbers. The Yen–Mullins model is consistent with numerous molecular and colloidal studies employing a broad array of methodologies. Moreover, the Yen–Mullins model provides a foundation for the development of the first asphaltene equation of state for predicting asphaltene gradients in oil reservoirs, the Flory–Huggins–Zuo equation of state (FHZ EoS). In turn, the FHZ EoS has proven applicability in oil reservoirs containing condensates, black oils, and heavy oils. While the development of the Yen–Mullin...
Fox Chase Cancer Center1, Stanford University2, University of Paris3, Washington University in St. Louis4, University of Miami5, National Health Service6, Wayne State University7, University of Texas MD Anderson Cancer Center8, University of British Columbia9, Seattle Genetics10, University of Washington11
TL;DR: Targeted therapy with this CD30-directed antibody-drug conjugate brentuximab vedotin may be an effective treatment for relapsed or refractory systemic ALCL and warrants further studies in front-line therapy.
Abstract: Purpose Systemic anaplastic large-cell lymphoma (ALCL) is an aggressive subtype of T-cell lymphoma characterized by the uniform expression of CD30. The antibody-drug conjugate brentuximab vedotin delivers the potent antimicrotubule agent monomethylauristatin E to CD30-positive malignant cells. A phase II multicenter trial was conducted to evaluate the efficacy and safety of brentuximab vedotin in patients with relapsed or refractory systemic ALCL. Patients and Methods Patients with systemic ALCL and recurrent disease after at least one prior therapy received brentuximab vedotin 1.8 mg/kg intravenously every 3 weeks over 30 minutes as an outpatient infusion. The primary end point of the study was overall objective response rate as assessed by independent central review. Results Of 58 patients treated in the study, 50 patients (86%) achieved an objective response, 33 patients (57%) achieved a complete remission (CR), and 17 patients (29%) achieved a partial remission. The median durations of overall respons...
TL;DR: This guideline updates the 2002 Infectious Diseases Society of America guideline and discusses diagnosis and management, and recommendations are provided regarding antibiotic choices and dosing.
Abstract: The guideline is intended for use by healthcare providers who care for adult and pediatric patients with group A streptococcal pharyngitis. The guideline updates the 2002 Infectious Diseases Society of America guideline and discusses diagnosis and management, and recommendations are provided regarding antibiotic choices and dosing. Penicillin or amoxicillin remain the treatments of choice, and recommendations are made for the penicillin-allergic patient, which now include clindamycin.
TL;DR: Among US Hispanic/Latino adults of diverse backgrounds, a sizeable proportion of men and women had adverse major risk factors; prevalence of adverse CVD risk profiles was higher among participants with Puerto Rican background, lower SES, and higher levels of acculturation.
Abstract: Results Age-standardized prevalence of CVD risk factors varied by Hispanic/Latino background; obesity and current smoking rates were highest among Puerto Rican participants (for men, 40.9% and 34.7%; for women, 51.4% and 31.7%, respectively); hypercholesterolemia prevalence was highest among Central American men (54.9%) and Puerto Rican women (41.0%). Large proportions of participants (80% of men, 71% of women) had at least 1 risk factor. Age- and sex-adjusted prevalence of 3 or more risk factors was highest in Puerto Rican participants (25.0%) and significantly higher (P.001) among participants with less education (16.1%), those who were US-born (18.5%), those who had lived in the United States 10 years or longer (15.7%), and those who preferred English (17.9%). Overall, self-reported CHD and stroke prevalence were low (4.2% and 2.0% in men; 2.4% and 1.2% in women, respectively). In multivariate-adjusted models, hypertension and smoking were directly associated with CHD in both sexes as were hypercholesterolemia and obesity in women and diabetes in men (odds ratios [ORs], 1.5-2.2). For stroke, associations were positive with hypertension in both sexes, diabetes in men, and smoking in women (ORs, 1.7-2.6). Conclusion Among US Hispanic/Latino adults of diverse backgrounds, a sizeable proportion of men and women had adverse major risk factors; prevalence of adverse CVD risk profiles was higher among participants with Puerto Rican background, lower SES, and higher levels of acculturation.
