Regulation of the aldosterone synthase gene-role in human hypertension and adrenal corticosteroid production

Despite many advances in technology and significant levels of funding, the genetic factors that regulate blood pressure in the population remain unclear. The public health implications of this lack of knowledge are conspicuous and a better understanding of the mechanisms behind hypertension would lead to better management of this important risk factor. The myriad of physiological systems involved in maintaining blood pressure can be variably dysregulated in patients with hypertension. Therefore, taking more account of hypertension as a heterogeneous condition may be a useful approach. Given the lack of success in dissecting the genetic factors to date, it seems reasonable to refocus attention on more carefully phenotyped groups of subjects, with the aim of identifying mechanisms specific to them

Higher cognitive ability buffers stress-related depressive symptoms in adolescent girls

Stress has been shown to have a causal effect on risk for depression. We investigated the role of cognitive ability as a moderator of the effect of stressful life events on depressive symptoms and whether this varied by gender. Data were analyzed in two adolescent data sets: one representative community sample aged 11–12 years (n = 460) and one at increased familial risk of depression aged 9–17 years (n = 335). In both data sets, a three-way interaction was found whereby for girls, but not boys, higher cognitive ability buffered the association between stress and greater depressive symptoms. The interaction was replicated when the outcome was a diagnosis of major depressive disorder. This buffering effect in girls was not attributable to coping efficacy. However, a small proportion of the variance was accounted for by sensitivity to environmental stressors. Results suggest that this moderating effect of cognitive ability in girls is largely attributable to greater available resources for cognitive operations that offer protection against stress-induced reductions in cognitive processing and cognitive control which in turn reduces the likelihood of depressive symptomatology

The re-birth of the "beat": A hyperlocal online newsgathering model

This is an Author's Accepted Manuscript of an article published in Journalism Practice, 6(5-6), 754 - 765, 2012, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/17512786.2012.667279.Scholars have long lamented the death of the 'beat' in news journalism. Today's journalists generate more copy than they used to, a deluge of PR releases often keeping them in the office, and away from their communities. Consolidation in industry has dislodged some journalists from their local sources. Yet hyperlocal online activity is thriving if journalists have the time and inclination to engage with it. This paper proposes an exploratory, normative schema intended to help local journalists systematically map and monitor their own hyperlocal online communities and contacts, with the aim of re-establishing local news beats online as networks. This model is, in part, technologically-independent. It encompasses proactive and reactive news-gathering and forward planning approaches. A schema is proposed, developed upon suggested news-gathering frameworks from the literature. These experiences were distilled into an iterative, replicable schema for local journalism. This model was then used to map out two real-world 'beats' for local news-gathering. Journalists working within these local beats were invited to trial the models created. It is hoped that this research will empower journalists by improving their information auditing, and could help re-define journalists' relationship with their online audiences

Common Polymorphisms at the <i>CYP17A1 </i>Locus Associate With Steroid Phenotype:Support for Blood Pressure Genome-Wide Association Study Signals at This Locus

Genome-wide association studies implicate the CYP17A1 gene in human blood pressure regulation although the causative polymorphisms are as yet unknown. We sought to identify common polymorphisms likely to explain this association. We sequenced the CYP17A1 locus in 60 normotensive individuals and observed 24 previously identified single-nucleotide polymorphisms with minor allele frequency &gt;0.05. From these, we selected, for further studies, 7 polymorphisms located ≤2 kb upstream of the CYP17A1 transcription start site. In vitro reporter gene assays identified 3 of these (rs138009835, rs2150927, and rs2486758) as having significant functional effects. We then analyzed the association between the 7 polymorphisms and the urinary steroid metabolites in a hypertensive cohort (n=232). Significant associations included that of rs138009835 with aldosterone metabolite excretion; rs2150927 associated with the ratio of tetrahydrodeoxycorticosterone to tetrahydrodeoxycortisol, which we used as an index of 17α-hydroxylation. Linkage analysis showed rs138009835 to be the only 1 of the 7 polymorphisms in strong linkage disequilibrium with the blood pressure–associated polymorphisms identified in the previous studies. In conclusion, we have identified, characterized, and investigated common polymorphisms at the CYP17A1 locus that have functional effects on gene transcription in vitro and associate with corticosteroid phenotype in vivo. Of these, rs138009835—which we associate with changes in aldosterone level—is in strong linkage disequilibrium with polymorphisms linked by genome-wide association studies to blood pressure regulation. This finding clearly has implications for the development of high blood pressure in a large proportion of the population and justifies further investigation of rs138009835 and its effects

Pupil mental health, concerns and expectations about secondary school as predictors of adjustment across the transition to secondary school: A longitudinal multi-informant study

