Showing papers by "Tufts University published in 2014"
TL;DR: The review as discussed by the authors summarizes much of particle physics and cosmology using data from previous editions, plus 3,283 new measurements from 899 Japers, including the recently discovered Higgs boson, leptons, quarks, mesons and baryons.
Abstract: The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,283 new measurements from 899 Japers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as heavy neutrinos, supersymmetric and technicolor particles, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Supersymmetry, Extra Dimensions, Particle Detectors, Probability, and Statistics. Among the 112 reviews are many that are new or heavily revised including those on: Dark Energy, Higgs Boson Physics, Electroweak Model, Neutrino Cross Section Measurements, Monte Carlo Neutrino Generators, Top Quark, Dark Matter, Dynamical Electroweak Symmetry Breaking, Accelerator Physics of Colliders, High-Energy Collider Parameters, Big Bang Nucleosynthesis, Astrophysical Constants and Cosmological Parameters.
7,337 citations
Medical University of Vienna1, University of Amsterdam2, Leiden University Medical Center3, Chapel Allerton Hospital4, Leeds Teaching Hospitals NHS Trust5, Humboldt State University6, Oregon Health & Science University7, Utrecht University8, VU University Medical Center9, University of Montpellier10, University of Belgrade11, Erasmus University Rotterdam12, University of Paris-Sud13, Charles University in Prague14, Radboud University Nijmegen Medical Centre15, University of Cologne16, Weston Education Centre17, Tufts University18
TL;DR: These recommendations intend informing rheumatologists, patients, national rheumology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.
Abstract: In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at
4,730 citations
TL;DR: This guideline addresses the wide array of SSTIs that occur in this population and emphasizes the importance of clinical skills in promptly diagnosing SSTI, identifying the pathogen, and administering effective treatments in a timely fashion.
Abstract: A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.
1,856 citations
TL;DR: It is shown that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects.
1,445 citations
Catholic University of the Sacred Heart1, University of Nice Sophia Antipolis2, Autonomous University of Baja California3, Kyoto University4, Institut national de la recherche agronomique5, Taipei Veterans General Hospital6, Tufts University7, Guy's and St Thomas' NHS Foundation Trust8, University of Central Florida9, University of Pittsburgh10, French Institute of Health and Medical Research11, The Chinese University of Hong Kong12, University of Verona13, Uppsala University14
TL;DR: Prevalence of sarcopenia is substantial in most geriatric settings, and well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed.
Abstract: OBJECTIVE: to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP).METHODS: PubMed and Dialog databases were searched (January 2000-October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected.RESULTS: prevalence of sarcopenia was, with regional and age-related variations, 1-29% in community-dwelling populations, 14-33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function.CONCLUSION: prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes.
1,415 citations
TL;DR: This guideline addresses the wide array of SSTIs that occur in this population and emphasizes the importance of clinical skills in promptly diagnosing SSTI, identifying the pathogen, and administering effective treatments in a timely fashion.
Abstract: A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.
1,041 citations
TL;DR: It is proposed that astrocytes mainly signal through high-affinity slowly desensitizing receptors to modulate neurons and perform integration in spatiotemporal domains complementary to those of neurons.
990 citations
Yale University1, Goddard Space Flight Center2, Space Telescope Science Institute3, Leiden University4, Max Planck Society5, University of Arizona6, University of California, Berkeley7, University of Wisconsin-Madison8, University of California, Santa Cruz9, Tufts University10, Yonsei University11, Carnegie Institution for Science12, Open University13
TL;DR: In this paper, a photometric analysis of the CANDELS and 3D-HST HST imaging and the ancillary imaging data at wavelengths 0.3-8 μm is presented, where objects were selected in the WFC3 near-IR bands and their spectral energy distributions were determined by carefully taking the effects of the point-spread function in each observation into account.
