An application of the sports logistics framework: the case of the Dallas Cowboys

Global, national and regional sport organizations heavily rely on logistics management practices in their operations. However, scientific research in sports logistics is in its infancy, with conceptualizations of the sport logistics domain proposed only recently. In response and by using a reoccurring professional sport event as a case, this study applies the Sports Logistics Framework (SLF) to systematically assess logistics activities, organizational structures, resources and components. Based on semi-structured interviews, unstructured participant observation, internal documents and additional secondary data, our findings not only provide insights into the logistics operations behind a matchday of one of the leading and most valuable sport competitions in the world, but also contextualize, illustrate and refine the logistical tasks of the SLF, thereby providing a template which can be used for further comparison and examination of logistics activities at similar sport events

An Important Role for Syndecan-1 in Herpes Simplex Virus Type-1 Induced Cell-to-Cell Fusion and Virus Spread

Herpes simplex virus type-1 (HSV-1) is a common human pathogen that relies heavily on cell-to-cell spread for establishing a lifelong latent infection. Molecular aspects of HSV-1 entry into host cells have been well studied; however, the molecular details of the spread of the virus from cell-to-cell remain poorly understood. In the past, the role of heparan sulfate proteoglycans (HSPG) during HSV-1 infection has focused solely on the role of HS chains as an attachment receptor for the virus, while the core protein has been assumed to perform a passive role of only carrying the HS chains. Likewise, very little is known about the involvement of any specific HSPGs in HSV-1 lifecycle. Here we demonstrate that a HSPG, syndecan-1, plays an important role in HSV-1 induced membrane fusion and cell-to-cell spread. Interestingly, the functions of syndecan-1 in fusion and spread are independent of the presence of HS on the core protein. Using a mutant CHO-K1 cell line that lacks all glycosaminoglycans (GAGs) on its surface (CHO-745) we demonstrate that the core protein of syndecan-1 possesses the ability to modulate membrane fusion and viral spread. Altogether, we identify a new role for syndecan-1 in HSV-1 pathogenesis and demonstrate HS-independent functions of its core protein in viral spread

An association study on contrasting cystic fibrosis endophenotypes recognizes KRT8 but not KRT18 as a modifier of cystic fibrosis disease severity and CFTR mediated residual chloride secretion

<p>Abstract</p> <p>Background</p> <p>F508del-CFTR, the most frequent disease-causing mutation among Caucasian cystic fibrosis (CF) patients, has been characterised as a mutant defective in protein folding, processing and trafficking. We have investigated the two neighbouring cytokeratin genes <it>KRT8 </it>and <it>KRT18 </it>in a candidate gene approach to ask whether variants in <it>KRT8 </it>and/or <it>KRT18 </it>modify the impaired ion conductance known as the CF basic defect, and whether they are associated with correct trafficking of mutant CFTR and disease severity of CF.</p> <p>Methods</p> <p>We have selected contrasting F508del-<it>CFTR </it>homozygous patient subpopulations stratified for disease severity, comparing 13 concordant mildly affected sib pairs vs. 12 concordant severely affected sib pairs, or manifestation of the CF basic defect in intestinal epithelium, comparing 22 individuals who exhibit CFTR-mediated residual chloride secretion vs. 14 individuals who do not express any chloride secretion, for an association. The <it>KRT8</it>/<it>KRT18 </it>locus was initially interrogated with one informative microsatellite marker. Subsequently, a low density SNP map with four SNPs in KRT8 and two SNPs in KRT18, each selected for high polymorphism content, was used to localize the association signal.</p> <p>Results</p> <p><it>KRT8</it>, but not <it>KRT18</it>, showed an association with CF disease severity (P_best= 0.00131; P_corr= 0.0185) and CFTR mediated residual chloride secretion (P_best= 0.0004; P_corr= 0.0069). Two major four-marker-haplotypes spanning 13 kb including the entire <it>KRT8 </it>gene accounted for 90% of chromosomes, demonstrating strong linkage disequilibrium at that locus. Absence of chloride secretion was associated with the recessive haplotype 1122 at rs1907671, rs4300473, rs2035878 and rs2035875. The contrasting haplotype 2211 was dominant for the presence of CFTR mediated residual chloride secretion. In consistency, the <it>KRT8 </it>haplotype 2211 was associated with mild CF disease while 1122 was observed as risk haplotype. Analysis of microsatellite allele distributions on the SNP background suggests that the mild <it>KRT8 </it>haplotype 2211 is phylogenetically older than its severe counterpart.</p> <p>Conclusions</p> <p>The two opposing <it>KRT8 </it>alleles which have been identified as a benign and as a risk allele in this work are likely effective in the context of epithelial cell differentiation. As the mild <it>KRT8 </it>allele is associated with CFTR mediated residual chloride secretion among F508del-<it>CFTR </it>homozygotes, the KRT8/KRT18 heterodimeric intermediary filaments of the cytoskeleton apparently are an essential component for the proper targeting of CFTR to the apical membrane in epithelial cells.</p

