Influence of healthy candidate bias in assessing clinical effectiveness for implantable cardioverter-defibrillators: cohort study of older patients with heart failure

Objective: To assess the potential contribution of unmeasured general health status to patient selection in assessments of the clinical effectiveness of implantable cardioverter-defibrillator (ICD) therapy. Design: Retrospective cohort study. Setting: Linked data from an ICD registry, heart failure registry, and Medicare claims data for ICDs implanted in 2005 through 2009. Participants: 29 426 patients admitted to hospital with heart failure aged 66 years or older and eligible for ICD therapy for primary prevention. Main outcome measures Non-traumatic hip fracture, admission to a skilled nursing facility, and 30 day mortality—outcomes unlikely to be improved by ICD therapy. Results: Compared with 17 853 patients without ICD therapy, 11 573 patients with ICD therapy were younger and had lower ejection fraction and more cardiac admissions to hospital but fewer non-cardiac admissions to hospital and comorbid conditions. Patients with ICD therapy had greater freedom from unrelated events after adjusting for age and sex: hip fracture (hazard ratio 0.77, 95% confidence interval 0.64 to 0.92), skilled nursing facility admission (0.53, 0.50 to 0.55), and 30 day mortality (0.12, 0.10 to 0.15). Conclusions: Lower risks of measured outcomes likely reflect unmeasured differences in comorbidity and frailty. The findings highlight potential pitfalls of observational comparative effectiveness research and support physician consideration of general health status in selecting patients for ICD therapy

An investigation of temperature separation phenomenon in the vortex chamber

Paper presented to the 10th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Florida, 14-16 July 2014.The vortex chamber is a simple device with no moving parts that separates compressed gas into a high temperature region and a low temperature region. Recently, vortex chamber is being received much attention but also high industrial demand because of its structural simplicity and better performance of the temperature separation, compared with the previous vortex tubes. In the present study, both experimental and numerical analysis has been carried out to investigate the temperature separation inside a vortex chamber. Working fluid enters the chamber through four tangential inlet ports and exits through one central exit port. To investigate the temperature separation phenomenon, static pressures and temperatures at several points inside the vortex chamber were measured using highly sensitive pressure transducers and thermocouples. Data obtained from experiments was used to verify the computational results. 3-D unsteady RANS equations were considered to simulate compressible flow inside the vortex chamber. Numerical results were observed to be in good agreement with experimental ones. Many hypotheses are discussed in terms of energy transfer mechanisms and Pressure Gradient Waves (PGW) in the paper.dc201

A Small Molecule Inhibitor of Redox-Regulated Protein Translocation into Mitochondria

SummaryThe mitochondrial disulfide relay system of Mia40 and Erv1/ALR facilitates import of the small translocase of the inner membrane (Tim) proteins and cysteine-rich proteins. A chemical screen identified small molecules that inhibit Erv1 oxidase activity, thereby facilitating dissection of the disulfide relay system in yeast and vertebrate mitochondria. One molecule, mitochondrial protein import blockers from the Carla Koehler laboratory (MitoBloCK-6), attenuated the import of Erv1 substrates into yeast mitochondria and inhibited oxidation of Tim13 and Cmc1 in in vitro reconstitution assays. In addition, MitoBloCK-6 revealed an unexpected role for Erv1 in the carrier import pathway, namely transferring substrates from the translocase of the outer membrane complex onto the small Tim complexes. Cardiac development was impaired in MitoBloCK-6-exposed zebrafish embryos. Finally, MitoBloCK-6 induced apoptosis via cytochrome c release in human embryonic stem cells (hESCs) but not in differentiated cells, suggesting an important role for ALR in hESC homeostasis

Pressure Ulcer prediction using ADT

Objective : To develop a prediction model for pressure ulcer cases that continue to occur at an acute care hospital with a low occurrence rate of pressure ulcers. Methods : Analyzing data were collected from patients hospitalized at Tokushima University Hospital during 2012 using an alternating decision tree (ADT) data mining method. Results : The ADT-based analysis revealed transfer activity, operation time, and low body mass index (BMI) as important factors for predicting pressure ulcer development. Discussion : Among the factors identified, only “transfer activity” can be modified by nursing intervention. While shear force and friction are known to lead to pressure ulcers, transfer activity has not been identified as such. Our results suggest that transfer activities creating shear force and friction correlate with pressure ulcer development. The ADT algorithm was effective in determining prediction factors, especially for highly imbalanced data. Our three stumps ADT yielded accuracy, sensitivity, and specificity values of 72.1%±3.7%, 79.3%±18.1%, and 72.1%±3.8%, respectively. Conclusion : Transfer activity, identified as an interventional factor, can be modified through nursing interventions to prevent pressure ulcer formation. The ADT method was effective in identifying factors within largely imbalanced data

Fast ignitor research at the Institute of Laser Engineering, Osaka University

Copyright 2001 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in Physics of Plasmas, 8(5), 2268-2274, 2001 and may be found at http://dx.doi.org/10.1063/1.135259

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Targeting and Function of the Mitochondrial Fission Factor GDAP1 Are Dependent on Its Tail-Anchor

Proteins controlling mitochondrial dynamics are often targeted to and anchored into the mitochondrial outer membrane (MOM) by their carboxyl-terminal tail-anchor domain (TA). However, it is not known whether the TA modulates protein function. GDAP1 is a mitochondrial fission factor with two neighboring hydrophobic domains each flanked by basic amino acids (aa). Here we define GDAP1 as TA MOM protein. GDAP1 carries a single transmembrane domain (TMD) that is, together with the adjacent basic aa, critical for MOM targeting. The flanking N-terminal region containing the other hydrophobic domain is located in the cytoplasm. TMD sequence, length, and high hydrophobicity do not influence GDAP1 fission function if MOM targeting is maintained. The basic aa bordering the TMD in the cytoplasm, however, are required for both targeting of GDAP1 as part of the TA and GDAP1-mediated fission. Thus, this GDAP1 region contains critical overlapping motifs defining intracellular targeting by the TA concomitant with functional aspects

Studies of ultra-intense laser plasma interactions for fast ignition

Copyright 2000 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in Physics of Plasmas, 7(5), 2014-2022, 2000 and may be found at http://dx.doi.org/10.1063/1.87402

Application of Healthcare 'Big Data' in CNS Drug Research: The Example of the Neurological and mental health Global Epidemiology Network (NeuroGEN)

Neurological and psychiatric (mental health) disorders have a large impact on health burden globally. Cognitive disorders (including dementia) and stroke are leading causes of disability. Mental health disorders, including depression, contribute up to one-third of total years lived with disability. The Neurological and mental health Global Epidemiology Network (NeuroGEN) is an international multi-database network that harnesses administrative and electronic medical records from Australia, Asia, Europe and North America. Using these databases NeuroGEN will investigate medication use and health outcomes in neurological and mental health disorders. A key objective of NeuroGEN is to facilitate high-quality observational studies to address evidence-practice gaps where randomized controlled trials do not provide sufficient information on medication benefits and risks that is specific to vulnerable population groups. International multi-database research facilitates comparisons across geographical areas and jurisdictions, increases statistical power to investigate small subpopulations or rare outcomes, permits early post-approval assessment of safety and effectiveness, and increases generalisability of results. Through bringing together international researchers in pharmacoepidemiology, NeuroGEN has the potential to be paradigm-changing for observational research to inform evidence-based prescribing. The first focus of NeuroGEN will be to address evidence-gaps in the treatment of chronic comorbidities in people with dementia