Abstract: The 3D-HST and CANDELS programs have provided WFC3 and ACS spectroscopy and photometry over ≈900 arcmin2 in five fields: AEGIS, COSMOS, GOODS-North, GOODS-South, and the UKIDSS UDS field. All these fields have a wealth of publicly available imaging data sets in addition to the Hubble Space Telescope (HST) data, which makes it possible to construct the spectral energy distributions (SEDs) of objects over a wide wavelength range. In this paper we describe a photometric analysis of the CANDELS and 3D-HST HST imaging and the ancillary imaging data at wavelengths 0.3-8 μm. Objects were selected in the WFC3 near-IR bands, and their SEDs were determined by carefully taking the effects of the point-spread function in each observation into account. A total of 147 distinct imaging data sets were used in the analysis. The photometry is made available in the form of six catalogs: one for each field, as well as a master catalog containing all objects in the entire survey. We also provide derived data products: photometric redshifts, determined with the EAZY code, and stellar population parameters determined with the FAST code. We make all the imaging data that were used in the analysis available, including our reductions of the WFC3 imaging in all five fields. 3D-HST is a spectroscopic survey with the WFC3 and ACS grisms, and the photometric catalogs presented here constitute a necessary first step in the analysis of these grism data. All the data presented in this paper are available through the 3D-HST Web site (http://3dhst.research.yale.edu).
957 citations
TL;DR: It is shown that Monte Carlo confidence intervals and Bayesian credible intervals closely reflect the sampling distribution of reliability estimates under most conditions and that small cluster size can lead to overestimates of reliability at the between level of analysis.
Abstract: Scales with varying degrees of measurement reliability are often used in the context of multistage sampling, where variance exists at multiple levels of analysis (e.g., individual and group). Because methodological guidance on assessing and reporting reliability at multiple levels of analysis is currently lacking, we discuss the importance of examining level-specific reliability. We present a simulation study and an applied example showing different methods for estimating multilevel reliability using multilevel confirmatory factor analysis and provide supporting Mplus program code. We conclude that (a) single-level estimates will not reflect a scale's actual reliability unless reliability is identical at each level of analysis, (b) 2-level alpha and composite reliability (omega) perform relatively well in most settings, (c) estimates of maximal reliability (H) were more biased when estimated using multilevel data than either alpha or omega, and (d) small cluster size can lead to overestimates of reliability at the between level of analysis. We also show that Monte Carlo confidence intervals and Bayesian credible intervals closely reflect the sampling distribution of reliability estimates under most conditions. We discuss the estimation of credible intervals using Mplus and provide R code for computing Monte Carlo confidence intervals.
897 citations
University of Texas Health Science Center at Houston1, Broad Institute2, Harvard University3, University of Wisconsin–Milwaukee4, University of Washington5, Washington University in St. Louis6, University of North Carolina at Chapel Hill7, Icahn School of Medicine at Mount Sinai8, University of Michigan9, Lund University10, University of Leicester11, Queen Mary University of London12, University of Oxford13, University of Milan14, University of Verona15, Merck & Co.16, National Institutes of Health17, Levanger Hospital18, Norwegian University of Science and Technology19, University of Ottawa20, Stanford University21, University of Iowa22, George Washington University23, Umeå University24, University of Dundee25, Cambridge University Hospitals NHS Foundation Trust26, Technische Universität München27, University of Kiel28, University of Lübeck29, University of Bonn30, Group Health Cooperative31, Baylor College of Medicine32, Houston Methodist Hospital33, IMDEA34, Tufts University35, University of Leeds36, King Abdulaziz University37, Wellcome Trust Sanger Institute38, University of Mississippi39, Fred Hutchinson Cancer Research Center40, University of Virginia41, University of Vermont42, Boston University43
TL;DR: Rare mutations that disrupt AP OC3 function were associated with lower levels of plasma triglycerides and APOC3, and carriers of these mutations were found to have a reduced risk of coronary heart disease.
Abstract: Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G→A and IVS3+1G→T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1×10 − 20 ), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8×10 − 10 ). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4×10 − 6 ). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.)
