This paper presents HyFlex, a software framework for the development of cross-domain search methodologies. The framework features a common software interface for dealing with different combinatorial optimisation problems and provides the algorithm components that are problem specific. In this way, the algorithm designer does not require a detailed knowledge of the problem domains and thus can concentrate his/her efforts on designing adaptive general-purpose optimisation algorithms. Six hard combinatorial problems are fully implemented: maximum satisfiability, one dimensional bin packing, permutation flow shop, personnel scheduling, traveling salesman and vehicle routing. Each domain contains a varied set of instances, including real-world industrial data and an extensive set of state-of-the-art problem specific heuristics and search operators. HyFlex represents a valuable new benchmark of heuristic search generality, with which adaptive cross-domain algorithms are being easily developed and reliably compared.This article serves both as a tutorial and a as survey of the research achievements and publications so far using HyFlex.

OBJECTIVE -In adults, adiponectin is reduced in association with excess adiposity, type 2 diabetes, and hyperinsulinemia. We assessed whether adiponectin was 1) present in the fetal circulation, 2) altered in the fetal circulation in the presence of maternal diabetes, and 3) had relations to fetal cord blood insulin or adiposity.RESEARCH DESIGN AND METHODS -We assessed adiponectin in cord blood in a large cohort of singleton offspring of diabetic mothers (ODM; n ϭ 134) and control mothers (n ϭ 45).RESULTS -Adiponectin was present in cord blood and, in ODM, was higher in those delivered at later gestational ages (Spearman r ϭ 0.18, P ϭ 0.03). Adiponectin was slightly lower in ODM than control subjects (ODM 19.7 Ϯ 6.1 vs. control 21.8 Ϯ 5.3 g/ml; P ϭ 0.04), although this difference could potentially reflect different gestational ages in the two groups (ODM 37.6 Ϯ 1.5 and control 40.1 Ϯ 1.1 weeks). In contrast to adults, adiponectin levels in the fetus were unrelated to the degree of adiposity, blood insulin, or leptin in either control subjects or ODM.CONCLUSIONS -Adiponectin is present in cord blood but does not show expected physiological relations with adiposity as observed in adults. Diabetes Care 26:2244 -2249, 2003A dipose tissue expresses a variety of secretory proteins of importance to metabolic and vascular disease. Recently, adiponectin, a 244 -amino acid adipocyte-derived protein (1) has been described that is paradoxically reduced in obesity (2) and inversely related to leptin concentrations (3), despite being solely derived from adipose tissue in humans. Both type 2 diabetes and relative insulin resistance (in nondiabetic subjects) are associated with decreased adiponectin concentrations (4,5), while improvement of insulin sensitivity by either weight reduction (6) or administration of thiazolidinediones (7) is associated with increased adiponectin concentrations. Furthermore, in people matched for BMI, higher adiponectin concentrations are protective against later development of type 2 diabetes (8).Exposure to maternal diabetes in utero is associated with increased adiposity at birth (9), as well as increases in fetal leptin (10) and insulin (11). Furthermore, the presence of maternal diabetes during pregnancy influences the longterm health of offspring with increases in future risk of obesity (12,13), type 2 diabetes (14), and impaired glucose tolerance (15-17).Adiponectin has not been previously assessed in cord blood specimens. We wished to examine whether 1) adiponectin was present in cord blood, 2) relations to adiposity, sex, and circulating insulin and leptin observed in adults were also present in utero, and 3) offspring of mothers with type 1 diabetes, a group at high risk of later development of metabolic disease, would have lower concentrations of adiponectin at birth. RESEARCH DESIGN AND METHODS Recruitment and clinical protocolRecruitment, which began in January 1999 and ended in May 2001, took place in eight hospital-based antenatal centers in Scotland. A total of 250 women with type 1 ...

OBJECTIVETo assess the relationship between glycemic control, pre-eclampsia, and gestational hypertension in women with type 1 diabetes.RESEARCH DESIGN AND METHODSPregnancy outcome (pre-eclampsia or gestational hypertension) was assessed prospectively in 749 women from the randomized controlled Diabetes and Pre-eclampsia Intervention Trial (DAPIT). HbA1c (A1C) values were available up to 6 months before pregnancy (n = 542), at the first antenatal visit (median 9 weeks) (n = 721), at 26 weeks’ gestation (n = 592), and at 34 weeks’ gestation (n = 519) and were categorized as optimal (<6.1%: referent), good (6.1–6.9%), moderate (7.0–7.9%), and poor (≥8.0%) glycemic control, respectively.RESULTSPre-eclampsia and gestational hypertension developed in 17 and 11% of pregnancies, respectively. Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy compared with women who did not develop pre-eclampsia (P < 0.05, respectively). In early pregnancy, A1C ≥8.0% was associated with a significantly increased risk of pre-eclampsia (odds ratio 3.68 [95% CI 1.17–11.6]) compared with optimal control. At 26 weeks’ gestation, A1C values ≥6.1% (good: 2.09 [1.03–4.21]; moderate: 3.20 [1.47–7.00]; and poor: 3.81 [1.30–11.1]) and at 34 weeks’ gestation A1C values ≥7.0% (moderate: 3.27 [1.31–8.20] and poor: 8.01 [2.04–31.5]) significantly increased the risk of pre-eclampsia compared with optimal control. The adjusted odds ratios for pre-eclampsia for each 1% decrement in A1C before pregnancy, at the first antenatal visit, at 26 weeks’ gestation, and at 34 weeks’ gestation were 0.88 (0.75–1.03), 0.75 (0.64–0.88), 0.57 (0.42–0.78), and 0.47 (0.31–0.70), respectively. Glycemic control was not significantly associated with gestational hypertension.CONCLUSIONSWomen who developed pre-eclampsia had significantly higher A1C values before and during pregnancy. These data suggest that optimal glycemic control both early and throughout pregnancy may reduce the risk of pre-eclampsia in women with type 1 diabetes.

SummaryBackgroundResults of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia, but the effect in women with diabetes is unknown. We aimed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes.MethodsWe enrolled women from 25 UK antenatal metabolic clinics in a multicentre randomised placebo-controlled trial. Eligibility criteria were type 1 diabetes preceding pregnancy, presentation between 8 weeks' and 22 weeks' gestation, singleton pregnancy, and age 16 years or older. Women were randomly allocated in a 1:1 ratio to receive 1000 mg vitamin C and 400 IU vitamin E (α-tocopherol) or matched placebo daily until delivery. The randomisation sequence was stratified by centre with balanced blocks of eight patients. All trial personnel and participants were masked to treatment allocation. The primary endpoint was pre-eclampsia, which we defined as gestational hypertension with proteinuria. Analysis was by modified intention to treat. This study is registered, ISRCTN27214045.FindingsBetween April, 2003, and June, 2008, 762 women were randomly allocated to treatment groups (379 vitamin supplementation, 383 placebo). The primary endpoint was assessed for 375 women allocated to receive vitamins, and 374 allocated to placebo. Rates of pre-eclampsia did not differ between vitamin (15%, n=57) and placebo (19%, 70) groups (risk ratio 0·81, 95% CI 0·59–1·12). No adverse maternal or neonatal outcomes were reported.InterpretationSupplementation with vitamins C and E did not reduce risk of pre-eclampsia in women with type 1 diabetes. However, the possibility that vitamin supplementation might be beneficial in women with a low antioxidant status at baseline needs further testing.FundingThe Wellcome Trust.