SNAP-2 EPICCS: the second Sprint National Anaesthesia Project-EPIdemiology of Critical Care after Surgery: protocol for an international observational cohort study.

INTRODUCTION: The admission of high-risk patients to critical care after surgery is a recommended standard of care. Nevertheless, poor compliance against this recommendation has been repeatedly demonstrated in large epidemiological studies. It is unclear whether this is due to reasons of capacity, equipoise, poor quality clinical care or because hospitals are working creatively to create capacity for augmented care on normal surgical wards. The EPIdemiology of Critical Care after Surgery study aims to address these uncertainties. METHODS AND ANALYSIS: One-week observational cohort study in the UK and Australasia. All patients undergoing inpatient (overnight stay) surgery will be included. All will have prospective data collection on risk factors, surgical procedure and postoperative outcomes including the primary outcome of morbidity (measured using the Postoperative Morbidity Survey on day 7 after surgery) and secondary outcomes including length of stay and mortality. Data will also be collected on critical care referral and admission, surgical cancellations and critical care occupancy. The epidemiology of patient characteristics, processes and outcomes will be described. Inferential techniques (multilevel multivariable regression, propensity score matching and instrumental variable analysis) will be used to evaluate the relationship between critical care admission and postoperative outcome. ETHICS AND DISSEMINATION: The study has received ethical approval from the National Research Ethics Service in the UK and equivalent in Australasia. The collection of patient identifiable data without prior consent has been approved by the Confidentiality Advisory Group (England and Wales) and the Public Privacy and Patient Benefit Panel (Scotland). In these countries, patient identifiable data will be used to link prospectively collected data with national registers of death and inpatient administrative data. The study findings will be disseminated using a multimedia approach with the support of our lay collaborators, to patients, public, policy-makers, clinical and academic audiences

Direct Dark Matter Search using CCDs

There is currently vast evidence for Dark Matter (DM) from astronomical observations. However, in spite of tremendous efforts by large experimental groups, there is no confirmed direct detection of the dark matter in our galaxy. Recent experimental results and theoretical developments suggest the possibility of a DM particle with mass below 10 GeV, such a particle would escape most of the direct searches due to the large thresholds for the detection of nuclear recoils typically used. In this work we study the possibility of a new Dark Matter search with an unprecedented low threshold for the detection of nuclear recoils using high-resistivity CCD detectors (hr-CCD). Due to their extremely low readout noise and the relatively large active mass, these detectors present a unique opportunity in this field.Comment: paper presented at the Taup2009 Conferenc

Developing and validating subjective and objective risk-assessment measures for predicting mortality after major surgery: An international prospective cohort study

