Researcher allegiance in psychotherapy outcome research: an overview of reviews

Researcher allegiance (RA) is widely discussed as a risk of bias in psychotherapy outcome research. The relevance attached to RA bias is related to meta-analyses demonstrating an association of RA with treatment effects. However, recent meta-analyses have yielded mixed results. To provide more clarity on the magnitude and robustness of the RA-outcome association this article reports on a meta-meta-analysis summarizing all available meta-analytic estimates of the RA-outcome association. Random-effects methods were used. Primary study overlap was controlled. Thirty meta-analyses were included. The mean RA-outcome association was r=.262 (p=.002, I(2)=28.98%), corresponding to a moderate effect size. The RA-outcome association was robust across several moderating variables including characteristics of treatment, population, and the type of RA assessment. Allegiance towards the RA bias hypothesis moderated the RA-outcome association. The findings of this meta-meta-analysis suggest that the RA-outcome association is substantial and robust. Implications for psychotherapy outcome research are discussed.

Analysis of liver stage development in and merozoite release from hepatocytes

Exoerythrocytic Plasmodium parasites infect hepatocytes and develop to huge multinucleated schizonts inside a parasitophorous vacuole. Finally, thousands of merozoites are formed and released into the host cell cytoplasm by complete disintegration of the parasitophorous vacuole membrane. This, in turn, results in death and detachment of the infected hepatocyte, followed by the formation of merosomes. The fast growth of the parasite and host cell detachment are hallmarks of liver stage development and can easily be monitored. Here, we describe how to translate these observations into assays for characterizing parasite development. Additionally, other recently introduced techniques and tools to analyze and manipulate liver stage parasites are also discussed.

Atypical visual processing in posttraumatic stress disorder

BACKGROUND: Many patients with Posttraumatic Stress Disorder (PTSD) feel overwhelmed in situations with high levels of sensory input, as in crowded situations with complex sensory characteristics. These difficulties might be related to subtle sensory processing deficits similar to those that have been found for sounds in electrophysiological studies. METHOD: Visual processing was investigated with functional magnetic resonance imaging in trauma-exposed participants with (N = 18) and without PTSD (N = 21) employing a picture-viewing task. RESULTS: Activity observed in response to visual scenes was lower in PTSD participants 1) in the ventral stream of the visual system, including striate and extrastriate, inferior temporal, and entorhinal cortices, and 2) in dorsal and ventral attention systems (P < 0.05, FWE-corrected). These effects could not be explained by the emotional salience of the pictures. CONCLUSIONS: Visual processing was substantially altered in PTSD in the ventral visual stream, a component of the visual system thought to be responsible for object property processing. Together with previous reports of subtle auditory deficits in PTSD, these findings provide strong support for potentially important sensory processing deficits, whose origins may be related to dysfunctional attention processes.

Microscopic analysis of chromatin localization and dynamics in C. elegans

During development, the genome undergoes drastic reorganization within the nuclear space. To determine tridimensional genome folding, genome-wide techniques (damID/Hi-C) can be applied using cell populations, but these have to be calibrated using microscopy and single-cell analysis of gene positioning. Moreover, the dynamic behavior of chromatin has to be assessed on living samples. Combining fast stereotypic development with easy genetics and microscopy, the nematode C. elegans has become a model of choice in recent years to study changes in nuclear organization during cell fate acquisition. Here we present two complementary techniques to evaluate nuclear positioning of genes either by fluorescence in situ hybridization in fixed samples or in living worm embryos using the GFP-lacI/lacO chromatin-tagging system.

Whole Proteome Analysis of the Protozoan Parasite Trypanosoma brucei using Stable Isotope Labeling by Amino Acids in Cell Culture and Mass Spectrometry

The single-celled protozoan Trypanosoma brucei spp. is the causative agent of human African trypanosomiasis and nagana in cattle. Quantitative proteomics for the first time allowed for the characterization of the proteome from several different life stages of the parasite (1-3). To achieve this, stable isotope labeling by amino acids in cell culture (SILAC; (4)) was adapted to T. brucei spp. cultures. T. brucei cells grown in standard media with dialyzed fetal calf serum containing heavy isotope-labeled amino acids (arginine and lysine) show efficient incorporation of the labeled amino acids into the whole cell proteome (8-12 divisions) and no detectable amino acid conversions. The method can be applied to both of the major life stages of the parasite and in combination with RNAi or gene knock-out approaches.

