.
Current orthodoxy states that coronary heart disease results from the unhealthy lifestyles of westernized adults together with a contribution from genetic inheritance. This does not provide a ...secure basis for prevention of the disease. Geographical studies gave the first clue that the disease originates during intra‐uterine development. Variations in mortality from the disease across England and Wales were shown to correlate closely with past differences in death rates among newborn babies. In the past most deaths among newborns were attributed to low birthweight. This led to the hypothesis that undernutrition in utero permanently changes the body's structure, function and metabolism in ways that lead to coronary heart disease in later life. The association between low birthweight and coronary heart disease has been confirmed in longitudinal studies of men and women around the world. The developmental model of the origins of the disease offers a new way forward.
Abstract Particular paths of fetal growth are now known to predict a range of disorders in adult life. This is thought to reflect fetal programming, the phenomenon whereby nutrition and other ...influences during development set the body's organs and systems for life. The thesis of this review is that normal variations in the processes of placental development lead to variations in the supply of nutrients to the fetus and programme a small number of key systems that are linked to later disease. A baby's growth and nutrition depend both on the function of the placenta, reflected in its gross morphology at birth, and on the mother's lifetime nutrition, reflected in her height and weight. In many studies, the effects of placental size and shape on later disease have been examined within different categories of mother's body size. The review shows that variations in gross placental morphology at birth predict a wide range of disorders in later life. Any particular placental phenotype seems to predict a limited number of diseases. Further research into the links between the processes of placentation and the morphology of the placenta at birth is now required. We need to know more about the relative importance of nutrient flow, nutrient balance and the timing of nutritional events in determining disorders in later life. We also need to understand why, compared to other placental mammals, the human placenta is so variable in its morphology and functional capacity.
We describe the development and testing of the hybrid ensemble/4D‐Var global data assimilation system that was implemented operationally at the Met Office in July 2011, giving an average reduction of ...RMS errors of just under 1%. The scheme uses the extended control variable technique to implement a hybrid background error covariance that combines the standard climatological covariance with a covariance derived from the 23‐member operational ensemble MOGREPS‐G. Unique features of the Met Office scheme include application of a horizontal ‘anti‐aliasing’ filter to the ensemble error modes, a vertical localization scheme based uniquely on a modification of the climatological stream function covariance, and inflation of the climatological covariance to maintain the analysis fit to observations. Findings during development include a significantly greater impact of the scheme in 3D‐Var than 4D‐Var, a clear positive impact from the combination of the anti‐aliasing filter and vertical localization, and a relatively small sensitivity to full coupling of the ensemble and 4D‐Var systems. Supplementary experiments suggest that the ability of the ensemble to capture coherent ‘Errors of the Day’ is key to the improvements in forecast skill.
A particular problem encountered during development was significantly poorer tropical verification scores when measured against own analyses. In contrast, verification against independent (ECMWF) analyses gave scores that were much more consistent with those against observations.
Developmental or fetal programming has emerged as a major model for understanding the early and persisting effects of prenatal exposures on the health and development of the child and adult. We ...leverage the power of a 14-year prospective study to examine the persisting effects of prenatal anxiety, a key candidate in the developmental programming model, on symptoms of behavioral and emotional problems across five occasions of measurement from age 4 to 13 years. The study is based on the Avon Longitudinal Study of Parents and Children cohort, a prospective, longitudinal study of a large community sample in the west of England (n = 7,944). Potential confounders included psychosocial and obstetric risk, postnatal maternal mood, paternal pre- and postnatal mood, and parenting. Results indicated that maternal prenatal anxiety predicted persistently higher behavioral and emotional symptoms across childhood with no diminishment of effect into adolescence. Elevated prenatal anxiety (top 15%) was associated with a twofold increase in risk of a probable child mental disorder, 12.31% compared with 6.83%, after allowing for confounders. Results were similar with prenatal depression. These analyses provide some of the strongest evidence to date that prenatal maternal mood has a direct and persisting effect on her child's psychiatric symptoms and support an in utero programming hypothesis.
The North American distributional potential of the recently invaded tick, Haemaphysalis longicornis, was estimated using occurrence data from its geographic range in other parts of the world and ...relevant climatic data sets. Several hundred candidate models were built using a correlative maximum entropy approach, and best-fitting models were selected based on statistical significance, predictive ability, and complexity. The median of the best-fitting models indicates a broad potential distribution for this species, but restricted to three sectors-the southeastern United States, the Pacific Northwest, and central and southern Mexico.
Research suggests that physical education (PE) in Western countries is not providing equitable experiences for non-white students. Responsibility for shortcomings has often been ascribed to white PE ...teachers. Scholars have claimed that teachers lack cultural competence and know little about how physical cultures or health are understood by the young people with whom they work. The objective of this investigation was to investigate this claim and generate an understanding of how white PE teachers in a culturally diverse high school make sense of their work with non-white students. Data with three Swedish teachers of varying experience were produced using semi-structured interviewing. A series of school visits provided a complementary line of data. Four themes emerged from the data. These related to: (1) differences between white and non-white values; (2) the knowledge and dispositions necessary for success in PE; (3) the broad purpose of PE, and; (4) the differences between boys' and girls' experiences of PE. Data were interpreted using a Critical Race Theory (CRT) perspective, with the notion of 'whiteness' providing a specific analytic concept. The general thesis developed in the second part of the paper is that problems result not from insensitivity or incompetence but from discourses of whiteness in which many teachers live and work. By building on critical research both in general education and physical education literature and by utilizing whiteness as an analytical concept, the investigation shows how three PE teachers draw extensively on the racial discourse of whiteness and how this disadvantages non-white students. The paper is concluded with a consideration of how racial disadvantage could be challenged or disrupted.
Voltage ratings for HVdc point-to-point connections are not standardized and tend to depend on the latest available cable technology. DC/DC conversion at HV is required for interconnection of such ...HVdc schemes as well as to interface dc wind farms. Modular multilevel voltage source converters (VSCs), such as the modular multilevel converter (MMC) or the alternate arm converter (AAC), have been shown to incur significantly lower switching losses than previous two- or three-level VSCs. This paper presents a dc/ac/dc system using a transformer coupling two modular multilevel VSCs. In such a system, the capacitors occupy a large fraction of the volume of the cells but a significant reduction in volume can be achieved by raising the ac frequency. Using high frequency can also bring benefits to other passive components such as the transformer but also results in higher switching losses due to the higher number of waveform steps per second. This leads to a tradeoff between volume and losses which has been explored in this study and verified by simulation results with a transistor level model of 30-MW case study. The outcome of the study shows that a frequency of 350 Hz provides a significant improvement in volume but also a penalty in losses compared to 50 Hz.
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
Summary Coronary heart disease, type 2 diabetes, breast cancer and many other chronic diseases are unnecessary. Their occurrence is not mandated by genes passed down to us through thousands of years ...of evolution. Chronic diseases are not the inevitable lot of humankind. They are the result of the changing pattern of human development. We could readily prevent them, had we the will to do so. Prevention of chronic disease, and an increase in healthy ageing require improvement in the nutrition of girls and young women. Many babies in the womb in the Western world today are receiving unbalanced and inadequate diets. Many babies in the developing world are malnourished because their mothers are chronically malnourished. Protecting the nutrition and health of girls and young women should be the cornerstone of public health. Not only will this prevent chronic disease, but it will produce new generations who have better health and well-being through their lives.
PDF
