What do cyclists need to see to avoid single-bicycle crashes?

The number of single-bicycle crash victims is substantial in countries with high levels of cycling. To study the role of visual characteristics of the infrastructure, such as pavement markings, in single-bicycle crashes, a study in two steps was conducted. In Study 1, a questionnaire study was conducted among bicycle crash victims (n = 734). Logistic regression was used to study the relationship between the crashes and age, light condition, alcohol use, gaze direction and familiarity with the crash scene. In Study 2, the image degrading and edge detection method (IDED-method) was used to investigate the visual characteristics of 21 of the crash scenes. The results of the studies indicate that crashes, in which the cyclist collided with a bollard or road narrowing or rode off the road, were related to the visual characteristics of bicycle facilities. Edge markings, especially in curves of bicycle tracks, and improved conspicuity of bollards are recommended. Statement of Relevance: Elevated single-bicycle crash numbers are common in countries with high levels of cycling. No research has been conducted on what cyclists need to see to avoid this type of crash. The IDED-method to investigate crash scenes is new and proves to be a powerful tool to quantify 'visual accessibility'. © 2011 Taylor & Francis

Glucocorticoid receptor mRNA levels are selectively decreased in neutrophils of children with sepsis

Objective: Corticosteroids are used in sepsis treatment to benefit outcome. However, discussion remains on which patients will benefit from treatment. Inter-individual variations in cortisol sensitivity, mediated through the glucocorticoid receptor, might play a role in the observed differences. Our aim was to study changes in mRNA levels of three glucocorticoid receptor splice variants in neutrophils of children with sepsis. Patients and design: Twenty-three children admitted to the pediatric intensive care unit with sepsis or septic shock were included. Neutrophils were isolated at days 0, 3 and 7, and after recovery (>3 months). mRNA levels of the glucocorticoid receptor splice variants GR-α (determining most of the cortisol effect), GR-P (increasing GR-α effect) and GR-β (inhibitor of GR-α) were measured quantitatively. Main results: Neutrophils from sepsis patients showed decreased levels of glucocorticoid receptor mRNA of the GR-α and GR-P splice variants on day 0 compared to after recovery. GR-α and GR-P mRNA levels showed a gradual recovery on days 3 and 7 and normalized after recovery. GR-β mRNA levels did not change significantly during sepsis. GR expression was negatively correlated to interleukin-6 (a measure of disease severity, r = -0.60, P = 0.009). Conclusions: Children with sepsis or septic shock showed a transient depression of glucocorticoid receptor mRNA in their neutrophils. This feature may represent a tissue-specific adaptation during sepsis leading to increased cortisol resistance of neutrophils. Our study adds to understanding the mechanism of cortisol sensitivity in immune cells. Future treatment strategies, aiming at timing and tissue specific regulation of glucocorticoids, might benefit patients with sepsis or septic shock

Polinomno filtriranje: postizanje bilo kojeg stupnja na nepravilno uzorkovanim podacima

Conventionally, polynomial filters are derived for evenly spaced points. Here, a derivation of polynomial filters for irregularly spaced points is provided and illustrated by example. The filter weights and variance reduction factors (VRFs) for both expanding memory polynomial (EMP) and fading-memory polynomial (FMP) filters are programmatically derived so that the expansion up to any degree can be generated. (Matlab was used for doing the symbolic weight derivations utilizing Symbolic Toolbox functions.) Order-switching and length-adaption are briefly considered. Outlier rejection and Cramer-Rao Lower Bound consistency are touched upon. In terms of performance, the VRF and its decay for the EMP filter is derived as a function of length (n) and the switch-over point is calculated where the VRFs of the EMP and FMP filters are equal. Empirical results verifying the derivation and implementation are reported.Polinomni filtri uobičajeno se rade za ravnomjerno raspoređene točke u prostoru. U ovom radu dana je derivacija polinomnih filtara za neravnomjerno raspoređene točke. Težinske vrijednosti filtra i faktori smanjenja varijance (VRF-ovi) za polinom proširene memorije (EMP) i polinom oslabljenje memorije (FMP) su programski podržani tako da se može napraviti ekspanzija do bilo kojeg stupnja. Kratko su razmotreni i promjena poretka i adaptacija dužine filtra. Dotaknute su i metode odbijanja jako raspršenih rezultata i Cramer-Raove konzistencije donje granice. VRF i njegovo opadanje za EMP filtar izvedeno je kao funkcija duljine (n) i izračunata je točka prijelaza gdje su VRF-ovi od EMP i FMP filtara jednaki. Predočeni su empirijski rezultati koji verificiraju izvod i implementaciju

Bayesian Integration and Non-Linear Feedback Control in a Full-Body Motor Task

A large number of experiments have asked to what degree human reaching movements can be understood as being close to optimal in a statistical sense. However, little is known about whether these principles are relevant for other classes of movements. Here we analyzed movement in a task that is similar to surfing or snowboarding. Human subjects stand on a force plate that measures their center of pressure. This center of pressure affects the acceleration of a cursor that is displayed in a noisy fashion (as a cloud of dots) on a projection screen while the subject is incentivized to keep the cursor close to a fixed position. We find that salient aspects of observed behavior are well-described by optimal control models where a Bayesian estimation model (Kalman filter) is combined with an optimal controller (either a Linear-Quadratic-Regulator or Bang-bang controller). We find evidence that subjects integrate information over time taking into account uncertainty. However, behavior in this continuous steering task appears to be a highly non-linear function of the visual feedback. While the nervous system appears to implement Bayes-like mechanisms for a full-body, dynamic task, it may additionally take into account the specific costs and constraints of the task

