Search

Study Purpose The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. Methods The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. Results Not applicable. Conclusion DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. Trial Registration Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

Additional file 6. Translation METC document.

Additional file 2. Chemotherapy administration.

Additional file 1. Eligibility criteria RFA.

Additional file 4. SPIRIT checklist.

Additional file 5. Translation grant.

Additional file 1: Appendix 1. Design of the Algorithm. Appendix 2. Interpretation And Rationale of the Algorithm.

In hydraulic control valves, fast-switching electromagnetic actuators are commonly applied. A low-power, passive holding force is obtained by including a biasing permanent magnet. Meanwhile, valve lifetime improvements require impact velocities close to soft-landing. As an alternative to position control, this paper proposes to integrate passive eddy current damping into the valve actuator. Alternative solutions to generate sufficient eddy currents are explored, including inserting conductive materials at locations of high magnetic field gradient, and short-circuiting the actuation coil. Impact velocities are reduced by 24.7% to 1.62m/s, while respecting the limited transition time.

Low levels of 25-hydroxyvitamin D (25(OH)D) has been associated with many negative health outcomes including falls and fractures. 25(OH)D is largely bound to vitamin D binding protein (VDBP). There is increasing evidence that free or bioavailable 25(OH)D may be a better measure of vitamin D deficiency. To determine the prevalence of 25(OH)D deficiency and VDBP levels in multi-ethnic population, and its impact on muscle strength. Cross-sectional study of older adults in Western region of Singapore. 295 participants from three ethnic groups were selected from the Healthy Older People Everyday (HOPE) cohort for measurements of total 25(OH)D and VDBP levels. Total 25(OH)D, VDBP, frailty status, Timed-Up-and-Go (TUG) and grip strength (GS) were assessed. Albumin, free and bioavailable 25(OH)D were only available for 256 participants. 53% of Malay and 55% of Indians were deficient in 25(OH)D compared with 18.2% of ethnic Chinese participants. Chinese also had higher total 25(OH)D concentrations with a mean of 29.1 ug/l, (p =

An automotive, fluid-control solenoid valve is composed of an electromagnetic reluctance actuator and a near-constant-force spring. Reluctance actuators are applied as electromagnetic brakes in aerospace applications [1], as valves that perform fast sorting tasks by means of short air-pulses in the manufacturing industry [2], as accurate fluid-control valves in petrochemical processes [3], and in the automotive industry to achieve variable valve timing in camless engines [4]. Common desires are a fast switching and low noise upon impact. Preferably, these objectives are met with minimized energy consumption, especially during constant position operation. In addition, minimizing the impact velocity improves valve lifetime and reduces the audible noise, vibration, and harshness (NVH). This paper considers cylindrical reluctance actuators due to their low cost. However, this complicates the use of laminations to minimize eddy current effects in a cost-effective manner. Proper analysis, design, and optimization of the reluctance actuator can, therefore, only be performed if these dynamic effects in the actuator are accounted for. This paper will focus on incorporating the eddy current effect in the models and their effect on performance, as well as control methods to improve the performance and minimize energy consumption. The performance of a classical reluctance actuator (Fig. 1a) is compared to a PM-biased topology (Fig. 1b) which reduces the energy consumption. Modeling is performed using transient, axisymmetric, nonlinear finite element (FE) simulations, coupled to Matlab-Simulink. Actuator topology and constraints Two single-coil reluctance actuators are shown in Fig. 1. One is a classical reluctance actuator with a stationary coil and a moving plunger (CLA). A second actuator includes a permanent magnet atop the core (PMB) to allow zero-power latching by means of a passive attraction force [1], [3], [5]. In addition, the actuator height and diameter are 16 and 13 mm, with a stroke of 0.25 mm. Moreover, the plunger of mass 1.2 g experiences an opposing force of 4 to 12N. Finally, the closed-toopen transition can last maximally 4 ms, with a typical valve-open time of several seconds. Open-loop simulation results In an open-loop co-simulation between Simulink and FE software, predefined voltage profiles are applied to the actuators, while the current is limited. In Fig. 2a, the electromagnetic force develops 0.075 ms slower in cases with eddy currents, and the final position is reached 0.115 ms later. This indicates the inherent eddy current damping in the device, slowing down the plunger. In addition, once the movement commences and the airgap closes, the developed electromagnetic force increases rapidly while the opposing force decreases, resulting in a quickly moving plunger. As a result of applying the voltage profiles in Fig. 2b, the corresponding coil currents develop. Note that equal voltages are applied to CLA and PMB until 1.15 ms, after which CLA requires a small hold voltage (1V) to hold the valve open (latch), whereas PMB achieves this passively. Therefore, the hold power can be reduced to zero using PMB. Fig. 2c shows the (in)ability of the actuators to passively latch the valve. The plunger in CLA retracts quickly after (

Background The interpretation of previous studies on the association of physical activity and sedentary behaviour with psychological health is limited by the use of mostly self-reported physical activity and sedentary behaviour, and a focus on Western populations. We aimed to explore the association of self-reported and devise-based measures of physical activity and sedentary behaviour domains on psychological distress in an urban multi-ethnic Asian population. Methods From a population-based cross-sectional study of adults aged 18–79 years, data were used from an overall sample (n = 2653) with complete self-reported total physical activity/sedentary behaviour and domain-specific physical activity data, and a subsample (n = 703) with self-reported domain-specific sedentary behaviour and accelerometry data. Physical activity and sedentary behaviour data were collected using the Global Physical Activity Questionnaire (GPAQ), a domain-specific sedentary behaviour questionnaire and accelerometers. The Kessler Screening Scale (K6) and General Health Questionnaire (GHQ-12) were used to assess psychological distress. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals, adjusted for socio-demographic and lifestyle characteristics. Results The sample comprised 45.0% men (median age = 45.0 years). The prevalence of psychological distress based on the K6 and GHQ-12 was 8.4% and 21.7%, respectively. In the adjusted model, higher levels of self-reported moderate-to-vigorous physical activity (MVPA) were associated with significantly higher odds for K6 (OR = 1.47 [1.03–2.10]; p-trend = 0.03) but not GHQ-12 (OR = 0.97 [0.77–1.23]; p-trend = 0.79), when comparing the highest with the lowest tertile. Accelerometry-assessed MVPA was not significantly associated with K6 (p-trend = 0.50) nor GHQ-12 (p-trend = 0.74). The highest tertile of leisure-time physical activity, but not work- or transport-domain activity, was associated with less psychological distress using K6 (OR = 0.65 [0.43–0.97]; p-trend = 0.02) and GHQ-12 (OR = 0.72 [0.55–0.93]; p-trend = 0.01). Self-reported sedentary behaviour was not associated with K6 (p-trend = 0.90) and GHQ-12 (p-trend = 0.33). The highest tertile of accelerometry-assessed sedentary behaviour was associated with significantly higher odds for K6 (OR = 1.93 [1.00–3.75]; p-trend = 0.04), but not GHQ-12 (OR = 1.34 [0.86–2.08]; p-trend = 0.18). Conclusions Higher levels of leisure-time physical activity and lower levels of accelerometer-based sedentary behaviour were associated with lower psychological distress. This study underscores the importance of assessing accelerometer-based and domain-specific activity in relation to mental health, instead of solely focusing on total volume of activity. Electronic supplementary material The online version of this article (10.1186/s12966-018-0669-1) contains supplementary material, which is available to authorized users.

Background Laparoscopic left lateral sectionectomy (LLLS) has been associated with shorter hospital stay and reduced overall morbidity compared with open left lateral sectionectomy (OLLS). Strong evidence has not, however, been provided. Methods In this multicentre double-blind RCT, patients (aged 18–80 years with a BMI of 18–35 kg/m2 and ASA fitness grade of III or below) requiring left lateral sectionectomy (LLS) were assigned randomly to OLLS or LLLS within an enhanced recovery after surgery (ERAS) programme. All randomized patients, ward physicians and nurses were blinded to the procedure undertaken. A parallel prospective registry (open non-randomized (ONR) versus laparoscopic non-randomized (LNR)) was used to monitor patients who were not enrolled for randomization because of doctor or patient preference. The primary endpoint was time to functional recovery. Secondary endpoints were length of hospital stay (LOS), readmission rate, overall morbidity, composite endpoint of liver surgery-specific morbidity, mortality, and reasons for delay in discharge after functional recovery. Results Between January 2010 and July 2014, patients were recruited at ten centres. Of these, 24 patients were randomized at eight centres, and 67 patients from eight centres were included in the prospective registry. Owing to slow accrual, the trial was stopped on the advice of an independent Data and Safety Monitoring Board in the Netherlands. No significant difference in median (i.q.r.) time to functional recovery was observed between laparoscopic and open surgery in the randomized or non-randomized groups: 3 (3–5) days for OLLSversus 3 (3–3) days for LLLS; and 3 (3–3) days for ONRversus 3 (3–4) days for LNR. There were no significant differences with regard to LOS, morbidity, reoperation, readmission and mortality rates. Conclusion This RCT comparing open and laparoscopic LLS in an ERAS setting was not able to reach a conclusion on time to functional recovery, because it was stopped prematurely owing to slow accrual. Registration number: NCT00874224 (https://www.clinicaltrials.gov).

The Health Promotion Board (HPB) has developed the Clinical Practice Guidelines (CPG) on Obesity to provide health professionals in Singapore with recommendations for evidence-based interventions for obesity. This article summarises the introduction, epidemiology and executive summary of the key recommendations from the HPB-MOH CPG on Obesity for the information of SMJ readers. The chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Health Promotion Board website: http://www.hpb.gov.sg/cpg-obesity. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Many modern advanced electromagnetic devices, e.g. motors and actuators, use permanent magnets as a source of magnetic fields. The strong and reliable magnetic fields of today’s rare-earth permanent magnets increase their force density. Most of them are based on the interaction between the magnetic field of permanent magnets and current-carrying coils. However, magnetic couplings or electromagnetic vibration isolation systems rely on the strong and position-dependent passive force between permanent magnets instead of an active force resulting from a current. An accurate, noise-free computational description of these interactions is therefore essential for future developments of these high-performance devices. The considered configurations are free-space unbounded problems and do not exhibit structural periodicity. As a three-dimensional magnetic field solution is required, the analytical surface charge method is the model of choice. The expressions for the interaction force between PMs with an (anti-)parallel, perpendicular, and rotated magnetization are derived considering a configuration with two PMs. These could be extended to include various otherelectromagnetic device structures. Further, the developments in the analytical surface charge expressions of the interaction forces between cuboidal permanent magnets are addressed. Finally, extensions to the surface charge method are proposed, aiming to create a fully 6-DoF permanent magnet interaction model, which can serve as a fast, analytical replacement to the finite element method.

Background Routine laxatives may expedite gastrointestinal recovery and early tolerance of food within an enhanced recovery after surgery (ERAS) programme. Combined with carbohydrate loading and oral nutritional supplements (ONS), it may further enhance recovery of gastrointestinal function and promote earlier overall recovery. Methods Seventy-four patients undergoing liver resection were randomized in a two-by-two factorial design to receive either postoperative magnesium hydroxide as a laxative, preoperative carbohydrate loading and postoperative ONS, their combination or a control group. Patients were managed within an ERAS programme of care. The primary outcome measure was time to first passage of stool. Secondary outcome measures were gastric emptying, postoperative oral calorie intake, time to functional recovery and length of hospital stay. Results Sixty-eight patients completed the trial. The laxative group had a significantly reduced time to passage of stool: median (interquartile range) 4 (3–5) versus 5 (4–6) days (P = 0·034). The ONS group showed a trend towards a shorter time to passage of stool (P = 0·076) but there was no evidence of interaction in patients randomized to the combination regimen. Median length of hospital stay was 6 (4–7) days. There were no differences in secondary outcomes between groups. Conclusion Within an ERAS protocol for patients undergoing liver resection, routine postoperative laxatives result in an earlier first passage of stool but the overall rate of recovery is unaltered. Registration number: NCT00538954 (http://www.clinicaltrials.gov).

Background: Vitamin D deficiency is frequently observed in heart failure patients and it has been shown that vitamin D exerts various effects on the heart that may be relevant for the pathogenesis of myocardial diseases. Aims: We aimed to elucidate the largely unknown association of 25-hydroxyvitamin D [25(OH)D] serum levels with echocardiographic measures of left ventricular (LV) structure and function. Material/Subjects and methods: We measured 25(OH)D serum levels and performed standardized LV chocardiograms in 614 persons from a population-based cohort of older men and women. Echocardiographic data were used to calculate LV mass and geometry and for classification of systolic and diastolic dysfunction. To consider the seasonal variations of 25(OH)D levels we categorized our study participants according to season-specific 25(OH)D quartiles. Resuits: LV systolic function, mass and geometry were not significantly associated with 25(OH)D serum levels. In binary logistic regression analyses, the prevalence of LV diastolic dysfunction was significantly higher in the first season-specific 25(OH)D quartile when compared to the fourth quartile [odds ratio 2.32 (95% Cl: 1.42-3.80); p=0.001] but significance was lost after adjustments for age [odds ratio 1.51 (0.89-2.57); p=0.123] and established risk factors for heart failure [odds ratio 1.47 (0.84-2.59); p=0.178]. Conclusions: Serum levels of 25(OH)D are not significantly associated with LV structure and function but a non-significant trend towards increased risk of diastolic dysfunction in persons with vitamin D deficiency warrants further studies. ©2010, Editrice Kurtis.

Summary Diet and exercise are two of the commonest strategies to reduce weight. Whether a diet-plus-exercise intervention is more effective for weight loss than a diet-only intervention in the long-term has not been conclusively established. The objective of this study was to systemically review the effect of diet-plus-exercise interventions vs. diet-only interventions on both long-term and short-term weight loss. Studies were retrieved by searching MEDLINE and Cochrane Library (1966 – June 2008). Studies were included if they were randomized controlled trials comparing the effect of diet-plus-exercise interventions vs. diet-only interventions on weight loss for a minimum of 6 months among obese or overweight adults. Eighteen studies met our inclusion criteria. Data were independently extracted by two investigators using a standardized protocol. We found that the overall standardized mean differences between diet-plus-exercise interventions and diet-only interventions at the end of follow-up were −0.25 (95% confidence interval [CI]−0.36 to −0.14), with a P-value for heterogeneity of 0.4. Because there were two outcome measurements, weight (kg) and body mass index (kg m−2), we also stratified the results by weight and body mass index outcome. The pooled weight loss was 1.14 kg (95% CI 0.21 to 2.07) or 0.50 kg m−2 (95% CI 0.21 to 0.79) greater for the diet-plus-exercise group than the diet-only group. We did not detect significant heterogeneity in either stratum. Even in studies lasting 2 years or longer, diet-plus-exercise interventions provided significantly greater weight loss than diet-only interventions. In summary, a combined diet-plus-exercise programme provided greater long-term weight loss than a diet-only programme. However, both diet-only and diet-plus-exercise programmes are associated with partial weight regain, and future studies should explore better strategies to limit weight regain and achieve greater long-term weight loss.

Objective Vitamin D deficiency is common among the elderly and may contribute to cardiovascular disease. The aim of our study was to elucidate whether low serum levels of 25-hydroxyvitamin D [25(OH)D] are associated with an increased risk of all-cause and cardiovascular mortality. Design and patients The Hoorn Study is a prospective population-based study among older men and women. Measurements Fasting serum 25(OH)D was determined in 614 study participants at the follow-up visit in 2000-2001, the baseline for the present analysis. To account for sex differences and seasonal variations of 25(OH)D levels we formed sex-specific quartiles, which were calculated from the 25(OH)D values of each season. Results After a mean follow-up period of 6·2 years, 51 study participants died including 20 deaths due to cardiovascular causes. Unadjusted Cox proportional hazard ratios (HRs; with 95% confidence intervals) for all-cause and cardiovascular mortality in the first when compared with the upper three 25(OH)D quartiles were 2·24 (1·28- 3·92; P = 0·005) and 4·78 (1·95-11·69; P = 0·001), respectively. After adjustment for age, sex, diabetes mellitus, smoking status, arterial hypertension, high-density lipoprotein-cholesterol, glomerular filtration rate and waist-to-hip ratio, the HRs remained significant for all-cause [1·97 (1·08-3·58; P = 0·027)] and for cardiovascular mortality [5·38 (2·02-14·34; P = 0·001)]. Conclusions Low 25(OH)D levels are associated with all-cause mortality and even more pronounced with cardiovascular mortality, but it remains unclear whether vitamin D deficiency is a cause or a consequence of a poor health status. Therefore, intervention studies are warranted to evaluate whether vitamin D supplementation reduces mortality and cardiovascular diseases. © 2009 Blackwell Publishing Ltd.

Aims Recent studies indicate transcription factor hepatocyte nuclear factor 4 alpha ( HNF-4 alpha, HNF4A) modulates the transcription of the pancreatic B-cell ATP-sensitive K+ ( K-ATP) channel subunit Kir6.2 gene ( KCNJ11). Both HNF4A and KCNJ11 have previously been associated with diabetes risk but little is known whether the variations in these genes interact with each other. Methods We conducted a prospective, nested case-control study of 714 incident cases of Type 2 diabetes and 1120 control subjects from the Nurses' Health Study. Results KCNJ11 E23K was significantly associated with an increased diabetes risk ( odds ratio 1.26, 95% CI 1.03-1.53) while HNF4A P2 promoter polymorphisms were associated with a moderately increased risk at borderline significance. By using a logistic regression model, we found significant interactions between HNF4A rs2144908, rs4810424 and rs1884613 and KCNJ11 E23K ( P for interaction = 0.017, 0.012 and 0.004, respectively). Carrying the minor alleles of the three HNF4A polymorphisms was associated with significantly greater diabetes risk in women carrying the KCNJ11 allele 23K, but not in those who did not carry this allele. Analyses using the multifactor dimensionality reduction ( MDR) method confirmed the gene-gene interaction. We identified that the best interaction model included HNF4A rs2144908 and KCNJ11 E23K. Such a two-locus model showed the maximum cross-validation consistency of 10 out of 10 and a significant prediction accuracy of 54.2% ( P = 0.01) on the basis of 1000-fold permutation testing. Conclusions Our data indicate that HNF4A P2 promoter polymorphisms may interact with KCNJ11 E23K in predicting Type 2 diabetes in women.

BACKGROUND: To consider the changes in overall diet quality following migration we examined the associations of acculturation variables and education level with diet in Surinamese South Asian and Surinamese Afro-Caribbean origin on the one hand, and ethnic Dutch residents of the Netherlands on the other. Surinam is a former Dutch colony in South America. METHODS: We randomly selected men and women aged 35-60 years: ethnic Dutch, n = 552; South Asian, n = 306; Afro-Caribbean, n = 660. Intakes of fruit, vegetables, red meat, fish, vegetable oils, breakfast and salt were measured using a short questionnaire that formed the basis for a 'diet quality indicator' score. Highest education was measured and acculturation of the Surinamese groups was assessed by age at migration, number of resident years and a scale measure of social contacts with ethnic Dutch. RESULTS: Compared with ethnic Dutch, both Surinamese groups scored higher on overall diet quality (P < or = 0.001) but some aspects of diet (breakfast and salt use) were less prudent. Education was positively associated with diet quality in ethnic Dutch (P < or = 0.01), but not consistently so in Surinamese. Associations with social contact with ethnic Dutch varied for different quality aspects of the diet. Residence duration (mean = 22 years) and age at migration (mean = 21 years) were not associated with diet. CONCLUSIONS: A greater degree of acculturation does not necessarily lead to a less healthful diet in migrants. In addition, the association of education level with diet may differ for migrant groups. The diet of migrants differ from host populations, suggesting that migrant groups should be considered in the development of nutrition health promotion activities

Although diet and nutrition are widely believed to play an important part in the development of Type II (non-insulin-dependent) diabetes mellitus, specific dietary factors have not been clearly defined. Much controversy exists about the relations between the amount and types of dietary fat and carbohydrate and the risk of diabetes. In this article, we review in detail the current evidence regarding the associations between different types of fats and carbohydrates and insulin resistance and Type II diabetes. Our findings indicate that a higher intake of polyunsaturated fat and possibly long-chain n-3 fatty acids could be beneficial, whereas a higher intake of saturated fat and trans-fat could adversely affect glucose metabolism and insulin resistance. In dietary practice, exchanging nonhydrogenated polyunsaturated fat for saturated and trans-fatty acids could appreciably reduce risk of Type II diabetes. In addition, a low-glycaemic index diet with a higher amount of fiber and minimally processed whole grain products reduces glycaemic and insulinaemic responses and lowers the risk of Type II diabetes. Dietary recommendations to prevent Type II diabetes should focus more on the quality of fat and carbohydrate in the diet than quantity alone, in addition to balancing total energy intake with expenditure to avoid overweight and obesity.

Background: Low intake of fat and high intake of specific vitamins have been hypothesized to reduce risk of basal cell carcinoma of the skin (BCC). Objective: Our objective was to examine intakes of fat, antioxidant nutrients, retinol, folate, and vitamin D in relation to risk of BCC. Design: In 1986, diet was assessed by a validated food-frequency questionnaire in 43217 male participants of the Health Professionals Follow-up Study who were 40-75 y of age and free of cancer. During 8 y of follow-up, we ascertained 3190 newly diagnosed cases of BCC. Results: Total fat consumption was associated with a lower risk of BCC [relative risk (RR): 0.81; 95% CI: 0.72, 0.90 for the highest compared with the lowest quintile of intake; P for trend

Aims The relation between selenium status and risk of Type 2 diabetes is controversial. We aimed to evaluate associations of serum selenium, a marker of dietary selenium, with measures of glucose metabolism and risk of diabetes. Methods We used data from a population-based, longitudinal cohort of 1925 Swedish men who were 50 years old and did not have diabetes at baseline in the 1970s. At baseline, an intravenous glucose tolerance test was performed and, at a follow-up examination after 20 years, an oral glucose tolerance test and a hyperinsulinaemic euglycaemic clamp for the assessment of insulin sensitivity were conducted. Results At baseline, the mean (standard deviation) selenium concentration was 75.6 (14.3) μg/l. During 20 years of follow-up, 88 incident cases of diabetes occurred in 1024 participants with follow-up data. Baseline serum selenium levels were not associated with risk of diabetes (odds ratio 1.06; 95% CI 0.83–1.38). Higher selenium levels were associated with lower early insulin response (standardized β –0.08; 95% CI –0.14 to –0.03) at baseline after adjusting for potential confounders, but not with any other measures of β-cell function or insulin sensitivity at baseline or follow-up. The association with early insulin response was non-significant after taking multiple testing into account. Conclusions Our results do not support a role of dietary selenium in the development of disturbances in glucose metabolism or diabetes in older individuals.

To the editor: We are delighted by the encouraging results reported in the meta-analysis of van der Meer et al 1 regarding lower hospitalisation rates for patients with heart failure (HF) receiving erythropoiesis-stimulating agents. However, the possibility of bias in the studies included in the meta-analysis might be greater than assessed by the authors. First, the methodological quality of the …

Coffee has been linked to both beneficial and harmful health effects, but data on its relationship with cardiovascular disease and mortality in patients with type 2 diabetes are sparse. This was a prospective cohort study including 7,170 women with diagnosed type 2 diabetes but free of cardiovascular disease or cancer at baseline. Coffee consumption was assessed in 1980 and then every 2–4 years using validated questionnaires. A total of 658 incident cardiovascular events (434 coronary heart disease and 224 stroke) and 734 deaths from all causes were documented between 1980 and 2004. After adjustment for age, smoking and other cardiovascular risk factors, the relative risks were 0.76 (95% CI 0.50–1.14) for cardiovascular diseases (p trend = 0.09) and 0.80 (95% CI 0.55–1.14) for all-cause mortality (p trend = 0.05) for the consumption of ≥4 cups/day of caffeinated coffee compared with non-drinkers. Similarly, multivariable RRs were 0.96 (95% CI 0.66–1.38) for cardiovascular diseases (p trend = 0.84) and 0.76 (95% CI 0.54–1.07) for all-cause mortality (p trend = 0.08) for the consumption of ≥2 cups/day of decaffeinated coffee compared with non-drinkers. Higher decaffeinated coffee consumption was associated with lower concentrations of HbA1c (6.2% for ≥2 cups/day versus 6.7% for

Recent studies indicate transcription factor hepatocyte nuclear factor 4 alpha (HNF-4 alpha, HNF4A) modulates the transcription of the pancreatic B-cell ATP-sensitive K+ (KATP) channel subunit Kir6.2 gene (KCNJ11). Both HNF4A and KCNJ11 have previously been associated with diabetes risk but little is known whether the variations in these genes interact with each other.We conducted a prospective, nested case-control study of 714 incident cases of Type 2 diabetes and 1120 control subjects from the Nurses' Health Study.KCNJ11 E23K was significantly associated with an increased diabetes risk (odds ratio 1.26, 95% CI 1.03-1.53) while HNF4A P2 promoter polymorphisms were associated with a moderately increased risk at borderline significance. By using a logistic regression model, we found significant interactions between HNF4A rs2144908, rs4810424 and rs1884613 and KCNJ11 E23K (P for interaction = 0.017, 0.012 and 0.004, respectively). Carrying the minor alleles of the three HNF4A polymorphisms was associated with significantly greater diabetes risk in women carrying the KCNJ11 allele 23K, but not in those who did not carry this allele. Analyses using the multifactor dimensionality reduction (MDR) method confirmed the gene-gene interaction. We identified that the best interaction model included HNF4A rs2144908 and KCNJ11 E23K. Such a two-locus model showed the maximum cross-validation consistency of 10 out of 10 and a significant prediction accuracy of 54.2% (P = 0.01) on the basis of 1000-fold permutation testing.Our data indicate that HNF4A P2 promoter polymorphisms may interact with KCNJ11 E23K in predicting Type 2 diabetes in women.

The Scientific Update involved consideration of a number of key issues that have arisen since the Joint FAO/WHO Expert Consultation on Carbohydrates in Human Nutrition was held in 1997 (FAO, 1998) or where new data may have altered conclusions drawn some 10 years ago. The Scientific Update enabled some firm conclusions to be drawn and identified a number of areas where more research is required to enable definitive recommendations. The review papers prepared as part of this Scientific Update applied the criteria used by the 2002 WHO/FAO Expert Consultation on Diet, Nutrition and the Prevention of Chronic Diseases to describe strength of evidence for drawing the conclusions of the scientific review (WHO, 2003). The following are agreedupon summaries of both the review papers, and discussions from the authors’ meeting (Geneva, 17–18 July 2006) on each issue area. The experts who participated at the authors meeting were: John H Cummings, Hans Englyst Timothy Key, Simin Liu, Jim Mann (Chairman), Rob van Dam, Bernard Venn, Carolyn Summerbell (Rapporteur), Gabriele Riccardi, Ricardo Uauy, HH Vorster (Rapporteur) and Martin Wiseman. The FAO Secretariat members were Kraisid Tontisirin and Frank Martinez Nocito and the WHO Secretariat members were Chizuru Nishida and Denise Costa Coitinho.

Coffee is among the most commonly consumed beverages in The Netherlands. Caffeine can acutely lower insulin sensitivity, but it is not clear whether tolerance for this effect develops after long-term regular intake. Furthermore, it is plausible that the effects of coffee are different from those of caffeine. Coffee contains hundreds of substances and there are indications that certain components may partly counter-act the effect of caffeine or may have independent beneficial effects. Intake of the coffee components chlorogenic acid, quinides, lignans, and trigonelline improved glucose metabolism in animal studies. Habitual coffee consumption has been studied in relation to the risk of diabetes mellitus type 2 in 12 cohort studies in Europe, the USA, and Japan. Generally, high coffee consumption was associated with a substantially lower risk of type-2 diabetes. The findings were similar for caffeinated and decaffeinated coffee, suggesting that the non-caffeine components of coffee may be responsible. Identification of these coffee components may lead to the development or selection of coffee types with improved effects on health.

To obtain insight into the attitude of Dutch women of Turkish ancestry towards various possible measures for the prevention and treatment of vitamin D deficiency.Qualitative, focus group interviews.Four focus group meetings of 4-13 women of Turkish ancestry (mean age: 31.8-47.1 years) were held in community centres in Amsterdam. Discussions were held with the aid of an interpreter in response to questions about exposure to sunlight, vitamin D supplements, fortification of foods with vitamin D, and the consumption of vitamin D rich foods. The discussions were recorded, translated, and transcribed, and the recurring themes were analysed.Participants had a strong preference for vitamins from 'natural sources' as compared with vitamin supplements. Concerns about weight gain and overdose as a result of vitamin supplement use were expressed frequently. Most women only found the use of vitamin D supplements acceptable if prescribed by a physician. For religious/cultural reasons, many women were not willing to alter their dress to expose more skin to sunlight, or were only willing to do so in the strict absence of men that are not members of the family. Participants were reluctant to consume vitamin D-fortified margarine products because of concern about the possible presence of pork fat and the fear that consumption of these products would induce weight gain.Among Dutch women of Turkish ancestry, cultural and religious beliefs and concern about the possible side effects can impede the acceptance of advice on how to combat vitamin D deficiency. This should be taken into consideration when giving information on the prevention and treatment of vitamin D deficiency.

To evaluate the relation between common variants in the ATP-sensitive K+ channel genes and glucose intolerance.We conducted a meta-analysis of reported association studies in Caucasian populations for common variants in the ABCC8 (exons 16 and 18) and the KCNJ11 (E23K) gene and examined sources of heterogeneity in the results. The meta-analysis was based on 7768-10216 subjects (depending on the gene variant), and included two new population-based studies in the Netherlands with 725 cases and 742 controls.For the KCNJ11 variant, the summary odds ratio (OR) for glucose intolerance was 1.12 (1.01-1.23, P=0.03) for the EK genotype and 1.44 (1.17-1.78, P=0.0007) for the KK genotype, as compared with the EE genotype. For the ABCC8 exon 16 variant, the OR was 1.06 (0.94-1.19, P=0.34) for ct and 0.93 (0.71-1.20, P=0.56) for tt, as compared with the cc genotype. For ABCC8 exon 18, the OR was 1.20 (0.97-1.49, P=0.10) for CT/TT, as compared with the CC genotype. Studies of the ABCC8 variants that were published first or had smaller sample sizes (for the exon 18 variant) showed stronger associations, which may indicate publication bias. For the ABCC8 exon 18 and the KCNJ11 variant, associations were stronger for studies of clinical diabetes than newly detected glucose intolerance. The population attributable risk for clinical Type 2 diabetes was 6.2% for the KCNJ11 KK genotype and 10.1% for the KCNJ11 EK and KK genotype combined.The common KCNJ11 E23K gene variant, but not the ABCC8 exon 16 or exon 18 variant, was consistently associated with Type 2 diabetes.

The insulin receptor substrate-1 (IRS-1) gene is among the most frequently studied candidate genes for Type 2 diabetes, but findings have been inconsistent. This may have been due to generally small study sizes, or to interaction with body fatness as suggested by studies of insulin sensitivity. The aim of this study was to test the hypothesis that the IRS-1 Gly972Arg variant increases risk of Type 2 diabetes.We conducted two large population-based studies including a total of 725 cases and 742 control subjects, who were Caucasian Dutch men and women aged 40-70 years. We calculated odds ratios adjusted for body mass index, study centre, sex and age.Carriers of the Arg allele did not have a higher prevalence of newly detected (OR 0.49, 95% CI 0.24-1.01) or treated (OR 0.71, 0.37-1.35) Type 2 diabetes in the first study, or a higher prevalence of glucose intolerance (OR 1.07, 0.71-1.59) in the second study. The summary odds ratio was 0.86 (0.62-1.17) for carrying the Arg allele as compared with the Gly/Gly genotype. Associations did not differ appreciably by degree of obesity. Also, the Arg variant was not associated with detrimental values for body mass index, waist circumference, plasma HDL-and total cholesterol or hypertension.Our findings indicate that the IRS-1 Gly972Arg variant does not substantially increase risk of common Type 2 diabetes, or Type 2 diabetes in obese persons.

