Early infant feeding and adiposity risk: from infancy to adulthood

Introduction: Systematic reviews suggest that a longer duration of breast-feeding is associated with a reduction in the risk of later overweight and obesity. Most studies examining breast-feeding in relation to adiposity have not used longitudinal analysis. In our study, we aimed to examine early infant feeding and adiposity risk in a longitudinal cohort from birth to young adulthood using new as well as published data. Methods: Data from the Western Australian Pregnancy Cohort (Raine) Study in Perth, W.A., Australia, were used to examine associations between breast-feeding and measures of adiposity at 1, 2, 3, 6, 8, 10, 14, 17, and 20 years. Results: Breast-feeding was measured in a number of ways. Longer breast-feeding (in months) was associated with reductions in weight z-scores between birth and 1 year (β = -0.027; p \u3c 0.001) in the adjusted analysis. At 3 years, breast-feeding for \u3c4 months increased the odds of infants experiencing early rapid growth (OR 2.05; 95% CI 1.43-2.94; p \u3c 0.001). From 1 to 8 years, children breast-fed for ≤4 months compared to ≥12 months had a significantly greater probability of exceeding the 95th percentile of weight. The age at which breast-feeding was stopped and a milk other than breast milk was introduced (introduction of formula milk) played a significant role in the trajectory of the BMI from birth to 14 years; the 4-month cutoff point was consistently associated with a higher BMI trajectory. Introduction of a milk other than breast milk before 6 months compared to at 6 months or later was a risk factor for being overweight or obese at 20 years of age (OR 1.47; 95% CI 1.12-1.93; p = 0.005). Discussion: Breast-feeding until 6 months of age and beyond should be encouraged and is recommended for protection against increased adiposity in childhood, adolescence, and young adulthood. Adverse long-term effects of early growth acceleration are fundamental in later overweight and obesity. Formula feeding stimulates a higher postnatal growth velocity, whereas breast-feeding promotes slower growth and a reduced likelihood of overweight and obesity. Biological mechanisms underlying the protective effect of breast-feeding against obesity are based on the unique composition and metabolic and physiological responses to human milk

Coronary microvascular ischemia in hypertrophic cardiomyopathy - a pixel-wise quantitative cardiovascular magnetic resonance perfusion study.

BACKGROUND: Microvascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness. METHODS: CMR perfusion imaging was undertaken during adenosine-induced hyperemia and again at rest in 35 patients together with late gadolinium enhancement (LGE) imaging. Myocardial blood flow (MBF) was quantified on a pixel-by-pixel basis from CMR perfusion images using a Fermi-constrained deconvolution algorithm. Regions-of-interest (ROI) in hypoperfused and hyperemic myocardium were identified from the MBF pixel maps. The myocardium was also divided into 16 AHA segments. RESULTS: Resting MBF was significantly higher in the endocardium than in the epicardium (mean ± SD: 1.25 ± 0.35 ml/g/min versus 1.20 ± 0.35 ml/g/min, P < 0.001), a pattern that reversed with stress (2.00 ± 0.76 ml/g/min versus 2.36 ± 0.83 ml/g/min, P < 0.001). ROI analysis revealed 11 (31%) patients with stress MBF lower than resting values (1.05 ± 0.39 ml/g/min versus 1.22 ± 0.36 ml/g/min, P = 0.021). There was a significant negative association between hyperemic MBF and wall thickness (β = −0.047 ml/g/min per mm, 95% CI: −0.057 to −0.038, P < 0.001) and a significantly lower probability of fibrosis in a segment with increasing hyperemic MBF (odds ratio per ml/g/min: 0.086, 95% CI: 0.078 to 0.095, P = 0.003). CONCLUSIONS: Pixel-wise quantitative CMR perfusion imaging identifies a subgroup of patients with HCM that have localised severe microvascular dysfunction which may give rise to myocardial ischemia

The energy budget in Rayleigh-Benard convection

It is shown using three series of Rayleigh number simulations of varying aspect ratio AR and Prandtl number Pr that the normalized dissipation at the wall, while significantly greater than 1, approaches a constant dependent upon AR and Pr. It is also found that the peak velocity, not the mean square velocity, obeys the experimental scaling of Ra^{0.5}. The scaling of the mean square velocity is closer to Ra^{0.46}, which is shown to be consistent with experimental measurements and the numerical results for the scaling of Nu and the temperature if there are strong correlations between the velocity and temperature.Comment: 5 pages, 3 figures, new version 13 Mar, 200

Safety of an intravenous formulation of lamotrigine

AbstractPurposeIntravenous (IV) formulations are useful when treating patients where oral administration is not possible and to study certain pharmacokinetic parameters such as bioavailability. We developed a stable-labeled IV formulation of lamotrigine (LTG) for studying pharmacokinetics in epilepsy patients.MethodsStable-labeled IV LTG was given to 20 persons with epilepsy (6 men; 14 women) with a mean age of 34.8 years (SD 11.7). A 50mg dose of LTG (stable labeled) was given intravenously and replaced 50mg of the regular morning oral dose of LTG (unlabeled, commercially available formulation).ResultsNo significant changes in blood pressure, heart rate, or adverse events including rash were attributed to administration of a 50-mg dose of the intravenous LTG formulation.ConclusionOur results show that LTG base that is complexed with 2-hydroxypropyl-β-cyclodextrin and stable-labeled can be given safely as a tracer replacement dose

