Showing papers by "University of Vermont published in 2013"
TL;DR: Ibrutinib was associated with a high frequency of durable remissions in patients with relapsed or refractory CLL and small lymphocytic lymphoma, including patients with high-risk genetic lesions.
Abstract: Background The treatment of relapsed chronic lymphocytic leukemia (CLL) has resulted in few durable remissions. Bruton's tyrosine kinase (BTK), an essential component of B-cell–receptor signaling, mediates interactions with the tumor microenvironment and promotes the survival and proliferation of CLL cells. Methods We conducted a phase 1b–2 multicenter study to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ibrutinib (PCI-32765), a first-in-class, oral covalent inhibitor of BTK designed for treatment of B-cell cancers, in patients with relapsed or refractory CLL or small lymphocytic lymphoma. A total of 85 patients, the majority of whom were considered to have high-risk disease, received ibrutinib orally once daily; 51 received 420 mg, and 34 received 840 mg. Results Toxic effects were predominantly grade 1 or 2 and included transient diarrhea, fatigue, and upper respiratory tract infection; thus, patients could receive extended treatment with minimal hematologic toxic effects. The...
1,988 citations
National University of Río Negro1, University of Würzburg2, Rutgers University3, National University of Comahue4, Swedish University of Agricultural Sciences5, Commonwealth Scientific and Industrial Research Organisation6, University of California, Berkeley7, Naturalis8, University of Leeds9, University of Calgary10, Hebrew University of Jerusalem11, ETH Zurich12, Lüneburg University13, National University of Tucumán14, Federal University of Ceará15, Federal University of Bahia16, Plant & Food Research17, Michigan State University18, Agriculture and Agri-Food Canada19, The Nature Conservancy20, University of Göttingen21, University of Queensland22, Cornell University23, University of Reading24, Stockholm University25, University of Vermont26, Lund University27, University of Bern28, University of Koblenz and Landau29, Jagiellonian University30, Universidad de las Américas Puebla31, University of California, Davis32
TL;DR: Overall, wild insects pollinated crops more effectively; an increase in wild insect visitation enhanced fruit set by twice as much as an equivalent increase in honey bee visitation.
Abstract: The diversity and abundance of wild insect pollinators have declined in many agricultural landscapes. Whether such declines reduce crop yields, or are mitigated by managed pollinators such as honey bees, is unclear. We found universally positive associations of fruit set with flower visitation by wild insects in 41 crop systems worldwide. In contrast, fruit set increased significantly with flower visitation by honey bees in only 14% of the systems surveyed. Overall, wild insects pollinated crops more effectively; an increase in wild insect visitation enhanced fruit set by twice as much as an equivalent increase in honey bee visitation. Visitation by wild insects and honey bees promoted fruit set independently, so pollination by managed honey bees supplemented, rather than substituted for, pollination by wild insects. Our results suggest that new practices for integrated management of both honey bees and diverse wild insect assemblages will enhance global crop yields.
1,881 citations
University of St Andrews1, University of Oldenburg2, Natural History Museum3, Naturalis4, Centre national de la recherche scientifique5, Michigan State University6, University of Lausanne7, University of Wyoming8, Queen Mary University of London9, University of Sheffield10, International Institute for Applied Systems Analysis11, University of Oslo12, University of Vienna13, University of Vermont14, University of East Anglia15, Spanish National Research Council16, University of Cambridge17, University of Konstanz18, University of Zurich19, Royal Botanic Garden Edinburgh20, Harvard University21, Autonomous University of Madrid22, Swiss Federal Institute of Aquatic Science and Technology23, Boston University24, Max Planck Society25, University of Neuchâtel26, University of North Carolina at Chapel Hill27, Lehigh University28, American Museum of Natural History29, University of Montpellier30, University of Liverpool31, Jagiellonian University32, Uppsala University33, German Primate Center34
TL;DR: A perspective on the context and evolutionary significance of hybridization during speciation is offered, highlighting issues of current interest and debate and suggesting that the Dobzhansky–Muller model of hybrid incompatibilities requires a broader interpretation.
Abstract: Hybridization has many and varied impacts on the process of speciation. Hybridization may slow or reverse differentiation by allowing gene flow and recombination. It may accelerate speciation via adaptive introgression or cause near-instantaneous speciation by allopolyploidization. It may have multiple effects at different stages and in different spatial contexts within a single speciation event. We offer a perspective on the context and evolutionary significance of hybridization during speciation, highlighting issues of current interest and debate. In secondary contact zones, it is uncertain if barriers to gene flow will be strengthened or broken down due to recombination and gene flow. Theory and empirical evidence suggest the latter is more likely, except within and around strongly selected genomic regions. Hybridization may contribute to speciation through the formation of new hybrid taxa, whereas introgression of a few loci may promote adaptive divergence and so facilitate speciation. Gene regulatory networks, epigenetic effects and the evolution of selfish genetic material in the genome suggest that the Dobzhansky-Muller model of hybrid incompatibilities requires a broader interpretation. Finally, although the incidence of reinforcement remains uncertain, this and other interactions in areas of sympatry may have knock-on effects on speciation both within and outside regions of hybridization.
