Avoiding redundant columns by adding classical Benders cuts to column generation subproblems

This is the author accepted manuscript. The final version is available fro,m Elsevier via the DOI in this recordWhen solving the linear programming (LP) relaxation of a mixed-integer program (MIP) with column generation, columns might be generated that are not needed to express any integer optimal solution. Such columns are called strongly redundant and the dual bound obtained by solving the LP relaxation is potentially stronger if these columns are not generated. We introduce a sufficient condition for strong redundancy that can be checked by solving a compact LP. Using a dual solution of this compact LP we generate classical Benders cuts for the subproblem so that the generation of strongly redundant columns can be avoided. The potential of these cuts to improve the dual bound of the column generation master problem is evaluated computationally using an implementation in the branch-price-and-cut solver GCG. While their efficacy is limited on classical problems, the benefit of applying the cuts is demonstrated on structured models to which a temporal decomposition can be applied.Engineering and Physical Sciences Research Council (EPSRC

Organ Biodistribution of Radiolabelled γδ T Cells Following Liposomal Alendronate Administration in Different Mouse Tumour Models.

Vγ9Vδ2 T cell immunotherapy has been shown to be effective in delaying tumour growth in both pre-clinical and clinical studies. It has been pointed out the importance of the ability of cells to accumulate within tumours and the association with therapeutic efficacy in clinical studies of adoptive T cell transfer. We have previously reported that alendronate liposomes (L-ALD) increase the efficacy of this therapy after localised or systemic injection of γδ T cells in mice, inoculated with ovarian, melanoma, pancreatic or experimental lung metastasis tumour models, respectively. This study aimed to examine the organ biodistribution and tumour uptake of human γδ T cells in subcutaneous (SC), intraperitoneal (IP) or experimental metastatic lung tumours, established in NOD-SCID gamma (NSG) mice using the melanoma cell line A375Pβ6.luc. pre-injected with L-ALD. Overall, small variations in blood profiles and organ biodistribution of γδ T cells among the different tumour models were observed. Exceptionally, IP-tumour and experimental metastatic lung-tumour bearing mice pre-injected with L-ALD showed a significant decrease in liver accumulation, and highest uptake of γδ T cells in lungs and tumour-bearing lungs, respectively. Lower γδ T cell count was found in the SC and IP tumours

Whole-genome association analysis of treatment response in obsessive-compulsive disorder.

Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n=514) or 'non-response' (n=290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 × 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P<10(-5)) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877 and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave P-values of 2.86 × 10(-6) and 8.41 × 10(-6), respectively. The other 35 variations with signals of potential significance (P<10(-4)) involve multiple genes expressed in the brain, including GRIN2B, PCDH10 and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (false discovery rate (FDR)=0.0097) and the serotonergic system (FDR=0.0213). Although the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed

Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS.

Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based samples (resulting in a total sample of 5061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at single-nucleotide polymorphism (SNP) and gene levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13 × 10(-)(7)). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of genome-wide association study (GWAS) signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high-confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2 and PTPRD. Analyses at the gene level revealed association of IQCK and C16orf88 (both P<1 × 10(-)(6), experiment-wide significant), as well as OFCC1 (P=6.29 × 10(-)(5)). The suggestive findings in this study await replication in larger samples

Reliability of two goniometric methods of measuring active inversion and eversion range of motion at the ankle

BACKGROUND: Active inversion and eversion ankle range of motion (ROM) is widely used to evaluate treatment effect, however the error associated with the available measurement protocols is unknown. This study aimed to establish the reliability of goniometry as used in clinical practice. METHODS: 30 subjects (60 ankles) with a wide variety of ankle conditions participated in this study. Three observers, with different skill levels, measured active inversion and eversion ankle ROM three times on each of two days. Measurements were performed with subjects positioned (a) sitting and (b) prone. Intra-class correlation coefficients (ICC([2,1])) were calculated to determine intra- and inter-observer reliability. RESULTS: Within session intra-observer reliability ranged from ICC([2,1] )0.82 to 0.96 and between session intra-observer reliability ranged from ICC([2,1] )0.42 to 0.80. Reliability was similar for the sitting and the prone positions, however, between sessions, inversion measurements were more reliable than eversion measurements. Within session inter-observer measurements in sitting were more reliable than in prone and inversion measurements were more reliable than eversion measurements. CONCLUSION: Our findings show that ankle inversion and eversion ROM can be measured with high to very high reliability by the same observer within sessions and with low to moderate reliability by different observers within a session. The reliability of measures made by the same observer between sessions varies depending on the direction, being low to moderate for eversion measurements and moderate to high for inversion measurements in both positions

Direct Measurement of Nuclear Dependence of Charged Current Quasielastic-like Neutrino Interactions using MINERvA

Charged-current $\nu_{\mu}$ interactions on carbon, iron, and lead with a final state hadronic system of one or more protons with zero mesons are used to investigate the influence of the nuclear environment on quasielastic-like interactions. The transfered four-momentum squared to the target nucleus, $Q^2$, is reconstructed based on the kinematics of the leading proton, and differential cross sections versus $Q^2$ and the cross-section ratios of iron, lead and carbon to scintillator are measured for the first time in a single experiment. The measurements show a dependence on atomic number. While the quasielastic-like scattering on carbon is compatible with predictions, the trends exhibited by scattering on iron and lead favor a prediction with intranuclear rescattering of hadrons accounted for by a conventional particle cascade treatment. These measurements help discriminate between different models of both initial state nucleons and final state interactions used in the neutrino oscillation experiments

