reliability analysis of centralized versus decentralized zoning strategies for paratransit services

Abstract ADA paratransit services are a very large and ever-growing industry providing door-to-door transportation services for people with disability and elderly customers. Paratransit system, however, just like all other public transportation systems, suffers from travel time variability due to various factors and as a result gives its customers unreliable services. Although service reliability is a very important aspect in transportation study, it has not received much attention in the paratransit research community. A quantitative study evaluating the paratransit service reliability under different zoning strategies is yet to be found. This research filled this gap. Statistical models were proposed to represent travel time variability. Simulation experiments based on real demand data from Houston, Los Angeles and Boston were performed to quantitatively compare the reliability performance of centralized and decentralized operating strategies under different travel time variability levels. Results showed that the decentralized strategy, compared to the centralized no-zoning strategy, substantially improves the reliability of paratransit in terms of on-time performance. This research provides a framework for paratransit agencies to evaluate the service reliability of different organizational strategies through the simulation method

FIRST TRIMESTER SCREENING FOR HYPERTENSIVE DISORDER OF PLACENTAL AND MATERNOGENIC ORIGIN

FIRST TRIMESTER SCREENING OF HYPERTENSIVE DISORDERS OF PLACENTAL AND MATERNOGENIC ORIGIN Background: Hypertensive disorders (HD) constitute a heterogeneous group of conditions. They complicate around 10% of pregnancies, and are a major cause of maternal and perinatal morbidity and mortality. The most used classification is based on temporal criteria: diagnosis (or delivery) before/after 34 weeks\u2019 of gestation. Early-onset HD (before 34 weeks) is commonly associated with abnormal uterine artery Doppler, fetal growth restriction, evidence of ischemic lesions on placental examination and adverse maternal and neonatal outcomes. In contrast, late-onset HD (after 34 weeks) is mostly associated with normal or slightly increased uterine resistance index, a low rate of fetal involvement, and more favourable perinatal outcomes. Nevertheless, the phenotypes of HD do not fit entirely into the temporal classification. Thus, it has been hypothesized that phenotypes of HD, rather than temporal classification, reflect the underlying aetiology of HD: 1) HD of placental origin, when the defect in placentation causes an altered remodelling of the spiral arteries leading to reduced placental flow, activation of coagulation cascade, organ damage and intrauterine fetal growth restriction (IUGR); and 2) HD of maternogenic origin, associated with normal feto-placental perfusion and normal fetal growth, probably related to chronic inflammation and insuline resistance, typical aspects of metabolic syndrome. The early identification of pregnancies at risk of HD is a major challenge. Extensive research has identified a series of 1st trimester biophysical and biochemical markers of impaired placentation. The combination of these markers and maternal history have been used by clinicians as a 1st trimester screening for the recognition of pregnancies at risk of early/late onset HD. The aim of the study is to evaluate a new classification of hypertensive disease based on physiopathology, and not on temporary factors and to evaluate the effectiveness of 1st trimester screening for HD of placental and maternal origin by Doppler velocimetry of uterine arteries (UtA). Material and Methods: This is a prospective longitudinal cohort study of pregnant women followed in two hospital: prenatal diagnosis and gynaecologic Unit of the Institute for Maternal and Child Health \u2013 IRCCS \u201cBurlo Garofolo\u201d in Trieste and Obstetrics and Gynecologic Unit of Children\u2019s Hospital \u2013 ICP \u201cVittore Buzzi\u201d in Milan, Italy. This study was offered to pregnant women at the time of first trimester ultrasound aneuploidy screening. All women were recruited consecutively from October 2007 to April 2009 in Triest and from October 2009 to December 2012 in Milan. We enrolled singleton pregnancies between 11+0 and 13+6 weeks of gestation. The inclusion criteria were: single pregnancy, gestational age between 11+0 and 13+6 weeks confirmed by scan measurements, and signed informed consent. Multiple pregnancies or pregnancies complicated by fetal malformation or aneuploidy, spontaneous abortion, intrauterine fetal death, maternal neurodevelopment delay or psychiatric disorders were excluded. The following data were collected at the time of the scan: maternal history, previous disease, age, body mass index (BMI), parity, mode of conception (spontaneous or IVF), and gestational age. Doppler velocimetry of both UtA was added to routine ultrasound measurements. Doppler study was performed trans-abdominally, after identifying with the Color Doppler each uterine artery along the side of the cervix and uterus at the level of the internal os. Pulsed wave Doppler was used with the sampling gate set at 2\u2009mm to cover the whole vessel ensuring the angle of insonation <30\ub0. When three similar consecutive waveforms were obtained the pulsatility index (PI) was measured, and the mean PI of the left and right arteries was