Showing papers by "Nova Southeastern University published in 2013"

The State of US Health, 1990-2010: Burden of Diseases, Injuries, and Risk Factors

Abstract: Importance Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy. Objectives To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries. Design We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages. Results US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th. Conclusions and Relevance From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.

Improved contact prediction in proteins : Using pseudolikelihoods to infer Potts models

Abstract: Spatially proximate amino acids in a protein tend to coevolve. A protein's three-dimensional (3D) structure hence leaves an echo of correlations in the evolutionary record. Reverse engineering 3D structures from such correlations is an open problem in structural biology, pursued with increasing vigor as more and more protein sequences continue to fill the data banks. Within this task lies a statistical inference problem, rooted in the following: correlation between two sites in a protein sequence can arise from firsthand interaction but can also be network-propagated via intermediate sites; observed correlation is not enough to guarantee proximity. To separate direct from indirect interactions is an instance of the general problem of inverse statistical mechanics, where the task is to learn model parameters (fields, couplings) from observables (magnetizations, correlations, samples) in large systems. In the context of protein sequences, the approach has been referred to as direct-coupling analysis. Here we show that the pseudolikelihood method, applied to 21-state Potts models describing the statistical properties of families of evolutionarily related proteins, significantly outperforms existing approaches to the direct-coupling analysis, the latter being based on standard mean-field techniques. This improved performance also relies on a modified score for the coupling strength. The results are verified using known crystal structures of specific sequence instances of various protein families. Code implementing the new method can be found at http://plmdca.csc.kth.se/.

Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci.

Abstract: Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis-associated haplotypes at 11 loci. Two ankylosing spondylitis-associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression.

Better tests, better care: improved diagnostics for infectious diseases.

Abstract: In this IDSA policy paper, we review the current diagnostic landscape, including unmet needs and emerging technologies, and assess the challenges to the development and clinical integration of improved tests. To fulfill the promise of emerging diagnostics, IDSA presents recommendations that address a host of identified barriers. Achieving these goals will require the engagement and coordination of a number of stakeholders, including Congress, funding and regulatory bodies, public health agencies, the diagnostics industry, healthcare systems, professional societies, and individual clinicians.

Adrenergic nervous system in heart failure: pathophysiology and therapy.

Abstract: Heart failure (HF), the leading cause of death in the western world, develops when a cardiac injury or insult impairs the ability of the heart to pump blood and maintain tissue perfusion. It is characterized by a complex interplay of several neurohormonal mechanisms that become activated in the syndrome to try and sustain cardiac output in the face of decompensating function. Perhaps the most prominent among these neurohormonal mechanisms is the adrenergic (or sympathetic) nervous system (ANS), whose activity and outflow are enormously elevated in HF. Acutely, and if the heart works properly, this activation of the ANS will promptly restore cardiac function. However, if the cardiac insult persists over time, chances are the ANS will not be able to maintain cardiac function, the heart will progress into a state of chronic decompensated HF, and the hyperactive ANS will continue to push the heart to work at a level much higher than the cardiac muscle can handle. From that point on, ANS hyperactivity becomes a major problem in HF, conferring significant toxicity to the failing heart and markedly increasing its morbidity and mortality. The present review discusses the role of the ANS in cardiac physiology and in HF pathophysiology, the mechanisms of regulation of ANS activity and how they go awry in chronic HF, methods of measuring ANS activity in HF, the molecular alterations in heart physiology that occur in HF, along with their pharmacological and therapeutic implications, and, finally, drugs and other therapeutic modalities used in HF treatment that target or affect the ANS and its effects on the failing heart.

Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report.

Abstract: Allergy immunotherapy (AIT) is an effective treatment for allergic asthma and rhinitis, as well as venom-induced anaphylaxis. In addition to reducing symptoms, AIT can change the course of allergic disease and induce allergen-specific immune tolerance. In current clinical practice immunotherapy is delivered either subcutaneously or sublingually; some allergens, such as grass pollen, can be delivered through either route, whereas others, such as venoms, are only delivered subcutaneously. Both subcutaneous and sublingual immunotherapy appear to have a duration of efficacy of up to 12 years, and both can prevent the development of asthma and new allergen sensitivities. In spite of the advances with AIT, safer and more effective AIT strategies are needed, especially for patients with asthma, atopic dermatitis, or food allergy. Novel approaches to improve AIT include use of adjuvants or recombinant allergens and alternate routes of administration. As part of the PRACTALL initiatives, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology nominated an expert team to develop a comprehensive consensus report on the mechanisms of AIT and its use in clinical practice, as well as unmet needs and ongoing developments in AIT. This resulting report is endorsed by both academies.

