Investigation of associations between retinal microvascular parameters and albuminuria in UK Biobank: a cross-sectional case-control study

BACKGROUND: Associations between microvascular variation and chronic kidney disease (CKD) have been reported previously. Non-invasive retinal fundus imaging enables evaluation of the microvascular network and may offer insight to systemic risk associated with CKD. METHODS: Retinal microvascular parameters (fractal dimension [FD] - a measure of the complexity of the vascular network, tortuosity, and retinal arteriolar and venular calibre) were quantified from macula-centred fundus images using the Vessel Assessment and Measurement Platform for Images of the REtina (VAMPIRE) version 3.1 (VAMPIRE group, Universities of Dundee and Edinburgh, Scotland) and assessed for associations with renal damage in a case-control study nested within the multi-centre UK Biobank cohort study. Participants were designated cases or controls based on urinary albumin to creatinine ratio (ACR) thresholds. Participants with ACR ≥ 3 mg/mmol (ACR stages A2-A3) were characterised as cases, and those with an ACR < 3 mg/mmol (ACR stage A1) were categorised as controls. Participants were matched on age, sex and ethnic background. RESULTS: Lower FD (less extensive microvascular branching) was associated with a small increase in odds of albuminuria independent of blood pressure, diabetes and other potential confounding variables (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03-1.34 for arterioles and OR 1.24, CI 1.05-1.47 for venules). Measures of tortuosity or retinal arteriolar and venular calibre were not significantly associated with ACR. CONCLUSIONS: This study supports previously reported associations between retinal microvascular FD and other metabolic disturbances affecting the systemic vasculature. The association between retinal microvascular FD and albuminuria, independent of diabetes and blood pressure, may represent a useful indicator of systemic vascular damage associated with albuminuria

Coupling models of cattle and farms with models of badgers for predicting the dynamics of bovine tuberculosis (TB)

Bovine TB is a major problem for the agricultural industry in several countries. TB can be contracted and spread by species other than cattle and this can cause a problem for disease control. In the UK and Ireland, badgers are a recognised reservoir of infection and there has been substantial discussion about potential control strategies. We present a coupling of individual based models of bovine TB in badgers and cattle, which aims to capture the key details of the natural history of the disease and of both species at approximately county scale. The model is spatially explicit it follows a very large number of cattle and badgers on a different grid size for each species and includes also winter housing. We show that the model can replicate the reported dynamics of both cattle and badger populations as well as the increasing prevalence of the disease in cattle. Parameter space used as input in simulations was swept out using Latin hypercube sampling and sensitivity analysis to model outputs was conducted using mixed effect models. By exploring a large and computationally intensive parameter space we show that of the available control strategies it is the frequency of TB testing and whether or not winter housing is practised that have the most significant effects on the number of infected cattle, with the effect of winter housing becoming stronger as farm size increases. Whether badgers were culled or not explained about 5%, while the accuracy of the test employed to detect infected cattle explained less than 3% of the variance in the number of infected cattle

Guidelines for the deployment and implementation of manufacturing scheduling systems