1,715 citations
University of Pittsburgh1, Veterans Health Administration2, University of Washington3, Emory University4, Baylor College of Medicine5, Icahn School of Medicine at Mount Sinai6, Yale University7, University of Maryland, Baltimore8, University of Vermont9, University of California, Los Angeles10, University of South Carolina11, National Institutes of Health12
TL;DR: Investigating whether HIV is associated with an increased risk of acute myocardial infarction after adjustment for all standard Framingham risk factors among a large cohort of HIV-positive and demographically and behaviorally similar uninfected veterans in care found infections with HIV are associated with a 50% increased risk beyond that explained by recognized risk factors.
Abstract: Importance Whether people infected with human immunodeficiency virus (HIV) are at an increased risk of acute myocardial infarction (AMI) compared with uninfected people is not clear. Without demographically and behaviorally similar uninfected comparators and without uniformly measured clinical data on risk factors and fatal and nonfatal AMI events, any potential association between HIV status and AMI may be confounded. Objective To investigate whether HIV is associated with an increased risk of AMI after adjustment for all standard Framingham risk factors among a large cohort of HIV-positive and demographically and behaviorally similar (ie, similar prevalence of smoking, alcohol, and cocaine use) uninfected veterans in care. Design and Setting Participants in the Veterans Aging Cohort Study Virtual Cohort from April 1, 2003, through December 31, 2009. Participants After eliminating those with baseline cardiovascular disease, we analyzed data on HIV status, age, sex, race/ethnicity, hypertension, diabetes mellitus, dyslipidemia, smoking, hepatitis C infection, body mass index, renal disease, anemia, substance use, CD4 cell count, HIV-1 RNA, antiretroviral therapy, and incidence of AMI. Main Outcome Measure Acute myocardial infarction. Results We analyzed data on 82 459 participants. During a median follow-up of 5.9 years, there were 871 AMI events. Across 3 decades of age, the mean (95% CI) AMI events per 1000 person-years was consistently and significantly higher for HIV-positive compared with uninfected veterans: for those aged 40 to 49 years, 2.0 (1.6-2.4) vs 1.5 (1.3-1.7); for those aged 50 to 59 years, 3.9 (3.3-4.5) vs 2.2 (1.9-2.5); and for those aged 60 to 69 years, 5.0 (3.8-6.7) vs 3.3 (2.6-4.2) (P Conclusions and Relevance Infection with HIV is associated with a 50% increased risk of AMI beyond that explained by recognized risk factors.
1,100 citations
TL;DR: Ibrutinib, a novel BTK-targeting inhibitor, is well tolerated, with substantial activity across B-cell histologies, consistent with the irreversible mechanism.
Abstract: Purpose Survival and progression of mature B-cell malignancies depend on signals from the B-cell antigen receptor, and Bruton tyrosine kinase (BTK) is a critical signaling kinase in this pathway. We evaluated ibrutinib (PCI-32765), a small-molecule irreversible inhibitor of BTK, in patients with B-cell malignancies. Patients and Methods Patients with relapsed or refractory B-cell lymphoma and chronic lymphocytic leukemia received escalating oral doses of ibrutinib. Two schedules were evaluated: one, 28 days on, 7 days off; and two, once-daily continuous dosing. Occupancy of BTK by ibrutinib in peripheral blood was monitored using a fluorescent affinity probe. Dose escalation proceeded until either the maximumtolerated dose (MTD) was achieved or, in the absence of MTD, until three dose levels above full BTK occupancy by ibrutinib. Response was evaluated every two cycles. Results Fifty-six patients with a variety of B-cell malignancies were treated over seven cohorts. Most adverse events were grade 1 and 2 in severity and self-limited. Dose-limiting events were not observed, even with prolonged dosing. Full occupancy of the BTK active site occurred at 2.5 mg/kg per day, and dose escalation continued to 12.5 mg/kg per day without reaching MTD. Pharmacokinetic data indicated rapid absorption and elimination, yet BTK occupancy was maintained for at least 24 hours, consistent with the irreversible mechanism. Objective response rate in 50 evaluable patients was 60%, including complete response of 16%. Median progression-free survival in all patients was 13.6 months. Conclusion Ibrutinib, a novel BTK-targeting inhibitor, is well tolerated, with substantial activity across B-cell histologies. J Clin Oncol 31:88-94. © 2012 by American Society of Clinical Oncology
1,020 citations
TL;DR: Among patients with HFPEF, phosphodiesterase-5 inhibition with administration of sildenafil for 24 weeks, compared with placebo, did not result in significant improvement in exercise capacity or clinical status.
Abstract: Importance Studies in experimental and human heart failure suggest that phosphodiesterase-5 inhibitors may enhance cardiovascular function and thus exercise capacity in heart failure with preserved ejection fraction (HFPEF). Objective To determine the effect of the phosphodiesterase-5 inhibitor sildenafil compared with placebo on exercise capacity and clinical status in HFPEF. Design Multicenter, double-blind, placebo-controlled, parallel-group, randomized clinical trial of 216 stable outpatients with HF, ejection fraction ≥50%, elevated N-terminal brain-type natriuretic peptide or elevated invasively measured filling pressures, and reduced exercise capacity. Participants were randomized from October 2008 through February 2012 at 26 centers in North America. Follow-up was through August 30, 2012. Interventions Sildenafil (n = 113) or placebo (n = 103) administered orally at 20 mg, 3 times daily for 12 weeks, followed by 60 mg, 3 times daily for 12 weeks. Main Outcome Measures Primary end point was change in peak oxygen consumption after 24 weeks of therapy. Secondary end points included change in 6-minute walk distance and a hierarchical composite clinical status score (range, 1-n, a higher value indicates better status; expected value with no treatment effect, 95) based on time to death, time to cardiovascular or cardiorenal hospitalization, and change in quality of life for participants without cardiovascular or cardiorenal hospitalization at 24 weeks. Results Median age was 69 years, and 48% of patients were women. At baseline, median peak oxygen consumption (11.7 mL/kg/min) and 6-minute walk distance (308 m) were reduced. The median E/e′ (16), left atrial volume index (44 mL/m 2 ), and pulmonary artery systolic pressure (41 mm Hg) were consistent with chronically elevated left ventricular filling pressures. At 24 weeks, median (IQR) changes in peak oxygen consumption (mL/kg/min) in patients who received placebo (−0.20 [IQR, −0.70 to 1.00]) or sildenafil (−0.20 [IQR, −1.70 to 1.11]) were not significantly different (P = .90) in analyses in which patients with missing week-24 data were excluded, and in sensitivity analysis based on intention to treat with multiple imputation for missing values (mean between-group difference, 0.01 mL/kg/min, [95% CI, −0.60 to 0.61]). The mean clinical status rank score was not significantly different at 24 weeks between placebo (95.8) and sildenafil (94.2) (P = .85). Changes in 6-minute walk distance at 24 weeks in patients who received placebo (15.0 m [IQR, −26.0 to 45.0]) or sildenafil (5.0 m [IQR, −37.0 to 55.0]; P = .92) were also not significantly different. Adverse events occurred in 78 placebo patients (76%) and 90 sildenafil patients (80%). Serious adverse events occurred in 16 placebo patients (16%) and 25 sildenafil patients (22%). Conclusion and Relevance Among patients with HFPEF, phosphodiesterase-5 inhibition with administration of sildenafil for 24 weeks, compared with placebo, did not result in significant improvement in exercise capacity or clinical status. Trial Registration clinicaltrials.gov Identifier: NCT00763867
1,003 citations
TL;DR: Axillary dissection could be avoided in patients with early breast cancer and limited sentinel-node involvement, thus eliminating complications of axillary surgery with no adverse effect on survival.
Abstract: Summary Background For patients with breast cancer and metastases in the sentinel nodes, axillary dissection has been standard treatment. However, for patients with limited sentinel-node involvement, axillary dissection might be overtreatment. We designed IBCSG trial 23–01 to determine whether no axillary dissection was non-inferior to axillary dissection in patients with one or more micrometastatic (≤2 mm) sentinel nodes and tumour of maximum 5 cm. Methods In this multicentre, randomised, non-inferiority, phase 3 trial, patients were eligible if they had clinically non-palpable axillary lymph node(s) and a primary tumour of 5 cm or less and who, after sentinel-node biopsy, had one or more micrometastatic (≤2 mm) sentinel lymph nodes with no extracapsular extension. Patients were randomly assigned (in a 1:1 ratio) to either undergo axillary dissection or not to undergo axillary dissection. Randomisation was stratified by centre and menopausal status. Treatment assignment was not masked. The primary endpoint was disease-free survival. Non-inferiority was defined as a hazard ratio (HR) of less than 1·25 for no axillary dissection versus axillary dissection. The analysis was by intention to treat. Per protocol, disease and survival information continues to be collected yearly. This trial is registered with ClinicalTrials.gov, NCT00072293. Findings Between April 1, 2001, and Feb 28, 2010, 465 patients were randomly assigned to axillary dissection and 469 to no axillary dissection. After the exclusion of three patients, 464 patients were in the axillary dissection group and 467 patients were in the no axillary dissection group. After a median follow-up of 5·0 (IQR 3·6–7·3) years, we recorded 69 disease-free survival events in the axillary dissection group and 55 events in the no axillary dissection group. Breast-cancer-related events were recorded in 48 patients in the axillary dissection group and 47 in the no axillary dissection group (ten local recurrences in the axillary dissection group and eight in the no axillary dissection group; three and nine contralateral breast cancers; one and five regional recurrences; and 34 and 25 distant relapses). Other non-breast cancer events were recorded in 21 patients in the axillary dissection group and eight in the no axillary dissection group (20 and six second non-breast malignancies; and one and two deaths not due to a cancer event). 5-year disease-free survival was 87·8% (95% CI 84·4–91·2) in the group without axillary dissection and 84·4% (80·7–88·1) in the group with axillary dissection (log-rank p=0·16; HR for no axillary dissection vs axillary dissection was 0·78, 95% CI 0·55–1·11, non-inferiority p=0·0042). Patients with reported long-term surgical events (grade 3–4) included one sensory neuropathy (grade 3), three lymphoedema (two grade 3 and one grade 4), and three motor neuropathy (grade 3), all in the group that underwent axillary dissection, and one grade 3 motor neuropathy in the group without axillary dissection. One serious adverse event was reported, a postoperative infection in the axilla in the group with axillary dissection. Interpretation Axillary dissection could be avoided in patients with early breast cancer and limited sentinel-node involvement, thus eliminating complications of axillary surgery with no adverse effect on survival. Funding None.
989 citations
Lincoln Park Zoo1, University of Maryland, College Park2, University of California, Davis3, University of Vermont4, Rutgers University5, Swedish University of Agricultural Sciences6, Lüneburg University7, University of Queensland8, University of Pretoria9, Commonwealth Scientific and Industrial Research Organisation10, Cornell University11, University of Göttingen12, Simon Fraser University13, University of Wisconsin-Madison14, National Scientific and Technical Research Council15, University of Würzburg16, Michigan State University17, University of Texas at Austin18, Hebrew University of Jerusalem19, University of Reading20, Lund University21, Federal University of Bahia22, University of California, Berkeley23
TL;DR: This synthesis reveals that pollinator persistence will depend on both the maintenance of high-quality habitats around farms and on local management practices that may offset impacts of intensive monoculture agriculture.
Abstract: Bees provide essential pollination services that are potentially affected both by local farm management and the surrounding landscape. To better understand these different factors, we modelled the relative effects of landscape composition (nesting and floral resources within foraging distances), landscape configuration (patch shape, interpatch connectivity and habitat aggregation) and farm management (organic vs. conventional and local-scale field diversity), and their interactions, on wild bee abundance and richness for 39 crop systems globally. Bee abundance and richness were higher in diversified and organic fields and in landscapes comprising more high-quality habitats; bee richness on conventional fields with low diversity benefited most from high-quality surrounding land cover. Landscape configuration effects were weak. Bee responses varied slightly by biome. Our synthesis reveals that pollinator persistence will depend on both the maintenance of high-quality habitats around farms and on local management practices that may offset impacts of intensive monoculture agriculture.
904 citations
TL;DR: Emerging evidence suggests that exploiting epithelial targets with nonabsorbable serotonergic agents could provide safe and effective therapies, and this work provides an overview of theseserotonergic actions and treatment strategies.
Abstract: Serotonin (5-HT) has been recognized for decades as an important signalling molecule in the gut, but it is still revealing its secrets. Novel gastrointestinal functions of 5-HT continue to be discovered, as well as distant actions of gut-derived 5-HT, and we are learning how 5-HT signalling is altered in gastrointestinal disorders. Conventional functions of 5-HT involving intrinsic reflexes include stimulation of propulsive and segmentation motility patterns, epithelial secretion and vasodilation. Activation of extrinsic vagal and spinal afferent fibres results in slowed gastric emptying, pancreatic secretion, satiation, pain and discomfort, as well as nausea and vomiting. Within the gut, 5-HT also exerts nonconventional actions such as promoting inflammation and serving as a trophic factor to promote the development and maintenance of neurons and interstitial cells of Cajal. Platelet 5-HT, originating in the gut, promotes haemostasis, influences bone development and serves many other functions. 5-HT3 receptor antagonists and 5-HT4 receptor agonists have been used to treat functional disorders with diarrhoea or constipation, respectively, and the synthetic enzyme tryptophan hydroxylase has also been targeted. Emerging evidence suggests that exploiting epithelial targets with nonabsorbable serotonergic agents could provide safe and effective therapies. We provide an overview of these serotonergic actions and treatment strategies.
728 citations
TL;DR: Individually optimised energy supplementation with SPN starting 4 days after ICU admission could reduce nosocomial infections and should be considered as a strategy to improve clinical outcome in patients in the ICU for whom EN is insufficient.
627 citations
Chinese Ministry of Education1, Harvard University2, University of Hong Kong3, Concord Repatriation General Hospital4, Harbin Medical University5, University of Ulsan6, Yonsei University7, Nippon Medical School8, Nara Medical University9, Iwate Medical University10, Ajou University11, University of Vermont12, Mayo Clinic13, University of Pittsburgh14, St. Jude Medical15, Icahn School of Medicine at Mount Sinai16
TL;DR: Optical coherence tomography is a promising modality for identifying OCT-erosion and OCT-CN in vivo in patients with acute coronary syndrome and is more common in older patients.
TL;DR: It is likely that knowledge gained on how inflammation affects health in HIV disease could have implications for the understanding of other chronic inflammatory diseases and the biology of aging.
TL;DR: These guidelines are inclusive, and not prescriptive, and intended for the use of all practitioners, health care workers, and patients who desire information about the management of the conditions addressed by the topics covered in these guidelines.
Abstract: The American Society of Colon and Rectal Surgeons is dedicated to assuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus. The Standards Committee is composed of Society members who are chosen because they have demonstrated expertise in the specialty of colon and rectal surgery. This Committee was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus. This is accompanied by developing Clinical Practice Guidelines based on the best available evidence. These guidelines are inclusive, and not prescriptive. Their purpose is to provide information on which decisions can be made, rather than dictate a specific form of treatment. These guidelines are intended for the use of all practitioners, health care workers, and patients who desire information about the management of the conditions addressed by the topics covered in these guidelines. It should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all of the circumstances presented by the individual patient.
TL;DR: The results show how social media may potentially be used to estimate real-time levels and changes in population-scale measures such as obesity rates.
