MicroRNAs in a hypertrophic heart: from foetal life to adulthood

The heart is the first organ to form and undergoes adaptive remodelling with age. Ventricular hypertrophy is one such adaptation, which allows the heart to cope with an increase in cardiac demand. This adaptation is necessary as part of natural growth from foetal life to adulthood. It may also occur in response to resistance in blood flow due to various insults on the heart and vessels that accumulate with age. The heart can only compensate to this increase in workload to a certain extent without losing its functional architecture, ultimately resulting in heart failure. Many genes have been implicated in cardiac hypertrophy, however none have been shown conclusively to be responsible for pathological cardiac hypertrophy. MicroRNAs offer an alternative mechanism for cellular regulation by altering gene expression. Since 1993 when the function of a non-coding DNA sequence was first discovered in the model organism Caenorhabditis elegans, many microRNAs have been implicated in having a central role in numerous physiological and pathological cellular processes. The level of control these antisense oligonucleotides offer can often be exploited to manipulate the expression of target genes. Moreover, altered levels of microRNAs can serve as diagnostic biomarkers, with the prospect of diagnosing a disease process as early as during foetal life. Therefore, it is vital to ascertain and investigate the function of microRNAs that are involved in heart development and subsequent ventricular remodelling. Here we present an overview of the complicated network of microRNAs and their target genes that have previously been implicated in cardiogenesis and hypertrophy. It is interesting to note that microRNAs in both of these growth processes can be of possible remedial value to counter a similar disease pathophysiology.

Factors associated with common mental disorders during the transition to adulthood : do emerging adults and ‘early starters’ differ? Findings from an Australian birth cohort study

