Probing many-body dynamics in a two-dimensional dipolar spin ensemble.

The most direct approach for characterizing the quantum dynamics of a strongly interacting system is to measure the time evolution of its full many-body state. Despite the conceptual simplicity of this approach, it quickly becomes intractable as the system size grows. An alternate approach is to think of the many-body dynamics as generating noise, which can be measured by the decoherence of a probe qubit. Here we investigate what the decoherence dynamics of such a probe tells us about the many-body system. In particular, we utilize optically addressable probe spins to experimentally characterize both static and dynamical properties of strongly interacting magnetic dipoles. Our experimental platform consists of two types of spin defects in nitrogen delta-doped diamond: nitrogen-vacancy colour centres, which we use as probe spins, and a many-body ensemble of substitutional nitrogen impurities. We demonstrate that the many-body system's dimensionality, dynamics and disorder are naturally encoded in the probe spins' decoherence profile. Furthermore, we obtain direct control over the spectral properties of the many-body system, with potential applications in quantum sensing and simulation.

Association between fear of hypoglycemia and physical activity in youth with type 1 diabetes: The SEARCH for diabetes in youth study.

BACKGROUND: Youth with type 1 diabetes (T1D) are encouraged to participate in physical activity (PA). Studies have identified fear of hypoglycemia (FOH) as a barrier to participating in PA. OBJECTIVES: To examine (a) PA patterns in youth with T1D by age group and (b) the relationship between both parental and youth FOH and youth PA. METHODS: A cross-sectional analysis from the SEARCH cohort study visit of youth ages 10 to 17 years with T1D (n = 1129) was conducted. Linear regression models estimated the association between self-reported number of days of vigorous PA (VPA) and moderate PA (MPA) and both youth- and parent-reported FOH. Multivariable models were adjusted for age, sex, race, duration of T1D, HbA1c, use of continuous glucose monitoring (CGM), recent severe hypoglycemia, primary insulin regimen, and BMI. RESULTS: Participants were 52% female, had mean (sd) age 14.4 (4.2) years, diabetes duration 7.5 years (1.8), HbA1c 9.2% (1.7). Older youth were less likely to engage in VPA (P < .01), or sports teams (P < .01), but more likely to engage in MPA (P < .01). Higher youth FOH (behavior subscale) was associated with increased levels of VPA (ß (se) 0.30 (0.11), P = .01) but not significantly associated with MPA (P = .06). There was no statistically significant association between parental FOH and youth PA. CONCLUSIONS: In SEARCH participants with T1D, VPA, and team sports participation declined with age, while MPA increased. We observed that higher scores on the youth FOH behavioral subscale were associated with increased VPA levels, suggesting that FOH may be less of a barrier to PA than previously thought.

Socio-economic, demographic, and clinical correlates of poor glycaemic control within insulin regimens among children with Type 1 diabetes: the SEARCH for Diabetes in Youth Study.

AIM: To examine the distribution and association of sociodemographic, adherence, and barriers-to-care factors in relation to glycaemic control within insulin regimens in US children with Type 1 diabetes in the SEARCH for Diabetes in Youth Study. METHODS: Self- or parent-reported data from 1095 children with Type 1 diabetes aged 10-17 years were collected on insulin regimen, sociodemographics, diabetes self-management, diabetes-related family conflict and barriers to care. Multivariable logistic regression analysis identified poor glycaemic control correlates within each insulin regimen. RESULTS: Participants included 694 children on insulin pump therapy, 188 receiving basal-bolus injections, and 213 on a mixed insulin regimen. Of these, 28.5%, 45.2% and 51.2%, respectively, had poor glycaemic control [HbA1c ≥ 80 mmol/mol (9.5%)]. Family conflict between parent and child regarding diabetes management was the only factor significantly associated with poor glycaemic control in all insulin regimens (insulin pump, P≤ 0.0001; basal-bolus injections, P=0.0002; mixed insulin regimen, P=0.0103). For children on insulin pump, poor control was significantly associated with non-white race (P=0.0008), living in multiple households (P=0.0331), having Medicaid insurance (P=0.0090), and decreased insulin adherence (P<0.0001). For children on a mixed insulin regimen, living in multiple households (P=0.0256) and not spending enough time with healthcare provider (P=0.0058) correlated with poor control. CONCLUSIONS: A high percentage of US children with Type 1 diabetes had poor glycaemic control, especially those not using an insulin pump. Early identification of children with risk factors associated with poor glycaemic control within insulin regimens and addressing diabetes-related family conflict may allow interventions to improve diabetes management.

Behavioural implications of traditional treatment and closed-loop automated insulin delivery systems in Type 1 diabetes: applying a cognitive restraint theory framework.

As the prevalence of obesity in Type 1 diabetes rises, the effects of emerging therapy options should be considered in the context of both weight and glycaemic control outcomes. Artificial pancreas device systems will 'close the loop' between blood glucose monitoring and automated insulin delivery and may transform day-to-day dietary management for people with Type 1 diabetes in multiple ways. In the present review, we draw directly from cognitive restraint theory to consider unintended impacts that closed-loop systems may have on ingestive behaviour and food intake. We provide a brief overview of dietary restraint theory and its relation to weight status in the general population, discuss the role of restraint in traditional Type 1 diabetes treatment, and lastly, use this restraint framework to discuss the possible behavioural implications and opportunities of closed-loop systems in the treatment of Type 1 diabetes. We hypothesize that adopting closed-loop systems will lift the diligence and restriction that characterizes Type 1 diabetes today, thus requiring a transition from a restrained eating behaviour to a non-restrained eating behaviour. Furthermore, we suggest this transition be leveraged as an opportunity to teach people lifelong eating behaviour to promote healthy weight status by incorporating education and cognitive reappraisal. Our aim was to use a transdisciplinary approach to highlight critical aspects of the emerging closed-loop technologies relating to eating behaviour and weight effects and to promote discussion of strategies to optimize long-term health in Type 1 diabetes via two key outcomes: glycaemic control and weight management.

Association of adherence to a Mediterranean diet with glycemic control and cardiovascular risk factors in youth with type I diabetes: the SEARCH Nutrition Ancillary Study.

BACKGROUND/OBJECTIVES: This study aimed to determine the association between a Mediterranean diet and glycemic control and other cardiovascular risk factors among youth with type I diabetes (TID). SUBJECTS/METHODS: Incident TID cases aged <20 years at diagnosis between 2002 and 2005 were included. Participants were seen at baseline (N=793), 1-year (N=512) and 5-year follow-up visits (N=501). Mediterranean diet score was assessed using a modified KIDMED index (mKIDMED). Multivariate linear regression and longitudinal mixed model were applied to determine the association between mKIDMED score and log-HbA1c, lipids, blood pressure (BP) and obesity. RESULTS: In cross-sectional analyses using baseline data, for individuals with the hemoglobin A1c (HbA1c) of 7.5%, a two-point higher mKIDMED score (1 s.d.) was associated with 0.15% lower HbA1c (P=0.02). A two-point higher mKIDMED score was associated with 4.0 mg/dl lower total cholesterol (TC) (P=0.006), 3.4 mg/dl lower low-density lipoprotein cholesterol (LDL-C) (P=0.004), 3.9 mg/dl lower non-high-density lipoprotein cholesterol (non-HDL-C) (P=0.004) and 0.07 lower LDL-C/HDL-C ratio (P=0.02). Using longitudinal data, a two-point increase in mKIDMED score was associated with 0.01% lower log-HbA1c (P=0.07), 1.8 mg/dl lower TC (P=0.05), 1.6 mg/dl lower LDL-C (P=0.03) and 1.8 mg/dl lower non-HDL-C (P=0.03) than would otherwise have been expected. HbA1c mediated ∼20% of the association for lipids in both cross-sectional and longitudinal models. An unexpected positive association between mKIDMED score and systolic BP was found among non-Hispanic white youth in cross-sectional analyses (P=0.009). Mediterranean diet was not associated with obesity. CONCLUSIONS: Mediterranean diet may improve glycemic control and cardiovascular health in TID youth.

Implications of iron deficiency/anemia on the classification of diabetes using HbA1c.

