An approach for computing AS/R systems travel times in a class-based storage configuration

This study provides an approach to compute the travel time for AS/R systems in a class-based storage environment. A regression analysis is completed in order to define the importance of the key predictors taken into account and to propose a formulation of travel times. The results show the reliability of the model and allow to evaluate the travel time through the identification of a complete list of predictors. The proposed approach supports managers in theex-ante definition of travel times for a warehouse. A correct evaluation of travel times enables a better monitoring of the performance of warehouse operations and can support practitioners in the choice of the configuration not only in terms of kind of cycle, but also from a policy assignment perspective. From a theoretical point of view, this work can be considered as an attempt to refine the existing methods to compute travel times

l-Acetyl-carnitine in Patients with Carpal Tunnel Syndrome: Effects on Nerve Protection, Hand Function and Pain

Background and Aim: l-Acetyl-carnitine (LAC) exerts an energetic effect on nerves and muscles. Recently, preclinical experiments have demonstrated a central anti-nociceptive action. Objective: Our objective was to assess the effects of LAC on neuroprotection, pain, and function in carpal tunnel syndrome (CTS), a very frequent chronic compressive neuropathy. Methods: In a multicentre, examiner-blinded, clinical and neurophysiological 4-month study, we enrolled 82 patients and examined 120 hands with CTS of mild to moderate severity. Patients were assessed at baseline and 10, 60 and 120\uc2 days after treatment with LAC 500\uc2 mg twice daily (BID). All patients underwent a conduction study of the median nerve, the Boston Carpal Tunnel Questionnaire (BCTQ) and the Neuropathic Pain Symptom Inventory (NPSI). The primary endpoint was the sensory conduction velocity (SCV) of the median nerve. Results: The primary endpoint was met, with significant improvement of the SCV (P\uc2&nbsp

Risk-stratified patients with resectable soft tissue sarcoma benefit from epirubicin-based adjuvant chemotherapy

As adjuvant chemotherapy (AC) for soft tissue sarcomas is controversial, we performed a retrospective analysis of patients seen at Washington University in St. Louis to evaluate whether it benefited our patient population. Patients were risk-assessed using the Memorial Sloan Kettering Predictive Nomogram (MSKPN). We defined high-risk patients by a MSKPN 4-year postoperative probability of sarcoma-specific death of ≥0.3 and investigated if they benefited from AC. Retrospective review was performed on patients seen between 15 February 1996 and 6 February 2010. A propensity score method in the logistic regression framework was used to model the likelihood of receiving AC. To make causal inference on the effect of AC on survival outcomes, a propensity score inverse probability of treatment weighting approach was applied to survival analysis. Overall, 135 high-grade patients were assessed, 33 were treated with Ifosfamide/Epirubicin (I/Epi) and 102 were non AC patients. The stratified MSKPN risk was not significantly associated with any survival endpoint in the whole cohort, but trended for overall survival (OS) when evaluated against non AC patients. After adjustment for MSKPN risk and other variables, patients not receiving chemotherapy had significantly worse OS, recurrent free survival, and disease-specific survival (DSS) with adjusted hazard ratios of 4.18 (95% CI: 2.22–7.90), 8.96 (95% CI: 3.85–20.83), and 5.42 (95% CI: 2.09–14.06), respectively. In retrospective analyses, risk-stratified patients with soft tissue sarcoma benefited from I/Epi-based AC. Randomized I/Epi versus I/Doxorubicin clinical trials may determine the optimal adjuvant treatment

Detection of influenza A(H1N1)pdm09 virus in a patient travelling from Shanghai to Italy in July 2018: An uncommon clinical presentation in a non-seasonal period

Influenza is one of the most common infectious diseases in travellers, especially in those returning from subtropical and tropical regions. In late June 2018 an influenza A(H1N1)pdm09 virus infection was diagnosed in a 36-years-old man, returned from a travel in Shanghai and hospitalized at the Ospedale Policlinico San Martino, Genoa, Italy, with a diagnosis of fever and an uncommon clinical presentation characterised by a persistent leukopenia. Phylogenetic analysis revealed a closeness with influenza A(H1N1)pdm09 strains circulating in the US in May-June 2018. Prompt recognition of influenza infection led to a proper case management, demonstrating the crucial role of the continuous influenza surveillance programme

Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer.

Functional redundancy shared by paralog genes may afford protection against genetic perturbations, but it can also result in genetic vulnerabilities due to mutual interdependency1-5. Here, we surveyed genome-scale short hairpin RNA and CRISPR screening data on hundreds of cancer cell lines and identified MAGOH and MAGOHB, core members of the splicing-dependent exon junction complex, as top-ranked paralog dependencies6-8. MAGOHB is the top gene dependency in cells with hemizygous MAGOH deletion, a pervasive genetic event that frequently occurs due to chromosome 1p loss. Inhibition of MAGOHB in a MAGOH-deleted context compromises viability by globally perturbing alternative splicing and RNA surveillance. Dependency on IPO13, an importin-β receptor that mediates nuclear import of the MAGOH/B-Y14 heterodimer9, is highly correlated with dependency on both MAGOH and MAGOHB. Both MAGOHB and IPO13 represent dependencies in murine xenografts with hemizygous MAGOH deletion. Our results identify MAGOH and MAGOHB as reciprocal paralog dependencies across cancer types and suggest a rationale for targeting the MAGOHB-IPO13 axis in cancers with chromosome 1p deletion

Loxoscelismo en Chile: estudios epidemiológicos, clínicos y experimentales

Se presenta un enfoque panorámico de estudios epidemiológicos, clínicos y experimentales referentes a Loxosceles laeta y loxoscelismo efectuados en 1955-1988 en Santiago, Chile. Se estudiaron 216 casos de loxoscelismo. Los hechos más relevantes fueron: 52,8% correspondió a mujeres; edad entre 7 meses y 78 años; 84,3% fué loxoscelismo cutáneo (LO y 15,7% loxoscelismo cutáneo-visceral (LCV); 73,6% sucedió en época calurosa; en 86,6% el accidente ocurrió en la vivienda, especialmente en dormitorios, mientras la persona dormía o se vestía. La araña fué vista en 60,2% de los casos e identificada en laboratorio como L. laeta en 17,7% (10,6% de los 216 casos). Los sitios más frecuen temente afectados fueron las extremidades con 67,6%, lancetazo urente fué el síntoma inicial más frecuente. Dolor, edema y placa livedoide, la cual posteriormente se transformaría en escara necrótica, fueron las manifestaciones locales predominantes. En LCV hematuria y hemoglobinuria fueron constantes, ictericia, fiebre y compromiso de conciencia se presentaron en la mayoría de los casos. Tratamiento: LC con antihistamínicos o corticoides inyectables, LCV con corti-coides inyectables. La condición de los pacientes en el último control fué: curación completa en 75,5%, curación con secuela cicatrizal en 8,3%, muerte en 3,7% (todos con LCV) y abandono en 12,5%. Adicionalmente, se ha efectuado una serie de estudios experimentales, tanto in vivo como in vitro para esclarecer aspectos básicos sobre el veneno de L. laeta y el tratamiento del loxoscelismo.A panoramic sight of epidemiological, clinical and experimental studies, referring to Loxosceles laeta and loxoscelism, carried out in 1955-1988, in Santiago, Chile is presented. Two-hundred and sixteen cases of loxosce lism were studied. The most relevant features were: 84.3% corresponded to cutaneous loxosce lism (CD and 15.7% to viscerocutaneous loxos celism (VCD; 73.6% ocurred in hot season; in 86.6% of cases the accident happened in the hou se, particularly in bedrooms, while the people were sleeping or dressing. The spider was seen in 60.2%r of cases and identified in the laboratory as L. laeta in 10.69c of all cases. The sites more frequently bitten were the limbs with 67.6% ; a burning stinging was the most frequent initial symptom. Pain, edema and livedoid plaque, which developed later into a necrotic eschar, we re the predominant local manifestations. In VCL, hematuria and hemoglobinuria were cons tant, while jaundice, fever and sensorial involve ment were present in most of the cases. CL patients were parenterally treated with antihistamine drugs or corticoids, while VCL ones were treated with corticoids by injection. The condition of patients in the last follow up was: complete cure in 75.5% , cure with a scarfed sequela in 8.3%, death in 3.7% (all VCL) and abandonment in 12.5%. Additionally, a series of experimental studies, both in vivo and in vitro, has been performed in order to clarify basic aspects on L. laeta venom and the treatment of loxoscelism

Antiproliferative and pro-apoptotic effects afforded by novel Src-kinase inhibitors in human neuroblastoma cells

<p>Abstract</p> <p>Background</p> <p>Neuroblastoma (NB) is the second most common solid malignancy of childhood that usually undergoes rapid progression with a poor prognosis upon metastasis. The Src-family tyrosine kinases (SFKs) are a group of proteins involved in cancer development and invasiveness that seem to play an important role in the NB carcinogenesis.</p> <p>Methods</p> <p>To determine cell proliferation, the growth rate was evaluated by both MTT test and cells counted. Analysis of DNA content was performed for the evaluation of the cell cycle and apoptosis. To characterize the mechanisms underlying the antiproliferative effects induced by SI 34, a novel pyrazolo-pyrimidine derivative provided with Src inhibitory activity, the involvement of some cellular pathways that are important for cell proliferation and survival was investigated by western blot assays. In particular, the contribution of cyclins, Src and ERK were examined. Finally, experiments of cell adhesion and invasiveness were performed.</p> <p>Results</p> <p>Treatment of SH-SY5Y human NB cells and CHP100 human neuroepithelioma (NE) cultures with three novel pyrazolo[3,4-<it>d</it>]pyrimidine derivatives, namely SI 34, SI 35 and SI 83, inhibits the cell proliferation in a time and concentration-dependent manner. The maximal effect was obtained after 72 hours incubation with SI 34 10 μM. Fluorescence microscopy experiments, flow cytometry analysis and determination of caspase-3 activity by fluorimetric assays showed that SI 34 induced SH-SY5Y apoptosis. Moreover, SI 34 determined cell cycle arrest at the G0/G1 phase, paralleled by a decreased expression of cyclin D1. Furthermore, our data indicate that SI 34 reduces the SH-SY5Y cells adhesion and invasiveness. Evidence that SI 34 inhibits the Src and the ERK-phosphorylation, suggests the mechanism through which it exerts its effects in SH-SY5Y cells.</p> <p>Conclusions</p> <p>Our study shows the ability of this pyrazolo-pyrimidine Src inhibitor in reducing the growth and the invasiveness of human NB cells, suggesting a promising role as novel drug in the treatment of neuroblastoma.</p