A short-turning policy for the management of demand disruptions in rapid transit systems

Rapid transit systems timetables are commonly designed to accommodate passenger demand in sections with the highest passenger load. However, disruptions frequently arise due to an increase in the demand, infrastructure incidences or as a consequence of fleet size reductions. All these circumstances give rise to unsupplied demand at certain stations, which generates passenger overloads in the available vehicles. The design of strategies that guarantee reasonable user waiting time with small increases of operation costs is now an important research topic. This paper proposes a tactical approach to determine optimal policies for dealing with such situations. Concretely, a short-turning strategy is analysed, where some vehicles perform short cycles in order to increase the frequency among certain stations of the lines and to equilibrate the train occupancy level. Turn-back points should be located and service offset should be determined with the objective of diminishing the passenger waiting time while preserving certain level of quality of service. Computational results and analysis for a real case study are provided.Junta de Andalucía P09-TEP-5022Natural Sciences and Engineering Research Council of Canada (NSERC) 39682-1

Analyzing the theoretical capacity of railway networks with a radial-backbone topology

In this work we propose a mechanism to optimize the capacity of the main corridor within a railway network with a radial-backbone or X-tree structure. The radial-backbone (or Xtree) structure is composed of two types of lines: the primary lines that travel exclusively on the common backbone (main corridor) and radial lines which, starting from the common backbone, branch out to individual locations. We define possible line configurations as binary strings and propose operators on them for their analysis, yielding an effective algorithm for generating an optimal design and train frequencies. We test our algorithm on real data for the high speed line Madrid-Seville. A frequency plan consistent with the optimal capacity is then proposed in order to eliminate the number of transfers between lines as well as to minimize the network fleet size, determining the minimum number of vehicles needed to serve all travel demand at maximum occupancy.Ministerio de Economía y Competitividad MTM2012-37048Junta de Andalucía P09-TEP-5022Junta de Andalucía P10-FQM-5849Canadian Natural Sciences and Engineering Research Council 39682-1

Open-access quantitative MRI data of the spinal cord and reproducibility across participants, sites and manufacturers

Databases; Imaging techniques; Spinal cord diseasesBases de datos; Tècnicas de imagen; Enfermedades de la médula espinalBases de dades; Tècniques d'imatge; Malalties de la medul·la espinalIn a companion paper by Cohen-Adad et al. we introduce the spine generic quantitative MRI protocol that provides valuable metrics for assessing spinal cord macrostructural and microstructural integrity. This protocol was used to acquire a single subject dataset across 19 centers and a multi-subject dataset across 42 centers (for a total of 260 participants), spanning the three main MRI manufacturers: GE, Philips and Siemens. Both datasets are publicly available via git-annex. Data were analysed using the Spinal Cord Toolbox to produce normative values as well as inter/intra-site and inter/intra-manufacturer statistics. Reproducibility for the spine generic protocol was high across sites and manufacturers, with an average inter-site coefficient of variation of less than 5% for all the metrics. Full documentation and results can be found at https://spine-generic.rtfd.io/. The datasets and analysis pipeline will help pave the way towards accessible and reproducible quantitative MRI in the spinal cord

Propuesta de un plan de mejora y un plan de trazabilidad para la panificadora Gabriel.

referenciasCon el presente trabajo se pretende hacer un estudio enfocado en la sanidad, calidad e inocuidad de alimentos aplicado a la Panificadora Gabriel a partir de diferentes casos hipotéticos engranados entre sí que lleven al desarrollo de cada una de las etapas para dar alternativas de solución a los posibles problemas encontrados. Debido a que dicha panificadora se ha visto envuelta en situaciones problemáticas, sus operaciones podrían detenerse por parte de las autoridades competentes ya que uno de sus productos desato un caso de ETA a un grupo de consumidores, poniendo en peligro la vida. Por este motivo se requiere con urgencia una reevaluación de la situación de la empresa panificadora, mediante estudios que permitan identificar sus falencias y necesidades para hacer que continúe, pero con responsabilidad y bajo el amparo de las normas alimentarias. Para este estudio se parte de varias herramientas que han sido proporcionadas por el caso de estudio. Se tiene una descripción inicial de la empresa, su historia, productos que produce, Proyectos de infraestructura y algunos datos sobres quiénes son sus trabajadores, proveedores y clientes. Por otra parte, se tiene la ficha de visita a la planta por parte de las autoridades Sanitarias, resultados de laboratorio de las muestras del caso de ETA en el cual se vio involucrada esta empresa, entre otros pormenores.With the present work is intended to make a study focused on the health, quality and safety of food applied to the Bakery Gabriel from different hypothetical cases geared to each other leading to the development of each of the stages to provide alternative solutions to the possible problems encountered. Because the bakery has been involved in problematic situations, its operations could stop by the competent authorities, since one of their products unleashed a case of ETA to a group of consumers, endangering life. For this reason, a reassessment of the situation of the bakery company is urgently required, through studies that identify its shortcomings and needs to continue, but with responsibility and under the protection of food standards. For this study, we start with several tools that have been provided by the case study. It has an initial description of the company, its history, products it produces, Infrastructure projects and some data about whom They are your workers, suppliers and customers. On the other hand, you have the file to visit the plant by the authorities Sanitary, laboratory results of the samples of the case of ETA in which this company was involved, among other details

A computer-aided diagnosis of multiple sclerosis based on mfVEP recordings.

Introduction: The aim of this study is to develop a computer-aided diagnosis system to identify subjects at differing stages of development of multiple sclerosis (MS) using multifocal visual-evoked potentials (mfVEPs). Using an automatic classifier, diagnosis is performed first on the eyes and then on the subjects. Patients: MfVEP signals were obtained from patients with Radiologically Isolated Syndrome (RIS) (n = 30 eyes), patients with Clinically Isolated Syndrome (CIS) (n = 62 eyes), patients with definite MS (n = 56 eyes) and 22 control subjects (n = 44 eyes). The CIS and MS groups were divided into two subgroups: those with eyes affected by optic neuritis (ON) and those without (non-ON). Methods: For individual eye diagnosis, a feature vector was formed with information about the intensity, latency and singular values of the mfVEP signals. A flat multiclass classifier (FMC) and a hierarchical classifier (HC) were tested and both were implemented using the k-Nearest Neighbour (k-NN) algorithm. The output of the best eye classifier was used to classify the subjects. In the event of divergence, the eye with the best mfVEP recording was selected. Results: In the eye classifier, the HC performed better than the FMC (accuracy = 0.74 and extended Matthew Correlation Coefficient (MCC) = 0.68). In the subject classification, accuracy = 0.95 and MCC = 0.93, confirming that it may be a promising tool for MS diagnosis. Chirped-pulse φOTDR provides distributed strain measurement via a time-delay estimation process. We propose a lower bound for performance, after reducing sampling error and compensating phase-noise. We attempt to reach the limit, attaining unprecedented pε/√Hz sensitivities. Conclusion: In addition to amplitude (axonal loss) and latency (demyelination), it has shown that the singular values of the mfVEP signals provide discriminatory information that may be used to identify subjects with differing degrees of the disease.Secretaría de Estado de Investigación, Desarrollo e InnovaciónInstituto de Salud Carlos II

Neural correlates of moral sensitivity in obsessive-compulsive disorder

Context: heightened moral sensitivity seems to characterize patients with obsessive-compulsive disorder (OCD). Recent advances in social cognitive neuroscience suggest that a compelling relationship may exist between this disorder-relevant processing bias and the functional activity of brain regions implicated in OCD. Objective: to test the hypothesis that patients with OCD demonstrate an increased response of relevant ventromedial prefrontal and orbitofrontal cortex regions in a functional magnetic resonance imaging study of difficult moral decision making. Design: case-control cross-sectional study. Setting: hospital referral OCD unit and magnetic resonance imaging facility. Participants: seventy-three patients with OCD (42 men and 31 women) and 73 control participants matched for age, sex, and education level. Main outcome measures: functional magnetic resonance imaging activation maps representing significant changes in blood oxygenation level-dependent signal in response to 24 hypothetical moral dilemma vs nondilemma task vignettes and additional activation maps representing significant linear associations between patients' brain responses and symptom severity ratings. Results: in both groups, moral dilemma led to robust activation of frontal and temporoparietal brain regions. Supporting predictions, patients with OCD demonstrated significantly increased activation of the ventral frontal cortex, particularly of the medial orbitofrontal cortex. In addition, the left dorsolateral prefrontal cortex and left middle temporal gyrus were more robustly activated in patients with OCD. These results were unexplained by group differences in comorbid affective symptoms. Patients' global illness severity predicted the relative magnitude of orbitofrontal-striatal activation. The severity of 'harm/checking' symptoms and 'sexual/religious' obsessions predicted the magnitude of posterior temporal and amygdala-paralimbic activation, respectively. Conclusions: the neural correlates of moral sensitivity in patients with OCD partly coincide with brain regions that are of general interest to pathophysiologic models of this disorder. In particular, these findings suggest that the orbitofrontal cortex together with the left dorsolateral prefrontal cortex may be relevant for understanding the link between neurobiological processes and certain maladaptive cognitions in OCD

Efficacy of Anakinra in Refractory Adult-Onset Still's Disease: Multicenter Study of 41 Patients and Literature Review

Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients. Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent. Forty-one patients (26 women/15 men) were recruited. They had a mean age of 34.4 ± 14 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2-6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3-47.5] mg/day at ANK onset to 5 [0-10] at 12 months. After a median [IQR] follow-up of 16 [5-50] months, the most important side effects were cutaneous manifestations (n = 8), mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5). ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations

Factors associated with the clinical outcome of patients with relapsed/refractory CD19+acute lymphoblastic leukemia treated with ARI-0001 CART19-cell therapy

The prognosis of patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) remains poor, particularly for those relapsing after allogeneic hema-topoietic cell transplantation (alloHCT). Novel agents such as inotuzumab ozogamicin or blinatumomab achieve increased response rates, but these are generally transient unless followed by alloHCT. Chimeric antigen receptors (CAR) targeting CD19 have shown promising results in R/R ALL, and one of these products (tisagenlecleucel) has been approved for the treatment of patients with R/R ALL up to 25 years of age

Tocilizumab in refractory Caucasian Takayasu's arteritis: a multicenter study of 54 patients and literature review

Objective: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu's arteritis (TAK) in clinical practice. Methods: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZMONO) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZCOMBO) was performed. Results: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5-50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0-31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5-50.0) to 5.0 (0.0-5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0-14.0) months. Twenty-three (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n = 28), cyclosporine A (n = 2), azathioprine (n = 1). Patients on TCZCOMBO were younger [38.0 (27.0-46.0) versus 45.0 (38.0-57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0-38.0) versus 6.0 (1.0-23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7-5.6) versus 1.3 (0.3-3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal. Conclusion: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin.Funding: This work was partially supported by RETICS Programs, RD08/0075 (RIER), RD12/0009/0013 and RD16/0012 from “Instituto de Salud Carlos III” (ISCIII) (Spain)