Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of missing data on standardised mortality ratios for acute myocardial infarction: evidence from the Myocardial Ischaemia National Audit Project (MINAP) 2004–7

Background Standardised mortality ratios (SMR) are often used to depict cardiovascular care. Data missingness, data quality, temporal variation and case-mix can, however, complicate the assessment of clinical performance. Objectives To study Primary Care Trust (PCT) 30-day SMRs for STEMI and NSTEMI whilst considering the impact of missing data for age, sex and IMD score. Design Observational study using data from the Myocardial Ischaemia National Audit Project (MINAP) database to generate PCT SMR maps and funnel plots for England, 2004–2007. Patients 217,157 patients: 40.4% STEMI and 59.6% NSTEMI. Results 95% CI 30-day unadjusted mortality: STEMI 5.8% to 6.2%; NSTEMI 6.6% to 6.9%; relative risk, 95% CI 1.14, 1.10 to 1.19. Median (IQR) data missingess by PCT for composite of age, sex and IMD score was 1.4% (0.7% to 2.2%). For STEMI and NSTEMI statistically significant predictors of mortality were mean age (STEMI: P<0.001; NSTEMI: P<0.001), proportion of females (STEMI: P<0.001; NSTEMI: P<0.001) and proportion of missing ages (STEMI: P=0.02; NSTEMI: P<0.001). Proportion of missing sex also predicted 30-day mortality for NSTEMI (P=0.01). Maps of SMRs demonstrated substantial mortality variation, but no evidence of North / South divide. There were significant correlations between STEMI and NSTEMI observed (R2 0.72) and standardised mortality (R2 0.49) rates. PCT data aggregation gave an acceptable model fit in terms of deviance explained. For STEMI there were 33 (21.7%) regions below the 99.8% lower limit of the associated performance funnel plot, and 28 (18.4%) for NSTEMI; the inclusion of missing data did not affect the distribution of SMRs. Conclusions The proportion of missing data was associated with 30-day mortality for STEMI and NSTEMI, however it did not influence the distribution of PCTs within the funnel plots. There was considerable variation in mortality not attributable to key patient-specific factors, supporting the notion of regional-dependent variation in STEMI and NSTEMI care.
Therapeutics , Targets , and Chemical Biology Hedgehog Signaling Drives Cellular Survival in Human Colon Carcinoma Cells

Aberrant activation of Hedgehog (HH) signaling is implicated in many human cancers. Classical HH signaling is characterized by Smoothened (Smo)-dependent activation of Gli1 and Gli2, which transcriptionally regulate target genes. A small molecule inhibitor of Gli1 and Gli2, GANT61, was used to block HH signaling in human colon carcinoma cell lines that express HH signaling components. GANT61 administration induced robust cytotoxicity in 5 of 6 cell lines and moderate cytotoxicity in the remaining 1 cell line. In comparison, the classical Smo inhibitor, cyclopamine, induced modest cytotoxicity. Further, GANT61 treatment abolished the clonogenicity of all six human colon carcinoma cell lines. Analysis of the molecular mechanisms of GANT61-induced cytotoxicity in HT29 cells showed increased Fas expression and decreased expression of PDGFRa, which also regulates Fas. Furthermore, DR5 expression was increased whereas Bcl-2 (direct target of Gli2) was downregulated following GANT61 treatment. Suppression of Gli1 by shRNA mimicked the changes in gene expression observed in GANT61-treated cells. Overexpression of dominant-negative FADD (to abrogate Fas/DR5-mediated death receptor signaling) and/or Bcl-2 (to block mitochondria-mediated apoptosis) partially rescued GANT61induced cytotoxicity in HT29 cells. Thus, activated GLI genes repress DR5 and Fas expressions while upregulating Bcl-2 and PDGFRa expressions to inhibit Fas and facilitate cell survival. Collectively, these results highlight the importance of Gli activation downstream of Smo as a therapeutic target in models of human colon carcinoma. Cancer Res; 71(3); 1092–102. 2010 AACR.
Biomechanical Comparison of Flexible Stainless Steel and Titanium Nails with External Fixation Using a Femur Fracture Model

