Dock Assignment and Truck Scheduling Problems at Cross-docking Terminals

In this paper, we consider the integration of dock assignment and truck scheduling problem at cross-docking terminals. The problem is first formulated as a 0-1 integer programming model. Since both dock assignment and truck scheduling problems are NP-hard, its integration is more difficult to solve. Thus we propose reduced variable neighborhood search (RVNS) algorithms to solve the problem. Computational experiments are carried out on four set of instances. The results show that RVNS is capable of finding good solutions in a much shorter computation time when it is compared with optimization solver Gurobi’s solutions

Use of sonic tomography to detect and quantify wood decay in living trees.

Premise of the studyField methodology and image analysis protocols using acoustic tomography were developed and evaluated as a tool to estimate the amount of internal decay and damage of living trees, with special attention to tropical rainforest trees with irregular trunk shapes.Methods and resultsLiving trunks of a diversity of tree species in tropical rainforests in the Republic of Panama were scanned using an Argus Electronic PiCUS 3 Sonic Tomograph and evaluated for the amount and patterns of internal decay. A protocol using ImageJ analysis software was used to quantify the proportions of intact and compromised wood. The protocols provide replicable estimates of internal decay and cavities for trees of varying shapes, wood density, and bark thickness.ConclusionsSonic tomography, coupled with image analysis, provides an efficient, noninvasive approach to evaluate decay patterns and structural integrity of even irregularly shaped living trees

Genetic polymorphisms located in genes related to immune and inflammatory processes are associated with end-stage renal disease: a preliminary study