Prospective evaluation of weekly concomitant tumor bed boost with three-week hypofractionated whole breast irradiation in early breast cancer

Objectives: A prospective study was conducted to assess the acute and late toxicity of hypofractionated whole breast irradiation with a weekly concomitant boost for women with early breast cancer (EBC). Methods: Women with EBC who underwent breast-conserving surgery were eligible. A dose of 40Gy in 15 fractions over 3 weeks was delivered to the whole breast with a concomitant weekly boost to the post-operative cavity of 3Gy in three fractions. Toxicity was graded using the Radiation Therapy Oncology Group (RTOG) acute toxicity and RTOG/EORTC late toxicity scales. Results: A total of 67 women were enrolled with a median age of 49 years (range 31–69). Median follow-up was 25 months (range 11–34). Acute skin reactions included grade (G) 1 (n = 47, 70%), G2 (n = 10, 13%), and G3 (n = 1, 1.5%). Late skin toxicity was observed in 13 patients (19%), all of whom experienced G1 toxicity only. On multivariable analysis, diabetes mellitus was predictive of acute skin toxicity (p = 0.003), while age less than 50 years (p = 0.029) and diabetes mellitus (p = 0.013) were predictive of late skin toxicity. Conclusions: Whole breast irradiation with concomitant weekly boost appears feasible and safe. Further investigation is required to fully evaluate this schedule as an alternative to conventional whole breast irradiation with a sequential boost

Comparison of Strategies to Detect Epistasis from eQTL Data

Genome-wide association studies have been instrumental in identifying genetic variants associated with complex traits such as human disease or gene expression phenotypes. It has been proposed that extending existing analysis methods by considering interactions between pairs of loci may uncover additional genetic effects. However, the large number of possible two-marker tests presents significant computational and statistical challenges. Although several strategies to detect epistasis effects have been proposed and tested for specific phenotypes, so far there has been no systematic attempt to compare their performance using real data. We made use of thousands of gene expression traits from linkage and eQTL studies, to compare the performance of different strategies. We found that using information from marginal associations between markers and phenotypes to detect epistatic effects yielded a lower false discovery rate (FDR) than a strategy solely using biological annotation in yeast, whereas results from human data were inconclusive. For future studies whose aim is to discover epistatic effects, we recommend incorporating information about marginal associations between SNPs and phenotypes instead of relying solely on biological annotation. Improved methods to discover epistatic effects will result in a more complete understanding of complex genetic effects

Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells

Efficacy of chemotherapy in advanced stages of colorectal tumours is limited. The quinolone antibiotic ciprofloxacin was recently shown to inhibit growth and to induce apoptosis in human bladder carcinomas cells. We investigated the effect of ciprofloxacin on colon carcinoma lines in vitro. CC-531, SW-403 and HT-29 colon carcinoma and HepG2 hepatoma cells (control cells) were exposed to ciprofloxacin. Proliferation was assessed by bromodeoxyuridine-incorporation into DNA and apoptosis was measured by flow cytometry after propidium iodide or JC-1 staining. Expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax was analyzed by semiquantitative Western blot analysis and activity of caspases 3, 8 and 9 by substrate-cleavage assays. Ciprofloxacin suppressed DNA synthesis of all colon carcinoma cells time- and dose-dependently, whereas the hepatoma cells remained unaffected. Apoptosis reached its maximum between 200 and 500 μg ml−1. This was accompanied by an upregulation of Bax and of the activity of caspases 3, 8 and 9, and paralleled by a decrease of the mitochondrial membrane potential. Ciprofloxacin decreases proliferation and induces apoptosis of colon carcinoma cells, possibly in part by blocking mitochondrial DNA synthesis. Therefore, qualification of ciprofloxacin as adjunctive agent for colorectal cancer should be evaluated

