Fast Update of Conditional Simulation Ensembles

Gaussian random field (GRF) conditional simulation is a key ingredient in many spatial statistics problems for computing Monte-Carlo estimators and quantifying uncertainties on non-linear functionals of GRFs conditional on data. Conditional simulations are known to often be computer intensive, especially when appealing to matrix decomposition approaches with a large number of simulation points. This work studies settings where conditioning observations are assimilated batch sequentially, with one point or a batch of points at each stage. Assuming that conditional simulations have been performed at a previous stage, the goal is to take advantage of already available sample paths and by-products to produce updated conditional simulations at mini- mal cost. Explicit formulae are provided, which allow updating an ensemble of sample paths conditioned on n ≥ 0 observations to an ensemble conditioned on n + q observations, for arbitrary q ≥ 1. Compared to direct approaches, the proposed formulae proveto substantially reduce computational complexity. Moreover, these formulae explicitly exhibit how the q new observations are updating the old sample paths. Detailed complexity calculations highlighting the benefits of this approach with respect to state-of-the-art algorithms are provided and are complemented by numerical experiments.

Effectiveness of meticillin-resistant Staphylococcus aureus decolonization in long-term haemodialysis patients: a systematic review and meta-analysis.

BACKGROUND Chronic haemodialysis patients are a high-risk population for meticillin-resistant Staphylococcus aureus (MRSA) colonization, which is a precursor of infection. AIM To summarize the effect of nasal (± whole-body wash) MRSA decolonization in haemodialysis patients by means of a systematic review and meta-analysis. METHODS We identified eligible studies using Medline, Embase, the Cochrane database, clinicaltrials.org, and conference abstracts investigating the success of MRSA decolonization in haemodialysis patients. For the statistical analysis, we used Stata 13 to express study-specific proportions with 95% confidence intervals. A likelihood ratio test was used to assess inter-study heterogeneity. FINDINGS Six published prospective cohort studies and one study described in a conference abstract met our inclusion criteria. From 1150 haemodialysis patients enrolled in these studies, MRSA was isolated from nasal swabs of 147 (12.8%) patients. Six of the trials used mupirocin nasal ointment and combined it with chlorhexidine body washes for decolonization. The most widely used protocol was a five-day course of mupirocin nasal ointment application three times a day, and chlorhexidine body wash once daily. The pooled success rate of decolonization was 0.88 (95% confidence interval: 0.75-0.95). A likelihood ratio test of the fixed versus the random-effects model showed significant inter-study heterogeneity (P = 0.047). Four of seven studies determined subsequent MRSA infections in 94 carriers overall, two (2%) of which experienced infection. CONCLUSION The use of mupirocin together with whole-body decolonization is highly effective in eradicating MRSA carriage in haemodialysis patients. The current literature, however, is characterized by a lack of comparative effectiveness studies for this intervention.

Irrational Beliefs and Psychological Distress: A Meta-Analysis

Background: Since the cognitive revolution of the early 1950s, cognitions have been discussed as central components in the understanding and treatment of mental illnesses. Even though there is an extensive literature on the association between therapy-related cognitions such as irrational beliefs and psychological distress over the past 60 years, there is little meta-analytical knowledge about the nature of this association. Methods: The relationship between irrational beliefs and distress was examined based on a systematic review that included 100 independent samples, gathered in 83 primary studies, using a random-effect model. The overall effects as well as potential moderators were examined: (a) distress measure, (b) irrational belief measure, (c) irrational belief type, (d) method of assessment of distress, (e) nature of irrational beliefs, (f) time lag between irrational beliefs and distress assessment, (g) nature of stressful events, (h) sample characteristics (i.e. age, gender, income, and educational, marital, occupational and clinical status), (i) developer/validator status of the author(s), and (k) publication year and country. Results: Overall, irrational beliefs were positively associated with various types of distress, such as general distress, anxiety, depression, anger, and guilt (omnibus: r = 0.38). The following variables were significant moderators of the relationship between the intensity of irrational beliefs and the level of distress: irrational belief measure and type, stressful event, age, educational and clinical status, and developer/validator status of the author. Conclusions: Irrational beliefs and distress are moderately connected to each other; this relationship remains significant even after controlling for several potential covariates.

Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia: A Network Meta-analysis.

Importance In treatment-resistant schizophrenia, clozapine is considered the standard treatment. However, clozapine use has restrictions owing to its many adverse effects. Moreover, an increasing number of randomized clinical trials (RCTs) of other antipsychotics have been published. Objective To integrate all the randomized evidence from the available antipsychotics used for treatment-resistant schizophrenia by performing a network meta-analysis. Data Sources MEDLINE, EMBASE, Biosis, PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, World Health Organization International Trial Registry, and clinicaltrials.gov were searched up to June 30, 2014. Study Selection At least 2 independent reviewers selected published and unpublished single- and double-blind RCTs in treatment-resistant schizophrenia (any study-defined criterion) that compared any antipsychotic (at any dose and in any form of administration) with another antipsychotic or placebo. Data Extraction and Synthesis At least 2 independent reviewers extracted all data into standard forms and assessed the quality of all included trials with the Cochrane Collaboration's risk-of-bias tool. Data were pooled using a random-effects model in a Bayesian setting. Main Outcomes and Measures The primary outcome was efficacy as measured by overall change in symptoms of schizophrenia. Secondary outcomes included change in positive and negative symptoms of schizophrenia, categorical response to treatment, dropouts for any reason and for inefficacy of treatment, and important adverse events. Results Forty blinded RCTs with 5172 unique participants (71.5% men; mean [SD] age, 38.8 [3.7] years) were included in the analysis. Few significant differences were found in all outcomes. In the primary outcome (reported as standardized mean difference; 95% credible interval), olanzapine was more effective than quetiapine (-0.29; -0.56 to -0.02), haloperidol (-0. 29; -0.44 to -0.13), and sertindole (-0.46; -0.80 to -0.06); clozapine was more effective than haloperidol (-0.22; -0.38 to -0.07) and sertindole (-0.40; -0.74 to -0.04); and risperidone was more effective than sertindole (-0.32; -0.63 to -0.01). A pattern of superiority for olanzapine, clozapine, and risperidone was seen in other efficacy outcomes, but results were not consistent and effect sizes were usually small. In addition, relatively few RCTs were available for antipsychotics other than clozapine, haloperidol, olanzapine, and risperidone. The most surprising finding was that clozapine was not significantly better than most other drugs. Conclusions and Relevance Insufficient evidence exists on which antipsychotic is more efficacious for patients with treatment-resistant schizophrenia, and blinded RCTs-in contrast to unblinded, randomized effectiveness studies-provide little evidence of the superiority of clozapine compared with other second-generation antipsychotics. Future clozapine studies with high doses and patients with extremely treatment-refractory schizophrenia might be most promising to change the current evidence.

Diagnostic value of immunoassays for heparin-induced thrombocytopenia: a systematic review and meta-analysis.

Immunoassays are essential in the workup of patients with suspected heparin-induced thrombocytopenia. However, the diagnostic accuracy is uncertain with regard to different classes of assays, antibody specificities, thresholds, test variations, and manufacturers. We aimed to assess diagnostic accuracy measures of available immunoassays and to explore sources of heterogeneity. We performed comprehensive literature searches and applied strict inclusion criteria. Finally, 49 publications comprising 128 test evaluations in 15 199 patients were included in the analysis. Methodological quality according to the revised tool for quality assessment of diagnostic accuracy studies was moderate. Diagnostic accuracy measures were calculated with the unified model (comprising a bivariate random-effects model and a hierarchical summary receiver operating characteristics model). Important differences were observed between classes of immunoassays, type of antibody specificity, thresholds, application of confirmation step, and manufacturers. Combination of high sensitivity (>95%) and high specificity (>90%) was found in 5 tests only: polyspecific enzyme-linked immunosorbent assay (ELISA) with intermediate threshold (Genetic Testing Institute, Asserachrom), particle gel immunoassay, lateral flow immunoassay, polyspecific chemiluminescent immunoassay (CLIA) with a high threshold, and immunoglobulin G (IgG)-specific CLIA with low threshold. Borderline results (sensitivity, 99.6%; specificity, 89.9%) were observed for IgG-specific Genetic Testing Institute-ELISA with low threshold. Diagnostic accuracy appears to be inadequate in tests with high thresholds (ELISA; IgG-specific CLIA), combination of IgG specificity and intermediate thresholds (ELISA, CLIA), high-dose heparin confirmation step (ELISA), and particle immunofiltration assay. When making treatment decisions, clinicians should be a aware of diagnostic characteristics of the tests used and it is recommended they estimate posttest probabilities according to likelihood ratios as well as pretest probabilities using clinical scoring tools.

