The electric vehicle routing problem with non-linear charging functions

International audienceThe use of electric vehicles (EVs) in freight and passenger transportation gives birth to a new family of vehicle routing problems (VRPs), the so-called electric VRPs (e-VRPs). As their name suggests, e-VRPs extend classical VRPs to account (mainly) for two constraining EV features: the short driving range and the long battery charging time. As a matter of fact, routes performed by EVs usually need to include time-consuming detours to charging stations. Most of the existing literature on e-VRPs relies on one of the following assumptions: i) vehicles recharge to their battery to its maximum level every time they reach a charging station or ii) the amount of battery charge is a linear function of the charging time. In practical situations, however, the amount of charge (and thus the time spent at each charging point) is a decision variable and battery charge levels are a concave function of the charging times. In this research we introduce the electric vehicle routing problem with non-linear charging functions (e-VRP-NLCF). We propose a mixed-integer linear programming (MILP) formulation that, running on a commercial solver, is able to solve small instances of the problem. To tackle large-scale instances we propose a metaheuristic that uses a MILP formulation to find the optimal charging policy. We report on extensive computational experiments evaluating the performance of the proposed methods and analyzing the impact on the solutions of different charging policy assumptions

Onset Patterns and Course of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Background: Epidemiologic studies of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) have examined different aspects of this disease separately but few have explored them together.Objective: Describe ME/CFS onset and course in one United States-based cohort.Methods: One hundred and fifty subjects fitting Fukuda 1994 CFS criteria completed a detailed survey concerning the initial and subsequent stages of their illness. Descriptive statistics, graphs, and tables were used to illustrate prevalence and patterns of characteristics.Results: The most common peri-onset events reported by subjects were infection-related episodes (64%), stressful incidents (39%), and exposure to environmental toxins (20%). For 38% of subjects, more than 6 months elapsed from experiencing any initial symptom to developing the set of symptoms comprising their ME/CFS. Over time, the 12 most common symptoms persisted but declined in prevalence, with fatigue, unrefreshing sleep, exertion-related sickness, and flu-like symptoms declining the most (by 20–25%). Conversely, cognitive symptoms changed the least in prevalence, rising in symptom ranking. Pregnancy, menopause, and menstrual cycles exacerbated many women's symptoms. Fatigue-related function was not associated with duration of illness or age; during the worst periods of their illness, 48% of subjects could not engage in any productive activity. At the time of survey, 47% were unable to work and only 4% felt their condition was improving steadily with the majority (59%) describing a fluctuating course. Ninety-seven percent suffered from at least one other illness: anxiety (48%), depression (43%), fibromyalgia (39%), irritable bowel syndrome (38%), and migraine headaches (37%) were the most diagnosed conditions. Thirteen percent came from families where at least one other first-degree relative was also afflicted, rising to 27% when chronic fatigue of unclear etiology was included.Conclusions: This paper offers a broad epidemiologic overview of one ME/CFS cohort in the United States. While most of our findings are consistent with prior studies, we highlight underexamined aspects of this condition (e.g., the evolution of symptoms) and propose new interpretations of findings. Studying these aspects can offer insight and solutions to the diagnosis, etiology, pathophysiology, and treatment of this condition

Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome

There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV‐6) and Epstein–Barr virus (EBV) have been proposed as infectious triggers. Thirty CFS patients with elevated IgG antibody titers against HHV‐6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double‐blind, placebo‐controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI‐20) and Fatigue Severity Scale (FSS) scores, self‐reported cognitive function, and physician‐determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels. VGCV patients experienced a greater improvement by MFI‐20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI‐20 mental fatigue subscore ( P  = 0.039), FSS score ( P  = 0.006), and cognitive function ( P  = 0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders ( P  = 0.029). In the VGCV arm, monocyte counts decreased ( P  < 0.001), neutrophil counts increased ( P  = 0.037) and cytokines were more likely to evolve towards a Th1‐profile ( P  < 0.001). Viral IgG antibody titers did not differ between arms. VGCV may have clinical benefit in a subset of CFS patients independent of placebo effect, possibly mediated by immunomodulation and/or antiviral effect. Further investigation with longer treatment duration and a larger sample size is warranted. J. Med. Virol. 85:2101–2109, 2013 . © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100139/1/jmv23713.pd