TL;DR: An overview on the potential of applying game theory for addressing relevant and timely open problems in three emerging areas that pertain to the smart grid: microgrid systems, demand-side management, and communications is provided.
Abstract: The future smart grid is envisioned as a large scale cyberphysical system encompassing advanced power, communications, control, and computing technologies. To accommodate these technologies, it will have to build on solid mathematical tools that can ensure an efficient and robust operation of such heterogeneous and large-scale cyberphysical systems. In this context, this article is an overview on the potential of applying game theory for addressing relevant and timely open problems in three emerging areas that pertain to the smart grid: microgrid systems, demand-side management, and communications. In each area, the state-of-the-art contributions are gathered and a systematic treatment, using game theory, of some of the most relevant problems for future power systems is provided. Future opportunities for adopting game-theoretic methodologies in the transition from legacy systems toward smart and intelligent grids are also discussed. In a nutshell, this article provides a comprehensive account of the application of game theory in smart grid systems tailored to the interdisciplinary characteristics of these systems that integrate components from power systems, networking, communications, and control.
TL;DR: In this article, the effect of aerosols on convective precipitation processes has been studied in the context of cloud resolution models (CRMs) and the results from (CRM) simulations.
Abstract: Aerosols are a critical.factor in the atmospheric hydrological cycle and radiation budget. As a major agent for clouds to form and a significant attenuator of solar radiation, aerosols affect climate in several ways. Current research suggests that aerosols have a major impact on the dynamics, microphysics, and electrification properties of continental mixed-phase convective clouds. In addition, high aerosol concentrations in urban environments could affect precipitation variability by providing a significant source of cloud condensation nuclei (CCN). Such pollution . effects on precipitation potentially have enormous climatic consequences both in terms of feedbacks involving the land surface via rainfall as well as the surface energy budget and changes in latent heat input to the atmosphere. Basically, aerosol concentrations can influence cloud droplet size distributions, the warm-rain process, the cold-rain process, cloud-top heights, the depth of the mixed-phase region, and the occurrence of lightning. Recently, many cloud resolution models (CRMs) have been used to examine the role of aerosols on mixed-phase convective clouds. These modeling studies have many differences in terms of model configuration (two- or three-dimensional), domain size, grid spacing (150-3000 m), microphysics (two-moment bulk, simple or sophisticated spectral-bin), turbulence (1st or 1.5 order turbulent kinetic energy (TKE)), radiation, lateral boundary conditions (i.e., closed, radiative open or cyclic), cases (isolated convection, tropical or midlatitude squall lines) and model integration time (e.g., 2.5 to 48 hours). Among these modeling studies, the most striking difference is that cumulative precipitation can either increase or decrease in response to higher concentrations of CCN. In this presentation, we review past efforts and summarize our current understanding of the effect of aerosols on convective precipitation processes. Specifically, this paper addresses the following topics: observational evidence of the effect of aerosols on precipitation processes, and results from (CRM) simulations. Note that this presentation is mainly based on a recent paper published in Geophy. Rev. (Tao et al. 2012).
Utrecht University1, University of Calgary2, University College London3, VU University Amsterdam4, Lund University5, Wake Forest University6, Radboud University Nijmegen7, University of Malaya8, Erasmus University Rotterdam9, Osaka University10, McMaster University11, Goethe University Frankfurt12, University of Tromsø13, Tufts University14, University of Edinburgh15, University of Virginia16, University of Miami17, Analytical Services18, Maastricht University19
TL;DR: The addition of common CIMT measurements to the Framingham Risk Score was associated with small improvement in 10-year risk prediction of first-time myocardial infarction or stroke, but this improvement is unlikely to be of clinical importance.
