Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation.

Lymphatic valves are essential for efficient lymphatic transport, but the mechanisms of early lymphatic-valve morphogenesis and the role of biomechanical forces are not well understood. We found that the transcription factors PROX1 and FOXC2, highly expressed from the onset of valve formation, mediate segregation of lymphatic-valve-forming cells and cell mechanosensory responses to shear stress in vitro. Mechanistically, PROX1, FOXC2, and flow coordinately control expression of the gap junction protein connexin37 and activation of calcineurin/NFAT signaling. Connexin37 and calcineurin are required for the assembly and delimitation of lymphatic valve territory during development and for its postnatal maintenance. We propose a model in which regionally increased levels/activation states of transcription factors cooperate with mechanotransduction to induce a discrete cell-signaling pattern and morphogenetic event, such as formation of lymphatic valves. Our results also provide molecular insights into the role of endothelial cell identity in the regulation of vascular mechanotransduction.

Rural Health Partnership

This is their 3rd BCPP project and this is a Level 3 project. Rural Health Partnership is a community based initiative which assists people to recover from a mental illness. Previous BCPP projects focussed on supporting the needs of women in relation to mental health and more specifically, those experiencing post natal depression through the 2nd BCPP project using a lay health approach. This project seeks to build on this previous work. A very good working relationship has developed between the pharmacist and RHP. A programme of activities that can enhance the skills and knowledge base of the participants will be developed and so will relationships with other services eg GPs, primary care team etc. The project aims to educate the community at large on the issues faced by vulnerable women, with particular emphasis on symptoms of postnatal depression and anxiety.

Expression and developmental regulation of Ehk-1, a neuronal Elk-like receptor tyrosine kinase in brain.

Protein tyrosine kinases are pivotal in central nervous tissue development and maintenance. Here we focus on the expression of Ehk-1, a novel Elk-related receptor tyrosine kinase. Ehk-1 gene expression is observed in the developing and adult central nervous system and is highly regulated throughout development at both the messenger RNA and protein levels. Three messenger RNA transcripts of 8.5, 5.9 and 5.1 kb are detectable in the rat brain and a variety of splice possibilities have been identified. However, a major protein species of around M(r) 120,000 predominates throughout development. Ehk-1 messenger RNA and protein levels are highest in the first postnatal week. By in situ messenger RNA hybridization the gene is expressed by all neurons of the adult brain, but mostly in the hippocampus, cerebral cortex and large neurons of the deep cerebellar nuclei, as well as the Purkinje and granular cells of the cerebellum. At earlier stages of development, transcripts are most prominent in the periventricular germinal layers of the brain. Immunohistochemistry reveals a pronounced membrane associated protein expression in immature neurons. In the adult animal, peak reactivity was found in the neuropil with sparing of most perikarya. The spatial and temporal pattern of ehk-1 gene expression suggests a role in both the development and maintenance of differentiated neurons of the central nervous system.

Three essays in international finance

Executive Summary The first essay of this dissertation investigates whether greater exchange rate uncertainty (i.e., variation over time in the exchange rate) fosters or depresses the foreign investment of multinational firms. In addition to the direct capital financing it supplies, foreign investment can be a source of valuable technology and know-how, which can have substantial positive effects on a host country's economic growth. Thus, it is critically important for policy makers and central bankers, among others, to understand how multinationals base their investment decisions on the characteristics of foreign exchange markets. In this essay, I first develop a theoretical framework to improve our knowledge regarding how the aggregate level of foreign investment responds to exchange rate uncertainty when an economy consists of many firms, each of which is making decisions. The analysis predicts a U-shaped effect of exchange rate uncertainty on the total level of foreign investment of the economy. That is, the effect is negative for low levels of uncertainty and positive for higher levels of uncertainty. This pattern emerges because the relationship between exchange rate volatility and 'the probability of investment is negative for firms with low productivity at home (i.e., firms that find it profitable to invest abroad) and the relationship is positive for firms with high productivity at home (i.e., firms that prefer exporting their product). This finding stands in sharp contrast to predictions in the existing literature that consider a single firm's decision to invest in a unique project. The main contribution of this research is to show that the aggregation over many firms produces a U-shaped pattern between exchange rate uncertainty and the probability of investment. Using data from industrialized countries for the period of 1982-2002, this essay offers a comprehensive empirical analysis that provides evidence in support of the theoretical prediction. In the second essay, I aim to explain the time variation in sovereign credit risk, which captures the risk that a government may be unable to repay its debt. The importance of correctly evaluating such a risk is illustrated by the central role of sovereign debt in previous international lending crises. In addition, sovereign debt is the largest asset class in emerging markets. In this essay, I provide a pricing formula for the evaluation of sovereign credit risk in which the decision to default on sovereign debt is made by the government. The pricing formula explains the variation across time in daily credit spreads - a widely used measure of credit risk - to a degree not offered by existing theoretical and empirical models. I use information on a country's stock market to compute the prevailing sovereign credit spread in that country. The pricing formula explains a substantial fraction of the time variation in daily credit spread changes for Brazil, Mexico, Peru, and Russia for the 1998-2008 period, particularly during the recent subprime crisis. I also show that when a government incentive to default is allowed to depend on current economic conditions, one can best explain the level of credit spreads, especially during the recent period of financial distress. In the third essay, I show that the risk of sovereign default abroad can produce adverse consequences for the U.S. equity market through a decrease in returns and an increase in volatility. The risk of sovereign default, which is no longer limited to emerging economies, has recently become a major concern for financial markets. While sovereign debt plays an increasing role in today's financial environment, the effects of sovereign credit risk on the U.S. financial markets have been largely ignored in the literature. In this essay, I develop a theoretical framework that explores how the risk of sovereign default abroad helps explain the level and the volatility of U.S. equity returns. The intuition for this effect is that negative economic shocks deteriorate the fiscal situation of foreign governments, thereby increasing the risk of a sovereign default that would trigger a local contraction in economic growth. The increased risk of an economic slowdown abroad amplifies the direct effect of these shocks on the level and the volatility of equity returns in the U.S. through two channels. The first channel involves a decrease in the future earnings of U.S. exporters resulting from unfavorable adjustments to the exchange rate. The second channel involves investors' incentives to rebalance their portfolios toward safer assets, which depresses U.S. equity prices. An empirical estimation of the model with monthly data for the 1994-2008 period provides evidence that the risk of sovereign default abroad generates a strong leverage effect during economic downturns, which helps to substantially explain the level and the volatility of U.S. equity returns.

Psycho-oncological interventions and psychotherapy in the oncology setting.

A person who faces the diagnosis of cancer is subjected to changes within his body, but also with regard to his view of himself and his social relationships. Cancer-related psychological distress occurs frequently and has been reported to have different prevalence according to cancer type and stage of disease. Psychological disorders are known to be underdiagnosed and thus undertreated in the oncology setting, since clinicians might miss the symptoms of psychological distress, misinterpret them, or lack the time and resources to respond adequately. The main psychiatric disturbances observed in patients with cancer are adjustment disorders and affective disorders (anxiety and depression), which in the majority of patients are due to stressors related to the disease and pre-existing psychological vulnerabilities; however, they might also be a direct consequence of biological causes either resulting from treatment side effects or from modifications induced by the cancer. This chapter aims to provide theoretical and practical information concerning psycho-oncological approaches, complemented by some reflexions on their clinical and scientific evidence, focussing essentially on verbal psychological interventions and especially on psychotherapy in patients with cancer.

