Bilevel optimization approach to design of network of bike lanes

A bike lane is an effective way to improve cycling safety and to decrease greenhouse gas emissions with the promotion of cycling. Improvements include high-quality off-road facilities and on-road bike lanes. Whereas construction of off-road lanes is not always possible because of urban land constraints and construction costs, on-road lanes can be a cost-effective alternative. An optimization framework for the design of a network of bike lanes in an urban road network was proposed. This framework identified links on which a bike lane could be introduced. Allocation of a lane to cyclists would increase the use of cycling, although it could disadvantage auto traffic. The presented approach balances the effects of a bike lane for all stakeholders. A bilevel optimization was proposed to encompass the benefits of cyclists and car users at the upper level and a model for traffic and bike demand assignment at the lower level. The objective function was defined by a weighted sum of a measure for private car users (total travel time) versus a measure for bike users (total travel distance on bike lanes). A genetic algorithm was developed to solve the bilevel formulation, which included introduction of a special crossover technique and a mutation technique. The proposed optimization will help transport authorities at the planning stage to quantify the outcomes of various strategies for active transport

Hyperkalemia and electrocardiogram manifestations in end-stage renal disease

Hyperkalemia is one of the more common acute life-threatening metabolic emergencies. The aim of our study is to determine the correlation and accuracy of abnormal ECG parameters as a function of serum potassium concentration in the end-stage renal disease (ESRD) population. We performed a retrospective chart review of emergency department patients presenting with ESRD and receiving emergent hemodialysis treatment. A total of 96 patients, each with five independent ED visits, provided 480 sets of ECGs and electrolytes. Of these, four ECGs were excluded for inability to interpret, leaving a total of 476 patient encounters that met all inclusion criteria. Linear regression analysis on the limited data set for serum potassium versus T/R in V2, V3, and V4, PR, and QRS found weak correlations (

NOD2 Gene Status in Pediatric and Adult Crohn Disease Patients in Algerian Population

Background: Chronic Inflammatory Bowel Diseases (IBD), including Crohn disease (CD) and ulcerative colitis (UC) are gastrointestinal disorders under the influence of a complex genetic basis. One hundred sixty-three predisposition loci were identified by genome-wide association (GWAS) studies, refocusing the pathogenesis of IBD on immunity genes. The NOD2 gene has been widely implicated in the pathogenesis of IBD in different geographical populations. Three most common mutations within NOD2 gene were selected, namely SNP8, C/T (R702W variant), SNP12, G/C (G908R variant) and SNP13, (1007fsinsC variant). We investigated these three SNP in a pediatric Algerian cohort for the first time, since no previous association studies between pediatric IBD and the NOD2 gene were available for the Algerian population. Methods: A case-control study was performed in the pediatric IBD population. PCR-RFLP was used to detect the three NOD2 gene mutations in 46 CD patients and 100 healthy control subjects. All samples were genotyped for the NOD2 gene Polymorphisms by the PCR-RFLP method. Statistical study was performed by the Fisher exact test or Chi-2 using the GraphPad Prism 7.0 software. Then data from the pediatric cohort were compared to our precedent published data from a case-control study performed on a cohort including 132 IBD patients and 114 healthy control subjects. Results: In the pediatric cohort, there is no statistically differences in allelic frequencies between cases and controls respectively R702W (6.36% vs. 6.38%; p=1), G908R (2.72% vs. 1.06%; p=0.6) and 1007fsinsC mutation was found neither in the CD patients nor in control. In the adult cohort, the R702W allelic variant showed the highest frequency in CD patients (8%) (p = 0.09, OR = 3.67, 95%CI: 0.48-4.87) but its frequency was also high in controls (5%) (p = 0.4; OR = 1.4; 95%CI: 0.65-3.31). Likewise, G908R and 1007fsinsC mutations showed similar frequency in CD patients and in controls (3% vs. 2%; p= 0.5; OR=1.67; 95%CI: 0.44-6.34; 2% vs.1%; p=0.4, OR=2.69; 95%CI: 0.48-14.87, respectively). The total frequency of the mutated NOD2 chromosomes was higher in adult CD patients (13%) than in pediatric CD patients (9%). In our precedent study on the adult cohort, we have confirmed that the NOD2 gene is significantly associated with a specific clinical sub-phenotype in CD, indicating that the NOD2 gene is involved in IBD susceptibility across Algerian adult population. However, we failed to show any association between the three variants of the NOD2 gene across Algerian pediatric CD patients. Conclusion: In our precedent study, we have confirmed that the NOD2 gene is significantly associated with a specific clinical sub-phenotype in adult CD patients. Here, our results show no association of NOD2 gene variants with pediatric MC. The low penetrance of the at-risk genotypes we observed indicates that the NOD2 gene does not delineate a subgroup of simple Mendelian diseases

Increased prevalence of clonal hematopoiesis of indeterminate potential amongst people living with HIV

People living with human immunodeficiency virus (PLWH) have significantly increased risk for cardiovascular disease in part due to inflammation and immune dysregulation. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related acquisition and expansion of hematopoietic stem cells due to leukemogenic driver mutations, increases risk for both hematologic malignancy and coronary artery disease (CAD). Since increased inflammation is hypothesized to be both a cause and consequence of CHIP, we hypothesized that PLWH have a greater prevalence of CHIP. We searched for CHIP in multi-ethnic cases from the Swiss HIV Cohort Study (SHCS, n = 600) and controls from the Atherosclerosis Risk in the Communities study (ARIC, n = 8111) from blood DNA-derived exome sequences. We observed that HIV is associated with a twofold increase in CHIP prevalence, both in the whole study population and in a subset of 230 cases and 1002 matched controls selected by propensity matching to control for demographic imbalances (SHCS 7%, ARIC 3%, p = 0.005). We also observed that ASXL1 is the most commonly mutated CHIP-associated gene in PLWH. Our results suggest that CHIP may contribute to the excess cardiovascular risk observed in PLWH

Model Predictive Control of an Integrated Continuous Pharmaceutical Manufacturing Pilot Plant

This paper considers the model predictive control (MPC) of critical quality attributes (CQAs) of products in an end-to-end continuous pharmaceutical manufacturing pilot plant, which was designed and constructed at the Novartis-MIT Center for Continuous Manufacturing. Feedback control is crucial for achieving the stringent regulatory requirements on CQAs of pharmaceutical products in the presence of process uncertainties and disturbances. To this end, a key challenge arises from complex plant-wide dynamics of the integrated process units in a continuous pharmaceutical process, that is, dynamical interactions between several process units. This paper presents two plant-wide MPC designs for the end-to-end continuous pharmaceutical manufacturing pilot plant using the quadratic dynamic matrix control algorithm. The plant-wide MPC designs are based on different modeling approaches - subspace identification and linearization of nonlinear differential-algebraic equations that yield, respectively, linear low-dimensional and high-dimensional state-space models for the plant-wide dynamics. The closed-loop performance of the plant-wide MPC designs is evaluated using a nonlinear plant simulator equipped with a stabilizing control layer. The closed-loop simulation results demonstrate that the plant-wide MPC systems can facilitate effective regulation of CQAs and flexible process operation in the presence of uncertainties in reaction kinetics, persistent drifts in efficiency of filtration units, temporary disturbances in purity of intermediate compounds, and set point changes. The plant-wide MPC allows for incorporating quality-by-design considerations into the control problem through input and output constraints to ensure regulatory compliant process operation

Temporizing management vs immediate delivery in early-onset severe preeclampsia between 28 and 34 weeks of gestation (TOTEM study) : An open-label randomized controlled trial

Peer reviewedPublisher PD

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London