calculated. The measurements were performed by sonographers qualified by Fetal Medicine Foundation. Once the ultrasound examination was performed and the gestational age confirmed, a blood sample (around 5 cc) was taken from each woman. Maternal serum PAPP-A and B-hCG were measured and converted in multiple of the median (MoM). Definitions: Placental HD was defined as gestational hypertension, with or without proteinuria, associated to IUGR (defined as the AC 40 centiles). Maternal HD was defined as gestational hypertension, with or without proteinuria, associated to appropriate for gestational age fetal growth. Chronic hypertension was defined as history of known hypertension or blood pressure 65140/90 mmHg in two or more occasions with a distance at least of 4 hours before 20 weeks of gestation. The HD were also distinguished into early-onset, diagnosed <34 weeks\u2019 gestation, and late-onset, with diagnosis 65 34 weeks. Intra-uterine growth restriction (IUGR) was defined as ultrasound abdominal circumference below the 10th percentile according to standards references based on gestational age. Other causes of IUGR such as infection, anomalies and abnormal chromosomes were excluded in all cases. Pregnancy outcome data were collected as follows: fetal and maternal outcomes were obtained either directly from the clinical record if the delivery occurred in \u201cVittore Buzzi\u201d Hospital or in \u201cBurlo Garofolo\u201d hospital or by a telephone questionnaires to the women after delivery. Statistical analysis: The distribution of data was evaluated with Kruskall-Wallis test. In case of non-uniformely distributed data a log transformation was applied. The results are represented as mean value and standard deviation (SD). Logistic regression models were computed to evaluate the significance of the variables considered. The following variables were included: UtA mean PI, BMI, parity, gestational age at time of recruitment and fetal sex. The receiver operating curves (ROC) constructed on regression models were computed and area under the ROC (AUC) calculated to evaluate the performance of the model. We evaluated the 1st trimester model to identify: firstly, women at risk of developing placental or maternogenic HD, and, secondly, the early and late-onset HD. Each disease was evaluated against the whole cohort. The analysis was performed with the program Stata/IC 11.2 for Windows (Stata Corp LP, College Station, USA). Results: 4218 women were enrolled in the study. 712 patients were lost to follow up or excluded because incomplete data acquisition. Overall 34 women were excluded because of: spontaneous abortion, aneuploidies or fetal malformations, and intrauterine fetal death. Among 3472 pregnancies included in the study, 122 women (3,5%) developed some hypertensive gestational disease, 56 fetuses were IUGR (1,6%), 10 women had chronic hypertension (0.3%) and 3284 women were unaffected (94.6%). If we considered classification based on the aetiology, 16 women (0.5%) developed placental HD, 106 (3.0%) presented maternal HD. If we considered classification based on time of delivery, 11 women (0.3%) developed early-HD, 111 women (3.2%) presented late-HD. The mean uterine artery PI was significantly higher in placental HD (2.36 p<0.01) when compared with the unaffected group (1.60). If we consider the early-late group, the mean uterine artery PI was significantly higher in early HD group (2.30, p<0.01) respect control group and in late HD group (1.71, p< 0.05). PAPP-A was significant lower in maternal-HD, late-HD and IUGR group (p< 0.01) and in CH group (p<0.05). There was no significant difference in BhCG levels through study group. Concerning prediction of the logistic regression, the validity of the uterine arteries Doppler velocimetry has been confirmed for early identification of women at risk of developing a hypertensive disease, especially of placental origin. In effect the area under the ROC curve for placental hypertensive diseases was 0.879, whereas for early diseases was 0.858. Conclusions: The main findings of the study are: 1) the UtA mean PI is altered in placental HD, while there were no differences in maternogenic HD; 2) the UtA mean PI is altered in early-onset HD and late-onset HD; 3) the predictive value of UtA mean PI is higher for placental HD than for early-onset HD; and 4) the performance of the model based on UtA PI in the 1st trimester performs best in the prediction of the placental HD compared to all other groups. Our study has some limitations: we acknowledge that the number of cases in the study is too small (the prevalence of HD in our cohort is low) to draw firm conclusions, and confirmation from larger studies will be required. Smoking habit was not considered. Diagnosis of early and late preeclampsia is based on time at delivery and not at time of diagnosis. Despite these limitations, the study shows that the classification based on phenotypes of HD is more appropriate than that based on temporal criteria. Indeed, our findings underline the importance of the \u201cetiology\u201d based classification in order to use, in the most appropriate way, the biophysical or biochemical marker screening tools. Thus, the usefulness of Doppler velocimetry of the uterine arteries to identify HD not associated with IUGR or simply based on temporal criteria appears to be of limited value. This finding is important when evaluating the performance of the screening programs or preventive policies

