| 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. |
- Hedman, Erik, et al.
(författare)
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Sudden gains in internet-based cognitive behaviour therapy for severe health anxiety
- 2014
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Ingår i: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 54, s. 22-29
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: A sudden gain is defined as a large and stable individual improvement occurring between two consecutive treatment sessions. Sudden gains have been shown to predict better long-term improvement in several treatment studies, including cognitive behavioural therapy for depression and anxiety disorders, but have not been studied in the treatment of health anxiety or any form of internet-based cognitive behavioural therapy. The aim of this study was to investigate the role of sudden gains in internet-based cognitive behavioural therapy for severe health anxiety.METHOD: We examined the occurrence and significance of sudden gains in measures of health anxiety in 81 participants receiving internet-based cognitive behavioural therapy. We compared patients with sudden gains, patients without sudden gains, and patients with gradual gains.RESULTS: Thirteen participants (16%) experienced one sudden gain in health anxiety with individual sudden gains distributed across the treatment. As expected, patients with a sudden gain showed larger improvements than patients without a sudden gain at post-treatment (d = 1.04) and at one-year follow-up (d = 0.91) on measures of health anxiety.CONCLUSIONS: Consistent with previous studies, sudden gains in internet-based cognitive behavioural therapy are associated with significantly larger and stable treatment effects up to one-year follow-up.
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| 3. |
- Cuijpers, Pim, et al.
(författare)
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Self-reported versus clinician-rated symptoms of depression as outcome measures in psychotherapy research on depression: A meta-analysis
- 2010
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Ingår i: CLINICAL PSYCHOLOGY REVIEW. - : Elsevier Science B.V., Amsterdam.. - 0272-7358 .- 1873-7811. ; 30:6, s. 768-778
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Forskningsöversikt (refereegranskat)abstract
- It is not well-known whether self-report measures and clinician-rated instruments for depression result in comparable outcomes in research on psychotherapy. We conducted a meta-analysis in which randomized controlled trials were included examining the effects of psychotherapy for adult depression. Only studies were included in which both a self-report and a clinician-rated instrument were used. We calculated the effect size (Hedges g) based on the self-report measures, the effect size based on the clinician-rated instruments, and the difference between these two effect sizes (Delta g). A total of 48 studies including a total of 2462 participants was included in the meta-analysis. The differential effect size was Delta g=0.20 (95% CI: 0.10-0.30), indicating that clinician-rated instruments resulted in a significantly higher effect size than self-report instruments from the same studies. When we limited the effect size analysis to those studies comparing the HRSD with the BDI, the differential effect was somewhat smaller, but still statistically significant (Delta g=0.15; 95% CI: 0.03-0.27). This meta-analysis has made it clear that clinician-rated and self-report measures of improvement following psychotherapy for depression are not equivalent. Different symptoms may be more suitable for self-report or ratings by clinicians and in clinical trials it is probably best to include both.
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| 4. |
- Emmelkamp, Paul M.G., et al.
(författare)
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Advancing psychotherapy and evidence-based psychological interventions
- 2014
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Ingår i: International Journal of Methods in Psychiatric Research. - : John Wiley & Sons. - 1049-8931 .- 1557-0657. ; 23:S1, s. 58-91
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Tidskriftsartikel (refereegranskat)abstract
- Psychological models of mental disorders guide research into psychological and environmental factors that elicit and maintain mental disorders as well as interventions to reduce them. This paper addresses four areas. (1) Psychological models of mental disorders have become increasingly transdiagnostic, focusing on core cognitive endophenotypes of psychopathology from an integrative cognitive psychology perspective rather than offering explanations for unitary mental disorders. It is argued that psychological interventions for mental disorders will increasingly target specific cognitive dysfunctions rather than symptom-based mental disorders as a result. (2) Psychotherapy research still lacks a comprehensive conceptual framework that brings together the wide variety of findings, models and perspectives. Analysing the state-of-the-art in psychotherapy treatment research, “component analyses” aiming at an optimal identification of core ingredients and the mechanisms of change is highlighted as the core need towards improved efficacy and effectiveness of psychotherapy, and improved translation to routine care. (3) In order to provide more effective psychological interventions to children and adolescents, there is a need to develop new and/or improved psychotherapeutic interventions on the basis of developmental psychopathology research taking into account knowledge of mediators and moderators. Developmental neuroscience research might be instrumental to uncover associated aberrant brain processes in children and adolescents with mental health problems and to better examine mechanisms of their correction by means of psychotherapy and psychological interventions. (4) Psychotherapy research needs to broaden in terms of adoption of large-scale public health strategies and treatments that can be applied to more patients in a simpler and cost-effective way. Increased research on efficacy and moderators of Internet-based treatments and e-mental health tools (e.g. to support “real time” clinical decision-making to prevent treatment failure or relapse) might be one promising way forward.
