Cognitive-behavior therapy for children and adolescents with anxiety disorders:A meta-analysis of secondary outcomes

Anxiety-focused cognitive-behavioral therapy (CBT) effectively reduces anxiety in children and adolescents. An important remaining question is to what extent anxiety-focused CBT also affects broader outcome domains. Additionally, it remains unclear whether parental involvement in treatment may have impact on domains other than anxiety. A meta-analysis (nstudies = 42, nparticipants = 3239) of the effects of CBT and the moderating role of parental involvement was conducted on the following major secondary outcomes: depressive symptoms, externalizing behaviors, general functioning, and social competence. Randomized controlled trials were included when having a waitlist or active control condition, a youth sample (aged<19) with a primary anxiety disorder diagnosis receiving anxiety-focused CBT and reported secondary outcomes. Controlled effect sizes (Cohen's d) were calculated employing random effect models. CBT had a large effect on general functioning (-1.25[-1.59;0.90], nstudies = 17), a small to moderate effect on depressive symptoms (-0.31[-0.41;-0.22], nstudies = 31) and a small effect on externalizing behaviors (-0.23[-0.38;-0.09], nstudies = 12) from pre-to post-treatment. Effects remained or even further improved at follow-up. Social competence only improved at follow-up (nstudies = 6). Concluding, anxiety-focused CBT has a positive effect on broader outcome domains than just anxiety. Higher parental involvement seemed to have beneficial effects at follow-up, with improvements in general functioning and comorbid symptoms

Using bundle embeddings to predict daily cortisol levels in human subjects

BACKGROUND: Many biological variables sampled from human subjects show a diurnal pattern, which poses special demands on the techniques used to analyze such data. Furthermore, most biological variables belong to nonlinear dynamical systems, which may make linear statistical techniques less suitable to analyze their dynamics. The current study investigates the usefulness of two analysis techniques based on nonlinear lagged vector embeddings: sequentially weighted global linear maps (SMAP), and bundle embeddings. METHODS: Time series of urinary cortisol were collected in 10 participants, in the morning ('night' measurement) and the evening ('day' measurement), resulting in 126 consecutive measurements. These time series were used to create lagged vector embeddings, which were split into 'night' and 'day' bundle embeddings. In addition, embeddings were created based on time series that were corrected for the average time-of-day (TOD) values. SMAP was used to predict future values of cortisol in these embeddings. Global (linear) and local (non-linear) predictions were compared for each embedding. Bootstrapping was used to obtain confidence intervals for the model parameters and the prediction error. RESULTS: The best cortisol predictions were found for the night bundle embeddings, followed by the full embeddings and the time-of-day corrected embeddings. The poorest predictions were found for the day bundle embeddings. The night bundle embeddings, the full embeddings and the TOD-corrected embeddings all showed low dimensions, indicating the absence of dynamical processes spanning more than one day. The dimensions of the day bundles were higher, indicating the presence of processes spanning more than one day, or a higher amount of noise. In the full embeddings, local models gave the best predictions, whereas in the bundles the best predictions were obtained from global models, indicating potential nonlinearity in the former but not the latter. CONCLUSIONS: Using a bundling approach on time series of cortisol may reveal differences between the predictions of night and day cortisol that are difficult to find with conventional time-series methods. Combination of this approach with SMAP may especially be useful when analyzing time-series data with periodic components

Empirical evidence for definitions of episode, remission, recovery, relapse and recurrence in depression:a systematic review