Influence of EMS-physician presence on survival after out-of-hospital cardiopulmonary resuscitation: systematic review and meta-analysis

BACKGROUND Evidence suggests that EMS-physician-guided cardiopulmonary resuscitation (CPR) in out-of-hospital cardiac arrest (OOHCA) may be associated with improved outcomes, yet randomized controlled trials are not available. The goal of this meta-analysis was to determine the association between EMS-physician- versus paramedic-guided CPR and survival after OOHCA. METHODS AND RESULTS Studies that compared EMS-physician- versus paramedic-guided CPR in OOHCA published until June 2014 were systematically searched in MEDLINE, EMBASE and Cochrane databases. All studies were required to contain survival data. Data on study characteristics, methods, and as well as survival outcomes were extracted. A random-effects model was used for the meta-analysis due to a high degree of heterogeneity among the studies (I (2)  = 44 %). Return of spontaneous circulation [ROSC], survival to hospital admission, and survival to hospital discharge were the outcome measures. Out of 3,385 potentially eligible studies, 14 met the inclusion criteria. In the pooled analysis (n = 126,829), EMS-physician-guided CPR was associated with significantly improved outcomes compared to paramedic-guided CPR: ROSC 36.2 % (95 % confidence interval [CI] 31.0 - 41.7 %) vs. 23.4 % (95 % CI 18.5 - 29.2 %) (pooled odds ratio [OR] 1.89, 95 % CI 1.36 - 2.63, p < 0.001); survival to hospital admission 30.1 % (95 % CI 24.2 - 36.7 %) vs. 19.2 % (95 % CI 12.7 - 28.1 %) (pooled OR 1.78, 95 % CI 0.97 - 3.28, p = 0.06); and survival to discharge 15.1 % (95 % CI 14.6 - 15.7 %) vs. 8.4 % (95 % CI 8.2 - 8.5 %) (pooled OR 2.03, 95 % CI 1.48 - 2.79, p < 0.001). CONCLUSIONS This systematic review suggests that EMS-physician-guided CPR in out-of-hospital cardiac arrest is associated with improved survival outcomes.

Temporally Coherent Disparity Maps Using CRFs with Fast 4D Filtering

State of the art methods for disparity estimation achieve good results for single stereo frames, but temporal coherence in stereo videos is often neglected. In this paper we present a method to compute temporally coherent disparity maps. We define an energy over whole stereo sequences and optimize their Conditional Random Field (CRF) distributions using mean-field approximation. We introduce novel terms for smoothness and consistency between the left and right views, and perform CRF optimization by fast, iterative spatio-temporal filtering with linear complexity in the total number of pixels. Our results rank among the state of the art while having significantly less flickering artifacts in stereo sequences.

An examination of the relationship between maternal and neighborhood-level characteristics and intrauterine growth retardation in Harris County, Texas, 1999--2001