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| 5. |
- Hassan, S. Fawad, et al.
(författare)
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Brane induced gravity, its ghost and the cosmological constant problem
- 2011
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :1, s. 020-
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Tidskriftsartikel (refereegranskat)abstract
- Brane Induced Gravity is regarded as a promising framework for addressing the cosmological constant problem, but it also suffers from a ghost instability for parameter values that make it phenomenologically viable. We carry out a detailed analysis of codimension > 2 models employing gauge invariant variables in a flat background approximation. It is argued that using instead a curved background sourced by the brane would not resolve the ghost issue, unless a very specific condition is satisfied (if satisfiable at all). As for other properties of the model, from an explicit analysis of the 4-dimensional graviton propagator we extract a mass, a decay width and a momentum dependent modification of the gravitational coupling for the spin 2 mode. In the flat space approximation, the mass of the problematic spin 0 ghost is instrumental in filtering out a brane cosmological constant. The mass replaces a background curvature that would have had the same function. The optical theorem is used to demonstrate the suppression of graviton leakage into the uncompactified bulk. Then, we derive the 4-dimensional effective action for gravity and show that general covariance is spontaneously broken by the bulk-brane setup. This provides a natural realization of the gravitational Higgs mechanism. We also show that the addition of extrinsic curvature dependent terms has no bearing on linearized brane gravity.
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| 6. |
- Hofmann, Jan Philipp, et al.
(författare)
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Dynamic response of chlorine atoms on a RuO2(110) model catalyst surface
- 2010
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Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 12:47, s. 15358-15366
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Tidskriftsartikel (refereegranskat)abstract
- The dynamic behavior of surface accommodated chlorine atoms on RuO2(110) was studied by a variety of experimental methods including high resolution core level shift, thermal desorption-, and in situ infrared spectroscopy as well as in situ surface X-ray diffraction in combination with state-of-the-art density functional theory calculations. On the chlorinated RuO2(110) surface the undercoordinated oxygen atoms have been selectively replaced by chlorine. These strongly bound surface chlorine atoms shift from bridging to on-top sites when the sample is annealed in oxygen, while the reverse shift of Cl from on-top into bridge positions is observed during CO exposure; the vacant bridge position is then occupied by either chlorine or CO. For the CO oxidation reaction over chlorinated RuO2(110), the reactant induced site switching of chlorine causes a site-blocking of the catalytically active one-fold coordinatively unsaturated (1f-cus) Ru sites. This site blocking reduces the number of active sites and, even more important, on-top Cl blocks the free migration of the adsorbed reactants along the one-dimensional 1f-cus Ru rows, thus leading to a loss of catalytic activity.
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| 7. |
- Hofmann, Jan Philipp, et al.