Abstract: Context: The evidence that measurement of the common carotid intima-media thickness (CIMT) improves the risk scores in prediction of the absolute risk of cardiovascular events is inconsistent. Objective: To determine whether common CIMT has added value in 10-year risk prediction of first-time myocardial infarctions or strokes, above that of the Framingham Risk Score. Data Sources: Relevant studies were identified through literature searches of databases (PubMed from 1950 to June 2012 and EMBASE from 1980 to June 2012) and expert opinion. Study Selection: Studies were included if participants were drawn from the general population, common CIMT was measured at baseline, and individuals were followed up for first-time myocardial infarction or stroke. Data Extraction: Individual data were combined into 1 data set and an individual participant data meta-analysis was performed on individuals without existing cardiovascular disease. Results: We included 14 population-based cohorts contributing data for 45 828 individuals. During a median follow-up of 11 years, 4007 first-time myocardial infarctions or strokes occurred. We first refitted the risk factors of the Framingham Risk Score and then extended the model with common CIMT measurements to estimate the absolute 10-year risks to develop a first-time myocardial infarction or stroke in both models. The C statistic of both models was similar (0.757; 95% CI, 0.749-0.764; and 0.759; 95% CI, 0.752-0.766). The net reclassification improvement with the addition of common CIMT was small (0.8%; 95% CI, 0.1%-1.6%). In those at intermediate risk, the net reclassification improvement was 3.6% in all individuals (95% CI, 2.7%-4.6%) and no differences between men and women. Conclusion: The addition of common CIMT measurements to the Framingham Risk Score was associated with small improvement in 10-year risk prediction of first-time myocardial infarction or stroke, but this improvement is unlikely to be of clinical importance.
TL;DR: In this paper, the authors compared intra-aortic balloon pump (IABP) and Impella 2.5 for percutaneous coronary intervention in patients with complex multivessel, or left main disease.
Abstract: Background—Although coronary artery bypass grafting is generally preferred in symptomatic patients with severe, complex multivessel, or left main disease, some patients present with clinical features that make coronary artery bypass grafting clinically unattractive. Percutaneous coronary intervention with hemodynamic support may be feasible for these patients. Currently, there is no systematic comparative evaluation of hemodynamic support devices for this indication. Methods and Results—We randomly assigned 452 symptomatic patients with complex 3-vessel disease or unprotected left main coronary artery disease and severely depressed left ventricular function to intra-aortic balloon pump (IABP) (n=226) or Impella 2.5 (n=226) support during nonemergent high-risk percutaneous coronary intervention. The primary end point was the 30-day incidence of major adverse events. A 90-day follow-up was required, as well, by protocol. Impella 2.5 provided superior hemodynamic support in comparison with IABP, with maximal...
TL;DR: This article systematically review the applications and recent progresses of RF for genomic data, including prediction and classification, variable selection, pathway analysis, genetic association and epistasis detection, and unsupervised learning.
University of Pennsylvania1, University of Miami2, University of Minnesota3, Baylor University Medical Center4, University of Illinois at Chicago5, University of Wisconsin-Madison6, Southern Illinois University Carbondale7, University of Texas Southwestern Medical Center8, University of Geneva9, Vita-Salute San Raffaele University10, University of Alberta11, University of California, San Francisco12, Northwestern University13, Harvard University14, Emory University15, University of Chicago16, Westmead Hospital17, Virginia Mason Medical Center18, Mayo Clinic19, University of Virginia20, Cornell University21, St. Vincent's Health System22
TL;DR: The CITR shows improvement in primary efficacy and safety outcomes of islet transplantation in recipients who received transplants in 2007–2010 compared with those in 1999–2006, with fewer islet infusions and adverse events per recipient.
Abstract: OBJECTIVE To describe trends of primary efficacy and safety outcomes of islet transplantation in type 1 diabetes recipients with severe hypoglycemia from the Collaborative Islet Transplant Registry (CITR) from 1999 to 2010. RESEARCH DESIGN AND METHODS A total of 677 islet transplant-alone or islet-after-kidney recipients with type 1 diabetes in the CITR were analyzed for five primary efficacy outcomes and overall safety to identify any differences by early (1999–2002), mid (2003–2006), or recent (2007–2010) transplant era based on annual follow-up to 5 years. RESULTS Insulin independence at 3 years after transplant improved from 27% in the early era (1999–2002, n = 214) to 37% in the mid (2003–2006, n = 255) and to 44% in the most recent era (2007–2010, n = 208; P = 0.006 for years-by-era; P = 0.01 for era alone). C-peptide ≥0.3 ng/mL, indicative of islet graft function, was retained longer in the most recent era ( P 1c and resolution of severe hypoglycemia exhibited enduring long-term effects. Fasting blood glucose stabilization also showed improvements in the most recent era. There were also modest reductions in the occurrence of adverse events. The islet reinfusion rate was lower: 48% by 1 year in 2007–2010 vs. 60–65% in 1999–2006 ( P P CONCLUSIONS The CITR shows improvement in primary efficacy and safety outcomes of islet transplantation in recipients who received transplants in 2007–2010 compared with those in 1999–2006, with fewer islet infusions and adverse events per recipient.