It has frequently been stated that there exists a gap between production scheduling theory and practice. In order to put theoretical findings into practice, advances in scheduling models and solution procedures should be embedded into a piece of software - a scheduling system - in companies. This results in a process that entails (1) determining its functional features, and (2) adopting a successful strategy for its development and deployment. In this paper we address the latter question and review the related literature in order to identify descriptions and recommendations of the main aspects to be taken into account when developing such systems. These issues are then discussed and classified, resulting in a set of guidelines that can help practitioners during the process of developing and deploying a scheduling system. In addition, identification of these issues can provide some insights to drive theoretical scheduling research towards those topics more in demand by practitioners, and thus help to close the aforementioned gap.Framiñan Torres, JM.; Ruiz García, R. (2012). Guidelines for the deployment and implementation of manufacturing scheduling systems. International Journal of Production Research. 50(7):1799-1812. doi:10.1080/00207543.2011.564670S17991812507Baek, D. H. (1999). A visualized human-computer interactive approach to job shop scheduling. International Journal of Computer Integrated Manufacturing, 12(1), 75-83. doi:10.1080/095119299130489Comesaña Benavides, J. A., & Carlos Prado, J. (2002). Creating an expert system for detailed scheduling. International Journal of Operations & Production Management, 22(7), 806-819. doi:10.1108/01443570210433562Bensana, E. 1986. An expert-system approach to industrial job-shop scheduling. In: Proceedings of the 1986 IEEE international conference on robotics and automation. 1986. Vol. 3, pp.1645–1650.Berglund, M., & Karltun, J. (2007). Human, technological and organizational aspects influencing the production scheduling process. International Journal of Production Economics, 110(1-2), 160-174. doi:10.1016/j.ijpe.2007.02.024Besbes, W., Teghem, J., & Loukil, T. (2010). Scheduling hybrid flow shop problem with non-fixed availability constraints. European J. of Industrial Engineering, 4(4), 413. doi:10.1504/ejie.2010.035652Bhattacharyya, S., & Koehler, G. J. (1998). Learning by Objectives for Adaptive Shop-Floor Scheduling. Decision Sciences, 29(2), 347-375. doi:10.1111/j.1540-5915.1998.tb01580.xBitran, G. R., & Tirupati, D. (1988). OR Practice—Development and Implementation of a Scheduling System for a Wafer Fabrication Facility. Operations Research, 36(3), 377-395. doi:10.1287/opre.36.3.377Buxey, G. (1989). Production scheduling: Practice and theory. European Journal of Operational Research, 39(1), 17-31. doi:10.1016/0377-2217(89)90349-4Chen, J.-F. (2004). Unrelated parallel machine scheduling with secondary resource constraints. The International Journal of Advanced Manufacturing Technology, 26(3), 285-292. doi:10.1007/s00170-003-1622-1Collinot, A., Le Pape, C., & Pinoteau, G. (1988). SONIA: A knowledge-based scheduling system. Artificial Intelligence in Engineering, 3(2), 86-94. doi:10.1016/0954-1810(88)90024-6Cowling, P. (2003). A flexible decision support system for steel hot rolling mill scheduling. Computers & Industrial Engineering, 45(2), 307-321. doi:10.1016/s0360-8352(03)00038-xDudek, R. A., Panwalkar, S. S., & Smith, M. L. (1992). The Lessons of Flowshop Scheduling Research. Operations Research, 40(1), 7-13. doi:10.1287/opre.40.1.7Dumond, E. J. (2005). Understanding and using the capabilities of finite scheduling. Industrial Management & Data Systems, 105(4), 506-526. doi:10.1108/02635570510592398Fox, M. S., & Smith, S. F. (1984). ISIS?a knowledge-based system for factory scheduling. Expert Systems, 1(1), 25-49. doi:10.1111/j.1468-0394.1984.tb00424.xFraminan, J. M., & Ruiz, R. (2010). Architecture of manufacturing scheduling systems: Literature review and an integrated proposal. European Journal of Operational Research, 205(2), 237-246. doi:10.1016/j.ejor.2009.09.026Freed, T., Doerr, K. H., & Chang, T. (2007). In-house development of scheduling decision support systems: case study for scheduling semiconductor device test operations. International Journal of Production Research, 45(21), 5075-5093. doi:10.1080/00207540600818351Gao, C and Tang, L. 2008. A decision support system for color-coating line in steel industry. In: Proceedings of the IEEE international conference on automation and logistics, ICAL 2008. 