Abstract: There are several options available for surgical stabilization of pediatric femoral shaft fractures. The purpose of this study was to compare the stability afforded by Ender stainless steel nails, titanium elastic nails, and one-plane unilateral external fixators for the fixation using a synthetic adolescent midshaft femur fracture model. The anterior-posterior (sagittal plane) bending, lateral (coronal plane) bending, torsional, and axial stiffness values were calculated using 6 different fixation configurations. These included pairs of 3.5-mm-diameter Ender nails with and without distal locking, 3.5- and 4.0-mm-diameter titanium elastic nails as well as single- and double-stacked monolateral external fixators. Eight synthetic femur models, 4 each with simulated transverse and comminuted fracture patterns, were sequentially tested for stability afforded by the various fracture fixation configurations. External fixation exhibited significantly greater control of anterior-posterior angulation compared with all flexible-nailing systems. Although Ender nails were slightly superior to titanium nails in control of sagittal plane angulation, this was not statistically significant. Compared with the external fixation constructs, all 4 flexible nail constructs demonstrated higher torsional stability. For prevention of axial shortening, all fixation methods were similar for the transverse fracture pattern, whereas external fixation was superior to flexible nails in the comminuted fracture model. No significant benefit was demonstrated with double stacking of external fixators. These findings may help guide clinicians choose the optimal fixation method for treatment of pediatric femoral shaft fractures.
Software Project Risk Drivers as Project Manager Stressors and Coping Resources

Although the stressful nature of high risk exposure software projects and the adverse repercussions of stress on project participants and performance have long been recognized, there is still little research on the subject. This paper builds upon two foundations - the cognitive-transactional theory of stress and the concept of software project risk exposure - to propose a model of software project risk drivers as software project manager stressors and coping resources. The model posits that some software project risk drivers - core project characteristics and project objectives - play the role of stressors and that other risk drivers - project environment characteristics - play the role of coping resources. The model further suggests that software project managers are faced with both chronic stress and acute stress, which have different antecedents. This paper broadens current understanding of the role of software project risk drivers; it also contributes to knowledge on software project management by focusing on the emotional components this activity.
Microglial major histocompatibility complex glycoprotein‐1 in the axotomized facial motor nucleus: Regulation and role of tumor necrosis factor receptors 1 and 2

Presentation of antigen is key to the development of the immune response, mediated by association of antigen with major histocompatibility complex glycoproteins abbreviated as MHC1 and MHC2. In the current study, we examined the regulation of MHC1 in the brain after facial axotomy. The normal facial motor nucleus showed no immunoreactivity for MHC1 (MHC1‐IR). Transection of the facial nerve led to a strong and selective up‐regulation of MHC1‐IR on the microglia in the affected nucleus, beginning at day 2 and reaching a maximum 14 days after axotomy, coinciding with a peak influx of the T lymphocytes that express CD8, the lymphocyte coreceptor for MHC1. Specificity of the MHC1 staining was confirmed in β2‐microglobulin‐deficient mice, which lack normal cell surface MHC1‐IR. MHC1‐IR was particularly strong on phagocytic microglia, induced by delayed neuronal cell death, and correlated with the induction of mRNA for tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, and interferon‐γ and the influx of T lymphocytes. Mice with severe combined immunodeficiency (scid), lacking T and B cells, showed an increase in the number of MHC1‐positive nodules but no significant effect on overall MHC1‐IR. Transgenic deletion of the IL1 receptor type I, or the interferon‐γ receptor type 1 subunit, did not affect the microglial MHC1‐IR. However, a combined deletion of TNF receptors 1 and 2 (TNFR1&2‐KO) led to a decrease in microglial MHC1‐IR and to a striking absence of the phagocytic microglial nodules. Deletion of TNFR2 (p75) did not have an effect; deletion of TNFR1 (p55) reduced the diffuse microglial staining for MHC1‐IR but did not abolish the MHC1+ microglial nodules. In summary, neural injury leads to the induction of MHC1‐IR on the activated, phagocytic microglia. This induction of MHC1 precedes the interaction with the immune system, at least in the facial motor nucleus model. Finally, the impaired induction of these molecules, up to now, only in the TNFR‐deficient mice underscores the central role of TNF in the immune activation of the injured nervous system. J. Comp. Neurol. 470:382–399, 2004. © 2004 Wiley‐Liss, Inc.
Comparison of different winding schemes of an asynchronous machine driven by a multi-functional converter system

