Surface Modification of Melt Extruded Poly(ε-caprolactone) Nanofibers: Toward a New Scalable Biomaterial Scaffold.

A photochemical modification of melt-extruded polymeric nanofibers is described. A bioorthogonal functional group is used to decorate fibers made exclusively from commodity polymers, covalently attach fluorophores and peptides, and direct cell growth. Our process begins by using a layered coextrusion method, where poly(ε-caprolactone) (PCL) nanofibers are incorporated within a macroscopic poly(ethylene oxide) (PEO) tape through a series of die multipliers within the extrusion line. The PEO layer is then removed with a water wash to yield rectangular PCL nanofibers with controlled cross-sectional dimensions. The fibers can be subsequently modified using photochemistry to yield a "clickable" handle for performing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction on their surface. We have attached fluorophores, which exhibit dense surface coverage when using ligand-accelerated CuAAC reaction conditions. In addition, an RGD peptide motif was coupled to the surface of the fibers. Subsequent cell-based studies have shown that the RGD peptide is biologically accessible at the surface, leading to increased cellular adhesion and spreading versus PCL control surfaces. This functionalized coextruded fiber has the advantages of modularity and scalability, opening a potentially new avenue for biomaterials fabrication

DIAGNOSING ACUTE CORONARY SYNDROME IN THE EMERGENCY DEPARTMENT USING HIGH SENSITIVITY TROPONIN I

Timely diagnosis of acute coronary syndrome (ACS), the most lethal manifestation of ischemic heart disease, remains challenging. Due to limitations in the diagnostic accuracy and costs associated with current methods for diagnosing ACS, evaluating patients for ACS in the emergency department (ED) can last up to 24 hours. The consequences of such prolonged ED evaluation are: high personal cost to the patient, significant financial costs to the healthcare system (estimated at $3 to$4 billion annually), and additional strain on an already overstretched emergency medical care system. Measurement of circulating levels of cardiac troponin (cTn) is central to the diagnosis of acute myocardial infarction. Recent advances in clinical chemistry have yielded significant improvements in the analytic performance of cardiac troponin assays (cTn), resulting in superior sensitivity and precision. These high sensitivity cTn (hsTn) assays are able to detect up to ten-fold lower concentrations of cTn than current generation cTn, resulting in earlier diagnosis of acute myocardial infarction (AMI), reclassification of some unstable angina patients as AMI and shortened duration of the rule out AMI period for some patients. However, they also result in an increase in the number of non-ACS patients who will have elevated hsTn values, amplifying the clinical challenge of determining which patients with elevated cTn warrant inpatient admission versus outpatient management. There are insufficient data to guide the use of hsTn for diagnosing ACS in the ED. Chapter 1 is an introductory chapter that discusses the current paradigm of ACS evaluation in the emergency department (ED), and the promise and challenges associated with clinical use of hsTnI to diagnose ACS in the ED. Chapter 2 is a prospective cohort study that quantifies for the first time in an ED located in the United States of America (USA), the frequency and prognostic implications of new cTn elevations when a high sensitivity troponin I (hsTnI) assay is used. This chapter also characterizes factors associated with new cTn elevations and explores the effects of these new elevations on potential hospital admissions. Chapter 3 is a cross-sectional study that examines the frequency and determinants of high sensitivity troponin I (hsTnI) values in emergency department (ED) patients with a primary non-cardiac diagnosis. Chapter 4 is a cross-sectional study that determines whether hsTnI can be used as a screening test to identify suspected ACS patients who do not have significant coronary artery stenosis (candidates for early discharge). In the concluding chapter 5, I will discuss future directions of this work and propose a new paradigm for evaluating ACS in the ED using hsTnI

Dynamic Changes in High‐Sensitivity Cardiac Troponin I Are Associated with Dynamic Changes in Sum Absolute QRST Integral on Surface Electrocardiogram in Acute Decompensated Heart Failure

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135259/1/anec12379_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135259/2/anec12379.pd

Bayesian hierarchical EMAX model for doseâ response in early phase efficacy clinical trials

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149669/1/sim8167_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149669/2/sim8167.pd