Testing demand responsive shared transport services via agent-based simulations

Demand Responsive Shared Transport DRST services take advantage of Information and Communication Technologies ICT, to provide on demand transport services booking in real time a ride on a shared vehicle. In this paper, an agent-based model ABM is presented to test different the feasibility of different service configurations in a real context. First results show the impact of route choice strategy on the system performance

Immunoglobulin A response against Gardnerella vaginalis hemolysin and sialidase activity in bacterial vaginosis

OBJECTIVE: The aim of this study was to investigate the correlation between the immunoglobulin A immune response to Gardnerella vaginalis hemolysin and sialidase activity in vaginal fluids from patients with bacterial vaginosis. STUDY DESIGN: Nonpregnant women who were examined at a gynecologic clinic, in an age range of 18 to 62 years, were enrolled. The study population comprised 131 healthy volunteers, 32 women with bacterial vaginosis that was positive for immunoglobulin A to Gardnerella vaginalis hemolysin, 40 women with bacterial vaginosis that was negative for immunoglobulin A to Gardnerella vaginalis hemolysin, and 19 women with Candida vaginitis. Bacterial vaginosis was diagnosed by clinical criteria and Gram stain. RESULTS: Sialidase activity was present in 75% (54/72) of patients with bacterial vaginosis. Women having bacterial vaginosis and lacking a specific immunoglobulin A response had a significantly higher level of sialidase activity than patients who had an immune response against Gardnerella vaginalis hemolysin. Sialidase activity was detected in 87% (35/40) of the former subgroup of patients with bacterial vaginosis and in 59% (19/32) of women of the latter subgroup. No sialidase activity was measured in patients with candidiasis. Specificity of the assay for healthy controls was 95% (124/131 women without sialidase activity). CONCLUSIONS: Sialidases produced by Prevotella bivia and other microorganisms present in the microflora of patients with bacterial vaginosis are very likely a virulence factor not only by destroying the mucins and enhancing adherence of bacteria but also by impairing a specific immunoglobulin A immune response against other virulence factors such as cytotoxin from Gardnerella vaginalis

Vaginal hydrolytic enzymes, immunoglobulin A against Gardnerella vaginalis toxin, and risk of early preterm birth among women in preterm labor with bacterial vaginosis or intermediate flora

Objective: The purpose of this study was to determine whether the microbial hydrolytic enzymes, sialidase and prolidase, and immunoglobulin A against the Gardnerella vaginalis cytolysin (anti-Gvh IgA) increase the risk for early preterm birth ( 6434 weeks of gestation) among women with bacterial vaginosis or intermediate flora. Study Design: Two hundred eighteen afebrile women in preterm labor with intact membranes had a vaginal Gram stain performed, and sialidase, prolidase, and anti-Gvh IgA concentrations were determined. Results: Women with bacterial vaginosis or intermediate flora had significantly higher sialidase and prolidase concentrations than women with normal flora. Among women with bacterial vaginosis or intermediate flora, the women with sialidase had a higher rate of early preterm birth (P =.05). Sialidase had a sensitivity of 43% and specificity of 77% for early preterm birth. Prolidase and anti-Gvh IgA did not predict early preterm birth. Conclusion: Women in preterm labor with bacterial vaginosis or intermediate flora and detectable sialidase are at increased risk of early preterm birth

Activation of APE1/Ref-1 is dependent on reactive oxygen species generated after purinergic receptor stimulation by ATP

