Investigating a training supporting shared decision making (IT'S SDM 2011): study protocol for a randomized controlled trial

<p/> <p>Background</p> <p>Shared Decision Making (SDM) is regarded as the best practice model for the communicative challenge of decision making about treatment or diagnostic options. However, randomized controlled trials focusing the effectiveness of SDM trainings are rare and existing measures of SDM are increasingly challenged by the latest research findings. This study will 1) evaluate a new physicians' communication training regarding patient involvement in terms of SDM, 2) validate SDM_MASS, a new compound measure of SDM, and 3) evaluate the effects of SDM on the perceived quality of the decision process and on the elaboration of the decision.</p> <p>Methods</p> <p>In a multi-center randomized controlled trial with a waiting control group, 40 physicians from 7 medical fields are enrolled. Each physician contributes a sequence of four medical consultations including a diagnostic or treatment decision.</p> <p>The intervention consists of two condensed video-based individual coaching sessions (15min.) supported by a manual and a DVD. The interventions alternate with three measurement points plus follow up (6 months).</p> <p>Realized patient involvement is measured using the coefficient SDM_MASSdrawn from the Multifocal Approach to the Sharing in SDM (MAPPIN'SDM) which includes objective involvement, involvement as perceived by the patient, and the doctor-patient concordance regarding their judges of the involvement. For validation purposes, all three components of SDM_MASSare supplemented by similar measures, the OPTION observer scale, the Shared Decision Making Questionnaire (SDM-Q) and the dyadic application of the Decisional Conflict Scale (DCS). Training effects are analyzed using t-tests. Spearman correlation coefficients are used to determine convergent validities, the influence of involvement (SDM_MASS) on the perceived decision quality (DCS) and on the elaboration of the decision. The latter is operationalised by the ELAB coefficient from the UP24 (Uncertainty Profile, 24 items version).</p> <p>Discussion</p> <p>Due to the rigorous blinded randomized controlled design, the current trial promises valid and reliable results. On the one hand, we expect this condensed time-saving training to be adopted in clinical routine more likely than previous trainings. On the other hand, the exhaustivity of the MAPPIN'SDM measurement system qualifies it as a reference measure for simpler instruments and to deepen understanding of decision-making processes.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN78716079">ISRCTN78716079</a></p

Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo

Influence of non-local thermodynamic equilibrium and Zeeman effects on magnetic equilibrium reconstruction using spectral motional Stark effect diagnostic

The Motional Stark Effect (MSE) diagnostic is a well established technique to infer the local internal magnetic field in fusion plasmas. In this paper, the existing forward model which describes the MSE data is extended by the Zeeman effect, fine-structure, and relativistic corrections in the interpretation of the MSE spectra for different experimental conditions at the tokamak ASDEX Upgrade. The contribution of the non-Local Thermodynamic Equilibrium (non-LTE) populations among the magnetic sub-levels and the Zeeman effect on the derived plasma parameters is different. The obtained pitch angle is changed by 3°…4° and by 0.5°…1° including the non-LTE and the Zeeman effects into the standard statistical MSE model. The total correction is about 4°. Moreover, the variation of the magnetic field strength is significantly changed by 2.2% due to the Zeeman effect only. While the data on the derived pitch angle still could not be tested against the other diagnostics, the results from an equilibrium reconstruction solver confirm the obtained values for magnetic field strength

History of Reading Struggles Linked to Enhanced Learning in Low Spatial Frequency Scenes

People with dyslexia, who face lifelong struggles with reading, exhibit numerous associated low-level sensory deficits including deficits in focal attention. Countering this, studies have shown that struggling readers outperform typical readers in some visual tasks that integrate distributed information across an expanse. Though such abilities would be expected to facilitate scene memory, prior investigations using the contextual cueing paradigm failed to find corresponding advantages in dyslexia. We suggest that these studies were confounded by task-dependent effects exaggerating known focal attention deficits in dyslexia, and that, if natural scenes were used as the context, advantages would emerge. Here, we investigate this hypothesis by comparing college students with histories of severe lifelong reading difficulties (SR) and typical readers (TR) in contexts that vary attention load. We find no differences in contextual-cueing when spatial contexts are letter-like objects, or when contexts are natural scenes. However, the SR group significantly outperforms the TR group when contexts are low-pass filtered natural scenes [F(3, 39) = 3.15, p<.05]. These findings suggest that perception or memory for low spatial frequency components in scenes is enhanced in dyslexia. These findings are important because they suggest strengths for spatial learning in a population otherwise impaired, carrying implications for the education and support of students who face challenges in school

Haematopoietic stem cells in perisinusoidal niches are protected from ageing.