Rising Annual Costs of Dizziness Presentations to U.S. Emergency Departments

Objectives Dizziness and vertigo account for roughly 4% of chief symptoms in the emergency department ( ED ). Little is known about the aggregate costs of ED evaluations for these patients. The authors sought to estimate the annual national costs associated with ED visits for dizziness. Methods This cost study of adult U.S. ED visits presenting with dizziness or vertigo combined public‐use ED visit data (1995 to 2009) from the National Hospital Ambulatory Medical Care Survey ( NHAMCS ) and cost data (2003 to 2008) from the Medical Expenditure Panel Survey ( MEPS ). We calculated total visits, test utilization, and ED diagnoses from NHAMCS . Diagnosis groups were defined using the Healthcare Cost and Utilization Project's Clinical Classifications Software ( HCUP ‐ CCS ). Total visits and the proportion undergoing neuroimaging for future years were extrapolated using an autoregressive forecasting model. The average ED visit cost‐per‐diagnosis‐group from MEPS were calculated, adjusting to 2011 dollars using the Hospital Personal Health Care Expenditures price index. An overall weighted mean across the diagnostic groups was used to estimate total national costs. Year 2011 data are reported in 2011 dollars. Results The estimated number of 2011 US ED visits for dizziness or vertigo was 3.9 million (95% confidence interval [ CI ] = 3.6 to 4.2 million). The proportion undergoing diagnostic imaging by computed tomography ( CT ), magnetic resonance imaging ( MRI ), or both in 2011 was estimated to be 39.9% (39.4% CT , 2.3% MRI ). The mean per‐ ED ‐dizziness‐visit cost was $1,004 in 2011 dollars. The total extrapolated 2011 national costs were$3.9 billion. HCUP ‐ CCS key diagnostic groups for those presenting with dizziness and vertigo included the following (fraction of dizziness visits, cost‐per‐ ED ‐visit, attributable annual national costs): otologic/vestibular (25.7%; $768;$757 million), cardiovascular (16.5%, $1,489;$941 million), and cerebrovascular (3.1%; $1059;$127 million). Neuroimaging was estimated to account for about 12% of the total costs for dizziness visits in 2011 ( CT scans $360 million, MRI scans$110 million). Conclusions Total U.S. national costs for patients presenting with dizziness to the ED are substantial and are estimated to now exceed $4 billion per year (about 4% of total ED costs). Rising costs over time appear to reflect the rising prevalence of ED visits for dizziness and increased rates of imaging use. Future economic studies should focus on the specific breakdown of total costs, emphasizing areas of high cost and use that might be safely reduced. Resumen Incremento Anual de los Costes de las Atenciones por Mareo en los Servicios de Urgencias de Estados Unidos Objectivos El mareo y el vértigo suman aproximadamente el 4% de los motivos de consulta en el servicio de urgencias ( SU ). Se conoce poco sobre los costes globales de las evaluaciones del SU en estos pacientes. Se buscó estimar los costes anuales nacionales asociados con las visitas al SU por mareo. Metodología Este estudio de costes de visitas al SU de adultos norteamericanos que acudieron con mareo o vértigo combinó los datos públicos de las visitas a los SU (1995 a 2009) recogidos por el National Hospital Ambulatory Medical Care Survey ( NHAMCS ) y los costes (2003 a 2008) recogidos por el Medical Expenditure Panel Survey ( MEPS ). Se calcularon el total de visitas, el uso de pruebas diagnósticas y los diagnósticos del SU del NHAMCS . Los grupos diagnósticos se definieron según el Healthcare Cost and Utilization Project's Clinical Classifications Software ( HCUP ‐ CCS ). Los datos del año 2011 se documentaron en dólares de 2011. El total de visitas y la proporción de neuroimagen llevada a cabo en los futuros años se extrapoló usando un modelo predictivo autorregresivo. La media del coste por visita al SU por grupo diagnóstico del MEPS se calculó, ajustándose a dólares de 2011, mediante el índice de precios de los Hospital Personal Health Care Expenditures. Se utilizó una media ponderada global entre los grupos diagnósticos para estimar los costes totales nacionales. Resultados El número de visitas al SU en Estados Unidos en 2011 por mareo o vértigo fue de 3,9 millones ( IC 95% = 3,6 a 4,2 millones). El porcentaje de pruebas diagnósticas de imagen llevadas a cabo por tomografía computarizada ( TC ), resonancia magnética ( RM ) o ambas en 2011 se estimó en un 39,9% (39,4% TC , 2,3% RM ). La media de coste por visita al SU por mareo fue de 1.004 dólares de 2011. Los costes totales, extrapolados para todo el país, fueron de 3.900 millones de dólares. Los grupos diagnósticos HCUP ‐ CCS para aquéllos que presentaron mareo o vértigo incluyeron los siguientes (proporción de visitas por mareo; coste por visita al SU ; costes anuales nacionales atribuibles): otológico/vestibular (25,7%; 768 dólares; 757 millones de dólares), cardiovascular (16,5%, 1.489 dólares; 941 millones de dólares) y cerebrovascular (3,1%; 1.059 dólares; 127 millones de dólares). Se estimó una suma en la neuroimagen del 12% del total de costes para las visitas por mareo en 2011 (360 millones de dólares para la TC y 110 millones de dólares para la RM ). Conclusiones Los costes totales en Estados Unidos para los pacientes que acuden por mareo al SU son sustanciales, y se estima que sobrepasan en estos momentos los 4.000 millones de dólares por año (aproximadamente un 4% de los costes totales del SU ). El incremento de los costes con el paso del tiempo parece reflejar el crecimiento de la prevalencia de las visitas al SU por mareo y el aumento de porcentajes de utilización de la neuroimagen. Futuros estudios económicos deberían centrarse en el desglose de los costes totales, y hacer énfasis en las áreas de alto uso y coste que pueden ser reducidas sin riesgo.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99059/1/acem12168.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99059/2/acem12168-sup-0001-DataSupplementS1.pd

