Does neuregulin-1 play a role in Type A behavior? The cardiovascular risk in young Finns study

BACKGROUND: Neuregulin-1 proteins are related to physiological correlates of Type A in terms of cardiac reactivity. Furthermore, neuregulin-1 gene (NRG1) may play a role in cardiovascular disease such as atherosclerosis and coronary heart disease i.e. the suggested "outcomes" of Type A behavior. Therefore, NRG1 is hypothesized to be associated with Type A behavior. METHODS: The study examined whether Type A behavior pattern is associated with the single nucleotide polymorphism (SNP) SNP8NRG221533 of the NRG1. The subjects were 631 men and women participating in the population-based Cardiovascular Risk in Young Finns study in 1992 and 2001. Type A was self-assessed with the Framingham Type A Scale and reassessed nine years later. RESULTS: Type A was associated with NRG1 genotype. Carriers of genotype CC scored lower on Type A compared to the others. CONCLUSION: Our study has pinpointed a SNP in NRG1 that predicts Type A behavior. As previous evidence suggests an association for NRG1 with beta-adrenergic stimulation, its role underlying Type A is discussed

Simcluster: clustering enumeration gene expression data on the simplex space

Transcript enumeration methods such as SAGE, MPSS, and sequencing-by-synthesis EST "digital northern", are important high-throughput techniques for digital gene expression measurement. As other counting or voting processes, these measurements constitute compositional data exhibiting properties particular to the simplex space where the summation of the components is constrained. These properties are not present on regular Euclidean spaces, on which hybridization-based microarray data is often modeled. Therefore, pattern recognition methods commonly used for microarray data analysis may be non-informative for the data generated by transcript enumeration techniques since they ignore certain fundamental properties of this space.

Here we present a software tool, Simcluster, designed to perform clustering analysis for data on the simplex space. We present Simcluster as a stand-alone command-line C package and as a user-friendly on-line tool. Both versions are available at: http://xerad.systemsbiology.net/simcluster.

Simcluster is designed in accordance with a well-established mathematical framework for compositional data analysis, which provides principled procedures for dealing with the simplex space, and is thus applicable in a number of contexts, including enumeration-based gene expression data

The Finnish therapy navigator – Digital support system for introducing stepped care in Finland

Introduction: The need to improve quick access to effective psychological treatments is urgent. Success requires effective tools for identifying what kind of therapies an individual is likely to benefit from and managing a comprehensive therapy offering that matches an individual’s needs. First-line therapies initiative (Terapiat etulinjaan–toimintamalli) is a national initiative started 2020 in Finland. It aims to help Finnish regions in building locally sustainable stepped care systems and providing the support services needed. One key service of First-line therapies initiative is the Finnish therapy navigator (FTN). The FTN is a digital tool to help assess individual needs for psychosocial treatments and to build a regionally sustainable stepped care treatment offering, as part of the national reform of social and health services. This paper describes the development, content, implementation and feasibility of the FTN. Materials and Methods: The system was piloted in six regions in Finland between October 2021 and May 2022, with a catchment area of around 600 000. The feasibility data was collected from professionals (n = 48) using the system at 1 and 4 months after implementation, and from the anonymous FTN responses (n = 2630). Results: Professionals estimated the FTN had a positive impact on their work, quality of assessment and notes, and patient experience at 1 month after starting to use the FTN. Satisfaction scores improved further at 4 months, and 93% of users wanted to keep FTN as a permanent tool. The mean time patients used to fill the FTN was 24 minutes; 75% of clinical interviews lasted under 30 minutes. The FTN provides important data on treatment seekers. In our sample 57% of respondents scored between 10-19 points on PHQ-9 and 59% between 5-14 on GAD-7, suggesting mild-to-moderate depressive and anxiety symptoms. 28% reported no previous psychosocial treatments and 33% previous treatments shorter than 6 months. Thus, it seems that a significant proportion of treatment seekers in Finland could benefit from readily available, short-term, evidence-based psychosocial treatments that the First-line therapies initiative supports. Conclusions: FTN is a feasible tool for first assessment of mental health issues in primary care. Implemented and localized using the manualized co-creation process results in very high user satisfaction and acceptability of the system. The FTN provides important real-time data on mental health treatment seekers to support service development and planning. The First-line therapies model that includes introducing FTN in combination with regionally adapted care pathway development, education in short evidence-based psychological interventions and increase in use of digital support systems appears a feasible way to build regionally sustainable stepped systems.publishedVersionPeer reviewe