Affective disorders and risk of developing dementia: systematic review

Abstract: Background Affective disorders are associated with cognitive disturbances but their role as risk factors for dementia is still not fully investigated. Aims To evaluate the risk of developing dementia in individuals with a history of affective disorder. Method We conducted a systematic review of case–control and cohort studies addressing the risk of developing dementia in people with affective disorders. To the best of our knowledge, this is the first systematic review that has included studies evaluating this risk specifically in people with bipolar disorder. Results Fifty-one studies were included. Most of the studies found an increased risk for developing dementia in individuals with depression. Greater frequency and severity of depressive episodes seem to increase this risk. The evidence is contradictory regarding whether there is a difference in risk in people with early- or late-onset depression. The few available risk estimates for dementia in people with bipolar disorder suggest an even higher risk than for those with depression. Conclusions Affective disorders appear to be associated with an increased risk of developing dementia, and one that is dependent on clinical and demographic variables. Depression may be both a prodrome and a risk factor for dementia. Future research should aim to elucidate the mechanisms that mediate these links.

Search for direct third-generation squark pair production in final states with missing transverse momentum and two b-jets in √s = 8 TeV pp collisions with the ATLAS detector

Abstract: The results of a search for pair production of supersymmetric partners of the Standard Model third-generation quarks are reported. This search uses 20.1 fb-1 of pp collisions at sqrt{s}=8 TeV collected by the ATLAS experiment at the Large Hadron Collider. The lightest bottom and top squarks (b1 and t1 respectively) are searched for in a final state with large missing transverse momentum and two jets identified as originating from b-quarks. No excess of events above the expected level of Standard Model background is found. The results are used to set upper limits on the visible cross section for processes beyond the Standard Model. Exclusion limits at the 95% confidence level on the masses of the third-generation squarks are derived in phenomenological supersymmetric R-parity-conserving models in which either the bottom or the top squark is the lightest squark. The b1 is assumed to decay via b1->b chi0 and the t via t1->b chipm, with undetectable products of the subsequent decay of the chipm due to the small mass splitting between the chipm and the chi0.

Search for dark matter candidates and large extra dimensions in events with a jet and missing transverse momentum with the ATLAS detector

Abstract: A search for new phenomena in events with a high-energy jet and large missing transverse momentum is performed using data from proton-proton collisions at root s = 7 TeV with the ATLAS experiment at the Large flatiron Collider. Four kinematic regions are explored using a dataset corresponding to an integrated luminosity of 4.7 fb(-1). No excess of events beyond expectations from Standard Model processes is observed, and limits are set on large extra dimensions and the pair production of dark matter particles.

The tiger genome and comparative analysis with lion and snow leopard genomes

Abstract: Tigers and their close relatives (Panthera) are some of the world’s most endangered species. Here we report the de novo assembly of an Amur tiger whole-genome sequence as well as the genomic sequences of a white Bengal tiger, African lion, white African lion and snow leopard. Through comparative genetic analyses of these genomes, we find genetic signatures that may reflect molecular adaptations consistent with the big cats’ hypercarnivorous diet and muscle strength. We report a snow leopard-specific genetic determinant in EGLN1 (Met394Lys39), which is likely to be associated with adaptation to high altitude. We also detect a TYR260G4 Am utation likely responsible for the white lion coat colour. Tiger and cat genomes show similar repeat composition and an appreciably conserved synteny. Genomic data from the five big cats provide an invaluable resource for resolving easily identifiable phenotypes evident in very close, but distinct, species.

Florbetapir (F18-AV-45) PET to assess amyloid burden in Alzheimer's disease dementia, mild cognitive impairment, and normal aging.

Abstract: Objective To evaluate the performance characteristics of florbetapir F18 positron emission tomography (PET) in patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy control subjects (HCs). Methods Florbetapir PET was acquired in 184 subjects (45 AD patients, 60 MCI patients, and 79 HCs) within a multicenter phase 2 study. Amyloid burden was assessed visually and quantitatively, and was classified as positive or negative. Results Florbetapir PET was rated visually amyloid positive in 76% of AD patients, 38% of MCI patients, and 14% of HCs. Eighty-four percent of AD patients, 45% of MCI patients, and 23% of HCs were classified as amyloid positive using a quantitative threshold. Amyloid positivity and mean cortical amyloid burden were associated with age and apolipoprotein E e4 carrier status. Conclusions: The data are consistent with expected rates of amyloid positivity among individuals with clinical diagnoses of AD and MCI, and indicate the potential value of florbetapir F18 PET as an adjunct to clinical diagnosis.