877 citations
Icahn School of Medicine at Mount Sinai1, Centre national de la recherche scientifique2, French Institute of Health and Medical Research3, Pierre-and-Marie-Curie University4, University of Toronto5, Trinity College, Dublin6, University of Pittsburgh7, Utrecht University8, McMaster University9, Our Lady's Children's Hospital10, University College Dublin11, University of Oxford12, University of Lisbon13, Instituto Nacional de Saúde Dr. Ricardo Jorge14, University of California, Los Angeles15, University of Miami16, Goethe University Frankfurt17, University of Pennsylvania18, Vanderbilt University19, Temple University20, University of Bologna21, Cancer Care Ontario22, University of Southern California23, University of Alberta24, University of Birmingham25, Université de Montréal26, Rush University Medical Center27, University of Coimbra28, Kaiser Permanente29, Cornell University30, Newcastle University31, University of Minnesota32, University of Illinois at Chicago33, University of Gothenburg34, Memorial University of Newfoundland35, Duke University36, University of Paris37, King's College London38, Centre for Mental Health39, University of Washington40, Nationwide Children's Hospital41, Indiana University42, Tufts University43, German Cancer Research Center44, University of Utah45, Stanford University46
TL;DR: For example, the authors analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability.
Abstract: Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
TL;DR: Findings show that HIV integration sites can play a critical role in expansion and persistence of HIV-infected cells, and may determine the size of the latent reservoir.
Abstract: The persistence of HIV-infected cells in individuals on suppressive combination antiretroviral therapy (cART) presents a major barrier for curing HIV infections. HIV integrates its DNA into many sites in the host genome; we identified 2410 integration sites in peripheral blood lymphocytes of five infected individuals on cART. About 40% of the integrations were in clonally expanded cells. Approximately 50% of the infected cells in one patient were from a single clone, and some clones persisted for many years. There were multiple independent integrations in several genes, including MKL2 and BACH2; many of these integrations were in clonally expanded cells. Our findings show that HIV integration sites can play a critical role in expansion and persistence of HIV-infected cells.
TL;DR: All aflibercept and ranibizumab groups were equally effective in improving BCVA and preventing BCVA loss at 96 weeks, and the 2q8 a flibercept group was similar to ranibIZumab in visual acuity outcomes during 96 weeks, but with an average of 5 fewer injections.
TL;DR: Overall incidences of ocular and nonocular adverse events and serious adverse events, including the Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events and vascular deaths, were similar across treatment groups, and IAI was well-tolerated.
TL;DR: Overall, the study demonstrates that kindergartners were both interested in and able to learn many aspects of robotics, programming, and computational thinking with the TangibleK curriculum design, and suggest effective curricular designs and areas warranting redesign.
Abstract: By engaging in construction-based robotics activities, children as young as four can play to learn a range of concepts. The TangibleK Robotics Program paired developmentally appropriate computer programming and robotics tools with a constructionist curriculum designed to engage kindergarten children in learning computational thinking, robotics, programming, and problem-solving. This paper documents three kindergarten classrooms' exposure to computer programming concepts and explores learning outcomes. Results point to strengths of the curriculum and areas where further redesign of the curriculum and technologies would be appropriate. Overall, the study demonstrates that kindergartners were both interested in and able to learn many aspects of robotics, programming, and computational thinking with the TangibleK curriculum design. We explore the efficacy of an early childhood robotics and programming curriculum.53 kindergarteners used developmentally appropriate robotics and programming tools.Children's concept mastery tended to be high but varied with concept difficulty.Results suggest effective curricular designs and areas warranting redesign.
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16 Oct 2014
TL;DR: This text takes a proactive, systematic and rational approach to medical decision making and provides an essential resource for trainees and researchers involved in medical decision modelling, evidence-based medicine, clinical epidemiology, comparative effectiveness, public health, health economics, and health technology assessment.