2008. pp.1463–1468.Grant, T. J. (1986). Lessons for O.R. from A.I.: A Scheduling Case Study. Journal of the Operational Research Society, 37(1), 41-57. doi:10.1057/jors.1986.7Graves, S. C. (1981). A Review of Production Scheduling. Operations Research, 29(4), 646-675. doi:10.1287/opre.29.4.646HALSALL, D. N., MUHLEMANN, A. P., & PRICE, D. H. R. (1994). A review of production planning and scheduling in smaller manufacturing companies in the UK. Production Planning & Control, 5(5), 485-493. doi:10.1080/09537289408919520Higgins, P. G. (1996). Interaction in hybrid intelligent scheduling. International Journal of Human Factors in Manufacturing, 6(3), 185-203. doi:10.1002/(sici)1522-7111(199622)6:33.0.co;2-6Kanet, J. J., & Adelsberger, H. H. (1987). Expert systems in production scheduling. European Journal of Operational Research, 29(1), 51-59. doi:10.1016/0377-2217(87)90192-5Kathawala, Y., & Allen, W. R. (1993). Expert Systems and Job Shop Scheduling. International Journal of Operations & Production Management, 13(2), 23-35. doi:10.1108/01443579310025286Kerr, R. M. (1992). Expert systems in production scheduling: Lessons from a failed implementation. Journal of Systems and Software, 19(2), 123-130. doi:10.1016/0164-1212(92)90063-pKnolmayer, G., Mertens, P., & Zeier, A. (2002). Supply Chain Management Based on SAP Systems. doi:10.1007/978-3-540-24816-3Leachman, R. C., Benson, R. F., Liu, C., & Raar, D. J. (1996). IMPReSS: An Automated Production-Planning and Delivery-Quotation System at Harris Corporation—Semiconductor Sector. Interfaces, 26(1), 6-37. doi:10.1287/inte.26.1.6MACCARTHY, B. L., & LIU, J. (1993). Addressing the gap in scheduling research: a review of optimization and heuristic methods in production scheduling. International Journal of Production Research, 31(1), 59-79. doi:10.1080/00207549308956713McKay, K. N., & Black, G. W. (2007). The evolution of a production planning system: A 10-year case study. Computers in Industry, 58(8-9), 756-771. doi:10.1016/j.compind.2007.02.002McKay, K. N., Safayeni, F. R., & Buzacott, J. A. (1988). Job-Shop Scheduling Theory: What Is Relevant? Interfaces, 18(4), 84-90. doi:10.1287/inte.18.4.84McKay, K. N., Morton, T. E., Ramnath, P., & Wang, J. (2000). ?Aversion dynamics? scheduling when the system changes. Journal of Scheduling, 3(2), 71-88. doi:10.1002/(sici)1099-1425(200003/04)3:23.0.co;2-0MCKAY, K., PINEDO, M., & WEBSTER, S. (2009). PRACTICE-FOCUSED RESEARCH ISSUES FOR SCHEDULING SYSTEMS*. Production and Operations Management, 11(2), 249-258. doi:10.1111/j.1937-5956.2002.tb00494.xMissbauer, H., Hauber, W., & Stadler, W. (2009). A scheduling system for the steelmaking-continuous casting process. A case study from the steel-making industry. International Journal of Production Research, 47(15), 4147-4172. doi:10.1080/00207540801950136Numao, M and Morishita, S. 1989. A scheduling environment for steel-making processes. In: Proceedings of the 5th conference on artificial intelligence applications. 1989. pp.279–286.Olhager, J., & Rapp, B. (1995). Operations Research Techniques in Manufacturing Planning and Control Systems. International Transactions in Operational Research, 2(1), 29-43. doi:10.1111/j.1475-3995.1995.tb00003.xPerez-Gonzalez, P., & Framinan, J. M. (2009). Scheduling permutation flowshops with initial availability constraint: Analysis of solutions and constructive heuristics. Computers & Operations Research, 36(10), 2866-2876. doi:10.1016/j.cor.2008.12.018Pinedo, M., & Yen, B. P.-C. (1997). Annals of Operations Research, 70, 359-378. doi:10.1023/a:1018986524234Portougal, V., & Robb, D. J. (2000). Production Scheduling Theory: Just Where Is It Applicable? Interfaces, 30(6), 64-76. doi:10.1287/inte.30.6.64.11623Reisman, A., Kumar, A., & Motwani, J. (1997). Flowshop scheduling/sequencing research: a statistical review of the literature, 1952-1994. IEEE Transactions on Engineering Management, 44(3), 316-329. doi:10.1109/17.618173Steffen, MS. 1986. A survey of artificial intelligence-based scheduling systems. In: Proceedings of the fall industrial engineering conference. 1986.Storer, R. H., Wu, S. D., & Vaccari, R. (1992). New Search Spaces for Sequencing Problems with Application to Job Shop Scheduling. Management Science, 38(10), 1495-1509. doi:10.1287/mnsc.38.10.1495Tang, L., & Wang, G. (2008). Decision support system for the batching problems of steelmaking and continuous-casting production. Omega, 36(6), 976-991. doi:10.1016/j.omega.2007.11.002T’kindt, V., Billaut, J.-C., Bouquard, J.-L., Lenté, C., Martineau, P., Néron, E., … Tacquard, C. (2005). The e-OCEA project: towards an Internet decision system for scheduling problems. Decision Support Systems, 40(2), 329-337. doi:10.1016/j.dss.2004.04.001Wiers, VCS. 1997. Human–computer interaction in production scheduling: Analysis and design of decision support systems for production scheduling tasks. Ph.D. Thesis, Technische Universiteit Eindhoven, NetherlandsWiers, V. C. S. (2002). A case study on the integration of APS and ERP in a steel processing plant. Production Planning & Control, 13(6), 552-560. doi:10.1080/09537280210160321Wiers, V. C. S., & Van Der Schaaf, T. W. (1997). A framework for decision support in production scheduling tasks. Production Planning & Control, 8(6), 533-544. doi:10.1080/095372897234876Zhang, L., Krishnamurthy, A., Malmborg, C. J., & Heragu, S. S. (2009). Variance-based approximations of transaction waiting times in autonomous vehicle storage and retrieval systems. European J. of Industrial Engineering, 3(2), 146. doi:10.1504/ejie.2009.02360