AIMS: For the past quarter of a century, Frank et al.'s (1991) consensus-based definitions of major depressive disorder (MDD) episode, remission, recovery, relapse and recurrence have been the paramount driving forces for consistency in MDD research as well as in clinical practice. This study aims to review the evidence for the empirical validation of Frank et al.'s proposed concept definitions and to discuss evidence-based modifications. METHODS: A literature search of Web of Science and PubMed from 1/1/1991 to 08/30/2017 identified all publications which referenced Frank et al.'s request for definition validation. Publications with data relevant for validation were included and checked for referencing other studies providing such data. RESULTS: A total of 56 studies involving 39 315 subjects were included, mainly presenting data to validate the severity and duration thresholds for defining remission and recovery. Most studies indicated that the severity threshold for defining remission should decrease. Additionally, specific duration thresholds to separate remission from recovery did not add any predictive value to the notion that increased remission duration alleviates the risk of reoccurrence of depressive symptoms. Only limited data were available to validate the severity and duration criteria for defining a depressive episode. CONCLUSIONS: Remission can best be defined as a less symptomatic state than previously assumed (Hamilton Rating Scale for Depression, 17-item version (HAMD-17) ⩽4 instead of ⩽7), without applying a duration criterion. Duration thresholds to separate remission from recovery are not meaningful. The minimal duration of depressive symptoms to define a depressive episode should be longer than 2 weeks, although further studies are required to recommend an exact duration threshold. These results are relevant for researchers and clinicians aiming to use evidence-based depression outcomes

Effects of urinary cortisol levels and resting heart rate on the risk for fatal and nonfatal cardiovascular events

AbstractBackground and aimsHigher cortisol levels are associated with cardiovascular mortality in the elderly. It is unclear whether this association also exists in a general population of younger adults and for non-fatal cardiovascular events. Likewise, resting heart rate is associated with cardiovascular mortality, but fewer studies have also considered non-fatal events. The goal of this study was to investigate whether twenty-four-hour urinary cortisol (24-h UFC) levels and resting heart rate (RHR) predict major adverse fatal and non-fatal cardiovascular events (MACE) in the general population.MethodsWe used data from a subcohort of the PREVEND study, a prospective general population based cohort study with a follow-up of 6.4 years for 24-h UFC and 10.6 years for RHR. Participants were 3432 adults (mean age 49 years, range 28–75). 24-h UFC was collected and measured by liquid chromatography—tandem mass spectrometry. RHR was measured at baseline in a supine position for 10 min with the Dinamap XL Model 9300. Information about cardiovascular events and mortality was obtained from the Dutch national registry of hospital discharge diagnoses and the municipal register respectively.Results24-h UFC did not significantly increase the hazard of MACE (hazard ratio = 0.999, 95% confidence interval = 0.993–1.006, p = 0.814). RHR increased the risk for MACE with 17% per 10 extra heart beats per minute (hazard ratio = 1.016, 95% confidence interval = 1.001–1.031, p = 0.036) after adjustment for conventional risk factors.ConclusionsIn contrast to 24-h UFC, RHR is a risk marker for MACE in the general population

Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positive B-cells

This paper describes a bi-specific antibody, which was called BIS20x3. It retargets CD3ɛ-positive cells (T-cells) to CD20-positive cells and was obtained by hybrid–hybridoma fusion. BIS20x3 could be isolated readily from quadroma culture supernatant and retained all the signalling characteristics associated with both of its chains. Cross-linking of BIS20x3 on Ramos cells leads to DNA fragmentation percentages similar to those obtained after Rituximab-cross-linking. Cross-linking of BIS20x3 on T-cells using cross-linking F(ab′)2-fragments induced T-cell activation. Indirect cross-linking of T-cell-bound BIS20x3 via Ramos cells hyper-activated the T-cells. Furthermore, it was demonstrated that BIS20x3 effectively re-targets T-cells to B-cells, leading to high B-cell cytotoxicity. The results presented in this paper show that BIS20x3 is fully functional in retargeting T-cells to B-cells and suggest that B-cell lymphomas may represent ideal targets for T-cell retargeting bi-specific antibodies, because the retargeted T-cell is maximally stimulated in the presence of B-cells. Additionally, since B-cells may up-regulate CD95/ Fas expression upon binding of CD20-directed antibodies, B-cells will become even more sensitive for T-cell mediated killing via CD95L/ Fas L, and therefore supports the intention to use T-cell retargeting bi-specific antibodies recognizing CD20 on B-cell malignancies as a treatment modality for these diseases. © 2001 Cancer Research Campaign http://www.bjcancer.co

