Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction - (TOPCARE-AMI)

Background - Experimental studies suggest that transplantation of blood-derived or bone marrow–derived progenitor cells beneficially affects postinfarction remodeling. The safety and feasibility of autologous progenitor cell transplantation in patients with ischemic heart disease is unknown

Toward harmonized phenotyping of human myeloid-derived suppressor cells by flow cytometry: results from an interim study

There is an increasing interest for monitoring circulating myeloid-derived suppressor cells (MDSCs) in cancer patients, but there are also divergences in their phenotypic definition. To overcome this obstacle, the Cancer Immunoguiding Program under the umbrella of the Association of Cancer Immunotherapy is coordinating a proficiency panel program that aims at harmonizing MDSC phenotyping. After a consultation period, a two-stage approach was designed to harmonize MDSC phenotype. In the first step, an international consortium of 23 laboratories immunophenotyped 10 putative MDSC subsets on pretested, peripheral blood mononuclear cells of healthy donors to assess the level of concordance and define robust marker combinations for the identification of circulating MDSCs. At this stage, no mandatory requirements to standardize reagents or protocols were introduced. Data analysis revealed a small intra-laboratory, but very high inter-laboratory variance for all MDSC subsets, especially for the granulocytic subsets. In particular, the use of a dead-cell marker altered significantly the reported percentage of granulocytic MDSCs, confirming that these cells are especially sensitive to cryopreservation and/or thawing. Importantly, the gating strategy was heterogeneous and associated with high inter-center variance. Overall, our results document the high variability in MDSC phenotyping in the multicenter setting if no harmonization/standardization measures are applied. Although the observed variability depended on a number of identified parameters, the main parameter associated with variation was the gating strategy. Based on these findings, we propose further efforts to harmonize marker combinations and gating parameters to identify strategies for a robust enumeration of MDSC subsets

Timescales of spike-train correlation for neural oscillators with common drive

We examine the effect of the phase-resetting curve (PRC) on the transfer of correlated input signals into correlated output spikes in a class of neural models receiving noisy, super-threshold stimulation. We use linear response theory to approximate the spike correlation coefficient in terms of moments of the associated exit time problem, and contrast the results for Type I vs. Type II models and across the different timescales over which spike correlations can be assessed. We find that, on long timescales, Type I oscillators transfer correlations much more efficiently than Type II oscillators. On short timescales this trend reverses, with the relative efficiency switching at a timescale that depends on the mean and standard deviation of input currents. This switch occurs over timescales that could be exploited by downstream circuits

Prevention is better than cure, but...: Preventive medication as a risk to ordinariness?

Preventive health remains at the forefront of public health concerns; recent initiatives, such as the NHS health check, may lead to recommendations for medication in response to the identification of 'at risk' individuals. Little is known about lay views of preventive medication. This paper uses the case of aspirin as a prophylactic against heart disease to explore views among people invited to screening for a trial investigating the efficacy of such an approach. Qualitative interviews (N=46) and focus groups (N=5, participants 31) revealed dilemmas about preventive medication in the form of clashes between norms: first, in general terms, assumptions about the benefit of prevention were complicated by dislike of medication; second, the individual duty to engage in prevention was complicated by the need not to be over involved with one's own health; third, the potential appeal of this alternative approach to health promotion was complicated by unease about the implications of encouraging irresponsible behaviour among others. Though respondents made different decisions about using the drug, they reported very similar ways of trying to resolve these conflicts, drawing upon concepts of necessity and legitimisation and the special ordinariness of the particular dru

Classical phase transitions in a one-dimensional short-range spin model

Ising's solution of a classical spin model famously demonstrated the absence of a positive-temperature phase transition in one-dimensional equilibrium systems with short-range interactions. No-go arguments established that the energy cost to insert domain walls in such systems is outweighed by entropy excess so that symmetry cannot be spontaneously broken. An archetypal way around the no-go theorems is to augment interaction energy by increasing the range of interaction. Here we introduce new ways around the no-go theorems by investigating entropy depletion instead. We implement this for the Potts model with invisible states.Because spins in such a state do not interact with their surroundings, they contribute to the entropy but not the interaction energy of the system. Reducing the number of invisible states to a negative value decreases the entropy by an amount sufficient to induce a positive-temperature classical phase transition. This approach is complementary to the long-range interaction mechanism. Alternatively, subjecting positive numbers of invisible states to imaginary or complex fields can trigger such a phase transition. We also discuss potential physical realisability of such systems.Comment: 29 pages, 11 figure

The treatment of segmental tibial fractures: does patient preference differ from surgeon choice?

INTRODUCTION: Segmental tibial fractures are complex injuries with a prolonged recovery time. Current definitive treatment options include intramedullary fixation or a circular external fixator. However, there is uncertainty as to which surgical option is preferable and there are no sufficiently rigorous multi-centre trials that have answered this question. The objective of this study was to determine whether patient and surgeon opinion was permissive for a randomised controlled trial (RCT) comparing intramedullary nailing to the application of a circular external fixator. MATERIALS AND METHODS: A convenience questionnaire survey of attending surgeons was conducted during the United Kingdom's Orthopaedic Trauma Society annual meeting 2017 to determine the treatment modalities used for a segmental tibial fracture (n=63). Patient opinion was obtained from clinical patients who had been treated for a segmental tibial fracture as part of a patient and public involvement focus group with questions covering the domains of surgical preference, treatment expectations, outcome, the consent process and follow-up regime (n=5). RESULTS: Based on the surgeon survey, 39% routinely use circular frame fixation following segmental tibial fracture compared to 61% who use nail fixation. Nail fixation was reported as the treatment of choice for a closed injury in a healthy patient in 81% of surgeons, and by 86% for a patient with a closed fracture who was obese. Twenty-one percent reported that they would use a nail for an open segmental tibia fracture in diabetics who smoked, whilst 57% would opt for a nail for a closed injury with compartment syndrome, and only 27% would use a nail for an open segmental injury in a young fit sports person. The patient and public preference exercise identified that sleep, early functional outcomes and psychosocial measures of outcomes are important. CONCLUSION: We concluded that a RCT comparing definitive fixation with an intramedullary nail and a circular external fixator is justified as there remains uncertainty on the optimal surgical management for segmental tibial fractures. Furthermore, psychosocial factors and early post-operative outcomes should be reported as core outcome measures as part of such a trial

A serial qualitative interview study of infant feeding experiences: idealism meets realism

Objective: To investigate the infant feeding experiences of women and their significant others from pregnancy until 6 months after birth to establish what would make a difference. Design: Qualitative serial interview study. Setting: Two health boards in Scotland. Participants: 72 of 541 invited pregnant women volunteered. 220 interviews approximately every 4 weeks with 36 women, 26 partners, eight maternal mothers, one sister and two health professionals took place. Results: The overarching theme was a clash between overt or covert infant feeding idealism and the reality experienced. This is manifest as pivotal points where families perceive that the only solution that will restore family well-being is to stop breast feeding or introduce solids. Immediate family well-being is the overriding goal rather than theoretical longer term health benefits. Feeding education is perceived as unrealistic, overly technical and rules based which can undermine women's confidence. Unanimously families would prefer the balance to shift away from antenatal theory towards more help immediately after birth and at 3-4 months when solids are being considered. Family-orientated interactive discussions are valued above breastfeeding-centred checklist style encounters. Conclusions: Adopting idealistic global policy goals like exclusive breast feeding until 6 months as individual goals for women is unhelpful. More achievable incremental goals are recommended. Using a proactive family-centred narrative approach to feeding care might enable pivotal points to be anticipated and resolved. More attention to the diverse values, meanings and emotions around infant feeding within families could help to reconcile health ideals with reality

A qualitative study of cardiac rehabilitation patients’ perspectives on taking medicines: implications for the ‘medicines-resistance’ model of medicine-taking

Background The appropriate use of medicines continues to be an important area of inter-disciplinary research activity both in the UK and beyond. Key qualitative work in this area in the last decade has included the ‘medicines resistance’ model of medicine-taking, which was based on a meta-ethnography of 37 qualitative studies. This model proposed that patients approach medicine-taking as ‘passive accepters’, ‘active accepters’, ‘active modifiers’ or ‘complete rejecters’, of which the latter two categories were considered to show ‘resistance’ to medicines. However, critical assessment of the model appears to be currently lacking, particularly in terms of its use in clinical practice. This paper seeks to contribute to the literature in this area by critically examining the practical application of the model in light of the findings from a qualitative, follow-up study of cardiac rehabilitation patients’ perspectives and experiences of using medicines. Methods Following ethical approval, in-depth, audiotaped, qualitative interviews were conducted with fifteen patients who had completed a UK hospital-based cardiac rehabilitation programme. Participants were aged 42–65, white British and from a variety of socioeconomic backgrounds. Interview topics included perspectives on coronary heart disease, medicine-taking and lifestyle changes. Follow-up interviews with ten patients approximately nine months later explored whether their perspectives had changed. Results The findings suggest that the active/passive and accepter/modifier distinctions may not allow for clear determination of which profile a patient fits into at any given point, and that definitions such as ‘accepter’ and ‘resistance’ may be insufficiently discerning to categorise patients’ use of medicines in practice. These problems appear to arise when the issue of patients’ accounts about medicines adherence are considered, since patients may have concerns or disquiet about medicines whether or not they are adherent and the model does not consider disquiet in isolation from adherence. Conclusions Practical application of the ‘medicines resistance’ model of medicine-taking may be problematic in this patient group. Dissociation of disquiet about medicines from medicines adherence may allow for a focus on helping patients to resolve their disquiet, if possible, without this necessarily having to be viewed in terms of its potential effect on adherence

The Effect of Transposable Element Insertions on Gene Expression Evolution in Rodents

Background:Many genomes contain a substantial number of transposable elements (TEs), a few of which are known to be involved in regulating gene expression. However, recent observations suggest that TEs may have played a very important role in the evolution of gene expression because many conserved non-genic sequences, some of which are know to be involved in gene regulation, resemble TEs. Results:Here we investigate whether new TE insertions affect gene expression profiles by testing whether gene expression divergence between mouse and rat is correlated to the numbers of new transposable elements inserted near genes. We show that expression divergence is significantly correlated to the number of new LTR and SINE elements, but not to the numbers of LINEs. We also show that expression divergence is not significantly correlated to the numbers of ancestral TEs in most cases, which suggests that the correlations between expression divergence and the numbers of new TEs are causal in nature. We quantify the effect and estimate that TE insertion has accounted for ~20% (95% confidence interval: 12% to 26%) of all expression profile divergence in rodents. Conclusions:We conclude that TE insertions may have had a major impact on the evolution of gene expression levels in rodents