Adipose energy stores, physical work, and the metabolic syndrome: lessons from hummingbirds

Hummingbirds and other nectar-feeding, migratory birds possess unusual adaptive traits that offer important lessons concerning obesity, diabetes and the metabolic syndrome. Hummingbirds consume a high sugar diet and have fasting glucose levels that would be severely hyperglycemic in humans, yet these nectar-fed birds recover most glucose that is filtered into the urine. Hummingbirds accumulate over 40% body fat shortly before migrations in the spring and autumn. Despite hyperglycemia and seasonally elevated body fat, the birds are not known to become diabetic in the sense of developing polyuria (glucosuria), polydipsia and polyphagia. The tiny (3–4 g) Ruby-throated hummingbird has among the highest mass-specific metabolic rates known, and loses most of its stored fat in 20 h by flying up to 600 miles across the Gulf of Mexico. During the breeding season, it becomes lean and maintains an extremely accurate energy balance. In addition, hummingbirds can quickly enter torpor and reduce resting metabolic rates by 10-fold. Thus, hummingbirds are wonderful examples of the adaptive nature of fat tissue, and may offer lessons concerning prevention of metabolic syndrome in humans

A one-year exercise intervention program in pre-pubertal girls does not influence hip structure

<p>Abstract</p> <p>Background</p> <p>We have previously reported that a one-year school-based exercise intervention program influences the accrual of bone mineral in pre-pubertal girls. This report aims to evaluate if also hip structure is affected, as geometry independent of bone mineral influences fracture risk.</p> <p>Methods</p> <p>Fifty-three girls aged 7 – 9 years were included in a curriculum-based exercise intervention program comprising 40 minutes of general physical activity per school day (200 minutes/week). Fifty healthy age-matched girls who participated in the general Swedish physical education curriculum (60 minutes/week) served as controls. The hip was scanned by dual X-ray absorptiometry (DXA) and the hip structural analysis (HSA) software was applied to evaluate bone mineral content (BMC), areal bone mineral density (aBMD), periosteal and endosteal diameter, cortical thickness, cross-sectional moment of inertia (CSMI), section modulus (Z) and cross-sectional area (CSA) of the femoral neck (FN). Annual changes were compared. Group comparisons were done by independent student's <it>t</it>-test between means and analyses of covariance (ANCOVA). Pearson's correlation test was used to evaluate associations between activity level and annual changes in FN. All children remained at Tanner stage 1 throughout the study.</p> <p>Results</p> <p>No between-group differences were found during the 12 months study period for changes in the FN variables. The total duration of exercise during the year was not correlated with the changes in the FN traits.</p> <p>Conclusion</p> <p>Evaluated by the DXA technique and the HSA software, a general one-year school-based exercise program for 7–9-year-old pre-pubertal girls seems not to influence the structure of the hip.</p