Background Chronic kidney disease progression has been linked to pro-inflammatory cytokines and markers of inflammation. These markers are also elevated in end-stage renal disease (ESRD), which constitutes a serious public health problem. Objective To investigate whether single nucleotide polymorphisms (SNPs) located in genes related to immune and inflammatory processes, could be associated with ESRD development. Design and methods A retrospective case-control study was carried out on 276 patients with ESRD and 288 control subjects. Forty-eight SNPs were genotyped via SNPlex platform. Logistic regression was used to assess the relationship between each sigle polymorphism and the development of ESRD. Results Four polymorphisms showed association with ESRD: rs1801275 in the interleukin 4 receptor (IL4R) gene (OR: 0.66 (95%CI=0.46-0.95); p=0.025; overdominant model), rs4586 in chemokine (C-C motif) ligand 2 (CCL2) gene (OR: 0.70 (95%CI=0.54-0.90); p=0.005; additive model), rs301640 located in an intergenic binding site for signal transducer and activator of transcription 4 (STAT4) (OR: 1.82 (95%CI=1.17-2.83); p=0.006; additive model) and rs7830 in the nitric oxide synthase 3 (NOS3) gene (OR: 1.31 (95%CI=1.01-1.71); p=0.043; additive model). After adjusting for multiple testing, results lost significance. Conclusion Our preliminary data suggest that four genetic polymorphisms located in genes related to inflammation and immune processes could help to predict the risk of developing ESRD.This work was supported by grants from Instituto de Salud Carlos III (Ref: PI08/0738 and PI11/00245) to SR and Junta de Castilla y Leon (Ref: GRS 234/A/08) to ET. MAJS is supported by a grant from Instituto de Salud Carlos III (CM10/00105).Jimenez-Sousa, MA.; López, E.; Fernandez-Rodriguez, A.; Tamayo, E.; Fernández-Navarro, P.; Segura Roda, L.; Heredia, M.... (2012). Genetic polymorphisms located in genes related to immune and inflammatory processes are associated with end-stage renal disease: a preliminary study. BMC Medical Genetics. 13(58):1-6. https://doi.org/10.1186/1471-2350-13-58S161358Otero A, de Francisco A, Gayoso P, Garcia F: Prevalence of chronic renal disease in Spain: results of the EPIRCE study. Nefrologia. 2010, 30 (1): 78-86.Kottgen A: Genome-wide association studies in nephrology research. Am J Kidney Dis. 2010, 56 (4): 743-758. 10.1053/j.ajkd.2010.05.018.Gansevoort RT, Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, Jong PE, Coresh J, de Jong PE, El-Nahas M, et al: Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes in both general and high-risk populations. A collaborative meta-analysis of general and high-risk population cohorts. Kidney Int. 2011, 80 (1): 93-104. 10.1038/ki.2010.531.Reich HN, Gladman DD, Urowitz MB, Bargman JM, Hladunewich MA, Lou W, Fan SC, Su J, Herzenberg AM, Cattran DC, et al: Persistent proteinuria and dyslipidemia increase the risk of progressive chronic kidney disease in lupus erythematosus. Kidney Int. 2011, 9 (8): 914-920.Rao M, Wong C, Kanetsky P, Girndt M, Stenvinkel P, Reilly M, Raj DS: Cytokine gene polymorphism and progression of renal and cardiovascular diseases. Kidney Int. 2007, 72 (5): 549-556. 10.1038/sj.ki.5002391.Munshi R, Hsu C, Himmelfarb J: Advances in understanding ischemic acute kidney injury. BMC Med. 2011, 9 (1): 11-10.1186/1741-7015-9-11.Kottgen A, Pattaro C, Boger CA, Fuchsberger C, Olden M, Glazer NL, Parsa A, Gao X, Yang Q, Smith AV, et al: New loci associated with kidney function and chronic kidney disease. Nat Genet. 2010, 42 (5): 376-384. 10.1038/ng.568.Chambers JC, Zhang W, Lord GM, van der Harst P, Lawlor DA, Sehmi JS, Gale DP, Wass MN, Ahmadi KR, Bakker SJ, et al: Genetic loci influencing kidney function and chronic kidney disease. Nat Genet. 2010, 42 (5): 373-375. 10.1038/ng.566.Ribases M, Ramos-Quiroga JA, Sanchez-Mora C, Bosch R, Richarte V, Palomar G, Gastaminza X, Bielsa A, Arcos-Burgos M, Muenke M, et al: Contribution of LPHN3 to the genetic susceptibility to ADHD in adulthood: a replication study. Genes Brain Behav. 2010, 10 (2): 149-157.Sole X, Guino E, Valls J, Iniesta R, Moreno V: SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006, 22 (15): 1928-1929. 10.1093/bioinformatics/btl268.Fried L, Solomon C, Shlipak M, Seliger S, Stehman-Breen C, Bleyer AJ, Chaves P, Furberg C, Kuller L, Newman A: Inflammatory and prothrombotic markers and the progression of renal disease in elderly individuals. J Am Soc Nephrol. 2004, 15 (12): 3184-3191. 10.1097/01.ASN.0000146422.45434.35.Wolkow PP, Niewczas MA, Perkins B, Ficociello LH, Lipinski B, Warram JH, Krolewski AS: Association of urinary inflammatory markers and renal decline in microalbuminuric type 1 diabetics. J Am Soc Nephrol. 