BACKGROUND/OBJECTIVES: Nonglycemic factors like iron deficiency (ID) or anemia may interfere with classification of diabetes and prediabetes using hemoglobin A1c (HbA1c). However, few population-based studies of diabetes in areas with endemic ID/anemia have been conducted. We aimed to determine how mutually exclusive categories of ID alone, anemia alone and iron-deficiency anemia (IDA) were each associated with prediabetes and diabetes prevalence using fasting blood glucose (FBG) versus HbA1c in a population-based study of adults with endemic ID/anemia. SUBJECTS/METHODS: We used data from the China Health and Nutrition Survey, a longitudinal, population-based study across 228 communities within nine provinces of China. This analysis included 7308 adults seen in the 2009 survey aged 18-75 years. We used descriptive and covariate-adjusted models to examine relative risk of prediabetes and diabetes using FBG alone, HbA1c alone, HbA1c and FBG, or neither (normoglycemia) by anemia alone, ID alone, IDA or normal iron/hemoglobin. RESULTS: Approximately 65% of individuals with diabetes in our sample were concordantly classified with diabetes using both FBG and HbA1c, while 35% had a discordant diabetes classification: they were classified using either FBG or HbA1c, but not both. Fewer participants with ID alone versus normal iron/hemoglobin were classified with diabetes using HbA1c only. From covariate-adjusted, multinomial regression analyses, the adjusted prevalence of prediabetes using HbA1c only was 22% for men with anemia alone, but 13% for men with normal iron/hemoglobin. In contrast, the predicted prevalence of prediabetes using HbA1c only was 8% for women with ID alone, compared with 13% for women with normal iron/hemoglobin. CONCLUSIONS: These findings suggest potential misclassification of diabetes using HbA1c in areas of endemic ID/anemia. Estimating diabetes prevalence using HbA1c may result in under-diagnosis in women with ID and over-diagnosis in men with anemia.

Doxorubicin plus the IGF-1R antibody cixutumumab in soft tissue sarcoma: a phase I study using the TITE-CRM model.

BACKGROUND: Insulin-like growth factor receptor (IGF-1R) has been studied as an oncologic target in soft tissue sarcoma (STS), but its role in sarcoma biology is unclear. Anti-IGF-1R antibody cixutumumab demonstrated acceptable toxicity but limited activity as a single agent in STS. We carried out a dose-escalation study of cixutumumab with doxorubicin to evaluate safety and dosing of the combination. PATIENTS AND METHODS: Eligible patients with advanced STS were treated with cixutumumab intravenously on days 1/8/15 at one of three dose levels (A: 1 mg/kg, B: 3 mg/kg, C: 6 mg/kg) with doxorubicin at 75 mg/m(2) as a 48 h infusion on day 1 of a 21 day cycle. After six cycles of the combination, patients could receive cixutumumab alone. The Time-to-Event Continual Reassessment Method was used to estimate the probability of dose-limiting toxicity (DLT) and to assign patients to the dose with an estimated probability of DLT≤20%. RESULTS: Between September 2008 and January 2012, 30 patients with advanced STS received a median of six cycles of therapy (range <1-22). Two DLTs were observed, grade 3 mucositis (dose level B) and grade 4 hyperglycemia (dose level C). Grade 2 and 3 reduced left ventricular ejection fraction was seen in three and two patients, respectively. Five partial responses were observed, and estimated progression-free survival was 5.3 months (95% confidence interval 3.0-6.3) in 26 response-assessable patients. Immunohistochemical staining of 11 available tumor samples for IGF-1R and phospho-IGF-1R was not significantly different among responders and non-responders, and serum analysis of select single-nucleotide polymorphisms did not predict for cardiotoxicity. CONCLUSION: The maximum tolerated dose was doxorubicin 75 mg/m(2) on day 1 and cixitumumab 6 mg/kg on days 1/8/15 of a 21 day cycle. Cardiac toxicity was observed and should be monitored in subsequent studies, which should be considered in STS only if a predictive biomarker of benefit to anti-IGF-1R therapy is identified. TRIAL REGISTRATION: ClinicalTrials.gov:NCT00720174.

Diabetes nutrition therapy and dietary intake among individuals with Type 1 diabetes in China.