Constraining the Nature of Dark Energy using the SKA

We investigate the potential of the Square Kilometer Array Telescope (SKA) to constrain the sound speed of dark energy. The Integrated Sachs Wolfe (ISW) effect results in a significant power spectrum signal when CMB temperature anisotropies are cross-correlated with galaxies detectable with the SKA in HI. We consider using this measurement, the autocorrelation of HI galaxies and the CMB temperature power spectrum to derive constraints on the sound speed. We study the contributions to the cross-correlation signal made by galaxies at different redshifts and use redshift tomography to improve the signal-to-noise. We use a chi-square analysis to estimate the significance of detecting a sound speed different from that expected in quintessence models, finding that there is potential to distinguish very low sound speeds from the quintessence value.Comment: 8 pages, 8 figures; updated references for publication MNRA

Design of Experiments for Screening

The aim of this paper is to review methods of designing screening experiments, ranging from designs originally developed for physical experiments to those especially tailored to experiments on numerical models. The strengths and weaknesses of the various designs for screening variables in numerical models are discussed. First, classes of factorial designs for experiments to estimate main effects and interactions through a linear statistical model are described, specifically regular and nonregular fractional factorial designs, supersaturated designs and systematic fractional replicate designs. Generic issues of aliasing, bias and cancellation of factorial effects are discussed. Second, group screening experiments are considered including factorial group screening and sequential bifurcation. Third, random sampling plans are discussed including Latin hypercube sampling and sampling plans to estimate elementary effects. Fourth, a variety of modelling methods commonly employed with screening designs are briefly described. Finally, a novel study demonstrates six screening methods on two frequently-used exemplars, and their performances are compared

Using Touchscreen Electronic Medical Record Systems to Support and Monitor National Scale-Up of Antiretroviral Therapy in Malawi

Gerry Douglas and colleagues describe the rationale and their experience with scaling up electronic health records in six antiretroviral treatment sites in Malawi

Pathobiological Implications of MUC16 Expression in Pancreatic Cancer

MUC16 (CA125) belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC), the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient) in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease

A symmoriiform chondrichthyan braincase and the origin of chimaeroid fishes

Chimaeroid fishes (Holocephali) are one of the four principal divisions of modern gnathostomes (jawed vertebrates). Despite only 47 described living species1, chimaeroids are the focus of resurgent interest as potential archives of genomic data2 and for the unique perspective they provide on chondrichthyan and gnathostome ancestral conditions. Chimaeroids are also noteworthy for their highly derived body plan1,3,4. However, like other living groups with distinctive anatomies5, fossils have been of limited use in unravelling their evolutionary origin, as the earliest recognized examples already exhibit many of the specializations present in modern forms6,7. Here we report the results of a computed tomography analysis of Dwykaselachus, an enigmatic chondrichthyan braincase from the ~280 million year old Karoo sediments of South Africa8. Externally, the braincase is that of a symmoriid shark9,10,11,12,13and is by far the most complete uncrushed example yet discovered. Internally, the morphology exhibits otherwise characteristically chimaeroid specializations, including the otic labyrinth arrangement and the brain space configuration relative to exceptionally large orbits. These results have important implications for our view of modern chondrichthyan origins, add robust structure to the phylogeny of early crown group gnathostomes, reveal preconditions that suggest an initial morpho-functional basis for the derived chimaeroid cranium, and shed new light on the chondrichthyan response to the extinction at the end of the Devonian period