287 research outputs found
Clinical and economic consequences of pharmacogenetic-guided dosing of warfarin
Patients using warfarin for oral anticoagulant therapy need to be frequently monitored because of warfarins narrow therapeutic range and the large variation in dose requirements among patients. Patients receiving the wrong dose have an increased risk of bleeding or thromboembolic events. The required dose is influenced by environmental factors, such as gender, age, diet and concomitant medication, as well as genetic factors. Pharmacogenetic testing prior to warfarin initiation might improve dosing accuracy and, therefore, safety and efficacy of warfarin treatment. Meckley et al. studied the clinical consequences and costs of genotyping before warfarin treatment. The results of their study suggest that pharmacogenetic-guided dosing of patients initiating warfarin could improve health (quality-adjusted life-years) but at a high cost per quality-adjusted life-year gained. Owing to the inevitable assumptions that have to be made in all cost-effectiveness models, great uncertainty remains regarding the cost-effectiveness of pharmacogenetic-guided warfarin dosing
Laser-Cluster-Interaction in a Nanoplasma-Model with Inclusion of Lowered Ionization Energies
The interaction of intense laser fields with silver and argon clusters is
investigated theoretically using a modified nanoplasma model. Single pulse and
double pulse excitations are considered. The influence of the dense cluster
environment on the inner ionization processes is studied including the lowering
of the ionization energies. There are considerable changes in the dynamics of
the laser-cluster interaction. Especially, for silver clusters, the lowering of
the ionization energies leads to increased yields of highly charged ions.Comment: 10 pages, 11 figure
Unintentional high density p-type modulation doping of a GaAs/AlAs core-multi-shell nanowire
Achieving significant doping in GaAs/AlAs core/shell nanowires (NWs) is of
considerable technological importance but remains a challenge due to the
amphoteric behavior of the dopant atoms. Here we show that placing a narrow
GaAs quantum well in the AlAs shell effectively getters residual carbon
acceptors leading to an \emph{unintentional} p-type doping. Magneto-optical
studies of such a GaAs/AlAs core multi-shell NW reveal quantum confined
emission. Theoretical calculations of NW electronic structure confirm quantum
confinement of carriers at the core/shell interface due to the presence of
ionized carbon acceptors in the 1~nm GaAs layer in the shell.
Micro-photoluminescence in high magnetic field shows a clear signature of
avoided crossings of the Landau level emission line with the Landau
level TO phonon replica. The coupling is caused by the resonant hole-phonon
interaction, which points to a large 2D hole density in the structure.Comment: just published in Nano Letters
(http://pubs.acs.org/doi/full/10.1021/nl500818k
Towards a data publishing framework for primary biodiversity data: challenges and potentials for the biodiversity informatics community
Background: Currently primary scientific data, especially that dealing with biodiversity, is neither
easily discoverable nor accessible. Amongst several impediments, one is a lack of professional
recognition of scientific data publishing efforts. A possible solution is establishment of a ‘Data
Publishing Framework’ which would encourage and recognise investments and efforts by
institutions and individuals towards management, and publishing of primary scientific data
potentially on a par with recognitions received for scholarly publications.
Discussion: This paper reviews the state-of-the-art of primary biodiversity data publishing, and
conceptualises a ‘Data Publishing Framework’ that would help incentivise efforts and investments by
institutions and individuals in facilitating free and open access to biodiversity data. It further
postulates the institutionalisation of a ‘Data Usage Index (DUI)’, that would attribute due recognition
to multiple players in the data collection/creation, management and publishing cycle.
Conclusion: We believe that institutionalisation of such a ‘Data Publishing Framework’ that
offers socio-cultural, legal, technical, economic and policy environment conducive for data
publishing will facilitate expedited discovery and mobilisation of an exponential increase in quantity
of ‘fit-for-use’ primary biodiversity data, much of which is currently invisible
Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci
To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 x 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p <2.4 x 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 x 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 x 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 x 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups
Cost Effectiveness of New Oral Anticoagulants for Stroke Prevention in Patients with Atrial Fibrillation in Two Different European Healthcare Settings
Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19
Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe
Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies
There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity
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