Chemical characterization and antioxidant potential of wild ganoderma species from Ghana

The chemical characterization and antioxidant potential of twelve wild strains of Ganoderma sp. from Ghana, nine (LS1-LS9) of which were found growing wild simultaneously on the same dying Delonix regia tree, were evaluated. Parameters evaluated included the nutritional value, composition in sugars, fatty acids, phenolic and other organic compounds and some vitamins and vitamin precursors. Antioxidant potential was evaluated by investigating reducing power, radical scavenging activity and lipid peroxidation inhibition using five in vitro assays. Protein, carbohydrate, fat, ash and energy contents ranged between 15.7-24.5 g/100 gdw, 73.31-81.90 g/100 g, 0.48-1.40 g/100 g, 0.68-2.12 g/100 g ash and 396.1-402.02 kcal/100 g, respectively. Fatty acids such as linoleic, oleic and palmitic acids were relatively abundant. Free sugars included rhamnose, fructose, mannitol, sucrose and trehalose. Total tocopherols, organic acids and phenolic compounds' content ranged between 741-3191 µg/100 g, 77-1003 mg/100 g and 7.6-489 µg/100 g, respectively. There were variations in the ß-glucans, ergosterol and vitamin D 2 contents. The three major minerals in decreasing order were K > P > S. Ganoderma sp. strain AM1 showed the highest antioxidant activity. This study reveals, for the first time, chemical characteristics of Ganoderma spp. which grew simultaneously on the same tree.The authors thank H.N.A. Wellington of University of Ghana for showing us the location of the LS1–9 samples and for aiding in the sample collection. The authors also thank the Foundation for Science and Technology (FCT, Lisbon, Portugal) and FEDER under Program PT2020 for financial support to CIMO (Pest-OE/AGR/UI0690/2015) and L. Barros (SFRH/BPD/107855/2015) grant. To POCI-01-0145-FEDER-006984 (LA LSRE-LCM), funded by FEDER, through POCI-COMPETE2020 and FCT. We also thank the Nutrient and Phytochemical Analytic Shared Resource, part of the OSU Comprehensive Cancer Center (NIH P30 CA016058), where ergosterol and vitamin D2 were analyzed, the OSU Food Innovation Center for financial support, and the OSU Center for Advanced Functional Foods Research and Entrepreneurship for in-kind support. Author Contributions: Mary Obodai designed the study and participated in the manuscript writing. Deborah L. Narh. Mensah and Nii Korley Kortei conducted bibliographic research, data organization and participated in the manuscript writing. Angela Fernandes, Lillian Barros and Isabel C. F. R. Ferreira performed all the chemical analysis, the statistics and participated in the manuscript writing. Deborah L. Narh Mensah, Matilda Dzomeku, Juanita Prempeh and Richard K. Takli collected all the samples. Matthew Teegarden and Steven J. Schwartz conducted analysis on bioactive compounds and edited manuscript. Mary Obodai, Deborah L. Narh. Mensah, Nii Korley Kortei and Isabel C.F.R. Ferreira revised the manuscript writing.info:eu-repo/semantics/publishedVersio

Association of High-Sensitivity Troponin with Cardiac CT Angiography Evidence of Myocardial and Coronary Disease in a Primary Prevention Cohort of Men: Results from MACS.