Background: Preoperative risk prediction is important for guiding clinical decision-making and resource allocation. Clinicians frequently rely solely on their own clinical judgement for risk prediction rather than objective measures. We aimed to compare the accuracy of freely available objective surgical risk tools with subjective clinical assessment in predicting 30-day mortality. Methods and findings: We conducted a prospective observational study in 274 hospitals in the United Kingdom (UK), Australia, and New Zealand. For 1 week in 2017, prospective risk, surgical, and outcome data were collected on all adults aged 18 years and over undergoing surgery requiring at least a 1-night stay in hospital. Recruitment bias was avoided through an ethical waiver to patient consent; a mixture of rural, urban, district, and university hospitals participated. We compared subjective assessment with 3 previously published, open-access objective risk tools for predicting 30-day mortality: the Portsmouth-Physiology and Operative Severity Score for the enUmeration of Mortality (P-POSSUM), Surgical Risk Scale (SRS), and Surgical Outcome Risk Tool (SORT). We then developed a logistic regression model combining subjective assessment and the best objective tool and compared its performance to each constituent method alone. We included 22,631 patients in the study: 52.8% were female, median age was 62 years (interquartile range [IQR] 46 to 73 years), median postoperative length of stay was 3 days (IQR 1 to 6), and inpatient 30-day mortality was 1.4%. Clinicians used subjective assessment alone in 88.7% of cases. All methods overpredicted risk, but visual inspection of plots showed the SORT to have the best calibration. The SORT demonstrated the best discrimination of the objective tools (SORT Area Under Receiver Operating Characteristic curve [AUROC] = 0.90, 95% confidence interval [CI]: 0.88–0.92; P-POSSUM = 0.89, 95% CI 0.88–0.91; SRS = 0.85, 95% CI 0.82–0.87). Subjective assessment demonstrated good discrimination (AUROC = 0.89, 95% CI: 0.86–0.91) that was not different from the SORT (p = 0.309). Combining subjective assessment and the SORT improved discrimination (bootstrap optimism-corrected AUROC = 0.92, 95% CI: 0.90–0.94) and demonstrated continuous Net Reclassification Improvement (NRI = 0.13, 95% CI: 0.06–0.20, p < 0.001) compared with subjective assessment alone. Decision-curve analysis (DCA) confirmed the superiority of the SORT over other previously published models, and the SORT–clinical judgement model again performed best overall. Our study is limited by the low mortality rate, by the lack of blinding in the ‘subjective’ risk assessments, and because we only compared the performance of clinical risk scores as opposed to other prediction tools such as exercise testing or frailty assessment. Conclusions: In this study, we observed that the combination of subjective assessment with a parsimonious risk model improved perioperative risk estimation. This may be of value in helping clinicians allocate finite resources such as critical care and to support patient involvement in clinical decision-making

Spatial gradients in the cosmological constant

It is possible that there may be differences in the fundamental physical parameters from one side of the observed universe to the other. I show that the cosmological constant is likely to be the most sensitive of the physical parameters to possible spatial variation, because a small variation in any of the other parameters produces a huge variation of the cosmological constant. It therefore provides a very powerful {\em indirect} evidence against spatial gradients or temporal variation in the other fundamental physical parameters, at least 40 orders of magnitude more powerful than direct experimental constraints. Moreover, a gradient may potentially appear in theories where the variability of the cosmological constant is connected to an anthropic selection mechanism, invoked to explain the smallness of this parameter. In the Hubble damping mechanism for anthropic selection, I calculate the possible gradient. While this mechanism demonstrates the existence of this effect, it is too small to be seen experimentally, except possibly if inflation happens around the Planck scale.Comment: 12 page

Constraints on the CMB temperature redshift dependence from SZ and distance measurements

The relation between redshift and the CMB temperature, $T_{CMB}(z)=T_0(1+z)$ is a key prediction of standard cosmology, but is violated in many non-standard models. Constraining possible deviations to this law is an effective way to test the $\Lambda$CDM paradigm and search for hints of new physics. We present state-of-the-art constraints, using both direct and indirect measurements. In particular, we point out that in models where photons can be created or destroyed, not only does the temperature-redshift relation change, but so does the distance duality relation, and these departures from the standard behaviour are related, providing us with an opportunity to improve constraints. We show that current datasets limit possible deviations of the form $T_{CMB}(z)=T_0(1+z)^{1-\beta}$ to be $\beta=0.004\pm0.016$ up to a redshift $z\sim 3$. We also discuss how, with the next generation of space and ground-based experiments, these constraints can be improved by more than one order of magnitude.Comment: 27 pages, 11 figure

Supernova / Acceleration Probe: A Satellite Experiment to Study the Nature of the Dark Energy