Background: Despite increasing diversity in pathways to adulthood, choices available to young people are influenced by environmental, familial and individual factors, namely access to socioeconomic resources, family support and mental and physical health status. Young people from families with higher socioeconomic position (SEP) are more likely to pursue tertiary education and delay entry to adulthood, whereas those from low socioeconomic backgrounds are less likely to attain higher education or training, and more likely to partner and become parents early. The first group are commonly termed ‘emerging adults’ and the latter group ‘early starters’. Mental health disorders during this transition can seriously disrupt psychological, social and academic development as well as employment prospects. Depression, anxiety and most substance use disorders have early onset during adolescence and early adulthood with approximately three quarters of lifetime psychiatric disorders having emerged by 24 years of age. Aims: This thesis aimed to explore the relationships between mental health, sociodemographic factors and family functioning during the transition to adulthood. Four areas were investigated: 1) The key differences between emerging adults and ‘early starters’, were examined and focused on a series of social, economic, and demographic factors as well as DSM-IV diagnoses; 2) Methodological issues associated with the measurement of depression and anxiety in young adults were explored by comparing a quantitative measure of symptoms of anxiety and depression (Achenbach’s YSR and YASR internalising scales) with DSM-IV diagnosed depression and anxiety. 3) The association between family SEP and DSM-IV depression and anxiety was examined in relation to the different pathways to adulthood. 4) Finally, the association between pregnancy loss, abortion and miscarriage, and DSM-IV diagnoses of common psychiatric disorders was assessed in young women who reported early parenting, experiencing a pregnancy loss, or who had never been pregnant. Methods: Data were taken from the Mater University Study of Pregnancy (MUSP), a large birth cohort started in 1981 in Brisbane, Australia. 7223 mothers and their children were assessed five times, at 6 months, 5, 14 and 21 years after birth. Over 3700 young adults, aged 18 to 23 years, were interviewed at the 21-year phase. Respondents completed an extensive series of self-reported questionnaires and a computerised structured psychiatric interview. Three outcomes were assessed at the 21-year phase. Mental health disorders diagnosed by a computerised structured psychiatric interview (CIDI-Auto), the prevalence of DSM-IV depression, anxiety and substance use disorders within the previous 12-month, during the transition (between ages of 18 and 23 years) or lifetime were examined. The primary outcome “current stage in the transition to adulthood” was developed using a measure conceptually constructed from the literature. The measure was based on important demographic markers, and these defined four independent groups: emerging adults (single with no children and living with parents), and three categories of ‘early starter’, singles (with no children or partner, living independently), those with a partner (married or cohabitating but without children) and parents. Early pregnancy loss was assessed using a measure that also defined four independent groups and was based on pregnancy outcomes in the young women This categorised the young women into those who were never pregnant, women who gave birth to a live child, and women who reported some form of pregnancy loss, either an abortion or a spontaneous miscarriage. A series of analyses were undertaken to test the study aims. Potential confounding and mediating factors were prospectively measured between the child’s birth and the 21-year phase. Binomial and multinomial logistic regression was used to estimate the risk of relevant outcomes, and the associations were reported as odds ratios (OR) and 95% confidence intervals (95%CI). Key findings: The thesis makes a number of important contributions to our understanding of the transition to adulthood, particularly in relation to the mental health consequences associated with different pathways. Firstly, findings from the thesis clearly showed that young people who parented or partnered early fared worse across most of the economic and social factors as well as the common mental disorders when compared to emerging adults. That is, young people who became early parents were also more likely to experience recent anxiety (OR=2.0, 95%CI 1.5-2.8) and depression (OR=1.7, 95%CI 1.1-2.7) than were emerging adults after taking into account a range of confounding factors. Singles and those partnering early also had higher rates of lifetime anxiety and depression than emerging adults. Young people who partnered early, but were without children, had decreased odds of recent depression; this may be due to the protective effect of early marriage against depression. It was also found that young people who form families early had an increased risk of cigarette smoking (parents OR=3.7, 95%CI 2.9-4.8) compared to emerging adults, but not heavy alcohol (parents OR=0.4, 95%CI 0.3-0.6) or recent illicit drug use. The high rates of cigarette smoking and tobacco use disorders in ‘early starters’ were explained by common risk factors related to early adversity and lower SEP. Having a child and early marriage may well function as a ‘turning point’ for some young people, it is not clear whether this is due to a conscious decision to disengage from a previous ‘substance using’ lifestyle or simply that they no longer have the time to devote to such activities because of child caring. In relation to the methodological issues associated with assessing common mental disorders in young adults, it was found that although the Achenbach empirical internalising scales successfully predicted both later DSM-IV depression (YSR OR=2.3, 95%CI 1.7-3.1) and concurrently diagnosed depression (YASR OR=6.9, 95%CI 5.0- 9.5) and anxiety (YASR OR=5.1, 95%CI 3.8- 6.7), the scales discriminated poorly between young people with or without DSM-IV diagnosed mood disorder. Sensitivity values (the proportion of true positives) for the internalising scales were surprisingly low. Only a third of young people with current DSM-IV depression (range for each of the scales was between 34% to 42%) were correctly identified as cases by the YASR internalising scales, and only a quarter with current anxiety disorder (range of 23% to 31%) were correctly identified. Also, use of the DSM-oriented scales increased sensitivity only marginally (for depression between 2-8%, and anxiety between 2-6%) above the standard Achenbach scales. This is despite the fact that the DSM-oriented scales were originally developed to overcome the poor prediction of DSM-IV diagnoses by the Achenbach scales. The internalising scales, both standard and DSM-oriented, were much more effective at identifying young people with comorbid depression and anxiety, with OR’s 10.1 to 21.7 depending on the internalising scale used. SEP is an important predictor of both an early transition to adulthood and the experience of anxiety during that time Family income during adolescence was a strong predictor of early parenting and partnering before age 24 but not early independent living. Compared to families in the upper quintile, young people from families with low income were nearly twice as likely to live with a partner and four times more likely to become parents (OR ranged from 2.6 to 4.0). This association remained after adjusting for current employment and education level. Children raised in low income families were 30% more likely to have an anxiety disorder (OR=1.3, 95%CI 0.9-1.9), but not depression, as young adults when compared to children from wealthier families. Emerging adults and ‘early starters’ from low income families did not differ in their likelihood of having a later anxiety disorder. Young women reporting a pregnancy loss had nearly three times the odds of experiencing a lifetime illicit drug disorder (excluding cannabis) [abortion OR=3.6, 95%CI 2.0-6.7 and miscarriage OR=2.6, 95%CI 1.2-5.4]. Abortion was associated with alcohol use disorder (OR=2.1, 95%CI 1.3- 3.5) and 12-month depression (OR=1.9, 95%CI 1.1- 3.1). These finding suggest that the association identified by Fergusson et al between abortion and later psychiatric disorders in young women may be due to pregnancy loss and not to abortion, per se. Conclusion: Findings from this thesis support the view that young people who parent or partner early have a greater burden of depression and anxiety when compared to emerging adults. As well, young women experiencing pregnancy loss, from either abortion or miscarriage, are more likely to experience depression and anxiety than are those who give birth to a live infant or who have never been pregnant. Depression, anxiety and substance use disorders often go unrecognised and untreated in young people; this is especially true in young people from lower SEP. Early identification of these common mental health disorders is important, as depression and anxiety experienced during the transition to adulthood have been found to seriously disrupt an individual’s social, educational and economic prospects in later life.

