A model for studying the hemostatic consumption or destruction of platelets

A fundamental issue in understanding homeostasis of the hematopoietic system is to what extent intrinsic and extrinsic factors regulate cell fate. We recently revisited this issue for the case of blood platelets and concluded that platelet life span is largely regulated by internal factors, in contrast to the long-held view that accumulated damage from the environment triggers clearance. However, it is known that in humans there is an ongoing fixed requirement for platelets to maintain hemostasis and prevent bleeding; hence a proportion of platelets may be consumed in such processes before the end of their natural life span. Whether it is possible to detect this random loss of platelets in normal individuals at steady-state is unknown. To address this question, we have developed a mathematical model that independently incorporates age-independent random loss and age-dependent natural senescent clearance. By fitting to population survival curves, we illustrate the application of the model in quantifying the fixed requirement for platelets to maintain hemostasis in mice, and discuss the relationship with previous work in humans. Our results suggest a higher requirement for platelets in mice than in humans, however experimental uncertainty in the data limits our ability to constrain this quantity. We then explored the relationship between experimental uncertainty and parameter constraint using simulated data. We conclude that in order to provide useful constraint on the random loss fraction the standard error in the mean of the data must be reduced substantially, either through improving experimental uncertainty or increasing the number of experimental replicates to impractical levels. Finally we find that parameter constraint is improved at higher values of the random loss fraction; thus the model find utility in situations where the random loss fraction is expected to be high, for example during active bleeding or some types of thrombocytopenia.Mark R. Dowling, Emma C. Josefsson, Katya J. Henley, Benjamin T. Kile, Philip D. Hodgki

Citizen Science and Open Data: a model for Invasive Alien Species in Europe

Invasive Alien Species (IAS) are a growing threat to Europe's biodiversity. The implementation of European Union Regulation on IAS can benefit from the involvement of the public in IAS recording and management through Citizen Science (CS) initiatives. Aiming to tackle issues related with the use of CS projects on IAS topics, a dedicated workshop titled “Citizen Science and Open Data: a model for Invasive Alien Species in Europe” was organized by the Joint Research Centre (JRC) and the European Cooperation in Science and Technology (COST Association). Fifty key stakeholders from all Europe, including two Members of the European Parliament, attended the workshop. With a clear focus on IAS, the workshop aimed at addressing the following issues: a) CS and policy, b) citizen engagement, and c) CS data management. Nine short presentations provided input on CS and IAS issues. Participants discussed specific topics in several round tables (“world café” style) and reported back their conclusions to the audience and full assembly moderated discussions. Overall, the workshop enabled the sharing of ideas, approaches and best practices regarding CS and IAS. Specific opportunities and pitfalls of using CS data in the whole policy cycle for IAS were recognized. Concerning the implementation of the IAS Regulation, CS data could complement official surveillance systems, and contribute to the early warning of the IAS of Union concern after appropriate validation by the Member States’ competent authorities. CS projects can additionally increase awareness and empower citizens. Attendees pointed out the importance for further public engagement in CS projects on IAS that demonstrate specific initiatives and approaches and analyze lessons learned from past experiences. In addition, the workshop noted that the data gathered from different CS projects on IAS are fragmented. It highlighted the need for using an open and accessible platform to upload data originating from CS sources or to mirror validated data into a single, easy-to-use web service, in line with the EU Open Science Strategic Priority. The workshop provided ten key recommendations of best practices for CS projects on IAS, addressed to researchers, policy makers and implementing authorities, indicating future research and policy directions and opportunities

Women's experiences of sexual health when living with Rheumatoid Arthritis - an explorative qualitative study

