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Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: “Some College” (yes/no, for any education beyond high school) and “Graduated College” (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10−8) and suggestive (p < 1 × 10−6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue. Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.
White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
This thesis offers a comprehensive guide for startups, using the case study of Smart Break to illustrate a systematic approach in five stages: defining a product, developing a product/strategy, launching a strategy and product, scaling the idea, and the maturing stage. Smart Break serves as a practical guideline for internationalization. The narrative traced the inception of Smart Break in 2015, highlighting its evolution from identifying workplace health issues to the development and launch of a web app. A significant shift occurred in 2018 when a new manager took on the challenge of managing Smart Break internationally, marking the startup's entry into the global arena. The thesis promises to unveil the challenges faced at each stage, providing valuable insights and practical advice for startups. The story of Smart Break took an unexpected turn in 2022 when Raisoft, its parent company, was acquired, leading to a shift in Smart Break's trajectory. Despite facing challenges and market dynamics, Smart Break's journey reflects the stages outlined in the guide. The narrative serves as a reminder that even well-structured startups may encounter unforeseen obstacles, emphasizing the importance of adaptability and viability within the market. The thesis concluded by acknowledging the dynamic nature of internationalization and its potential for both growth and setbacks. Readers can expect to gain a profound understanding of the startup world through Smart Break's compelling case study, offering inspiration and practical insights for their entrepreneurial endeavours.
The aim of this study was to show how loyalty of a brand in the sports spectrum can affect that brand in a tremendous way. I also got to know how some followers chose that brand and what makes the brand so special. Why does a supporter choose to follow a brand and remain loyal to this brand? Why do some brands remain successful over the years? How do these brands keep from being re-placed? And lastly, how does a brand impact a life or a lifestyle? All of these questions helped in the aide in answering in depth throughout this study. This idea stemmed from a strong desire to learn what causes brand loyalty in sports. The theory that I had was that emotion and satisfaction from the brand creates a strong bond with the brand. Looking into separate sports and organizations, I was able to understand different approaches used to garner the loyalty they desired. using the empirical framework thesis I read and visited many resources to reach an outcome. The findings that came from this research changed from demographic. Using information on sports teams and there structure to capitalize on brand loyalty, and also sports products that want a loyal fol-lowing, it began to unfold what is important. Customer loyalty and the four levels that comprise of it, help define the framework on setting out to capture brand loyalty. In conclusion, the findings made were close to what I was originally thinking. Emotion plays a large role in attracting and keeping sports loyalty. By appealing to the hearts of the customer, a brand or team can count on reoccurrence. Satisfaction and authenticity drives the brand in positive way to keep loyalty strong. Whether it be a team or a sports clothing brand, both follow a similar set of guidelines and structures to maintain loyalty within their brand.
Herbivores alter plant biodiversity (species richness) in many of the world’s ecosystems, but the magnitude and the direction of herbivore effects on biodiversity vary widely within and among ecosystems. One current theory predicts that herbivores enhance plant biodiversity at high productivity but have the opposite effect at low productivity. Yet, empirical support for the importance of site productivity as a mediator of these herbivore impacts is equivocal. Here, we synthesize data from 252 large-herbivore exclusion studies, spanning a 20-fold range in site productivity, to test an alternative hypothesis—that herbivore-induced changes in the competitive environment determine the response of plant biodiversity to herbivory irrespective of productivity. Under this hypothesis, when herbivores reduce the abundance (biomass, cover) of dominant species (for example, because the dominant plant is palatable), additional resources become available to support new species, thereby increasing biodiversity. By contrast, if herbivores promote high dominance by increasing the abundance of herbivory-resistant, unpalatable species, then resource availability for other species decreases reducing biodiversity. We show that herbivore-induced change in dominance, independent of site productivity or precipitation (a proxy for productivity), is the best predictor of herbivore effects on biodiversity in grassland and savannah sites. Given that most herbaceous ecosystems are dominated by one or a few species, altering the competitive environment via herbivores or by other means may be an effective strategy for conserving biodiversity in grasslands and savannahs globally.
Objective Interventions to increase physical activity (PA) in cancer survivors have often adopted a ‘one‐size‐fits‐all’ approach, and may benefit from being tailored to psychological constructs associated with behavior. The study objective was to investigate the exercise preferences and psychological constructs related to PA among cancer survivors. Methods Post‐treatment colorectal, endometrial, and breast cancer survivors (n=183) living in metropolitan and non‐metropolitan areas completed survey measures of PA, exercise preferences, attitudes, self‐efficacy, perceived behavioral control (PBC), and intention toward PA. Results A structural equation model with adequate fit and quality indices revealed that instrumental attitude and self‐efficacy were related to PA intention. Intention was related to behavior and mediated the relationship between self‐efficacy and behavior. Preferred exercise intensity was related to self‐efficacy, PBC, attitudes, and intention, while preferred exercise company was related to self‐efficacy and PBC. Participants preferred moderate‐intensity PA (71%), specifically self‐paced (52%) walking (65%) in an outdoor environment (58%). Conclusions Since instrumental attitude and self‐efficacy were associated with PA, incorporating persuasive communications targeting attitudes in PA interventions may promote PA participation. As cancer survivors who prefer low‐intensity exercise and exercising with others report lower self‐efficacy and PBC, interventions targeting confidence and successful experience in this group may also be warranted.
3C 279 is an archetypal blazar with a prominent radio jet that show broadband flux density variability across the entire electromagnetic spectrum. We use an ultra-high angular resolution technique - global Very Long Baseline Interferometry (VLBI) at 1.3mm (230 GHz) - to resolve the innermost jet of 3C 279 in order to study its fine-scale morphology close to the jet base where highly variable-ray emission is thought to originate, according to various models. The source was observed during four days in April 2017 with the Event Horizon Telescope at 230 GHz, including the phased Atacama Large Millimeter/submillimeter Array, at an angular resolution of ∼20 μas (at a redshift of z = 0:536 this corresponds to ∼0:13 pc ∼ 1700 Schwarzschild radii with a black hole mass MBH = 8 × 108 M⊙). Imaging and model-fitting techniques were applied to the data to parameterize the fine-scale source structure and its variation.We find a multicomponent inner jet morphology with the northernmost component elongated perpendicular to the direction of the jet, as imaged at longer wavelengths. The elongated nuclear structure is consistent on all four observing days and across diffierent imaging methods and model-fitting techniques, and therefore appears robust. Owing to its compactness and brightness, we associate the northern nuclear structure as the VLBI "core". This morphology can be interpreted as either a broad resolved jet base or a spatially bent jet.We also find significant day-to-day variations in the closure phases, which appear most pronounced on the triangles with the longest baselines. Our analysis shows that this variation is related to a systematic change of the source structure. Two inner jet components move non-radially at apparent speeds of ∼15 c and ∼20 c (∼1:3 and ∼1:7 μas day-1, respectively), which more strongly supports the scenario of traveling shocks or instabilities in a bent, possibly rotating jet. The observed apparent speeds are also coincident with the 3C 279 large-scale jet kinematics observed at longer (cm) wavelengths, suggesting no significant jet acceleration between the 1.3mm core and the outer jet. The intrinsic brightness temperature of the jet components are ≤1010 K, a magnitude or more lower than typical values seen at ≥7mm wavelengths. The low brightness temperature and morphological complexity suggest that the core region of 3C 279 becomes optically thin at short (mm) wavelengths.
A round-robin study has been carried out to estimate the impact of the human element in small-angle scattering data analysis. Four corrected datasets were provided to participants ready for analysis. All datasets were measured on samples containing spherical scatterers, with two datasets in dilute dispersions and two from powders. Most of the 46 participants correctly identified the number of populations in the dilute dispersions, with half of the population mean entries within 1.5% and half of the population width entries within 40%. Due to the added complexity of the structure factor, far fewer people submitted answers on the powder datasets. For those that did, half of the entries for the means and widths were within 44 and 86%, respectively. This round-robin experiment highlights several causes for the discrepancies, for which solutions are proposed.