Abstract: We conduct a detailed investigation of correlations between real-time expressions of individuals made across the United States and a wide range of emotional, geographic, demographic, and health characteristics. We do so by combining (1) a massive, geo-tagged data set comprising over 80 million words generated in 2011 on the social network service Twitter and (2) annually-surveyed characteristics of all 50 states and close to 400 urban populations. Among many results, we generate taxonomies of states and cities based on their similarities in word use; estimate the happiness levels of states and cities; correlate highly-resolved demographic characteristics with happiness levels; and connect word choice and message length with urban characteristics such as education levels and obesity rates. Our results show how social media may potentially be used to estimate real-time levels and changes in population-scale measures such as obesity rates.
University of Sydney1, University of Michigan2, Cardiff University3, Max Planck Society4, Maine Medical Center5, University of Vermont6, Children's Hospital of Eastern Ontario7, University of Texas MD Anderson Cancer Center8, Duke University9, University of California, San Francisco10, Ohio State University11, VU University Medical Center12, The Dartmouth Institute for Health Policy and Clinical Practice13
TL;DR: Current “best practices” in communication of evidence-based numeric outcomes for developers of patient decision aids (PtDAs) and other health communication tools are summarized.
Abstract: Making evidence-based decisions often requires comparison of two or more options. Research-based evidence may exist which quantifies how likely the outcomes are for each option. Understanding these numeric estimates improves patients’ risk perception and leads to better informed decision making. This paper summarises current “best practices” in communication of evidence-based numeric outcomes for developers of patient decision aids (PtDAs) and other health communication tools. An expert consensus group of fourteen researchers from North America, Europe, and Australasia identified eleven main issues in risk communication. Two experts for each issue wrote a “state of the art” summary of best evidence, drawing on the PtDA, health, psychological, and broader scientific literature. In addition, commonly used terms were defined and a set of guiding principles and key messages derived from the results. The eleven key components of risk communication were: 1) Presenting the chance an event will occur; 2) Presenting changes in numeric outcomes; 3) Outcome estimates for test and screening decisions; 4) Numeric estimates in context and with evaluative labels; 5) Conveying uncertainty; 6) Visual formats; 7) Tailoring estimates; 8) Formats for understanding outcomes over time; 9) Narrative methods for conveying the chance of an event; 10) Important skills for understanding numerical estimates; and 11) Interactive web-based formats. Guiding principles from the evidence summaries advise that risk communication formats should reflect the task required of the user, should always define a relevant reference class (i.e., denominator) over time, should aim to use a consistent format throughout documents, should avoid “1 in x” formats and variable denominators, consider the magnitude of numbers used and the possibility of format bias, and should take into account the numeracy and graph literacy of the audience. A substantial and rapidly expanding evidence base exists for risk communication. Developers of tools to facilitate evidence-based decision making should apply these principles to improve the quality of risk communication in practice.
01 Jan 2013
TL;DR: Key methods include rarefaction, extrapolation, and non-parametric estimation of the asymptote of species richness, which control for sampling effects in biodiversity data and can be applied to many important questions in ecology.
Abstract: This article reviews modern statistical approaches to estimating species diversity and biotic similarity from empirical samples of species abundance or incidence Key methods include rarefaction, extrapolation, and non-parametric estimation of the asymptote of species richness Hill numbers are presented as unifying indices of species diversity that take into account the relative abundance of different species Species richness estimators, Hill numbers, and measures of biotic similarity can be extended to account for phylogenetic, taxonomic, and functional diversity of biological assemblages These statistical methods control for sampling effects in biodiversity data and can be applied to many important questions in ecology
International Agency for Research on Cancer1, National Health Service2, University of Oxford3, Imperial College London4, University of Surrey5, Royal Surrey County Hospital6, Erasmus University Rotterdam7, Leeds Teaching Hospitals NHS Trust8, University of Dundee9, Stavanger University Hospital10, University of Zagreb11, Mario Negri Institute for Pharmacological Research12, Karolinska Institutet13, German Cancer Research Center14, University of Oslo15, Queen Mary University of London16, Peking Union Medical College17, American Cancer Society18, University of Amsterdam19, FH Joanneum20, University of Burgundy21, University of Ljubljana22, University of Vermont23, National Cancer Research Institute24, University of Caen Lower Normandy25, Catholic University of Korea26, St George's Hospital27, University of Latvia28, Oregon Health & Science University29, University of Copenhagen30, GlaxoSmithKline31, Centers for Disease Control and Prevention32, University of North Carolina at Chapel Hill33, Ruhr University Bochum34, Institute of Oncology Ljubljana35, Cancer Care Ontario36, University of Toronto37, University of Coimbra38, University of Chicago39, University Hospitals Coventry and Warwickshire NHS Trust40, Charles University in Prague41, Katholieke Universiteit Leuven42, University of Miami43, Niigata University44, Memorial Sloan Kettering Cancer Center45, Flinders University46
TL;DR: An overview of the principles, recommendations and standards in the guidelines for quality assurance in CRC screening and diagnosis are presented in journal format in an open-access Supplement of Endoscopy.
Abstract: Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010. They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines.
University of Chicago1, Mayo Clinic2, University of Texas MD Anderson Cancer Center3, University Hospital of Wales4, Mount Sinai Hospital5, Columbia University Medical Center6, University of Vermont7, Brigham and Women's Hospital8, University of British Columbia9, University of Pittsburgh10, University of Massachusetts System11, University of Pennsylvania12, Cedars-Sinai Medical Center13, Duke University14, Memorial Sloan Kettering Cancer Center15, University of Virginia16
TL;DR: These guidelines are meant to be a practical reference for the pathologist and recommend that immunohistochemical markers have either sensitivity or specificity greater than 80% for the lesions in question.
