A Measurement of the Proton Structure Function F ⁣2(x,Q2)F_{\!2}(x,Q^2)

A measurement of the proton structure function $F_{\!2}(x,Q^2)$ is reported for momentum transfer squared $Q^2$ between 4.5 $GeV^2$ and 1600 $GeV^2$ and for Bjorken $x$ between $1.8\cdot10^{-4}$ and 0.13 using data collected by the HERA experiment H1 in 1993. It is observed that $F_{\!2}$ increases significantly with decreasing $x$, confirming our previous measurement made with one tenth of the data available in this analysis. The $Q^2$ dependence is approximately logarithmic over the full kinematic range covered. The subsample of deep inelastic events with a large pseudo-rapidity gap in the hadronic energy flow close to the proton remnant is used to measure the "diffractive" contribution to $F_{\!2}$.Comment: 32 pages, ps, appended as compressed, uuencoded fil

Fetal growth and programming of the hypothalamic-pituitary-adrenal axis

1. Epidemiological studies have shown that small size at birth is associated with an increased risk of coronary heart disease and its risk factors, including hypertension and type 2 diabetes.2. It is suggested that these observed links between low birthweight with disease result from an imbalance between fetal nutrient demand and supply. This imbalance results in metabolic and endocrine adaptations that benefit the fetus in the short term by reducing fetal growth and increasing fuel availability but, in the longer term, are maladaptive, leading to an increased risk of coronary heart disease.3. Experimental data in animals and recent human observations have suggested that an alteration in the set point of the hypothalamic–pituitary–adrenal axis is an important long-term change that occurs in association with reduced fetal growth.4. These data raise the possibility that the nature and amplitude of the stress response may be determined by intra-uterine factors

Endocrine programming and fetal origins of adult disease

Low birthweight and other indices of reduced fetal growth are associated with a raised prevalence of cardiovascular disease in adult life and its antecedents, including raised blood pressure, glucose intolerance and dyslipidaemia

The effects of sex and hormonal status on the physiological response to acute psychosocial stress

Whether one is male or female is one of the most important determinants of human health. While males are more susceptible to cardiovascular and infectious disease, they are outnumbered by women for many autoimmune disorders, fibromyalgia and chronic pain. Recently, individual differences in the physiological response to stress have emerged as a potentially important risk factor for these disorders. This raises the possibility that sex differences in prevalence of disease could at least in part be explained by sex differences in the nature of the physiological response to stress. In a psychophysiological laboratory, the autonomic nervous system response can be provoked by many different stressors including physical, mental and psychosocial tasks, while the hypothalamic-pituitary-adrenal axis (HPAA) response seems to be more specific to a psychosocial challenge incorporating ego involvement. The responses of both systems to different psychosocial challenges have been subject to extensive research, although in respect of sex differences the HPAA response has probably been more systematically studied. In this review, we focus on sex differences in HPAA and autonomic nervous system responses to acute psychosocial stress. Although some differences are dependent on the stressor used, the responses of both systems show marked and consistent differences according to sex, with the phase of the menstrual cycle, menopausal status and pregnancy having marked effects. Between puberty and menopause, adult women usually show lower HPAA and autonomic responses than men of same age. However, the HPAA response is higher in the luteal phase, when for example poststress free cortisol levels approach those of men. After menopause, there is an increase in sympathoadrenal responsiveness, which is attenuated during oral hormone replacement therapy, with most evidence suggesting that HPAA activity shows the same trends. Interestingly, pregnancy is associated with an attenuated response of the sympathoadrenal and HPAA systems at least as assessed by biochemical stimulation. It is likely that these sex differences in autonomic function are a result of estrogen exposure which attenuates sympathoadrenal responsiveness. The HPAA is however somewhat more complex and evidence now suggests the influence of other modifiers such as arginine vasopressin (AVP) and the regulation of circulating cortisol bioavailability by corticosteroid-binding globulin (CBG). The pronounced and multi-faceted sex differences in stress responsiveness suggest that they are a product of a strong evolutionary pressure. We hypothesise that this has to a great deal been driven by the need to protect the fetus from the adverse effects of maternal stress responses, in particular excess glucocorticoid exposure. Studying this hypothesis may have a fundamental impact on our understanding about how adult health is set during early life and how adult disease could be prevented in men and women