(författare)
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Hydrogen-Promoted Chlorination of RuO2(110)
- 2010
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 114:24, s. 10901-10909
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Tidskriftsartikel (refereegranskat)abstract
- High-resolution core-level photoemission spectroscopy and temperature-programmed reaction experiments together with density functional theory calculations were used to elucidate on the atomic scale the chlorination mechanism of ruthenium dioxide RuO2(110) by hydrogen chloride exposure. The surface-selective chlorination accounts for the extraordinary stability of the RuO2 catalyst in the Sumitomo process-the heterogeneously catalyzed oxidation of hydrogen chloride by oxygen. The selective replacement of bridging oxygen atoms by chlorine atoms depends on the formation of water molecules serving as leaving groups. Water is produced by the chlorine-assisted recombination of two neighboring surface hydroxyl groups at around 450 K, a temperature where water instantaneously leaves the surface. Finally, the bridging vacancy is rapidly filled in by chlorine atoms, thereby forming bridging chlorine atoms. Preadsorbed hydrogen has shown to facilitate the chlorination process for stoichiometry reasons. The general strategy of transforming bridging O atoms into a good leaving group has been corroborated by the chlorination of RuO2(110) via CO pretreatment with CO2 as the leaving group and subsequent Cl-2 exposure.
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| 8. |
- Hofmann, R, et al.
(författare)
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DETermination of the role of OXygen in suspected Acute Myocardial Infarction trial
- 2014
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Ingår i: American Heart Journal. - : Mosby, Inc.. - 0002-8703 .- 1097-6744. ; 167:3, s. 322-328
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of supplemental oxygen in the setting of suspected acute myocardial infarction (AMI) is recommended in international treatment guidelines and established in prehospital and hospital clinical routine throughout the world. However, to date there is no conclusive evidence from adequately designed and powered trials supporting this practice. Existing data are conflicting and fail to clarify the role of supplemental oxygen in AMI. METHODS: A total of 6,600 normoxemic (oxygen saturation [SpO2] ≥90%) patients with suspected AMI will be randomly assigned to either supplemental oxygen 6 L/min delivered by Oxymask (MedCore Sweden AB, Kista, Sweden) for 6 to 12 hours in the treatment group or room air in the control group. Patient inclusion and randomization will take place at first medical contact, either before hospital admission or at the emergency department. The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry will be used for online randomization, allowing inclusion of a broad population of all-comers. Follow-up will be carried out in nationwide health registries and Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies. The primary objective is to evaluate whether oxygen reduces 1-year all-cause mortality. Secondary end points include 30-day mortality, major adverse cardiac events, and health economy. Prespecified subgroups include patients with confirmed AMI and certain risk groups. In a 3-month pilot study, the study concept was found to be safe and feasible. CONCLUSION: The need to clarify the uncertainty of the role of supplemental oxygen therapy in the setting of suspected AMI is urgent. The DETO2X-AMI trial is designed and powered to address this important issue and may have a direct impact on future recommendations.
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| 9. |
- Kuckertz, Jennie M., et al.
(författare)
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Moderation and mediation of the effect of attention training in social anxiety disorder
- 2014
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Ingår i: Behaviour Research and Therapy. - : Elsevier BV. - 0005-7967 .- 1873-622X. ; 53, s. 30-40
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Tidskriftsartikel (refereegranskat)abstract
- While attention modification programs (AMP) have shown promise as laboratory-based treatments for social anxiety disorder, trials of internet-delivered AMP have not yielded significant differences between active and control conditions. To address these inconsistencies, we examined the moderational and mediational role of attention bias in the efficacy of attention training. We compared data reported by Carlbring et al. (2012) to an identical AMP condition, with the exception that participants were instructed to activate social anxiety fears prior to each attention training session (AMP + FACT; n = 39). We also compared all attention training groups to an internet-delivered cognitive-behavioral therapy (iCBT) condition (n = 40). Participants in the AMP + FACT group experienced greater reductions in social anxiety symptoms than both active (n = 40) and control (n = 39) groups reported by Carlbring et al., and did not differ in symptom reductions from the iCBT group. Higher attention bias predicted greater symptom reductions for participants who completed AMP, but not for the control group. Moreover, change in attention bias mediated the relationship between AMP group (active condition reported by Carlbring et al. versus AMP + FACT) and change in social anxiety symptoms. These results suggest the importance of interpreting findings related to symptom change in attention training studies in the context of bias effects.
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| 10. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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