Abstract: Context.—Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose. Objective.—To provide updated practical guidelines for the pathologic diagnosis of MM. Data Sources.—Pathologists involved in the International Mesothelioma Interest Group and others with an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks. Conclusions.—There was consensus opinion regarding (1) distinction of benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiation of epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid mesothelioma, (7) use of molecular markers in the diagnosis of MM,...
TL;DR: This article presents a systematic approach to ecosystem service flow quantification as a class of agent-based models termed “Service Path Attribution Networks” (SPANs), developed as part of the Artificial Intelligence for Ecosystem Services (ARIES) project.
Abstract: Recent ecosystem services research has highlighted the importance of spatial connectivity between ecosystems and their beneficiaries. Despite this need, a systematic approach to ecosystem service flow quantification has not yet emerged. In this article, we present such an approach, which we formalize as a class of agent-based models termed “Service Path Attribution Networks” (SPANs). These models, developed as part of the Artificial Intelligence for Ecosystem Services (ARIES) project, expand on ecosystem services classification terminology introduced by other authors. Conceptual elements needed to support flow modeling include a service's rivalness, its flow routing type (e.g., through hydrologic or transportation networks, lines of sight, or other approaches), and whether the benefit is supplied by an ecosystem's provision of a beneficial flow to people or by absorption of a detrimental flow before it reaches them. We describe our implementation of the SPAN framework for five ecosystem services and discuss how to generalize the approach to additional services. SPAN model outputs include maps of ecosystem service provision, use, depletion, and flows under theoretical, possible, actual, inaccessible, and blocked conditions. We highlight how these different ecosystem service flow maps could be used to support various types of decision making for conservation and resource management planning.
Mayo Clinic1, Duke University2, Harvard University3, Hennepin County Medical Center4, University of Utah5, University of Vermont6, Tufts University7, Université de Montréal8, Cleveland Clinic9, Emory University10, Baylor College of Medicine11, Thomas Jefferson University12, University of Pennsylvania13, Morehouse School of Medicine14, Washington University in St. Louis15, National Institutes of Health16
TL;DR: In participants with acute heart failure and renal dysfunction, neitherLow-dose dopamine nor low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy.
Abstract: RESULTS Compared with placebo, low-dose dopamine had no significant effect on 72-hour cumulative urine volume (dopamine, 8524 mL; 95% CI, 7917-9131 vs placebo, 8296 mL; 95% CI, 7762-8830 ; difference, 229 mL; 95% CI, −714 to 1171 mL; P = .59) or on the change in cystatin C level (dopamine, 0.12 mg/L; 95% CI, 0.06-0.18 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, 0.01; 95% CI, −0.08 to 0.10; P = .72). Similarly, low-dose nesiritide had no significant effect on 72-hour cumulative urine volume (nesiritide, 8574 mL; 95% CI, 8014-9134 vs placebo, 8296mL; 95% CI, 7762-8830; difference, 279 mL; 95% CI, −618 to 1176 mL; P = .49) or on the change in cystatin C level (nesiritide, 0.07 mg/L; 95% CI, 0.01-0.13 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, −0.04; 95% CI, −0.13 to 0.05; P = .36). Compared with placebo, there was no effect of low-dose dopamine or nesiritide on secondary end points reflective of decongestion, renal function, or clinical outcomes.
Radboud University Nijmegen1, Erasmus University Rotterdam2, Boğaziçi University3, University of Manchester4, Autonomous University of Barcelona5, University of Vermont6, Versailles Saint-Quentin-en-Yvelines University7, National Autonomous University of Mexico8, Autonomous University of Madrid9, Rensselaer Polytechnic Institute10, McGill University11, National University of Costa Rica12, Universidade Federal Rural do Rio de Janeiro13, Institut de recherche pour le développement14, Estácio S.A.15, University of California, Berkeley16, Ikerbasque17, University of Cambridge18, University of Valle19, University of Oxford20, Norwegian University of Life Sciences21
TL;DR: In this paper, the suitability of payments for ecosystem services and the most important challenges they face are discussed, while over-reliance on payments as win-win solutions might lead to ineffective outcomes.
Abstract: In this commentary we critically discuss the suitability of payments for ecosystem services and the most important challenges they face. While such instruments can play a role in improving environmental governance, we argue that over-reliance on payments as win-win solutions might lead to ineffective outcomes, similar to earlier experience with integrated conservation and development projects. Our objective is to raise awareness, particularly among policy makers and practitioners, about the limitations of such instruments and to encourage a dialogue about the policy contexts in which they might be appropriate.
TL;DR: It is demonstrated for the first time to the authors' knowledge that dose-intensive consolidation for PCNSL is feasible in the multicenter setting and yields rates of PFS and OS at least comparable to those of regimens involving WBRT.
