| 1. |
- Bieniossek, Christoph, et al.
(författare)
-
Automated unrestricted multigene recombineering for multiprotein complex production
- 2009
-
Ingår i: Nature Methods. - 1548-7091 .- 1548-7105. ; 6:6, s. 447-U68
-
Tidskriftsartikel (refereegranskat)abstract
- Structural and functional studies of many multiprotein complexes depend on recombinant-protein overexpression. Rapid revision of expression experiments and diversification of the complexes are often crucial for success of these projects; therefore, automation is increasingly indispensable. We introduce Acembl, a versatile and automatable system for protein-complex expression in Escherichia coli that uses recombineering to facilitate multigene assembly and diversification. We demonstrated protein-complex expression using Acembl, including production of the complete prokaryotic holotranslocon.
|
|
| 2. |
- Hollestelle, Antoinette, et al.
(författare)
-
No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
-
Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
-
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.
|
|
| 3. |
- Ackeret, Nadja, et al.
(författare)
-
Six-month stability of individual differences in sports coaches’ burnout, self-compassion and social support
- 2022
-
Ingår i: Psychology of Sport And Exercise. - : Elsevier. - 1469-0292 .- 1878-5476. ; 61, s. 237-
-
Tidskriftsartikel (refereegranskat)abstract
- Using a three-wave prospective cross-lagged panel design, the study examined six-month stability of burnout, self-compassion and social support among sports coaches in terms of measurement invariance, mean-level change, rank-order stability, and structural stability. The participating coaches (N = 422; Mage = 44.48, SD = 11.03) completed an online questionnaire measuring self-compassion, social support, coach burnout and demographics at baseline and two follow-ups at three months and six months. The various forms of stability were assessed using structural equation modeling. There was no significant mean-level change in burnout, self-compassion, or social support, and all three constructs exhibited measurement invariance. Rank-order stability remained relatively high, ranging from 0.78 to 0.94 across the three time points. For all three constructs, covariances between latent factors were invariant over time, indicating high structural stability. While self-compassion and social support were positively related, both were negatively related to coach burnout. These results confirm the importance of preventing and addressing symptoms of burnout, low self-compassion and poor social support in sports settings.
|
|
| 4. |
- Ardo, Shane, et al.
(författare)
-
Pathways to electrochemical solar-hydrogen technologies
- 2018
-
Ingår i: Energy & Environmental Science. - : Royal Society of Chemistry. - 1754-5692 .- 1754-5706. ; 11:10, s. 2768-2783
-
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.
|
|
| 5. |
- Berger, Thorsten, 1981, et al.
(författare)
-
The state of adoption and the challenges of systematic variability management in industry
- 2020
-
Ingår i: Empirical Software Engineering. - : Springer Science and Business Media LLC. - 1382-3256 .- 1573-7616. ; :25, s. 1755-1797
-
Tidskriftsartikel (refereegranskat)abstract
- Handling large-scale software variability is still a challenge for many organizations. After decades of research on variability management concepts, many industrial organizations have introduced techniques known from research, but still lament that pure textbook approaches are not applicable or efficient. For instance, software product line engineering-an approach to systematically develop portfolios of products-is difficult to adopt given the high upfront investments; and even when adopted, organizations are challenged by evolving their complex product lines. Consequently, the research community now mainly focuses on re-engineering and evolution techniques for product lines; yet, understanding the current state of adoption and the industrial challenges for organizations is necessary to conceive effective techniques. In this multiple-case study, we analyze the current adoption of variability management techniques in twelve medium- to large-scale industrial cases in domains such as automotive, aerospace or railway systems. We identify the current state of variability management, emphasizing the techniques and concepts they adopted. We elicit the needs and challenges expressed for these cases, triangulated with results from a literature review. We believe our results help to understand the current state of adoption and shed light on gaps to address in industrial practice.
|
|
| 6. |
- Entekhabi, Sina, 1989, et al.
(författare)
-
Visualization of feature locations with the tool FeatureDashboard
- 2019
-
Ingår i: ACM International Conference Proceeding Series. - New York, NY, USA : ACM. ; B
-
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.
|
|
| 7. |
- Frazier-Wood, Alexis C., et al.
(författare)
-
Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
-
Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
-
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.
|
|
| 8. |
- Furukawa, Toshi A., et al.
(författare)
-
Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression : a systematic review and component network meta-analysis using individual data
- 2021
-
Ingår i: Lancet psychiatry. - London, United Kingdom : Elsevier. - 2215-0374 .- 2215-0366. ; 8:6, s. 500-511
-
Forskningsöversikt (refereegranskat)abstract
- Findings We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42.0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1.83 [95% credible interval (CrI) -2.90 to -0.80]) and that relaxation might be harmful (1.20 [95% CrI 0.17 to 2.27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0.32 [95% CrI 0.13 to 0.93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. 511
|
|
| 9. |
- García Gonzalo, Sergio, 1989, et al.
