| 1. |
- Locke, Adam E, et al.
(author)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Journal article (peer-reviewed)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 2. |
- Shungin, Dmitry, et al.
(author)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Journal article (peer-reviewed)abstract
- 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.
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| 3. |
- Wang, Anqi, et al.
(author)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Journal article (peer-reviewed)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 4. |
- Conti, David, V, et al.
(author)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Journal article (peer-reviewed)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 5. |
- Wöhri, Annemarie, 1976, et al.
(author)
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Light-Induced Structural Changes in a Photosynthetic Reaction Center Caught by Laue Diffraction
- 2010
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 328:5978, s. 630-633
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Journal article (peer-reviewed)abstract
- Photosynthetic reaction centers convert the energy content of light into a transmembrane potential difference and so provide the major pathway for energy input into the biosphere. We applied time-resolved Laue diffraction to study light-induced conformational changes in the photosynthetic reaction center complex of Blastochloris viridis. The side chain of TyrL162, which lies adjacent to the special pair of bacteriochlorophyll molecules that are photooxidized in the primary light conversion event of photosynthesis, was observed to move 1.3 angstroms closer to the special pair after photoactivation. Free energy calculations suggest that this movement results from the deprotonation of this conserved tyrosine residue and provides a mechanism for stabilizing the primary charge separation reactions of photosynthesis.
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| 6. |
- Rose, Linda M, 1963-, et al.
(author)
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RAMP - A new tool for MSD risk management in manualhandling
- 2017
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In: Conference Proceedings 48th Annual Conference of the Association of Canadian Ergonomists & 12th International Symposium on Human Factors in Organizational Design and Management "Organizing for High Performance ".
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Conference paper (peer-reviewed)abstract
- Summative Statement: In this conference contribution RAMP (Risk Assessment and Management tool for Manual Handling - Proactively) will be presented. It is developed for managing MSD risks in manual handling jobs. The presentation will include a demonstration of the digitalised tool and information about upcoming Massive Open Online Courses about it.Problem statement: Manual handling work is regarded as one of the main causes to increased risks of developing Musculoskeletal disorders (MSDs). Several MSD risk assessment tools have been developed, but have been found to have insufficiencies in managing MSD risks in manual handling. The insufficiencies include that tools only assess certain body parts or certain types of work, are not freely accessible, assess exposure but not risks, and don´t support the whole risk management process. In 2009 there was a call from a global company, which had identified a need for a scientifically based, freely accessible, risk assessment and risk management tool. The tool should support systematic risk management of MSD risks in manual handling jobs and be able to be used by companies themselves. To meet this call the development of the RAMP tool (Risk Assessment and Management tool for Manual Handling – Proactively) was started. It has been developed in a research and development (R&D) project in close co-operation between researchers and practitioners at companies.Research Objective: The objective of this conference contribution is to present the results of a seven year long R&D project: to describe the RAMP tool and its development, present the digitalised version, share some experiences from its use, and inform about upcoming RAMP Massive Open Online Courses (MOOCs), aimed at educating and training users in the RAMP tool.Methodology: RAMP is scientifically based and was developed with a participative R&D methodology. The participating organisations as well as the methodology, including the base for the development, ranging from scientific publications and legislation to user testing and feed-back, will be described in the presentation.Results: The RAMP tool consists of four parts: RAMP I, RAMP II, The Results module and the Action module. At the conference, these will be presented and the digitalised version of RAMP will be demonstrated. In addition, information about three Massive Open Online Courses (MOOCs) about the RAMP tool which are being developed will be presented and user experiences from applying RAMP will be shared. In addition to the oral presentation a workshop on RAMP is planned to be held at the conference.Discussion: The discussion focuses on how methods like RAMP, which are freely accessible, can be spread after the R&D project is finished. Another question is how to secure updates in the future for methods which do not bring any profit for the developers/owners.Conclusions: It is concluded that RAMP, a scientifically based new tool for risk management of MSD risks in manual handling, is freely available via KTH’s homepage and that a MOOC-package for disseminating knowledge and training on how to use the tool will be accessible from the autumn 2017.
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| 7. |
- Rose, Linda, 1963-, et al.
(author)
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The RAMP package for MSD risk management in manual handling – A freely accessible tool, with website and training courses
- 2020
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In: Applied Ergonomics. - : Elsevier BV. - 0003-6870 .- 1872-9126. ; 86
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Journal article (peer-reviewed)abstract
- In this paper the RAMP Package is presented with the objective to facilitate the application of the RAMP tool to systematically manage MSD risks. The package consists of the RAMP tool (Risk Assessment and Management tool for manual handling Proactively), the RAMP website, and free, globally available online, training courses (MOOCs). An Action module used for managing identified MSD risks is introduced. The tool, encompassing a wide range of risks, is applicable to the whole risk management process. Furthermore, RAMP is openly available for download, and free to use. The RAMP tool and training materials were developed using a participative iterative methodology including researchers and practitioners. RAMP was downloaded in 86 countries in the first 26 months since its' launch and over 2400 learners from high-, middle- and low-income countries have joined the MOOCs. The RAMP Package meets organisations’ needs for an accessible, comprehensive risk assessment and management tool.
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| 8. |
- Eklund, Linda M., et al.