Abstract: Purpose Concerns regarding neurocognitive toxicity of whole-brain radiotherapy (WBRT) have motivated development of alternative, dose-intensive chemotherapeutic strategies as consolidation in primary CNS lymphoma (PCNSL). We performed a multicenter study of high-dose consolidation, without WBRT, in PCNSL. Objectives were to determine: one, rate of complete response (CR) after remission induction therapy with methotrexate, temozolomide, and rituximab (MT-R); two, feasibility of a two-step approach using high-dose consolidation with etoposide plus cytarabine (EA); three, progression-free survival (PFS); and four, correlation between clinical and molecular prognostic factors and outcome. Patients and Methods Forty-four patients with newly diagnosed PCNSL were treated with induction MT-R, and patients who achieved CR received EA consolidation. We performed a prospective analysis of molecular prognostic biomarkers in PCNSL in the setting of a clinical trial. Results The rate of CR to MT-R was 66%. The overall 2-year PFS was 0.57, with median follow-up of 4.9 years. The 2-year time to progression was 0.59, and for patients who completed consolidation, it was 0.77. Patients age 60 years did as well as younger patients, and the most significant clinical prognostic variable was treatment delay. High BCL6 expression correlated with shorter survival. Conclusion CALGB 50202 demonstrates for the first time to our knowledge that dose-intensive consolidation for PCNSL is feasible in the multicenter setting and yields rates of PFS and OS at least comparable to those of regimens involving WBRT. On the basis of these encouraging results, an intergroup study has been activated comparing EA consolidation with myeloablative chemotherapy in this randomized trial in PCNSL, in which neither arm involves WBRT. J Clin Oncol 31:3061-3068. © 2013 by American Society of Clinical Oncology
TL;DR: Systemic MSC administration appears to be safe in patients with moderate to severe COPD and provides a basis for subsequent cell therapy investigations.
TL;DR: R-MPV combined with consolidation rdWBRT and cytarabine is associated with high response rates, long-term disease control, and minimal neurotoxicity in primary CNS lymphoma.
Abstract: Purpose A multicenter phase II study was conducted to assess the efficacy of rituximab, methotrexate, procarbazine, and vincristine (R-MPV) followed by consolidation reduced-dose whole-brain radiotherapy (rdWBRT) and cytarabine in primary CNS lymphoma. Patients and Methods Patients received induction chemotherapy with R-MPV (five to seven cycles); those achieving a complete response (CR) received rdWBRT (23.4 Gy), and otherwise, standard WBRT was offered (45 Gy). Consolidation cytarabine was given after the radiotherapy. The primary end point was 2-year progression-free survival (PFS) in patients receiving rdWBRT. Exploratory end points included prospective neuropsychological evaluation, analysis of magnetic resonance imaging (MRI) white matter changes using the Fazekas scale, and evaluation of the apparent diffusion coefficient (ADC) as a prognostic factor. Results Fifty-two patients were enrolled, with median age of 60 years (range, 30 to 79 years) and median Karnofsky performance score of 70 (range, 50...
TL;DR: This work discusses what is known about the human health implications of changes in the structure and function of natural systems and proposes that these changes are affecting human health in a variety of important ways.
Abstract: Human activity is rapidly transforming most of Earth’s natural systems How this transformation is impacting human health, whose health is at greatest risk, and the magnitude of the associated disease burden are relatively new subjects within the field of environmental health We discuss what is known about the human health implications of changes in the structure and function of natural systems and propose that these changes are affecting human health in a variety of important waysWe identify several gaps and limitations in the research that has been done to date and propose a more systematic and comprehensive approach to applied research in this field Such efforts could lead to a more robust understanding of the human health impacts of accelerating environmental change and inform decision making in the land-use planning, environmental conservation, and public health policy realms global change | ecosystem services | ecology | planetary boundaries | ecological footprint
National Institutes of Health1, University of California, Davis2, University of California3, Georgetown University4, Hokkaido University5, National University of Costa Rica6, Nagasaki University7, University of Vermont8, Center for Disease Dynamics, Economics & Policy9, University of Florida10, Emory University11, Harvard University12, Johns Hopkins University13, QIMR Berghofer Medical Research Institute14, University of Oxford15, Columbia University16, Princeton University17, University of Notre Dame18, Imperial College London19, University of London20, Durham University21, North Carolina State University22, University of Southampton23
TL;DR: In this article, a bibliography of 325 publications from 1970 through 2010 that included at least one mathematical model of mosquito-borne pathogen transmission and then used a 79-part questionnaire to classify each of the associated models according to its biological assumptions.
Abstract: Mathematical models of mosquito-borne pathogen transmission originated in the early twentieth century to provide insights into how to most effectively combat malaria. The foundations of the Ross–Macdonald theory were established by 1970. Since then, there has been a growing interest in reducing the public health burden of mosquito-borne pathogens and an expanding use of models to guide their control. To assess how theory has changed to confront evolving public health challenges, we compiled a bibliography of 325 publications from 1970 through 2010 that included at least one mathematical model of mosquito-borne pathogen transmission and then used a 79-part questionnaire to classify each of 388 associated models according to its biological assumptions. As a composite measure to interpret the multidimensional results of our survey, we assigned a numerical value to each model that measured its similarity to 15 core assumptions of the Ross–Macdonald model. Although the analysis illustrated a growing acknowledgement of geographical, ecological and epidemiological complexities in modelling transmission, most models during the past 40 years closely resemble the Ross–Macdonald model. Modern theory would benefit from an expansion around the concepts of heterogeneous mosquito biting, poorly mixed mosquito-host encounters, spatial heterogeneity and temporal variation in the transmission process.
