Use of cumulative mortality data in patients with acute myocardial infarction for early detection of variation in clinical practice: observational study

OBJECTIVES: Use of cumulative mortality adjusted for case mix in patients with acute myocardial infarction for early detection of variation in clinical practice. DESIGN: Observational study. SETTING: 20 hospitals across the former Yorkshire region. PARTICIPANTS: All 2153 consecutive patients with confirmed acute myocardial infarction identified during three months. MAIN OUTCOME MEASURES: Variable life­adjusted displays showing cumulative differences between observed and expected mortality of patients; expected mortality calculated from risk model based on admission characteristics of age, heart rate, and systolic blood pressure. RESULTS: The performance of two individual hospitals over three months was examined as an example. One, the smallest district hospital in the region, had a series of 30 consecutive patients but had five more deaths than predicted. The variable life­adjusted display showed minimal variation from that predicted for the first 15 patients followed by a run of unexpectedly high mortality. The second example was the main tertiary referral centre for the region, which admitted 188 consecutive patients. The display showed a period of apparently poor performance followed by substantial improvement, where the plot rose steadily from a cumulative net lives saved of - 4 to 7. These variations in patient outcome are unlikely to have been revealed during conventional audit practice. CONCLUSIONS: Variable life­adjusted display has been integrated into surgical care as a graphical display of risk­adjusted survival for individual surgeons or centres. In combination with a simple risk model, it may have a role in monitoring performance and outcome in patients with acute myocardial infarction

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

Spatial memory in aged rats is related to PKCγ-dependent G-protein coupling of the M1 receptor

In the present study, individual differences in spatial memory in aged Fischer 344 (F344) rats were associated with the extent of G-protein coupling of the M1 muscarinic receptor and the dendritic-to-somal ratio of hippocampal PKCγ (d/sPKCγ) immunogenicity. Following testing in the eight-arm radial maze task, 7 young and 13 aged rat brains were sectioned through the dorsal hippocampal formation (HF). G-protein coupling of the M1 receptor was assessed autoradiographically using competition binding studies in the presence and absence of a G-protein uncoupler to determine high ( K H) and low ( K L) affinity states for agonist in the HF, neocortex, and amygdala. In aged animals, a relationship between choice accuracy in the maze and K H, a measure of M1 receptor–G-protein coupling was seen in the dentate gyrus, CA3, CA1, and neocortex. Furthermore, choice accuracy and d/sPKCγ immunogenicity showed a significant relationship in CA1. Lastly, a correlation was seen in the CA1 of aged animals between K H and d/sPKCγ. These relationships did not hold for the amygdala. Thus, individual differences in a naturally occurring age-dependent disruption of cholinergic-PKCγ signal transduction is associated with spatial memory dysfunction

The Standardizability of Type Ia Supernovae in the Near-Infrared:Evidence for a Peak-Luminosity Versus Decline-Rate Relation in the Near-Infrared

Artículo de publicación ISIWe analyze the standardizability of Type Ia supernovae (SNe Ia) in the near-infrared (NIR) by investigating the correlation between observed peak NIR (Y JH) absolute magnitude and postmaximum B-band decline rate [Delta m(15)(B)]. A sample of 27 low-redshift SNe Ia with well-observed NIR light curves observed by the Carnegie Supernova Project (CSP) between 2004 and 2007 is used. All 27 objects have premaximum coverage in optical bands, with a subset of 13 having premaximum NIR observations as well; coverage of the other 14 begins shortly after NIR maximum brightness. We describe the methods used to derive light-curve parameters (absolute peak magnitudes and decline rates) from both spline-and template-fitting procedures, and we confirm prior findings that fitting templates to SNe Ia light curves in the NIR is problematic due to the diversity of postmaximum behavior of objects that are characterized by similar Delta m(15)(B) values, especially at high decline rates. Nevertheless, we show that NIR light curves can be reasonably fit with a template, especially if the observations begin within 5 days after NIR maximum. SNe Ia appear to be better "standardizable candles" in the NIR bands than in the optical bands. For the subset of 13 objects in our data set that excludes the highly reddened and fast-declining SNe Ia and includes only those objects for which NIR observations began prior to 5 days after maximum light, we find modest (1.7 sigma) evidence for a peak-luminosity versus decline-rate relation in Y, and stronger evidence (2.8 sigma) in J and H. Using R-V values differing from the canonical value (R-V = 3.1) is shown to have little effect on the results. A Hubble diagram is presented for the NIR bands and the B band. The resulting scatter for the combined NIR bands is 0.13 mag, while the B band produces a scatter of 0.22 mag. Finally, we find evidence for a bimodal distribution in the NIR absolute magnitudes of fast-declining SNe Ia [Delta m(15)(B) > 1.7]. These data suggest that applying a correction to SNe Ia peak luminosities for decline rate is likely to be beneficial in the J and H bands to make SNe Ia more precise distance indicators, but of only marginal importance in the Y band.National Science Foundation (NSF) AST-0306969 AST-0607438 AST-1008343 AST-1009571 NASA through Space Telescope Science Institute AR-10673 NASA NAS5-26555 Millennium Center for Supernova Science from Iniciativa Cientifica Milenio P10-064-F Millennium Center for Supernova Science from Centro de Astrofisica FONDAP 15010003 Millennium Center for Supernova Science from Center of Excellence in Astrophysics and Associated Technologies PFB 06 FONDECYT 309000

Markets, transaction costs and institutions: compensating for nuclear risk in Japan

This article explores the nature, role and effectiveness of compensation mechanisms in managing the political constraints to the siting or development of nuclear projects in Japan. Statistical analysis reveals that the relationship between compensation and income is a key dynamic characterising the history of the marketplace for nuclear facilities in Japan. The commodification and trading of risks for benefits is governed by a sophisticated institutional and policy framework which acts to lower the transaction costs of market exchange. The interaction between the market and the institutional dynamic has generated a curious pattern of both NIMBY ('not in my backyard') and YIMBY ('yes, in my backyard') responses to nuclear development in Japan