Nonparametric estimation of concave production technologies by entropic methods

An econometric methodology is developed for nonparametric estimation of concave production technologies. The methodology, bases on the priciple of maximum likelihood, uses entropic distance and concvex programming techniques to estimate production functions.convex programming, production functions, entropy

Simplified citrate anticoagulation for continuous renal replacement therapy

Simplified citrate anticoagulation for continuous renal replacement therapy.BackgroundRegional anticoagulation with trisodium citrate is an effective form of anticoagulation for continuous renal replacement therapy (CRRT) for patients with contraindications to heparin. However, because of the metabolic complications of trisodium citrate, it is a complicated technique requiring specialized dialysis solutions. We have designed a simplified protocol for citrate regional anticoagulation for CRRT.MethodsTwo percent trisodium citrate was delivered at 250 mL/h via the prefilter port of a COBE PRISMA device, with the rate adjusted to maintain a postfilter ionized calcium (iCa++) <0.5mmol/L. A central calcium gluconate infusion was used to maintain a systemic iCa++ at 1.1mmol/L. A standard dialysate solution consisting of 0.9% saline, KCl 3mmol/L, and MgSO4 1mmol/L was delivered at 1000 mL/h. We retrospectively reviewed the outcomes and complications associated with this protoco1 in 29 patients treated from July 1999 to October 1999, evaluating the frequency of clotting of the dialyzer, bleeding complications, citrate toxicity, and patient mortality.ResultsThe Kaplan–Meier curve for dialyzer survival demonstrated a 61% survival rate at 48 hours. There were no episodes of significant bleeding or citrate toxicity. Seventy-two percent of patients died for reasons unrelated to CRRT.ConclusionsA CRRT protocol using regional 2% trisodium citrate anticoagulation is not associated with significant bleeding complications or citrate toxicity, and represents a simplified approach compared with previous applications using 4% trisodium citrate

Effect of preoperative sonographic mapping on vascular access outcomes in hemodialysis patients

Effect of preoperative sonographic mapping on vascular access outcomes in hemodialysis patients.BackgroundCurrent DOQI guidelines encourage placing arteriovenous (AV) fistulas in more hemodialysis patients. However, many new fistulas fail to mature sufficiently to be useable for hemodialysis. Preoperative vascular mapping to identify suitable vessels may improve vascular access outcomes. The present study prospectively evaluated the effect of routine preoperative vascular mapping on the type of vascular accesses placed and their outcomes.MethodsDuring a 17-month period, preoperative sonographic evaluation of the upper extremity arteries and veins was obtained routinely. The surgeons used the information obtained to plan the vascular access procedure. The types of access placed, their initial adequacy for dialysis, and their long-term outcomes were compared to institutional historical controls placed on the basis of physical examination alone.ResultsThe proportion of fistulas placed increased from 34% during the historical control period to 64% with preoperative vascular mapping (P < 0.001). When all fistulas were assessed, the initial adequacy rate for dialysis increased mildly from 46 to 54% (P = 0.34). For the subset of forearm fistulas, the initial adequacy increased substantially from 34 to 54% (P = 0.06); the greatest improvement occurred among women (from 7 to 36%, P = 0.06) and diabetic patients (from 21 to 50%, P = 0.055). In contrast, the initial adequacy rate of upper arm fistulas was not improved by preoperative vascular mapping (59 vs. 56%, P = 0.75). Primary access failure was higher for fistulas than grafts (46.4 vs. 20.6%, P = 0.001), but the subsequent long-term failure rate was higher for grafts than fistulas (P < 0.05). Moreover, grafts required a threefold higher intervention rate (1.67 vs. 0.57 per year, P < 0.001) to maintain their patency. The overall effect of this strategy was to double the proportion of patients dialyzing with a fistula in our population from 16 to 34% (P < 0.001).ConclusionsRoutine preoperative vascular mapping results in a marked increase in placement of AV fistulas, as well as an improvement in the adequacy of forearm fistulas for dialysis. This approach resulted in a substantial increase in the proportion of patients dialyzing with a fistula in our patient population. Fistulas have a higher primary failure rate than grafts, but have a lower subsequent failure rate and require fewer procedures to maintain their long-term patency

The experience of mortgage distress in Western Sydney

Mortgage distress is affecting a growing number of Australian households. Distress ranges from arrears in mortgage payments to defaults, foreclosures and repossessions. The impacts of mortgage distress are complex and include issues relating to the ongoing financial viability of the affected households, wider neighbourhood effects, and a range of psychological and social impacts. In recent years, mortgage stress has had a consistently higher prevalence in certain parts of Western Sydney than in any other region across Australia.This study is an attempt to uncover the experiences of mortgage distress in Western Sydney and of mortgage holders’ coping strategies. While not claiming to be a representative sample of mortgagors in distress, the report reveals much about the circumstances contributing to mortgage distress and its considerable impacts on the lives of those affected

Injury activates transient olfactory stem cell states with diverse lineage capacities

Tissue homeostasis and regeneration are mediated by programs of adult stem cell renewal and differentiation. However, the mechanisms that regulate stem cell fates under such widely varying conditions are not fully understood. Using single-cell techniques, we assessed the transcriptional changes associated with stem cell self-renewal and differentiation and followed the maturation of stem cell-derived clones using sparse lineage tracing in the regenerating mouse olfactory epithelium. Following injury, quiescent olfactory stem cells rapidly shift to activated, transient states unique to regeneration and tailored to meet the demands of injury-induced repair, including barrier formation and proliferation. Multiple cell fates, including renewed stem cells and committed differentiating progenitors, are specified during this early window of activation. We further show that Sox2 is essential for cells to transition from the activated to neuronal progenitor states. Our study highlights strategies for stem cell-mediated regeneration that may be conserved in other adult stem cell niches