Quality of life of women with lower limb swelling or lymphedema 3-5 years following endometrial cancer

Objective To quantitatively assess and compare the quality of life (QoL) of women with a self-reported diagnosis of lower limb lymphedema (LLL), to women with lower limb swelling (LLS), and to women without LLL or LLS following treatment for endometrial cancer. Methods 1399 participants in the Australian National Endometrial Cancer Study were sent a follow-up questionnaire 3–5 years after diagnosis. Women were asked if they had experienced swelling in the lower limbs and, if so, whether they had received a diagnosis of lymphedema by a health professional. The 639 women who responded were categorised as: Women with LLL (n = 68), women with LLS (n = 177) and women without LLL or LLS (n = 394). Multivariable-adjusted generalized linear models were used to compare women’s physical and mental QoL by LLL status. Results On average, women were 65 years of age and 4 years after diagnosis. Women with LLL had clinically lower physical QoL (M= 41.8, SE= 1.4) than women without LLL or LLS (M= 45.1, SE= 0.8, p = .07), however, their mental QoL was within the normative range (M= 49.6; SE= 1.1 p = 1.0). Women with LLS had significantly lower physical (M= 41.0, SE= 1.0, p = .003) and mental QoL (M= 46.8; SE= 0.8, p < .0001) than women without LLL or LLS (Mental QoL: M= 50.6, SE= 0.8). Conclusion Although LLL was associated with reductions in physical QoL, LLS was related to reductions in both physical and mental QoL 3-5 years after cancer treatment. Early referral to evidence-based lymphedema programs may prevent long-term impairments to women’s QoL.

FluMum : a prospective cohort study of mother-infant pairs assessing the effectiveness of maternal influenza vaccination in prevention of influenza in early infancy

INTRODUCTION Influenza vaccination in pregnancy is recommended for all women in Australia, particularly those who will be in their second or third trimester during the influenza season. However, there has been no systematic monitoring of influenza vaccine uptake among pregnant women in Australia. Evidence is emerging of benefit to the infant with respect to preventing influenza infection in the first 6 months of life. The FluMum study aims to systematically monitor influenza vaccine uptake during pregnancy in Australia and determine the effectiveness of maternal vaccination in preventing laboratory-confirmed influenza in their offspring up to 6 months of age. METHODS AND ANALYSIS A prospective cohort study of 10 106 mother-infant pairs recruited between 38 weeks gestation and 55 days postdelivery in six Australian capital cities. Detailed maternal and infant information is collected at enrolment, including influenza illness and vaccination history with a follow-up data collection time point at infant age 6 months. The primary outcome is laboratory-confirmed influenza in the infant. Case ascertainment occurs through searches of Australian notifiable diseases data sets once the infant turns 6 months of age (with parental consent). The primary analysis involves calculating vaccine effectiveness against laboratory-confirmed influenza by comparing the incidence of influenza in infants of vaccinated mothers to the incidence in infants of unvaccinated mothers. Secondary analyses include annual and pooled estimates of the proportion of mothers vaccinated during pregnancy, the effectiveness of maternal vaccination in preventing hospitalisation for acute respiratory illness and modelling to assess the determinants of vaccination. ETHICS AND DISSEMINATION The study was approved by all institutional Human Research Ethics Committees responsible for participating sites. Study findings will be published in peer review journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER The study is registered with the Australia and New Zealand Clinical Trials Registry (ANZCTR) number: 12612000175875.

