Different indices of fetal growth predict bone size and volumetric density at 4 years of age.

We have demonstrated previously that higher birth weight is associated with greater peak and later-life bone mineral content and that maternal body build, diet, and lifestyle influence prenatal bone mineral accrual. To examine prenatal influences on bone health further, we related ultrasound measures of fetal growth to childhood bone size and density. We derived Z-scores for fetal femur length and abdominal circumference and conditional growth velocity from 19 to 34 weeks' gestation from ultrasound measurements in participants in the Southampton Women's Survey.

Response to BMP4 signalling during ES cell differentiation defines intermediates of the ectoderm lineage.

The formation and differentiation of multipotent precursors underlies the generation of cell diversity during mammalian development. Recognition and analysis of these transient cell populations has been hampered by technical difficulties in accessing them in vivo. In vitro model systems, based on the differentiation of embryonic stem (ES) cells, provide an alternative means of identifying and characterizing these populations.

Weight gain in pregnancy and childhood body composition: findings from the Southampton Women's Survey.

Background: Intrauterine life may be a critical period for the programming of later obesity, but there is conflicting evidence about whether pregnancy weight gain is an important determinant of offspring adiposity.

Objective: The purpose of this study was to examine the relation of pregnancy weight gain with neonatal and childhood body composition.

Design: The participants (n = 948) were children born to women in the Southampton Women's Survey who had dual-energy X-ray absorptiometry measurements of body composition at birth, 4 y, or 6 y.

Microneedle-based intradermal delivery enables rapid lymphatic uptake and distribution of protein drugs.

Purpose: The purpose of this research was to examine the pharmacokinetics (PK) of drug uptake for microneedle-based intradermal (ID) delivery of several classes of protein drugs compared to standard subcutaneous (SC) administration.

Methods: Systemic absorption kinetics of various proteins were analyzed following microneedle-based ID delivery and standard injection methods in the swine model. Comparative PK data were determined using standard non-compartmental techniques based on blood serum levels.

Promoter control over foreign antigen expression in a murine cytomegalovirus vaccine vector.

Previous studies have reported on the development of a recombinant murine cytomegalovirus (rMCMV) containing the mouse zona pellucida 3 (mZP3) gene for use as a virally vectored immunocontraceptive (VVIC). This study aimed to alter promoter control over foreign antigen expression and cellular localisation of the antigen expressed in order to overcome virus attenuation previously encountered. Early studies reported on the mZP3 gene expressed by a strong constitutive human cytomegalovirus immediate-early 1 promoter (pHCMV IE1).

Canal cristae growth and fiber extension to the outer hair cells of the mouse ear require Prox1 activity.

Background: The homeobox gene Prox1 is required for lens, retina, pancreas, liver, and lymphatic vasculature development and is expressed in inner ear supporting cells and neurons.

Methodology/principal Findings: We have investigated the role of Prox1 in the developing mouse ear taking advantage of available standard and conditional Prox1 mutant mouse strains using Tg(Pax2-Cre) and Tg(Nes-Cre). A severe reduction in the size of the canal cristae but not of other vestibular organs or the cochlea was identified in the E18.

Osteoporosis: impact on health and economics.

Osteoporosis is a major public health problem through associated fragility fractures. The most common sites of fracture are the hip, spine and wrist, and these have an enormous health and economic impact. All fractures result in some degree of morbidity, but fractures at the hip are associated with the worst outcomes.

Maternal predictors of neonatal bone size and geometry: the Southampton Women's Survey.

Early growth is associated with later risk of osteoporosis and fractures. In this study, we aimed to evaluate the relationships between maternal lifestyle and body composition and neonatal bone size, geometry and density in the offspring. Participants were recruited from the Southampton Women's Survey, a unique prospective cohort of 12,500 initially non-pregnant women aged 20-34 years, resident in Southampton, UK.

Early life factors in the pathogenesis of osteoporosis.

Osteoporosis is a major public health burden through associated fragility fractures. Bone mass, a composite of bone size and volumetric density, increases through early life and childhood to a peak in early adulthood. The peak bone mass attained is a strong predictor of future risk of osteoporosis.

Session 2: Other diseases: Dietary management of osteoporosis throughout the life course.

Osteoporosis-related fractures have a major impact on health at the individual and societal levels, through associated morbidity and increased mortality. Up to 50% of women and 20% of men at age 50 years may have a fragility fracture in their remaining lifetimes. Nutrition is important throughout the life course.

Automated estimation of elder activity levels from anonymized video data.

Significant declines in quality of life for elders in assisted living communities are typically triggered by health events. Given the necessary information, such events can often be predicted, and thus, be avoided or reduced in severity. Statistics on activities of daily living and activity level over an extended period of time provide important data for functional assessment and health prediction.

Validation of a maternal questionnaire on correlates of physical activity in preschool children.

Background: Valid measures of physical activity correlates in preschool children are lacking. This study aimed to assess the validity, factor structure and internal consistency of a maternal questionnaire on potential correlates of four-year-old children's physical activity.

Methods: The questionnaire was designed to measure the following constructs: child personal factors; parental support and self-efficacy for providing support; parental rules and restrictions; maternal attitudes and perceptions; maternal behaviour; barriers to physical activity; and the home and local environments.

A genetic linkage map of Venturia inaequalis, the causal agent of apple scab.

Background: Venturia inaequalis is an economically-important disease of apple causing annual epidemics of scab worldwide. The pathogen is a heterothallic ascomycete with an annual cycle of sexual reproduction on infected apple leaf litter, followed by several cycles of asexual reproduction during the apple growing season. Current disease control is achieved mainly through scheduled applications of fungicides.

