The Chelsea Critical Care Physical Assessment Tool (CPAx): validation of an innovative new tool to measure physical morbidity in the general adult critical care population; an observational proof-of-concept pilot study.

Objective To develop a scoring system to measure physical morbidity in critical care – the Chelsea Critical Care Physical Assessment Tool (CPAx). Method The development process was iterative involving content validity indices (CVI), a focus group and an observational study of 33 patients to test construct validity against the Medical Research Council score for muscle strength, peak cough flow, Australian Therapy Outcome Measures score, Glasgow Coma Scale score, Bloomsbury sedation score, Sequential Organ Failure Assessment score, Short Form 36 (SF-36) score, days of mechanical ventilation and inter-rater reliability. Participants Trauma and general critical care patients from two London teaching hospitals. Results Users of the CPAx felt that it possessed content validity, giving a final CVI of 1.00 (P < 0.05). Construct validation data showed moderate to strong significant correlations between the CPAx score and all secondary measures, apart from the mental component of the SF-36 which demonstrated weak correlation with the CPAx score (r = 0.024, P = 0.720). Reliability testing showed internal consistency of α = 0.798 and inter-rater reliability of κ = 0.988 (95% confidence interval 0.791 to 1.000) between five raters. Conclusion This pilot work supports proof of concept of the CPAx as a measure of physical morbidity in the critical care population, and is a cogent argument for further investigation of the scoring system

Working With Deaf Alcoholics in a Vocational Training Program

Non

Production of Li, Be \& B from Baryon Inhomogeneous Primordial Nucleosynthesis

We investigate the possibility that inhomogeneous nucleosynthesis may eventually be used to explain the abundances of \li6, \be9 and B in population II stars. The present work differs from previous studies in that we have used a more extensive reaction network. It is demonstrated that in the simplest scenario the abundances of the light elements with $A\le7$ constrain the separation of inhomogeneities to sufficiently small scales that the model is indistinguishable from homogeneous nucleosynthesis and that the abundances of \li6, \be9\ and B are then below observations by several orders of magnitude. This conclusion does not depend on the \li7 constraint. We also examine alternative scenarios which involve a post-nucleosynthesis reprocessing of the light elements to reproduce the observed abundances of Li and B, while allowing for a somewhat higher baryon density (still well below the cosmological critical density). Future B/H measurements may be able to exclude even this exotic scenario and further restrict primordial nucleosynthesis to approach the homogeneous model conclusions.Comment: 18 pages; Plain TeX; UMN-TH-1131/9

Multiple uncontrolled conditions and blood pressure medication intensification: an observational study

Abstract Background Multiple uncontrolled medical conditions may act as competing demands for clinical decision making. We hypothesized that multiple uncontrolled cardiovascular risk factors would decrease blood pressure (BP) medication intensification among uncontrolled hypertensive patients. Methods We observed 946 encounters at two VA primary care clinics from May through August 2006. After each encounter, clinicians recorded BP medication intensification (BP medication was added or titrated). Demographic, clinical, and laboratory information were collected from the medical record. We examined BP medication intensification by presence and control of diabetes and/or hyperlipidemia. 'Uncontrolled' was defined as hemoglobin A1c &#8805; for diabetes, BP &#8805; 140/90 mmHg (&#8805; 130/80 mmHg if diabetes present) for hypertension, and low density lipoprotein cholesterol (LDL-c) &#8805; 130 mg/dl (&#8805; 100 mg/dl if diabetes present) for hyperlipidemia. Hierarchical regression models accounted for patient clustering and adjusted medication intensification for age, systolic BP, and number of medications. Results Among 387 patients with uncontrolled hypertension, 51.4% had diabetes (25.3% were uncontrolled) and 73.4% had hyperlipidemia (22.7% were uncontrolled). The BP medication intensification rate was 34.9% overall, but higher in individuals with uncontrolled diabetes and uncontrolled hyperlipidemia: 52.8% overall and 70.6% if systolic BP &#8805; 10 mmHg above goal. Intensification rates were lowest if diabetes or hyperlipidemia were controlled, lower than if diabetes or hyperlipidemia were not present. Multivariable adjustment yielded similar results. Conclusions The presence of uncontrolled diabetes and hyperlipidemia was associated with more guideline-concordant hypertension care, particularly if BP was far from goal. Efforts to understand and improve BP medication intensification in patients with controlled diabetes and/or hyperlipidemia are warranted.http://deepblue.lib.umich.edu/bitstream/2027.42/78266/1/1748-5908-5-55.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78266/2/1748-5908-5-55.pdfPeer Reviewe

Gastrointestinal and liver disease in patients with schizophrenia:A narrative review