2008, 19 (4): 789-797. 10.1681/ASN.2007050556.Nakamura E, Megumi Y, Kobayashi T, Kamoto T, Ishitoya S, Terachi T, Tachibana M, Matsushiro H, Habuchi T, Kakehi Y, et al: Genetic polymorphisms of the interleukin-4 receptor alpha gene are associated with an increasing risk and a poor prognosis of sporadic renal cell carcinoma in a Japanese population. Clin Cancer Res. 2002, 8 (8): 2620-2625.Burgos PI, Causey ZL, Tamhane A, Kelley JM, Brown EE, Hughes LB, Danila MI, van Everdingen A, Conn DL, Jonas BL, et al: Association of IL4R single-nucleotide polymorphisms with rheumatoid nodules in African Americans with rheumatoid arthritis. Arthritis Res Ther. 2010, 12 (3): R75-10.1186/ar2994.Tachdjian R, Mathias C, Al Khatib S, Bryce PJ, Kim HS, Blaeser F, O'Connor BD, Rzymkiewicz D, Chen A, Holtzman MJ, et al: Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma. J Exp Med. 2009, 206 (10): 2191-2204. 10.1084/jem.20091480.Zheng G, Wang Y, Xiang SH, Tay YC, Wu H, Watson D, Coombes J, Rangan GK, Alexander SI, Harris DC: DNA vaccination with CCL2 DNA modified by the addition of an adjuvant epitope protects against "nonimmune" toxic renal injury. J Am Soc Nephrol. 2006, 17 (2): 465-474. 10.1681/ASN.2005020164.Kang YS, Lee MH, Song HK, Ko GJ, Kwon OS, Lim TK, Kim SH, Han SY, Han KH, Lee JE, et al: CCR2 antagonism improves insulin resistance, lipid metabolism, and diabetic nephropathy in type 2 diabetic mice. Kidney Int. 2010, 78 (9): 883-894. 10.1038/ki.2010.263.Dai R, Ahmed SA: MicroRNA, a new paradigm for understanding immunoregulation, inflammation, and autoimmune diseases. Transl Res. 2011, 157 (4): 163-179. 10.1016/j.trsl.2011.01.007.Messeguer X, Escudero R, Farre D, Nunez O, Martinez J, Alba MM: PROMO: detection of known transcription regulatory elements using species-tailored searches. Bioinformatics. 2002, 18 (2): 333-334. 10.1093/bioinformatics/18.2.333.Farre D, Roset R, Huerta M, Adsuara JE, Rosello L, Alba MM, Messeguer X: Identification of patterns in biological sequences at the ALGGEN server: PROMO and MALGEN. Nucleic Acids Res. 2003, 31 (13): 3651-3653. 10.1093/nar/gkg605.Wei L, Vahedi G, Sun HW, Watford WT, Takatori H, Ramos HL, Takahashi H, Liang J, Gutierrez-Cruz G, Zang C, et al: Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation. Immunity. 2010, 32 (6): 840-851. 10.1016/j.immuni.2010.06.003.Nakayama T, Sato W, Kosugi T, Zhang L, Campbell-Thompson M, Yoshimura A, Croker BP, Johnson RJ, Nakagawa T: Endothelial injury due to eNOS deficiency accelerates the progression of chronic renal disease in the mouse. Am J Physiol Renal Physiol. 2009, 296 (2): F317-327.Webber JL, Tooze SA: New insights into the function of Atg9. FEBS Lett. 2010, 584 (7): 1319-1326. 10.1016/j.febslet.2010.01.020.Kullo IJ, Greene MT, Boerwinkle E, Chu J, Turner ST, Kardia SL: Association of polymorphisms in NOS3 with the ankle-brachial index in hypertensive adults. Atherosclerosis. 2008, 196 (2): 905-912. 10.1016/j.atherosclerosis.2007.02.008.Popov AF, Hinz J, Schulz EG, Schmitto JD, Wiese CH, Quintel M, Seipelt R, Schoendube FA: The eNOS 786C/T polymorphism in cardiac surgical patients with cardiopulmonary bypass is associated with renal dysfunction. Eur J Cardiothorac Surg. 2009, 36 (4): 651-656. 10.1016/j.ejcts.2009.04.049.Wang CH, Li F, Hiller S, Kim HS, Maeda N, Smithies O, Takahashi N: A modest decrease in endothelial NOS in mice comparable to that associated with human NOS3 variants exacerbates diabetic nephropathy. Proc Natl Acad Sci U S A. 2011, 108 (5): 2070-2075. 10.1073/pnas.1018766108.Desmet FO, Hamroun D, Lalande M, Collod-Beroud G, Claustres M, Beroud C: Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res. 2009, 37 (9): e67-10.1093/nar/gkp215.Sironi M, Menozzi G, Riva L, Cagliani R, Comi GP, Bresolin N, Giorda R, Pozzoli U: Silencer elements as possible inhibitors of pseudoexon splicing. Nucleic Acids Res. 2004, 32 (5): 1783-1791. 10.1093/nar/gkh341.Perneger TV: What's wrong with Bonferroni adjustments. BMJ. 1998, 316 (7139): 1236-1238. 10.1136/bmj.316.7139.1236.Sterne JA, Davey Smith G: Sifting the evidence-what's wrong with significance tests?. BMJ. 2001, 322 (7280): 226-231. 10.1136/bmj.322.7280.226

Training future generations to deliver evidence-based conservation and ecosystem management

1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis. 2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice. 3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses. 4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.Peer reviewe

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe