Translational perspectives on perfusion-diffusion mismatch in ischemic stroke

Magnetic resonance imaging has tremendous potential to illuminate ischemic stroke pathophysiology and guide rational treatment decisions. Clinical applications to date have been largely limited to trials. However, recent analyses of the major clinical studies have led to refinements in selection criteria and improved understanding of the potential implications for the risk vs. benefit of thrombolytic therapy. In parallel, preclinical studies have provided complementary information on the evolution of stroke that is difficult to obtain in humans due to the requirement for continuous or repeated imaging and pathological verification. We review the clinical and preclinical advances that have led to perfusion–diffusion mismatch being applied in phase 3 randomized trials and, potentially, future routine clinical practice

Regularizing Portfolio Optimization

The optimization of large portfolios displays an inherent instability to estimation error. This poses a fundamental problem, because solutions that are not stable under sample fluctuations may look optimal for a given sample, but are, in effect, very far from optimal with respect to the average risk. In this paper, we approach the problem from the point of view of statistical learning theory. The occurrence of the instability is intimately related to over-fitting which can be avoided using known regularization methods. We show how regularized portfolio optimization with the expected shortfall as a risk measure is related to support vector regression. The budget constraint dictates a modification. We present the resulting optimization problem and discuss the solution. The L2 norm of the weight vector is used as a regularizer, which corresponds to a diversification "pressure". This means that diversification, besides counteracting downward fluctuations in some assets by upward fluctuations in others, is also crucial because it improves the stability of the solution. The approach we provide here allows for the simultaneous treatment of optimization and diversification in one framework that enables the investor to trade-off between the two, depending on the size of the available data set

N-[3-(2,6-Dimethylanilino)-1-methylbut-2-enylidene]-2,6-dimethylanilinium chloride1

The title salt, C21H27N2 +·Cl− resulted from the condensation between 2,6-dimethyl­aniline and acetyl­acetone in acidified ethanol. The bulky cation is stabilized in a β-imino­enamine tautomeric form, and presents a W-shaped conformation. The benzene rings are arranged almost parallel, with a dihedral angle of 6.58 (4)° between the mean planes. Both N—H groups in the cation form strong hydrogen bonds with two symmetry-related chloride anions. The resulting supra­molecular structure is a one dimensional polymer running along [001], alternating cations and anions. The π–π inter­action observed in the mol­ecule, characterized by a centroid–centroid separation of 4.298 (4) Å, is thus extended to the chains, with separations of 5.222 (4) Å between benzene rings of neighbouring cations in the crystal

Determination of the scalar polarizabilities of the proton using beam asymmetry Σ3\Sigma_{3} in Compton scattering

The scalar dipole polarizabilities, $\alpha_{E1}$ and $\beta_{M1}$, are fundamental properties related to the internal dynamics of the nucleon. The currently accepted values of the proton polarizabilities were determined by fitting to unpolarized proton Compton scattering cross section data. The measurement of the beam asymmetry $\Sigma_{3}$ in a certain kinematical range provides an alternative approach to the extraction of the scalar polarizabilities. At the Mainz Microtron (MAMI) the beam asymmetry was measured for Compton scattering below pion photoproduction threshold for the first time. The results are compared with model calculations and the influence of the experimental data on the extraction of the scalar polarizabilities is determined.Comment: 6 pages, 5 figure

From wormhole to time machine: Comments on Hawking's Chronology Protection Conjecture

The recent interest in ``time machines'' has been largely fueled by the apparent ease with which such systems may be formed in general relativity, given relatively benign initial conditions such as the existence of traversable wormholes or of infinite cosmic strings. This rather disturbing state of affairs has led Hawking to formulate his Chronology Protection Conjecture, whereby the formation of ``time machines'' is forbidden. This paper will use several simple examples to argue that the universe appears to exhibit a ``defense in depth'' strategy in this regard. For appropriate parameter regimes Casimir effects, wormhole disruption effects, and gravitational back reaction effects all contribute to the fight against time travel. Particular attention is paid to the role of the quantum gravity cutoff. For the class of model problems considered it is shown that the gravitational back reaction becomes large before the Planck scale quantum gravity cutoff is reached, thus supporting Hawking's conjecture.Comment: 43 pages,ReV_TeX,major revision