The persistence of low birth weight and intrauterine growth retardation (IUGR) in the United States has puzzled researchers for decades. Much of the work that has been conducted on adverse birth outcomes has focused on low birth weight in general and not on IUGR. Studies that have examined IUGR specifically thus far have focused primarily on individual-level maternal risk factors. These risk factors have only been able to explain a small portion of the variance in IUGR. Therefore, recent work has begun to focus on community-level risk factors in addition to the individual-level maternal characteristics. This study uses Social Ecology to examine the relationship of individual and community-level risk factors and IUGR. Logistic regression was used to establish an individual-level model based on 155, 856 births recorded in Harris County, TX during 1999-2001. IUGR was characterized using a fetal growth ratio method with race/ethnic and sex specific mean birth weights calculated from national vital records. The spatial distributions of 114,460 birth records spatially located within the City of Houston were examined using choropleth, probability and density maps. Census tracts with higher than expected rates of IUGR and high levels of neighborhood disadvantage were highlighted. Neighborhood disadvantage was constructed using socioeconomic variables from the 2000 U.S. Census. Factor analysis was used to create a unified single measure. Lastly, a random coefficients model was used to examine the relationship between varying levels of community disadvantage, given the set of individual-level risk factors for 152,997 birth records spatially located within Harris County, TX. Neighborhood disadvantage was measured using three different indices adapted from previous work. The findings show that pregnancy-induced hypertension, previous preterm infant, tobacco use and insufficient weight gain have the highest association with IUGR. Neighborhood disadvantage only slightly further increases the risk of IUGR (OR 1.12 to 1.23). Although community level disadvantage only helped to explain a small proportion of the variance of IUGR, it did have a significant impact. This finding suggests that community level risk factors should be included in future work with IUGR and that more work needs to be conducted. ^

A meta-analysis: Obesity and colorectal cancer screening

Of cancer death, colorectal cancer death ranks second in the United States. Obesity is an important risk factor for colorectal cancer (1). Early detection of colorectal cancer when it is localized can effectively reduce mortality of colorectal cancer and increase survival time of patients if they are treated. Also, previous studies showed that obese women were more likely to delay breast cancer screening and cervical cancer screening than normal weight women (2-5). However, results from prior studies demonstrating the relationship between obesity and colorectal cancer screening are not consistent. This research was done to conduct a meta-analysis of previous cross-sectional studies selected from the Medline database and to evaluate the association between obesity and colorectal cancer screening. While the odds ratio was not statistically different from one, the results from this meta-analysis under the random effects model showed that obese people are slightly less likely to have colorectal cancer screening compared to normal weight individuals (OR,0.93;95% CI 0.75-1.15). This meta-analysis was particularly sensitive to one individual study (6) and the effect of obesity on colorectal cancer screening was statistically significant (OR, 0.87; 95% CI, 0.81-0.92) after removing Heo's study. Further systematic studies focused on whether the effect of obesity on colorectal cancer screening is limited to women only are suggested. ^

The determinants of improvements in health outcomes and of cost reduction in hospital inpatient care

This study aims to address two research questions. First, ‘Can we identify factors that are determinants both of improved health outcomes and of reduced costs for hospitalized patients with one of six common diagnoses?’ Second, ‘Can we identify other factors that are determinants of improved health outcomes for such hospitalized patients but which are not associated with costs?’ The Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) database from 2003 to 2006 was employed in this study. The total study sample consisted of hospitals which had at least 30 patients each year for the given diagnosis: 954 hospitals for acute myocardial infarction (AMI), 1552 hospitals for congestive heart failure (CHF), 1120 hospitals for stroke (STR), 1283 hospitals for gastrointestinal hemorrhage (GIH), 979 hospitals for hip fracture (HIP), and 1716 hospitals for pneumonia (PNE). This study used simultaneous equations models to investigate the determinants of improvement in health outcomes and of cost reduction in hospital inpatient care for these six common diagnoses. In addition, the study used instrumental variables and two-stage least squares random effect model for unbalanced panel data estimation. The study concluded that a few factors were determinants of high quality and low cost. Specifically, high specialty was the determinant of high quality and low costs for CHF patients; small hospital size was the determinant of high quality and low costs for AMI patients. Furthermore, CHF patients who were treated in Midwest, South, and West region hospitals had better health outcomes and lower hospital costs than patients who were treated in Northeast region hospitals. Gastrointestinal hemorrhage and pneumonia patients who were treated in South region hospitals also had better health outcomes and lower hospital costs than patients who were treated in Northeast region hospitals. This study found that six non-cost factors were related to health outcomes for a few diagnoses: hospital volume, percentage emergency room admissions for a given diagnosis, hospital competition, specialty, bed size, and hospital region.^