AIMS: To describe the contribution of diabetes nutrition therapy to disease self-management among individuals with Type 1 diabetes in China and to estimate the association of diabetes nutrition therapy with dietary intake. METHODS: The 3C Study was an epidemiological study of the coverage, cost and care of Type 1 diabetes in China. The data reported in the present study are from the 3C Nutrition Ancillary Study, a follow-up study conducted a mean ± sd of 1.6 ± 0.2 years later. Diabetes nutrition therapy was assessed by an interviewer-administered questionnaire. Dietary intake was assessed using three 24-h recalls. The association of diabetes nutrition therapy with dietary intake was estimated using ancova. RESULTS: Participants (n = 100; 54% male) had a mean ± sd age of 41.7 ± 16.3 years and a mean ± sd diabetes duration of 11.8 ± 9.7 years. Fewer than half of the participants reported that they had 'ever' met with a dietitian. While 64% of participants were taught carbohydrate counting, only 12% 'ever' use this tool. Participants on insulin pumps and those testing ≥ 1 time/day reported greater dietary flexibility and higher fruit intakes compared with participants on other insulin regimens and testing less frequently. After adjustment for confounding by age and occupation, there were no consistent differences in dietary intake across subgroups of diabetes nutrition therapy. CONCLUSIONS: In this sample of individuals with Type 1 diabetes in China there is little dietitian involvement or carbohydrate counting. Increased frequency of nutrition education in conjunction with intensified self-monitoring of blood glucose is needed to improve care.

Flexible Lifestyles for Youth (FL3X) behavioural intervention for at-risk adolescents with Type 1 diabetes: a randomized pilot and feasibility trial.

AIM: To determine the potential effect sizes for the Flexible Lifestyle for Youth (FL3X) behavioural intervention to improve glycaemic control (HbA(1c)) and quality of life for at-risk adolescents with Type 1 diabetes. METHODS: Participants [n = 61; age 12-16 years, HbA(1c) 64-119 mmol/mol (8-13%)] were randomized to FL3X (minimum three sessions) or usual care. Effect sizes (Cohen's d), comparing the mean difference between the groups, were calculated. RESULTS: Study retention (95%), attendance at intervention sessions (87% attended all three sessions) and acceptability were high (100% of the adolescents and 91% of parents would recommend the programme to others). Overall, 41% of participants in the intervention group and 24% of participants in the control group were 'responders' [HbA(1c) decreased by > 6 mmol/mol (0.5%); d = 0.37]. HbA(1c) levels decreased (d = -0.18), diabetes-specific quality of life increased (d = 0.29), but generic quality of life decreased (d = -0.23) in the intervention compared with the control group. CONCLUSIONS: The FL3X programme merits further study for improving HbA(1c) and diabetes-specific quality of life in adolescents with Type 1 diabetes. (Clinical trials registry no.: NCT01286350).

Self-organizing behaviour of glycosteroidal bolaphiles: insights into lipidic microsegregation.

In this article we describe work on the synthesis of bolaphile biomimics composed of glucose head groups and steroidal units linked together by a methylene chain of varying length. The condensed phases formed by self-organization of the products as a function of temperature were characterized by differential scanning calorimetry and thermal polarized light microscopy. The results of these studies show that the thermal stabilities of the lamellar mesophases formed vary linearly as a function of increasing aliphatic composition, which reflects a linear hydrophobic-hydrophilic balance with respect to transition temperatures.

Timing of complementary food introduction and age at diagnosis of type 1 diabetes: the SEARCH nutrition ancillary study (SNAS).

The association between timing of complementary food introduction and age at diagnosis of type 1 diabetes was investigated among 1077 children in the SEARCH for Diabetes in Youth study. Age at diagnosis was 5 months earlier for children introduced to sugar-sweetened beverages (SSB) in the first 12 months of life compared with those who were not (9.0±0.2 vs 9.5±0.1; P=0.02) independent of human leukocyte antigen (HLA) risk status. Analyses stratified by HLA risk status found that children with a high-risk HLA genotype had an earlier age at diagnosis if they were introduced to fruit juice in the first year of life (mean age at diagnosis=9.3±0.1, 9.1±0.1 and 9.6±0.2 for introduction at ⩽6 months, between 7 and 11 months and ⩾12 months, respectively; P=0.04). Introduction of SSB in the first year of life may accelerate the onset of type 1 diabetes independent of HLA risk status.