The transition from primary to secondary schooling is challenging and involves a degree of apprehension. The extent to which pre-existing mental health difficulties, as well as pupil, parent, and teacher concerns and expectations about secondary school predict adaptation to secondary school, is unclear. In a three wave, prospective longitudinal study, we examined associations between pre-transition concerns and expectations about moving to secondary school with mental health difficulties and demographic factors. We then evaluated whether these constructs predicted multiple indicators of adaptive pupil functioning at the end of the first year of secondary school (academic attainment, classmate behaviour rating, school liking and loneliness at school). We found children’s concerns reduced across the transition period. Concurrent associations were identified between both concerns about secondary school and lower parent and teacher expectations that children would settle in well at secondary school, with mental health difficulties and special educational needs. Investigating associations with multiple indicators of adaptive functioning at secondary school, multivariable regression analyses controlling for a range of baseline factors (e.g. special educational needs), found children’s concerns about secondary school to be specifically associated with loneliness. In contrast, children’s mental health difficulties and both parent and teacher expectations of how well children would settle into secondary school were associated with a wider range of indicators of adaptive functioning at secondary school. When examining all predictors simultaneously, primary school teacher expectations showed longitudinal association with a wide range of indicators of successful transition. These findings suggest that assessing primary school teacher expectations may be useful for monitoring and supporting pupils through this transition period and could usefully inform school-based interventions to support transition and mental health

Investigating friendship difficulties in the pathway from ADHD to depressive symptoms. Can parent-child relationships compensate?

Attention deficit/hyperactivity disorder (ADHD) is associated with friendship difficulties. This may partly account for the increasingly recognised association between ADHD and subsequent depression. Little is known about the types of friendship difficulties that could contribute to the association between ADHD and depressive symptoms and whether other relationships, such as parent–child relationships, can mitigate against potential adverse effects of friendship difficulties. In a representative UK school sample (n = 1712), three main features of friendship (presence of friends, friendship quality and characteristics of the individual’s classroom friendship group) were assessed in a longitudinal study with two assessment waves (W1, W2) during the first year of secondary school (children aged 11-12 years). These friendship features (W1) were investigated as potential mediators of the prospective association between teacher-rated ADHD symptoms (W1) and self-rated depressive symptoms (W2) seven months later. Parent–child relationship quality (W1) was tested as a moderator of any indirect effects of ADHD on depression via friendship. ADHD symptoms were inversely associated with friendship presence, friendship quality and positive characteristics of classroom friendship groups. Depressive symptoms were inversely associated with presence and quality of friendships. Friendship quality had indirect effects in the association between ADHD and subsequent depressive symptoms. There was some evidence of moderated mediation, whereby indirect effects via friendship quality attenuated slightly as children reported warmer parent–child relationships. This highlights the importance of considering the quality of friendships and parent–child relationships in children with ADHD symptoms. Fostering good quality relationships may help disrupt the link between ADHD symptomology and subsequent depression risk

Towards greater transparency and coherence in funding for sustainable marine fisheries and healthy oceans

This final manuscript in the special issue on “Funding for ocean conservation and sustainable fisheries” is the result of a dialogue aimed at connecting lead authors of the special issue manuscripts with relevant policymakers and practitioners. The dialogue took place over the course of a two-day workshop in December 2018, and this “coda” manuscript seeks to distil thinking around a series of key recurring topics raised throughout the workshop. These topics are collected into three broad categories, or “needs”: 1) a need for transparency, 2) a need for coherence, and 3) a need for improved monitoring of project impacts. While the special issue sought to collect new research into the latest trends and developments in the rapidly evolving world of funding for ocean conservation and sustainable fisheries, the insights collected during the workshop have helped to highlight remaining knowledge gaps. Therefore, each of the three “needs” identified within this manuscript is followed by a series of questions that the workshop participants identified as warranting further attention as part of a future research agenda. The crosscutting nature of many of the issues raised as well as the rapid pace of change that characterizes this funding landscape both pointed to a broader need for continued dialogue and study that reaches across the communities of research, policy and practice.S

Intervention planning for a digital intervention for self-management of hypertension: a theory-, evidence- and person-based approach.