Consultation launched on Community Development Strategy - your views matter

Issued jointly by the Health and Social Care Board and Public Health AgencyThe Health and Social Care Board and the Public Health Agency have today launched, for public consultation, a new Community Development Strategy.The consultation period will run for 12 weeks from Friday 10 June until Friday 2 September 2011.The Board and Agency want to see strong, resilient communities where everyone has good health and wellbeing, places where people look out for each other and have community pride in where they live.Residents from deprived areas in Northern Ireland experience;lower life expectancy;higher rates of emergency admission to hospital;higher rates of lung cancer;higher rates of suicide; andhigher rates of smoking and alcohol related deaths.The kinds of health and social care issues which can be improved by community development approaches include depression; isolation; falls amongst elderly people; child protection; teenage pregnancy; childhood asthma; postnatal depression; drug and alcohol abuse; and ultimately also long term conditions such as obesity, diabetes and cancer.The Board and Agency seek a number of benefits from implementing this strategy such as; a reduction in health and wellbeing inequalities, which also means addressing the social factors that affect health; strengthening partnership working with service users, the community and voluntary sectors and other organisations; strengthening families and communities; supporting volunteering and making best use of our resources.John Compton, Chief Executive of the Health and Social Care Board said: "Community development is an important way to improving health and wellbeing - driving a message that 'prevention is better than cure' between different groups and communities, and helping to ensure the most effective use of the health and social care budget."Now more than ever we need to work in partnership with families and communities to achieve better health and wellbeing for those living in Northern Ireland.No one organisation can meet this challenge on its own and strong partnerships are needed. "Chief Executive of the Public Health Agency, Eddie Rooney added: "Every health and social care organisation should incorporate a community development approach into their programmes, and this strategy assists them to do so."The Board and Agency have jointly held pre-consultation workshops over the past few months across Northern Ireland on their Community Development Strategy and have engaged widely with the community and voluntary sectors. We are now keen to receive feedback from individuals, families and the wider community as your views are very important to us - they will help shape the future of community development across the province," he said.The draft Community Development Strategy, as well as information on how you can respond, can be found in the attachments below.

Douleurs chroniques chez les personnes âgées: dimensions psychologiques [Chronic pain in elderly people: psychosocial dimension].

Chronic pain in elderly people requires to take into account somatic co-morbidities as well as its psychosocial dimensions. Chronic pain often represents a distress signal addressed to the environment and the care providers. Psychological suffering or mood disorders can be presented in the form of somatic complaints often associated with functional impairments, sometimes severe. Therapeutic care has to address functionality through an image-enhancing approach aiming to summon the patients' resources. The treatment of a concomitant depressive state necessitates a true commitment from the therapist. Its benefits are documented in elderly patients. Analgesic treatment as a whole will seek in particular to restore feelings of self-esteem and help the patient recover a good quality of life.

Headline Annual Report 2007

Headline is Ireland's national media monitoring programme, working to promote responsible and accurate coverage of mental health and suicide related issues within the Irish media. Headline aims to highlight mental health issues and address the stigma attached to emotional distress, suicidal behaviour and mental illness through the promotion of responsible media coverage.

Headline Annual Report 2008

Headline is Ireland's national media monitoring programme, working to promote responsible and accurate coverage of mental health and suicide related issues within the Irish media. Headline aims to highlight mental health issues and address the stigma attached to emotional distress, suicidal behaviour and mental illness through the promotion of responsible media coverage.

Persistent pulmonary arterial hypertension in the newborn (PPHN): a frequent manifestation of TMEM70 defective patients.