Early gene expression analysis in 9L orthotopic tumor-bearing rats identifies immune modulation in molecular response to synchrotron microbeam radiation therapy

Synchrotron Microbeam Radiation Therapy (MRT) relies on the spatial fractionation of the synchrotron photon beam into parallel micro-beams applying several hundred of grays in their paths. Several works have reported the therapeutic interest of the radiotherapy modality at preclinical level, but biological mechanisms responsible for the described efficacy are not fully understood to date. The aim of this study was to identify the early transcriptomic responses of normal brain and glioma tissue in rats after MRT irradiation (400Gy). The transcriptomic analysis of similarly irradiated normal brain and tumor tissues was performed 6 hours after irradiation of 9 L orthotopically tumor-bearing rats. Pangenomic analysis revealed 1012 overexpressed and 497 repressed genes in the irradiated contralateral normal tissue and 344 induced and 210 repressed genes in tumor tissue. These genes were grouped in a total of 135 canonical pathways. More than half were common to both tissues with a predominance for immunity or inflammation (64 and 67% of genes for normal and tumor tissues, respectively). Several pathways involving HMGB1, toll-like receptors, C-type lectins and CD36 may serve as a link between biochemical changes triggered by irradiation and inflammation and immunological challenge. Most immune cell populations were involved: macrophages, dendritic cells, natural killer, T and B lymphocytes. Among them, our results highlighted the involvement of Th17 cell population, recently described in tumor. The immune response was regulated by a large network of mediators comprising growth factors, cytokines, lymphokines. In conclusion, early response to MRT is mainly based on inflammation and immunity which appear therefore as major contributors to MRT efficacy.

CT dose and image quality in the last three scanner generations.

AIM To compare the computed tomography (CT) dose and image quality with the filtered back projection against the iterative reconstruction and CT with a minimal electronic noise detector. METHODS A lung phantom (Chest Phantom N1 by Kyoto Kagaku) was scanned with 3 different CT scanners: the Somatom Sensation, the Definition Flash and the Definition Edge (all from Siemens, Erlangen, Germany). The scan parameters were identical to the Siemens presetting for THORAX ROUTINE (scan length 35 cm and FOV 33 cm). Nine different exposition levels were examined (reference mAs/peek voltage): 100/120, 100/100, 100/80, 50/120, 50/100, 50/80, 25/120, 25/100 and 25 mAs/80 kVp. Images from the SOMATOM Sensation were reconstructed using classic filtered back projection. Iterative reconstruction (SAFIRE, level 3) was performed for the two other scanners. A Stellar detector was used with the Somatom Definition Edge. The CT doses were represented by the dose length products (DLPs) (mGycm) provided by the scanners. Signal, contrast, noise and subjective image quality were recorded by two different radiologists with 10 and 3 years of experience in chest CT radiology. To determine the average dose reduction between two scanners, the integral of the dose difference was calculated from the lowest to the highest noise level. RESULTS When using iterative reconstruction (IR) instead of filtered back projection (FBP), the average dose reduction was 30%, 52% and 80% for bone, soft tissue and air, respectively, for the same image quality (P < 0.0001). The recently introduced Stellar detector (Sd) lowered the radiation dose by an additional 27%, 54% and 70% for bone, soft tissue and air, respectively (P < 0.0001). The benefit of dose reduction was larger at lower dose levels. With the same radiation dose, an average of 34% (22%-37%) and 25% (13%-46%) more contrast to noise was achieved by changing from FBP to IR and from IR to Sd, respectively. For the same contrast to noise level, an average of 59% (46%-71%) and 51% (38%-68%) dose reduction was produced for IR and Sd, respectively. For the same subjective image quality, the dose could be reduced by 25% (2%-42%) and 44% (33%-54%) using IR and Sd, respectively. CONCLUSION This study showed an average dose reduction between 27% and 70% for the new Stellar detector, which is equivalent to using IR instead of FBP.