Genetic risk score and adiposity interact to influence triglyceride levels in a cohort of Filipino women.

BACKGROUND/OBJECTIVES: Individually, genetic variants only moderately influence cardiometabolic (CM) traits, such as lipid and inflammatory markers. In this study we generated genetic risk scores from a combination of previously reported variants influencing CM traits, and used these scores to explore how adiposity levels could mediate genetic contributions to CM traits. SUBJECTS/METHODS: Participants included 1649 women from the 2005 Cebu Longitudinal Health and Nutrition Survey. Three genetic risk scores were constructed for C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs). We used linear regression models to assess the association between each genetic risk score and its related trait. We also tested for interactions between each score and measures of adiposity. RESULTS: Each genetic risk score explained a greater proportion of variance in trait levels than any individual genetic variant. We found an interaction between the TG genetic risk score (2.29-14.34 risk alleles) and waist circumference (WC) (Pinteraction=1.66 × 10(-2)). Based on model predictions, for individuals with a higher TG genetic risk score (75th percentile=12), having an elevated WC (⩾80 cm) increased TG levels from 1.32 to 1.71 mmol l(-1). However, for individuals with a lower score (25th percentile=7), having an elevated WC did not significantly change TG levels. CONCLUSIONS: The TG genetic risk score interacted with adiposity to synergistically influence TG levels. For individuals with a genetic predisposition to elevated TG levels, our results suggest that reducing adiposity could possibly prevent further increases in TG levels and thereby lessen the likelihood of adverse health outcomes such as cardiovascular disease.

Long-term changes in dietary and food intake behaviour in the Diabetes Prevention Program Outcomes Study.

AIMS: To compare change in dietary intake, with an emphasis on food groups and food intake behaviour, over time across treatment arms in a diabetes prevention trial and to assess the differences in dietary intake among demographic groups within treatment arms. METHODS: Data are from the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study. Participants were randomized to a lifestyle intervention (n = 1079), metformin (n = 1073) or placebo (n = 1082) for an average of 3 years, after which the initial results regarding the benefits of the lifestyle intervention were released and all participants were offered a modified lifestyle intervention. Dietary intake was assessed using a food frequency questionnaire at baseline and at 1, 5, 6 and 9 years after randomization. RESULTS: Compared with the metformin and placebo arms, participants in the lifestyle arm maintained a lower total fat and saturated fat and a higher fibre intake up to 9 years after randomization and lower intakes of red meat and sweets were maintained for up to 5 years. Younger participants had higher intakes of poultry and lower intakes of fruits compared with their older counterparts, particularly in the lifestyle arm. Black participants tended to have lower dairy and higher poultry intakes compared with white and Hispanic participants. In the lifestyle arm, men tended to have higher grain, fruit and fish intakes than women. CONCLUSIONS: Changes in nutrient intake among participants in the lifestyle intervention were maintained for up to 9 years. Younger participants reported more unhealthy diets over time and thus may benefit from additional support to achieve and maintain dietary goals.

Associations of dietary intake patterns identified using reduced rank regression with markers of arterial stiffness among youth with type 1 diabetes.

BACKGROUND/OBJECTIVES: Youth with type 1 diabetes (T1DM) are at substantially increased risk for adverse vascular outcomes, but little is known about the influence of dietary behavior on cardiovascular disease (CVD) risk profile. We aimed to identify dietary intake patterns associated with CVD risk factors and evaluate their impact on arterial stiffness (AS) measures collected thereafter in a cohort of youth with T1DM. SUBJECTS/METHODS: Baseline diet data from a food frequency questionnaire and CVD risk factors (triglycerides, low density lipoprotein-cholesterol, systolic blood pressure, hemoglobin A1c, C-reactive protein and waist circumference) were available for 1153 youth aged ⩾10 years with T1DM from the SEARCH for Diabetes in Youth Study. A dietary intake pattern was identified using 33 food groups as predictors and six CVD risk factors as responses in reduced rank regression (RRR) analysis. Associations of this RRR-derived dietary pattern with AS measures (augmentation index (AIx75), n=229; pulse wave velocity, n=237; and brachial distensibility, n=228) were then assessed using linear regression. RESULTS: The RRR-derived pattern was characterized by high intakes of sugar-sweetened beverages (SSB) and diet soda, eggs, potatoes and high-fat meats and low intakes of sweets/desserts and low-fat dairy; major contributors were SSB and diet soda. This pattern captured the largest variability in adverse CVD risk profile and was subsequently associated with AIx75 (ß=0.47; P<0.01). The mean difference in AIx75 concentration between the highest and the lowest dietary pattern quartiles was 4.3% in fully adjusted model. CONCLUSIONS: Intervention strategies to reduce consumption of unhealthy foods and beverages among youth with T1DM may significantly improve CVD risk profile and ultimately reduce the risk for AS.

Synthesis and characterisation of an unsymmetrical, ether-linked, fluorinated bimesogen exhibiting a new polymorphism containing the N(TB) or 'twist-bend' phase.

In this article we report on the liquid crystal phases and properties of the bimesogen 4-((11-((4'-fluoro-[1,1'-biphenyl]-4-yl)oxy)undecyl)oxy)-2,3-difluoro-4'-(4-propylcyclohexyl)-1,1'-biphenyl. This material was shown to exhibit an Iso Liq-N-NTB-SmA phase sequence, thereby clearly indicating that the NTB phase possesses an ordering of the constituent molecules that is between that of a conventional nematic and the smectic A phase. This compound allows us to better understand the relationship between molecular structure and the NTB phase, and we conclude it is the gross topology that dictates the incidence of this fascinating phase and not molecular properties such as dipole moment and bend angle.

Change in DASH diet score and cardiovascular risk factors in youth with type 1 and type 2 diabetes mellitus: The SEARCH for Diabetes in Youth Study.

Youth with diabetes are at an increased risk of cardiovascular disease (CVD). Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet has been shown to improve CVD risk. In this study, we evaluated whether changes in diet quality as characterized by DASH are associated with changes in CVD risk factors in youth with diabetes over time. Longitudinal mixed models were applied to data from 797 participants in the SEARCH for Diabetes in Youth Study representing three time points: baseline, 12- and 60-month follow-up. Data were restricted to youth whose diabetes was first diagnosed in 2002-2005. DASH-related adherence was poor and changed very little over time. However, an increase in DASH diet score was significantly associated with a decrease in HbA1c levels in youth with type 1 diabetes (ß=-0.20, P-value=0.0063) and a decrease in systolic blood pressure among youth with type 2 diabetes (ß=-2.02, P-value=0.0406). Improvements in dietary quality may be beneficial in youth with type 1 or type 2 diabetes. However, further work in larger groups of youth with type 1 and 2 diabetes is desirable.

Infant BMI trajectories are associated with young adult body composition.

The dynamic aspect of early life growth is not fully captured by typical analyses, which focus on one specific time period. To better understand how infant and young child growth relate to the development of adult body composition, the authors characterized body mass index (BMI) trajectories using latent class growth analysis (LCGA) and evaluated their association with adult body composition. Data are from the Cebu Longitudinal Health and Nutrition Survey, which followed a birth cohort to age 22 years (n = 1749). In both males and females, LCGA identified seven subgroups of respondents with similar BMI trajectories from 0 to 24 months (assessed with bimonthly anthropometrics). Trajectory groups were compared with conventional approaches: (1) accelerated growth between two time points (0-4 months), (2) continuous BMI gain between two points (0-4 months and 0-24 months) and (3) BMI measured at one time point (24 months) as predictors of young adult body composition measures. The seven trajectory groups were distinguished by age-specific differences in tempo and timing of BMI gain in infancy. Infant BMI trajectories were better than accelerated BMI gain between 0 and 4 months at predicting young adult body composition. After controlling for BMI at age 2 years, infant BMI trajectories still explained variation in adult body composition. Using unique longitudinal data and methods, we find that distinct infant BMI trajectories have long-term implications for the development of body composition.