A comparison between different winding schemes has been carried out to optimize an asynchronous machine for an automotive electrical power steering system. The machine is driven from a multi-functional converter that consists of an inverter with integrated converter. This integrated converter provides an increased dc-link voltage to the inverter, but forces additional dc currents to flow through the machine windings. A detailed analysis is performed to describe the influence of the dc currents to the behavior of the machine and four most suitable winding schemes have been selected for the investigation. Results of the analysis demonstrate the requirement to carefully select the winding scheme when an asynchronous machine is operated from a multi-functional converter system. FEM simulations verify the results of the analysis. Four machines with different winding schemes have been built and tested together with the multi-functional converter. Experimental results are in close correlation with theoretical predictions.
Semi‐quantitative characterization of electroporation‐assisted disinfection processes for inactivation of Giardia and Cryptosporidium

The effect of electroporation (very short duration pulses of high voltage electricity) on the viability of Giardia cysts and Cryptosporidium oocysts, and on the viability of these organisms in the presence of free chlorine, combined chlorine, hydrogen peroxide and potassium permanganate, was examined. While electroporation itself had only a minor effect on survival, the combination of electrical and chemical treatment produced superior inactivation, particularly with combined chlorine, hydrogen peroxide and potassium permanganate. This enhancement may provide a relatively practical way of achieving enhanced inactivation of resistant protozoa by water disinfection processes. Further study of kinetics and optimum treatment combinations is needed.
Implementation of an electromagnetic imaging system to facilitate nasogastric and post-pyloric feeding tube placement in patients with and without critical illness.

BACKGROUND Artificial nutrition support is required to optimise nutritional status in many patients. Traditional methods of placing feeding tubes may incur clinical risk and financial costs. A technique facilitating placement of nasogastric and post-pyloric tubes via electromagnetic visual guidance may reduce the need for X-ray exposure, endoscopy time and the use of parenteral nutrition. The present study aimed to audit use of such a system at initial implementation in patients within an acute NHS Trust. METHODS A retrospective review was undertaken of dietetic and medical records for the first 14 months of using the Cortrak system. Data were collected on referral origin, preparation of the patient prior to insertion, placement success rates and need for X-ray. Cost analysis was also performed. RESULTS Referrals were received from primary consultants or consultant intensivists, often on the advice of the dietitian. Fifty-nine percent of patients received prokinetic therapy at the time of placement. Thirty-nine tube placements were attempted. Sixty-nine percent of referrals for post-pyloric tube placement resulted in successful placement. X-ray films were requested for 22% of all attempted post-pyloric placements. Less than half of nasogastric tubes were successfully passed, although none of these required X-ray confirmation. The mean cost per tube insertion attempt was 111 pounds. CONCLUSIONS This system confers advantages, particularly in terms of post-pyloric tube placement, even at this early stage of implementation. A reduction in clinical risk and cost avoidance related to X-ray exposure, the need for endoscopic tube placement and parenteral nutrition have been achieved. The implementation of this system should be considered in other centres.
F.D.I. for the induction motor using elimination theory

This paper is concerned with Fault Detection and Isolation for induction motors. A new procedure for the calculation of the ARR (Analytical Redundancy Relations) is presented. This method is based on the elimination of the unknown variables (states, unknown inputs, .) in the model equations. Simulation results are presented in normal situation and in presence of a speed sensor fault.
Ets‐1 triggers and orchestrates the malignant phenotype of mammary cancer cells within their matrix environment

