I‐SPY 2 (investigation of serial studies to predict your therapeutic response with imaging and molecular analysis 2) is a process targeting the rapid, focused clinical development of paired oncologic ...therapies and biomarkers. The framework is an adaptive phase II clinical trial design in the neoadjuvant setting for women with locally advanced breast cancer. I‐SPY 2 is a collaborative effort among academic investigators, the National Cancer Institute, the US Food and Drug Administration, and the pharmaceutical and biotechnology industries under the auspices of the Foundation for the National Institutes of Health Biomarkers Consortium.
Clinical Pharmacology & Therapeutics (2009); 86, 1, 97–100 doi:10.1038/clpt.2009.68
We studied fetal and childhood growth patterns that are associated with IGT and type 2 diabetes in adult life.
We examined clinically 2,003 subjects born in Helsinki between 1934 and 1944. They had ...on average 11 measurements of height and weight between birth and 2 years of age, and seven measurements between 2 and 11 years of age. Glucose tolerance in adult life was assessed by a 75-g oral glucose tolerance test.
We identified 311 subjects with type 2 diabetes and 496 with IGT. Both IGT and type 2 diabetes were associated with low birthweight (p < 0.0001 adjusting for current BMI). The risk of these conditions was increased by low weight gain between birth and 2 years. A 1 SD increase in weight at 2 years was associated with an odds ratio for either type 2 diabetes or IGT of 0.76 (95% CI 0.69-0.84). This effect was greatest in people who had low birthweight. Low growth in the first 6 months after birth was a critical period for the development of insulin resistance in later life; other critical periods were associated with slow fetal growth and rapid increase in BMI between age 2 and 11 years.
Low weight gain during infancy increases the risk of IGT and type 2 diabetes. The effect is greater in people who had low birthweight. The first 6 months after birth may be the most critical period for growth, in relation to development of glucose intolerance.
THE EARTHCARE SATELLITE Illingworth, A. J.; Barker, H. W.; Beljaars, A. ...
Bulletin of the American Meteorological Society,
08/2015, Letnik:
96, Številka:
8
Journal Article
Recenzirano
Odprti dostop
The collective representation within global models of aerosol, cloud, precipitation, and their radiative properties remains unsatisfactory. They constitute the largest source of uncertainty in ...predictions of climatic change and hamper the ability of numerical weather prediction models to forecast high-impact weather events. The joint European Space Agency (ESA)–Japan Aerospace Exploration Agency (JAXA) Earth Clouds, Aerosol and Radiation Explorer (EarthCARE) satellite mission, scheduled for launch in 2018, will help to resolve these weaknesses by providing global profiles of cloud, aerosol, precipitation, and associated radiative properties inferred from a combination of measurements made by its collocated active and passive sensors. EarthCARE will improve our understanding of cloud and aerosol processes by extending the invaluable dataset acquired by the A-Train satellitesCloudSat, Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO), andAqua. Specifically, EarthCARE’s cloud profiling radar, with 7 dB more sensitivity thanCloudSat, will detect more thin clouds and its Doppler capability will provide novel information on convection, precipitating ice particle, and raindrop fall speeds. EarthCARE’s 355-nm high-spectral-resolution lidar will measure directly and accurately cloud and aerosol extinction and optical depth. Combining this with backscatter and polarization information should lead to an unprecedented ability to identify aerosol type. The multispectral imager will provide a context for, and the ability to construct, the cloud and aerosol distribution in 3D domains around the narrow 2D retrieved cross section. The consistency of the retrievals will be assessed to within a target of ±10 W m−2on the (10 km)² scale by comparing the multiview broadband radiometer observations to the top-of-atmosphere fluxes estimated by 3D radiative transfer models acting on retrieved 3D domains.
Phosphorus losses from land to water will be impacted by climate change and land management for food production, with detrimental impacts on aquatic ecosystems. Here we use a unique combination of ...methods to evaluate the impact of projected climate change on future phosphorus transfers, and to assess what scale of agricultural change would be needed to mitigate these transfers. We combine novel high-frequency phosphorus flux data from three representative catchments across the UK, a new high-spatial resolution climate model, uncertainty estimates from an ensemble of future climate simulations, two phosphorus transfer models of contrasting complexity and a simplified representation of the potential intensification of agriculture based on expert elicitation from land managers. We show that the effect of climate change on average winter phosphorus loads (predicted increase up to 30% by 2050s) will be limited only by large-scale agricultural changes (e.g., 20-80% reduction in phosphorus inputs).The impact of climate change on phosphorus (P) loss from land to water is unclear. Here, the authors use P flux data, climate simulations and P transfer models to show that only large scale agricultural change will limit the effect of climate change on average winter P loads in three catchments across the UK.