With ageing, intrinsic haematopoietic stem cell (HSC) activity decreases, resulting in impaired tissue homeostasis, reduced engraftment following transplantation and increased susceptibility to diseases. However, whether ageing also affects the HSC niche, and thereby impairs its capacity to support HSC function, is still widely debated. Here, by using in-vivo long-term label-retention assays we demonstrate that aged label-retaining HSCs, which are, in old mice, the most quiescent HSC subpopulation with the highest regenerative capacity and cellular polarity, reside predominantly in perisinusoidal niches. Furthermore, we demonstrate that sinusoidal niches are uniquely preserved in shape, morphology and number on ageing. Finally, we show that myeloablative chemotherapy can selectively disrupt aged sinusoidal niches in the long term, which is linked to the lack of recovery of endothelial Jag2 at sinusoids. Overall, our data characterize the functional alterations of the aged HSC niche and unveil that perisinusoidal niches are uniquely preserved and thereby protect HSCs from ageing

Paxillin and Hic-5 Interaction with Vinculin Is Differentially Regulated by Rac1 and RhoA

Cell migration is of paramount importance to organism development and maintenance as well as multiple pathological processes, including cancer metastasis. The RhoGTPases Rac1 and RhoA are indispensable for cell migration as they regulate cell protrusion, cell-extracellular matrix (ECM) interactions and force transduction. However, the consequences of their activity at a molecular level within the cell remain undetermined. Using a combination of FRET, FRAP and biochemical analyses we show that the interactions between the focal adhesion proteins vinculin and paxillin, as well as the closely related family member Hic-5 are spatially and reciprocally regulated by the activity of Rac1 and RhoA. Vinculin in its active conformation interacts with either paxillin or Hic-5 in adhesions in response to Rac1 and RhoA activation respectively, while inactive vinculin interacts with paxillin in the membrane following Rac1 inhibition. Additionally, Rac1 specifically regulates the dynamics of paxillin as well as its binding partner and F-actin interacting protein actopaxin (α-parvin) in adhesions. Furthermore, FRET analysis of protein:protein interactions within cell adhesions formed in 3D matrices revealed that, in contrast to 2D systems vinculin interacts preferentially with Hic-5. This study provides new insight into the complexity of cell-ECM adhesions in both 2D and 3D matrices by providing the first description of RhoGTPase-coordinated protein:protein interactions in a cellular microenvironment. These data identify discrete roles for paxillin and Hic-5 in Rac1 and RhoA-dependent cell adhesion formation and maturation; processes essential for productive cell migration

High-Resolution Quantification of Focal Adhesion Spatiotemporal Dynamics in Living Cells

Focal adhesions (FAs) are macromolecular complexes that provide a linkage between the cell and its external environment. In a motile cell, focal adhesions change size and position to govern cell migration, through the dynamic processes of assembly and disassembly. To better understand the dynamic regulation of focal adhesions, we have developed an analysis system for the automated detection, tracking, and data extraction of these structures in living cells. This analysis system was used to quantify the dynamics of fluorescently tagged Paxillin and FAK in NIH 3T3 fibroblasts followed via Total Internal Reflection Fluorescence Microscopy (TIRF). High content time series included the size, shape, intensity, and position of every adhesion present in a living cell. These properties were followed over time, revealing adhesion lifetime and turnover rates, and segregation of properties into distinct zones. As a proof-of-concept, we show how a single point mutation in Paxillin at the Jun-kinase phosphorylation site Serine 178 changes FA size, distribution, and rate of assembly. This study provides a detailed, quantitative picture of FA spatiotemporal dynamics as well as a set of tools and methodologies for advancing our understanding of how focal adhesions are dynamically regulated in living cells. A full, open-source software implementation of this pipeline is provided at http://gomezlab.bme.unc.edu/tools

Generation of dendritic cell-based vaccines for cancer therapy

Dendritic cells play a major role in the generation of immunity against tumour cells. They can be grown under various culture conditions, which influence the phenotypical and functional properties of dendritic cells and thereby the consecutive immune response mainly executed by T cells. Here we discuss various conditions, which are important during generation and administration of dendritic cells to elicit a tumouricidal T cell-based immune response

Prevalence of Borderline Personality Disorder in University Samples: Systematic Review, Meta-Analysis and Meta-Regression.

OBJECTIVE: To determine pooled prevalence of clinically significant traits or features of Borderline Personality Disorder among college students, and explore the influence of methodological factors on reported prevalence figures, and temporal trends. DATA SOURCES: Electronic databases (1994-2014: AMED; Biological Abstracts; Embase; MEDLINE; PsycARTICLES; CINAHL Plus; Current Contents Connect; EBM Reviews; Google Scholar; Ovid Medline; Proquest central; PsychINFO; PubMed; Scopus; Taylor & Francis; Web of Science (1998-2014), and hand searches. STUDY SELECTION: Forty-three college-based studies reporting estimates of clinically significant BPD symptoms were identified (5.7% of original search). DATA EXTRACTION: One author (RM) extracted clinically relevant BPD prevalence estimates, year of publication, demographic variables, and method from each publication or through correspondence with the authors. RESULTS: The prevalence of BPD in college samples ranged from 0.5% to 32.1%, with lifetime prevalence of 9.7% (95% CI, 7.7-12.0; p &lt; .005). Methodological factors contributing considerable between-study heterogeneity in univariate meta-analyses were participant anonymity, incentive type, research focus and participant type. Study and sample characteristics related to between study heterogeneity were sample size, and self-identifying as Asian or "other" race. The prevalence of BPD varied over time: 7.8% (95% CI 4.2-13.9) between 1994 and 2000; 6.5% (95% CI 4.0-10.5) during 2001 to 2007; and 11.6% (95% CI 8.8-15.1) from 2008 to 2014, yet was not a source of heterogeneity (p = .09). CONCLUSIONS: BPD prevalence estimates are influenced by the methodological or study sample factors measured. There is a need for consistency in measurement across studies to increase reliability in establishing the scope and characteristics of those with BPD engaged in tertiary study