Delay and disruption management in local public transportation via real-time vehicle and crew re-scheduling: a case study

Local public transport companies, especially in large cities, are facing every day the problem of managing delays and small disruptions. Disruption management is a well-established practice in airlines and railways. However, in local public transport the approaches to these problems have followed a different path, mainly focusing on holding and short-turning strategies not directly associated with the driver scheduling. In this paper we consider the case of the management of urban surface lines of Azienda Trasporti Milanese (ATM) of Milan. The main issues are the service regularity as a measure of the quality of service, and the minimization of the operational costs due to changes in the planned driver scheduling. We propose a simulation-based optimization system to cope with delays and small disruptions that can be effectively used in a real-time environment and takes into account both vehicle and driver scheduling. The proposed approach is tested on real data to prove its actual applicability

LOCATION AND ROUTING PROBLEMS: A UNIFIED APPROACH

This thesis is about location and routing problems. We propose a unified algorithmic approach, based on the branch-and-cut-and-price paradigm, for the exact solution of general location and routing problems involving both costs and profits. In particular three different types of N P -hard problems are taken into account: the first is an extension, arising in the context of waste collection management, of the well studied Vehicle Routing Problem. The second is based on the Multi-Depot Vehicle Routing Problem with profits and has applications in the exploration of planetary surfaces. The last problem is about the distribution of drugs in emergency situations. For every problem a detailed description and a mathematical formulation are given. The largest part of the thesis is dedicated to the careful explanation of how our method can be efficiently implemented in every of the problems taken into account. In particular we propose new algorithmic ideas and several modifications and extensions to many procedures already presented in the literature. However, all components of our algorithms are fully presented and analyzed pointing out every methodological and practical issue. Extensive computational experiments and comparisons are carried out to evaluate the performance of our approach and the tractability of the problems addressed

Delay Management in Public Transportation: Service Regularity Issues and Crew Re-scheduling

In this paper, we propose a decision support tool to assist a local public transportation company in tackling service delays and small disruptions. We discuss different ways to assess and improve the regularity of the service, and we propose a simulation based optimization system that can be effectively used in a real-time environment taking into account both vehicle and driver shifts. In particular, we describe a tabu-search procedure for the online vehicle scheduling optimizing the regularity of the service and a column generation approach for the consequential crew re-scheduling minimizing the driver extra-time. As a case study, we analyze the management of urban surface lines of Azienda Trasporti Milanese (ATM) of Milan. In the last part of the paper we report a detailed analysis of the experimental phase showing the effectiveness of the proposed approach

Generation of donor-specific Tr1 cells to be used after kidney transplantation and definition of the timing of their in vivo infusion in the presence of immunosuppression

Background: Operational tolerance is an alternative to lifelong immunosuppression after transplantation. One strategy to achieve tolerance is by T regulatory cells. Safety and feasibility of a T regulatory type 1 (Tr1)-cell-based therapy to prevent graft versus host disease in patients with hematological malignancies has been already proven. We are now planning to perform a Tr1-cell-based therapy after kidney transplantation. Methods: Upon tailoring the lab-grade protocol to patients on dialysis, aims of the current work were to develop a clinical-grade compatible protocol to generate a donor-specific Tr1-cell-enriched medicinal product (named T10 cells) and to test the Tr1-cell sensitivity to standard immunosuppression in vivo to define the best timing of cell infusion. Results: We developed a medicinal product that was enriched in Tr1 cells, anergic to donor-cell stimulation, able to suppress proliferation upon donor- but not third-party stimulation in vitro, and stable upon cryopreservation. The protocol was reproducible upon up scaling to leukapheresis from patients on dialysis and was effective in yielding the expected number of T10 cells necessary for the planned infusions. The tolerogenic gene signature of circulating Tr1 cells was minimally compromised in kidney transplant recipients under standard immunosuppression and it eventually started to recover 36weeks post-transplantation, providing rationale for selecting the timings of the cell infusions. Conclusions: These data provide solid ground for proceeding with the trial and establish robust rationale for defining the correct timing of cell infusion during concomitant immunosuppressive treatment

Normative and validation data of an articulation test for Italian-speaking children

