| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Bower, Peter, et al.
(författare)
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Influence of initial severity of depression on effectiveness of low intensity interventions : meta-analysis of individual patient data
- 2013
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Ingår i: BMJ (Clinical Research Edition). - : BMJ Publishing Group: BMJ. - 0959-8138 .- 1756-1833. ; 346
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Tidskriftsartikel (refereegranskat)abstract
- Objective To assess how initial severity of depression affects the benefit derived from low intensity interventions for depression.Design Meta-analysis of individual patient data from 16 datasets comparing low intensity interventions with usual care.Setting Primary care and community settings.Participants 2470 patients with depression.Interventions Low intensity interventions for depression (such as guided self help by means of written materials and limited professional support, and internet delivered interventions).Main outcome measures Depression outcomes (measured with the Beck Depression Inventory or Center for Epidemiologic Studies Depression Scale), and the effect of initial depression severity on the effects of low intensity interventions.Results Although patients were referred for low intensity interventions, many had moderate to severe depression at baseline. We found a significant interaction between baseline severity and treatment effect (coefficient −0.1 (95% CI −0.19 to −0.002)), suggesting that patients who are more severely depressed at baseline demonstrate larger treatment effects than those who are less severely depressed. However, the magnitude of the interaction (equivalent to an additional drop of around one point on the Beck Depression Inventory for a one standard deviation increase in initial severity) was small and may not be clinically significant.Conclusions The data suggest that patients with more severe depression at baseline show at least as much clinical benefit from low intensity interventions as less severely depressed patients and could usefully be offered these interventions as part of a stepped care model.
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| 3. |
- 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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| 4. |
- Karyotaki, Eirini, et al.
(författare)
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Is self-guided internet-based cognitive behavioural therapy (iCBT) harmful? An individual participant data meta-analysis
- 2018
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Ingår i: Psychological Medicine. - : CAMBRIDGE UNIV PRESS. - 0033-2917 .- 1469-8978. ; 48:15, s. 2456-2466
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Forskningsöversikt (refereegranskat)abstract
- Background. Little is known about potential harmful effects as a consequence of self-guided internet-based cognitive behaviour therapy (iCBT), such as symptom deterioration rates. Thus, safety concerns remain and hamper the implementation of self-guided iCBT into clinical practice. We aimed to conduct an individual participant data (IPD) meta-analysis to determine the prevalence of clinically significant deterioration (symptom worsening) in adults with depressive symptoms who received self-guided iCBT compared with control conditions. Several socio-demographic, clinical and study-level variables were tested as potential moderators of deterioration. Methods. Randomised controlled trials that reported results of self-guided iCBT compared with control conditions in adults with symptoms of depression were selected. Mixed effects models with participants nested within studies were used to examine possible clinically significant deterioration rates. Results. Thirteen out of 16 eligible trials were included in the present IPD meta-analysis. Of the 3805 participants analysed, 7.2% showed clinically significant deterioration (5.8% and 9.1% of participants in the intervention and control groups, respectively). Participants in self-guided iCBT were less likely to deteriorate (OR 0.62, p amp;lt; 0.001) compared with control conditions. None of the examined participant- and study-level moderators were significantly associated with deterioration rates. Conclusions. Self-guided iCBT has a lower rate of negative outcomes on symptoms than control conditions and could be a first step treatment approach for adult depression as well as an alternative to watchful waiting in general practice.
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| 5. |
- Klein, Jan Philipp, et al.
(författare)
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The EVIDENT-trial: protocol and rationale of a multicenter randomized controlled trial testing the effectiveness of an online-based psychological intervention
- 2013
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Ingår i: BMC Psychiatry. - : BioMed Central. - 1471-244X. ; 13
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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.
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| 6. |
- Mehta, Raghav, et al.
(författare)
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QU-BraTS : MICCAI BraTS 2020 Challenge on QuantifyingUncertainty in Brain Tumor Segmentation - Analysis of Ranking Scores and Benchmarking Results
- 2022
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Ingår i: Journal of Machine Learning for Biomedical Imaging. - 2766-905X. ; , s. 1-54
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Tidskriftsartikel (refereegranskat)abstract
- Deep learning (DL) models have provided the state-of-the-art performance in a wide variety of medical imaging benchmarking challenges, including the Brain Tumor Segmentation (BraTS) challenges. However, the task of focal pathology multi-compartment segmentation (e.g., tumor and lesion sub-regions) is particularly challenging, and potential errors hinder the translation of DL models into clinical workflows. Quantifying the reliability of DL model predictions in the form of uncertainties, could enable clinical review of the most uncertain regions, thereby building trust and paving the way towards clinical translation. Recently, a number of uncertainty estimation methods have been introduced for DL medical image segmentation tasks. Developing scores to evaluate and compare the performance of uncertainty measures will assist the end-user in making more informed decisions. In this study, we explore and evaluate a score developed during the BraTS 2019-2020 task on uncertainty quantification (QU-BraTS), and designed to assess and rank uncertainty estimates for brain tumor multi-compartment segmentation. This score (1) rewards uncertainty estimates that produce high confidence in correct assertions, and those that assign low confidence levels at incorrect assertions, and (2) penalizes uncertainty measures that lead to a higher percentages of under-confident correct assertions. We further benchmark the segmentation uncertainties generated by 14 independent participating teams of QU-BraTS 2020, all of which also participated in the main BraTS segmentation task. Overall, our findings confirm the importance and complementary value that uncertainty estimates provide to segmentation algorithms, and hence highlight the need for uncertainty quantification in medical image analyses. Our evaluation code is made publicly available at https://github.com/RagMeh11/QU-BraTS
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| 7. |
- Moritz, Steffen, et al.
(författare)
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Beyond words : Sensory properties of depressive thoughts
- 2014
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Ingår i: Cognition & Emotion. - : ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD. - 0269-9931 .- 1464-0600. ; 28:6, s. 1047-1056
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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.
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| 8. |
- 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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| 9. |
- Shumilova, Oleksandra, et al.
(författare)
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Simulating rewetting events in intermittent rivers and ephemeral streams : A global analysis of leached nutrients and organic matter
- 2019
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Ingår i: Global Change Biology. - : WILEY. - 1354-1013 .- 1365-2486. ; 25:5, s. 1591-1611
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Tidskriftsartikel (refereegranskat)abstract
- Climate change and human pressures are changing the global distribution and the extent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico-chemical changes (preconditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experimentally simulated, under standard laboratory conditions, rewetting of leaves, riverbed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative characteristics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dissolved substances during rewetting events (56%-98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contributed most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached OM. The opposite pattern was found in the arid zone. Environmental variables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached substances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying events.
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| 10. |
- Solmi, Marco, et al.
(författare)
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Validation of the Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) questionnaire for adults
- 2023
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Ingår i: Journal of Affective Disorders. - : ELSEVIER. - 0165-0327 .- 1573-2517. ; 326, s. 249-261
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the in-ternal validity of the co-primary outcome, a composite psychopathology "P-score". Methods: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r >= 0.5 with validated companion question-naires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. Results: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (omega = 0.95). Factor structure was consistent across age and sex. Conclusions: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health.
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