Bioengineering of Improved Biomaterials Coatings for Extracorporeal Circulation Requires Extended Observation of Blood-Biomaterial Interaction under Flow

Extended use of cardiopulmonary bypass (CPB) systems is often hampered by thrombus formation and infection. Part of these problems relates to imperfect hemocompatibility of the CPB circuitry. The engineering of biomaterial surfaces with genuine long-term hemocompatibility is essentially virgin territory in biomaterials science. For example, most experiments with the well-known Chandler loop model, for evaluation of blood-biomaterial interactions under flow, have been described for a maximum duration of 2 hours only. This study reports a systematic evaluation of two commercial CPB tubings, each with a hemocompatible coating, and one uncoated control. The experiments comprised (i) testing over 5 hours under flow, with human whole blood from 4 different donors; (ii) measurement of essential blood parameters of hemocompatibility; (iii) analysis of the luminal surfaces by scanning electron microscopy and thrombin generation time measurements. The dataset indicated differences in hemocompatibility of the tubings. Furthermore, it appeared that discrimination between biomaterial coatings can be made only after several hours of blood-biomaterial contact. Platelet counting, myeloperoxidase quantification, and scanning electron microscopy proved to be the most useful methods. These findings are believed to be relevant with respect to the bioengineering of extracorporeal devices that should function in contact with blood for extended time

LEAK study:design of a nationwide randomised controlled trial to find the best way to treat wound leakage after primary hip and knee arthroplasty

INTRODUCTION: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are highly successful treatment modalities for advanced osteoarthritis. However, prolonged wound leakage after arthroplasty is linked to prosthetic joint infection (PJI), which is a potentially devastating complication. On the one hand, wound leakage is reported as a risk factor for PJI with a leaking wound acting as a porte d'entrée for micro-organisms. On the other hand, prolonged wound leakage can be a symptom of PJI. Literature addressing prolonged wound leakage is scarce, contradictory and of poor methodological quality. Hence, treatment of prolonged wound leakage varies considerably with both non-surgical and surgical treatment modalities. There is a definite need for evidence concerning the best way to treat prolonged wound leakage after joint arthroplasty. METHODS AND ANALYSIS: A prospective nationwide randomised controlled trial will be conducted in 35 hospitals in the Netherlands. The goal is to include 388 patients with persistent wound leakage 9-10 days after THA or TKA. These patients will be randomly allocated to non-surgical treatment (pressure bandages, (bed) rest and wound care) or surgical treatment (debridement, antibiotics and implant retention (DAIR)). DAIR will also be performed on all non-surgically treated patients with persistent wound leakage at day 16-17 after index surgery, regardless of amount of wound leakage, other clinical parameters or C reactive protein. Clinical data are entered into a web-based database. Patients are asked to fill in questionnaires about disease-specific outcomes, quality of life and cost effectiveness at 3, 6 and 12 months after surgery. Primary outcome is the number of revision surgeries due to infection within a year of arthroplasty. ETHICS AND DISSEMINATION: The Review Board of each participating hospital has approved the local feasibility. The results will be published in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NTR5960;Pre-results

The bii4africa dataset of faunal and floral population intactness estimates across Africa’s major land uses

Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species’ population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate ‘intactness scores’: the remaining proportion of an ‘intact’ reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the region’s major land uses (urban, cropland, rangeland, plantation, protected, etc.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/ taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems

Corticotropin-releasing hormone receptor subtype 1 and subtype 2 mRNA expression and protein localization in the myometrium in pregnancy

grantor: University of TorontoThe human placenta secretes increasing concentrations of corticotropin-releasing hormone (CRH) in late pregnancy and in labour. CRH has been implicated in the regulation of myometrial contractility. We hypothesized that CRH receptors, CRH-R1 and CRH-R2, mRNA in the myometrium would be upregulated in labour. Myometrial samples were collected from nonpregnant, pregnant and laboring patients from the upper and lower uterine segment. CRH-R1 mRNA and protein were downregulated with pregnancy and significantly upregulated at labour. This rise appeared to be exclusive to the lower segment. CRH-R2 mRNA did not change. Rats have been used extensively to study the regulation of CRH receptors. We examined CRH receptor mRNA in rat myometrium. CRH-R1 mRNA was undetectable. CRH-R2 mRNA was significantly increased at labour concomitant with a rise in connexin 4; mRNA, a gap junction protein associated with labour. In conclusion, at the time of labour CRH-R1 mRNA is upregulated in the human but in the rat CRH-R2 mRNA is upregulated.M.Sc

Molecular recognition by anti-DNA autoantibodies.

Systemic lupus erythematosus (SLE) is a multiple system autoimmune disease characterized by spontaneous production of autoantibodies. A subset of autoantibodies, directed against double- and single-stranded DNA (dsDNA and ssDNA respectively), has been implicated in the inflammatory response that often leads to kidney damage. Defining the molecular basis of anti-DNA-DNA complex formation and stability may therefore provide insight into the mechanism of anti-DNA autoantibody production in SLE and in turn, the pathogenesis of the disease. To more fully characterize antibody-DNA interactions, the problem was treated from the perspective of protein recognition of DNA rather than that of antibody-antigen binding. Three different aspects of protein-DNA recognition were examined. A modified gel shift assay was developed to measure the affinity of anti-DNA for DNA. Combining this assay with chemistry that allows disulfide cross-links to be selectively engineered into nucleic acids provides a powerful method to evaluate changes in nucleic acid conformation resulting from protein binding. This is the only method short of a high resolution structure to address this question and the sole method available to address the energetics of induced fit in protein-nucleic acid binding. Nuclear magnetic resonance studies were performed to ensure the disulfide cross-links did not perturb DNA conformation. In vitro selection (SELEX) was employed to evaluate the specificity of anti-ssDNA recognition of DNA. The answer to this question may provide insight into whether affinity maturation of anti-DNA is driven by a specific antigen. High affinity ligands specific for several antibodies were isolated and indicate that anti-ssDNA can interact with DNA in a sequence specific manner. A model of sequence specific recognition of single-stranded DNA that incorporates aspects of protein recognition of dsDNA as well as RNA was developed. This is the first report of an ideal ligand unambiguously identified for a single-stranded DNA binding protein. Small molecule inhibitors to anti-DNA were derived from a combinatorial library of 1,4-benzodiazepines. A preliminary characterization of the structure activity relationship of the anti-DNA-benzodiazepine interaction is reported.Ph.D.BiochemistryHealth and Environmental SciencesImmunologyPure SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/130592/2/9732189.pd

What are pregnant women told about models of maternity care in Australia? A retrospective study of women's reports

Objective To describe women’s reports of the model of care options General Practitioners (GPs) discussed with them at the first pregnancy consultation and women’s self-reported role in decisionmaking about model of care. Methods Women who had recently given birth responded to survey items about the models of care GPs discussed, their role in final decision-making, and socio-demographic, obstetric history, and early pregnancy characteristics. Results The proportion of women with whom each model of care was discussed varied between 8.2% (for private midwifery care with home birth) and 64.4% (GP shared care). Only 7.7% of women reported that all seven models were discussed. Exclusive discussion about private obstetric care and about all public models was common, and women’s health insurance status was the strongest predictor of the presence of discussions about each model. Most women (82.6%) reported active involvement in final decision-making about model of care. Conclusion Although most women report involvement in maternity model of care decisions, they remain largely uninformed about the breadth of available model of care options. Practical implications Strategies that facilitate women’s access to information on the differentiating features and outcomes for all models of care should be prioritized to better ensure equitable and quality decisions

Panel with Taylor, Stevens, Wyatt

Presented November 15, 2010 at the Technology Square Research Building, Atlanta, Georgia.Runtime: 32:31 minute

2 Learning Behind Bars: Exploring Prison Educators ’ Facilitation of Inmates ’ Self-directed Learning through Garrison’s Model

Abstract: Formal education programs in prisons have had success in reducing recidivism, but the introduction of informal learning can have additional benefits and longer lasting effects. This paper addresses recidivism and its effects on inmates and society at large and how prison educators can facilitate self-directed learning in prisons through Garrison’s model. On any given day more than 2 million people are incarcerated in the United States. Within three years of their release, 67 % of them are rearrested among which 52 % are reincarcerated (Bureau of Statistics, 2011). This re-offensive behavior is known as recidivism. Recidivism costs taxpayers almost $60 billion a year (Bureau of Statistics, 2011). Internal violence, overcrowding, poor medical and mental health care, and numerous other failings plague America's 5,000 prisons and jails. Ninety-five percent of inmates are eventually released back into society, ill-equipped to lead productive lives (Bureau of Statistics, 2011). The effect of prison or jail sentences on recidivism concerns public safety and the cost-effectiveness of putting convicted offenders back in prisons. Opinions are divided between those advocating longer sentences in the interest of public safety and those advocating shorter sentences with th

Gatekeepers to maternity services in Australia: Potential for facilitating or impeding patient’s informed decision making about model of maternity care

Background: Access to Australian maternity services (whether publicly or privately funded) requires referral from a general practitioner (GP). Several available models of maternity care differ in their features and capabilities. Ensuring alignment between a consumer's model of care and her unique circumstances and preferences is critical to maximising satisfaction, avoiding insufficiently- or overly-specialised care, and preventing costly and disruptive care transitions. Achieving this alignment relies on comprehensive information provision and support for deliberation and decision-making. Aims: We sought to determine maternity care consumer's perspectives on the extent to which they were informed and involved in decisions about their referral to a maternity model of care by their GP, and assess factors associated with being more or less informed. Method: We surveyed a statewide sample of recent maternity care consumers who visited a GP gatekeeper (n=5100) to assess the models of care GPs discussed with them, and their perceived role in decision-making about their model of care referral. Results: The proportion of consumers with which each model of care was discussed varied between 8.2% (for private midwifery care with home birth) and 64.4% (care coordinated by the GP themselves). Only 7.7% of consumers reported that all available models were discussed. Discussion of only one model was common, and consumers' health insurance status was the strongest predictor of whether information about specific models was shared. Most women (82.6%) reported active involvement in final decision-making about model of care. Implications: Although most women report active participation in maternity model of care decision-making, they remain largely uninformed about the breadth of available models, offsetting potential benefits of their involvement in decision-making. Without better supporting GP gatekeepers to facilitate comprehensive information provision and deliberation, consumers' capacity to choose a model of maternity care aligned with their circumstances and preferences will likely remain limited