A frequentist framework of inductive reasoning

Reacting against the limitation of statistics to decision procedures, R. A. Fisher proposed for inductive reasoning the use of the fiducial distribution, a parameter-space distribution of epistemological probability transferred directly from limiting relative frequencies rather than computed according to the Bayes update rule. The proposal is developed as follows using the confidence measure of a scalar parameter of interest. (With the restriction to one-dimensional parameter space, a confidence measure is essentially a fiducial probability distribution free of complications involving ancillary statistics.) A betting game establishes a sense in which confidence measures are the only reliable inferential probability distributions. The equality between the probabilities encoded in a confidence measure and the coverage rates of the corresponding confidence intervals ensures that the measure's rule for assigning confidence levels to hypotheses is uniquely minimax in the game. Although a confidence measure can be computed without any prior distribution, previous knowledge can be incorporated into confidence-based reasoning. To adjust a p-value or confidence interval for prior information, the confidence measure from the observed data can be combined with one or more independent confidence measures representing previous agent opinion. (The former confidence measure may correspond to a posterior distribution with frequentist matching of coverage probabilities.) The representation of subjective knowledge in terms of confidence measures rather than prior probability distributions preserves approximate frequentist validity.Comment: major revisio

Midline fascial plication under continuous digital transrectal control: which factors determine anatomic outcome?

Contains fulltext : 88897.pdf (publisher's version ) (Closed access)INTRODUCTION AND HYPOTHESIS: The aim of the study was to report anatomic and functional outcome of midline fascial plication under continuous digital transrectal control and to identify predictors of anatomic failure. METHODS: Prospective observational cohort. Anatomic success defined as POP-Q stage or= II underwent midline fascial plication under continuous digital transrectal control. Median follow-up was 14 months (12-35 months), and anatomic success was 80.3% (95% CI 75-86). Independent predictors of failure were posterior compartment POP stage >or= III [OR 8.7 (95% CI 2.7-28.1)] and prior colposuspension [OR 5.6 (95% CI 1.1-27.8)]. Sixty-three percent of patients bothered by obstructed defaecation experienced relief after surgery. CONCLUSIONS: Anatomic and functional outcomes were good. Risk factors for anatomic failure were initial size of posterior POP (stage >or= III) and prior colposuspension.1 juni 201

Glioblastoma Subclasses Can Be Defined by Activity among Signal Transduction Pathways and Associated Genomic Alterations

Glioblastoma multiforme (GBM) is an umbrella designation that includes a heterogeneous group of primary brain tumors. Several classification strategies of GBM have been reported, some by clinical course and others by resemblance to cell types either in the adult or during development. From a practical and therapeutic standpoint, classifying GBMs by signal transduction pathway activation and by mutation in pathway member genes may be particularly valuable for the development of targeted therapies.We performed targeted proteomic analysis of 27 surgical glioma samples to identify patterns of coordinate activation among glioma-relevant signal transduction pathways, then compared these results with integrated analysis of genomic and expression data of 243 GBM samples from The Cancer Genome Atlas (TCGA). In the pattern of signaling, three subclasses of GBM emerge which appear to be associated with predominance of EGFR activation, PDGFR activation, or loss of the RAS regulator NF1. The EGFR signaling class has prominent Notch pathway activation measured by elevated expression of Notch ligands, cleaved Notch receptor, and downstream target Hes1. The PDGF class showed high levels of PDGFB ligand and phosphorylation of PDGFRbeta and NFKB. NF1-loss was associated with lower overall MAPK and PI3K activation and relative overexpression of the mesenchymal marker YKL40. These three signaling classes appear to correspond with distinct transcriptomal subclasses of primary GBM samples from TCGA for which copy number aberration and mutation of EGFR, PDGFRA, and NF1 are signature events.Proteomic analysis of GBM samples revealed three patterns of expression and activation of proteins in glioma-relevant signaling pathways. These three classes are comprised of roughly equal numbers showing either EGFR activation associated with amplification and mutation of the receptor, PDGF-pathway activation that is primarily ligand-driven, or loss of NF1 expression. The associated signaling activities correlating with these sentinel alterations provide insight into glioma biology and therapeutic strategies

Coexistence between renal cell cancer and Hodgkin's lymphoma: A rare coincidence

BACKGROUND: Renal cell carcinoma is the most common kidney tumor in adults and accounts for approximately 3% of adult malignancies. An increased incidence of second malignancies has been well documented in a number of different disorders, such as head and neck tumors, and hairy cell leukemia. In addition, treatment associated second malignancies (usually leukemias and lymphomas but also solid tumors) have been described in long term survivors of Hodgkin's lymphoma (HL), Non Hodgkin's lymphoma and in various pediatric tumors. CASE PRESENTATION: We present the case of a 66 year-old woman with abdominal pain and dyspnea. We performed a thorax CT scan that showed lymph nodes enlargement and subsequently by presence of abdominal pain was performed an abdominal and pelvis CT scan that showed a right kidney tumor of 4 × 5 cms besides of abdominal lymph nodes enlargement. A radical right nephrectomy was designed and Hodgkin's lymphoma was diagnosed in the abdominal lymph nodes while renal cell tumor exhibited a renal cell cancer. Patient received EVA protocol achieving complete response. CONCLUSION: We described the first case reported in the medical literature of the coexistence between Hodgkin's lymphoma and renal cell cancer. Previous reports have shown the relationship of lymphoid neoplasms with solid tumors, but they have usually described secondary forms of cancer related to chemotherapy