The Finnish therapy navigator – Digital support system for introducing stepped care in Finland

Introduction: The need to improve quick access to effective psychological treatments is urgent. Success requires effective tools for identifying what kind of therapies an individual is likely to benefit from and managing a comprehensive therapy offering that matches an individual’s needs. First-line therapies initiative (Terapiat etulinjaan–toimintamalli) is a national initiative started 2020 in Finland. It aims to help Finnish regions in building locally sustainable stepped care systems and providing the support services needed. One key service of First-line therapies initiative is the Finnish therapy navigator (FTN). The FTN is a digital tool to help assess individual needs for psychosocial treatments and to build a regionally sustainable stepped care treatment offering, as part of the national reform of social and health services. This paper describes the development, content, implementation and feasibility of the FTN. Materials and Methods: The system was piloted in six regions in Finland between October 2021 and May 2022, with a catchment area of around 600 000. The feasibility data was collected from professionals (n = 48) using the system at 1 and 4 months after implementation, and from the anonymous FTN responses (n = 2630). Results: Professionals estimated the FTN had a positive impact on their work, quality of assessment and notes, and patient experience at 1 month after starting to use the FTN. Satisfaction scores improved further at 4 months, and 93% of users wanted to keep FTN as a permanent tool. The mean time patients used to fill the FTN was 24 minutes; 75% of clinical interviews lasted under 30 minutes. The FTN provides important data on treatment seekers. In our sample 57% of respondents scored between 10-19 points on PHQ-9 and 59% between 5-14 on GAD-7, suggesting mild-to-moderate depressive and anxiety symptoms. 28% reported no previous psychosocial treatments and 33% previous treatments shorter than 6 months. Thus, it seems that a significant proportion of treatment seekers in Finland could benefit from readily available, short-term, evidence-based psychosocial treatments that the First-line therapies initiative supports. Conclusions: FTN is a feasible tool for first assessment of mental health issues in primary care. Implemented and localized using the manualized co-creation process results in very high user satisfaction and acceptability of the system. The FTN provides important real-time data on mental health treatment seekers to support service development and planning. The First-line therapies model that includes introducing FTN in combination with regionally adapted care pathway development, education in short evidence-based psychological interventions and increase in use of digital support systems appears a feasible way to build regionally sustainable stepped systems.publishedVersionPeer reviewe

Dissemination of clinical practice guidelines: A content analysis of patient versions

Background. Clinical practice guidelines (CPGs) are typically written for health care professionals but are meant to assist patients with health care decisions. A number of guideline producers have started to develop patient versions of CPGs to reach this audience. Objective. To describe the content and purpose of patient versions of CPGs and compare with patient and public views of CPGs. Design. A descriptive qualitative study with a directed content analysis of a sample of patient versions of CPGs published and freely available in English from 2012 to 2014. Results. We included 34 patient versions of CPGs from 17 guideline producers. Over half of the patient versions were in dedicated patient sections of national/professional agency websites. There was essentially no information about how to manage care in the health care system. The most common purpose was to equip people with information about disease, tests or treatments, and recommendations, but few provided quantitative data about benefits and harms of treatments. Information about beliefs, values and preferences, accessibility, costs, or feasibility of the interventions was rarely addressed. Few provided personal stories or scenarios to personalize the information. Three versions described the strength of the recommendation or the level of evidence. Limitations. Our search for key institutions that produce patient versions of guidelines was comprehensive, but we only included English and freely available versions. Future work will include other languages. Conclusions. This review describes the current landscape of patient versions of CPGs and suggests that these versions may not address the needs of their targeted audience. Research is needed about how to personalize information, provide information about factors contributing to the recommendations, and provide access

Uncovering the complex genetics of human temperament

Experimental studies of learning suggest that human temperament may depend on the molecular mechanisms for associative conditioning, which are highly conserved in animals. The main genetic pathways for associative conditioning are known in experimental animals, but have not been identified in prior genome-wide association studies (GWAS) of human temperament. We used a data-driven machine learning method for GWAS to uncover the complex genotypic-phenotypic networks and environmental interactions related to human temperament. In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified 3 clusters of people with distinct temperament profiles measured by the Temperament and Character Inventory regardless of genotype. Third, we found 51 SNP sets that identified 736 gene loci and were significantly associated with temperament. The identified genes were enriched in pathways activated by associative conditioning in animals, including the ERK, PI3K, and PKC pathways. 74% of the identified genes were unique to a specific temperament profile. Environmental influences measured in childhood and adulthood had small but significant effects. We confirmed the replicability of the 51 Finnish SNP sets in healthy Korean (90%) and German samples (89%), as well as their associations with temperament. The identified SNPs explained nearly all the heritability expected in each sample (37-53%) despite variable cultures and environments. We conclude that human temperament is strongly influenced by more than 700 genes that modulate associative conditioning by molecular processes for synaptic plasticity and long-term memory.Peer reviewe

Value based maternal and newborn care requires alignment of adequate resources with high value activities

Evidence based practice has been associated with better quality of care in many situations, but it has not been able to address increasing need and demand in healthcare globally and stagnant or decreasing healthcare resources. Implementation of value-based healthcare could address many important challenges in health care systems worldwide. Scaling up exemplary high value care practices offers the potential to ensure values-driven maternal and newborn care for all women and babies. Increased use of healthcare interventions over the last century have been associated with reductions in maternal and newborn mortality and morbidity. However, over an optimum threshold, these are associated with increases in adverse effects and inappropriate use of scarce resources. The Quality Maternal and Newborn Care framework provides an example of what value based maternity care might look like. To deliver value based maternal and newborn care, a system-level shift is needed, 'from fragmented care focused on identification and treatment of pathology for the minority to skilled care for all'. Ideally, resources would be allocated at population and individual level to ensure care is woman-centred instead of institution/ profession centred but oftentimes, the drivers for spending resources are 'the demands and beliefs of the acute sector'. We argue that decisions to allocate resources to high value activities, such as continuity of carer, need to be made at the macro level in the knowledge that these investments will relieve pressure on acute services while also ensuring the delivery of appropriate and high value care in the long run. To ensure that high value preventive and supportive care can be delivered, it is important that separate staff and money are allocated to, for example, models of continuity of carer to prevent shortages of resources due to rising demands of the acute services. To achieve value based maternal and newborn care, mechanisms are needed to ensure adequate resource allocation to high value maternity care activities that should be separate from the resource demands of acute maternity services. Funding arrangements should support, where wanted and needed, seamless movement of women and neonates between systems of care

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Ornato e despojamento no mundo fabril

O artigo investiga algumas das tendências da arquitetura gerada por fábricas - galpões industriais, moradias, igrejas, escolas, clubes etc. -, erguida no Brasil entre as duas últimas décadas do século XIX e as primeiras do XX. Apoia-se em amplo inventário, como base para um esforço de análise que se propõe a identificar os temas e usos predominantes dos ornatos aplicados a construções geradas por fábricas, as referências historicistas mobilizadas e eventuais rupturas de signos arquitetônicos tipológicos, e, no limite, a abolição de ornatos e dos referidos signos. Assim, de um lado, trata da penetração da linguagem eclética nessas construções, investigando o repertório formal utilizado em diferentes tipologias. De outro, trata da simultânea difusão de uma estética tipicamente fabril, fundamentada em noções de economia, eficiência, utilidade e funcionalidade. Mostra como tais noções se expressam ora em uma simplificação ou ausência de ornatos, ora no uso de ornatos cujos temas remetem ao mundo das máquinas; às vezes, no distanciamento ou abandono de signos arquitetônicos tipológicos consagrados; ou, ainda, no emprego de materiais produzidos industrialmente e que se difundiram a partir, sobretudo, da arquitetura de fábricas.The article examines some aspects of the architecture created for factories - warehouses, houses, churches, schools, clubs etc. -, built in Brazil between the two last decades of the nineteenth century and early of the twentieth century. The research relies on extensive inventory, the basis on which an analysis effort is realized that aims to identify the themes and predominant use of ornament applied to constructions produced by factories, the historicist references mobilized and eventual disruption of typological architectural signs, and, ultimately, the elimination of ornament and of those signs. Therefore, on one side, it deals with the penetration of the eclectic language in these buildings, by examining the formal repertoire used in different typologies. On the other side, it deals with simultaneous diffusion of a typical manufacturing aesthetic, based on notions of economy, efficiency, utility and functionality. It shows how such notions are expressed in either a simplification or the lack of ornament, sometimes in the use of ornament whose themes relate to the world of machines, sometimes in the detachment or abandonment of embodied architectural typological signs, or even the use of industrially produced materials that have spread from mainly the architecture of factories