Coffee consumption and incidence of impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes: the Hoorn Study.van Dam RM, Dekker JM, Nijpels G, Stehouwer CD, Bouter LM, Heine RJ; Hoorn study.Department of Nutrition and Health, Faculty of Earth and Life Sciences, Vrije University Amsterdam, de Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands. rob.van.dam@falw.vu.nlAIMS/HYPOTHESIS: Coffee contains several substances that may affect glucose metabolism. The aim of this study was to evaluate the relationship between habitual coffee consumption and the incidence of IFG, IGT and type 2 diabetes. METHODS: We used cross-sectional and prospective data from the population-based Hoorn Study, which included Dutch men and women aged 50-74 years. An OGTT was performed at baseline and after a mean follow-up period of 6.4 years. Associations were adjusted for potential confounders including BMI, cigarette smoking, physical activity, alcohol consumption and dietary factors. RESULTS: At baseline, a 5 cup per day higher coffee consumption was significantly associated with lower fasting insulin concentrations (-5.6%, 95% CI -9.3 to -1.6%) and 2-h glucose concentrations (-8.8%, 95% CI -11.8 to -5.6%), but was not associated with lower fasting glucose concentrations (-0.8%, 95% CI -2.1 to 0.6%). In the prospective analyses, the odds ratio (OR) for IGT was 0.59 (95% CI 0.36-0.97) for 3-4 cups per day, 0.46 (95% CI 0.26-0.81) for 5-6 cups per day, and 0.37 (95% CI 0.16-0.84) for 7 or more cups per day, as compared with the corresponding values for the consumption of 2 or fewer cups of coffee per day (p=0.001 for trend). Higher coffee consumption also tended to be associated with a lower incidence of type 2 diabetes (OR 0.69, CI 0.31-1.51 for >/=7 vs /=7 vs

To determine if social support and the reaction of the spouse to the patient's pain are contributing factors to psychological distress in male and female patients with rheumatoid arthritis (RA).Physical, social, and psychological aspects of health were assessed in 97 male and 132 female patients who were living with a spouse. Differences between male and female patients were analyzed by means of analysis of covariance while controlling for age and duration of RA. In multiple regression analyses the influence of social support and reaction of the spouse concerning psychological distress was determined after age, duration of RA, and physical functioning had been controlled.Criticism of the spouse significantly contributed to anxiety in male patients and to depression and anxiety in female patients. In addition, male and female patients differed in the social support resources that contributed to psychological distress. A relatively low number of friends was associated with depression in males. A relatively low level of potential support was associated with more anxiety in females.High levels of criticism of the spouse and low levels of social support are associated with more psychological distress in male and female patients. The number of friends is a social support resource in male patients and potential emotional support a resource in female patients.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8–1.2×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p, Author Summary Serum adiponectin levels are highly heritable and are inversely correlated with the risk of type 2 diabetes (T2D), coronary artery disease, stroke, and several metabolic traits. To identify common genetic variants associated with adiponectin levels and risk of T2D and metabolic traits, we conducted a meta-analysis of genome-wide association studies of 45,891 multi-ethnic individuals. In addition to confirming that variants at the ADIPOQ and CDH13 loci influence adiponectin levels, our analyses revealed that 10 new loci also affecting circulating adiponectin levels. We demonstrated that expression levels of several genes in these candidate regions are associated with serum adiponectin levels. Using a powerful novel method to assess the contribution of the identified variants with other traits using summary-level results from large-scale GWAS consortia, we provide evidence that the risk alleles for adiponectin are associated with deleterious changes in T2D risk and metabolic syndrome traits (triglycerides, HDL, post-prandial glucose, insulin, and waist-to-hip ratio), demonstrating that the identified loci, taken together, impact upon metabolic disease.

An automotive, fluid-control solenoid valve is composed of an electromagnetic reluctance actuator and a near-constant-force spring. Its motion profile is characterized by short closed-To-open transition times which demand fast switching, while valve lifetime improves by minimizing the impact velocity, i.e. a soft landing. In this paper, a cascaded position-and current-feedback control is designed and implemented on nonlinear, axisymmetric magnetostatic finite element simulations of a low-energy solenoid valve actuator. By applying the cascaded control, actuator performance is improved considerably, as a soft landing, a timely actuation, and an increased energy-efficient device have been obtained.