Apurinic apyrimidinic endonuclease redox effector factor-1 (APE1/Ref-1) is involved both in the base excision repair (BER) of DNA lesions and in the eukaryotic transcriptional regulation. APE1/Ref-1 is regulated at both the transcriptional and post-translational levels, through control of subcellular localization and post-translational modification. In response to stress conditions, several cell types release ATP, which exerts stimulatory effects on eukaryotic cells via the purinergic receptors (P2) family. By using western blot and immunofluorescence analysis on a human tumour thyroid cell line (ARO), we demonstrate that purinergic stimulation by extracellular ATP induces quick cytoplasm to nucleus translocation of the protein at early times and its neosynthesis at later times. Continuous purinergic triggering by extracellular ATP released by ARO cells is responsible for the control of APE1/Ref-1 intracellular level. Interference with intracellular pathways activated by P2 triggering demonstrates that Ca(2+) mobilization and intracellular reactive oxygen species (ROS) production are responsible for APE1/Ref-1 translocation. The APE1/Ref-1 activities on activator protein-1 (AP-1) DNA binding and DNA repair perfectly match its nuclear enrichment upon ATP stimulation. The biological relevance of our data is reinforced by the observation that APE1/Ref-1 stimulation by ATP protects ARO cells by H(2)O(2)-induced cell death. Our data provide new insights into the complex mechanisms regulating APE1/Ref-1 functions

The Bacterial DNA Profiling of Chorionic Villi and Amniotic Fluids Reveals Overlaps with Maternal Oral, Vaginal, and Gut Microbiomes

The in utero microbiome hypothesis has been long debated. This hypothesis will change our comprehension of the pioneer human microbiome if proved correct. In 60 uncomplicated pregnancies, we profiled the microbiome of chorionic villi (CV) and amniotic fluids (AF) in relation to maternal saliva, rectum, and vagina and the soluble cytokines cascade in the vagina, CV and AF. In our series, 12/37 (32%) AF and 10/23 (44%) CV tested positive for bacterial DNA. CV and AF harbored bacterial DNA of Streptococcus and Lactobacillus, overlapping that of the matched oral and vaginal niches, which showed a dysbiotic microbiome. In these pregnant women, the immune profiling revealed an immune hyporesponsiveness in the vagina and a high intraamniotic concentration of inflammatory cytokines. To understand the eventual role of bacterial colonization of the CV and AF and the associated immune response in the pregnancy outcome, further appropriate studies are needed. In this context, further studies should highlight if the hematogenous route could justify the spread of bacterial DNA from the oral microbiome to the placenta and if vaginal dysbiosis could favor the likelihood of identifying CV and AF positive for bacterial DNA

Current use and performance of the different fetal growth charts in the Italian population

Objectives: The choice of growth charts impacts on screening, diagnosis and clinical management of fetal growth abnormalities. The objectives of the study were to evaluate: 1) the clinical practice at a national level among tertiary referral centers in the use of fetal biometric growth charts; and 2) the impact on fetal growth screening of existing national and international growth charts. Study design: A questionnaire was sent to 14 Italian tertiary referral centers to explore biometric reference growth charts used in clinical practice. National and international (Intergrowth-21st and World Health Organization) fetal growth charts were tested on a large national cohort of low risk women with singleton uneventful pregnancy derived from a retrospective cross-sectional multicenter study (21 centers). The percentage of fetuses with biometric measurements below and above the 10th and 90th percentile for each biometric parameter and gestational week were calculated for each growth chart. The percentile curves of the study population were calculated by non-linear quantile regressions. Results: Twelve Italian centers (86 %) answered to the questionnaire showing a wide discrepancy in the use of growth charts for fetal biometry. The cohort included 7347 pregnant women. By applying Intergrowth-21st growth charts the percentage of fetuses with head circumference, abdominal circumference and femur length below the 10th centile was 3.9 %, 3.6 % and 2.3 %, and above the 90th centile 29.9 %, 32.5 % and 46 %, respectively. The percentages for the World Health Organization growth charts for head and abdominal circumferences and femur length were: below the 10th centile 6.3 %, 7.2 % and 5.3 %, and above 90th centile 22.8 %, 21.3 % and 31.9 %, respectively. Conclusions: The wide discrepancy in clinical use of fetal growth charts in Italian centers warrants the adoption of an uniform set of charts. Our data suggest that immediate application into clinical practice of international growth charts might result into an under-diagnosis of small for gestational age fetuses and, especially, in an over-diagnosis of large for gestational age fetuses with major consequences for clinical practice. On these grounds, there is an urgent need for a nationwide study for the prospective evaluation of international growth charts and, if needed, the construction and adoption of methodologically robust national growth charts

Identification of secondary targets of N-containing bisphosphonates in mammalian cells via parallel competition analysis of the barcoded yeast deletion collection

Growth competition assays using barcoded yeast deletion-mutants reveal the molecular targets of nitrogen containing bisphosphonates used for the treatment of bone cancers and osteoporosis