BACKGROUND: This paper describes the intervention planning process for the Home and Online Management and Evaluation of Blood Pressure (HOME BP), a digital intervention to promote hypertension self-management. It illustrates how a Person-Based Approach can be integrated with theory- and evidence-based approaches. The Person-Based Approach to intervention development emphasises the use of qualitative research to ensure that the intervention is acceptable, persuasive, engaging and easy to implement. METHODS: Our intervention planning process comprised two parallel, integrated work streams, which combined theory-, evidence- and person-based elements. The first work stream involved collating evidence from a mixed methods feasibility study, a systematic review and a synthesis of qualitative research. This evidence was analysed to identify likely barriers and facilitators to uptake and implementation as well as design features that should be incorporated in the HOME BP intervention. The second work stream used three complementary approaches to theoretical modelling: developing brief guiding principles for intervention design, causal modelling to map behaviour change techniques in the intervention onto the Behaviour Change Wheel and Normalisation Process Theory frameworks, and developing a logic model. RESULTS: The different elements of our integrated approach to intervention planning yielded important, complementary insights into how to design the intervention to maximise acceptability and ease of implementation by both patients and health professionals. From the primary and secondary evidence, we identified key barriers to overcome (such as patient and health professional concerns about side effects of escalating medication) and effective intervention ingredients (such as providing in-person support for making healthy behaviour changes). Our guiding principles highlighted unique design features that could address these issues (such as online reassurance and procedures for managing concerns). Causal modelling ensured that all relevant behavioural determinants had been addressed, and provided a complete description of the intervention. Our logic model linked the hypothesised mechanisms of action of our intervention to existing psychological theory. CONCLUSION: Our integrated approach to intervention development, combining theory-, evidence- and person-based approaches, increased the clarity, comprehensiveness and confidence of our theoretical modelling and enabled us to ground our intervention in an in-depth understanding of the barriers and facilitators most relevant to this specific intervention and user population

Home and Online Management and Evaluation of Blood Pressure (HOME BP) using a digital intervention in poorly controlled hypertension:Randomised controlled trial

Objective The HOME BP (Home and Online Management and Evaluation of Blood Pressure) trial aimed to test a digital intervention for hypertension management in primary care by combining self-monitoring of blood pressure with guided self-management. Design Unmasked randomised controlled trial with automated ascertainment of primary endpoint. Setting 76 general practices in the United Kingdom. Participants 622 people with treated but poorly controlled hypertension (&gt;140/90 mm Hg) and access to the internet. Interventions Participants were randomised by using a minimisation algorithm to self-monitoring of blood pressure with a digital intervention (305 participants) or usual care (routine hypertension care, with appointments and drug changes made at the discretion of the general practitioner; 317 participants). The digital intervention provided feedback of blood pressure results to patients and professionals with optional lifestyle advice and motivational support. Target blood pressure for hypertension, diabetes, and people aged 80 or older followed UK national guidelines. Main outcome measures The primary outcome was the difference in systolic blood pressure (mean of second and third readings) after one year, adjusted for baseline blood pressure, blood pressure target, age, and practice, with multiple imputation for missing values. Results After one year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean blood pressure dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic blood pressure of -3.4 mm Hg (95% confidence interval -6.1 to -0.8 mm Hg) and a mean difference in diastolic blood pressure of -0.5 mm Hg (-1.9 to 0.9 mm Hg). Results were comparable in the complete case analysis and adverse effects were similar between groups. Within trial costs showed an incremental cost effectiveness ratio of £11 ($15, €12; 95% confidence interval £6 to £29) per mm Hg reduction. Conclusions The HOME BP digital intervention for the management of hypertension by using self-monitored blood pressure led to better control of systolic blood pressure after one year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded. Trial registration ISRCTN13790648.</p

Development and piloting of a primary school-based salt reduction programme: formative work and a process evaluation in rural and urban Malawi

Excess salt intake is a major modifiable risk factor for cardiovascular disease. Promoting salt reduction as part of routine school-health programming may be a pragmatic way to address this risk factor early in the life course but has not been tested in sub-Saharan Africa (SSA). Here we describe the formative work with stakeholders and process evaluation of pilot work to develop a school-based salt reduction programme for children aged 11–14 years, in preparation for a cluster-randomised trial in rural/urban Malawi. Collection of observational data and documentary evidence (meeting minutes/field notes) from the earliest key stakeholder engagement with Malawi Ministries of Health, Education, Local Government and Rural Development and Malawi Institute of Education, and non-governmental stakeholders; and a series of semi-structured interviews and focus groups (with head teachers (n = 2); teachers (n = 4); parents (n = 30); and learners (n = 40)). Data was analysed thematically and conceptualised through a Normalization Process Theory lens. Formative work illustrated a range of administrative, technical, and practical issues faced during development of the programme; including allocation of stakeholder roles and responsibilities, harmonisation with pre-existing strategies and competing priorities, resources required for programme development, and design of effective teaching materials. While participants were positive about the programme, the process evaluation identified features to be refined including perceived challenges to participation, recommended adaptations to the content and delivery of lessons, and concerns related to quantity/quality of learning resources provided. This study demonstrates the importance of comprehensive, sustained, and participatory stakeholder engagement in the development of a novel school health programme in SSA; and highlights the factors that were critical to successfully achieving this. We also demonstrate the value of detailed process evaluation in informing development of the programme to ensure that it was feasible and relevant to the context prior to evaluation through a cluster-randomised trial