A systematic review of clostridium difficile infection in patients with iatrogenic immunesuppression

Background: Incidence of C. difficile infection (CDI) has increased dramatically in the past decade and is the most frequent cause of nosocomial infectious diarrhea. The outcome of infection may range from mild diarrhea to life-threatening pseudomembranous colitis depending on the immunological response of the host, which is highly compromised in this special population that includes bone marrow transplant (BMT), solid organ transplant (SOT) and cancer patients on cytotoxic chemotherapy. ^ Objectives: We conducted a meta-analysis to assess the incidence rates of CDI and the time to onset of infection in patients with iatrogenic immune suppression. ^ Methods: Original studies were identified through an extensive search of electronic databases including PubMed, Ovid Medline (R), RefWorks and Biological Abstracts and their references. The overall incidence rate of CDI in the immune suppressed population was calculated using random effects model and their 95% confidence interval was derived. Differences in the incidence of CDI and time to onset of infection were calculated between the groups and within the groups. Publication bias was assessed using a funnel plot. Results: Twenty nine published articles involving 7,424 patients met the eligibility requirements. The overall incidence of CDI in the immune suppressed population is 11.1% (95% Confidence Interval (CI): 9.2–13.4%). The incidence of CDI was higher in SOT patients (14.2%, 95% CI: 6.8–21.5%); (p-value-0.022) and in cancer patients on cytotoxic chemotherapy (11.4%, 95% CI: 8.4–15.4%); (p = 0.042) than in BMT patients (10.5%, 95% CI: 7.9–13.1%). In a subgroup analysis of BMT population, the incidence of CDI is significantly higher in patients who received allogeneic BMT (15.1%, 95% CI: 11.2–20.0%; p value <0.0001). Similarly, in the SOT population, the incidence of CDI was higher in patients who underwent liver transplantation (11.0%, 95% CI: 5.6–20.3%); (p= 0.0672). The median time to onset of infection was shorter in BMT patients (p=0.0025). ^ Conclusions: It is evident from the combined analysis of these 29 published studies that the incidence of CDI in the immune suppressed population is higher. However, early diagnosis and treatment of CDI will help reduce the morbidity and mortality due to CDI in this special population.^

A systematic review of personalized therapy in patients with advanced cancer

Background: An increased understanding of the pathogenesis of cancer at the molecular level has led to the development of personalized cancer therapy based on the mutation status of the tumor. Tailoring treatments to genetic signatures has improved treatment outcomes in patients with advanced cancer. We conducted a meta-analysis to provide a quantitative summary of the response to treatment on a phase I clinical trial matched to molecular aberration in patients with advanced solid tumors. ^ Methods: Original studies that reported the results of phase I clinical trials in patients with advanced cancer treated with matched anti-cancer therapies between January 2006 and November 2011 were identified through an extensive search of Medline, Embase, Web of Science and Cochrane Library databases. Odds Ratio (OR) with 95% confidence interval (CI) was estimated for each study to assess the strength of an association between objective response rate (ORR) and mutation status. Random effects model was used to estimate the pooled OR and their 95% CI was derived. Funnel plot was used to assess publication bias. ^ Results: Thirteen studies published between January 2006 and November 2011that reported on responses to matched phase I clinical trials in patients with advanced cancer were included in the meta-analysis. Nine studies reported on the responses seen in 538 of the 835 patients with driver mutations responsive to therapy and seven studies on the responses observed in 234 of the 306 patients with mutation predictive for negative response. Random effects model was used to estimate pooled OR, which was 7.767(95% CI = 4.199 − 14.366; p-value=0.000) in patients with activating mutations that were responsive to therapy and 0.287 (95% CI = 0.119 − 0.694; p-value=0.009) in patients with mutation predictive of negative response. ^ Conclusion: It is evident from the meta-analysis that somatic mutations present in tumor tissue of patients are predictive of responses to therapy in patients with advanced cancer in phase I setting. Plethora of research and growing evidence base indicate that selection of patients based on mutation analysis of the tumor and personalizing therapy is a step forward in the war against cancer.^