Pathways to health : Determinants of health, health behaviour and health inequalities in early adulthood

There is increasing evidence that the origins of poor adult health and health inequalities can be traced back to circumstances preceding current socioeconomic position and living conditions. The life-course approach to examining the determinants of health has emphasised that exposure to adverse social and economic circumstances in earlier life or concurrent adverse circumstances due to unfavourable living conditions in earlier life may lead to poor health, health-damaging behaviour, disease or even premature death in adulthood. There is, however, still a lack of knowledge about the contribution of social and economic circumstances in childhood and youth to adult health and health inequalities, and even less is known about how environmental and behavioural factors in adulthood mediate the effects of earlier adverse experiences. The main purpose of this study was to deepen our understanding of the development of poor health, health-damaging behaviours and health inequalities during the life-course. Its aim was to find out which factors in earlier and current circumstances determine health, the most detrimental indicators of health behaviour (smoking, heavy drinking and obesity as a proxy for the balance between nutrition and exercise), and educational health differences in young adults in Finland. Following the ideas of the social pathway theory, it was assumed that childhood environment affects adult health and its proximal determinants via different pathways, including educational, work and family careers. Early adulthood was studied as a significant phase of life when many behavioural patterns and living conditions relevant to health are established. In addition, socioeconomic health inequalities seem to emerge rapidly when moving into adulthood; they are very small or non-existent in childhood and adolescence, but very marked by early middle age. The data of this study were collected in 2000 2001 as part of the Health 2000 Survey (N = 9,922), a cross-sectional and nationally representative health interview and examination survey. The main subset of data used in this thesis was the one comprising the age group 18 29 years (N = 1,894), which included information collected by standardised structured computer-aided interviews and self-administered questionnaires. The survey had a very high participation rate at almost 90% for the core questions. According to the results of this study, childhood circumstances predict the health of young adults. Almost all the childhood adversities studied were found to be associated with poor self-rated health and psychological distress in early adulthood, although fewer associations were found with the somatic morbidity typical of young adults. These effects seemed to be more or less independent of the young adult s own education. Childhood circumstances also had a strong effect on smoking and heavy drinking, although current circumstances and education in particular, played a role in mediating this effect. Parental smoking and alcohol abuse had an influence on the corresponding behaviours of offspring. Childhood circumstances had a role in the development of obesity and, to a lesser extent, overweight, particularly in women. The findings support the notion that parental education has a strong effect on early adult obesity, even independently of the young adult s own educational level. There were marked educational differences in self-rated health in early adulthood: those in the lowest educational category were most likely to have average or poorer health. Childhood social circumstances seemed to explain a substantial part of these educational differences. In addition, daily smoking and heavy drinking contributed substantially to educational health differences. However, the contribution of childhood circumstances was largely shared with health behaviours adopted by early adulthood. Employment also shared the effects of childhood circumstances on educational health differences. The results indicate that childhood circumstances are important in determining health, health behaviour and health inequalities in early adulthood. Early recognition of childhood adversities followed by relevant support measures may play an important role in preventing the unfortunate pathways leading to the development of poor health, health-damaging behaviour and health inequalities. It is crucially important to recognise the needs of children living in adverse circumstances as well as children of substance abusing parents. In addition, single-parent families would benefit from support. Differences in health and health behaviours between different sub-groups of the population mean that we can expect to see ever greater health differences when today s generation of young adults grows older. This presents a formidable challenge to national health and social policy as well as health promotion. Young adults with no more than primary level education are at greatest risk of poor health. Preventive policies should emphasise the role of low educational level as a key determinant of health-damaging behaviours and poor health. Keywords: health, health behaviour, health inequalities, life-course, socioeconomic position, education, childhood circumstances, self-rated health, psychological distress, somatic morbidity, smoking, heavy drinking, BMI, early adulthood

Topeliaaninen usko : Kirjailija Sakari Topelius uskontokasvattajana

ABSTRACT The author Zacharias Topelius as a religious educator The present study concerns the author Zacharias Topelius (1818-98) as a religious educator. The study´s main questions are as follows: What is the theological and pedagogical content of Topelius books and how is his religious instruction linked with the history of his time. The primary sources are his educational books Naturens bok (The Book of the Nature, 1856), Boken om vårt land (The Book of our Land, 1875) and Evangelium för Barnen (Gospel for Children, 1893), as well as his storybooks Läsning för barn I-VIII (Reading for Children I-VIII, 1865-96). The dissertation concerns the his-tory of religious education. Its primary method is background-based systematic analy-sis. In Topelius children s books the view of God is characterised both as an omnipresent spirit and as Providence, who guides world history according to his plan. In addition to Lutheranism this view is also influenced by Nationalism and Romanticism. The theological content of the books emphasises instruction in Christian life that is natural to normative children s books. Topelius strongly expresses the importance of a personal relationship to God, an idealistic Christian view of one s fellow man and of one s own nation as well as the value of nature conservation. The books of Topelius were some of the first educational works on nature preservation in Finland. The didactic quality of Topelius children s books was high for 19th century Finland. Their main emphasis in terms of educational goals is on civilisation (Bildung), self-awareness, national solidarity and living idealism. The pedagogical argumentation is mostly based on theological, historical, social and rational reasoning. The primary principles in Topelius teaching are Christian nationalism, idealistic harmony and the agrarian bourgeois. Christian nationalism is the main element of Topelius religious education. He considers the fatherland as a God-given project and the taking care of it as a part of holy service. Idealistic harmony is seen as the comprehensive development of one s character in the sense of romantic idealism. The agrarian bourgeois principle combines the Finnish peasant tradition with the values of 19th century modern bourgeois culture. I have named Topelius vision of religious education the Christian national project of civilisation (Bildung). Its main theses are home, religion and fatherland. The author himself strongly believed in this vision and never questioned it despite its national chauvinism and theological inconsistency. The religious ideology represented in Topelius educational works and storybooks was popular among pedagogues during the whole era of the Finnish folk school. It fit per-fectly with the Christian national discourse stemming from 19th century ideological ten-dencies. Due to their appropriate content combined with their practical language and pedagogical methods, the books were popular both at school and in the home for a long period of time. Therefore the books of Topelius aptly symbolise the religious education of their time and manifest their author s pedagogical talent as a national religious educator and as a populariser of Christian nationalism. Topelius books have had a lasting influence on Finnish religiosity. Key words: Topelius, theology, religion, education, nationalism and national project

A Chronological Framework for the Period 208 BC to AD 600

The period, from the Iron Age through to what is sometimes
called the Early Christian Period or the Early Middle Ages, includes
some of the most enigmatic centuries in the whole of Irish
history. In this article we intend to look at various strands of evidence
that have become available from the perspective of dendrochronology.
However, interpretation of dendrochronological
results works best when there is other information to push
against. In the case of this period one of the best sources of parallel
information – information essentially as well dated as tree
rings – has to be records of atmospheric chemistry from the ice
cores that have been drilled at several locations across Greenland.
Combining such information with evidence from tree rings,
palaeoecological research, and occasionally from history, allows
us to trace out a series of events and episodes that form the beginnings
of an understanding of this period between the Iron
Age flowering – with sites such as Emain Mache, Tara, Cruachain
– and the Early Christian flowering – widespread foundation of churches and monasteries.