TL;DR: Nitrofurantoin, trimethoprim–sulfamethoxazole, fosfomycin, and pivmecillinam are considered first-line agents for cystitis, but fluoroquinolones should not be routine first- line choices for cysts.
Abstract: Nitrofurantoin, trimethoprim–sulfamethoxazole, fosfomycin, and pivmecillinam are considered first-line agents for cystitis. Fluoroquinolones should not be routine first-line choices for cystitis, although they are first-line empirical therapy for pyelonephritis.
TL;DR: In this paper, the authors identify an HSF1-regulated transcriptional program specific to highly malignant cells and distinct from heat shock, which supports oncogenic processes: cell-cycle regulation, signaling, metabolism, adhesion and translation.
TL;DR: The data suggest that pharmacological approaches targeting NATs can confer locus-specific gene upregulation effects and that inhibition of NATs leads to increases in glial-derived neurotrophic factor (GDNF) and ephrin receptor B2 (EPHB2) mRNA.
Abstract: The ability to specifically upregulate genes in vivo holds great therapeutic promise. Here we show that inhibition or degradation of natural antisense transcripts (NATs) by single-stranded oligonucleotides or siRNAs can transiently and reversibly upregulate locus-specific gene expression. Brain-derived neurotrophic factor (BDNF) is normally repressed by a conserved noncoding antisense RNA transcript, BDNF-AS. Inhibition of this transcript upregulates BDNF mRNA by two- to sevenfold, alters chromatin marks at the BDNF locus, leads to increased protein levels and induces neuronal outgrowth and differentiation both in vitro and in vivo. We also show that inhibition of NATs leads to increases in glial-derived neurotrophic factor (GDNF) and ephrin receptor B2 (EPHB2) mRNA. Our data suggest that pharmacological approaches targeting NATs can confer locus-specific gene upregulation effects.
University of California, Davis1, University of Connecticut2, Erasmus University Rotterdam3, University of California, San Francisco4, Johns Hopkins University School of Medicine5, Duke University6, Veterans Health Administration7, University of Toronto8, The Royal Marsden NHS Foundation Trust9, University of Miami10
TL;DR: AS for PCa offers an opportunity to limit intervention to patients who will likely benefit the most from radical treatment, and confers a low risk of disease-specific mortality in the short to intermediate term.
TL;DR: It is shown that loss of the Drosophila Toll receptor adaptor dSarm cell-autonomously suppresses Wallerian degeneration for weeks after axotomy, providing direct evidence that axons actively promote their own destruction after injury and identify dSARM/Sarm1 as a member of an ancient axon death signaling pathway.
Abstract: Axonal and synaptic degeneration is a hallmark of peripheral neuropathy, brain injury, and neurodegenerative disease. Axonal degeneration has been proposed to be mediated by an active autodestruction program, akin to apoptotic cell death; however, loss-of-function mutations capable of potently blocking axon self-destruction have not been described. Here, we show that loss of the Drosophila Toll receptor adaptor dSarm (sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously suppresses Wallerian degeneration for weeks after axotomy. Severed mouse Sarm1 null axons exhibit remarkable long-term survival both in vivo and in vitro, indicating that Sarm1 prodegenerative signaling is conserved in mammals. Our results provide direct evidence that axons actively promote their own destruction after injury and identify dSarm/Sarm1 as a member of an ancient axon death signaling pathway.