(author)
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Cold air exposure at -15 °C induces more airway symptoms and epithelial stress during heavy exercise than rest without aggravated airway constriction
- 2022
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In: European Journal of Applied Physiology. - : Springer. - 1439-6319 .- 1439-6327. ; 122:12, s. 2533-2544
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Journal article (peer-reviewed)abstract
- Purpose: Exposure to cold air may harm the airways. It is unclear to what extent heavy exercise adds to the cold-induced effects on peripheral airways, airway epithelium, and systemic immunity among healthy individuals. We investigated acute effects of heavy exercise in sub-zero temperatures on the healthy airways.Methods: Twenty-nine healthy individuals underwent whole body exposures to cold air in an environmental chamber at − 15 °C for 50 min on two occasions; a 35-min exercise protocol consisting of a 5-min warm-up followed by 2 × 15 min of running at 85% of VO2max vs. 50 min at rest. Lung function was measured by impulse oscillometry (IOS) and spirometry before and immediately after exposures. CC16 in plasma and urine, and cytokines in plasma were measured before and 60 min after exposures. Symptoms were surveyed pre-, during and post-trials.Results: FEV1 decreased after rest (− 0.10 ± 0.03 L, p < 0.001) and after exercise (− 0.06 ± 0.02 L, p = 0.012), with no difference between trials. Exercise in − 15 °C induced greater increases in lung reactance (X5; p = 0.023), plasma CC16 (p < 0.001) as well as plasma IL-8 (p < 0.001), compared to rest. Exercise induced more intense symptoms from the lower airways, whereas rest gave rise to more general symptoms.Conclusion: Heavy exercise during cold air exposure at − 15 °C induced signs of an airway constriction to a similar extent as rest in the same environment. However, biochemical signs of airway epithelial stress, cytokine responses, and symptoms from the lower airways were more pronounced after the exercise trial.
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| 9. |
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| 10. |
- Mejtoft, Thomas, Universitetslektor, 1976-, et al.
(author)
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Medtech innovation guide : an empiric model to support medical technology innovation
- 2022
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In: Health and Technology. - : Springer. - 2190-7188 .- 2190-7196. ; 12:5, s. 911-922
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Journal article (peer-reviewed)abstract
- Innovation has become increasingly important for most industries to cope with rapid technological changes as well as changing societal needs. Even though there are many sectors with specific needs when it comes to supporting innovation, the medical technology sector is facing several unique challenges that both increases the lead-time from idea to finished product and decreases the number of innovations that are developed. This paper presents a proposed innovation guide that has been developed and evaluated as a support for the innovation process within medical technology research. The guide takes the unique characteristics of the medical technology sector into account and serves as a usable guide for the innovator. The complete guide contains both a structure for the process and a usable web application to support the journey from idea to finished products and services. The paper also includes a new readiness level, Sect. 4.2 to provide support both when developing and determining the readiness for clinical implementation of a medical technology innovation.
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| 11. |
- Rose, Linda M., 1963-, et al.
(author)
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The RAMP Tool for Risk Management in Manual Handling : A Seven Year R&D Project
- 2017
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In: NES2017 Conference Proceedings.
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Conference paper (peer-reviewed)abstract
- Background and purposeIn 2010 a research and development (R&D) project started after an initiative from a large global company. They needed a free, systematic musculoskeletal disorder (MSD) risk assessment and management tool, focused on manual handling. The development of the RAMP tool (Risk Assessment and Management tool for Manual Handling – Proactively) was therefore initiated, and the progress has since then been presented at several NES-conferences. The objective of this paper is to present the result of this 7 year R&D project: the digitalized RAMP tool and courses on the tool. MethodologyA participative methodology in close co-operation between researchers and practitioners at companies has been used. The participating companies and the methodology, including the base for the development, ranging from scientific papers to user feedback, and evaluations will be described at NES 2017. ResultsThe R&D project has resulted in the freely accessible RAMP tool consisting of four parts: RAMP I, RAMP II, the Action module and the Results module. A broad range of MSD risks are assessed, the results from assessments are visualized in a novel way and risk reducing actions for risk management are supported. The digitalised version has recently been released. Further, three massive open online courses (MOOCs) for professionals on the RAMP tool are under development, and will also be presented. Discussion The discussion focuses on the need of and dissemination of freely accessible methods such as RAMP, and how to enable users to acquire sufficient knowledge to use them. ConclusionsIn conclusion: The project has resulted in a new tool for MSD risk management in manual handling jobs, the RAMP tool. Evaluations of the tool show that it is regarded as usable from different usability aspects. It is argued that the upcoming online MOCCs may contribute to provide adequate knowledge for proper use of the tool. Keywords. musculoskeletal disorders, risk assessment, risk reducing measures, risk communication, digital tool.
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| 12. |
- Rose, Linda M, 1963-, et al.
(author)
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Workshop: learn how to use the ramp tool for risk assessment and risk management of msd risks in manual handling
- 2017
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Conference paper (other academic/artistic)abstract
- BackgroundManual handling work is regarded as one of the main causes to increased risks of developing Musculoskeletal disorders (MSDs). Several MSD risk assessment tools have been developed, but have been found to have insufficiencies for managing MSD risks in manual handling. The RAMP tool (Risk Assessment and Management tool for Manual Handling – Proactively), was developed to support the whole process of risk management of MSD risks in manual handling: from identification and assessment of risks to developing risk reducing suggestions and systematic risk management. What will you learn?In this workshop you will learn how to use the RAMP tool by participating in applying the tool on an example. RAMP consists of four parts:- The checklist based RAMP I for screening of MSD risks in manual handling,- RAMP II for a more in depth analysis of such risks,- The Action module to support development of risk reducing measures and support systematic risk management, and- The Results module, for communicating the results. It enables presentation of the results at different level of detail and scope, ranging from a work station to the whole company. In the workshop you will get experience from using the four parts of the RAMP tool, based on a film-based example. Bring your laptop to download and use the RAMP tool on your computer!
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| 13. |
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