Abstract: Preface 1 Elements of decision making in health care 2 Managing uncertainty 3 Choosing the best treatment 4 Valuing outcomes 5 Interpreting diagnostic information 6 Deciding when to test 7 Multiple test results 8 Finding and summarizing the evidence 9 Constrained resources 10 Recurring events 11 Variability and uncertainty 12 Proactive decision making: a way of life Index
Brown University1, Indiana University2, University of Minnesota3, University of Washington4, Yeshiva University5, California Pacific Medical Center6, Virginia Mason Medical Center7, Harvard University8, University of Alberta9, University of Michigan10, Tufts University11, Integris Baptist Medical Center12, Ochsner Medical Center13, Boston Children's Hospital14
TL;DR: This series demonstrates the effective use of FMT for CDI in IC patients with few SAEs or related AEs, and there were no related infectious complications in these high-risk patients.
23 Jun 2014
TL;DR: In this article, a tensor-Singular Value Decomposition (t-SVD) based tensor nuclear norm penalized algorithm was proposed for video completion from missing entries.
Abstract: In this paper we propose novel methods for completion (from limited samples) and de-noising of multilinear (tensor) data and as an application consider 3-D and 4- D (color) video data completion and de-noising. We exploit the recently proposed tensor-Singular Value Decomposition (t-SVD)[11]. Based on t-SVD, the notion of multilinear rank and a related tensor nuclear norm was proposed in [11] to characterize informational and structural complexity of multilinear data. We first show that videos with linear camera motion can be represented more efficiently using t-SVD compared to the approaches based on vectorizing or flattening of the tensors. Since efficiency in representation implies efficiency in recovery, we outline a tensor nuclear norm penalized algorithm for video completion from missing entries. Application of the proposed algorithm for video recovery from missing entries is shown to yield a superior performance over existing methods. We also consider the problem of tensor robust Principal Component Analysis (PCA) for de-noising 3-D video data from sparse random corruptions. We show superior performance of our method compared to the matrix robust PCA adapted to this setting as proposed in [4].
TL;DR: Weight loss outcomes for popular diets based on diet class (macronutrient composition) and named diet supports the practice of recommending any diet that a patient will adhere to in order to lose weight.
Abstract: low-carbohydrate diets (8.73 kg [95% credible interval {CI}, 7.27 to 10.20 kg] at 6-month follow-up and 7.25 kg [95% CI, 5.33 to 9.25 kg] at 12-month follow-up) and low-fat diets (7.99 kg [95% CI, 6.01 to 9.92 kg] at 6-month follow-up and 7.27 kg [95% CI, 5.26 to 9.34 kg] at 12-month follow-up). Weight loss differences between individual diets were minimal. For example, the Atkins diet resulted in a 1.71 kg greater weight loss than the Zone diet at 6-month follow-up. Between 6- and 12-month follow-up, the influence of behavioral support (3.23 kg [95% CI, 2.23 to 4.23 kg] at 6-month follow-up vs 1.08 kg [95% CI, −1.82 to 3.96 kg] at 12-month follow-up) and exercise (0.64 kg [95% CI, −0.35 to 1.66 kg] vs 2.13 kg [95% CI, 0.43 to 3.85 kg], respectively) on weight loss differed.
TL;DR: The addition of alkali ions (sodium or potassium) to gold on KLTL-zeolite and mesoporous MCM-41 silica stabilizes mononuclear gold in Au-O(OH)x-(Na or K) ensembles and paves the way for using earth-abundant supports to disperse and stabilize precious metal atoms with alkali additives for the WGS and potentially other fuel-processing reactions.