INTRODUCTION: Mutations in the TMEM70 are the most common cause of nuclear ATP synthase deficiency resulting in a distinctive phenotype characterized by severe neonatal hypotonia, hypertrophic cardiomyopathy (HCMP), facial dysmorphism, severe lactic acidosis, hyperammonemia and 3-methylglutaconic aciduria (3-MGA). METHODS AND RESULTS: We collected 9 patients with genetically confirmed TMEM70 defect from 8 different families. Six were homozygous for the c.317-2A>G mutation, 2 were compound heterozygous for mutations c.317-2A>G and c.628A>C and 1 was homozygous for the novel c.701A>C mutation. Generalized hypotonia, lactic acidosis, hyperammonemia and 3-MGA were present in all since birth. Five patients presented acute respiratory distress at birth requiring intubation and ventilatory support. HCMP was detected in 5 newborns and appeared a few months later in 3 additional children. Five patients showed a severe and persistent neonatal pulmonary hypertension (PPHN) requiring Nitric Oxide (NO) and/or sildenafil administration combined in 2 cases with high-frequency oscillatory (HFO) ventilation. In 3 of these patients, echocardiography detected signs of HCMP at birth. CONCLUSIONS: PPHN is a life-threatening poorly understood condition with bad prognosis if untreated. Pulmonary hypertension has rarely been reported in mitochondrial disorders and, so far, it has been described in association with TMEM70 deficiency only in one patient. This report further expands the clinical and genetic spectrum of the syndrome indicating PPHN as a frequent and life-threatening complication regardless of the type of mutation. Moreover, in these children PPHN appears even in the absence of an overt cardiomyopathy, thus representing an early sign and a clue for diagnosis.

Neurochemical profile of the developing mouse cortex determined by in vivo 1H NMR spectroscopy at 14.1 T and the effect of recurrent anaesthesia.

The neurochemical profile of the cortex develops in a region and time specific manner, which can be distorted by psychiatric and other neurological pathologies. Pre-clinical studies often involve experimental mouse models. In this study, we determined the neurochemical profile of C57BL/6 mice in a longitudinal study design to provide a reference frame for the normal developing mouse cortex. Using in vivo proton NMR spectroscopy at 14 T, we measured the concentrations of 18 metabolites in the anterior and posterior cortex on postnatal days (P) 10, 20, 30, 60 and 90. Cortical development was marked by alterations of highly concentrated metabolites, such as N-acetylaspartate, glutamate, taurine and creatine. Regional specificity was represented by early variations in the concentration of glutamine, aspartate and choline. In adult animals, regional concentration differences were found for N-acetylaspartate, creatine and myo-inositol. In this study, animals were exposed to recurrent isoflurane anaesthesia. Additional experiments showed that the latter was devoid of major effects on behaviour or cortical neurochemical profile. In conclusion, the high sensitivity and reproducibility of the measurements achieved at 14 T allowed us to identify developmental variations of cortical areas within the mouse cortex.

Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma.

BACKGROUND: The aim of this multicenter trial was to prospectively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) and radiotherapy, including quality of life as outcome. PATIENTS AND METHODS: Eligible patients had malignant pleural mesothelioma of all histological types, World Health Organization performance status of zero to two and clinical stage T1-T3, N0-2, M0 disease considered completely resectable. Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP. Postoperative radiotherapy was considered for all patients. RESULTS: In all, 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy. Forty-five patients (74%) underwent EPP and in 37 patients (61%) the resection was complete. Postoperative radiotherapy was initiated in 36 patients. The median survival of all patients was 19.8 months [95% confidence interval (CI) 14.6-24.5]. For the 45 patients undergoing EPP, the median survival was 23 months (95% CI 16.6-32.9). Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82% (N = 36) at baseline and 76% (N = 26) at 3 months after surgery (P = 0.5). CONCLUSIONS: The observed rate of operability is promising. A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery. This approach was not associated with an increase in psychological distress.

Cognitive behavioural therapy leaflet.