Objectives: As a standardized instrument to assess speech sound development in Italian-speaking children is currently lacking, norms used to diagnose speech sound disorders (SSD) are mainly based on studies including English-speaking participants. This application may result in misidentification of SSD due to linguistic differences. The aims of the study were to establish normative data on speech sound development of Italian-speaking children and to evaluate psychometric properties of Rossi's articulation test, the picture-naming test selected to assess speech sound development. Methods: A cross-sectional study including 694 normally-developing Italian-speaking children aged from 3 to 7 years was conducted. Children were administered Rossi's articulation test, and percentages of speech sound correct production were calculated. To evaluate inter-rater reliability of the test, audio-recordings of 50 children were scored by an additional examiner. The same rater scored the audio-recordings of 50 children twice with an interval of at least 1 week. To evaluate test-retest reliability, 144 participants were re-tested after 1-3 weeks by the same assessor. Scores were compared through Intraclass Correlation Coefficient (ICC). To assess construct validity, the developmental progression of total scores across age groups was verified by the estimation of the reference range for the test, using a regression procedure. Results: Almost all Italian children in the sample produced vowels and approximants correctly. Singleton consonants were acquired before consonant clusters. Ages of acquisition of each consonant were presented: plosives and nasals were early mastered by Italian children, while dental affricates, alveolar fricatives and the palatal lateral were the latest acquired segments. All ICCs were superior to 0.9 (reliability). A statistically significant improvement in test score with age was found (construct validity). Conclusions: The paper provides normative data for speech sound development of Italian-speaking children; preliminary psychometric analysis of Rossi's articulation test revealed satisfactory reliability and construct validity. Clinicians are recommended to use Rossi's articulation test to assess speech sound development in Italian children

Generation of donor-specific T regulatory type 1 cells from patients on dialysis for cell therapy after kidney transplantation

Background. Tregulatory type 1 (Tr1) cell-mediated induction of tolerance in preclinicalmodels of transplantation is remarkably effective. The clinical application of such a therapy in patients on dialysis undergoing kidney transplantation should take into account the possible alterations of the immune systemobserved in these patients. Herein, we aimed at testing the ability to generate donor-specific Tr1 cell-enriched lymphocytes from patients on dialysis on the waiting list for kidney transplantation. Methods. The Tr1 cell-enriched lymphocytes were generated by coculturing interleukin-10-producing dendritic cells obtained from healthy donors with peripheral bloodmononuclear cells (PBMCs) of patients on dialysis, following the same protocol used in a previous cell therapy clinical trial to prevent graft-versus-host disease. Alternatively, purified CD4+ Tcells were used instead of total PBMCs. The ability to generate clinical-grade Tr1 cell-enriched products was defined by testing the reduced response to restimulation withmature dendritic cells generated fromthe original donor (i.e., anergy assay). Results. The Tr1 cell-enrichedmedicinal products generated from PBMCs of patients on dialysis showed a low anergic phenotype, incompatible with their eventual clinical application. This was irrespective of HLA matching with the donor or the intrinsically reduced ability to proliferate in response to alloantigens. On the contrary, the use of purified CD4+ T cells isolated from patients on dialysis led to the generation of a highly anergic donor-specific medicinal product containing an average of 10% Tr1 cells. Conclusions. The Tr1 cell-enriched medicinal products can be efficiently generated from patients on dialysis by carefully tailoring the protocol on the patients' immunological characteristics

Changes in serum levels of TNF-α, IL-6, OPG, RANKL and their correlation with radiographic and clinical assessment in fragility fractures and high energy fractures

Stages of bone turnover during fracture repair can be assessed employing serum markers of osteoblastic and osteoclastic activity, inflammatory cytokines, clinical evaluation and imaging instruments. Our study compare the fracture healing process in fragility fractures and high energy fractures by evaluating serum changes of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), osteoprotegerin (OPG) and receptor activator of the nuclear factor-kB ligand (RANKL) in combination with radiographic (Radiographic Union Scale for Tibial fractures, RUST) and clinical (Lower extremity measure, LEM) assessments. We enrolled 56 patients divided into four corresponding groups: group A with high energy trauma fracture (tibial/femoral shaft); group B with low energy trauma fracture (femoral fractures); healthy (control A) and osteoporotic subjects (control B). Blood samples were collected before surgery (T0) and after 10 weeks (T10). Serum concentrations of IL-6, TNF-α, RANKL and OPG were quantified using commercial enzyme-linked immunosorbent assay (ELISA) kits. Our results show that RANKL values are significantly higher at T10 than at T0 in low energy trauma fractures (group B). OPG is significantly lower in each control group than that of the respective fractured group and its concentration at T0 and at T10 is significantly lower in high than in low energy fractures. RANKL/OPG ratio is significantly higher in both controls than in fractured groups, and significantly increases after 10 weeks. IL-6 and TNF-α concentrations significantly decrease during fracture healing and are higher in high (group A) than in low energy fractures (group B). Significant differences were also found in both RUST score and LEM between groups A and B. Changes in TNF-α and IL-6 levels correlate with RUST and LEM in fragility and high energy fractures, while RANKL/OPG ratio is associated with these clinical parameters only in fragility fractures. These findings suggest that serum levels of IL-6, TNF-α, RANKL and OPG might be used to monitor the stages of fracture repair. Further studies will be needed to confirm the role of these cytokines in fracture repair

Dataset of immune responses induced in swine by an inactivated Porcine Circovirus 2b vaccine

A whole virus, inactivated, Porcine Circovirus 2b (PCV2b) vaccine was submitted to a quantal assay of potency, as explained in detail in our companion paper [1]. To this purpose, twenty, 45-day old piglets, checked for maternally-derived antibody (MDA), were allocated to four groups of 5 animals each; these were vaccinated with 800/266/88/0 nanograms, respectively, of an inactivated PCV2b strain, consisting of two distinct virion populations. Twenty-six days later, all the pigs were challenged intranasally with the homologous PCV2b strain. In the presence of a clear dose-dependent protection in terms of viremia, no such effect was observed in terms of weight gain after challenge. The 800 and 266-ng payloads were associated with neutralizing antibody titers above the MDA levels in oral fluids. Higher levels of viremia in control and 88-ng groups [1] coincided with a higher Natural Killer activity of tracheobronchial lymph node cells from PCV2-infected pigs. The PCV2 ORF2-specific ELISPOT assay for IFN-g– secreting cells showed very few (2–4) ORF2-specific cells/105 peripheral blood mononuclear cells beyond the basal levels under our experimental conditions (non-significant differences among groups). Also, no significant differences were observed in the degree of lymphoid tissue hyperplasia among the different groups

An anti-CD45RO/RB monoclonal antibody modulates T cell responses via induction of apoptosis and generation of regulatory T cells

The effects of a chimeric monoclonal antibody (chA6 mAb) that recognizes both the RO and RB isoforms of the transmembrane protein tyrosine phosphatase CD45 on human T cells were investigated. Chimeric A6 (chA6) mAb potently inhibited antigen-specific and polyclonal T cell responses. ChA6 mAb induced activation-independent apoptosis in CD4+CD45RO/RBhigh T cells but not in CD8+ T cells. In addition, CD4+ T cell lines specific for tetanus toxoid (TT) generated in the presence of chA6 mAb were anergic and suppressed the proliferation and interferon (IFN)-γ production by TT-specific effector T cells by an interleukin-10–dependent mechanism, indicating that these cells were equivalent to type 1 regulatory T cells. Similarly, CD8+ T cell lines specific for the influenza A matrix protein-derived peptide (MP.58-66) generated in the presence of chA6 mAb were anergic and suppressed IFN-γ production by MP.58-66–specific effector CD8+ T cells. Furthermore, chA6 mAb significantly prolonged human pancreatic islet allograft survival in nonobese diabetic/severe combined immunodeficiency mice injected with human peripheral blood lymphocytes (hu-PBL-NOD/SCID). Together, these results demonstrate that the chA6 mAb is a new immunomodulatory agent with multiple modes of action, including deletion of preexisting memory and recently activated T cells and induction of anergic CD4+ and CD8+ regulatory T cells

[risk Factors Associated With The Acquisition Of Multiresistant Bacteria In A Pediatric Nursery]

OBJECTIVE: To identify the risk factors in patients who had a multiresistant bacteria during their staying in a Pediatric Intensive Care Unit and in a pediatric nursery of a tertiary teaching hospital.METHODS: Chart review of the patients who stayed in the units from January, 1995 to July, 1997 and had a multiresistant microorganism isolated (both infection and colonization). A case-control study was done using McNemar test for group comparison and using stepwise logistic regression to select independent risk factors. The following risk factors were tested: prior hospital staying, underlying disease, intensive care unit admission, surgical procedure, urinary catheter, central venous line, ventilator, prior antibiotic therapy and skin lesion.RESULTS: Among 52 patients, 66 multiresistant bacteria were identified (among them, 33 were gram-negative bacilli and 33 were methicillin-resistant S. aureus). The logistic regression analysis of the case-control study identified 2 risk factors: prior antibiotic therapy and skin lesion. A single risk factor was indicated for patients with gram-negative bacilli. Nevertheless, for patients with methicillin-resistant S. aureus, central venous lines and skin lesion were significant.CONCLUSION: Prior antibiotic therapy and skin lesion were the factors associated with the acquisition of multiresistant bacteria. Besides skin lesion, for oxacilin-resistant S. aureus colonized patients, central venous catheter use was a risk factor. The strategies employed to limit the spread of those bacteria in the hospital should consider these three factors.76275-8