Nitrogen compounds removal from oil-derived middle distillates by MIL-101(Cr) and its impact on ULSD production by hydrotreating

Es un articulo sobre sintesis caracterizacion de catalizadoresoil) for ultra-low sulfur diesel (ULSD) production by hydrotreating (HDT) were pretreated by selective nitrogen organic compounds (NOC) adsorption. Highly crystalline metal-organic framework (MOF) MIL-101(Cr) prepared with propylene oxide (proton scavenger) as textural improver was employed to that end. MOF was characterized by N2 physisorption, X-ray diffraction, thermal analysis, infrared, Raman and UV-vis spectroscopies, and electron microscopy (SEM and HR-TEM). NOC removal was performed at room temperature and atmospheric pressure, the adsorbent being easily regenerable under mild conditions. Extruded MOF efficiently removed NOC from real feedstocks to concentrations ~ 80 ppm, allowing ULSD production at much milder conditions to those used during pristine feedstocks HDT. Operating temperature could be greatly diminished (from 350°C to 330°C, at 56 kg/sq cm (5.77 MPa), LHSV = 1.5/h, H2/oil = 2500 cy ft/bbl (445 cu m/cu m)) which could notably prolong cycle life of NiMo/Al2O3 formulation used.SENER-CONACYT-HIDROCARBUROS FUND IMP 00117, 6105

Maternal Anti-Toxoplasma Treatment during Pregnancy Is Associated with Reduced Sensitivity of Diagnostic Tests for Congenital Infection in the Neonate

Neonatal diagnosis of congenital toxoplasmosis is based on a combination of serological and molecular tests. Maternal screening and treatment differ according to national policies and may impact the sensitivity of diagnostic methods in infants at birth. In this multicenter study, 115 neonates born to 61 treated (53%) and 54 (47%) untreated women were retrospectively included in three centers (France, Serbia, and the United States) to assess the impact of maternal anti-Toxoplasma treatment on the performance of neonatal workup at birth (neosynthesized anti-Toxoplasma IgM, IgA, and IgG and quantitative PCR [qPCR]) using univariate and multivariate approaches. Independently of the time of maternal seroconversion, the serological techniques were impacted differently by maternal treatment. The detection of IgM by immunosorbent agglutination assay (ISAGA) and Western blotting (WB) dropped from 90.7% and 88.2% in untreated neonates to 533% and 51.9% in treated neonates (P lt 0.05), whereas IgM enzyme-linked immunosorbent assay (ELISA) and IgA ISAGA were not significantly affected by maternal treatment. A 2-fold reduction in the sensitivity of neosynthesized IgG by WB was also observed in the case of treatment during pregnancy (37.7% versus 82.3%). Interestingly, the effect of treatment was shown to be duration dependent, especially for IgM detection, when the treatment course exceeded 8 weeks, whatever the therapy. The sensitivity of Toxoplasma PCR in blood was also lowered by maternal treatment from 39.1% to 23.2%. These results highlight that anti-Toxoplasma therapy during pregnancy may set back biological evidence of neonatal infection at birth and underline the need for a careful serological follow-up of infants with normal workup.This is the peer-reviewed version of the article: Guegan, H.; Štajner, T.; Bobić, B.; Press, C.; Olariu, R. T.; Olson, K.; Srbljanović, J.; Montoya, J. G.; Đurković-Đaković, O.; Robert-Gangneux, F. Maternal Anti-Toxoplasma Treatment during Pregnancy Is Associated with Reduced Sensitivity of Diagnostic Tests for Congenital Infection in the Neonate. Journal of Clinical Microbiology 2021, 59 (2). [https://doi.org/10.1128/JCM.01368-20

Point-of-care testing for <i>Toxoplasma gondii</i> IgG/IgM using <i>Toxoplasma</i> ICT IgG-IgM test with sera from the United States and implications for developing countries