Overcoming innate host resistance to vaccination: employing a genetically distinct strain of murine cytomegalovirus avoids vector-mediated resistance to virally vectored immunocontraception.

The laboratory strain of murine cytomegalovirus (MCMV), K181, has been successfully engineered as a vaccine expressing murine zona pellucida 3 (mZP3) for viral vectored immunocontraception (VVIC) in mice. However, certain laboratory strains of mice are resistant to infection with K181 and therefore demonstrate resistance to VVIC. Cmv1 is the best characterised innate resistance mechanism to MCMV and was first described in C57BL/6 mice.

Low maternal vitamin D status and fetal bone development: cohort study.

Recent findings suggest that maternal vitamin D insufficiency during pregnancy has consequences for the offspring's bone health in later life. To investigate whether maternal vitamin D insufficiency affects fetal femur growth in ways similar to those seen in childhood rickets and study the timing during gestation of any effect of maternal vitamin D status, we studied 424 pregnant women within a prospective longitudinal study of maternal nutrition and lifestyle before and during pregnancy (Southampton Women's Survey). Using high-resolution 3D ultrasound, we measured fetal femur length and distal metaphyseal cross-sectional area, together with the ratio of femoral metaphyseal cross-sectional area to femur length (femoral splaying index).

Randomized controlled trial on the cardioprotective effect of bone marrow cells in patients undergoing coronary bypass graft surgery.

Aims: This randomized study investigates whether bone marrow cells (BMCs) can reduce ischaemic injury during cardiac surgery.

Methods And Results: Forty-four elective coronary artery bypass grafting patients were randomized to control group or BMCs group (whereby autologous BMCs were administered with each dose of cardioplegia antegradely into the coronaries). Troponin I and CK-MB were measured during the first 48 h after surgery and were not significantly different between the control and BMCs groups.

Developmental origins of osteoporosis: the role of maternal nutrition.

Osteoporosis is a major cause of morbidity and mortality through its association with age-related fractures. Although most effort in fracture prevention has been directed at retarding the rate of age-related bone loss, and reducing the frequency and severity of trauma among elderly people, evidence is growing that peak bone mass is an important contributor to bone strength during later life. The normal patterns of skeletal growth have been well characterised in cross-sectional and longitudinal studies.

Variations in infant feeding practice are associated with body composition in childhood: a prospective cohort study.

Context: Most studies of infant diet and later body composition focus on milk feeding; few consider the influence of variations in the weaning diet.

Objective: Our objective was to examine how variations in milk feeding and the weaning diet relate to body composition at 4 yr.

Study Population: A total of 536 children participating in a prospective birth cohort study.

Breast-feeding and adherence to infant feeding guidelines do not influence bone mass at age 4 years.

The impact of variations in current infant feeding practice on bone mineral accrual is not known. We examined the associations between duration of breast-feeding and compliance with infant dietary guidelines and later bone size and density at age 4 years. At total of 599 (318 boys) mother-child pairs were recruited from the Southampton Women's Survey.

Prox1 maintains muscle structure and growth in the developing heart.

Impaired cardiac muscle growth and aberrant myocyte arrangement underlie congenital heart disease and cardiomyopathy. We show that cardiac-specific inactivation of the murine homeobox transcription factor Prox1 results in the disruption of expression and localisation of sarcomeric proteins, gross myofibril disarray and growth-retarded hearts. Furthermore, we demonstrate that Prox1 is required for direct transcriptional regulation of the genes encoding the structural proteins alpha-actinin, N-RAP and zyxin, which collectively function to maintain an actin-alpha-actinin interaction as the fundamental association of the sarcomere.

Contact factor deficiencies and cardiopulmonary bypass surgery: detection of the defect and monitoring of heparin.

Contact factor pathway deficiencies do not cause surgical bleeding but make heparin monitoring by the activated partial thromboplastin time (APTT) and activated clotting time (ACT) unreliable. Heparin monitoring during cardiopulmonary bypass (CPB) surgery in these patients is particularly challenging. Here we describe heparin monitoring during CPB using the chromogenic anti Xa assay in two patients with severe factor XII deficiency (FXII < 0.

Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity.

The activity of the homeobox gene Prox1 is necessary and sufficient for venous blood endothelial cells (BECs) to acquire a lymphatic endothelial cell (LEC) fate. We determined that the differentiated LEC phenotype is a plastic, reprogrammable condition that depends on constant Prox1 activity for its maintenance. We show that conditional down-regulation of Prox1 during embryonic, postnatal, or adult stages is sufficient to reprogram LECs into BECs.

The impact of discredited evidence.

How do people revise their beliefs when evidence is discredited? In three studies, mock jurors read simplified criminal cases and then judged the probability that a suspect was guilty on the basis of sequentially presented evidence. Study 1 showed an extension effect: When two items of incriminating evidence were presented, a subsequent discrediting of the second item also lessened belief in the first item, irrespective of whether it was directly related to the discredited item. Study 2 showed that this effect depended on the order of evidence presentation: When the discrediting evidence was presented early, rather than late, in the sequence, there was no extension to unrelated items.

Post-fracture management of patients with hip fracture: a perspective.

Background: Hip fracture creates a worldwide morbidity, mortality and economic burden. After surgery, many patients experience long-term disability or die as a consequence of the fracture. A fracture is a major risk factor for a subsequent fracture, which may occur within a short interval.