1,274 research outputs found
Studying learning performance using a M-Learning Approach
Author name used in this manuscript: G. T. S. HoRefereed conference paper2013-2014 > Academic research: refereed > Refereed conference paperOther Versio
α-Actinin and Filamin Cooperatively Enhance the Stiffness of Actin Filament Networks
BACKGROUND: The close subcellular proximity of different actin filament crosslinking proteins suggests that these proteins may cooperate to organize F-actin structures to drive complex cellular functions during cell adhesion, motility and division. Here we hypothesize that alpha-actinin and filamin, two major F-actin crosslinking proteins that are both present in the lamella of adherent cells, display synergistic mechanical functions. METHODOLOGY/PRINCIPAL FINDINGS: Using quantitative rheology, we find that combining alpha-actinin and filamin is much more effective at producing elastic, solid-like actin filament networks than alpha-actinin and filamin separately. Moreover, F-actin networks assembled in the presence of alpha-actinin and filamin strain-harden more readily than networks in the presence of either alpha-actinin or filamin. SIGNIFICANCE: These results suggest that cells combine auxiliary proteins with similar ability to crosslink filaments to generate stiff cytoskeletal structures, which are required for the production of internal propulsive forces for cell migration, and that these proteins do not have redundant mechanical functions
GWAS for discovery and replication of genetic loci associated with sudden cardiac arrest in patients with coronary artery disease
<p>Abstract</p> <p>Background</p> <p>Epidemiologic evidence suggests a heritable component to risk for sudden cardiac arrest independent of risk for myocardial infarction. Recent candidate gene association studies for community sudden cardiac arrests have focused on a limited number of biological pathways and yielded conflicting results. We sought to identify novel gene associations for sudden cardiac arrest in patients with coronary artery disease by performing a genome-wide association study.</p> <p>Methods</p> <p>Tagging SNPs (n = 338,328) spanning the genome were typed in a case-control study comparing 89 patients with coronary artery disease and sudden cardiac arrest due to ventricular tachycardia or ventricular fibrillation to 520 healthy controls.</p> <p>Results</p> <p>Fourteen SNPs including 7 SNPs among 7 genes (ACYP2, AP1G2, ESR1, DGES2, GRIA1, KCTD1, ZNF385B) were associated with sudden cardiac arrest (all p < 1.30 × 10<sup>-7</sup>), following Bonferroni correction and adjustment for population substructure, age, and sex; genetic variation in ESR1 (p = 2.62 × 10<sup>-8</sup>; Odds Ratio [OR] = 1.43, 95% confidence interval [CI]:1.277, 1.596) has previously been established as a risk factor for cardiovascular disease. In tandem, the role of 9 genes for monogenic long QT syndrome (LQT1-9) was assessed, yielding evidence of association with CACNA1C (LQT8; p = 3.09 × 10<sup>-4</sup>; OR = 1.18, 95% CI:1.079, 1.290). We also assessed 4 recently published gene associations for sudden cardiac arrest, validating NOS1AP (p = 4.50 × 10<sup>-2</sup>, OR = 1.15, 95% CI:1.003, 1.326), CSMD2 (p = 6.6 × 10<sup>-3</sup>, OR = 2.27, 95% CI:1.681, 2.859), and AGTR1 (p = 3.00 × 10<sup>-3</sup>, OR = 1.13, 95% CI:1.042, 1.215).</p> <p>Conclusion</p> <p>We demonstrate 11 gene associations for sudden cardiac arrest due to ventricular tachycardia/ventricular fibrillation in patients with coronary artery disease. Validation studies in independent cohorts and functional studies are required to confirm these associations.</p
Sensitive and low-potential electrochemical detection of hydroquinone using a nanodiamond modified glassy carbon electrode
© 2017 The Authors. The present work describes the sensitive and low-potential detection of hydroquinone (HQ) using a glassy carbon electrode (GCE) modified with nanodiamond (ND). The presence of ND was confirmed by high-resolution scanning electron microscopy, FTIR and Raman spectroscopy. The cyclic voltammetry results reveal that ND modified GCE has high electrocatalytic activity towards oxidation of HQ than unmodified GCE. In addition, the ND modified GCE shows a significantly lower oxidation potential towards CC than unmodified GCE, which is due to the presence of -OH functional groups in ND. The CV studies confirm that the redox electrochemical behavior of CC is a diffusion controlled electrochemical process on ND modified electrode. The ND modified electrode was able to detect the HQ across a linear response range from 1.0 to 78.0 μM. The limit of detection of the sensor was 0.19 μM. The sensor shows an appropriate selectivity in the presence of 20-fold concentrations of benzenediols and neurotransmitters. The practicality of the sensor is appropriate and shows excellent recovery of HQ in lab water samples
Entering and Exiting the Medicare Part D Coverage Gap: Role of Comorbidities and Demographics
Background: Some Medicare Part D enrollees whose drug expenditures exceed a threshold enter a coverage gap with full cost-sharing, increasing their risk for reduced adherence and adverse outcomes. Objective: To examine comorbidities and demographic characteristics associated with gap entry and exit. Design: We linked 2005-2006 pharmacy, outpatient, and inpatient claims to enrollment and Census data. We used logistic regression to estimate associations of 2006 gap entry and exit with 2005 medical comorbidities, demographics, and Census block characteristics. We expressed all results as predicted percentages. PATIENTS: 287,713 patients without gap coverage, continuously enrolled in a Medicare Advantage Part D (MAPD) plan serving eight states. Patients who received a low-income subsidy, could not be geocoded, or had no 2006 drug fills were excluded. Results: Of enrollees, 15.9% entered the gap, 2.6% within the first 180 days; among gap enterers, only 6.7% exited again. Gap entry was significantly associated with female gender and all comorbidities, particularly dementia (39.5% gap entry rate) and diabetes (28.0%). Among dementia patients entering the gap, anti-dementia drugs (donepezil, memantine, rivastigmine, and galantamine) and atypical antipsychoticmedications (risperidone, quetiapine, and olanzapine) together accounted for 40% of pre-gap expenditures. Among diabetic patients, rosiglitazone accounted for 7.2% of pre-gap expenditures. Having dementia was associated with twice the risk of gap exit. Conclusions: Certain chronically ill MAPD enrollees are at high risk of gap entry and exposure to unsubsidized medication costs. Clinically vulnerable populations should be counseled on how to best manage costs through drug substitution or discontinuation of specific, non-essential medications. © 2010 Society of General Internal Medicine
Patient-provider communication regarding drug costsin Medicare Part D beneficiaries with diabetes: a TRIAD Study
<p>Abstract</p> <p>Background</p> <p>Little is known about drug cost communications of Medicare Part D beneficiaries with chronic conditions such as diabetes. The purpose of this study is to assess Medicare Part D beneficiaries with diabetes' levels of communication with physicians regarding prescription drug costs; the perceived importance of these communications; levels of prescription drug switching due to cost; and self-reported cost-related medication non-adherence.</p> <p>Methods</p> <p>Data were obtained from a cross-sectional survey (58% response rate) of 1,458 Medicare beneficiaries with diabetes who entered the coverage gap in 2006; adjusted percentages of patients with communication issues were obtained from multivariate regression analyses adjusting for patient demographics and clinical characteristics.</p> <p>Results</p> <p>Fewer than half of patients reported discussing the cost of medications with their physicians, while over 75% reported that such communications were important. Forty-eight percent reported their physician had switched to a less expensive medication due to costs. Minorities, females, and older adults had significantly lower levels of communication with their physicians regarding drug costs than white, male, and younger patients respectively. Patients with < $25 K annual household income were more likely than higher income patients to have talked about prescription drug costs with doctors, and to report cost-related non-adherence (27% vs. 17%, p < .001).</p> <p>Conclusions</p> <p>Medicare Part D beneficiaries with diabetes who entered the coverage gap have low levels of communication with physicians about drug costs, despite the high perceived importance of such communication. Understanding patient and plan-level characteristics differences in communication and use of cost-cutting strategies can inform interventions to help patients manage prescription drug costs.</p
Phytoplankton dynamics in relation to seasonal variability and upwelling and relaxation patterns at the mouth of Ria de Aveiro (West Iberian Margin) over a four-year period
From June 2004 to December 2007, samples were weekly collected at a fixed station located at the mouth of Ria de Aveiro (West Iberian Margin). We examined the seasonal and inter-annual fluctuations in composition and community structure of the phytoplankton in relation to the main environmental drivers and assessed the influence of the oceano-graphic regime, namely changes in frequency and intensity of upwelling events, over the dynamics of the phytoplankton assemblage. The samples were consistently handled and a final subset of 136 OTUs (taxa with relative abundance > 0.01%) was subsequently submitted to various multivariate analyses. The phytoplankton assemblage showed significant changes at all temporal scales but with an overriding importance of seasonality over longer-(inter-annual) or shorter-term fluctuations (upwelling-related). Sea-surface temperature, salinity and maximum upwelling index were retrieved as the main driver of seasonal change. Seasonal signal was most evident in the fluctuations of chlorophyll a concentration and in the high turnover from the winter to spring phytoplankton assemblage. The seasonal cycle of production and succession was disturbed by upwelling events known to disrupt thermal stratification and induce changes in the phytoplankton assemblage. Our results indicate that both the frequency and intensity of physical forcing were important drivers of such variability, but the outcome in terms of species composition was highly dependent on the available local pool of species and the timing of those events in relation to the seasonal cycle. We conclude that duration, frequency and intensity of upwelling events, which vary seasonally and inter-annually, are paramount for maintaining long-term phytoplankton diversity likely by allowing unstable coexistence and incorporating species turnover at different scales. Our results contribute to the understanding of the complex mechanisms of coastal phytoplankton dynamics in relation to changing physical forcing which is fundamental to improve predictability of future prospects under climate change.Portuguese Foundation for Science and Technology (FCT, Portugal) [SFRH/BPD/ 94562/2013]; FEDER funds; national funds; CESAM [UID/AMB/50017]; FCT/MEC through national funds; FEDERinfo:eu-repo/semantics/publishedVersio
Towards the clinical implementation of pharmacogenetics in bipolar disorder.
BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD
Photocatalytic activity of nitrogen-doped TiO2-based nanowires: a photo-assisted Kelvin probe force microscopy study
The emerging industrial business partnerships, which feature cross-functional and cross-company development efforts, raise the barrier for the establishment of effective knowledge sharing practices in the larger organization. This chapter aims to highlight the role of knowledge as a key enabler for effective engineering activities in the light of such emerging enterprise collaboration models. Knowledge Enabled Engineering (KEE) is presented as an approach to enhance the extended organization’s capability to establish effective collaboration among its parts, in spite of different organizational structures, technologies or processes. KEE is analysed in its constituent parts, highlighting areas, methods and tools that are particularly interesting for leveraging companies’ knowledge sharing capabilities
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