BackgroundHigh-sensitivity cardiac troponin (hs-cTn) elevations are associated with incident cardiovascular disease events in primary prevention samples. However, the mechanisms underlying this association remain unclear.MethodsWe studied 458 men without known cardiovascular disease who participated in the cardiovascular disease substudy of the Multicenter AIDS Cohort Study and had cardiac CT angiography. We used multivariable linear and logistic regression models to examine the cross-sectional associations between coronary artery stenosis, coronary artery plaque, indexed left ventricular mass (LVMi), and the outcome of hs-cTnI. We also evaluated the associations between HIV serostatus or use of highly active antiretroviral therapy (HAART) and hs-cTnI.ResultsThe mean age was 54 years, 54% were white, and 61% were HIV infected. In multivariable-adjusted logistic models, comparing the highest quartile of LVMi with the lowest quartile, the odds ratio (OR) of hs-cTnI ≥75th percentile was 2.59 (95% CI, 1.20-5.75). There was no significant association between coronary stenosis severity or plaque type and hs-cTnI in linear models; however, in logistic regression models, coronary artery stenosis ≥70% (8% of sample) was marginally associated with a higher likelihood (OR, 2.75 [95% CI, 1.03, 7.27]) of having hs-cTnI ≥75th percentile. There were no associations between HIV serostatus or HAART use and hs-cTnI in either linear or logistic models.ConclusionAmong primary prevention men with or at risk for HIV, hs-cTnI concentrations were strongly associated with LVMi but were not associated with HIV infection or treatment status or with coronary plaque type or stenosis until the extremes of severity (≥70% stenosis)

Rendering polyurethane hydrophilic for efficient cellulose reinforcement in melt-spun nanocomposite fibers

Many commodity plastics, such as thermoplastic polyurethanes (PUs), require reinforcement for use as commercial products. Cellulose nanocrystals (CNCs) offer a “green” and scalable approach to polymer reinforcement as they are exceptionally stiff, recyclable, and abundant. Unfortunately, achieving efficient CNC reinforcement of PUs with industrial melt processing techniques is difficult, mostly due to the incompatibility of the hydrophobic PU with hydrophilic CNCs, limiting their dispersion. Here, a hydrophilic PU is synthesized to achieve strong reinforcement in melt‐processed nanocomposite fibers using filter paper‐sourced CNCs. The melt‐spun fibers, exhibiting smooth surfaces even at high CNC loading (up to 25 wt%) indicating good CNC dispersion, are bench‐marked against solvent‐cast films—solvent processing is not scalable but disperses CNCs well and produces strong CNC reinforcement. Mechanical analysis shows the CNC addition stiffens both nanocomposite films and fibers. The stress and strain at break, however, are not significantly affected in films, whereas adding CNCs to fibers increases the stress‐at‐break while reducing the strain‐at‐break. Compared to earlier studies employing a hydrophobic (and stiffer) PU, CNC addition to a hydrophilic PU substantially increases the fiber stiffness and strength. This work therefore suggests that rendering thermoplastics more hydrophilic might pave the way for “greener” polymer composite products using CNCs

Projected sensitivity of the LUX-ZEPLIN experiment to the 0νββ decay of Xe 136

The LUX-ZEPLIN (LZ) experiment will enable a neutrinoless double β decay search in parallel to the main science goal of discovering dark matter particle interactions. We report the expected LZ sensitivity to Xe136 neutrinoless double β decay, taking advantage of the significant (>600 kg) Xe136 mass contained within the active volume of LZ without isotopic enrichment. After 1000 live-days, the median exclusion sensitivity to the half-life of Xe136 is projected to be 1.06×1026 years (90% confidence level), similar to existing constraints. We also report the expected sensitivity of a possible subsequent dedicated exposure using 90% enrichment with Xe136 at 1.06×1027 years