| 1. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 2. |
- Ardo, Shane, et al.
(författare)
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Pathways to electrochemical solar-hydrogen technologies
- 2018
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Ingår i: Energy & Environmental Science. - : Royal Society of Chemistry. - 1754-5692 .- 1754-5706. ; 11:10, s. 2768-2783
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Forskningsöversikt (refereegranskat)abstract
- Solar-powered electrochemical production of hydrogen through water electrolysis is an active and important research endeavor. However, technologies and roadmaps for implementation of this process do not exist. In this perspective paper, we describe potential pathways for solar-hydrogen technologies into the marketplace in the form of photoelectrochemical or photovoltaic-driven electrolysis devices and systems. We detail technical approaches for device and system architectures, economic drivers, societal perceptions, political impacts, technological challenges, and research opportunities. Implementation scenarios are broken down into short-term and long-term markets, and a specific technology roadmap is defined. In the short term, the only plausible economical option will be photovoltaic-driven electrolysis systems for niche applications. In the long term, electrochemical solar-hydrogen technologies could be deployed more broadly in energy markets but will require advances in the technology, significant cost reductions, and/ or policy changes. Ultimately, a transition to a society that significantly relies on solar-hydrogen technologies will benefit from continued creativity and influence from the scientific community.
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| 3. |
- Entekhabi, Sina, 1989, et al.
(författare)
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Visualization of feature locations with the tool FeatureDashboard
- 2019
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Ingår i: ACM International Conference Proceeding Series. - New York, NY, USA : ACM. ; B
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Konferensbidrag (refereegranskat)abstract
- Modern development processes and issue trackers often use the notion of features to manage a software system. Features allow communicating system characteristics across stakeholders and keeping an overview understanding - especially important for systems that exist in many different variants. However, maintaining, evolving or reusing features (e.g., propagating across variants, or integrating into a platform) requires knowing their locations to prevent extensive feature-location recovery. We advocate the use of embedded annotations, added directly into software assets by the developers during development. To support this process and provide immediate benefits to developers when using such annotations, we present the open-source tool FeatureDashboard. It extracts and visualizes features and their locations using different views and metrics. As such, it encourages developers recording features and their locations early, to prevent feature identification and location efforts, as well as it supports system comprehension.
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| 4. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 5. |
- García Gonzalo, Sergio, 1989, et al.
(författare)
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Variability modeling of service robots: Experiences and challenges
- 2019
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Ingår i: ACM International Conference Proceeding Series. - New York, NY, USA : ACM.
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Konferensbidrag (refereegranskat)abstract
- Sensing, planning, controlling, and reasoning, are human-like capabilities that can be articially replicated in an autonomous robot. Such a robot implements data structures and algorithms devised on a large spectrum of theories, from probability theory, mechanics, and control theory to ethology, economy, and cognitive sciences. Software plays a key role in the development of robotic systems, as it is the medium to embody intelligence in the machine. During the last years, however, software development is increasingly becoming the bottleneck of robotic systems engineering due to three factors: (a) the software development is mostly based on community efforts and it is not coordinated by key stakeholders; (b) robotic technologies are characterized by a high variability that makes reuse of software a challenging practice; and (c) robotics developers are usually not specically trained in software engineering. In this paper, we illustrate our experiences from EU, academic, and industrial projects in identifying, modeling, and managing variability in the domain of service robots. We hope to raise awareness for the specic variability challenges in robotics software engineering and to inspire other researchers to advance thiseld.
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| 6. |
- Karyotaki, Eirini, et al.
(författare)
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Do guided internet-based interventions result in clinically relevant changes for patients with depression? : An individual participant data meta-analysis
- 2018
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Ingår i: Clinical Psychology Review. - : Elsevier. - 0272-7358 .- 1873-7811. ; 63, s. 80-92
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Forskningsöversikt (refereegranskat)abstract
- Little is known about clinically relevant changes in guided Internet-based interventions for depression. Moreover, methodological and power limitations preclude the identification of patients' groups that may benefit more from these interventions. This study aimed to investigate response rates, remission rates, and their moderators in randomized controlled trials (RCTs) comparing the effect of guided Internet-based interventions for adult depression to control groups using an individual patient data meta-analysis approach. Literature searches in PubMed, Embase, PsycINFO and Cochrane Library resulted in 13,384 abstracts from database inception to January 1, 2016. Twenty-four RCTs (4889 participants) comparing a guided Internet-based intervention with a control group contributed data to the analysis. Missing data were multiply imputed. To examine treatment outcome on response and remission, mixed-effects models with participants nested within studies were used. Response and remission rates were calculated using the Reliable Change Index. The intervention group obtained significantly higher response rates (OR = 2.49, 95% CI 2.17-2.85) and remission rates compared to controls (OR = 2.41, 95% CI 2.07-2.79). The moderator analysis indicated that older participants (OR = 1.01) and native-born participants (1.66) were more likely to respond to treatment compared to younger participants and ethnic minorities respectively. Age (OR = 1.01) and ethnicity (1.73) also moderated the effects of treatment on remission.Moreover, adults with more severe depressive symptoms at baseline were more likely to remit after receiving intemet-based treatment (OR = 1.19). Guided Internet-based interventions lead to substantial positive treatment effects on treatment response and remission at post-treatment. Thus, such interventions may complement existing services for depression and potentially reduce the gap between the need and provision of evidence-based treatments.
