Oxidative stress and the use of antioxidants in diabetes: Linking basic science to clinical practice

Cardiovascular complications, characterized by endothelial dysfunction and accelerated atherosclerosis, are the leading cause of morbidity and mortality associated with diabetes. There is growing evidence that excess generation of highly reactive free radicals, largely due to hyperglycemia, causes oxidative stress, which further exacerbates the development and progression of diabetes and its complications. Overproduction and/or insufficient removal of these free radicals result in vascular dysfunction, damage to cellular proteins, membrane lipids and nucleic acids. Despite overwhelming evidence on the damaging consequences of oxidative stress and its role in experimental diabetes, large scale clinical trials with classic antioxidants failed to demonstrate any benefit for diabetic patients. As our understanding of the mechanisms of free radical generation evolves, it is becoming clear that rather than merely scavenging reactive radicals, a more comprehensive approach aimed at preventing the generation of these reactive species as well as scavenging may prove more beneficial. Therefore, new strategies with classic as well as new antioxidants should be implemented in the treatment of diabetes

Effect of neutrophil depletion on gelatinase expression, edema formation and hemorrhagic transformation after focal ischemic stroke

BACKGROUND: While gelatinase (MMP-2 and -9) activity is increased after focal ischemia/reperfusion injury in the brain, the relative contribution of neutrophils to the MMP activity and to the development of hemorrhagic transformation remains unknown. RESULTS: Anti-PMN treatment caused successful depletion of neutrophils in treated animals. There was no difference in either infarct volume or hemorrhage between control and PMN depleted animals. While there were significant increases in gelatinase (MMP-2 and MMP-9) expression and activity and edema formation associated with ischemia, neutrophil depletion failed to cause any change. CONCLUSION: The main finding of this study is that, in the absence of circulating neutrophils, MMP-2 and MMP-9 expression and activity are still up-regulated following focal cerebral ischemia. Additionally, neutrophil depletion had no influence on indicators of ischemic brain damage including edema, hemorrhage, and infarct size. These findings indicate that, at least acutely, neutrophils are not a significant contributor of gelatinase activity associated with acute neurovascular damage after stroke

Nanomagnetic domains of chromium deposited on vertically-aligned carbon nanotubes

The drive to create ever smaller magnetic memory devices has led to the development of new nanomagnetic domains on surfaces. This paper reports the development of nano-chromium magnetic domains obtained using electrodeposition on vertically aligned carbon nanofibers arrays. Attempts to achieve this using conventional aqueous solutions were unsuccessful even after thin nickel underlayers were applied. The use of a novel electrolyte, a deep eutectic solvent, made from choline chloride: chromium (III) chloride enabled highly conformal overcoatings of chromium on individual bare carbon nanotubes to be obtained. Very high aspect ratio metal microstructures could be obtained by this novel technology. Magnetic imaging of the coated nanoarrays showed there to be clear magnetic character to the coating when the thin coatings were applied but this disappeared when the deposits were thicker and more contiguous

PACT: A pipeline for analysis of circulating tumor DNA

MOTIVATION: Detection of genomic alterations in circulating tumor DNA (ctDNA) is currently used for active clinical monitoring of cancer progression and treatment response. While methods for analysis of small mutations are more developed, strategies for detecting structural variants (SVs) in ctDNA are limited. Additionally, reproducibly calling small-scale mutations, copy number alterations, and SVs in ctDNA is challenging due to the lack to unified tools for these different classes of variants. RESULTS: We developed a unified pipeline for the analysis of ctDNA [Pipeline for the Analysis of ctDNA (PACT)] that accurately detects SVs and consistently outperformed similar tools when applied to simulated, cell line, and clinical data. We provide PACT in the form of a Common Workflow Language pipeline which can be run by popular workflow management systems in high-performance computing environments. AVAILABILITY AND IMPLEMENTATION: PACT is freely available at https://github.com/ChrisMaherLab/PACT

Lift-off dynamics in a simple jumping robot

We study vertical jumping in a simple robot comprising an actuated mass-spring arrangement. The actuator frequency and phase are systematically varied to find optimal performance. Optimal jumps occur above and below (but not at) the robot's resonant frequency $f_0$. Two distinct jumping modes emerge: a simple jump which is optimal above $f_0$ is achievable with a squat maneuver, and a peculiar stutter jump which is optimal below $f_0$ is generated with a counter-movement. A simple dynamical model reveals how optimal lift-off results from non-resonant transient dynamics.Comment: 4 pages, 4 figures, Physical Review Letters, in press (2012

Plant closures, precariousness and policy responses:revisiting MG Rover 10 years on

With automotive plants being closed in Australia and western Europe, this article reflects on the employment status of ex-MG Rover (MGR) workers following the closure of the Longbridge plant in 2005. In particular, it draws on Standing's typology of labour market insecurity and uses a mixed-methods approach including an analysis of a longitudinal survey of some 200 ex-MGR workers, and in-depth interviews with ex-workers and policy-makers. While the policy response to the closure saw significant successes in terms of the great majority of workers successfully adjusting into re-employment, and with positive findings in terms of re-training and education, the paper finds significant challenges in terms of security of employment, income, job quality and representation at work years after closure. In particular, the paper posits that the general lack of attention to employment security at the macrolevel effectively undermined elements of a positive policy response over the longer run. This in turn suggests longer-term policy measures are required to address aspects of precariousness at work

Validation of the treatment identification strategy of the HEDIS addiction quality measures: concordance with medical record review

<p>Abstract</p> <p>Background</p> <p>Strategies to accurately identify the occurrence of specific health care events in administrative data is central to many quality improvement and research efforts. Many health care quality measures have treatment identification strategies based on diagnosis and procedure codes - an approach that is inexpensive and feasible but usually of unknown validity. In this study, we examined if the diagnosis/procedure code combinations used in the 2006 HEDIS Initiation and Engagement quality measures to identify instances of addiction treatment have high concordance with documentation of addiction treatment in clinical progress notes.</p> <p>Methods</p> <p>Four type of records were randomly sampled from VHA electronic medical data: (a) Outpatient records from a substance use disorder (SUD) specialty clinic with a HEDIS-qualified substance use disorder (SUD) diagnosis/CPT code combination (n = 700), (b) Outpatient records from a non-SUD setting with a HEDIS-qualified SUD diagnosis/CPT code combination (n = 592), (c) Specialty SUD Inpatient/residential records that included a SUD diagnosis (n = 700), and (d) Non-SUD specialty Inpatient/residential records that included a SUD diagnosis (n = 700). Clinical progress notes for the sampled records were extracted and two raters classified each as documenting or not documenting addiction treatment. Rates of concordance between the HEDIS addiction treatment identification strategy and the raters' judgments were calculated for each record type.</p> <p>Results</p> <p>Within SUD outpatient clinics and SUD inpatient specialty units, 92% and 98% of sampled records had chart evidence of addiction treatment. Of outpatient encounters with a qualifying diagnosis/procedure code combination outside of SUD clinics, 63% had chart evidence of addiction treatment. Within non-SUD specialty inpatient units, only 46% of sampled records had chart evidence of addiction treatment.</p> <p>Conclusions</p> <p>For records generated in SUD specialty settings, the HEDIS strategy of identifying SUD treatment with diagnosis and procedure codes has a high concordance with chart review. The concordance rate outside of SUD specialty settings is much lower and highly variable between facilities. Therefore, some patients may be counted as meeting the 2006 HEDIS Initiation and Engagement criteria without having received the specified amount (or any) addiction treatment.</p

TeV Mini Black Hole Decay at Future Colliders

It is generally believed that mini black holes decay by emitting elementary particles with a black body energy spectrum. The original calculation lead to the conclusion that about the 90% of the black hole mass is radiated away in the form of photons, neutrinos and light leptons, mainly electrons and muons. With the advent of String Theory, such a scenario must be updated by including new effects coming from the stringy nature of particles and interactions.By taking for granted that black holes can be produced in hadronic collisions, then their decay must take into account that: (i) we live in a D3-Brane embedded into an higher dimensional bulk spacetime; (ii) fundamental interactions, including gravity, are unified at TeV energy scale. Thus, the formal description of the Hawking radiation mechanism has to be extended to the case of more than four spacetime dimensions and include the presence of D-branes. Furthermore, unification of fundamental interactions at an energy scale many order of magnitude lower than the Planck energy implies that any kind of fundamental particle, not only leptons, is expected to be emitted. A detailed understanding of the new scenario is instrumental for optimal tuning of detectors at future colliders, where, hopefully, this exciting new physics will be tested. In this article we review higher dimensional black hole decay, considering not only the emission of particles according to Hawking mechanism, but also their near horizon QED/QCD interactions. The ultimate motivation is to build up a phenomenologically reliable scenario, allowing a clear experimental signature of the event.Comment: 22 pages, 9 figures, 4 tables; ``quick review'' for Class. and Quantum Gra

The BCoS cognitive profile screen: Utility and predictive value for stroke

Objective: We examined the utility of the Birmingham Cognitive Screen (BCoS) in discriminating cognitive profiles and recovery of function across stroke survivors. BCoS was designed for stroke-specific problems across 5 cognitive domains: (a) controlled and spatial attention, (b) language, (c) memory, (d) number processing, and (e) praxis. Method: On the basis of specific inclusion criteria, this cross-section observational study analyzed cognitive profiles of 657 subacute stroke patients, 331 of them reassessed at 9 months. Impairments on 32 measures were evaluated by comparison with 100 matched healthy controls. Measures of affect, apathy, and activities of daily living were also taken. Between-subjects group comparisons of mean performance scores and impairment rates and within-subject examination of impairment rates over time were conducted. Logistic regressions and general linear modeling were used for multivariate analysis of domain-level effects on outcomes. Results: Individuals with repeated stroke experienced significantly less cognitive recovery at 9 months than those with a first stroke despite similar initial level of cognitive performance. Individuals with left hemisphere lesions performed more poorly than those with right hemisphere lesions, but both groups showed similar extent of recovery at 9 months. BCoS also revealed lesion-side-specific deficits and common areas of persistent problems. Functional outcome at 9 months correlated with domain-level deficits in controlled attention, spatial attention, and praxis over and above initial dependency and concurrent levels of affect and apathy. Conclusion: The study demonstrates how BCoS can identify differential cognitive profiles across patient groups. This can potentially help predict outcomes and inform rehabilitation. (PsycINFO Database Record (c) 2014 APA, all rights reserved)

Characterization of 3D Interconnected Microstructural Network in Mixed Ionic and Electronic Conducting Ceramic Composites

The microstructure and connectivity of the ionic and electronic conductive phases in composite ceramic membranes are directly related to device performance. Transmission electron microscopy (TEM) including chemical mapping combined with X-ray nanotomography (XNT) have been used to characterize the composition and 3-D microstructure of a MIEC composite model system consisting of a Ce0.8Gd0.2O2 (GDC) oxygen ion conductive phase and a CoFe2O4 (CFO) electronic conductive phase. The microstructural data is discussed, including the composition and distribution of an emergent phase which takes the form of isolated and distinct regions. Performance implications are considered with regards to the design of new material systems which evolve under non-equilibrium operating conditions