684 research outputs found
When to use stress echocardiography in the evaluation of patients with valvular heart disease
Stress testing and stress echocardiography are firmly established diagnostic tests in the evaluation of patients with suspected or known coronary artery disease, but less established in the evaluation of patients with valvular heart disease. However, there is emerging data supporting the incremental benefit of stress testing and stress echocardiography in patients with known valvular heart disease. Particular applications include hemodynamic assessment of valve function and pulmonary response during exercise induced or chemically-induced stress to correlate with the patientâs exertional symptoms. In addition, stress testing affords the opportunity for functional assessment of ventricular systolic function for prognostication and planning for surgery
Sex differences and survival in adults with bicuspid aortic valves : verification in 3 contemporary echocardiographic cohorts
Background-âSex-related differences in morbidity and survival in bicuspid aortic valve (BAV) adults are fundamentally unknown.
Contemporary studies portend excellent survival for BAV patients identified at early echocardiographic-clinical stages. Whether
BAV adults incur a survival disadvantage throughout subsequent echocardiographic-clinical stages remains undetermined.
Methods and Results-âAnalysis was done of 3 different cohorts of consecutive patients with echocardiographic diagnosis of BAV
identified retrospectively: (1) a community cohort of 416 patients with first BAV diagnosis (age 35 21 years, follow-up
16 7 years), (2) a tertiary clinical referral cohort of 2824 BAV adults (age 51 16 years, follow-up 9 6 years), and (3) a surgical
referral cohort of 2242 BAV adults referred for aortic valve replacement (AVR) (age 62 14 years, follow-up 6 5 years). For the
community cohort, 20-year risks of aortic regurgitation (AR), AVR, and infective endocarditis were higher in men (all P=0.04); for a
total BAV-related morbidity risk of 52 4% vs 35 6% in women (P=0.01). The cohortâs 25-year survival was identical to that in the
general population (P=0.98). AR independently predicted mortality in women (P=0.001). Baseline AR was more common in men
(P=0.02) in the tertiary cohort, with 20-year survival lower than that in the general population (P<0.0001); age-adjusted relative
death risk was 1.16 (95% confidence interval [CI] 1.05-1.29) for men versus 1.67 (95% CI 1.38-2.03) for women (P=0.001). AR
independently predicted mortality in women (P=0.01). Baseline AR and infective endocarditis were higher in men (both =0.001) for
the surgical referral cohort, with 15-year survival lower than that in the general population (P<0.0001); age-adjusted relative death
risk was 1.34 (95% CI 1.22-1.47) for men versus 1.63 (95% CI 1.40-1.89) for women (P=0.026). AR and NYHA class independently
predicted mortality in women (both P=0.04).
Conclusions-âWithin evolving echocardiographic-clinical stages, the long-term survival of adults with BAV is not benign, as both
men and women incur excess mortality. Although BAV-related morbidity is higher in men in the community, and AR and infective
endocarditis are more prevalent in men, women exhibit a significantly higher relative risk of death in tertiary and surgical referral
cohorts, which is independently associated with A
Stratiomyidae of Bimini
6 p. ; 24 cm.Includes bibliographical references
The Public Health Exposome: A Population-Based, Exposure Science Approach to Health Disparities Research
The lack of progress in reducing health disparities suggests that new approaches are needed if we are to achieve meaningful, equitable, and lasting reductions. Current scientific paradigms do not adequately capture the complexity of the relationships between environment, personal health and population level disparities. The public health exposome is presented as a universal exposure tracking framework for integrating complex relationships between exogenous and endogenous exposures across the lifespan from conception to death. It uses a social-ecological framework that builds on the exposome paradigm for conceptualizing how exogenous exposures âget under the skinâ. The public health exposome approach has led our team to develop a taxonomy and bioinformatics infrastructure to integrate health outcomes data with thousands of sources of exogenous exposure, organized in four broad domains: natural, built, social, and policy environments. With the input of a transdisciplinary team, we have borrowed and applied the methods, tools and terms from various disciplines to measure the effects of environmental exposures on personal and population health outcomes and disparities, many of which may not manifest until many years later. As is customary with a paradigm shift, this approach has far reaching implications for research methods and design, analytics, community engagement strategies, and research training
Patient-derived head and neck cancer organoids allow treatment stratification and serve as a tool for biomarker validation and identification