Impact of age and comorbidities on health-related quality of life for patients with prostate cancer: evaluation before a curative treatment

<p>Abstract</p> <p>Background</p> <p>Interpretation of comparative health-related quality of life (HRQOL) studies following different prostate cancer treatments is often difficult due to differing patient ages. Furthermore, age-related changes can hardly be discriminated from therapy-related changes. The evaluation of age-and comorbidity-related changes was in focus of this study.</p> <p>Methods</p> <p>HRQOL of 528 prostate cancer patients was analysed using a validated questionnaire (Expanded Prostate Cancer Index Composite) before a curative treatment. Patients were divided into age groups ≤65, 6670, 7175 and >75 years. The impact of specific comorbidities and the Charlson Comorbidity Index (CCI) were evaluated. The questionnaire comprises 50 items concerning the urinary, bowel, sexual and hormonal domains for function and bother. For assessment of sexual and hormonal domains, only patients without prior hormonal treatment were included (n = 336).</p> <p>Results</p> <p>Urinary incontinence was observed increasingly with higher age (mean function scores of 92/88/85/87 for patients ≤65, 6670, 7175 and >75 years) complete urinary control in 78%/72%/64%/58% (p < 0.01). Sexual function scores decreased particularly (48/43/35/30), with erections sufficient for intercourse in 68%/50%/36%/32% (p < 0.01) a decrease of more than a third comparing patients ≤65 vs. 6670 (36%) and 6670 vs. 7175 years (39%). The percentage of patients with comorbidities was lowest in the youngest group (48% vs. 66%/68%/63% for ages 6670/7175/>75 years; p < 0.05). A multivariate analysis revealed an independent influence of both age and comorbidities on urinary incontinence, specifically diabetes on urinary bother, and both age and diabetes on sexual function/bother. Rectal domain scores were not significantly influenced by age or comorbidities. A CCI>5 particularly predisposed for lower urinary and sexual HRQOL scores.</p> <p>Conclusion</p> <p>Urinary continence and sexual function are the crucial HRQOL domains with age-related and independently comorbidity-related decreasing scores. The results need to be considered for the interpretation of comparative studies or longitudinal changes after a curative treatment.</p

Interventional radiography and mortality risks in U.S. radiologic technologists

With the exponential increase in minimally invasive fluoroscopically guided interventional radiologic procedures, concern has increased about the health effects on staff and patients of radiation exposure from these procedures. There has been no systematic epidemiologic investigation to quantify serious disease risks or mortality. To quantify all-cause, circulatory system disease and cancer mortality risks in U.S. radiologic technologists who work with interventional radiographic procedures, we evaluated mortality risks in a nationwide cohort of 88,766 U.S. radiologic technologists (77% female) who completed a self-administered questionnaire during 1994–998 and were followed through 31 December 2003. We obtained information on work experience, types of procedures (including fluoroscopically guided interventional procedures), and protective measures plus medical, family cancer history, lifestyle, and reproductive information. Cox proportional hazards regression models were used to compute relative risks (RRs) with 95% confidence intervals (CIs). Between completion of the questionnaire and the end of follow-up, there were 3,581 deaths, including 1,209 from malignancies and 979 from circulatory system diseases. Compared to radiologic technologists who never or rarely performed or assisted with fluoroscopically guided interventional procedures, all-cause mortality risks were not increased among those working on such procedures daily. Similarly, there was no increased risk of mortality resulting from all circulatory system diseases combined, all cancers combined, or female breast cancer among technologists who daily performed or assisted with fluoroscopically guided interventional procedures. Based on small numbers of deaths (n=151), there were non-significant excesses (40%–0%) in mortality from cerebrovascular disease among technologists ever working with these procedures. The absence of significantly elevated mortality risks in radiologic technologists reporting the highest frequency of interventional radiography procedures must be interpreted cautiously in light of the small number of deaths during the relatively short follow-up. The present study cannot rule out increased risks of cerebrovascular disease, specific cancers, and diseases with low case-fatality rates or a long latency period preceding death