Abstract: We report that the addition of alkali ions (sodium or potassium) to gold on KLTL-zeolite and mesoporous MCM-41 silica stabilizes mononuclear gold in Au-O(OH)x-(Na or K) ensembles. This single-site gold species is active for the low-temperature (<200°C) water-gas shift (WGS) reaction. Unexpectedly, gold is thus similar to platinum in creating -O linkages with more than eight alkali ions and establishing an active site on various supports. The intrinsic activity of the single-site gold species is the same on irreducible supports as on reducible ceria, iron oxide, and titania supports, apparently all sharing a common, similarly structured gold active site. This finding paves the way for using earth-abundant supports to disperse and stabilize precious metal atoms with alkali additives for the WGS and potentially other fuel-processing reactions.
TL;DR: A framework for the assessment of point-of-care tests is proposed, and the term test efficacy is suggested to describe the ability of a diagnostic test to support a clinical decision within its operational context, and revised criteria for an ideal diagnostic point- of-care test in resource-limited settings are proposed.
Abstract: Summary The aim of diagnostic point-of-care testing is to minimise the time to obtain a test result, thereby allowing clinicians and patients to make a quick clinical decision. Because point-of-care tests are used in resource-limited settings, the benefits need to outweigh the costs. To optimise point-of-care testing in resource-limited settings, diagnostic tests need rigorous assessments focused on relevant clinical outcomes and operational costs, which differ from assessments of conventional diagnostic tests. We reviewed published studies on point-of-care testing in resource-limited settings, and found no clearly defined metric for the clinical usefulness of point-of-care testing. Therefore, we propose a framework for the assessment of point-of-care tests, and suggest and define the term test efficacy to describe the ability of a diagnostic test to support a clinical decision within its operational context. We also propose revised criteria for an ideal diagnostic point-of-care test in resource-limited settings. Through systematic assessments, comparisons between centralised testing and novel point-of-care technologies can be more formalised, and health officials can better establish which point-of-care technologies represent valuable additions to their clinical programmes.
Tufts University1, University of Alabama at Birmingham2, University of Michigan3, Indiana University4, Lund University5, University of Illinois at Chicago6, Uniformed Services University of the Health Sciences7, Mayo Clinic8, University of North Carolina at Chapel Hill9, Oregon Health & Science University10, Medical University of Vienna11, University of Texas Health Science Center at San Antonio12, Harvard University13, Duke University14
TL;DR: Thomas F. O'Donnell, MD, Marc A. Passman and Peter K. Gloviczki as mentioned in this paper, MD, PhD, Bo G. Eklof et al.
TL;DR: The combination of bevacizumab and ipilimumab can be safely administered and VEGF-A blockade influences on inflammation, lymphocyte trafficking, and immune regulation, and their synergistic therapeutic effects are revealed.
Abstract: Ipilimumab improves survival in advanced melanoma and can induce immune-mediated tumor vasculopathy. Besides promoting angiogenesis, vascular endothelial growth factor (VEGF) suppresses dendritic cell maturation and modulates lymphocyte endothelial trafficking. This study investigated the combination of CTLA4 blockade with ipilimumab and VEGF inhibition with bevacizumab. Patients with metastatic melanoma were treated in four dosing cohorts of ipilimumab (3 or 10 mg/kg) with four doses at 3-week intervals and then every 12 weeks, and bevacizumab (7.5 or 15 mg/kg) every 3 weeks. Forty-six patients were treated. Inflammatory events included giant cell arteritis (n = 1), hepatitis (n = 2), and uveitis (n = 2). On-treatment tumor biopsies revealed activated vessel endothelium with extensive CD8(+) and macrophage cell infiltration. Peripheral blood analyses demonstrated increases in CCR7(+/-)/CD45RO(+) cells and anti-galectin antibodies. Best overall response included 8 partial responses, 22 instances of stable disease, and a disease-control rate of 67.4%. Median survival was 25.1 months. Bevacizumab influences changes in tumor vasculature and immune responses with ipilimumab administration. The combination of bevacizumab and ipilimumab can be safely administered and reveals VEGF-A blockade influences on inflammation, lymphocyte trafficking, and immune regulation. These findings provide a basis for further investigating the dual roles of angiogenic factors in blood vessel formation and immune regulation, as well as future combinations of antiangiogenesis agents and immune checkpoint blockade.