Background: Organoids are in vitro three-dimensional structures that can be grown from patient tissue. Head and neck cancer (HNC) is a collective term used for multiple tumor types including squamous cell carcinomas and salivary gland adenocarcinomas.Methods: Organoids were established from HNC patient tumor tissue and characterized using immunohistochemistry and DNA sequencing. Organoids were exposed to chemo- and radiotherapy and a panel of targeted agents. Organoid response was correlated with patient clinical response. CRISPR-Cas9-based gene editing of organoids was applied for biomarker validation.Findings: A HNC biobank consisting of 110 models, including 65 tumor models, was generated. Organoids retained DNA alterations found in HNC. Comparison of organoid and patient response to radiotherapy (primary [n = 6] and adjuvant [n = 15]) indicated potential for guiding treatment options in the adjuvant setting. In organoids, the radio-sensitizing potential of cisplatin and carboplatin could be validated. However, cetuximab conveyed radioprotection in most models. HNC-targeted treatments were tested on 31 models, indicating possible novel treatment options with the potential for treatment stratification in the future. Activating PIK3CA mutations did not predict alpelisib response in organoids. Protein arginine methyltransferase 5 (PRMT5) inhibitors were identified as a potential treatment option for cyclin-dependent kinase inhibitor 2A (CDKN2A) null HNC.Conclusions: Organoids hold potential as a diagnostic tool in personalized medicine for HNC. In vitro organoid response to radiotherapy (RT) showed a trend that mimics clinical response, indicating the predictive potential of patient-derived organoids. Moreover, organoids could be used for biomarker discovery and validation.</p
Cerebral malaria is associated with differential cytoadherence to brain endothelial cells
Sequestration of Plasmodium falciparumâinfected erythrocytes (IE) within the brain microvasculature is a hallmark of cerebral malaria (CM). Using a microchannel flow adhesion assay with TNFâactivated primary human microvascular endothelial cells, we demonstrate that IE isolated from Malawian paediatric CM cases showed increased binding to brain microvascular endothelial cells compared to IE from uncomplicated malaria (UM) cases. Further, UM isolates showed significantly greater adhesion to dermal than to brain microvascular endothelial cells. The major mediator of parasite adhesion is P. falciparum erythrocyte membrane protein 1, encoded by var genes. Higher levels of var gene transcripts predicted to bind host endothelial protein C receptor (EPCR) and ICAMâ1 were detected in CM isolates. These data provide further evidence for differential tissue binding in severe and uncomplicated malaria syndromes, and give additional support to the hypothesis that CM pathology is based on increased cytoadherence of IE in the brain microvasculature
A global database of sea surface dimethylsulfide (DMS) measurements and a procedure to predict sea surface DMS as a function of latitude, longitude, and month
47 pages, 13 figures, 7 tablesA database of 15,617 point measurements of dimethylsulfide (DMS) in surface waters along with lesser amounts of data for aqueous and particulate dimethylsulfoniopropionate concentration, chlorophyll concentration, sea surface salinity and temperature, and wind speed has been assembled. The database was processed to create a series of climatological annual and monthly 1°x1°latitude-longitude squares of data. The results were compared to published fields of geophysical and biological parameters. No significant correlation was found between DMS and these parameters, and no simple algorithm could be found to create monthly fields of sea surface DMS concentration based on these parameters. Instead, an annual map of sea surface DMS was produced using an algorithm similar to that employed by Conkright et al. [1994]. In this approach, a first-guess field of DMS sea surface concentration measurements is created and then a correction to this field is generated based on actual measurements. Monthly sea surface grids of DMS were obtained using a similar scheme, but the sparsity of DMS measurements made the method difficult to implement. A scheme was used which projected actual data into months of the year where no data were otherwise presen
Measurement of the cosmic ray spectrum above eV using inclined events detected with the Pierre Auger Observatory
A measurement of the cosmic-ray spectrum for energies exceeding
eV is presented, which is based on the analysis of showers
with zenith angles greater than detected with the Pierre Auger
Observatory between 1 January 2004 and 31 December 2013. The measured spectrum
confirms a flux suppression at the highest energies. Above
eV, the "ankle", the flux can be described by a power law with
index followed by
a smooth suppression region. For the energy () at which the
spectral flux has fallen to one-half of its extrapolated value in the absence
of suppression, we find
eV.Comment: Replaced with published version. Added journal reference and DO
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