Manufactured but not imported: new directions for research in shared decision making support and skills

Significant conceptual work on shared decision making has taken place but there are still significant challenges in achieving it in routine clinical practice. This paper outlines what research has identified to date that may promote shared decision making, and the further research that is required to enable continuing progress. Greater understanding of the models of decision making and instruments to identify them in practice are still required. Specifying consumer competences, developing instruments to assess these and interventions to enhance them may also be important. Clarifying all these aspects may enable those charged with training professionals to improve the content of professional development programmes. This may be particularly important in the field of cancer treatments where the stakes are high-patients usually desire much information but their desire for involvement in decision making is more variable. The consequences of getting this balance right or wrong are significant with much to be gained or lost. Continued development and evaluation of decision aids and decision explorers that use interactive technology will also be important in identifying how to progress with consumer involvement. If we can learn these lessons, then wider implementation of shared decision making or consumer involvement may become a nearer prospect.     

Quantitative and qualitative changes in V-J alpha rearrangements during mouse thymocytes differentiation: implication for a limited T cell receptor alpha chain repertoire

Knowledge of the complete nucleotide sequence of the mouse TCRAD locus allows an accurate determination V-J rearrangement status. Using multiplex genomic PCR assays and real time PCR analysis, we report a comprehensive and systematic analysis of the V-J recombination of TCR alpha chain in normal mouse thymocytes during development. These respective qualitative and quantitative approaches give rise to four major points describing the control of gene rearrangements. (a) The V-J recombination pattern is not random during ontogeny and generates a limited TCR alpha repertoire; (b) V-J rearrangement control is intrinsic to the thymus; (c) each V gene rearranges to a set of contiguous J segments with a gaussian-like frequency; (d) there are more rearrangements involving V genes at the 3' side than 5' end of V region. Taken together, this reflects a preferential association of V and J gene segments according to their respective positions in the locus, indicating that accessibility of both V and J regions is coordinately regulated, but in different ways. These results provide a new insight into TCR alpha repertoire size and suggest a scenario for V usage during differentiation.     

Mesenchymal stem cell inhibition of T-helper 17 cell- differentiation is triggered by cell-cell contact and mediated by prostaglandin E2 via the EP4 receptor

Mesenchymal stem cells (MSCs) inhibit T‐cell activation and proliferation but their effects on individual T‐cell‐effector pathways and on memory versus naïve T cells remain unclear. MSC influence on the differentiation of naïve and memory CD4⁺ T cells toward the Th17 phenotype was examined. CD4⁺ T cells exposed to Th17‐skewing conditions exhibited reduced CD25 and IL‐17A expression following MSC co‐culture. Inhibition of IL‐17A production persisted upon re‐stimulation in the absence of MSCs. These effects were attenuated when cell–cell contact was prevented. Th17 cultures from highly purified naïve‐ and memory‐phenotype responders were similarly inhibited. Th17 inhibition by MSCs was reversed by indomethacin and a selective COX‐2 inhibitor. Media from MSC/Th17 co‐cultures contained increased prostaglandin E2 (PGE2) levels and potently suppressed Th17 differentiation in fresh cultures. MSC‐mediated Th17 inhibition was reversed by a selective EP4 antagonist and was mimicked by synthetic PGE2 and a selective EP4 agonist. Activation‐induced IL‐17A secretion by naturally occurring, effector‐memory Th17 cells from a urinary obstruction model was also inhibited by MSC co‐culture in a COX‐dependent manner. Overall, MSCs potently inhibit Th17 differentiation from naïve and memory T‐cell precursors and inhibit naturally‐occurring Th17 cells derived from a site of inflammation. Suppression entails cell‐contact‐dependent COX‐2 induction resulting in direct Th17 inhibition by PGE2 via EP4.     