Deconstructing olfactory stem cell trajectories at single-cell resolution

A detailed understanding of the paths that stem cells traverse to generate mature progeny is vital for elucidating the mechanisms governing cell fate decisions and tissue homeostasis. Adult stem cells maintain and regenerate multiple mature cell lineages in the olfactory epithelium. Here we integrate single-cell RNA sequencing and robust statistical analyses with in&nbsp;vivo lineage tracing to define a detailed map of the postnatal olfactory epithelium, revealing cell fate potentials and branchpoints in olfactory stem cell lineage trajectories. Olfactory stem cells produce support cells via direct fate conversion in the absence of cell division, and their multipotency at the population level reflects collective unipotent cell fate decisions by single stem cells. We further demonstrate that Wnt signaling regulates stem cell fate by promoting neuronal fate choices. This integrated approach reveals the mechanisms guiding olfactory lineage trajectories and provides a model for deconstructing similar hierarchies in other stem cell niches

Therapeutic potential of injectable Nano-mupirocin liposomes for infections involving multidrug-resistant bacteria

Antibiotic resistance is a global health threat. There are a few antibiotics under development, and even fewer with new modes of action and no cross-resistance to established antibiotics. Accordingly, reformulation of old antibiotics to overcome resistance is attractive. Nano-mupirocin is a PEGylated nano-liposomal formulation of mupirocin, potentially enabling parenteral use in deep infections, as previously demonstrated in several animal models. Here, we describe extensive in vitro profiling of mupirocin and Nano-mupirocin and correlate the resulting MIC data with the pharmacokinetic profiles seen for Nano-mupirocin in a rat model. Nano-mupirocin showed no cross-resistance with other antibiotics and retained full activity against vancomycin-, daptomycin-, linezolid- and methicillin- resistant Staphylococcus aureus, against vancomycin-resistant Enterococcus faecium, and cephalosporin-resistant Neisseria gonorrhoeae. Following Nano-mupirocin injection to rats, plasma levels greatly exceeded relevant MICs for > 24 h, and a biodistribution study in mice showed that mupirocin concentrations in vaginal secretions greatly exceeded the MIC 90 for N. gonorrhoeae (0.03 µg/mL) for > 24 h. In summary, Nano-mupirocin has excellent potential for treatment of several infection types involving multiresistant bacteria. It has the concomitant benefits from utilizing an established antibiotic and liposomes of the same size and lipid composition as Doxil®, an anticancer drug product now used for the treatment of over 700,000 patients globally

Single-Cell Analysis of Experience-Dependent Transcriptomic States in Mouse Visual Cortex

Activity-dependent transcriptional responses shape cortical function. However, we lack a comprehensive understanding of the diversity of these responses across the full range of cortical cell types, and how these changes contribute to neuronal plasticity and disease. Here we applied high-throughput single-cell RNA-sequencing to investigate the breadth of transcriptional changes that occur across cell types in mouse visual cortex following exposure to light. We identified significant and divergent transcriptional responses to stimulation in each of the 30 cell types characterized, revealing 611 stimulus-responsive genes. Excitatory pyramidal neurons exhibit inter- and intra-laminar heterogeneity in the induction of stimulus responsive genes. Non-neuronal cells demonstrated clear transcriptional responses that may regulate experience-dependent changes in neurovascular coupling and myelination. Together, these results reveal the dynamic landscape of stimulus-dependent transcriptional changes that occur across cell types in visual cortex, which are likely critical for cortical function and may be sites of de-regulation in developmental brain disorders

Canadian Guidelines for Controlled Pediatric Donation After Circulatory Determination of Death-Summary Report

OBJECTIVES: Create trustworthy, rigorous, national clinical practice guidelines for the practice of pediatric donation after circulatory determination of death in Canada. METHODS: We followed a process of clinical practice guideline development based on World Health Organization and Canadian Medical Association methods. This included application of Grading of Recommendations Assessment, Development, and Evaluation methodology. Questions requiring recommendations were generated based on 1) 2006 Canadian donation after circulatory determination of death guidelines (not pediatric specific), 2) a multidisciplinary symposium of national and international pediatric donation after circulatory determination of death leaders, and 3) a scoping review of the pediatric donation after circulatory determination of death literature. Input from these sources drove drafting of actionable questions and Good Practice Statements, as defined by the Grading of Recommendations Assessment, Development, and Evaluation group. We performed additional literature reviews for all actionable questions. Evidence was assessed for quality using Grading of Recommendations Assessment, Development, and Evaluation and then formulated into evidence profiles that informed recommendations through the evidence-to-decision framework. Recommendations were revised through consensus among members of seven topic-specific working groups and finalized during meetings of working group leads and the planning committee. External review was provided by pediatric, critical care, and critical care nursing professional societies and patient partners. RESULTS: We generated 63 Good Practice Statements and seven Grading of Recommendations Assessment, Development, and Evaluation recommendations covering 1) ethics, consent, and withdrawal of life-sustaining therapy, 2) eligibility, 3) withdrawal of life-sustaining therapy practices, 4) ante and postmortem interventions, 5) death determination, 6) neonatal pediatric donation after circulatory determination of death, 7) cardiac and innovative pediatric donation after circulatory determination of death, and 8) implementation. For brevity, 48 Good Practice Statement and truncated justification are included in this summary report. The remaining recommendations, detailed methodology, full Grading of Recommendations Assessment, Development, and Evaluation tables, and expanded justifications are available in the full text report. CONCLUSIONS: This process showed that rigorous, transparent clinical practice guideline development is possible in the domain of pediatric deceased donation. Application of these recommendations will increase access to pediatric donation after circulatory determination of death across Canada and may serve as a model for future clinical practice guideline development in deceased donation