FinnGen provides genetic insights from a well-phenotyped isolated population

Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.publishedVersionPeer reviewe

Inköp i Virtual Design and Construction : En fallstudie

Construction firms currently spend more than half of revenue on purchase of materials and services. This makes effective management of suppliers an important part of corporate strategy. Also, since firms become more specialized, more services have to be purchased; the consequence is an increased dependence of suppliers. This suggests that construction companies need to aim towards long-term open collaboration with suppliers. However, currently, purchasing is performed in a short-term and competitive manner. The current fixation on price obstructs a reduction of total costs of the entire supply chain. Price is just the tip of the iceberg and under the surface there are hidden costs for management of: operations, supplies, inventory, capital and supplier relationship as well as cost of administration, R&D, support and maintenance which all have to be considered in order to reduce the total cost of ownership. Also, alongside this, virtual construction technologies are introduced to improve the product. This creates opportunity for integration of new information in BIM-models to support the purchasing process. Only using BIM limits users to the product, which creates the risk of organizational and process costs being left behind. Virtual Design and Construction, VDC, is a more holistic approach that also takes into account the organization which designs and builds and the process followed by the organization to design and build the product. In this study VDC is explored as a possible aid in the construction company’s purchasing activities.The study is based on existing theory in the fields of purchasing, construction process and Virtual Design and Construction and a case study of the purchasing process at Veidekke Entreprenad AB. In the case study the purchasing process is mapped during tendering, production preparation and production through interviews. To make sure the entire process was covered respondents were selected to cover different roles in the construction company. From covered purchasing theory a specification for purchasing was created for comparison with the studied purchasing process.In the case study, a manual and experience-based purchasing process was identified where relationships with suppliers was primary transactional. Purchasing activities are primarily based on paper-based documentation and streamlining tools to facilitate the purchasing process is missing. Supplier selection is primarily based on past experience and available information about past suppliers are stored in old project archives which requires that a person looking for information have to know where to look. Selection of final supplier is based on price or estimated total cost. In the process, similar activities are carried out but a standardized approach to procurement is missing and the only measurement performed regarding purchasing was reduction of purchasing price from tendering estimates. However, the case study also showed a purchasing process in transition and henceforth project buyers will be responsible for all project purchases. Based on theory and the case study three areas are presented, where VDC can support the purchasing process:• Implementation of location-based scheduling (LBS) enables project management in aspects of time as well as in space. LBS creates an opportunity to improve delivery schedules and visualization of the production in time and space. These delivery schedules can be the basis for procurement of materials and delivery based on production needs. Visualisation of production can be used to prioritize purchasing work and to support material and service supplier selection. During negotiation visualization can be used as a tool to ensure that criteria for negotiation improve production flow.• At the centre of VDC lies continuous measurement to enable control and predictions of the process. Objectives are established in three levels: Project outcome objectives which are measurable at the end of the project; Project process objectives which influence project outcome are measured regularly; Project controllable factors used by leaders to support daily decisions. This framework can also be used for measuring purchasing- and supplier performance to support supplier selection and continuous improvement. • Integrated Concurrent Engineering (ICE) can be used to make sure that purchasing flexibility is not compromised. Through the usage of cross-functional teams of buyers, planning managers and production managers and an ICE procedure it is possible to explore alternative products and solutions. It is also possible to maintain flexibility in negotiation with suppliers to develop the most favorable technical- and financial solution. The method also opens up for the early involvement of suppliers in order to secure production flow. To achieve full effect, a procedure in which the construction company can affect project design is needed.The results show room for improvement in several areas. To facilitate the development of Veidekke’s future work in the field of VDC, a development model which covers all sub-disciplines of VDC is presented, exemplified using the purchasing process. The model is based on the three maturity levels of VDC implementation. The purpose is to provide support to the implementation and integration of the purchasing routines in the VDC process within the company.Validerat; 20130226 (global_studentproject_submitter

Feasibility of gamified mobile service aimed at physical activation in young men:population-based randomized controlled study (MOPO)