The addition of genetic testing and cardiovascular magnetic resonance to routine clinical data for stratification of aetiology in dilated cardiomyopathy

Background: Guidelines recommend genetic testing and cardiovascular magnetic resonance (CMR) for the investigation of dilated cardiomyopathy (DCM). However, the incremental value is unclear. We assessed the impact of these investigations in determining etiology. Methods: Sixty consecutive patients referred with DCM and recruited to our hospital biobank were selected. Six independent experts determined the etiology of each phenotype in a step-wise manner based on (1) routine clinical data, (2) clinical and genetic data and (3) clinical, genetic and CMR data. They indicated their confidence (1-3) in the classification and any changes to management at each step. Results: Six physicians adjudicated 60 cases. The addition of genetics and CMR resulted in 57 (15.8%) and 26 (7.2%) changes in the classification of etiology, including an increased number of genetic diagnoses and a reduction in idiopathic diagnoses. Diagnostic confidence improved at each step (p < 0.0005). The number of diagnoses made with low confidence reduced from 105 (29.2%) with routine clinical data to 71 (19.7%) following the addition of genetics and 37 (10.3%) with the addition of CMR. The addition of genetics and CMR led to 101 (28.1%) and 112 (31.1%) proposed changes to management, respectively. Interobserver variability showed moderate agreement with clinical data (κ = 0.44) which improved following the addition of genetics (κ = 0.65) and CMR (κ = 0.68). Conclusion: We demonstrate that genetics and CMR, frequently changed the classification of etiology in DCM, improved confidence and interobserver variability in determining the diagnosis and had an impact on proposed management

Fracture assessment of HSST Plate 14 shallow-flaw cruciform bend specimens tested under biaxial loading conditions

A technology to determine shallow-flaw fracture toughness of reactor pressure vessel (RPV) steels is being developed for application to the safety assessment of RPVs containing postulated shallow surface flaws. Matrices of cruciform beam tests were developed to investigate and quantify the effects of temperature, biaxial loading, and specimen size on fracture initiation toughness of two-dimensional (constant depth), shallow, surface flaws. The cruciform beam specimens were developed at Oak Ridge National Laboratory (ORNL) to introduce a far-field, out-of-plane biaxial stress component in the test section that approximates the nonlinear stresses resulting from pressurized-thermal-shock or pressure-temperature loading of an RPV. Tests were conducted under biaxial load ratios ranging from uniaxial to equibiaxial. These tests demonstrated that biaxial loading can have a pronounced effect on shallow-flaw fracture toughness in the lower transition temperature region for an RPV material. The cruciform fracture toughness data were used to evaluate fracture methodologies for predicting the observed effects of biaxial loading on shallow-flaw fracture toughness. Initial emphasis was placed on assessment of stress-based methodologies, namely, the J-Q formulation, the Dodds-Anderson toughness scaling model, and the Weibull approach. Applications of these methodologies based on the hydrostatic stress fracture criterion indicated an effect of loading-biaxiality on fracture toughness; the conventional maximum principal stress criterion indicated no effect. A three-parameter Weibull model based on the hydrostatic stress criterion is shown to correlate the experimentally observed biaxial effect on cleavage fracture toughness by providing a scaling mechanism between uniaxial and biaxial loading states

Model-based lamotrigine clearance changes during pregnancy: clinical implication

Objective: The objective of the study was to characterize changes in the oral clearance (CL/F) of lamotrigine (LTG) over the course of pregnancy and the postpartum period through a model-based approach incorporating clinical characteristics that may influence CL/F, in support of developing clinical management guidelines. Methods: Women receiving LTG therapy who were pregnant or planning pregnancy were enrolled. Maternal blood samples were collected at each visit. A pharmacokinetic analysis was performed using a population-based, nonlinear, mixed-effects model. Results: A total of 600 LTG concentrations from 60 women (64 pregnancies) were included. The baseline LTG CL/F was 2.16 L/h with a between-subject variability of 40.6%. The influence of pregnancy on CL/F was described by gestational week. Two subpopulations of women emerged based on the rate of increase in LTG CL/F during pregnancy. The gestational age-associated increase in CL/F displayed a 10-fold higher rate in 77% of the women (0.118 L/h per week) compared to 23% (0.0115 L/h per week). The between-subject variability in these slopes was 43.0%. The increased CL/F at delivery declined to baseline values with a half-life of 0.55 weeks. Interpretation The majority of women had a substantial increase in CL/F from 2.16 to 6.88 L/h by the end of pregnancy, whereas 23% of women had a minimal increase. An increase in CL/F may correspond to decreases in LTG blood concentrations necessitating the need for more frequent dosage adjustments and closer monitoring in some pregnant women with epilepsy. Postpartum doses should be tapered to preconception dose ranges within 3 weeks of delivery