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| 7. |
- Loza, M. J., et al.
(författare)
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Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study
- 2016
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Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013.
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| 8. |
- Meyer, Björn, et al.
(författare)
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Effects of an Internet intervention (Deprexis) on severe depression symptoms : Randomized controlled trial
- 2015
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Ingår i: Internet Interventions. - : Elsevier. - 2214-7829. ; 2:1, s. 48-59
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundStudies have shown that certain Internet interventions can help alleviate depression. However, many such interventions contain personal support elements, making it difficult to ascertain whether the program or the support drives the effects. Studies are needed to investigate whether Internet interventions contribute to symptom reduction even when they are delivered without personal support, and even among severely depressed individuals who often receive other forms of treatment.ObjectiveThis randomized controlled trial aimed to examine the effect of an Internet intervention that was deployed without personal support (“Deprexis”) among adults with initially severe depression symptoms.MethodsAdults recruited from a range of sources who had exceeded the threshold for severe depression (PHQ-9 ≥ 15) in a pre-screening assessment and met inclusion criteria were randomized (N = 163) to the intervention (3 months program access; n = 78) or care-as-usual/waitlist control (n = 85). A diagnostic screening interview was administered by telephone at baseline to all participants. Online assessments were administered at baseline, 3 months (post-treatment), and 6 months (follow-up). The main outcome was the Patient Health Questionnaire (PHQ-9) between baseline and post-treatment.ResultsEighty-two percent of randomized participants were reached for the post-treatment assessment. Results for the intention-to-treat (ITT) sample showed significant intervention effects on depression reduction between baseline and post-treatment (linear mixed model [MM], F1,155.6 = 9.00, p < .01, for the time by condition interaction), with a medium between-group effect size, Cohen's d = 0.57 (95% CI: 0.22–0.92). Group differences in depression severity at follow-up were marginally significant in the ITT sample, t (119) = 1.83, p = 0.07, and smaller than at post-treatment (PHQ-9, d = 0.33, 95% CI: − 0.03–0.69). The number needed to treat (NNT) at post-treatment was 5, with 38% of participants in the intervention group achieving response (at least 50% PHQ-9 symptom change, plus post-treatment score < 10), compared to 17% in the control group, p < 0.01. Effects on secondary outcomes, including anxiety, health-related quality of life, and somatic symptoms, were not significant, with the exception of significant effects on anxiety reduction in PP analyses. Early ratings of program helpfulness/alliance (after 3 weeks) predicted pre–post depression reduction, controlling for baseline severity and early symptom change.ConclusionsThese results replicate and extend previous findings by showing that Deprexis can facilitate symptomatic improvement over 3 months and, perhaps to a lesser degree, up until 6 months among adults with initially severe depression.
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| 9. |
- Mukelabai, Mukelabai, 1985, et al.
(författare)
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Tackling Combinatorial Explosion: A Study of Industrial Needs and Practices for Analyzing Highly Configurable Systems
- 2018
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Ingår i: Automated Software Engineering. - New York, NY, USA : ACM. - 1573-7535 .- 0928-8910. ; , s. 155-166
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Konferensbidrag (refereegranskat)abstract
- Highly configurable systems are complex pieces of software. To tackle this complexity, hundreds of dedicated analysis techniques have been conceived, many of which able to analyze system properties for all possible system configurations, as opposed to traditional, single-system analyses. Unfortunately, it is largely unknown whether these techniques are adopted in practice, whether they address actual needs, or what strategies practitioners actually apply to analyze highly configurable systems. We present a study of analysis practices and needs in industry. It relied on a survey with 27 practitioners engineering highly configurable systems and follow-up interviews with 15 of them, covering 18 different companies from eight countries. We confirm that typical properties considered in the literature (e.g., reliability) are relevant, that consistency between variability models and artifacts is critical, but that the majority of analyses for specifications of configuration options (a.k.a., variability model analysis) is not perceived as needed. We identified rather pragmatic analysis strategies, including practices to avoid the need for analysis. For instance, testing with experience-based sampling is the most commonly applied strategy, while systematic sampling is rarely applicable. We discuss analyses that are missing and synthesize our insights into suggestions for future research.
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| 10. |
- Möller, Per Werner, et al.