Hepatotoxicity and effectiveness of a Nevirapine-based antiretroviral therapy in HIV-infected patients with or without viral hepatitis B or C infection in Cameroon

Background: Coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) in HIV-infected patients receiving a commonly used nevirapine-based antiretroviral therapy is a major concern for African clinicians owing to its high prevalence, the infrequent testing and treatment of viral hepatitis, and the impact of liver disease on the tolerability and effectiveness of anti-HIV treatment. We compared the hepatotoxicity and the immunological, virological and clinical effectiveness of a nevirapine-based antiretroviral therapy between patients infected with HIV only and patients coinfected with hepatitis B or C virus in Cameroon. Methods: A retrospective cohort study was conducted among HIV-1-infected patients. Plasma HBV DNA and HCV RNA were tested in positive or indeterminate samples for HBsAg or HCV antibodies, respectively. All patients received nevirapine and lamivudine plus stavudine or zidovudine. Results: Of 169 HIV-1-infected patients with a median baseline CD4 count of 135 cells/mm(3) (interquartile range [IQR] 67 218), 21% were coinfected with HBV or HCV. In coinfected patients, the median viral load was 2.47 x 107 IU/mL for HBV (IQR 3680-1.59 x 10(8)) and 928 000 IU/mL for HCV (IQR 178 400-2.06 x 10(6)). Multivariate analyses showed that the risk of hepatotoxicity was 2-fold higher in coinfected patients (p < 0.01). The response to antiretroviral therapy was however comparable between monoinfected and coinfected patients in terms of CD4 cell count increase (p = 0.8), HIV-1 viral load below 400 copies/mL (p = 0.9), death (p = 0.3) and death or new AIDS-defining event (p = 0.1). Nevirapine was replaced by a protease inhibitor in 4 patients owing to hepatotoxicity. Conclusion: This study suggests that the nevirapine-based antiretroviral therapy could be used safely as first-line treatment in patients with low CD4 cell count in Africa despite frequent coinfections with HBV or HCV and infrequent testing of these infections. Although testing for HBV and HCV should be systematically performed before initiating antiretroviral therapy, transaminases elevations at baseline or during treatment should be a decisive argument for testing when hepatitis status is unknown

Artificial intelligence for detection of microsatellite instability in colorectal cancer-a multicentric analysis of a pre-screening tool for clinical application.

BACKGROUND Microsatellite instability (MSI)/mismatch repair deficiency (dMMR) is a key genetic feature which should be tested in every patient with colorectal cancer (CRC) according to medical guidelines. Artificial intelligence (AI) methods can detect MSI/dMMR directly in routine pathology slides, but the test performance has not been systematically investigated with predefined test thresholds. METHOD We trained and validated AI-based MSI/dMMR detectors and evaluated predefined performance metrics using nine patient cohorts of 8343 patients across different countries and ethnicities. RESULTS Classifiers achieved clinical-grade performance, yielding an area under the receiver operating curve (AUROC) of up to 0.96 without using any manual annotations. Subsequently, we show that the AI system can be applied as a rule-out test: by using cohort-specific thresholds, on average 52.73% of tumors in each surgical cohort [total number of MSI/dMMR = 1020, microsatellite stable (MSS)/ proficient mismatch repair (pMMR) = 7323 patients] could be identified as MSS/pMMR with a fixed sensitivity at 95%. In an additional cohort of N = 1530 (MSI/dMMR = 211, MSS/pMMR = 1319) endoscopy biopsy samples, the system achieved an AUROC of 0.89, and the cohort-specific threshold ruled out 44.12% of tumors with a fixed sensitivity at 95%. As a more robust alternative to cohort-specific thresholds, we showed that with a fixed threshold of 0.25 for all the cohorts, we can rule-out 25.51% in surgical specimens and 6.10% in biopsies. INTERPRETATION When applied in a clinical setting, this means that the AI system can rule out MSI/dMMR in a quarter (with global thresholds) or half of all CRC patients (with local fine-tuning), thereby reducing cost and turnaround time for molecular profiling

Hepatic safety of antibiotics used in primary care

Antibiotics used by general practitioners frequently appear in adverse-event reports of drug-induced hepatotoxicity. Most cases are idiosyncratic (the adverse reaction cannot be predicted from the drug's pharmacological profile or from pre-clinical toxicology tests) and occur via an immunological reaction or in response to the presence of hepatotoxic metabolites. With the exception of trovafloxacin and telithromycin (now severely restricted), hepatotoxicity crude incidence remains globally low but variable. Thus, amoxicillin/clavulanate and co-trimoxazole, as well as flucloxacillin, cause hepatotoxic reactions at rates that make them visible in general practice (cases are often isolated, may have a delayed onset, sometimes appear only after cessation of therapy and can produce an array of hepatic lesions that mirror hepatobiliary disease, making causality often difficult to establish). Conversely, hepatotoxic reactions related to macrolides, tetracyclines and fluoroquinolones (in that order, from high to low) are much rarer, and are identifiable only through large-scale studies or worldwide pharmacovigilance reporting. For antibiotics specifically used for tuberculosis, adverse effects range from asymptomatic increases in liver enzymes to acute hepatitis and fulminant hepatic failure. Yet, it is difficult to single out individual drugs, as treatment always entails associations. Patients at risk are mainly those with previous experience of hepatotoxic reaction to antibiotics, the aged or those with impaired hepatic function in the absence of close monitoring, making it important to carefully balance potential risks with expected benefits in primary care. Pharmacogenetic testing using the new genome-wide association studies approach holds promise for better understanding the mechanism(s) underlying hepatotoxicity

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

SCOPUS: ar.jinfo:eu-repo/semantics/publishe