Abstract Objective: To determine how growth during infancy and childhood modifies the increased risk of coronary heart disease associated with small body size at birth. Design: Longitudinal study. ...Setting: Helsinki, Finland. Subjects: 4630 men who were born in the Helsinki University Hospital during 1934–44 and who attended child welfare clinics in the city. Each man had on average 18.0 (SD 9.5) measurements of height and weight between birth and age 12 years. Main outcome measures: Hospital admission or death from coronary heart disease. Results: Low birth weight and low ponderal index (birth weight/length3) were associated with increased risk of coronary heart disease. Low height, weight, and body mass index (weight/height2) at age 1 year also increased the risk. Hazard ratios fell progressively from 1.83 (95% confidence interval 1.28 to 2.60) in men whose body mass index at age 1 year was below 16 kg/m2 to 1.00 in those whose body mass index was >19 (P for trend=0.0004). After age 1 year, rapid gain in weight and body mass index increased the risk of coronary heart disease. This effect was confined, however, to men with a ponderal index <26 at birth. In these men the hazard ratio associated with a one unit increase in standard deviation score for body mass index between ages 1 and 12 years was 1.27 (1.10 to 1.47; P=0.001). Conclusion: Irrespective of size at birth, low weight gain during infancy is associated with increased risk of coronary heart disease. After age 1 year, rapid weight gain is associated with further increase in risk, but only among boys who were thin at birth. In these boys the adverse effects of rapid weight gain on later coronary heart disease are already apparent at age 3 years. Improvements in fetal, infant, and child growth could lead to substantial reductions in the incidence of coronary heart disease. What is already known on this topic Coronary heart disease is associated with low birth weight One study has shown that irrespective of size at birth, low weight gain in infancy is also associated with increased risk of the disease among men Rapid weight gain after age 6 years is associated with further increase in risk What this study adds The association with low weight gain in infancy is confirmed The adverse effects of rapid childhood weight gain on risk of coronary heart disease are already apparent at age 3 years and occur only in boys who were thin at birth
Background Low birthweight has been consistently shown to be associated with coronary heart disease (CHD) and its biological risk factors. The effects of low birthweight are increased by slow infant ...growth and rapid weight gain in childhood. To quantify the importance of developmental processes in the genesis of CHD it is necessary to establish the impact of fetal, infant and childhood growth on major pathological events in later life—death, hospital treatment and the need for medication. Methods Longitudinal study of 13 517 men and women who were born in Helsinki University Hospital during 1924–1944, whose body sizes at birth and during childhood were recorded, and in whom deaths, hospital admissions, and prescription of medication for chronic disease are documented. Results The combination of small size at birth and during infancy, followed by accelerated weight gain from age 3 to 11 years, predicts large differences in the cumulative incidence of CHD, type 2 diabetes and hypertension. Conclusions Coronary heart disease and type 2 diabetes may originate through two widespread biological phenomena—developmental plasticity and compensatory growth.
Objective: Low birth weight has been linked to lower lean body mass and abdominal obesity later in life, whereas high birth weight has been suggested to predict later obesity as indicated by high ...body mass index (BMI). We examined how birth weight was related to adult body size, body composition and grip strength. Design/subjects: Cross-sectional study on 928 men and 1075 women born in 1934-1944, with measurements at birth recorded. Measurements: Height, weight, waist and hip circumference and isometric grip strength were measured. Lean and fat body mass were estimated by bioelectrical impedance with an eight-polar tactile electrode system. Results: A 1 kg increase in birth weight corresponded in men to a 4.1 kg (95% CI: 3.1, 5.1) and in women to a 2.9 kg (2.1, 3.6) increase in adult lean mass. This association remained significant after adjustment for age, adult body size, physical activity, smoking status, social class and maternal size. Grip strength was positively related to birth weight through its association with lean mass. The positive association of birth weight with adult BMI was explained by its association with lean mass. Low birth weight was related to higher body fat percentage only after adjustment for adult BMI. Abdominal obesity was not predicted by low birth weight. Conclusions: Low birth weight is associated with lower lean mass in adult life and thus contributes to the risk of relative sarcopenia and the related functional inability at the other end of the lifespan. At a given level of adult BMI, low birth weight predicts higher body fat percentage.
Type 2 diabetes is associated with a small body size at birth and a high BMI in adult life. The aim of our study was to assess the associations between Type 2 diabetes and birth size, infant growth ...and age at adiposity rebound.
We carried out a longitudinal study of 8760 subjects born in Helsinki during 1934 to 1944. On average, they had 18 measurements of height and weight between birth and 12 years of age. In western countries BMI usually decreases after the age of 2 years and rises again at around 6 years--the so-called adiposity rebound. We defined age at adiposity rebound by the age of lowest BMI between one and 12 years. We identified people with Type 2 diabetes using a national register.
A total of 290 individuals developed Type 2 diabetes in adult life. The cumulative incidence of Type 2 diabetes decreased progressively from 8.6% in persons whose adiposity rebound occurred before the age of 5 years to 1.8% in those in whom it occurred after 7 years ( p<0.001). Early adiposity rebound was preceded by low weight gain between birth and 1 year ( p<0.001).
Large differences in the incidence of Type 2 diabetes are associated with growth rates in utero, weight gain in infancy and age at adiposity rebound.
Impulsiveness is a pivotal personality trait representing a core domain in all major personality inventories. Recently, impulsiveness has been identified as an important modulator of cognitive ...processing, particularly in tasks that require the processing of large amounts of information. Although brain imaging studies have implicated the prefrontal cortex to be a common underlying representation of impulsiveness and related cognitive functioning, to date a fine-grain and detailed morphometric analysis has not been carried out. On the basis of ahigh-resolution magnetic resonance scans acquired in 1620 healthy adolescents (IMAGEN), the individual cortical thickness (CT) was estimated. Correlations between Cloninger's impulsiveness and CT were studied in an entire cortex analysis. The cluster identified was tested for associations with performance in perceptual reasoning tasks of the Wechsler Intelligence Scale for Children (WISC IV). We observed a significant inverse correlation between trait impulsiveness and CT of the left superior frontal cortex (SFC; Monte Carlo Simulation P<0.01). CT within this cluster correlated with perceptual reasoning scores (Bonferroni corrected) of the WISC IV. On the basis of a large sample of adolescents, we identified an extended area in the SFC as a correlate of impulsiveness, which appears to be in line with the trait character of this prominent personality facet. The association of SFC thickness with perceptual reasoning argues for a common neurobiological basis of personality and specific cognitive domains comprising attention, spatial reasoning and response selection. The results may facilitate the understanding of the role of impulsiveness in several psychiatric disorders associated with prefrontal dysfunctions and cognitive deficits.