Seal of transparency heritage in the CISMeF quality-controlled health gateway

BACKGROUND: It is an absolute necessity to continually assess the quality of health information on the Internet. Quality-controlled subject gateways are Internet services which apply a selected set of targeted measures to support systematic resource discovery. METHODS: The CISMeF health gateway became a contributor to the MedCIRCLE project to evaluate 270 health information providers. The transparency heritage consists of using the evaluation performed on providers that are referenced in the CISMeF catalogue for evaluating the documents they publish, thus passing on the transparency label from the publishers to their documents. RESULTS: Each site rated in CISMeF has a record in the CISMeF database that generates an RDF into HTML file. The search tool Doc'CISMeF displays information originating from every publisher evaluated with a specific MedCIRCLE button, which is linked to the MedCIRCLE central repository. Starting with 270 websites, this trust heritage has led to 6,480 evaluated resources in CISMeF (49.8% of the 13,012 resources included in CISMeF). CONCLUSION: With the MedCIRCLE project and transparency heritage, CISMeF became an explicit third party

An efficient and extensible approach for compressing phylogenetic trees

Biologists require new algorithms to efficiently compress and store their large collections of phylogenetic trees. TreeZip is a novel method for compressing phylogenetic trees. Recently, we extended our TreeZip algorithm to support branch lengths and show how it can be used to extract sets of trees of interest quickly. The key advantage of TreeZip over standard compression methods like 7zip is its ability to interpret and compress tree collections semantically, making it immune to branch rotations and allowing key operations (such calculating a consensus tree) to be performed quickly and without a loss of space savings. On unweighted phylogenetic trees, TreeZip is able to compress Newick files in excess of 98%. On weighted phylogenetic trees, TreeZip is able to compress a Newick file by at least 73%. TreeZip can be combined with 7zip with little overhead, allowing space savings in excess of 99 % (unweighted) and 92%(weighted). Unlike TreeZip, 7zip is not immune to branch rotations, and performs worse as the level of variability in the Newick string representation increases. Finally, since the TreeZip compressed text (TRZ) file contains all the semantic information in a collection of trees, we can easily filter and decompress a subset of trees of interest (such as the set of unique trees), or build the resulting consensus tree in a matter of seconds. We also show the ease of which set operations can be performed on TRZ files, at speeds quicker than those performed on Newick or 7zip compressed Newick files, and without loss of space savings. TreeZip is an efficient approach for compressing large collections of phylogenetic trees. The semantic and compact nature of the TRZ file allow it to be operated upon directly and quickly, without a need to decompress the original Newick file. We believe that TreeZip will be vital for compressing and archiving trees in the biological community.

An interactive health communication application for supporting parents managing childhood long-term conditions: outcomes of a randomized controlled feasibility trial

Background: Families living with chronic or long-term conditions such as chronic kidney disease (CKD), stages 3-5, face multiple challenges and respond to these challenges in various ways. Some families adapt well while others struggle, and family response to a condition is closely related to outcome. With families and professionals, we developed a novel condition-specific interactive health communication app to improve parents’ management ability—the online parent information and support (OPIS) program. OPIS consists of a comprehensive mix of clinical caregiving and psychosocial information and support. Objective: The purpose of this study was to (1) assess feasibility of a future full-scale randomized controlled trial (RCT) of OPIS in terms of recruitment and retention, data collection procedures, and psychometric performance of the study measures in the target population, and (2) investigate trends in change in outcome measures in a small-scale RCT in parents of children with CKD stages 3-5. Methods: Parents were recruited from a pediatric nephrology clinic and randomly assigned to one of two treatment groups: usual support for home-based clinical caregiving (control) or usual support plus password-protected access to OPIS for 20 weeks (intervention). Both groups completed study measures at study entry and exit. We assessed feasibility descriptively in terms of recruitment and retention rates overall; assessed recruitment, retention, and uptake of the intervention between groups; and compared family condition management, empowerment to deliver care, and fathers’ involvement between groups. Results: We recruited 55 parents of 39 children (42% of eligible families). Of those, about three-quarters of intervention group parents (19/26, 73%) and control group parents (22/29, 76%) were retained through completion of 20-week data collection. The overall retention rate was 41/55 (75%). The 41 parents completing the trial were asked to respond to the same 10 questionnaire scales at both baseline and 20 weeks later; 10 scores were missing at baseline and nine were missing at 20 weeks. Site user statistics provided evidence that all intervention group parents accessed OPIS. Analysis found that intervention group parents showed a greater improvement in perceived competence to manage their child’s condition compared to control group parents: adjusted mean Family Management Measure (FaMM) Condition Management Ability Scale intervention group 44.5 versus control group 41.9, difference 2.6, 95% CI -1.6 to 6.7. Differences between the groups in the FaMM Family Life Difficulty Scale (39.9 vs 36.3, difference 3.7, 95% CI -4.9 to 12.2) appeared to agree with a qualitative observation that OPIS helped parents achieve understanding and maintain awareness of the impact of their child’s condition. Conclusions: A full-scale RCT of the effectiveness of OPIS is feasible. OPIS has the potential to beneficially affect self-reported outcomes, including parents’ perceived competence to manage home-based clinical care for children with CKD stage 3-5. Our design and methodology can be transferred to the management of other childhood conditions. Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN): 84283190; http://www.controlled-trials.com/ISRCTN84283190 (Archived by WebCite at http://www.webcitation.org/6TuPdrXTF)

