Freight Service Design for the Italian Railways Company

In this paper, we present a mathematical model to design the service network, that is the set of origin-destination connections. The resulting model considers both full and empty freight car movements, and takes into account handling costs. More specifically, the model suggests the services to provide, as well as the number of trains and the number and type of cars traveling on each connection. Quality of service, which is measured as total travel time, is established by minimizing the waiting time of cars at intermediate stations. Our approach yields a multi-commodity network design problem with concave arc cost functions. To solve this problem, we implement a tabu search procedure which adopts ``perturbing\u27\u27 mechanisms to force the algorithm to explore a larger portion of the feasible region. Computational results on realistic instances show a significant improvement over current practice

Increased GLP-1 response to oral glucose in pre-pubertal obese children.

BACKGROUND: Gastrointestinal hormones, such as glucagon-like peptide (GLP-1), have been hypothesized to play a role in the pathogenesis of obesity-related complications. However, few data are available in youth. The objective of this study was to investigate the GLP-1 response to oral glucose load in obese pre-pubertal children and its relationship with insulin secretion. METHODS: Ten pre-pubertal obese children [five boys; 10.5±1.6 years; body mass index-standard deviation score (BMI-SDS): 2.2±0.5] and 10 controls (eight boys; 9.9±1.2 years; BMI-SDS: -0.7±0.5) underwent a modified oral glucose tolerance test (OGTT) to evaluate post-load glucose, insulin and GLP-1 responses. Insulin sensitivity [homeostasis model assessment of insulin resistance (HOMA-IR), whole body insulin sensitivity index (WBISI)] and secretion [HOMA-beta, insulinogenic index (IGI)] indexes, area under the curve (AUC) for glucose, insulin and GLP-1 were calculated. RESULTS: In obese children GLP-1 AUC values were higher and correlated with BMI-SDS (r=0.45; p=0.04), HOMA-IR (r=0.53; p=0.01) and fasting glucose (r=0.68; p=0.001). CONCLUSIONS: Obese children showed an increased GLP-1 response to oral glucose. These changes might likely represent a compensatory mechanism to avoid post-prandial hyperglycemia and allow a normal glucose tolerance

SURGICAL AND NON-SURGICAL THERAPY OF OBSTRUCTIVE SLEEP APNEA SYNDROME IN CHILDREN.

Interventions of paediatric obstructive sleep apnea syndrome are complex, varied and multidisciplinary. The goal of the treatment is to restore optimal breathing during the night and to relieve associated symptoms. Evidence suggests that the surgical intervention with removal of the tonsils and adenoids will lead to significant improvements in the most incomplicated cases, as recently reported from a meta-analysis. However, post-operative persistence of this syndrome in paediatric population is more frequent than expected, which supports the idea of the complexity of this syndrome. Adenotomy alone may not be sufficient in children with OSAS, because it does not address oropharyngeal obstruction secondary to tonsillar hyperplasia. Continuous positive airway pressure can effectively treat this syndrome in selected groups of children, improving both nocturnal and daytime symptoms, but poor adherence is a limiting factor. For this reason, CPAP is not recommended as first-line therapy for OSAS when adenotonsillectomy is an option. It is now being investigated the incorporation of nonsurgical approaches for milder forms and for residual OSAS after surgical intervention. Althought adeno­tonsillar hypertrophy is the most common for OSAS in children; obesity is emerging as an equally important etiological factor. Therefore an intensive weight reduction program and adequate sleep hygiene are also important lifestyle changes that may be very effective in mitigating the symptoms of this syndrome. Pharmacological therapy (leukotriene antagonists, topical nasal steroids) is usually use for mild forms of OSAS and in children with associated allergic diseases. Special orthodontic treatment and oropharyngeal exercises are a relatively new and promising alternative therapeutic modality used in selected groups of children with OSAS

Association between elevated TGA-IgA titers and older age at diagnosis with absence of HBV seroconversion in celiac children

Patients with celiac disease can have a low rate of protective hepatitis B (HBV) antibody titers after vaccination. We aimed to evaluate the HBV seroconversion in celiac disease (CD) children at the time of diagnosis as well as to identify the presence of possible predictive factors. Celiac disease children were prospectively enrolled and tested for antibodies against the S protein of HBV (HBsAg) at time of diagnosis between January 2009 and February 2020. Based on the serologic response to the vaccine, “responders” and “non-responders” were identified. Statistical analysis has been performed through R statistical software (3.5.1 version, R core Team) Of 96 CD children evaluated, 41.7% (n = 40) showed non-protective or absent antibody titers against HBV. Elevated IgA-antibodies against transglutaminase 2 (TGA-IgA) values and older age at diagnosis were associated with an absent seroconversion to HBV vaccine, while presenting symptoms were not significant. An elevated prevalence of absent seroconversion to HBV vaccine exists in this cohort of CD patients at the time of disease diagnosis. Elevated TGA-IgA titers and older age at diagnosis seem to negatively predict seroconversion. Further studies are needed to identify the real profile of “non-responders”, aiming to organize surveillance and eventual revaccination strategy

Screening salivare della malattia celiaca in bambini e adolescenti geneticamente predisposti

Introduzione: La celiachia (CD) è un disordine multifattoriale in cui il test genetico è di rilevanza clinica fondamentale. La malattia, infatti, solo raramente si sviluppa in assenza di aplotipi HLA-DQ2 e/o HLA-DQ8. Il quadro clinico della CD è estremamente variabile e, spesso, i pazienti sono asintomatici; pertanto, è di fondamentale importanza un intervento di prevenzione mirato alla diagnosi precoce di malattia nei soggetti a rischio. Obiettivo: Screening salivare mediante determinazione degli anticorpi anti-transglutaminasi IgA (TGA-IgA) con metodica radioimmunologica (RIA) per la diagnosi precoce di CD in una coorte di soggetti geneticamente predisposti. Metodi: Sono stati arruolati 883 bambini frequentanti due scuole primarie del Comune di Roma e 91 familiari di I grado di pazienti celiaci seguiti presso l’ambulatorio di Gastroenterologia Pediatrica del Policlinico Umberto I. 289 scolari e 70 familiari sono risultati geneticamente predisposti. 359 campioni di saliva sono stati raccolti e analizzati per il dosaggio dei TGA IgA con metodo RIA; contestualmente sono stati raccolti 359 campioni di siero per la determinazione dei TGA-IgA con metodo RIA ed ELISA. I bambini con TGA-IgA positivi sono stati successivamente inseriti nell’iter diagnostico previsto dalle Linee Guida ESPGHAN 2020. La sensibilità e la specificità di entrambe le metodiche sono state calcolate confrontando i risultati con le diagnosi eseguite secondo i criteri EPSGHAN 2020. Il test salivare è stato confrontato con la metodica ELISA su siero mediante l’utilizzo del test di Mc Nemar. Risultati: In una prima fase dello studio sono stati arruolati 359 soggetti geneticamente predisposti. Di questi, 19 bambini (5.3%) sono risultati positivi al test salivare: 16 bambini (84.2%) sono stati confermati alla determinazione sierologica con metodo RIA ed ELISA ed hanno ricevuto la diagnosi di CD; in particolare, 9 hanno mostrato valori di anticorpi TGA-IgA superiori di 10x il range di riferimento e anti-endomisio (EMA) positivi, mentre i restanti 7 bambini con valori inferiori a 10x sono stati sottoposti ad esofagogastroduodenoscopia (EGDS) che ha mostrato le tipiche lesioni istologiche. Un bambino (5.3%) con screening salivare positivo confermato con metodica RIA sul siero, ma con anticorpi negativi con ELISA è stato sottoposto ad EGDS che ha confermato la diagnosi. 2 bambini (10.5%) con valori salivari debolmente positivi non si sono confermati sul siero con entrambi i metodi e non hanno proseguito il follow-up. Due dei 340 bambini (0.6%) con screening salivare negativo hanno mostrato valori sierici positivi con metodo RIA ed ELISA e hanno ricevuto la conferma istologica di CD. I restanti 338 bambini (99.4%) negativi al test salivare si sono confermati negativi alle determinazioni sierologiche con entrambi i metodi. Il test salivare con metodo RIA ha mostrato una sensibilità pari a 94.4% (IC 95% 0.914-0.965) e una specificità pari a 99.4% (IC 95% 0.977-0.999); la sensibilità e specificità del metodo RIA su siero sono state del 100% (IC 95% 0.987-1); quelle del metodo ELISA sono state rispettivamente del 94.7% (IC 95% 0.918-0.967) e 100% (IC 95% 0.987-1). Il test di Mc Nemar ha mostrato la completa sovrapponibilità dei due test in esame (p=1). Conclusioni: La metodica RIA su saliva ha mostrato risultati sovrapponibili a quelli ottenuti su siero con metodica ELISA; potrebbe rappresentare pertanto un valido test di screening affidabile, semplice, riproducibile, economico e non invasivo. Insieme al kit Gene Celiac Screen, anch’esso poco invasivo, di facile utilizzo ed economico, potrebbe essere inserita in una strategia di screening di massa per la celiachia

Freight service design for an Italian railways company

In this paper, we present a mathematical model to design the service network, that is the set of origin-destination connections. The resulting model considers both full and empty freight car movements, and takes into account handling costs. More specifically, the model suggests the services to provide, as well as the number of trains and the number and type of cars traveling on each connection. Quality of service, which is measured as total travel time, is established by minimizing the waiting time of cars at intermediate stations. Our approach yields a multi-commodity network design problem with concave arc cost functions. To solve this problem, we implement a tabu search procedure which adopts "perturbing" mechanisms to force the algorithm to explore a larger portion of the feasible region. Computational results on realistic instances show a significant improvement over current practice

Celiac disease: New therapeutic options

Celiac disease (CD) is an autoimmune pathology, caused by a permanent intolerance to gluten contained in wheat and to similar prolamines present in barley and rye. It is a common disease as its prevalence, in Caucasian populations, is about 1-1.16%. There are several patterns of CD: symptomatic CD and silent CD, both characterized by typical histological lesions in the duodenum mucosa. The classic manifestation is distinguished by gastrointestinal symptoms such as diarrhoea, vomiting, abdominal distension and failure to thrive. On the other hand atypical forms are characterized by extraintestinal symptoms (anemia, low height, delayed puberty, headaches).The gluten-free diet for life is the only therapy currently available for CD. In this way it is ensured to coeliac patient a comparable growth and a state of health to that of a healthy subject. About 70% of the subjects respond with an improvement in symptoms within a few weeks from the start of the gluten-free diet, although histological healing is more delayed and not always complete. The ingestion of gluten in trace amounts can cause the persistence of enteric mucosal lesions. A recent study by Aziz et al. has shown that a large proportion of patients with celiac disease is not satisfied with the gluten-free diet.Considerable progress have been made regarding the biotechnology field, which led to a better understanding of the molecular mechanisms of coeliac disease and the identification of pathogenetic pathways that could be targeted by new drugs. We can distinguish different categories of drugs according to their mechanism of action:• Endopeptidases capable to detoxify gluten in order to decrease its immunogenic power.• Modulation of permeability by the pill AT-1001.• Block of antigen presentation made by inhibitors of TG2 and HLA-DQ2.• Inflammation modulation using monoclonal antibodies directed against inflammatory cytokines.• Block of the recruitment of lymphocytes by molecules that inhibit the migration to the intestinal mucosa.• Immunomodulation and induction of gluten tolerance. © 2013 Nova Science Publishers, Inc. All rights reserved

Autonomic imbalance during apneic episodes in pediatric obstructive sleep apnea

OBJECTIVES: To investigate the activity of the autonomic nervous system (ANS) during sleep in children with obstructive sleep apnea (OSA), in order to detect a possible cardiac ANS imbalance analyzing heart rate variability (HRV). METHODS: 43 subjects between 4 and 12years of age (7.26±2.8years), undergoing a diagnostic assessment for OSA were evaluated. A time domain index (R-apnea index) was developed to evaluate HRV strictly related to obstructive events during sleep. Poincaré plot of RR intervals during the whole night was calculated. RESULTS: R-apnea index was negatively correlated with apnea hypopnea index (AHI) (r=-0.360, p=0.028). AHI and the duration of the disease were the only variables that were significantly correlated with R-apnea index. Three groups were subsequently created according to polysomnographic findings considering AHI. R-apnea index resulted significantly lower in patient with severe OSA compared to primary snoring/mild OSA subjects (p<0.05). Looking at Poincaré plot, SD1 showed a diminishing trend with severity of OSA, however not reaching statistical significance. CONCLUSIONS: Our findings suggest an autonomic impairment in OSA children evidenced by the altered HRV both in the very short term (R-apnea index) and in short term (SD1)

Rapid maxillary expansion outcomes in treatment of obstructive sleep apnea in children

Objectives: Theobjectivesofthisstudyweretoconfirmtheefficacyofrapidmaxillaryexpansioninchildren withmoderateadenotonsillarhypertrophyinalargersampleandtoevaluateretrospectivelyitslong-term benefits in a group of children who underwent orthodontic treatment 10 years ago. Methods: After general clinical examination and overnight polysomnography, all eligible children underwent cephalometric evaluation and started 12 months of therapy with rapid maxillary expansion. Anewpolysomnographywasperformedattheendoftreatment(T1).Fourteenchildrenunderwentclinical evaluation and Brouilette questionnaire, 10 years after the end of treatment (T2). Results: Forty patients were eligible for recruitment. At T1, 34/40 (85%) patients showed a decrease of apnea–hypopneaindex(AHI)greaterthan20%(ΔAHI67.45%±25.73%)andweredefinedresponders.Only 6/40 (15%) showed a decrease &lt;20% of AHI at T1 and were defined as non-responders (ΔAHI −53.47%±61.57%).Moreover,57.5%ofpatientspresentedresidualOSA(AHI&gt;1ev/h)aftertreatment.Disease duration was significantly lower (2.5±1.4 years vs 4.8±1.9 years, p&lt;0.005) and age at disease onset was higher in responder patients compared to non-responders (3.8±1.5 years vs 2.3±1.9 years, p&lt;0.05). Cephalometric variables showed an increase of cranial base angle in non-responder patients (p&lt;0.05). Fourteen children (mean age 17.0±1.9 years) who ended orthodontic treatment 10 years previously showed improvement of Brouilette score. Conclusion: Starting an orthodontic treatment as early as symptoms appear is important in order to increase the efficacy of treatment. An integrated therapy is needed