<p>Abstract</p> <p>Background</p> <p>The ICF core sets for patients with Rheumatoid Arthritis (RA) acknowledge sexual function and intimate relationships as important since the patients' sexual health can be affected by the disease. About 36-70% of all RA-patients experience a reduced sexual health, and their perceived problems are directly or indirectly caused by their disease. Physiotherapy is often used as non-pharmacological treatment for RA. Mobility treatment, pain reduction, and physical activities are often included in physiotherapy for patients with RA. The aim of the study was to explore sexual health in relation to physiotherapy in women living with RA.</p> <p>Method</p> <p>An explorative qualitative interview study with a phenomenological approach was performed. The study consisted of ten interviews with women with RA. The analysis was performed according to Giorgi.</p> <p>Results</p> <p>The main theme that emerged in the material was that the body and the total life situation affected sexual health. Three categories were included in the theme: 1) sexual health - physical and psychological dimensions, 2) Impacts of RA, and 3) Possibilities to increase sexual health - does physiotherapy make a difference?</p> <p>Conclusions</p> <p>Sexual health was affected by RA in different ways for the informants. Possibilities to improve sexual health were improved partner communication and physiotherapy. Physiotherapy can play an active role in improving sexual health for patients with RA.</p

Staphylococcus aureus Host Cell Invasion and Virulence in Sepsis Is Facilitated by the Multiple Repeats within FnBPA

Entry of Staphylococcus aureus into the bloodstream can lead to metastatic abscess formation and infective endocarditis. Crucial to the development of both these conditions is the interaction of S. aureus with endothelial cells. In vivo and in vitro studies have shown that the staphylococcal invasin FnBPA triggers bacterial invasion of endothelial cells via a process that involves fibronectin (Fn) bridging to α5β1 integrins. The Fn-binding region of FnBPA usually contains 11 non-identical repeats (FnBRs) with differing affinities for Fn, which facilitate the binding of multiple Fn molecules and may promote integrin clustering. We thus hypothesized that multiple repeats are necessary to trigger the invasion of endothelial cells by S. aureus. To test this we constructed variants of fnbA containing various combinations of FnBRs. In vitro assays revealed that endothelial cell invasion can be facilitated by a single high-affinity, but not low-affinity FnBR. Studies using a nisin-inducible system that controlled surface expression of FnBPA revealed that variants encoding fewer FnBRs required higher levels of surface expression to mediate invasion. High expression levels of FnBPA bearing a single low affinity FnBR bound Fn but did not invade, suggesting that FnBPA affinity for Fn is crucial for triggering internalization. In addition, multiple FnBRs increased the speed of internalization, as did higher expression levels of FnBPA, without altering the uptake mechanism. The relevance of these findings to pathogenesis was demonstrated using a murine sepsis model, which showed that multiple FnBRs were required for virulence. In conclusion, multiple FnBRs within FnBPA facilitate efficient Fn adhesion, trigger rapid bacterial uptake and are required for pathogenesis

Functional treatment versus plaster for simple elbow dislocations (FuncSiE): a randomized trial

Background. Elbow dislocations can be classified as simple or complex. Simple dislocations are characterized by the absence of fractures, while complex dislocations are associated with fractures. After reduction of a simple dislocation, treatment options include immobilization in a static plaster for different periods of time or so-called functional treatment. Functional treatment is characterized by early active motion within the limits of pain with or without the use of a sling or hinged brace. Theoretically, functional treatment should prevent stiffness without introducing increased joint instability. The primary aim of this randomized controlled trial is to compare early functional treatment versus plaster immobilization following simple dislocations of the elbow. Methods/Design. The design of the study will be a multicenter randomized controlled trial of 100 patients who have sustained a simple elbow dislocation. After reduction of the dislocation, patients are randomized between a pressure bandage for 5-7 days and early functional treatment or a plaster in 90 degrees flexion, neutral position for pro-supination for a period of three weeks. In the functional group, treatment is started with early active motion within the limits of pain. Function, pain, and radiographic recovery will be evaluated at regular intervals over the subsequent 12 months. The primary outcome measure is the Quick Disabilities of the Arm, Shoulder, and Hand score. The secondary outcome measures are the Mayo Elbow Performance Index, Oxford elbow score, pain level at both sides, range of motion of the elbow joint at both sides, rate of secondary interventions and complication rates in both groups (secondary dislocation, instability, relaxation), health-related quality of life (Short-Form 36 and EuroQol-5D), radiographic appearance of the elbow joint (degenerative changes and heterotopic ossifications), costs, and cost-effectiveness. Discussion. The successful completion of this trial will provide evidence on the effectiveness of a functional treatment for the management of simple elbow dislocations. Trial Registration. The trial is registered at the Netherlands Trial Register (NTR2025)

Identifying recombination hotspots in the HIV-1 genome

HIV-1 infection is characterised by the rapid generation of genetic diversity that facilitates viral escape from immune selection and antiretroviral therapy. Despite recombination's crucial role in viral diversity and evolution, little is known about the genomic factors that influence recombination between highly similar genomes. In this study, we use a minimally modified full length HIV-1 genome and high throughput sequence analysis to study recombination in gag and pol in T cells. We find that recombination is favoured at a number of recombination hotspots, where recombination occurs six times more frequently than at corresponding coldspots. Interestingly, these hotspots occur near important features of the HIV-1 genome, but do not occur at sites immediately around protease inhibitor or reverse transcriptase inhibitor drug resistance mutations. We show that the recombination hot and cold spots are consistent across five blood donors and are independent of co-receptor mediated entry. Finally, we check common experimental confounders and find that these are not driving the location of recombination hotspots. This is the first study to identify the location of recombination hotspots, between two similar viral genomes with great statistical power and under conditions that closely reflect natural recombination events amongst HIV-1 quasispecies

Relationship between microstructure and fracture types in a UNS S32205 duplex stainless steel

Duplex stainless steels are susceptible to the formation of sigma phase at high temperature which could potentially be responsible for catastrophic service failure of components. Thermal treatments were applied to duplex stainless steels in order to promote the precipitation of different fractions of sigma phase into a ferrite-austenite microstructure. Quantitative image analysis was employed to characterize the microstructure and Charpy impact tests were used in order to evaluate the mechanical degradation caused by sigma phase presence. The fracture morphology of the Charpy test specimens were thoroughly observed in SEM, looking for a correlation between the microstructure and the fracture types in UNS S32205 duplex stainless steel. The main conclusion is the strong embrittlement effect of sigma phase since it is possible to observe a transition from transgranular fracture to intergranular fracture as increases the percentage of sigma phase. Thus, the mixed modes of fracture are predominant in the present study with high dependence on sigma phase percentages obtained by different thermal treatments

Transgene-Induced Gene Silencing Is Not Affected by a Change in Ploidy Level

BACKGROUND: Whole genome duplication, which results in polyploidy, is a common feature of plant populations and a recurring event in the evolution of flowering plants. Polyploidy can result in changes to gene expression and epigenetic instability. Several epigenetic phenomena, occurring at the transcriptional or post-transcriptional level, have been documented in allopolyploids (polyploids derived from species hybrids) of Arabidopsis thaliana, yet findings in autopolyploids (polyploids derived from the duplication of the genome of a single species) are limited. Here, we tested the hypothesis that an increase in ploidy enhances transgene-induced post-transcriptional gene silencing using autopolyploids of A. thaliana. METHODOLOGY/PRINCIPAL FINDINGS: Diploid and tetraploid individuals of four independent homozygous transgenic lines of A. thaliana transformed with chalcone synthase (CHS) inverted repeat (hairpin) constructs were generated. For each line diploids and tetraploids were compared for efficiency in post-transcriptional silencing of the endogenous CHS gene. The four lines differed substantially in their silencing efficiency. Yet, diploid and tetraploid plants derived from these plants and containing therefore identical transgene insertions showed no difference in the efficiency silencing CHS as assayed by visual scoring, anthocyanin assays and quantification of CHS mRNA. CONCLUSIONS/SIGNIFICANCE: Our results in A. thaliana indicated that there is no effect of ploidy level on transgene-induced post-transcriptional gene silencing. Our findings that post-transcriptional mechanisms were equally effective in diploids and tetraploids supports the use of transgene-driven post-transcriptional gene silencing as a useful mechanism to modify gene expression in polyploid species