Abstract Background: The majority of young people do not meet the recommendations on physical activity for health. New innovative ways to motivate young people to adopt a physically active lifestyle are needed. Objective: The study aimed to study the feasibility of an automated, gamified, tailored Web-based mobile service aimed at physical and social activation among young men. Methods: A population-based sample of 496 young men (mean age 17.8 years [standard deviation 0.6]) participated in a 6-month randomized controlled trial (MOPO study). Participants were randomized to an intervention (n=250) and a control group (n=246). The intervention group was given a wrist-worn physical activity monitor (Polar Active) with physical activity feedback and access to a gamified Web-based mobile service, providing fitness guidelines, tailored health information, advice of youth services, social networking, and feedback on physical activity. Through the trial, the physical activity of the men in the control group was measured continuously with an otherwise similar monitor but providing only the time of day and no feedback. The primary outcome was the feasibility of the service based on log data and questionnaires. Among completers, we also analyzed the change in anthropometry and fitness between baseline and 6 months and the change over time in weekly time spent in moderate to vigorous physical activity. Results: Mobile service users considered the various functionalities related to physical activity important. However, compliance of the service was limited, with 161 (64.4%, 161/250) participants visiting the service, 118 (47.2%, 118/250) logging in more than once, and 41 (16.4%, 41/250) more than 5 times. Baseline sedentary time was higher in those who uploaded physical activity data until the end of the trial (P=.02). A total of 187 (74.8%, 187/250) participants in the intervention and 167 (67.9%, 167/246) in the control group participated in the final measurements. There were no differences in the change in anthropometry and fitness from baseline between the groups, whereas waist circumference was reduced in the most inactive men within the intervention group (P=.01). Among completers with valid physical activity data (n=167), there was a borderline difference in the change in mean daily time spent in moderate to vigorous physical activity between the groups (11.9 min vs −9.1 min, P=.055, linear mixed model). Within the intervention group (n=87), baseline vigorous physical activity was inversely associated with change in moderate to vigorous physical activity during the trial (R=−.382, P=.01). Conclusions: The various functionalities related to physical activity of the gamified tailored mobile service were considered important. However, the compliance was limited. Within the current setup, the mobile service had no effect on anthropometry or fitness, except reduced waist circumference in the most inactive men. Among completers with valid physical activity data, the trial had a borderline positive effect on moderate to vigorous physical activity. Further development is needed to improve the feasibility and adherence of an integrated multifunctional service

Sleep apnoea is a risk factor for severe COVID-19

Background Obstructive sleep apnoea (OSA) is associated with higher body mass index (BMI), diabetes, older age and male gender, which are all risk factors for severe COVID-19.We aimed to study if OSA is an independent risk factor for COVID-19 infection or for severe COVID-19.Methods OSA diagnosis and COVID-19 infection were extracted from the hospital discharge, causes of death and infectious diseases registries in individuals who participated in the FinnGen study (n=260 405). Severe COVID-19 was defined as COVID-19 requiring hospitalisation. Multivariate logistic regression model was used to examine association. Comorbidities for either COVID-19 or OSA were selected as covariates. We performed a meta-analysis with previous studies.Results We identified 445 individuals with COVID-19, and 38 (8.5%) of them with OSA of whom 19 out of 91 (20.9%) were hospitalised. OSA associated with COVID-19 hospitalisation independent from age, sex, BMI and comorbidities (p-unadjusted=5.13×10−5, OR-adjusted=2.93 (95% CI 1.02 to 8.39), p-adjusted=0.045). OSA was not associated with the risk of contracting COVID-19 (p=0.25). A meta-analysis of OSA and severe COVID-19 showed association across 15 835 COVID-19 positive controls, and n=1294 patients with OSA with severe COVID-19 (OR=2.37 (95% 1.14 to 4.95), p=0.021).Conclusion Risk for contracting COVID-19 was the same for patients with OSA and those without OSA. In contrast, among COVID-19 positive patients, OSA was associated with higher risk for hospitalisation. Our findings are in line with earlier works and suggest OSA as an independent risk factor for severe COVID-19