TL;DR: The results not only have important implications for biological theories of tumor growth and the use of mathematical modeling in preclinical anti-cancer drug investigations, but also may assist in defining how mathematical models could serve as potential prognostic tools in the clinic.
Abstract: Despite internal complexity, tumor growth kinetics follow relatively simple laws that can be expressed as mathematical models. To explore this further, quantitative analysis of the most classical of these were performed. The models were assessed against data from two in vivo experimental systems: an ectopic syngeneic tumor (Lewis lung carcinoma) and an orthotopically xenografted human breast carcinoma. The goals were threefold: 1) to determine a statistical model for description of the measurement error, 2) to establish the descriptive power of each model, using several goodness-of-fit metrics and a study of parametric identifiability, and 3) to assess the models' ability to forecast future tumor growth. The models included in the study comprised the exponential, exponential-linear, power law, Gompertz, logistic, generalized logistic, von Bertalanffy and a model with dynamic carrying capacity. For the breast data, the dynamics were best captured by the Gompertz and exponential-linear models. The latter also exhibited the highest predictive power, with excellent prediction scores (≥80%) extending out as far as 12 days in the future. For the lung data, the Gompertz and power law models provided the most parsimonious and parametrically identifiable description. However, not one of the models was able to achieve a substantial prediction rate (≥70%) beyond the next day data point. In this context, adjunction of a priori information on the parameter distribution led to considerable improvement. For instance, forecast success rates went from 14.9% to 62.7% when using the power law model to predict the full future tumor growth curves, using just three data points. These results not only have important implications for biological theories of tumor growth and the use of mathematical modeling in preclinical anti-cancer drug investigations, but also may assist in defining how mathematical models could serve as potential prognostic tools in the clinic.
TL;DR: Clinicians and researchers with an interest in the effect of diet on health are asked to describe what constitutes a Mediterranean diet in different geographical settings, and how they can study the health benefits of this dietary pattern.
Abstract: The Mediterranean diet has been linked to a number of health benefits, including reduced mortality risk and lower incidence of cardiovascular disease. Definitions of the Mediterranean diet vary across some settings, and scores are increasingly being employed to define Mediterranean diet adherence in epidemiological studies. Some components of the Mediterranean diet overlap with other healthy dietary patterns, whereas other aspects are unique to the Mediterranean diet. In this forum article, we asked clinicians and researchers with an interest in the effect of diet on health to describe what constitutes a Mediterranean diet in different geographical settings, and how we can study the health benefits of this dietary pattern.
Jewish General Hospital1, McGill University2, Ottawa Hospital Research Institute3, University of Ottawa4, London Health Sciences Centre5, Dalhousie University6, Capital District Health Authority7, Tufts University8, Tufts Medical Center9, Université de Montréal10, St Mary's Hospital11, Montreal General Hospital12, University Health Network13, McMaster University14, Karolinska Institutet15, Hôpital Maisonneuve-Rosemont16, University of Manitoba17, St. Joseph Hospital18, Hurley Medical Center19, Sunnybrook Health Sciences Centre20, University of Oklahoma21, Duke University22
TL;DR: ECS did not prevent PTS after a first proximal DVT, hence the findings do not support routine wearing of ECS after DVT.
TL;DR: The CKD-EPI (CKD Epidemiology Collaboration) equations are the most accurate GFR estimating equations that have been evaluated in large diverse populations and are applicable for general clinical use.
Medical College of Wisconsin1, Vanderbilt University2, Tufts University3, University of California, San Francisco4, University of California, Davis5, Johns Hopkins University6, University of Maryland, Baltimore7, University of Colorado Denver8, Louisiana State University9, University of Washington10, Cleveland Clinic11, Harvard University12
TL;DR: Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction, and was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range.