Unravelling the migration decision-making process: English early retirees moving to rural mid-Wales

There are established migrant reasons to explain rural in-migration. These include quality of life, rural idyll and lifestyle motivations. However, such one-dimensional sound bites portray rural in-migration in overly simplistic and stereotypical terms. In contrast, this paper distinguishes the decision to move from the reason for moving and in doing so sheds new light on the interconnections between different domains (family, work, finance, health) of the migrant's life which contribute to migration behaviour. Focussing on early retirees to mid-Wales and adopting a life course perspective the overall decision to move is disaggregated into a series of decisions. Giving voices to the migrants themselves demonstrates the combination of life events necessary to lead to migration behaviour, the variable factors (and often economic dominance) considered in the choice of destination (including that many are reluctant migrants to Wales), and the perceived 'accidental' choice of location and/or property. It is argued that quality of life, rural idyll and lifestyle sound bites offer an inadequate understanding of rural in-migration and associated decision-making processes. Moreover, they disguise the true nature of migrant decision making.

Introduction to the Special Section Value Development from Middle Childhood to Early Adulthood: New Insights from Longitudinal and Genetically Informed Research

Research into values at an early age has only started recently, although it has expanded quickly and dynamically in the past years. The purpose of this article is twofold: First, it provides an introduction to a special section that aims to help fill the gap in value development research. The special section brings together four new longitudinal and genetically informed studies of value development from the beginning of middle childhood through early adulthood. Second, this article reviews recent research from this special section and beyond, aiming to provide new directions to the field. With new methods for assessing children's values and an increased awareness of the role of values in children's and adolescents' development, the field now seems ripe for an in-depth investigation. Our review of empirical evidence shows that, as is the case with adults, children's values are organized based on compatibilities and conflicts in their underlying motivations. Values show some consistency across situations, as well as stability across time. This longitudinal stability tends to increase with age, although mean changes are also observed. These patterns of change seem to be compatible with Schwartz's (1992) theory of values (e.g., if the importance of openness to change values increases, the importance of conservation values decreases). The contributions of culture, family, peers, significant life events, and individual characteristics to values are discussed, as well as the development of values as guides for behavior.

Pain, passion and faith : revisiting the place of Charles Wesley in early Methodism

Pain, Passion and Faith: Revisiting the Place of Charles Wesley in Early Methodism is a significant study of the 18th-century poet and preacher Charles Wesley. Wesley was an influential figure in 18th-century English culture and society; he was co-founder of the Methodist revival movement and one of the most prolific hymn-writers in the English language. His hymns depict the Christian life as characterized by a range of intense emotions, from ecstatic joy to profound suffering.

Presbyterian ethos and environment in the novels of John Buchan : a religious and historical study