(författare)
-
Variability modeling of service robots: Experiences and challenges
- 2019
-
Ingår i: ACM International Conference Proceeding Series. - New York, NY, USA : ACM.
-
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.
|
|
| 10. |
- Karyotaki, Eirini, et al.
(författare)
-
Do guided internet-based interventions result in clinically relevant changes for patients with depression? : An individual participant data meta-analysis
- 2018
-
Ingår i: Clinical Psychology Review. - : Elsevier. - 0272-7358 .- 1873-7811. ; 63, s. 80-92
-
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.
|
|
| 11. |
- Karyotaki, Eirini, et al.
(författare)
-
Internet-Based Cognitive Behavioral Therapy for Depression : A Systematic Review and Individual Patient Data Network Meta-analysis
- 2021
-
Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 78:4, s. 361-371
-
Forskningsöversikt (refereegranskat)abstract
- IMPORTANCE: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them.OBJECTIVE: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information.DATA SOURCES: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019.STUDY SELECTION: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization.DATA EXTRACTION AND SYNTHESIS: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression.MAIN OUTCOMES AND MEASURES: Patient Health Questionnaire-9 (PHQ-9) scores.RESULTS: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9.CONCLUSIONS AND RELEVANCE: In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.
|
|
| 12. |
- Klein, Jan Philipp, et al.
(författare)
-
The EVIDENT-trial: protocol and rationale of a multicenter randomized controlled trial testing the effectiveness of an online-based psychological intervention
- 2013
-
Ingår i: BMC Psychiatry. - : BioMed Central. - 1471-244X. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundDepressive disorders are among the leading causes of worldwide disability with mild to moderate forms of depression being particularly common. Low-intensity treatments such as online psychological treatments may be an effective way to treat mild to moderate depressive symptoms and prevent the emergence or relapse of major depression.Methods/DesignThis study is a currently recruiting multicentre parallel-groups pragmatic randomized-controlled single-blind trial. A total of 1000 participants with mild to moderate symptoms of depression from various settings including in- and outpatient services will be randomized to an online psychological treatment or care as usual (CAU). We hypothesize that the intervention will be superior to CAU in reducing depressive symptoms assessed with the Personal Health Questionnaire (PHQ-9, primary outcome measure) following the intervention (12 wks) and at follow-up (24 and 48 wks). Further outcome parameters include quality of life, use of health care resources and attitude towards online psychological treatments.DiscussionThe study will yield meaningful answers to the question of whether online psychological treatment can contribute to the effective and efficient prevention and treatment of mild to moderate depression on a population level with a low barrier to entry.
|
|
| 13. |
- Koch, Sina, et al.
(författare)
-
NRP1 Presented in trans to the Endothelium Arrests VEGFR2 Endocytosis, Preventing Angiogenic Signaling and Tumor Initiation
- 2014
-
Ingår i: Developmental Cell. - : Elsevier BV. - 1534-5807 .- 1878-1551. ; 28:6, s. 633-646
-
Tidskriftsartikel (refereegranskat)abstract
- Neuropilin 1 (NRP1) modulates angiogenesis by binding vascular endothelial growth factor (VEGF) and its receptor, VEGFR2. We examined the consequences when VEGFR2 and NRP1 were expressed on the same cell (cis) or on different cells (trans). In cis, VEGF induced rapid VEGFR2/NRP1 complex formation and internalization. In trans, complex formation was delayed and phosphorylation of phospholipase C gamma (PLC gamma) and extracellular regulated kinase 2 (ERK2) was prolonged, whereas ERK1 phosphorylation was reduced. Trans complex formation suppressed initiation and vascularization of NRP1-expressing mouse fibrosarcoma and melanoma. Suppression in trans required high-affinity, steady-state binding of VEGF to NRP1, which was dependent on the NRP1 C-terminal domain. Compatible with a trans effect of NRP1, quiescent vasculature in the developing retina showed continuous high NRP1 expression, whereas angiogenic sprouting occurred where NRP1 levels fluctuated between adjacent endothelial cells. Therefore, through communication in trans, NRP1 can modulate VEGFR2 signaling and suppress angiogenesis.
|
|
| 14. |
- Loch, Rolf Antonie, et al.
