A functor-valued invariant of tangles

We construct a family of rings. To a plane diagram of a tangle we associate a complex of bimodules over these rings. Chain homotopy equivalence class of this complex is an invariant of the tangle. On the level of Grothendieck groups this invariant descends to the Kauffman bracket of the tangle. When the tangle is a link, the invariant specializes to the bigraded cohomology theory introduced in our earlier work.Comment: 77 pages, 46 eps figures. Published by Algebraic and Geometric Topology at http://www.maths.warwick.ac.uk/agt/AGTVol2/agt-2-30.abs.htm

Mechanics Regulates Fate Decisions of Human Embryonic Stem Cells

Research on human embryonic stem cells (hESCs) has attracted much attention given their great potential for tissue regenerative therapy and fundamental developmental biology studies. Yet, there is still limited understanding of how mechanical signals in the local cellular microenvironment of hESCs regulate their fate decisions. Here, we applied a microfabricated micromechanical platform to investigate the mechanoresponsive behaviors of hESCs. We demonstrated that hESCs are mechanosensitive, and they could increase their cytoskeleton contractility with matrix rigidity. Furthermore, rigid substrates supported maintenance of pluripotency of hESCs. Matrix mechanics-mediated cytoskeleton contractility might be functionally correlated with E-cadherin expressions in cell-cell contacts and thus involved in fate decisions of hESCs. Our results highlighted the important functional link between matrix rigidity, cellular mechanics, and pluripotency of hESCs and provided a novel approach to characterize and understand mechanotransduction and its involvement in hESC function

Knowledge transfer activities in social sciences and humanities: Explaining the interactions of research groups with non-academic agents

The aim of this research is to achieve a better understanding of the processes underlying knowledge transfer (KT) in social sciences and humanities (SSH). The paper addresses: first, the extent of SSH research groups' engagement in KT and the formal KT activities used to interact with non-academic communities; and second, how the characteristics of research groups may influence engagement in various types of KT. The empirical analysis is at research group level using data derived from a questionnaire of SSH research groups belonging to the Spanish Council for Scientific Research (CSIC). We find that KT activities are based on relational rather than commercial activities. The most frequent relational activities in which SSH research groups engage are consultancy and contract research. We find also that the characteristics of research groups (e.g. size and multidisciplinarity) and individuals (e.g. academic status and star scientist) are associated with involvement in KT activities and that a deliberate focus on the societal impacts and relevance of the research conducted is strongly related to active engagement of research groups in all the modes of KT considered in this study. From a managerial perspective, our findings suggest that measures promoting a focus on the societal impact of research could enhance research groups' engagement in KT activitiesOlmos-Peñuela, J.; Castro-Martinez, E.; Deste Cukierman, P. (2014). Knowledge transfer activities in social sciences and humanities: Explaining the interactions of research groups with non-academic agents. Research Policy. 43(4):696-706. doi:10.1016/j.respol.2013.12.004S69670643

Annual Research Review: Sleep problems in childhood psychiatric disorders – a review of the latest science

Background Hippocrates flagged the value of sleep for good health. Nonetheless, historically, researchers with an interest in developmental psychopathology have largely ignored a possible role for atypical sleep. Recently, however, there has been a surge of interest in this area, perhaps reflecting increased evidence that disturbed or insufficient sleep can result in poor functioning in numerous domains. This review outlines what is known about sleep in the psychiatric diagnoses most relevant to children and for which associations with sleep are beginning to be understood. While based on a comprehensive survey of the literature, the focus of the current review is on the latest science (largely from 2010). There is a description of both concurrent and longitudinal links as well as possible mechanisms underlying associations. Preliminary treatment research is also considered which suggests that treating sleep difficulties may result in improvements in behavioural areas beyond sleep quality. Findings To maximise progress in this field, there now needs to be: (a) greater attention to the assessment of sleep in children; (b) sleep research on a wider range of psychiatric disorders; (c) a greater focus on and examination of mechanisms underlying associations; (d) a clearer consideration ofdevelopmental questions and (e) large-scale well-designed treatment studies. Conclusions While sleep problems may sometimes be missed by parents and healthcare providers; hence constituting a hidden risk for other psychopathologies – knowing about these difficulties creates unique opportunities. The current excitement in this field from experts in diverse areas including developmental psychology, clinical psychology, genetics and neuropsychology should make these opportunities a reality

Allele-specific RNA interference rescues the long-QT syndrome phenotype in human-induced pluripotency stem cell cardiomyocytes

Aims Long-QT syndromes (LQTS) are mostly autosomal-dominant congenital disorders associated with a 1:1000 mutation frequency, cardiac arrest, and sudden death. We sought to use cardiomyocytes derived from human-induced pluripotency stem cells (hiPSCs) as an in vitro model to develop and evaluate gene-based therapeutics for the treatment of LQTS. Methods and results We produced LQTS-type 2 (LQT2) hiPSC cardiomyocytes carrying a KCNH2 c.G1681A mutation in a IKr ion-channel pore, which caused impaired glycosylation and channel transport to cell surface. Allele-specific RNA interference (RNAi) directed towards the mutated KCNH2 mRNA caused knockdown, while leaving the wild-type mRNA unaffected. Electrophysiological analysis of patient-derived LQT2 hiPSC cardiomyocytes treated with mutation-specific siRNAs showed normalized action potential durations (APDs) and K+ currents with the concurrent rescue of spontaneous and drug-induced arrhythmias (presented as early-afterdepolarizations). Conclusions These findings provide in vitro evidence that allele-specific RNAi can rescue diseased phenotype in LQTS cardiomyocytes. This is a potentially novel route for the treatment of many autosomal-dominant-negative disorders, including those of the heart