Marketing research using single-item indicators in structural equation models

Abstract: This article analyzes the use of single-item indicators in marketing research and their utilization in structural equation modeling (SEM). The study provides a literature review regarding the debate of the use of single-item measures in social sciences research and methodologically in SEM. The analysis of recent studies that use single-item indicators from top marketing journals provides information regarding the types of constructs fit for single-item measurement and their use in SEM. The article presents clarifications to the debate regarding the use of single-item indicators in marketing research, gives examples of types of constructs measurable through single-item indicators and provides recommendations that add knowledge to the empirical analysis and methodology domains of marketing research.

Search for new phenomena in final states with large jet multiplicities and missing transverse momentum at √s = 8 TeV proton-proton collisions using the ATLAS experiment

Abstract: A search is presented for new particles decaying to large numbers (7 or more) of jets, with missing transverse momentum and no isolated electrons or muons. This analysis uses 20.3 fb−1 of pp collision data at s√=8 TeV collected by the ATLAS experiment at the Large Hadron Collider. The sensitivity of the search is enhanced by considering the number of b-tagged jets and the scalar sum of masses of large-radius jets in an event. No evidence is found for physics beyond the Standard Model. The results are interpreted in the context of various simplified supersymmetry-inspired models where gluinos are pair produced, as well as an mSUGRA/CMSSM model.

Measurement of the distributions of event-by-event flow harmonics in lead-lead collisions at √SNN = 2.76 TeV with the ATLAS detector at the LHC

Abstract: The distributions of event-by-event harmonic flow coefficients v (n) for n = 2- 4 are measured in = 2.76 TeV Pb + Pb collisions using the ATLAS detector at the LHC. The measurements are performed u ...

The acceptability and feasibility of an HIV preexposure prophylaxis (PrEP) trial with young men who have sex with men.

Abstract: Background This study examined the feasibility of a combination prevention intervention for young men who have sex with men (YMSM), an anticipated target population for HIV pre-exposure prophylaxis (PrEP).

Measurement of the Flux of Primary Cosmic Ray Antiprotons with Energies of 60 MeV to 350 GeV in the PAMELA Experiment

Abstract: It is interesting to measure the antiproton galactic component in cosmic rays in order to study the mechanisms by which particles and antiparticles are generated and propagate in the Galaxy and to search for new sources of, e.g., annihilation or decay of dark matter hypothetical particles. The antiproton spectrum and the ratio of the fluxes of primary cosmic ray antiprotons to protons with energies of 60 MeV to 350 GeV found from the data obtained from June 2006 to January 2010 in the PAMELA experiment are presented. The usage of the advanced data processing method based on the data classification mathematical model made it possible to increase statistics and analyze the region of higher energies than in the earlier works.

WNT10B/β-catenin signalling induces HMGA2 and proliferation in metastatic triple-negative breast cancer.

Abstract: Wnt/β-catenin signalling has been suggested to be active in basal-like breast cancer. However, in highly aggressive metastatic triple-negative breast cancers (TNBC) the role of β-catenin and the underlying mechanism(s) for the aggressiveness of TNBC remain unknown. We illustrate that WNT10B induces transcriptionally active β-catenin in human TNBC and predicts survival-outcome of patients with both TNBC and basal-like tumours. We provide evidence that transgenic murine Wnt10b-driven tumours are devoid of ERα, PR and HER2 expression and can model human TNBC. Importantly, HMGA2 is specifically expressed during early stages of embryonic mammogenesis and absent when WNT10B expression is lost, suggesting a developmentally conserved mode of action. Mechanistically, ChIP analysis uncovered that WNT10B activates canonical β-catenin signalling leading to up-regulation of HMGA2. Treatment of mouse and human triple-negative tumour cells with two Wnt/β-catenin pathway modulators or siRNA to HMGA2 decreases HMGA2 levels and proliferation. We demonstrate that WNT10B has epistatic activity on HMGA2, which is necessary and sufficient for proliferation of TNBC cells. Furthermore, HMGA2 expression predicts relapse-free-survival and metastasis in TNBC patients.

Vertical ecology of the pelagic ocean: classical patterns and new perspectives.

Abstract: Applications of acoustic and optical sensing and intensive, discrete-depth sampling, in concert with collaborative international research programmes, have substantially advanced knowledge of pelagic ecosystems in the 17 years since the 1996 Deepwater Fishes Symposium of the Fisheries Society of the British Isles. Although the epipelagic habitat is the best-known, and remote sensing and high-resolution modelling allow near-synoptic investigation of upper layer biophysical dynamics, ecological studies within the mesopelagic and deep-demersal habitats have begun to link lower and upper trophic level processes. Bathypelagic taxonomic inventories are far from complete, but recent projects (e.g. MAR-ECO and CMarZ, supported by the Census of Marine Life programme) have quantitatively strengthened distribution patterns previously described for fishes and have provided new perspectives. Synthesis of net and acoustic studies suggests that the biomass of deep-pelagic fishes may be two to three orders of magnitude greater than the total global commercial fisheries landings. Discrete-depth net sampling has revealed relatively high pelagic fish biomass below 1000 m in some regions, and that gelatinous zooplankton may be key energy vectors for deep-pelagic fish production. Lastly, perhaps, the most substantive paradigm shift is that vertical connectivity among fishes across classical depth zones is prevalent- suggesting that a whole-water column approach is warranted for deep ocean conservation and management.

Performance of jet substructure techniques for large-R jets in proton-proton collisions at √s=7 TeV using the ATLAS detector

Abstract: This paper presents the application of a variety of techniques to study jet substructure. The performance of various modified jet algorithms, or jet grooming techniques, for several jet types and event topologies is investigated for jets with transverse momentum larger than 300 GeV. Properties of jets subjected to the mass-drop filtering, trimming, and pruning algorithms are found to have a reduced sensitivity to multiple proton-proton interactions, are more stable at high luminosity and improve the physics potential of searches for heavy boosted objects. Studies of the expected discrimination power of jet mass and jet substructure observables in searches for new physics are also presented. Event samples enriched in boosted W and Z bosons and top-quark pairs are used to study both the individual jet invariant mass scales and the efficacy of algorithms to tag boosted hadronic objects. The analyses presented use the full 2011 ATLAS dataset, corresponding to an integrated luminosity of 4.7 +/- 0.1 fb(-1) from proton-proton collisions produced by the Large Hadron Collider at a centre-of-mass energy of root s = 7 TeV.

International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB)

Abstract: Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the use of beta-hydroxy-beta-methylbutyrate (HMB) as a nutritional supplement. The ISSN has concluded the following. 1. HMB can be used to enhance recovery by attenuating exercise induced skeletal muscle damage in trained and untrained populations. 2. If consuming HMB, an athlete will benefit from consuming the supplement in close proximity to their workout. 3. HMB appears to be most effective when consumed for 2 weeks prior to an exercise bout. 4. Thirty-eight mg·kg·BM-1 daily of HMB has been demonstrated to enhance skeletal muscle hypertrophy, strength, and power in untrained and trained populations when the appropriate exercise prescription is utilized. 5. Currently, two forms of HMB have been used: Calcium HMB (HMB-Ca) and a free acid form of HMB (HMB-FA). HMB-FA may increase plasma absorption and retention of HMB to a greater extent than HMB-CA. However, research with HMB-FA is in its infancy, and there is not enough research to support whether one form is superior. 6. HMB has been demonstrated to increase LBM and functionality in elderly, sedentary populations. 7. HMB ingestion in conjunction with a structured exercise program may result in greater declines in fat mass (FM). 8. HMB’s mechanisms of action include an inhibition and increase of proteolysis and protein synthesis, respectively. 9. Chronic consumption of HMB is safe in both young and old populations.

Grading local side effects of sublingual immunotherapy for respiratory allergy: Speaking the same language

Abstract: Sublingual immunotherapy (SLIT) is increasingly used worldwide. Despite its safety being well ascertained, there is no universally accepted system to grade and classify its adverse events (AEs). According to the literature, it seems reasonable to classify and grade systemic side effects by using the previously published World Allergy Organization recommendations. On the other hand, local side effects are the most frequent with SLIT, sometimes leading to its discontinuation. Therefore grading of the severity of local side effects was perceived as necessary for the purpose of uniform reporting, classification, and quantification of this aspect. A World Allergy Organization Taskforce, after examining the available literature and the postmarketing surveillance data, proposed a clinically based grading of the severity of local AEs caused by SLIT. The use of the Medical Dictionary for Regulatory Activities nomenclature for AEs was also included in this context. The proposed grading system for SLIT-induced local reactions is expected to improve and harmonize surveillance and reporting of the safety of SLIT.