Fetal origins of mental health: evidence and mechanisms

The concept of fetal programming states that changes in the fetal environment during sensitive periods of organ development may cause long-lasting changes in the structure and functioning of these organs later in life and influence the risk for chronic diseases such as coronary heart disease and type 2 diabetes. Fetal growth is a summary marker of the fetal environment and is reflected by relatively easy-to-obtain measures of size at birth such as birthweight. In the last two decades, a body of evidence emerged linking fetal growth with behavioural and mental health outcomes later in life. Cognitive functioning and behavioural problems in childhood, in particular inattention/hyperactivity, have been shown to be inversely related to fetal growth. Although results are mixed, risk for personality disorders and schizophrenia seems to be linked with fetal growth and adversity, while the evidence for mood disorders is weak. Vulnerability for psychopathology may also be influenced by prenatal adversity. There is evidence for associations of fetal growth with temperament in childhood as well as stress reactivity and distress. The associations of fetal growth with mental health later in life are potentially caused by specific prenatal factors such as maternal smoking, alcohol, toxins/drugs, nutrition, psychosocial stress and infection during pregnancy. The mechanisms likely involve changes in neurodevelopment and in the set point of neuroendocrine systems, and there is evidence that prenatal adversity interacts with genetic and postnatal environmental factors. Future studies should examine the effects of specific prenatal factors and attempt to disentangle genetic and prenatal environmental effects

Minireview: transgenerational inheritance of the stress response: a new frontier in stress research

It is well established in animal models that the prenatal environment can have a major impact on stress axis function throughout life. These changes can predispose to various metabolic, cardiovascular, and neurobiological pathophysiologies. Emerging evidence indicates that the same programming effects occur in humans. It is now becoming clear that the pathophysiological effects are not confined to the first-generation offspring and that there is transgenerational memory of fetal experience that can extend across multiple generations. The complex mechanisms by which transgenerational transmission of stress responsiveness occur are rapidly becoming a focus of investigation. Understanding these fundamental biological processes will allow for development of intervention strategies that prevent or reverse adverse programming of the stress response

Is perinatal neuroendocrine programming involved in the developmental origins of metabolic disorders?

The discovery that small size at birth and during infancy are associated with a higher risk of diabetes and related metabolic disease in later life has pointed to the importance of developmental factors in these conditions. The birth size associations are thought to reflect exposure to adverse environmental factors during early development but the mechanisms involved are still not fully understood. Animal and human work has pointed to the importance of changes in the set-point of a number of key hormonal systems controlling growth and development. These include the IGF-1/GH axis, gonadal hormones and, in particular, the systems mediating the classical stress response. Several studies show that small size at birth is linked with increased activity of the hypothalamic-pituitary-adrenal axis and sympathoadrenal system in adult life. More recent human studies have shown associations between specific adverse experiences during pregnancy, such as famine or the consumption of adverse diets, and enhanced stress responses many decades later. The mediators of these neuroendocrine responses are biologically potent and are likely to have a direct influence on the risk of metabolic disease. These neuroendocrine changes may also have an evolutionary basis being part of broader process, termed phenotypic plasticity, by which adverse environmental cues experienced during development modify the structure and physiology of the adult towards a phenotype adapted for adversity. The changes are clearly advantageous if they lead to a phenotype which is well-adapted for the adult environment, but may lead to disease if there is subsequent overnutrition or other unexpected environmental conditions

Size at birth and motor activity during stress in children aged 7-9 years

Objective: Small size at birth is linked with metabolic and cardiovascular disease. There is increasing evidence that it is also linked with physiological stress responses and abnormal behaviour, in particular symptoms of hyperactivity. We therefore investigated associations between size at birth and motor activity during psychosocial stress.Methods: In 123 children aged 7-9 years, we examined the relations of birth weight, head circumference, length and ponderal index at birth with motor activity upon exposure to both stress and non-stress situations. Videos were recorded while the children performed a story and a maths task in front of an audience (stress) and watched a movie (non-stress); motor activity was defined as lifting or tilting of a foot.Results: Children who had had a smaller head circumference at birth demonstrated greater motor activity during the stress test. There were marked gender differences in the results. In boys, lower birth weight, head circumference and ponderal index were associated with greater motor activity during the stress test, but not associated with motor activity during the non-stress situation. The findings remained significant when potential confounding variables were controlled for. There were no associations in girls.Conclusions: The findings suggest long-term effects of an adverse fetal environment on the behavioural stress response in boys, and parallel similar sex-specific effects on different stress response systems in humans and animals. The results could reflect permanent alterations of dopaminergic neurotransmission and have implications for the etiology of clinical hyperactivity