(författare)
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The Effects of Vasoconstriction And Volume Expansion on Veno-Arterial ECMO Flow
- 2019
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Ingår i: Shock. - 1073-2322. ; 51:5, s. 650-658
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Tidskriftsartikel (refereegranskat)abstract
- Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is gaining widespread use in the treatment of severe cardiorespiratory failure. Blood volume expansion is commonly used to increase ECMO flow (QECMO), with risk of positive fluid balance and worsening prognosis. We studied the effects of vasoconstriction on recruitment of blood volume as an alternative for increasing QECMO, based on the concepts of venous return.In a closed chest, centrally cannulated porcine preparation (n=9) in ventricular fibrillation and VA-ECMO with vented left atrium, mean systemic filling pressure (MSFP), and venous return driving pressure (VRdP) were determined in Euvolemia, during Vasoconstriction (norepinephrine 0.05, 0.125, and 0.2μg/kg/min) and after Volume Expansion (3 boluses of 10mL/kg Ringer's lactate). Maximum achievable QECMO was examined.Vasoconstriction and Volume Expansion both increased maximum achievable QECMO, delivery of oxygen (DO2), and MSFP, but right atrial pressure increased in parallel. VRdP did not change. The vascular elastance curve was shifted to the left by Vasoconstriction, with recruitment of stressed volume. It was shifted to the right by Volume Expansion with direct expansion of stressed volume. Volume Expansion decreased resistance to venous return and pump afterload.In a circulation completely dependent on ECMO support, maximum achievable flow directly depended on the vascular factors governing venous return-i.e., closing conditions, stressed vascular volume and the elastance and resistive properties of the vasculature. Both treatments increased maximum achievable ECMO flow at stable DO2, via increases in stressed volume by different mechanisms. Vascular resistance and pump afterload decreased with Volume Expansion.
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| 11. |
- Philipp Klein, Jan, et al.
(författare)
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Effects of a Psychological Internet Intervention in the Treatment of Mild to Moderate Depressive Symptoms: Results of the EVIDENT Study, a Randomized Controlled Trial
- 2016
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Ingår i: Psychotherapy and Psychosomatics. - : KARGER. - 0033-3190 .- 1423-0348. ; 85:4, s. 218-228
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mild to moderate depressive symptoms are common but often remain unrecognized and treated inadequately. We hypothesized that an Internet intervention in addition to usual care is superior to care as usual alone (CAU) in the treatment of mild to moderate depressive symptoms in adults. Methods: This trial was controlled, randomized and assessor-blinded. Participants with mild to moderate depressive symptoms (Patient Health Questionnaire, PHQ-9, score 5-14) were recruited from clinical and non-clinical set-tings and randomized to either CAU or a 12-week Internet intervention (Deprexis) adjunctive to usual care. Outcomes were assessed at baseline, 3 months (post-assessment) and 6 months (follow-up). The primary outcome measure was self-rated depression severity (PHQ-9). The main analysis was based on the intention-to-treat principle and used linear mixed models. Results: A total of 1,013 participants were randomized. Changes in PHQ-9 from baseline differed significantly between groups (t(825) = 6.12, p amp;lt; 0.001 for the main effect of group). The post-assessment between-group effect size in favour of the intervention was d = 0.39 (95% CI: 0.13-0.64). It was stable at follow-up, with d = 0.32 (95% CI: 0.06-0.69). The rate of participants experiencing at least minimally clinically important PHQ-9 change at the post-assessment was higher in the intervention group (35.6 vs. 20.2%) with a number needed to treat of 7 (95% CI: 5-10). Conclusions: The Internet intervention examined in this trial was superior to CAU alone in reducing mild to moderate depressive symptoms. The magnitude of the effect is clinically important and has public health implications. (C) 2016 S. Karger AG, Basel
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| 12. |
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| 13. |
- Sadovykh, Andrey, et al.
(författare)
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REVaMP2 Project: Towards Round-Trip Engineering of Software Product Lines - Approach, Intermediate Results and Challenges
- 2019
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Ingår i: TOOLS 2019. - Cham : Springer. - 0302-9743 .- 1611-3349.
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Konferensbidrag (refereegranskat)abstract
- © 2019, Springer Nature Switzerland AG. The REVaMP2 Project is a major European effort towards Round-Trip Engineering of Software Product Lines for software intensive systems. Indeed, software is predominant in almost every modern industry. The importance of time-to-market has grown tremendously in many business domains. Organizations are in a constant search for approaches for mass production of highly customizable systems. The software product lines engineering approach promises to provide up to 10× speed increase benefits in time-to-market. Traditionally, automated tools proposed a top-down approach, i.e., variants were generated from a model of the product line. However, the industry used a bottom-up approach that helped to re-create a product line out of various clones of a system. This operation is very costly and error prone. The goal of REVaMP2 is to automate the process of extracting a product line from various system artifacts and help with verification and the co-evolution of the product line. The project involves 27 partners that contribute with diverse research and industrial practices to address case study challenges stemming from 11 application domains. In this paper, we would like to present the motivation for the project, the current approach, the intermediate results and challenges.
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| 14. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 15. |
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