Designing an App for Immunosuppression Adherence and Communication: A Qualitative Approach

Background: Immunosuppression nonadherence may be the most important factor limiting long-term allograft survival. Objective: Following user-centered design, we explored the essential priorities and preferences of kidney transplant recipients and healthcare providers (HCP) to inform development of a smartphone app to improve immunosuppression adherence and communication. Design: A qualitative descriptive research design was used. Setting: The University of Alberta Hospital adult kidney transplant program in Edmonton, Canada. Participants: Participants were recruited by convenience sampling and included 32 kidney transplant recipients and 11 HCPs. Methods: Seven focus groups (5 with recipients and 2 with HCPs) were conducted to inform app development. Sessions were recorded, and transcripts were coded to elucidate themes. Results: App development to improve adherence was not a priority for HCP. Recipients prioritized choice: that all features be optional. Recipients preferred support while traveling; access to laboratory results; and use by younger or newly transplanted recipients. Both recipients and HCP preferred linkage to pharmacy; and self-management and accountability. For the app to improve communication, HCPs believed the priorities to be addressed included: clarity on scope of app; legal, ethical, and professional obligations; and charting. Both recipients and HCP prioritized HCP workload, and broader medication and health concerns. Healthcare providers preferred tech support; both recipients and HCPs preferred app access for nontransplant HCP. Limitations: Limitations include underrepresentation of physicians, recipients with racial/ethnic diversity, and potential selection bias of transplant recipients who perceived themselves to be adhering to immunosuppression medications. Conclusion: Future research is needed for the app to become a comprehensive, secure platform for broader communication between recipients and HCP, pharmacies, and nontransplant clinicians while streamlining HCP workload. </jats:sec

sj-docx-2-cjk-10.1177_20543581211072330 – Supplemental material for Designing an App for Immunosuppression Adherence and Communication: A Qualitative Approach

Supplemental material, sj-docx-2-cjk-10.1177_20543581211072330 for Designing an App for Immunosuppression Adherence and Communication: A Qualitative Approach by Kara Schick-Makaroff, Laura Lagendyk, Bethany Foster, Ngan N. Lam, Branko Braam, Aminu Bello, Soroush Shojai and Kevin Wen in Canadian Journal of Kidney Health and Disease</p

sj-docx-1-cjk-10.1177_20543581211072330 – Supplemental material for Designing an App for Immunosuppression Adherence and Communication: A Qualitative Approach

Supplemental material, sj-docx-1-cjk-10.1177_20543581211072330 for Designing an App for Immunosuppression Adherence and Communication: A Qualitative Approach by Kara Schick-Makaroff, Laura Lagendyk, Bethany Foster, Ngan N. Lam, Branko Braam, Aminu Bello, Soroush Shojai and Kevin Wen in Canadian Journal of Kidney Health and Disease</p

Outcomes Following Macrolide Use in Kidney Transplant Recipients

Background: Calcineurin inhibitors (CNI; cyclosporine, tacrolimus) are critical for kidney transplant immunosuppression, but have multiple potential drug interactions, such as with macrolide antibiotics. Macrolide antibiotics (clarithromycin, erythromycin, and azithromycin) are often used to treat atypical infections. Clarithromycin and erythromycin inhibit CNI metabolism and increase the risk of CNI nephrotoxicity, while azithromycin does not. Objective: To determine the frequency of CNI-macrolide co-prescriptions, the proportion who receive post-prescription monitoring, and the risk of adverse drug events in kidney transplant recipients. Design: Retrospective cohort study. Setting: We used linked health care databases in Alberta, Canada. Patients: We included 293 adult kidney transplant recipients from 2008-2015 who were co-prescribed a CNI and macrolide. Measurements: The primary outcome was a composite of all-cause hospitalization, acute kidney injury (creatinine increase ≥0.3 mg/dL or 1.5 times baseline), or death within 30 days of the macrolide prescription. Methods: We identified CNI-macrolide co-prescriptions and compared outcomes in those who received clarithromycin/erythromycin versus azithromycin. We used a linear mixed-effects model to examine the mean change in serum creatinine and estimated glomerular filtration rate (eGFR). Results: Of the 293 recipients who were co-prescribed a CNI and a macrolide, 38% (n = 112) were prescribed clarithromycin/erythromycin while 62% (n = 181) were prescribed azithromycin. Compared with azithromycin users, clarithromycin/erythromycin users were less likely to have outpatient serum creatinine monitoring post-prescription (56% vs 69%, P = .03). There was no significant difference in the primary outcome between the 2 groups (17% vs 11%, P = .11); however, the risk of all-cause hospitalization was higher in the clarithromycin/erythromycin group (10% vs 3%, P = .02). The mean decrement in eGFR was significantly greater in the clarithromycin/erythromycin versus azithromycin group (−5.4 vs −1.9 mL/min/1.73 m 2 , P < .05). Limitations: We did not have CNI levels to correlate with the timing of CNI-macrolide co-prescriptions. We also did not have information regarding the indications for macrolide prescriptions. Conclusion: Clarithromycin and erythromycin were frequently co-prescribed in kidney transplant recipients on CNIs despite known drug interactions. Clarithromycin/erythromycin use was associated with a higher risk of hospitalization compared with azithromycin users. Safer prescribing practices in kidney transplant recipients are warranted