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

The Therapeutic Efficacy of Domestic Violence Victim Interventions

Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

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

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

The transatlantic Thames: Anglo-American tensions on the Victorian “stream of pleasure”

While it is widely understood that rivers took on new symbolic power as avatars of nationalism in the late nineteenth century, less examined is their use as a space for Transatlantic cultural flow, and transnational commentary and critique. This article explores the ways in which a variety of Americans abroad in this period centred the Thames – newly charged with nationalist sentiment – in their accounts of Britain. In particular, it analyses Elizabeth Robins and Joseph Pennell’s travel narrative The Stream of Pleasure, first published as the lead article in the ‘Midsummer Holiday Issue’ of The Century Magazine in 1889, as an exemplary text in which both artist and writer play with the image of the river in ways that chime with much wider Transatlantic debates at this moment

Calibration of myocardial T2 and T1 against iron concentration.

BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron. METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy. RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001). CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies

T1 at 1.5T and 3T compared with conventional T2* at 1.5T for cardiac siderosis

Background: Myocardial black blood (BB) T2* relaxometry at 1.5T provides robust, reproducible and calibrated non-invasive assessment of cardiac iron burden. In vitro data has shown that like T2*, novel native Modified Look-Locker Inversion recovery (MOLLI) T1 shortens with increasing tissue iron. The relative merits of T1 and T2* are largely unexplored. We compared the established 1.5T BB T2* technique against native T1 values at 1.5T and 3T in iron overload patients and in normal volunteers. Methods: A total of 73 subjects (42 male) were recruited, comprising 20 healthy volunteers (controls) and 53 patients (thalassemia major 22, sickle cell disease 9, hereditary hemochromatosis 9, other iron overload conditions 13). Single mid-ventricular short axis slices were acquired for BB T2* at 1.5T and MOLLI T1 quantification at 1.5T and 3T. Results: In healthy volunteers, median T1 was 1014 ms (full range 939–1059 ms) at 1.5T and modestly increased to 1165ms (full range 1056–1224 ms) at 3T. All patients with significant cardiac iron overload (1.5T T2* values <20 ms) had T1 values <939 ms at 1.5T, and <1056 ms at 3T. Associations between T2* and T1 were found to be moderate with y =377 · x0.282 at 1.5T (R2 = 0.717), and y =406 · x0.294 at 3T (R2 = 0.715). Measures of reproducibility of T1 appeared superior to T2*. Conclusions: T1 mapping at 1.5T and at 3T can identify individuals with significant iron loading as defined by the current gold standard T2* at 1.5T. However, there is significant scatter between results which may reflect measurement error, but it is also possible that T1 interacts with T2*, or is differentially sensitive to aspects of iron chemistry or other biology. Hurdles to clinical implementation of T1 include the lack of calibration against human myocardial iron concentration, no demonstrated relation to cardiac outcomes, and variation in absolute T1 values between scanners, which makes inter-centre comparisons difficult. The relative merits of T1 at 3T versus T2* at 3T require further consideration

C-Terminal Substitution of MDM2 Interacting Peptides Modulates Binding Affinity by Distinctive Mechanisms

The complex between the proteins MDM2 and p53 is a promising drug target for cancer therapy. The residues 19–26 of p53 have been biochemically and structurally demonstrated to be a most critical region to maintain the association of MDM2 and p53. Variation of the amino acid sequence in this range obviously alters the binding affinity. Surprisingly, suitable substitutions contiguous to this region of the p53 peptides can yield tightly binding peptides. The peptide variants may differ by a single residue that vary little in their structural conformations and yet are characterized by large differences in their binding affinities. In this study a systematic analysis into the role of single C-terminal mutations of a 12 residue fragment of the p53 transactivation domain (TD) and an equivalent phage optimized peptide (12/1) were undertaken to elucidate their mechanistic and thermodynamic differences in interacting with the N-terminal of MDM2. The experimental results together with atomistically detailed dynamics simulations provide insight into the principles that govern peptide design protocols with regard to protein-protein interactions and peptidomimetic design

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis