Using participatory design methodologies to co-design and culturally adapt the Spanish version of the Mental Health eClinic: Qualitative study

Background: The Mental Health eClinic (MHeC) aims to deliver best-practice clinical services to young people experiencing mental health problems by making clinical care accessible, affordable, and available to young people whenever and wherever they need it most. The original MHeC consists of home page with a visible triage system for those requiring urgent help; a online physical and mental health self-report assessment; a results dashboard; a booking and videoconferencing system; and the generation of a personalized well-being plan. Populations who do not speak English and reside in English-speaking countries are less likely to receive mental health care. In Australia, international students have been identified as disadvantaged compared with their peers; have weaker social support networks; and have higher rates of psychological distress. This scenario is acquiring significant relevance as Spanish-speaking migration is rapidly growing in Australia, and the mental health services for culturally and linguistically diverse populations are limited. Having a Spanish version (MHeC-S) of the Mental Health eClinic would greatly benefit these students. Objective: We used participatory design methodologies with users (young people aged 16-30 years, supportive others, and health professionals) to (1) conduct workshops with users to co-design and culturally adapt the MHeC; (2) inform the development of the MHeC-S alpha prototype; (3) test the usability of the MHeC-S alpha prototype; (4) translate, culturally adapt, and face-validate the MHeC-S self-report assessment; and (5) collect information to inform its beta prototype. Methods: A research and development cycle included several participatory design phases: co-design workshops; knowledge translation; language translation and cultural adaptation; and rapid prototyping and user testing of the MHeC-S alpha prototype. Results: We held 2 co-design workshops with 17 users (10 young people, 7 health professionals). A total of 15 participated in the one-on-one user testing sessions (7 young people, 5 health professionals, 3 supportive others). We collected 225 source documents, and thematic analysis resulted in 5 main themes (help-seeking barriers, technology platform, functionality, content, and user interface). A random sample of 106 source documents analyzed by 2 independent raters revealed almost perfect agreement for functionality (kappa=.86; P\u3c.001) and content (kappa=.92; P\u3c.001) and substantial agreement for the user interface (kappa=.785; P\u3c.001). In this random sample, no annotations were coded for help-seeking barriers or the technology platform. Language was identified as the main barrier to getting medical or psychological services, and smartphones were the most-used device to access the internet. Acceptability was adequate for the prototype’s 5 main elements: home page and triage system, self-report assessment, dashboard of results, booking and video visit system, and personalized well-being plan. The data also revealed gaps in the alpha prototype, such as the need for tailored assessment tools and a greater integration with Spanish-speaking services and communities. Spanish-language apps and e-tools, as well as online mental health information, were lacking. Conclusions: Through a research and development process, we co-designed and culturally adapted, developed and user tested, and evaluated the MHeC-S. By translating and culturally adapting the MHeC to Spanish, we aimed to increase accessibility and availability of e-mental health care in the developing world, and assist vulnerable populations that have migrated to English-speaking countries

Entering and Exiting the Medicare Part D Coverage Gap: Role of Comorbidities and Demographics

Background: Some Medicare Part D enrollees whose drug expenditures exceed a threshold enter a coverage gap with full cost-sharing, increasing their risk for reduced adherence and adverse outcomes. Objective: To examine comorbidities and demographic characteristics associated with gap entry and exit. Design: We linked 2005-2006 pharmacy, outpatient, and inpatient claims to enrollment and Census data. We used logistic regression to estimate associations of 2006 gap entry and exit with 2005 medical comorbidities, demographics, and Census block characteristics. We expressed all results as predicted percentages. PATIENTS: 287,713 patients without gap coverage, continuously enrolled in a Medicare Advantage Part D (MAPD) plan serving eight states. Patients who received a low-income subsidy, could not be geocoded, or had no 2006 drug fills were excluded. Results: Of enrollees, 15.9% entered the gap, 2.6% within the first 180 days; among gap enterers, only 6.7% exited again. Gap entry was significantly associated with female gender and all comorbidities, particularly dementia (39.5% gap entry rate) and diabetes (28.0%). Among dementia patients entering the gap, anti-dementia drugs (donepezil, memantine, rivastigmine, and galantamine) and atypical antipsychoticmedications (risperidone, quetiapine, and olanzapine) together accounted for 40% of pre-gap expenditures. Among diabetic patients, rosiglitazone accounted for 7.2% of pre-gap expenditures. Having dementia was associated with twice the risk of gap exit. Conclusions: Certain chronically ill MAPD enrollees are at high risk of gap entry and exposure to unsubsidized medication costs. Clinically vulnerable populations should be counseled on how to best manage costs through drug substitution or discontinuation of specific, non-essential medications. © 2010 Society of General Internal Medicine

A Method for the Simultaneous Estimation of Selection Intensities in Overlapping Genes

Inferring the intensity of positive selection in protein-coding genes is important since it is used to shed light on the process of adaptation. Recently, it has been reported that overlapping genes, which are ubiquitous in all domains of life, seem to exhibit inordinate degrees of positive selection. Here, we present a new method for the simultaneous estimation of selection intensities in overlapping genes. We show that the appearance of positive selection is caused by assuming that selection operates independently on each gene in an overlapping pair, thereby ignoring the unique evolutionary constraints on overlapping coding regions. Our method uses an exact evolutionary model, thereby voiding the need for approximation or intensive computation. We test the method by simulating the evolution of overlapping genes of different types as well as under diverse evolutionary scenarios. Our results indicate that the independent estimation approach leads to the false appearance of positive selection even though the gene is in reality subject to negative selection. Finally, we use our method to estimate selection in two influenza A genes for which positive selection was previously inferred. We find no evidence for positive selection in both cases

A Combination of Dopamine Genes Predicts Success by Professional Wall Street Traders

What determines success on Wall Street? This study examined if genes affecting dopamine levels of professional traders were associated with their career tenure. Sixty professional Wall Street traders were genotyped and compared to a control group who did not trade stocks. We found that distinct alleles of the dopamine receptor 4 promoter (DRD4P) and catecholamine-O-methyltransferase (COMT) that affect synaptic dopamine were predominant in traders. These alleles are associated with moderate, rather than very high or very low, levels of synaptic dopamine. The activity of these alleles correlated positively with years spent trading stocks on Wall Street. Differences in personality and trading behavior were also correlated with allelic variants. This evidence suggests there may be a genetic basis for the traits that make one a successful trader

Intronic L1 Retrotransposons and Nested Genes Cause Transcriptional Interference by Inducing Intron Retention, Exonization and Cryptic Polyadenylation

Transcriptional interference has been recently recognized as an unexpectedly complex and mostly negative regulation of genes. Despite a relatively few studies that emerged in recent years, it has been demonstrated that a readthrough transcription derived from one gene can influence the transcription of another overlapping or nested gene. However, the molecular effects resulting from this interaction are largely unknown.Using in silico chromosome walking, we searched for prematurely terminated transcripts bearing signatures of intron retention or exonization of intronic sequence at their 3' ends upstream to human L1 retrotransposons, protein-coding and noncoding nested genes. We demonstrate that transcriptional interference induced by intronic L1s (or other repeated DNAs) and nested genes could be characterized by intron retention, forced exonization and cryptic polyadenylation. These molecular effects were revealed from the analysis of endogenous transcripts derived from different cell lines and tissues and confirmed by the expression of three minigenes in cell culture. While intron retention and exonization were comparably observed in introns upstream to L1s, forced exonization was preferentially detected in nested genes. Transcriptional interference induced by L1 or nested genes was dependent on the presence or absence of cryptic splice sites, affected the inclusion or exclusion of the upstream exon and the use of cryptic polyadenylation signals.Our results suggest that transcriptional interference induced by intronic L1s and nested genes could influence the transcription of the large number of genes in normal as well as in tumor tissues. Therefore, this type of interference could have a major impact on the regulation of the host gene expression

Transcranial direct current stimulation of the prefrontal cortex modulates working memory performance: combined behavioural and electrophysiological evidence

The present study demonstrates that tDCS can alter WM performance by modulating the underlying neural oscillations. This result can be considered an important step towards a better understanding of the mechanisms involved in tDCS-induced modulations of WM performance, which is of particular importance, given the proposal to use electrical brain stimulation for the therapeutic treatment of memory deficits in clinical settings

The emergence of health inequalities in early adulthood: evidence on timing and mechanisms from a West of Scotland cohort

Background Evidence is inconsistent as to whether or not there are health inequalities in adolescence according to socio-economic position (SEP) and whether or when they emerge in early adulthood. Despite the large health inequalities literature, few studies have simultaneously compared the relative importance of ?health selection? versus ?social causation? at this life-stage. This study followed a cohort through the youth-adult transition to: (1) determine whether, and if so, when, health inequalities became evident according to both class of origin and current SEP; (2) compare the importance of health selection and social causation mechanisms; and (3) investigate whether these phenomena vary by gender. Methods Data are from a West-of-Scotland cohort, surveyed five times between age 15 (in 1987, N=1,515, response=85%) and 36. Self-reported physical and mental health were obtained at each survey. SEP was based on parental occupational class at 15, a combination of own education or occupational status at 18 and own occupational class (with an additional non-employment category) at older ages. In respect of when inequalities emerged, we used the relative index of inequality to examine associations between both parental and own current SEP and health at each age. In respect of mechanisms, path models, including SEP and health at each age, investigated both inter and intra-generational paths from SEP to health (?causation?) and from health to SEP (?selection?). Analyses were conducted separately for physical and mental health, and stratified by gender. Results Associations between both physical and mental health and parental SEP were non-significant at every age. Inequalities according to own SEP emerged for physical health at 24 and for mental health at 30. There was no evidence of selection based on physical health, but some evidence of associations between mental health in early adulthood and later SEP (intra-generational selection). Paths indicated intra-generational (males) and inter-generational (females) social causation of physical health inequalities, and intra-generational (males and females) and inter-generational (females) social causation of mental health inequalities. Conclusions The results suggest complex and reciprocal relationships between SEP and health and highlight adolescence and early adulthood as a sensitive period for this process, impacting on future life-chances and health

The Lysosome and Intracellular Signalling.

In addition to being the terminal degradative compartment of the cell's endocytic and autophagic pathways, the lysosome is a multifunctional signalling hub integrating the cell's response to nutrient status and growth factor/hormone signalling. The cytosolic surface of the limiting membrane of the lysosome is the site of activation of the multiprotein complex mammalian target of rapamycin complex 1 (mTORC1), which phosphorylates numerous cell growth-related substrates, including transcription factor EB (TFEB). Under conditions in which mTORC1 is inhibited including starvation, TFEB becomes dephosphorylated and translocates to the nucleus where it functions as a master regulator of lysosome biogenesis. The signalling role of lysosomes is not limited to this pathway. They act as an intracellular Ca2+ store, which can release Ca2+ into the cytosol for both local effects on membrane fusion and pleiotropic effects within the cell. The relationship and crosstalk between the lysosomal and endoplasmic reticulum (ER) Ca2+ stores play a role in shaping intracellular Ca2+ signalling. Lysosomes also perform other signalling functions, which are discussed. Current views of the lysosomal compartment recognize its dynamic nature. It includes endolysosomes, autolysosome and storage lysosomes that are constantly engaged in fusion/fission events and lysosome regeneration. How signalling is affected by individual lysosomal organelles being at different stages of these processes and/or at different sites within the cell is poorly understood, but is discussed

The Emergence of Emotions

Emotion is conscious experience. It is the affective aspect of consciousness. Emotion arises from sensory stimulation and is typically accompanied by physiological and behavioral changes in the body. Hence an emotion is a complex reaction pattern consisting of three components: a physiological component, a behavioral component, and an experiential (conscious) component. The reactions making up an emotion determine what the emotion will be recognized as. Three processes are involved in generating an emotion: (1) identification of the emotional significance of a sensory stimulus, (2) production of an affective state (emotion), and (3) regulation of the affective state. Two opposing systems in the brain (the reward and punishment systems) establish an affective value or valence (stimulus-reinforcement association) for sensory stimulation. This is process (1), the first step in the generation of an emotion. Development of stimulus-reinforcement associations (affective valence) serves as the basis for emotion expression (process 2), conditioned emotion learning acquisition and expression, memory consolidation, reinforcement-expectations, decision-making, coping responses, and social behavior. The amygdala is critical for the representation of stimulus-reinforcement associations (both reward and punishment-based) for these functions. Three distinct and separate architectural and functional areas of the prefrontal cortex (dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex) are involved in the regulation of emotion (process 3). The regulation of emotion by the prefrontal cortex consists of a positive feedback interaction between the prefrontal cortex and the inferior parietal cortex resulting in the nonlinear emergence of emotion. This positive feedback and nonlinear emergence represents a type of working memory (focal attention) by which perception is reorganized and rerepresented, becoming explicit, functional, and conscious. The explicit emotion states arising may be involved in the production of voluntary new or novel intentional (adaptive) behavior, especially social behavior