(författare)
-
Cross interactions between Apolipoprotein E and amyloid proteins in neurodegenerative diseases
- 2023
-
Ingår i: Computational and Structural Biotechnology Journal. - : Elsevier BV. - 2001-0370. ; 21, s. 1189-1204
-
Tidskriftsartikel (refereegranskat)abstract
- Three common Apolipoprotein E isoforms, ApoE2, ApoE3, and ApoE4, are key regulators of lipid homeostasis, among other functions. Apolipoprotein E can interact with amyloid proteins. The isoforms differ by one or two residues at positions 112 and 158, and possess distinct structural conformations and functions, leading to isoform-specific roles in amyloid-based neurodegenerative diseases. Over 30 different amyloid proteins have been found to share similar characteristics of structure and toxicity, suggesting a common interactome. The molecular and genetic interactions of ApoE with amyloid proteins have been extensively studied in neurodegenerative diseases, but have not yet been well connected and clarified. Here we summarize essential features of the interactions between ApoE and different amyloid proteins, identify gaps in the understanding of the interactome and propose the general interaction mechanism between ApoE isoforms and amyloid proteins. Perhaps more importantly, this review outlines what we can learn from the interactome of ApoE and amyloid proteins; that is the need to see both ApoE and amyloid proteins as a basis to understand neurodegenerative diseases.
|
|
| 15. |
- Loza, M. J., et al.
(författare)
-
Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study
- 2016
-
Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1
-
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.
|
|
| 16. |
- Meyer, Björn, et al.
(författare)
-
Effects of an Internet intervention (Deprexis) on severe depression symptoms : Randomized controlled trial
- 2015
-
Ingår i: Internet Interventions. - : Elsevier. - 2214-7829. ; 2:1, s. 48-59
-
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.
|
|
| 17. |
- Moritz, Steffen, et al.
(författare)
-
Beyond words : Sensory properties of depressive thoughts
- 2014
-
Ingår i: Cognition & Emotion. - : ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD. - 0269-9931 .- 1464-0600. ; 28:6, s. 1047-1056
-
Tidskriftsartikel (refereegranskat)abstract
- Verbal thoughts (such as negative cognitions) and sensory phenomena (such as visual mental imagery) are usually conceptualised as distinct mental experiences. The present study examined to what extent depressive thoughts are accompanied by sensory experiences and how this is associated with symptom severity, insight of illness and quality of life. A large sample of mildly to moderately depressed patients (N = 356) was recruited from multiple sources and asked about sensory properties of their depressive thoughts in an online study. Diagnostic status and symptom severity were established over a telephone interview with trained raters. Sensory properties of negative thoughts were reported by 56.5% of the sample (i.e., sensation in at least one sensory modality). The highest prevalence was seen for bodily (39.6%) followed by auditory (30.6%) and visual (27.2%) sensations. Patients reporting sensory properties of thoughts showed more severe psychopathological symptoms than those who did not. The degree of perceptuality was marginally associated with quality of life. The findings support the notion that depressive thoughts are not only verbal but commonly accompanied by sensory experiences. The perceptuality of depressive thoughts and the resulting sense of authenticity may contribute to the emotional impact and pervasiveness of such thoughts, making them difficult to dismiss for their holder.
|
|
| 18. |
- Mukelabai, Mukelabai, 1985, et al.
(författare)
-
FeatRacer: Locating Features Through Assisted Traceability
- 2023
-
Ingår i: IEEE Transactions on Software Engineering. - 0098-5589 .- 1939-3520. ; 49:12, s. 5060-5083
-
Tidskriftsartikel (refereegranskat)abstract
- Locating features is one of the most common software development activities. It is typically done during maintenance and evolution, when developers need to identify the exact places in a codebase where specific features are implemented. Unfortunately, locating features is laborious and error-prone, since feature knowledge fades, projects are developed by different developers, and features are often scattered across the codebase. Recognizing the need, many automated feature location techniques have been proposed, which try to retroactively recover features, i.e., very domain-specific information from the codebase. Unfortunately, such techniques require large training datasets, only recover coarse-grained locations and produce too many false positives to be useful in practice. An alternative is recording features during development, when they are still fresh in a developer's mind. However, recording is easily forgotten and also costly, especially when the software evolves and such recordings need to be updated. We address the infamous feature location problem (a.k.a., concern location or concept assignment problem) differently. We present FeatRacer, which combines feature recording and automated feature location in a way that allows developers to proactively and continuously record features and their locations during development, while addressing the shortcomings of both strategies. Specifically, FeatRacer relies on embedded code annotations and a machine-learning-based recommender system. When a developer forgets to annotate, FeatRacer reminds the developer about potentially missing features, which it learned from the feature recording practices in the project at hand. FeatRacer also facilitates fine-grained locations as decided by the developer. Our evaluation shows that FeatRacer outperforms traditional automated feature location based on Latent Semantic Indexing (LSI) and Linear Discriminant Analysis (LDA) - two of the most common methods to realize such techniques - when predicting features for 4,650 commit changesets from the histories of 16 open-source projects spanning an average of three years between 1985 and 2015. Compared to the traditional techniques, FeatRacer showed a 3x higher precision and a 4.5x higher recall, with an average precision and recall of 89.6% among all 16 projects. It can accurately predict feature locations within the first five commits of our evaluation projects, being effective already for small datasets. FeatRacer takes on average 1.9ms to learn from past code fragments of a project, and 0.002ms to predict forgotten feature annotations in new code.
|
|
| 19. |
- Mukelabai, Mukelabai, 1985, et al.