This leaflet is for anyone who wants to know more about Cognitive Behavioural Therapy (CBT).It discusses how it works, why it is used, its effects, its side-effects, and alternative treatments. If you can't find what you want here, there are sources of further information at the end of this leaflet. What is CBT? It is a way of talking about: ï,§ how you think about yourself, the world and other people ï,§ how what you do affects your thoughts and feelings. CBT can help you to change how you think ('Cognitive') and what you do ('Behaviour'). These changes can help you to feel better. Unlike some of the other talking treatments, it focuses on the 'here and now' problems and difficulties. Instead of focusing on the causes of your distress or symptoms in the past, it looks for ways to improve your state of mind now. When does CBT help? CBT has been shown to help with many different types of problems. These include: anxiety, depression, panic, phobias (including agoraphobia and social phobia), stress, bulimia, obsessive compulsive disorder, post-traumatic stress disorder, bipolar disorder and psychosis. CBT may also help if you have difficulties with anger, a low opinion of yourself or physical health problems, like pain or fatigue. How does it work? CBT can help you to make sense of overwhelming problems by breaking them down into smaller parts. This makes it easier to see how they are connected and how they affect you. These parts are: ï,§ A Situation - a problem, event or difficult situation. From this can follow: ï,§ Thoughts ï,§ Emotions ï,§ Physical feelings ï,§ Actions Each of these areas can affect the others. How you think about a problem can affect how you feel physically and emotionally. All these areas of life can connect like this: {5 Areas - click related link below} What happens in one of these areas can affect all the others. There are helpful and unhelpful ways of reacting to most situations, depending on how you think about it. The way you think can be helpful - or unhelpful. An example: If you go home feeling depressed, you'll probably brood on what has happened and feel worse. If you get in touch with the other person, there's a good chance you'll feel better about yourself. If you avoid the other person, you won't be able to correct any misunderstandings about what they think of you - and you will probably feel worse. This 'vicious circle' can make you feel worse. It can even create new situations that make you feel worse. You can start to believe quite unrealistic (and unpleasant) things about yourself. This happens because, when we are distressed, we are more likely to jump to conclusions and to interpret things in extreme and unhelpful ways. CBT can help you to break this vicious circle of altered thinking, feelings and behaviour. When you see the parts of the sequence clearly, you can change them - and so change the way you feel. CBT aims to get you to a point where you can 'do it yourself', and work out your own ways of tackling these problems. [For full factsheet â?" click on link above]This resource was contributed by the National Documentation Centre on Drug Use.

Pluralized life courses? An exploration of the life trajectories of individuals with psychiatric disorders.

BACKGROUND: : Most of the existing research relating to the life courses of people with psychiatric symptoms focuses on the occurrence and the impact of non-normative events on the onsets of crises; it usually disregards the more regular dimensions of life, such as work, family and intimate partnerships that may be related to the timing and seriousness of psychiatric problems. An additional reason for empirically addressing life trajectories of individuals with psychiatric problems relates to recent changes of family and occupational trajectories in relation to societal trends such as individualization and pluralization of life courses.¦AIM: : This paper explores the life trajectories of 86 individuals under clinical supervision and proposes a typology of their occupational, co-residence and intimacy trajectories. The results are discussed in light of the life-course paradigm.¦METHOD: : A multidimensional optimal matching analysis was performed on a sample of 86 individuals under clinical supervision to create a typology of trajectories. The influence of these trajectories on psychiatric disorders, evaluated using a SCL-90-R questionnaire, was then assessed using linear regression modelling.¦RESULTS: : The typologies of trajectories showed that the patients developed a diversity of life trajectories. Individuals who have developed a standard life course with few institutionalization periods reported more symptoms and distress than individuals with an institutionalized life trajectory.¦CONCLUSION: : The results of this study stress that psychiatric patients are social actors who are influenced by society at large and its ongoing process of change. Therefore, it is essential to take into account the diversity of occupational and family trajectories when dealing with individuals in therapeutic settings.

Headline Annual Report 2010

Headline is Ireland's national media monitoring programme, working to promote responsible and accurate coverage of mental health and suicide related issues within the Irish media.Headline aims to highlight mental health issues and address the stigma attached to emotional distress, suicidal behaviour and mental illness through the promotion of responsible media coverage.