Schizophrenia is a severe mental illness which can have a devastating impact on an individual’s quality of life. Comorbidities are high amongst patients and life expectancy is approximately 15 years less than the general population. Despite the well-known increased mortality, little is known about the impact of gastrointestinal and liver disease on patients with schizophrenia. We aimed to review the literature and to make recommendations regarding future care. Literature searches were performed on PubMed to identify studies related to gastrointestinal and liver disease in patients with schizophrenia. High rates of chronic liver disease were reported, with Non-Alcoholic Fatty Liver Disease being of particular concern; antipsychotics and metabolic syndrome were contributing factors. Rates of acute liver failure were low but have been associated with antipsychotic use and paracetamol overdose. Coeliac disease has historically been linked to schizophrenia; however, recent research suggests that a causal link is yet to be proven. Evidence is emerging regarding the relationships between schizophrenia and peptic ulcer disease, inflammatory bowel disease and irritable bowel syndrome; clinical vigilance regarding these conditions should be high. Patients with schizophrenia poorly engage with bowel cancer screening programmes, leading to late diagnosis and increased mortality. Clozapine induced constipation is a significant issue for many patients and requires close monitoring. There is a significant burden of gastrointestinal and liver disease amongst patients with schizophrenia. Better levels of support from all members of the medical team are essential to ensure that appropriate, timely care is provided

A Comparative Study of High-Contrast Fluorescence Lifetime Probes for Imaging Amyloid in Tissue

Optical imaging of protein aggregates in living and post-mortem tissue can often be impeded by unwanted fluorescence, prompting the need for novel methods to extract meaningful signal in complex biological environments. Historically, benzothiazolium derivatives, prominently Thioflavin T, have been the state-of-the-art fluorescent probes for amyloid aggregates, but their optical, structural, and binding properties typically limit them to in vitro applications. This study compares the use of novel uncharged derivative, PAP_1, with parent Thioflavin T as a fluorescence lifetime imaging probe. This is applied specifically to imaging recombinant α-synuclein aggregates doped into brain tissue. Despite the 100-fold lower brightness of PAP_1 compared to that of Thioflavin T, PAP_1 binds to α-synuclein aggregates with an affinity several orders of magnitude greater than Thioflavin T; thus, we observe a specific decrease in the fluorescence lifetime of PAP_1 bound to α-synuclein aggregates, resulting in a separation of >1.4 standard deviations between PAP_1-stained brain tissue background and α-synuclein aggregates that is not observed with Thioflavin T. This enables contrast between highly fluorescent background tissue and amyloid fibrils that is attributed to the greater affinity of PAP_1 for α-synuclein aggregates, avoiding the substantial off-target staining observed with Thioflavin T

Classification of Generalized Symmetries for the Vacuum Einstein Equations

A generalized symmetry of a system of differential equations is an infinitesimal transformation depending locally upon the fields and their derivatives which carries solutions to solutions. We classify all generalized symmetries of the vacuum Einstein equations in four spacetime dimensions. To begin, we analyze symmetries that can be built from the metric, curvature, and covariant derivatives of the curvature to any order; these are called natural symmetries and are globally defined on any spacetime manifold. We next classify first-order generalized symmetries, that is, symmetries that depend on the metric and its first derivatives. Finally, using results from the classification of natural symmetries, we reduce the classification of all higher-order generalized symmetries to the first-order case. In each case we find that the generalized symmetries are infinitesimal generalized diffeomorphisms and constant metric scalings. There are no non-trivial conservation laws associated with these symmetries. A novel feature of our analysis is the use of a fundamental set of spinorial coordinates on the infinite jet space of Ricci-flat metrics, which are derived from Penrose's ``exact set of fields'' for the vacuum equations.Comment: 57 pages, plain Te

A Detailed Observational Analysis of V1324 Sco, the Most Gamma-Ray Luminous Classical Nova to Date

It has recently been discovered that some, if not all, classical novae emit GeV gamma rays during outburst, but the mechanisms involved in the production of the gamma rays are still not well understood. We present here a comprehensive multi-wavelength dataset---from radio to X-rays---for the most gamma-ray luminous classical nova to-date, V1324 Sco. Using this dataset, we show that V1324 Sco is a canonical dusty Fe-II type nova, with a maximum ejecta velocity of 2600 km s$^{-1}$ and an ejecta mass of few $\times 10^{-5}$ M$_{\odot}$. There is also evidence for complex shock interactions, including a double-peaked radio light curve which shows high brightness temperatures at early times. To explore why V1324~Sco was so gamma-ray luminous, we present a model of the nova ejecta featuring strong internal shocks, and find that higher gamma-ray luminosities result from higher ejecta velocities and/or mass-loss rates. Comparison of V1324~Sco with other gamma-ray detected novae does not show clear signatures of either, and we conclude that a larger sample of similarly well-observed novae is needed to understand the origin and variation of gamma rays in novae.Comment: 26 pages, 13 figure

A unified resource and configurable model of the synapse proteome and its role in disease

Genes encoding synaptic proteins are highly associated with neuronal disorders many of which show clinical co-morbidity. We integrated 58 published synaptic proteomic datasets that describe over 8000 proteins and combined them with direct protein–protein interactions and functional metadata to build a network resource that reveals the shared and unique protein components that underpin multiple disorders. All the data are provided in a flexible and accessible format to encourage custom use