The aim of this thesis is to establish, from a historical and religious perspective, that the Presbyterian ethos and environment in which John Buchan was reared was the predominating influence in the writing of his novels. Presbyterianism was not the only influence on Buchan that determined the character of his stories. Buchan was by temperament a romantic, and this had considerable influence on his literature. His novels are romances, peopled by romantic figures who pursue romantic adventures. There are the signs of Buchan's romantic nature in the contents of the novels: creative imagination, sensitivity to nature, and expectations of the intrusion of other worlds, with destiny-determining events to follow. But Buchan had also an acquired classicism. His studies at Glasgow and Oxford Universities brought him in touch with a whole range of the master-pieces of classical literature, especially the works of Plato and Virgil. This discipline gave him clarity and conciseness in style, and balanced the romantic element in him, keeping his work within the bounds of reason. At the heart of Buchan's life and work, however, was his deeply religious nature and this, while influenced by romanticism and classicism, was the dominant force behind his work. Buchan did not accept in its entirety the Presbyterian doctrine conveyed to him by his father and his Church. He was moderate by temperament and shrank from excesses in religious matters, and, being a romantic, he shied away from any fixed creeds. He did embrace the fundamentals of Christianity, however, which he learned from his father and his Church, even if he did put aside the Rev. John's orthodox Calvinism. The basic Christianity which underlies all Buchan's novels has the stamp of Presbyterianism upon it, and that stamp is evident in his characters and their adventures. The expression of Christianity which Buchan embraced was the Christian Platonism of seventeenth century theologians, who taught and preached at Cambridge University, They gave prominence to the place of reason and conscience in man's search for God, They believed that reason and conscience were the ‘candle of the Lord’ which was existed every one. It was their conviction that, if that light was followed, it would lead men and women to God. They were against superstition and fanaticism in religion, against all forms of persecution for religious beliefs, and insisted that God could only be known by renouncing evil and setting oneself to live according to God’s will. This teaching Buchan received, but the stamp of his Presbyterianism was not obliterated. The basic doctrines which arose from his father's Presbyterianism and are to be found in Buchan's novels are as follows: a. the fear (or awe) of God, as life's basic religious attitude; b. the Providence of God as the ultimate determinative force in the outcome of events; c. the reality, malignity and universality of evil which must be forcefully and constantly resisted; d. the dignity of human beings in bearing God's image; e. the conviction that life has meaning and that its ultimate goal, therefore, is a spiritual one - as opposed to the accumulation of wealth, the achieving of recognition from society, and the gaining access to power; f. the necessity of challenge in life for growth and fulfilment, and the importance of fortitude in successfully meeting such challenge; g. the belief that, in the purpose of God, the weak confound the strong. These emphases of Presbyterianism are to be found in all Buchan's novels, to a greater or lesser degree. All his characters are serious people, with a moral purpose in life. Like the pilgrims of the Bible, they seek a country: true fulfilment. This quest becomes more spiritual and more dearly defined as Buchan grows in age and maturity. The progress is to be traced from his early novels, where fulfilment is sought in honour and self-approving competence, as advocated by classicism; to the novels of his middle years, where fulfilment is sought in adventures suggested by romanticism. In his final novel Sick Heart River. Buchan appears to have moved somewhat from his earlier classicism and his romanticism as the road to fulfilment. In this novel, Buchan expresses what, for him, is ultimate fulfilment: a conversion to God that produces self-sacrificing love for others. The terminally-ill Edward Leithen sets out on a romantic adventure that will enable him to die with dignity, and so, in classic style, justify his existence. He has a belief in God, but in a God who is almighty, distant and largely irrelevant to Leithen's life. In the frozen North of Canada, where he expects to find his meagre beliefs in God's absolute power confirmed by the icy majesty of mountain and plain, he finds instead God's mercy and it melts his heart. In a Christ-like way, he brings life to others through his death, believing that, through death, he will find life. There is sufficient evidence to give plausibility to the view that Buchan is describing in Leithen his own pilgrimage. If so, it means that Buchan found his way back to the fundamental experience of the Christian life, conversion, so strongly emphasised in his orthodox Presbyterianism home and Church. However, Buchan reaches this conclusion in a Christian Platonist way, through the natural world, rather than through the more orthodox pathway of Scripture.

Early diagnosis of Gorlin-Goltz syndrome: case report

The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by keratocystic odontogenic tumors (KCOT) in the jaw, multiple basal cell nevi carcinomas and skeletal abnormities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the KCOTs are usually one of the first manifestations of the syndrome. This article paper reports the case of a patient, a 10-year-old boy with NBCCS, emphasizing its clinical and radiographic manifestations. This study highlights the importance of health professionals in the early diagnosis of NBCCS and in a preventive multidisciplinary approach to provide a better prognosis for the patient.

Maternal immune activation increases the corticosterone response to acute stress without affecting the hypothalamic monoamine content and sleep patterns in male mice offspring

Background/Aims: Early life experiences are homeostatic determinants for adult organisms. We evaluated the impact of prenatal immune activation during late gestation on the neuroimmune-endocrine function of adult offspring and its interaction with acute stress. Methods: Pregnant Swiss mice received saline or lipopolysaccharide (LPS) on gestational day 17. Adult male offspring were assigned to the control or restraint stress condition. We analyzed plasmatic corticosterone and catecholamine levels, the monoamine content in the hypothalamus, striatum and frontal cortex, and the sleep-wake cycle before and after acute restraint stress. Results and Conclusion: Offspring from LPS-treated dams had increased baseline norepinephrine levels and potentiated corticosterone secretion after the acute stressor, and no effect was observed on hypothalamic monoamine content or sleep behavior. The offspring of immune-activated dams exhibited impairments in stress-induced serotonergic and dopaminergic alterations in the striatum and frontal cortex. The data demonstrate a distinction between the plasmatic levels of corticosterone in response to acute stress and the hypothalamic monoamine content and sleep patterns. We provide new evidence regarding the influence of immune activation during late gestation on the neuroendocrine homeostasis of offspring.

Genetic dynamics across early life stages in the tropical tree Prunus africana (Rosaceae)

In many plant species, the genetic template of early life-stages is formed by animal-mediated pollination and seed dispersal and has profound impact on further recruitment and population dynamics. Understanding the impact of pollination and seed dispersal on genetic patterns is a central issue in plant population biology. In my thesis, I investigated (i) contemporary dispersal and gene flow distances as well as (ii) genetic diversity and spatial genetic structure (SGS) across subsequent recruitment stages in a population of the animal-pollinated and dispersed tree Prunus africana in Kakamega Forest, West Kenya. Using microsatellite markers and parentage analyses, I inferred distances of pollen dispersal (father-to-mother), seed dispersal/maternal gene flow (mother-to-offspring) as well as paternal gene flow (father-to-offspring) for four early life stages of the species (seeds and fruits, current year seedlings, seedlings ≤ 3yr, seedlings > 3yr). Distances of pollen and seed dispersal as well as paternal gene flow were significantly shorter than expected from the spatial arrangement of trees and sampling plots. They were not affected by the density of conspecific trees in the surrounding. At the propagule stage, mean pollen dispersal distances were considerably (23-fold) longer than seed dispersal distances, and paternal gene flow distances exceeded maternal gene flow by a factor of 25. Seed dispersal distances were remarkably restricted, potentially leading to a strong initial SGS. The initial genetic template created by pollination and seed dispersal was extensively altered during later recruitment stages. Potential Janzen-Connell effects led to markedly increasing distances between offspring and both parental trees in older life stages. This showed that distance and density-dependent mortality factors are not exclusively related to the mother tree, but also to the father. Across subsequent recruitment stages, the pollen to seed dispersal ratio and the paternal to maternal gene flow ratio dropped to 2.1 and 3.4, respectively, in seedlings > 3yr. The relative changes in effective pollen dispersal, seed dispersal, and paternal gene flow distances across recruitment stages elucidate the mechanisms affecting the contribution of the two processes pollen and seed dispersal to overall gene flow. Using the same six microsatellite loci, I analyzed genetic diversity and SGS across five life stages, from seed rain to adults. Levels of genetic diversity within the studied P. africana population were comparable to other Prunus species and did not vary across life stages. In congruence with the short seed dispersal distances, I found significant SGS in all life stages. SGS decreased from seed and early seedling stages to older juvenile stages, and it was higher in adults than in late juveniles of the next generation. A comparison of the data with direct assessments of contemporary gene flow patterns indicate that distance- or density-dependent mortality, potentially due to Janzen-Connell effects, led to the initial decrease in SGS. Intergeneration variation in SGS could have been driven by variation in demographic processes, the effect of overlapping generations, and local selection processes. Overall, my study showed that complex sequential processes during recruitment contribute to the spatial genetic structure of tree populations. It highlights the importance of a multistage perspective for a comprehensive understanding of the impact of animal-mediated pollen and seed dispersal on spatial population dynamics and genetic patterns of trees.