The Supernova / Acceleration Probe (SNAP) is a proposed space-based experiment designed to study the dark energy and alternative explanations of the acceleration of the Universe's expansion by performing a series of complementary systematics-controlled measurements. We describe a self-consistent reference mission design for building a Type Ia supernova Hubble diagram and for performing a wide-area weak gravitational lensing study. A 2-m wide-field telescope feeds a focal plane consisting of a 0.7 square-degree imager tiled with equal areas of optical CCDs and near infrared sensors, and a high-efficiency low-resolution integral field spectrograph. The SNAP mission will obtain high-signal-to-noise calibrated light-curves and spectra for several thousand supernovae at redshifts between z=0.1 and 1.7. A wide-field survey covering one thousand square degrees resolves ~100 galaxies per square arcminute. If we assume we live in a cosmological-constant-dominated Universe, the matter density, dark energy density, and flatness of space can all be measured with SNAP supernova and weak-lensing measurements to a systematics-limited accuracy of 1%. For a flat universe, the density-to-pressure ratio of dark energy can be similarly measured to 5% for the present value w0 and ~0.1 for the time variation w'. The large survey area, depth, spatial resolution, time-sampling, and nine-band optical to NIR photometry will support additional independent and/or complementary dark-energy measurement approaches as well as a broad range of auxiliary science programs. (Abridged)Comment: 40 pages, 18 figures, submitted to PASP, http://snap.lbl.go

Is there scope for community health nurses to address lifestyle risk factors? : the community nursing SNAP trial

Background: This paper examines the opportunity and need for lifestyle interventions for patients attending generalist community nursing services in Australia. This will help determine the scope for risk factor management within community health care by generalist community nurses (GCNs).Methods: This was a quasi-experimental study conducted in four generalist community nursing services in NSW, Australia. Prior to service contacts, clients were offered a computer-assisted telephone interview to collect baseline data on socio-demographics, health conditions, smoking status, physical activity levels, alcohol consumption, height and weight, fruit and vegetable intake and 'readiness-to-change' for lifestyle risk factors.Results: 804 clients participated (a response rate of 34.1%). Participants had higher rates of obesity (40.5% vs 32.1%) and higher prevalence of multiple risk factors (40.4% vs 29.5%) than in the general population. Few with a SNAPW (Smoking-Nutrition-Alcohol-Physical-Activity-Weight) risk factor had received advice or referral in the previous 3 months. The proportion of clients identified as at risk and who were open to change (i.e. contemplative, in preparation or in action phase) were 65.0% for obese/overweight; 73.8% for smokers; 48.2% for individuals with high alcohol intake; 83.5% for the physically inactive and 59.0% for those with poor nutrition.Conclusions: There was high prevalence of lifestyle risk factors. Although most were ready to change, few clients recalled having received any recent lifestyle advice. This suggests that there is considerable scope for intervention by GCNs. The results of this trial will shed light on how best to implement the lifestyle risk factor management in routine practice

A New Approach to Testing Dark Energy Models by Observations

We propose a new approach to the consistency test of dark energy models with observations. To test a category of dark energy models, we suggest introducing a characteristic Q(z) that in general varies with the redshift z but in those models plays the role of a (constant) distinct parameter. Then, by reconstructing dQ(z)/dz from observational data and comparing it with zero we can assess the consistency between data and the models under consideration. For a category of models that passes the test, we can further constrain the distinct parameter of those models by reconstructing Q(z) from data. For demonstration, in this paper we concentrate on quintessence. In particular we examine the exponential potential and the power-law potential via a widely used parametrization of the dark energy equation of state, w(z) = w_0 + w_a z/(1+z), for data analysis. This method of the consistency test is particularly efficient because for all models we invoke the constraint of only a single parameter space that by choice can be easily accessed. The general principle of our approach is not limited to dark energy. It may also be applied to the testing of various cosmological models and even the models in other fields beyond the scope of cosmology.Comment: 19 pages, 5 figure

The signature of dark energy perturbations in galaxy cluster surveys

All models of dynamical dark energy possess fluctuations, which affect the number of galaxy clusters in the Universe. We have studied the impact of dark energy clustering on the number of clusters using a generalization of the spherical collapse model and the Press-Schechter formalism. Our statistical analysis is performed in a 7-parameter space using the Fisher matrix method, for several hypothetical Sunyaev-Zel'dovich and weak lensing (shear maps) surveys. In some scenarios, the impact of these fluctuations is large enough that their effect could already be detected by existing instruments such as the South Pole Telescope, when its data is combined with WMAP and SDSS. Future observations could go much further and probe the nature of dark energy by distinguishing between different models on the basis of their perturbations, not only their expansion histories.Comment: 5 pages, 4 figure

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection