A Group Theoretic Tabu Search Methodology for Solving the Theater Distribution Vehicle Routing and Scheduling Problem

The application of Group Theory to Tabu Search is a new and exciting field of research. This dissertation applies and extends some of Colletti\u27s (1999) seminal work in group theory and metaheuristics in order to solve the theater distribution vehicle routing and scheduling problem (TDVRSP). This research produced a robust, efficient, effective and flexible generalized theater distribution model that prescribes the routing and scheduling of multi-modal theater transportation assets to provide economically efficient time definite delivery of cargo to customers. In doing so, advances are provided in the field of group theoretic tabu search and its application to difficult combinatorial optimization problems, e.g., the multiple trip multiple services vehicle routing and scheduling problem with hubs and other defining constraints

Globalization and mental distress

We study the effects of import competition on workers' mental distress, using unique longitudinal data on mental health for British residents, coupled with measures of import competition in more than 100 industries over 1995\u20132007. We find that import competition has a large negative impact on individual mental health. Compared to a worker employed in the industry at the 25th percentile of the import competition distribution, a worker employed in the industry at the 75th percentile would need a yearly monetary compensation of \ua3270 to make up for her greater utility loss. We find import competition to have larger effects on the right tail of the mental distress distribution, thereby increasing inequality in mental health not only across but also within industries. We show that this is consistent with import competition disproportionately hitting specific groups of workers in an industry, such as the youngest or those with a large family, a poor financial condition, a short job tenure, a temporary contract, and a blue-collar or tradable job. Using information on family ties, we find that import competition has negative spillovers to other family members. In particular, women's mental distress increases as a consequence of the import competition faced by their partners. Moreover, paternal import competition leads to reduced investment in child rearing and worsened children's self-esteem and life satisfaction. Finally, we provide evidence that import competition is likely to work through a complex set of channels. These include observable labor market outcomes such as higher likelihood of job displacement and lower wage growth, but also reduced job satisfaction and gloomier expectations about the future

Osimertinib in patients with advanced epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer: Rationale, evidence and place in therapy

The identification of epidermal growth factor receptor (EGFR) mutations represented a fundamental step forward in the treatment of advanced non-small cell lung cancer (NSCLC) as they define a subset of patients who benefit from the administration of specifically designed targeted therapies. The inhibition of mutant EGFR through EGFR-tyrosine kinase inhibitors (TKIs), either reversible, first-generation gefitinib and erlotinib, or irreversible, second-generation afatinib, has dramatically improved the prognosis of patients harboring this specific genetic alteration, leading to unexpected clinical benefit. Unfortunately, virtually all patients who initially respond to treatment develop acquired resistance to EGFR-TKIs within 9-14 months. The EGFR T790M secondary mutation has emerged as a cause of treatment failure in approximately 60% of resistant cases. To date, several compounds designed with the aim to overcome T790M-mediated resistance are under clinical investigation. The aim of this review is to discuss emerging data regarding the third-generation EGFR-TKI, osimertinib, for the treatment of EGFR T790M mutant advanced NSCLC

Diagnostic performance of endoscopic ultrasound-guided tissue acquisition of splenic lesions: systematic review with pooled analysis

Background: Focal splenic lesions are usually incidentally discovered on radiological assessments. Although percutaneous tissue acquisition (TA) under trans-abdominal ultrasound guidance is a well-established technique for obtaining cyto-histological diagnosis of focal splenic lesions, endoscopic ultrasound (EUS)-guided TA has been described in several studies, reporting different safety and outcomes. The aim was to assess the pooled safety, adequacy, and accuracy of EUS-TA of splenic lesions. Methods: A comprehensive review of available evidence was conducted at the end of November 2021. All studies including more than five patients and reporting about the safety, adequacy, and accuracy of EUS-TA of the spleen were included. Results: Six studies (62 patients) were identified; all studies have been conducted using fine-needle aspiration (FNA) needles. Pooled specimen adequacy and accuracy of EUS-TA for spleen characterization were 92.8% [95% confidence interval (CI), 86.3%-99.3%] and 88.2% (95% CI, 79.3%-97.1%), respectively. The pooled incidence of adverse events (six studies, 62 patients) was 4.7% (95% CI, 0.4%-9.7%). Conclusion: EUS-FNA of the spleen is a safe technique with high diagnostic adequacy and accuracy. The EUS-guided approach could be considered a valid alternative to the percutaneous approach for spleen TA

Treatment with class a CpG oligodeoxynucleotides in cats with naturally occurring feline parvovirus infection: A prospective study

Feline parvovirus (FPV) causes severe gastroenteritis and leukopenia in cats; the outcome is poor. Information regarding specific treatments is lacking. Class A CpG oligodeoxynucleotides (CpG-A) are short single-stranded DNAs, stimulating type I interferon production. In cats, CpG-A induced an antiviral response in vivo and inhibited FPV replication in vitro. The aim was to prospectively investigate the effects of CpG-A on survival, clinical score, hematological findings, antiviral response (cytokines), viremia, and fecal shedding (real-time qPCR) in cats naturally infected with FPV. Forty-two FPV-infected cats were randomized to receive 100 g/kg of CpG-A (n = 22) or placebo (n = 20) subcutaneously, on admission and after 48 h. Blood and fecal samples were collected on admission, after 1, 3, and 7 days. All 22 cats showed short duration pain during CpG-A injections. The survival rate, clinical score, leukocyte and erythrocyte counts, viremia, and fecal shedding at any time-point did not differ between cats treated with CpG-A (50%) and placebo (40%). Antiviral myxovirus resistance (Mx) gene transcription increased in both groups from day 1 to 3 (p = 0.005). Antibodies against FPV on admission were associated with survival in cats (p = 0.002). In conclusion, CpG-A treatment did not improve the outcome in cats with FPV infection. FPV infection produced an antiviral response

EGFR and HER2 Gene Copy Number and Response to First-Line Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer (NSCLC)

n/

MYC and human telomerase gene (TERC) copy number gain in early-stage non-small cell lung cancer

Objectives: We investigated the frequency of MYC and TERC increased gene copy number (GCN) in early-stage non-small cell lung cancer (NSCLC) and evaluated the correlation of these genomic imbalances with clinicopathologic parameters and outcome. Materials and Methods: Tumor tissues were obtained from 113 resected NSCLCs. MYC and TERC GCNs were tested by fluorescence in situ hybridization (FISH) according to the University of Colorado Cancer Center (UCCC) criteria and based on the receiver operating characteristic (ROC) classification. Results: When UCCC criteria were applied, 41 (36%) cases for MYC and 41 (36%) cases for TERC were considered FISH-positive. MYC and TERC concurrent FISH-positive was observed in 12 cases (11%): 2 (17%) cases with gene amplification and 10 (83%) with high polysomy. By using the ROC analysis, high MYC (mean ≥2.83 copies/cell) and TERC (mean ≥2.65 copies/cell) GCNs were observed in 60 (53.1%) cases and 58 (51.3%) cases, respectively. High TERC GCN was associated with squamous cell carcinoma (SCC) histology (P=0.001). In univariate analysis, increased MYC GCN was associated with shorter overall survival (P=0.032 [UCCC criteria] or P=0.02 [ROC classification]), whereas high TERC GCN showed no association. In multivariate analysis including stage and age, high MYC GCN remained significantly associated with worse overall survival using both the UCCC criteria (P=0.02) and the ROC classification (P=0.008). Conclusions: Our results confirm MYC as frequently amplified in early-stage NSCLC and increased MYC GCN as a strong predictor of worse survival. Increased TERC GCN does not have prognostic impact but has strong association with squamous histology