Flexible, capacity-limited activity of posterior parietal cortex in perceptual as well as visual short-term memory tasks

It has recently been shown, using functional magnetic resonance imaging with a change detection paradigm, that activity in posterior parietal cortex (PPC) correlates with the limited number of objects held in visual short-term memory (VSTM). We replicate this finding and extend it to tasks that use similar stimuli, but without explicit memory requirements. As well as a perceptual task used previously (detecting an item at fixation), 2 additional tasks were designed to increase attentional demands across space (searching for a red item anywhere in the array) and across both space and time (detecting a staggered offset after prolonged viewing of the array). During the VSTM task, a capacity-limited set-size effect was seen in PPC as well as occipital and frontal regions. However, the PPC showed similar activity during 2 of the tasks not requiring VSTM. These findings cannot easily be explained by behavioral performance measures or memory demands alone, suggesting a role of the PPC in processing a limited number of discrete object representations, whether in the current perceptual scene or working memory. The differential influence of item load across perceptual tasks is consistent with task requirements affecting the form of these representations.     

Reliability evaluation of inter-eminence line,Akagi and Dalury lines for intraoperative tibial rotation: An osteology-based study

Background

This large osteology study examined the reliability, reproducibility and correlation between previously described tibial tray rotation alignment lines (including Akagi and Dalury lines). In addition, it described a novel inter-eminence line utilising the tibial plateau inter-condylar eminences as a landmark.

Evaluating Affordable Cranial Ultrasonography in East African Neonatal Intensive Care Units

Neuroimaging is a valuable diagnostic tool for the early detection of neonatal brain injury, but equipment and radiologic staff are expensive and unavailable to most hospitals in developing countries. We evaluated an affordable, portable ultrasound machine as a quantitative and qualitative diagnostic tool and to establish whether a novice sonographer could effectively operate the equipment and obtain clinically important information. Cranial ultrasonography was performed on term healthy, pre-term and term asphyxiated neonates in Rwandan and Kenyan hospitals. To evaluate the detection of ventriculomegaly and compression injuries, we measured the size of the lateral ventricles and corpus callosum. The images were also assessed for the presence of other cerebral abnormalities. Measurements were reliable across images, and cases of clinically relevant ventriculomegaly were detected. A novice sonographer had good-to-excellent agreement with an expert. This study demonstrates that affordable equipment and cranial ultrasound protocols can be used in low-resource settings to assess the newborn brain.     

Pro‐B cells propagated in stromal cell‐free cultures reconstitute functional B‐cell compartments in immunodeficient mice

Up to now long‐term in vitro growth of pro‐B cells was thought to require stromal cells. However, here we show that fetal liver (FL) and bone marrow (BM) derived pro‐B cells can be propagated long‐term in stromal cell‐free cultures supplemented with IL‐7, stem cell factor and FLT3 ligand. Within a week, most cells expressed surface CD19, CD79A, λ5, and VpreB antigens and had rearranged immunoglobulin D‐J heavy chain genes. Both FL and BM pro‐B cells reconstituted the B‐cell compartments of immuno‐incompetent Rag2‐deficient mice, with FL pro‐B cells generating follicular, marginal zone (MZB) and B1a B cells, and BM pro‐B cells giving rise mainly to MZB cells. Reconstituted Rag2‐deficient mice generated significant levels of IgM and IgG antibodies to a type II T‐independent antigen; mice reconstituted with FL pro‐B cells generated surprisingly high IgG₁ titers. Finally, we show for the first time that mice reconstituted with mixtures of pro‐B and pro‐T cells propagated in stromal cell‐free in vitro cultures mounted a T‐cell‐dependent antibody response. This novel stromal cell‐free culture system facilitates our understanding of B‐cell development and might be applied clinically.     

T cell receptor repertoire of gamma delta cells generated from the 14-day embryonic mouse thymus.

Whole, undisrupted 14 day mouse fetal thymus lobes cultured in the presence of 10 U/ml IL-2 generate a heterogeneous population of gamma delta-expressing T cells. Phenotypic analysis has shown that the majority of gamma delta T cells in such cultures stain with the anti-V gamma 3-specific mAb 536. To investigate the V gamma T-cell receptor diversity of cultured fetal thymocytes, cDNA was prepared and amplified using the polymerase chain reaction. The DNA fragments obtained were subsequently cloned and sequenced and compared with those obtained from fresh and organ-cultured 14 day fetal thymus lobes. Results obtained tend to support a positive selection model of gamma delta T cell differentiation.