TL;DR: In patients with CAD, normal weight with central obesity is associated with the highest risk of mortality [corrected].
University of Florida1, University of Alaska Fairbanks2, University of Vermont3, Max Planck Society4, Bowdoin College5, CSIRO Marine and Atmospheric Research6, Florida State University7, Lund University8, Centre national de la recherche scientifique9, Idaho State University10, University of California11, United States Geological Survey12, Oak Ridge National Laboratory13, Stockholm University14, Argonne National Laboratory15, Lawrence Berkeley National Laboratory16, National Center for Atmospheric Research17, National Park Service18, Cooperative Institute for Research in Environmental Sciences19, University of Oxford20, University of Guelph21, Los Alamos National Laboratory22
TL;DR: In this article, the authors used a survey to quantify variability in the perception of the vulnerability of permafrost C to climate change and found that approximately 1700 Pg of soil carbon (C) are stored in the northern circumpolar permafure zone, more than twice as much C than in the atmosphere.
Abstract: Approximately 1700 Pg of soil carbon (C) are stored in the northern circumpolar permafrost zone, more than twice as much C than in the atmosphere. The overall amount, rate, and form of C released to the atmosphere in a warmer world will influence the strength of the permafrost C feedback to climate change. We used a survey to quantify variability in the perception of the vulnerability of permafrost C to climate change. Experts were asked to provide quantitative estimates of permafrost change in response to four scenarios of warming. For the highest warming scenario (RCP 8.5), experts hypothesized that C release from permafrost zone soils could be 19–45 Pg C by 2040, 162–288 Pg C by 2100, and 381–616 Pg C by 2300 in CO2 equivalent using 100-year CH4 global warming potential (GWP). These values become 50 % larger using 20-year CH4 GWP, with a third to a half of expected climate forcing coming from CH4 even though CH4 was only 2.3 % of the expected C release. Experts projected that two-thirds of this release could be avoided under the lowest warming scenario (RCP 2.6). These results highlight the potential risk from permafrost thaw and serve to frame a hypothesis about the magnitude of this feedback to climate change. However, the level of emissions proposed here are unlikely to overshadow the impact of fossil fuel burning, which will continue to be the main source of C emissions and climate forcing.
TL;DR: The first demonstration of the pacemaker activated by the physiologically produced electrical energy shows promise for future electronic implantable medical devices powered by electricity harvested from the human body as mentioned in this paper. But the system was designed for biomedical applications.
Abstract: Enzyme-based biofuel cells implanted into living lobsters or designed as fluidic systems mimicking human blood circulation were used for powering electronic devices. Two lobsters with implanted biofuel cells connected in series were able to generate open circuit voltage (Voc) up to 1.2 V and an electrical watch, selected as a model electronic device, was activated by the power extracted from the “living battery”. The fluidic system composed of five cells filled with human serum solution connected in series generated Voc of ca. 3 V and was able to power a pacemaker. Sustainable operation of the pacemaker was achieved with the system closely mimicking human physiological conditions characteristic of normal and pathophysiological glucose concentrations with the fluidic rate typical for a blood circulation upon resting or performing physical exercises. While the “cyborg” lobsters demonstrate a model system with future possible military, homeland security and environmental monitoring applications, the system activating a pacemaker presents practicality for biomedical applications. The first demonstration of the pacemaker activated by the physiologically produced electrical energy shows promise for future electronic implantable medical devices powered by electricity harvested from the human body.
TL;DR: The diversity and composition of both bacterial and fungal communities in compost produced at a commercial-scale were assessed using high-throughput sequencing approaches to assess the microbial communities involved in the composting process.
Abstract: Compost production is a critical component of organic waste handling, and compost applications to soil are increasingly important to crop production. However, we know surprisingly little about the microbial communities involved in the composting process and the factors shaping compost microbial dynamics. Here, we used high-throughput sequencing approaches to assess the diversity and composition of both bacterial and fungal communities in compost produced at a commercial-scale. Bacterial and fungal communities responded to both compost recipe and composting method. Specifically, bacterial communities in manure and hay recipes contained greater relative abundances of Firmicutes than hardwood recipes with hay recipes containing relatively more Actinobacteria and Gemmatimonadetes. In contrast, hardwood recipes contained a large relative abundance of Acidobacteria and Chloroflexi. Fungal communities of compost from a mixture of dairy manure and silage-based bedding were distinguished by a greater relative abundance of Pezizomycetes and Microascales. Hay recipes uniquely contained abundant Epicoccum, Thermomyces, Eurotium, Arthrobotrys, and Myriococcum. Hardwood recipes contained relatively abundant Sordariomycetes. Holding recipe constant, there were significantly different bacterial and fungal communities when the composting process was managed by windrow, aerated static pile, or vermicompost. Temporal dynamics of the composting process followed known patterns of degradative succession in herbivore manure. The initial community was dominated by Phycomycetes, followed by Ascomycota and finally Basidiomycota. Zygomycota were associated more with manure-silage and hay than hardwood composts. Most commercial composters focus on the thermophilic phase as an economic means to insure sanitation of compost from pathogens. However, the community succeeding the thermophilic phase begs further investigation to determine how the microbial dynamics observed here can be best managed to generate compost with the desired properties.