Paleomagnetic analysed of two sediment cores off Cape Ghir

Holocene records documenting variations in direction and intensity of the geomagnetic field during the last about seven and a half millennia are presented for Northwest Africa. High resolution paleomagnetic analyses of two marine sediment sequences recovered from around 900 meter water depth on the upper continental slope off Cape Ghir (30°51'N, 10°16'W) were supplemented by magnetic measurements characterizing composition, concentration, grain size and coercivity of the magnetic mineral assemblage. Age control for the high sedimentation rate deposits (~60 cm/kyr) was established by AMS radiocarbon dates. The natural remanent magnetization (NRM) is very predominantly carried by a fine grained, mostly single domain (titano-)magnetite fraction allowing the reliable definition of stable NRM inclinations and declinations from alternating field demagnetization and principal component analysis. Predictions of the Korte and Constable (2005) geomagnetic field model CALS7K.2 for the study area are in fair agreement with the Holocene directional records for the most parts, yet noticeable differences exist in some intervals. The magnetic mineral inventory of the sediments reveals various climate controlled variations, specifically in concentration and grain size. A very strong impact had the mid-Holocene environmental change from humid to arid conditions on the African continent which also clearly affects relative paleointensity (RPI) estimates based on different remanence normalizers. To overcome this problem the pseudo-Thellier RPI technique has been applied. The results represent the first Holocene record of Earth's magnetic field intensity variations in the NW Africa region. It displays long term trends similar to those of model predictions, but also conspicuous millennium scale differences.

Orbital debris mitigation through deorbiting with passive electrodynamic drag

The increase of orbital debris and the consequent proliferation of smaller objects through fragmentation are driving the need for mitigation strategies. The issue is how to deorbit the satellite with an efficient system that does not impair drastically the propellant budget of the satellite and, consequently, reduces its operating life. We have been investigating, in the framework of a European-Community-funded project, a passive system that makes use of an electrodynamics tether to deorbit a satellite through Lorentz forces. The deorbiting system will be carried by the satellite itself at launch and deployed from the satellite at the end of its life. From that moment onward the system operates passively without requiring any intervention from the satellite itself. The paper summarizes the results of the analysis carried out to show the deorbiting performance of the system starting from different orbital altitudes and inclinations for a reference satellite mass. Results can be easily scaled to other satellite masses. The results have been obtained by using a high-fidelity computer model that uses the latest environmental routines for magnetic field, ionospheric density, atmospheric density and a gravity field model. The tether dynamics is modelled by considering all the main aspects of a real system as the tether flexibility and its temperature-dependent electrical conductivity. Temperature variations are computed by including all the major external and internal input fluxes and the thermal flux emitted from the tether. The results shows that a relatively compact and light system can carry out the complete deorbit of a relatively large satellite in a time ranging from a month to less than a year starting from high LEO with the best performance occurring at low orbital inclinations.

Brain tissue segmentation on Diffusion Weighted Magnetic Resonance data

Introduction Diffusion weighted Imaging (DWI) techniques are able to measure, in vivo and non-invasively, the diffusivity of water molecules inside the human brain. DWI has been applied on cerebral ischemia, brain maturation, epilepsy, multiple sclerosis, etc. [1]. Nowadays, there is a very high availability of these images. DWI allows the identification of brain tissues, so its accurate segmentation is a common initial step for the referred applications. Materials and Methods We present a validation study on automated segmentation of DWI based on the Gaussian mixture and hidden Markov random field models. This methodology is widely solved with iterative conditional modes algorithm, but some studies suggest [2] that graph-cuts (GC) algorithms improve the results when initialization is not close to the final solution. We implemented a segmentation tool integrating ITK with a GC algorithm [3], and a validation software using fuzzy overlap measures [4]. Results Segmentation accuracy of each tool is tested against a gold-standard segmentation obtained from a T1 MPRAGE magnetic resonance image of the same subject, registered to the DWI space. The proposed software shows meaningful improvements by using the GC energy minimization approach on DTI and DSI (Diffusion Spectrum Imaging) data. Conclusions The brain tissues segmentation on DWI is a fundamental step on many applications. Accuracy and robustness improvements are achieved with the proposed software, with high impact on the application’s final result.