Weak signals in healthcare: The case study of the Mid-Staffordshire NHS Foundation Trust

Most organisational disasters have warning signals prior to the event occurring, which are increasingly appearing in accident reports. In the case of the Mid-Staffordshire Disaster, the disaster was not as a result of component failure or human error but rather an organisation that drifted into failure with precursory warning signals being ignored. It has been estimated that between 400 and 1200 patients died as a result of poor care between 2004 and 2009. The aim of this study was to identify the precursory signals and their rationalizations that occurred during this event. Qualitative document analysis was used to analyse the independent and public inquiry reports. Signals were present on numerous system levels. At a person level, there were cases of staff trying to make management aware of the problems, as well as the campaign “Cure the NHS” started by bereaved relatives. At an organisational level, examples of missed signals included the decrease in the trust’s star rating due to failure to meet targets, the NHS care regulator voicing concern regarding the unusually high death rates and auditors’ reports highlighting concerns regarding risk management. At an external level, examples included negative peer reviews from various external organizations

Diffusion of e-health innovations in 'post-conflict' settings: a qualitative study on the personal experiences of health workers.

BACKGROUND: Technological innovations have the potential to strengthen human resources for health and improve access and quality of care in challenging 'post-conflict' contexts. However, analyses on the adoption of technology for health (that is, 'e-health') and whether and how e-health can strengthen a health workforce in these settings have been limited so far. This study explores the personal experiences of health workers using e-health innovations in selected post-conflict situations. METHODS: This study had a cross-sectional qualitative design. Telephone interviews were conducted with 12 health workers, from a variety of cadres and stages in their careers, from four post-conflict settings (Liberia, West Bank and Gaza, Sierra Leone and Somaliland) in 2012. Everett Roger's diffusion of innovation-decision model (that is, knowledge, persuasion, decision, implementation, contemplation) guided the thematic analysis. RESULTS: All health workers interviewed held positive perceptions of e-health, related to their beliefs that e-health can help them to access information and communicate with other health workers. However, understanding of the scope of e-health was generally limited, and often based on innovations that health workers have been introduced through by their international partners. Health workers reported a range of engagement with e-health innovations, mostly for communication (for example, email) and educational purposes (for example, online learning platforms). Poor, unreliable and unaffordable Internet was a commonly mentioned barrier to e-health use. Scaling-up existing e-health partnerships and innovations were suggested starting points to increase e-health innovation dissemination. CONCLUSIONS: Results from this study showed ICT based e-health innovations can relieve information and communication needs of health workers in post-conflict settings. However, more efforts and investments, preferably driven by healthcare workers within the post-conflict context, are needed to make e-health more widespread and sustainable. Increased awareness is necessary among health professionals, even among current e-health users, and physical and financial access barriers need to be addressed. Future e-health initiatives are likely to increase their impact if based on perceived health information needs of intended users

Impact of age norms and stereotypes on managers' hiring decisions of retirees

Purpose -Our study investigates the role of managers in the re-employment of early retirees and asks what the effect is of managers’ age norms and stereotypes on managers’ employment decisions. Design/methodology/approach- A combination of a factorial study and a survey was conducted. First, information on the age norms and stereotypes was collected. Secondly, profiles of hypothetical retired job applicants were presented to the employers, who were asked to make a specific hiring decision. The information collected during both studies was combined in the analysis and multilevel models were estimated. Findings -The results indicate that higher age norms result in a higher propensity to hire an early retiree. Stereotypes, by contrast, do not influence managers’ decisions. Early retirees’ chances for re-employment are also related to their own circumstances (physical appearance and relevant experience) and organisational forces, as they are hired when organisations face labour force shortages. Research limitation / implications – with the use of vignettes study we deal with hypothetical hiring situation. Originality value- Although the effect of age norms and age stereotypes has been often suggested, not much empirical evidence was presented to support this notion. Our study estimates the effect of age norms and stereotypes on hiring decision. key words: bridge employment; early retirees; age norms; age stereotypes; multilevel models.

Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells

Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.Peer reviewe