(författare)
-
Tackling Combinatorial Explosion: A Study of Industrial Needs and Practices for Analyzing Highly Configurable Systems
- 2018
-
Ingår i: Automated Software Engineering. - New York, NY, USA : ACM. - 1573-7535 .- 0928-8910. ; , s. 155-166
-
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.
|
|
| 20. |
- Mylrea-Foley, Bronacha, et al.
(författare)
-
Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise : the TRUFFLE 2 randomised trial protocol
- 2022
-
Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:4
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years.Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (>= 4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire.Ethics and dissemination: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy.
|
|
| 21. |
- Möller, Per Werner, et al.
(författare)
-
The Effects of Vasoconstriction And Volume Expansion on Veno-Arterial ECMO Flow
- 2019
-
Ingår i: Shock. - 1073-2322. ; 51:5, s. 650-658
-
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.
|
|
| 22. |
- Nitzsche, Anja, 1985-, et al.
(författare)
-
Paladin is a phosphoinositide phosphatase regulating endosomal VEGFR2 signalling and angiogenesis
- 2021
-
Ingår i: EMBO Reports. - : EMBO Press. - 1469-221X .- 1469-3178. ; 22:2
-
Tidskriftsartikel (refereegranskat)abstract
- Cell signalling governs cellular behaviour and is therefore subject to tight spatiotemporal regulation. Signalling output is modulated by specialized cell membranes and vesicles which contain unique combinations of lipids and proteins. The phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2), an important component of the plasma membrane as well as other subcellular membranes, is involved in multiple processes, including signalling. However, which enzymes control the turnover of non-plasma membrane PI(4,5)P-2, and their impact on cell signalling and function at the organismal level are unknown. Here, we identify Paladin as a vascular PI(4,5)P-2 phosphatase regulating VEGFR2 endosomal signalling and angiogenesis. Paladin is localized to endosomal and Golgi compartments and interacts with vascular endothelial growth factor receptor 2 (VEGFR2) in vitro and in vivo. Loss of Paladin results in increased internalization of VEGFR2, over-activation of extracellular regulated kinase 1/2, and hypersprouting of endothelial cells in the developing retina of mice. These findings suggest that inhibition of Paladin, or other endosomal PI(4,5)P-2 phosphatases, could be exploited to modulate VEGFR2 signalling and angiogenesis, when direct and full inhibition of the receptor is undesirable.
|
|
| 23. |
|
|
| 24. |
- Philipp Klein, Jan, et al.
(författare)
-
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
-
Ingår i: Psychotherapy and Psychosomatics. - : KARGER. - 0033-3190 .- 1423-0348. ; 85:4, s. 218-228
-
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
|
|
| 25. |
|
|
| 26. |
- Roy, Sushmita, et al.
(författare)
-
Identification of functional elements and regulatory circuits by Drosophila modENCODE.
- 2010
-
Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6012, s. 1787-1797
-
Tidskriftsartikel (refereegranskat)abstract
- To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
|
|
| 27. |
- Sadovykh, Andrey, et al.
(författare)
-
REVaMP2 Project: Towards Round-Trip Engineering of Software Product Lines - Approach, Intermediate Results and Challenges
- 2019
-
Ingår i: TOOLS 2019. - Cham : Springer. - 0302-9743 .- 1611-3349.
-
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.
|
|
| 28. |
- Schunkert, Heribert, et al.
(författare)
-
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
- 2011
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:4, s. 153-333
-
Tidskriftsartikel (refereegranskat)abstract
- We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
|
|
| 29. |
- Smith, Jennifer A, et al.
(författare)
-
Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
-
Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
-
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.
|
|
| 30. |
|
|
| 31. |
- Vlasceanu, Madalina, et al.
(författare)
-
Addressing climate change with behavioral science: A global intervention tournament in 63 countries
- 2024
-
Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 10:6
-
Tidskriftsartikel (refereegranskat)abstract
- Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions’ effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior—several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people’s initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors.
|
|
| 32. |
- Voight, Benjamin F, et al.
(författare)
-
Plasma HDL cholesterol and risk of myocardial infarction : a mendelian randomisation study
- 2012
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 380:9841, s. 572-580
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12,482 cases of myocardial infarction and 41,331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.FINDINGS: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher, p=8×10(-13)) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93, 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13, 95% CI 1·69-2·69, p=2×10(-10)).INTERPRETATION: Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.
|
|