The topobiology of chemical elements in seabird feathers

The highly organized morphogenesis of bird feathers holds important phylo- and ontogenetic information on the evolution of birds, organogenesis, tissue regeneration, and the health status of individual animals. Altered topobiological patterns are regularly used as retrospective evidence for disturbed developmental trajectories due to the past exposure to environmental stressors. Using the most advanced high-resolution (5-70 μm) X-ray fluorescence microscopy (XFM), we describe in the feathers from three species of Procellariiformes hitherto unknown, depositions of elements (Zn, Ca, Br, Cu, Fe) that are independent of pigmentation or any underlying variation in density or polymer structure. In the case of Zn, the pattern across several species of Procellariiformes, but not other species, consisted of highly regular bands of Zn numbering 30-32, which may reflect the estimated number of days of active feather growth or the duration of the moult period. Thus, speculatively, the highly consistent Zn pattern might be the result of a so far unknown diurnal systemic regulation rather than local heterogeneity amongst the follicular stem cells

Identification and characterization of Cercospora beticola necrosis-inducing effector CbNip1

Cercospora beticola is a hemibiotrophic fungus that causes cercospora leaf spot disease of sugar beet (Beta vulgaris). After an initial symptomless biotrophic phase of colonization, necrotic lesions appear on host leaves as the fungus switches to a necrotrophic lifestyle. The phytotoxic secondary metabolite cercosporin has been shown to facilitate fungal virulence for several Cercospora spp. However, because cercosporin production and subsequent cercosporin‐initiated formation of reactive oxygen species is light‐dependent, cell death evocation by this toxin is only fully ensured during a period of light. Here, we report the discovery of the effector protein CbNip1 secreted by C. beticola that causes enhanced necrosis in the absence of light and, therefore, may complement light‐dependent necrosis formation by cercosporin. Infiltration of CbNip1 protein into sugar beet leaves revealed that darkness is essential for full CbNip1‐triggered necrosis, as light exposure delayed CbNip1‐triggered host cell death. Gene expression analysis during host infection shows that CbNip1 expression is correlated with symptom development in planta. Targeted gene replacement of CbNip1 leads to a significant reduction in virulence, indicating the importance of CbNip1 during colonization. Analysis of 89 C. beticola genomes revealed that CbNip1 resides in a region that recently underwent a selective sweep, suggesting selection pressure exists to maintain a beneficial variant of the gene. Taken together, CbNip1 is a crucial effector during the C. beticola–sugar beet disease process

Selective digestive and oropharyngeal decontamination in medical and surgical ICU patients:individual patient data meta-analysis

Objectives: Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) improved intensive care unit (ICU), hospital and 28-day survival in ICUs with low levels of antibiotic resistance. Yet it is unclear whether the effect differs between medical and surgical ICU patients.& para;& para;Methods: In an individual patient data meta-analysis, we systematically searched PubMed and included all randomized controlled studies published since 2000. We performed a two-stage meta-analysis with separate logistic regression models per study and per outcome (hospital survival and ICU survival) and subsequent pooling of main and interaction effects.& para;& para;Results: Six studies, all performed in countries with low levels of antibiotic resistance, yielded 16 528 hospital admissions and 17 884 ICU admissions for complete case analysis. Compared to standard care or placebo, the pooled adjusted odds ratios for hospital mortality was 0.82 (95% confidence interval (CI) 0.72-0.93) for SDD and 0.84 (95% CI 0.73-0.97) for SOD. Compared to SOD, the adjusted odds ratio for hospital mortality was 0.90 (95% CI 0.82-0.97) for SDD. The effects on hospital mortality were not modified by type of ICU admission (p values for interaction terms were 0.66 for SDD and control, 0.87 for SOD and control and 0.47 for SDD and SOD). Similar results were found for ICU mortality.& para;& para;Conclusions: In ICUs with low levels of antibiotic resistance, the effectiveness of SDD and SOD was not modified by type of ICU admission. SDD and SOD improved hospital and ICU survival compared to standard care in both patient populations, with SDD being more effective than SOD. (C) 2017 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases

The effect of offering a third-trimester routine ultrasound on pregnancy-specific anxiety and mother-to-infant bonding in low-risk women : a pragmatic cluster-randomized controlled trial

Background: Third-trimester routine ultrasounds are increasingly offered to monitor fetal growth. In addition to limited evidence for its clinical effectiveness, little is known about its importance for pregnancy-specific anxiety and mother-to-infant bonding. Methods: 1275 low-risk women participated in a Dutch nationwide pragmatic cluster-randomized trial and answered questionnaires on pregnancy-specific anxiety (PRAQ-R) and prenatal mother-to-infant bonding (MAAS) before and after a third-trimester routine ultrasound was offered to the intervention group. Linear mixed model regression analyses were performed to examine the effect of offering a third-trimester routine ultrasound on pregnancy-specific anxiety and mother-to-infant bonding. In addition, we examined whether the effect depended on maternal background characteristics and level of satisfaction with the ultrasound procedure. Results: We found no effect of offering a third-trimester routine ultrasound on pregnancy-specific anxiety and mother-to-infant bonding. However, interaction analyses showed that women with high levels of depressive symptoms at baseline and women who were very satisfied with the ultrasound procedure benefited somewhat more from offering a third-trimester routine ultrasound in terms of mother-to-infant bonding compared with women with low or no depressive symptoms, or less satisfied women. Conclusions: The relationship between offering a third-trimester routine ultrasound with pregnancy-specific anxiety and mother-to-infant bonding is limited. A beneficial effect only applies to some subgroups of women. This implies that, in terms of psychological outcomes, there are no counterarguments to implementing a third-trimester routine ultrasound. Strong evidence for offering all pregnant women a third-trimester routine ultrasound for psychological reasons, however, is lacking

Effects of mesenchymal stromal cells versus serum on tendon healing in a controlled experimental trial in an equine model

Abstract Background Mesenchymal stromal cells (MSC) have shown promising results in the treatment of tendinopathy in equine medicine, making this therapeutic approach seem favorable for translation to human medicine. Having demonstrated that MSC engraft within the tendon lesions after local injection in an equine model, we hypothesized that they would improve tendon healing superior to serum injection alone. Methods Quadrilateral tendon lesions were induced in six horses by mechanical tissue disruption combined with collagenase application 3 weeks before treatment. Adipose-derived MSC suspended in serum or serum alone were then injected intralesionally. Clinical examinations, ultrasound and magnetic resonance imaging were performed over 24 weeks. Tendon biopsies for histological assessment were taken from the hindlimbs 3 weeks after treatment. Horses were sacrificed after 24 weeks and forelimb tendons were subjected to macroscopic and histological examination as well as analysis of musculoskeletal marker expression. Results Tendons injected with MSC showed a transient increase in inflammation and lesion size, as indicated by clinical and imaging parameters between week 3 and 6 (p < 0.05). Thereafter, symptoms decreased in both groups and, except that in MSC-treated tendons, mean lesion signal intensity as seen in T2w magnetic resonance imaging and cellularity as seen in the histology (p < 0.05) were lower, no major differences could be found at week 24. Conclusions These data suggest that MSC have influenced the inflammatory reaction in a way not described in tendinopathy studies before. However, at the endpoint of the current study, 24 weeks after treatment, no distinct improvement was observed in MSC-treated tendons compared to the serum-injected controls. Future studies are necessary to elucidate whether and under which conditions MSC are beneficial for tendon healing before translation into human medicine