Acquisition of invasive characteristics is a hallmark of breast carcinoma progression. During this phenomenon, Ets‐1 transcription factor overexpression is induced and associated with breast cancer invasiveness, and poor prognosis. We hypothesized that Ets‐1 transcription factor could be the orchestrator of a genetic program inducing the expression of genes necessary for cell motility, as postulated by the tumor microenvironment invasion model. We aimed at elucidating the role of Ets‐1 in the molecular control of mammary cancer cell invasion and aggressiveness within their matrix environment. To that purpose, mouse mammary tumor MMT epithelial cells were engineered to stably overexpress Ets‐1, or the dominant negative Ets‐1 DNA Binding domain. The biological function of Ets‐1 was assessed in three‐dimensional extracellular matrix systems recreating a microenvironmental architecture resembling in vivo geometric constraints. Ets‐1 overexpression provided MMT cells with a motile and invasive phenotype, leading to cell scattering, and impairing multicellular organization in matrix‐mimicking gels. We evidenced that Ets‐1 promoted HGF/SF activation, and the expression of its receptor, c‐Met. Ets‐1 also orchestrated switches in integrin expression pattern, towards a pro‐migratory and malignant phenotype. Moreover, Ets‐1 concomitantly triggered matrix metalloproteinases (MMP) expression and activation, thus contributing to cell scattering. Functional relevance of these observations was confirmed with blocking antibodies or MMP inhibitors. Our data highlight a critical role for Ets‐1 in the orchestration of a network of molecular and phenotypic events, converging to enhance malignant features and invasion by mammary cancer cells of their environment. Ets‐1 overexpression hence appears as a probable key step for breast cancer progression. J. Cell. Physiol. 215: 782–793, 2008. © 2008 Wiley‐Liss, Inc.
Inflammatory Cytokines Determine the Susceptibility of Human CD8 T Cells to Fas-mediated Activation-induced Cell Death through Modulation of FasL and c-FLIPS Expression*

The nature of inflammatory signals determines the outcome of T cell responses. However, little is known about how inflammatory cytokines provided to human CD8 T cells during activation affects their susceptibility to post-activation cell death. We have examined and compared the effects of the inflammatory cytokine IL-12, as well as the combination of IL-1, IL-6, and IL-23 (IL-1/6/23) on the susceptibility of primary human CD8 T cells to post-activation cell death. Human CD8 T cells activated in the presence of IL-1/6/23 underwent significantly less cell death after activation as compared with those activated in IL-12. This was due to reduced susceptibility to Fas-mediated activation-induced cell death (AICD). Mechanistically, the reduced level of cell death in CD8 T cells activated in IL-1/6/23 was a result of a low level of FasL expression and high level of c-FLIPS expression. When the effect of IL-1, IL-6, and IL-23 individually was examined, IL-1 or IL-6 alone was sufficient to inhibit CD8 T cell death that occurs after activation in IL-12. IL-1, but not IL-6, inhibited expression of FasL, whereas IL-6, but not IL-1, increased c-FLIPS expression. Our findings show that the presence of IL-1 and/or IL-6 during activation of human CD8 T cells attenuates Fas-mediated AICD, whereas IL-12 increases the susceptibility of activated CD8 T cells to this form of cell death.
Correlates of children's moderate and vigorous physical activity during weekdays and weekends.

BACKGROUND Vigorous-intensity physical activity (VPA) may confer superior health benefits for children compared to moderate-intensity physical activity (MPA), but the correlates of MPA and VPA may differ. The study purpose was to investigate associations between selected enabling, predisposing, and demographic physical activity correlates, and MPA and VPA during weekdays and at weekends. METHODS Data were gathered from 175 children (aged 10 to 11 years). MPA and VPA were assessed using accelerometers. Correlates were measured at child and school levels. Multilevel analyses identified correlates that significantly predicted MPA and VPA. RESULTS Gender significantly predicted weekday MPA (P < .001), and weekend MPA (P = .022) and VPA (P = .035). Weekday VPA was predicted by gender (P < .001), indices of multiple deprivation score (P < .003), BMI (P = .018), and school playground area (P = .046). CONCLUSIONS Gender was the most significant correlate of MPA and VPA. Children most likely to engage in weekday VPA were boys with lower deprivation scores and BMI values, with access to larger playground areas.
Isotropic resolution diffusion tensor imaging with whole brain acquisition in a clinically acceptable time

Our objective was to develop a diffusion tensor MR imaging pulse sequence that allows whole brain coverage with isotropic resolution within a clinically acceptable time. A single‐shot, cardiac‐gated MR pulse sequence, optimized for measuring the diffusion tensor in human brain, was developed to provide whole‐brain coverage with isotropic (2.5 × 2.5 × 2.5 mm) spatial resolution, within a total imaging time of approximately 15 min. The diffusion tensor was computed for each voxel in the whole volume and the data processed for visualization in three orthogonal planes. Anisotropy data were further visualized using a maximum‐intensity projection algorithm. Finally, reconstruction of fiber‐tract trajectories i.e., ‘tractography’ was performed. Images obtained with this pulse sequence provide clear delineation of individual white matter tracts, from the most superior cortical regions down to the cerebellum and brain stem. Because the data are acquired with isotropic resolution, they can be reformatted in any plane and the sequence can therefore be used, in general, for macroscopic neurological or psychiatric neuroimaging investigations. The 3D visualization afforded by maximum intensity projection imaging and tractography provided easy visualization of individual white matter fasciculi, which may be important sites of neuropathological degeneration or abnormal brain development. This study has shown that it is possible to obtain robust, high quality diffusion tensor MR data at 1.5 Tesla with isotropic resolution (2.5 × 2.5 × 2.5 mm) from the whole brain within a sufficiently short imaging time that it may be incorporated into clinical imaging protocols. Hum. Brain Mapping 15:216–230, 2002. © 2002 Wiley‐Liss, Inc.
A General Approach for Sample Size and Power Calculations Based on the Haseman–Elston Method

Risch and Zhang (1995; Science 268: 1584‐9) reported a simple sample size and power calculation approach for the Haseman–Elston method and based their computations on the null hypothesis of no genetic effect. We argue that the more reasonable null hypothesis is that of no recombination. For this null hypothesis, we provide a general approach for sample size and power calculations within the Haseman–Elston framework. We demonstrate the validity of our approach in a Monte‐Carlo simulation study and illustrate the differences using data from published segregation analyses on body weight and heritability estimates on carotid artery artherosclerotic lesions. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Pressure Effects on the Optical Properties of NdVO4

We report on optical spectroscopic measurements in pure NdVO4 crystals at pressures up to 12 GPa. The influence of pressure on the fundamental absorption band gap and Nd3+ absorption bands has been correlated with structural changes in the crystal. The experiments indicate that a phase transition takes place between 4.7 and 5.4 GPa. We have also determined the pressure dependence of the band-gap and discussed the behavior of the Nd3+ absorption lines under compression. Important changes in the optical properties of NdVO4 occur at the phase transition, which, according to Raman measurements, corresponds to a zircon to monazite phase change. In particular, in these conditions a collapse of the band gap occurs, changing the color of the crystal. The changes are not reversible. The results are analyzed in comparison with those deriving from previous studies on NdVO4 and related vanadates.
NAD Acts as an Integral Regulator of Multiple Defense Layers1[OPEN]

NAD-mediated defense responses stimulate PAMP-triggered immunity in Arabidopsis by stimulating redox signaling and modulating the hormonal balance. Pyridine nucleotides, such as NAD, are crucial redox carriers and have emerged as important signaling molecules in stress responses. Previously, we have demonstrated in Arabidopsis (Arabidopsis thaliana) that the inducible NAD-overproducing nadC lines are more resistant to an avirulent strain of Pseudomonas syringae pv tomato (Pst-AvrRpm1), which was associated with salicylic acid-dependent defense. Here, we have further characterized the NAD-dependent immune response in Arabidopsis. Quinolinate-induced stimulation of intracellular NAD in transgenic nadC plants enhanced resistance against a diverse range of (a)virulent pathogens, including Pst-AvrRpt2, Dickeya dadantii, and Botrytis cinerea. Characterization of the redox status demonstrated that elevated NAD levels induce reactive oxygen species (ROS) production and the expression of redox marker genes of the cytosol and mitochondrion. Using pharmacological and reverse genetics approaches, we show that NAD-induced ROS production functions independently of NADPH oxidase activity and light metabolism but depends on mitochondrial respiration, which was increased at higher NAD. We further demonstrate that NAD primes pathogen-induced callose deposition and cell death. Mass spectrometry analysis reveals that NAD simultaneously induces different defense hormones and that the NAD-induced metabolic profiles are similar to those of defense-expressing plants after treatment with pathogen-associated molecular patterns. We thus conclude that NAD triggers metabolic profiles rather similar to that of pathogen-associated molecular patterns and discuss how signaling cross talk between defense hormones, ROS, and NAD explains the observed resistance to pathogens.