Background: Congenital toxoplasmosis is a serious but preventable and treatable disease. Gestational screening facilitates early detection and treatment of primary acquisition. Thus, fetal infection can be promptly diagnosed and treated and outcomes can be improved. Methods: We tested 180 sera with the Toxoplasma ICT IgG-IgM point-of-care (POC) test. Sera were from 116 chronically infected persons (48 serotype II; 14 serotype I-III; 25 serotype I-IIIa; 28 serotype Atypical, haplogroup 12; 1 not typed). These represent strains of parasites infecting mothers of congenitally infected children in the U.S. 51 seronegative samples and 13 samples from recently infected persons known to be IgG/IgM positive within the prior 2.7 months also were tested. Interpretation was confirmed by two blinded observers. A comparison of costs for POC vs. commercial laboratory testing methods was performed. Results: We found that this new Toxoplasma ICT IgG-IgM POC test was highly sensitive (100%) and specific (100%) for distinguishing IgG/IgM-positive from negative sera. Use of such reliable POC tests can be cost-saving and benefit patients. Conclusions: Our work demonstrates that the Toxoplasma ICT IgG-IgM test can function reliably as a point-of-care test to diagnose Toxoplasma gondii infection in the U.S. This provides an opportunity to improve maternal-fetal care by using approaches, diagnostic tools, and medicines already available. This infection has serious, lifelong consequences for infected persons and their families. From the present study, it appears a simple, low-cost POC test is now available to help prevent morbidity/disability, decrease cost, and make gestational screening feasible. It also offers new options for improved prenatal care in low- and middle-income countries.</p

Point-of-Care Testing for Toxoplasma Gondii IgG/IgM Using Toxoplasma ICT IgG-IgM Test with Sera from the United States and Implications for Developing Countries

Background Congenital toxoplasmosis is a serious but preventable and treatable disease. Gestational screening facilitates early detection and treatment of primary acquisition. Thus, fetal infection can be promptly diagnosed and treated and outcomes can be improved. Methods We tested 180 sera with the Toxoplasma ICT IgG-IgM point-of-care (POC) test. Sera were from 116 chronically infected persons (48 serotype II; 14 serotype I-III; 25 serotype I-IIIa; 28 serotype Atypical, haplogroup 12; 1 not typed). These represent strains of parasites infecting mothers of congenitally infected children in the U.S. 51 seronegative samples and 13 samples from recently infected persons known to be IgG/IgM positive within the prior 2.7 months also were tested. Interpretation was confirmed by two blinded observers. A comparison of costs for POC vs. commercial laboratory testing methods was performed. Results We found that this new Toxoplasma ICT IgG-IgM POC test was highly sensitive (100%) and specific (100%) for distinguishing IgG/IgM-positive from negative sera. Use of such reliable POC tests can be cost-saving and benefit patients. Conclusions Our work demonstrates that the Toxoplasma ICT IgG-IgM test can function reliably as a point-of-care test to diagnose Toxoplasma gondii infection in the U.S. This provides an opportunity to improve maternal-fetal care by using approaches, diagnostic tools, and medicines already available. This infection has serious, lifelong consequences for infected persons and their families. From the present study, it appears a simple, low-cost POC test is now available to help prevent morbidity/disability, decrease cost, and make gestational screening feasible. It also offers new options for improved prenatal care in low- and middle-income countries

Impact of the Mitochondrial Genetic Background in Complex III Deficiency

BACKGROUND: In recent years clinical evidence has emphasized the importance of the mtDNA genetic background that hosts a primary pathogenic mutation in the clinical expression of mitochondrial disorders, but little experimental confirmation has been provided. We have analyzed the pathogenic role of a novel homoplasmic mutation (m.15533 A>G) in the cytochrome b (MT-CYB) gene in a patient presenting with lactic acidosis, seizures, mild mental delay, and behaviour abnormalities. METHODOLOGY: Spectrophotometric analyses of the respiratory chain enzyme activities were performed in different tissues, the whole muscle mitochondrial DNA of the patient was sequenced, and the novel mutation was confirmed by PCR-RFLP. Transmitochondrial cybrids were constructed to confirm the pathogenicity of the mutation, and assembly/stability studies were carried out in fibroblasts and cybrids by means of mitochondrial translation inhibition in combination with blue native gel electrophoresis. PRINCIPAL FINDINGS: Biochemical analyses revealed a decrease in respiratory chain complex III activity in patient's skeletal muscle, and a combined enzyme defect of complexes III and IV in fibroblasts. Mutant transmitochondrial cybrids restored normal enzyme activities and steady-state protein levels, the mutation was mildly conserved along evolution, and the proband's mother and maternal aunt, both clinically unaffected, also harboured the homoplasmic mutation. These data suggested a nuclear genetic origin of the disease. However, by forcing the de novo functioning of the OXPHOS system, a severe delay in the biogenesis of the respiratory chain complexes was observed in the mutants, which demonstrated a direct functional effect of the mitochondrial genetic background. CONCLUSIONS: Our results point to possible pitfalls in the detection of pathogenic mitochondrial mutations, and highlight the role of the genetic mtDNA background in the development of mitochondrial disorders

Coefficient shifts in geographical ecology: an empirical evaluation of spatial and non-spatial regression

Copyright © 2009 The Authors. Copyright © ECOGRAPHY 2009.A major focus of geographical ecology and macro ecology is to understand the causes of spatially structured ecological patterns. However, achieving this understanding can be complicated when using multiple regressions, because the relative importance of explanatory variables, as measured by regression coefficients, can shift depending on whether spatially explicit or non-spatial modelling is used. However, the extent to which coefficients may shift and why shifts occur are unclear. Here, we analyze the relationship between environmental predictors and the geographical distribution of species richness, body size, range size and abundance in 97 multi-factorial data sets. Our goal was to compare standardized partial regression coefficients of non-spatial ordinary least squares regressions (i.e. models fitted using ordinary least squares without taking autocorrelation into account; “OLS models” hereafter) and eight spatial methods to evaluate the frequency of coefficient shifts and identify characteristics of data that might predict when shifts are likely. We generated three metrics of coefficient shifts and eight characteristics of the data sets as predictors of shifts. Typical of ecological data, spatial autocorrelation in the residuals of OLS models was found in most data sets. The spatial models varied in the extent to which they minimized residual spatial autocorrelation. Patterns of coefficient shifts also varied among methods and datasets, although the magnitudes of shifts tended to be small in all cases. We were unable to identify strong predictors of shifts, including the levels of autocorrelation in either explanatory variables or model residuals. Thus, changes in coefficients between spatial and non-spatial methods depend on the method used and are largely idiosyncratic, making it difficult to predict when or why shifts occur. We conclude that the ecological importance of regression coefficients cannot be evaluated with confidence irrespective of whether spatially explicit modelling is used or not. Researchers may have little choice but to be more explicit about the uncertainty of models and more cautious in their interpretation

Rationale and design of a randomised controlled trial evaluating the effectiveness of an exercise program to improve the quality of life of patients with heart failure in primary care : the EFICAR study protocol

Background: Quality of life (QoL) decreases as heart failure worsens, which is one of the greatest worries of these patients. Physical exercise has been shown to be safe for people with heart failure. Previous studies have tested heterogeneous exercise programs using different QoL instruments and reported inconsistent effects on QoL. The aim of this study is to evaluate the effectiveness of a new exercise program for people with heart failure (EFICAR), additional to the recommended optimal treatment in primary care, to improve QoL, functional capacity and control of cardiovascular risk factors. Methods/Design: Multicenter clinical trial in which 600 patients with heart failure in NYHA class II-IV will be randomized to two parallel groups: EFICAR and control. After being recruited, through the reference cardiology services, in six health centres from the Spanish Primary Care Prevention and Health Promotion Research Network (redIAPP), patients are followed for 1 year after the beginning of the intervention. Both groups receive the optimized treatment according to the European Society of Cardiology guidelines. In addition, the EFICAR group performs a 3 month supervised progressive exercise program with an aerobic (high-intensity intervals) and a strength component; and the programme continues linked with community resources for 9 months. The main outcome measure is the change in health-related QoL measured by the SF-36 and the Minnesota Living with Heart Failure Questionnaires at baseline, 3, 6 and 12 months. Secondary outcomes considered are changes in functional capacity measured by the 6-Minute Walking Test, cardiac structure (B-type natriuretic peptides), muscle strength and body composition. Both groups will be compared on an intention to treat basis, using multi-level longitudinal mixed models. Sex, age, social class, co-morbidity and cardiovascular risk factors will be considered as potential confounding and predictor variables. Discussion: A key challenges of this study is to guarantee the safety of the patients; however, the current scientific evidence supports the notion of there being no increase in the risk of decompensation, cardiac events, hospitalizations and deaths associated with exercise, but rather the opposite. Safety assurance will be based on an optimized standardised pharmacological therapy and health education for all the participants