Abstract: Background In the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS. Methods We conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a doubleblind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure–free days to day 14. Results The study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P = 0 .21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P = 0 .96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was assoc iated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P = 0 .01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P = 0 .003). Rosuvas tatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range. Conclusions Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis a ssociated ARDS and may have contributed to hepatic and renal organ dysfunction. (Funded by the National Heart, Lung, and Blood Institute and the Investigator-Sponsored Study Program of AstraZeneca; ClinicalTrials.gov number, NCT00979121.)
Columbia University1, Virginia Commonwealth University2, Tufts University3, University of Chicago4, University of California, San Francisco5, Johns Hopkins University6, Mayo Clinic7, University of California, Davis8, University of North Texas Health Science Center9, Oregon Health & Science University10, University of Alabama11, Cedars-Sinai Medical Center12
TL;DR: The group recommends that postmenopausal women and men aged 50 years should be diagnosed with osteoporosis if they have a demonstrable elevated risk for future fractures and should be used to diagnose individuals with an elevated fracture risk based on the World Health Organization Fracture Risk Algorithm, FRAX.
Abstract: Summary
Osteoporosis causes an elevated fracture risk. We propose the continued use of T-scores as one means for diagnosis but recommend that, alternatively, hip fracture; osteopenia-associated vertebral, proximal humerus, pelvis, or some wrist fractures; or FRAX scores with ≥3 % (hip) or 20 % (major) 10-year fracture risk also confer an osteoporosis diagnosis.
TL;DR: In early ADPKD, the combination of lisinopril and telmisartan did not significantly alter the rate of increase in total kidney volume and rigorous blood-pressure control was associated with a slower increase inTotal kidney volume, no overall change in the estimated GFR, a greater decline in the left-ventricular-mass index, and greater reduction in urinary albumin excretion.
Abstract: BACKGROUND Hypertension is common in autosomal dominant polycystic kidney disease (ADPKD) and is associated with increased total kidney volume, activation of the renin–angiotensin–aldosterone system, and progression of kidney disease. METHODS In this double-blind, placebo-controlled trial, we randomly assigned 558 hypertensive participants with ADPKD (15 to 49 years of age, with an estimated glomerular filtration rate [GFR] >60 ml per minute per 1.73 m 2 of body-surface area) to either a standard blood-pressure target (120/70 to 130/80 mm Hg) or a low blood-pressure target (95/60 to 110/75 mm Hg) and to either an angiotensin-converting–enzyme inhibitor (lisinopril) plus an angiotensin-receptor blocker (telmisartan) or lisinopril plus placebo. The primary outcome was the annual percentage change in the total kidney volume. RESULTS The annual percentage increase in total kidney volume was significantly lower in the low-blood-pressure group than in the standard-blood-pressure group (5.6% vs. 6.6%, P = 0.006), without significant differences between the lisinopril–telmisartan group and the lisinopril–placebo group. The rate of change in estimated GFR was similar in the two medication groups, with a negative slope difference in the short term in the low-blood-pressure group as compared with the standard-blood-pressure group (P<0.001) and a marginally positive slope difference in the long term (P = 0.05). The left-ventricular-mass index decreased more in the low-blood-pressure group than in the standard-blood-pressure group (−1.17 vs. −0.57 g per square meter per year, P<0.001); urinary albumin excretion was reduced by 3.77% with the low-pressure target and increased by 2.43% with the standard target (P<0.001). Dizziness and light-headedness were more common in the low-blood-pressure group than in the standard-blood-pressure group (80.7% vs. 69.4%, P = 0.002). CONCLUSIONS In early ADPKD, the combination of lisinopril and telmisartan did not significantly alter the rate of increase in total kidney volume. As compared with standard bloodpressure control, rigorous blood-pressure control was associated with a slower increase in total kidney volume, no overall change in the estimated GFR, a greater decline in the left-ventricular-mass index, and greater reduction in urinary albumin excretion. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; HALT-PKD [Study A] ClinicalTrials.gov number, NCT00283686.)