Quantum Memories. A Review based on the European Integrated Project "Qubit Applications (QAP)"

We perform a review of various approaches to the implementation of quantum memories, with an emphasis on activities within the quantum memory sub-project of the EU Integrated Project "Qubit Applications". We begin with a brief overview over different applications for quantum memories and different types of quantum memories. We discuss the most important criteria for assessing quantum memory performance and the most important physical requirements. Then we review the different approaches represented in "Qubit Applications" in some detail. They include solid-state atomic ensembles, NV centers, quantum dots, single atoms, atomic gases and optical phonons in diamond. We compare the different approaches using the discussed criteria.Comment: 22 pages, 12 figure

Synthesis and Application of Dye-Ligand Affinity Adsorbents

Dye-ligand affinity chromatography is a widely used technique in protein purification. The utility of the reactive dyes as affinity ligands results from their unique chemistry, which confers wide specificity towards a large number of proteins. They are commercially available, are inexpensive, and can easily be immobilized. Important factors that contribute to the successful operation of a dye-ligand chromatography include adsorbent properties, such as matrix type and ligand concentration, the buffer conditions used in the adsorption and elution stages, and contacting parameters like flow rate and column geometry. In general, with dye-ligand affinity chromatography, the specificity is provided by the adsorption and elution conditions employed in a particular purification, and these must often be worked out by trial and error. The present chapter provides protocols for the synthesis of dye-ligand affinity adsorbents as well as protocols for screening, selection, and optimization of a dye-ligand purification step. The purification of the glutathione transferases from Phaseolus vulgaris crude extract on Cibacron Blue 3GA-Sepharose is given as an example

We are all teacher educators now: understanding school-based teacher educators in times of change in England

Within the context of the European Commission’s recent policy gaze on teacher education (European Commission, Improving teacher quality: The EU agenda – lifelong learning: policies and programme. Brussels, April 2010, EAC.B.2. D (2010) PSH, 2010; European Commission, Supporting teacher educators for better learning outcomes. European Commission, Brussels, 2013; European Commission, Strengthening teaching in Europe: new evidence from teachers compiled by Eurydice and CRELL, June 2015. Available from: http://ec.europa.eu/education/library/policy/teaching-profession-practices_en.pdf, 2015), this chapter contributes to an improved understanding of the hybrid, poly-contextualised identities of school-based teacher educators. At a time of systemic change in the education systems of many countries, teachers in schools are increasingly being asked to be responsible for the education and training of future teachers. Within the English backdrop of a rapidly changing landscape for teacher education, we present initial findings from a small-scale study exploring, through interview data, how the knowledge bases and identities of two groups of insiders, university and school-based teacher educators, were perceived by those hybrid teacher educators (Zeichner 2010) working in schools. Our findings reveal differences in school-based teacher educators’ views on their work and the work of university-based teacher educators, school-based teacher educators’ views on the role educational research has in the work they do and the ways in which different professional pathways (e.g. occupational/university; primary/secondary) influence views on what it means to be a teacher educator

Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT), during antiretroviral therapy (ART) induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans

Evaluation of range of motion restriction within the hip joint

In Total Hip Arthroplasty, determining the impingement free range of motion requirement is a complex task. This is because in the native hip, motion is restricted by both impingement as well as soft tissue restraint. The aim of this study is to determine a range of motion benchmark which can identify motions which are at risk from impingement and those which are constrained due to soft tissue. Two experimental methodologies were used to determine motions which were limited by impingement and those motions which were limited by both impingement and soft tissue restraint. By comparing these two experimental results, motions which were limited by impingement were able to be separated from those motions which were limited by soft tissue restraint. The results show motions in extension as well as flexion combined with adduction are limited by soft tissue restraint. Motions in flexion, flexion combined with abduction and adduction are at risk from osseous impingement. Consequently, these motions represent where the maximum likely damage will occur in femoroacetabular impingement or at most risk of prosthetic impingement in Total Hip Arthroplasty

Utilization of a deoxynucleoside diphosphate substrate by HIV reverse transcriptase

Background: Deoxynucleoside triphosphates (dNTPs) are the normal substrates for DNA sysnthesis is catalyzed by polymerases such as HIV-1 reverse transcriptase (RT). However, substantial amounts of deoxynucleoside diphosphates (dNDPs) are also present in the cell. Use of dNDPs in HIV-1 DNA sysnthesis could have significant implications for the efficacy of nucleoside RT inhibitors such as AZT which are first line therapeutics fro treatment of HIV infection. Our earlier work on HIV-1 reverse transcriptase (RT) suggested that the interaction between the γ phosphate of the incoming dNTP and RT residue K65 in the active site is not essential for dNTP insertion, implying that this polymerase may be able to insert dNPs in addition to dNTPs. Methodology/Principal Findings: We examined the ability of recombinant wild type (wt) and mutant RTs with substitutions at residue K65 to utilize a dNDP substrate in primer extension reactions. We found that wild type HIV-1 RT indeed catalyzes incorporation of dNDP substrates whereas RT with mutations of residue K645 were unable to catalyze this reaction. Wild type HIV-1 RT also catalyzed the reverse reaction, inorganic phosphate-dependent phosphorolysis. Nucleotide-mediated phosphorolytic removal of chain-terminating 3′-terminal nucleoside inhibitors such as AZT forms the basis of HIV-1 resistance to such drugs, and this removal is enhanced by thymidine analog mutations (TAMs). We found that both wt and TAM-containing RTs were able to catalyze Pi-mediated phosphorolysis of 3′-terminal AZT at physiological levels of Pi with an efficacy similar to that for ATP-dependent AZT-excision. Conclusion: We have identified two new catalytic function of HIV-1 RT, the use of dNDPs as substrates for DNA synthesis, and the use of Pi as substrate for phosphorolytic removal of primer 3′-terminal nucleotides. The ability to insert dNDPs has been documented for only one other DNA polymerase The RB69 DNA polymerase and the reverse reaction employing inorganic phosphate has not been documented for any DNA polymerase. Importantly, our results show that Pi-mediated phosphorolysis can contribute to AZT resistance and indicates that factors that influence HIV resistance to AZT are more complex than previously appreciated. © 2008 Garforth et al

Neonatal umbilical cord blood transplantation halts skeletal disease progression in the murine model of MPS-I

Umbilical cord blood (UCB) is a promising source of stem cells to use in early haematopoietic stem cell transplantation (HSCT) approaches for several genetic diseases that can be diagnosed at birth. Mucopolysaccharidosis type I (MPS-I) is a progressive multi-system disorder caused by deficiency of lysosomal enzyme α-L-iduronidase, and patients treated with allogeneic HSCT at the onset have improved outcome, suggesting to administer such therapy as early as possible. Given that the best characterized MPS-I murine model is an immunocompetent mouse, we here developed a transplantation system based on murine UCB. With the final aim of testing the therapeutic efficacy of UCB in MPS-I mice transplanted at birth, we first defined the features of murine UCB cells and demonstrated that they are capable of multi-lineage haematopoietic repopulation of myeloablated adult mice similarly to bone marrow cells. We then assessed the effectiveness of murine UCB cells transplantation in busulfan-conditioned newborn MPS-I mice. Twenty weeks after treatment, iduronidase activity was increased in visceral organs of MPS-I animals, glycosaminoglycans storage was reduced, and skeletal phenotype was ameliorated. This study explores a potential therapy for MPS-I at a very early stage in life and represents a novel model to test UCB-based transplantation approaches for various diseases