The ATP-sensitive potassium (K(ATP)) channel plays a crucial role in insulin secretion and thus glucose homeostasis. K(ATP) channel activity in the pancreatic beta-cell is finely balanced; increased activity prevents insulin secretion, whereas reduced activity stimulates insulin release. The beta-cell metabolism tightly regulates K(ATP) channel gating, and if this coupling is perturbed, two distinct disease states can result. Diabetes occurs when the K(ATP) channel fails to close in response to increased metabolism, whereas congenital hyperinsulinism results when K(ATP) channels remain closed even at very low blood glucose levels. In general there is a good correlation between the magnitude of K(ATP) current and disease severity. Mutations that cause a complete loss of K(ATP) channels in the beta-cell plasma membrane produce a severe form of congenital hyperinsulinism, whereas mutations that partially impair channel function produce a milder phenotype. Similarly mutations that greatly reduce the ATP sensitivity of the K(ATP) channel lead to a severe form of neonatal diabetes with associated neurological complications, whilst mutations that cause smaller shifts in ATP sensitivity cause neonatal diabetes alone. This chapter reviews our current understanding of the pancreatic beta-cell K(ATP) channel and highlights recent structural, functional and clinical advances.

Wing patterning in Heliconius butterflies is a longstanding example of both Müllerian mimicry and phenotypic radiation under strong natural selection. The loci controlling such patterns are "hotspots" for adaptive evolution with great allelic diversity across different species in the genus. We characterise nucleotide variation, genotype-by-phenotype associations, linkage disequilibrium, and candidate gene expression at two loci and across multiple hybrid zones in Heliconius melpomene and relatives. Alleles at HmB control the presence or absence of the red forewing band, while alleles at HmYb control the yellow hindwing bar. Across HmYb two regions, separated by approximately 100 kb, show significant genotype-by-phenotype associations that are replicated across independent hybrid zones. In contrast, at HmB a single peak of association indicates the likely position of functional sites at three genes, encoding a kinesin, a G-protein coupled receptor, and an mRNA splicing factor. At both HmYb and HmB there is evidence for enhanced linkage disequilibrium (LD) between associated sites separated by up to 14 kb, suggesting that multiple sites are under selection. However, there was no evidence for reduced variation or deviations from neutrality that might indicate a recent selective sweep, consistent with these alleles being relatively old. Of the three genes showing an association with the HmB locus, the kinesin shows differences in wing disc expression between races that are replicated in the co-mimic, Heliconius erato, providing striking evidence for parallel changes in gene expression between Müllerian co-mimics. Wing patterning loci in Heliconius melpomene therefore show a haplotype structure maintained by selection, but no evidence for a recent selective sweep. The complex genetic pattern contrasts with the simple genetic basis of many adaptive traits studied previously, but may provide a better model for most adaptation in natural populations that has arisen over millions rather than tens of years.

Operating room teams consist of team members with diverse training backgrounds. In addition to differences in training, each team member has unique and complex decision making paths. As such, team members may function in the same environment largely unaware of their team members' perspectives. The goal of our work was to use a theory based approach to better understand the complexity of knowledge-based intra-operative decision making. Cognitive task analysis methods were used to extract the knowledge, thought processes, goal structures and critical decisions that provide the foundation for surgical task performance. A triangulated and iterative approach is presented.

Aims: To examine whether teenage binge drinking has an adverse effect upon everyday prospective memory (PM). Design: The study utilised an existing-groups design, with alcohol group: binge drinkers vs non-binge drinkers as the independent factor, and scores on the two PM memory subscales of the Prospective and Retrospective Memory Questionnaire (PRMQ) and the score on the Prospective Remembering Video Procedure (PRVP) as the dependent factors. Age, anxiety and depression scores, last alcohol use (in hours) and how many years spent drinking, were measured and analysed between the groups. Setting: Each participant was tested in a laboratory setting. Participants: An opportunity sample of 21 'binge drinkers'(those drinking above 6 units for females and 8 units for males on 2 or more occasions per week) and 29 non-bingers were compared. Measurements: Self-reported everyday PM lapses were measured using the PRMQ. The PRVP was used as an objective measure of PM. Alcohol and other drug use were assessed by the University of East London Recreational Drug Use Questionnaire. The Hospital Anxiety and Depression Scale gauged self-reported levels of anxiety and depression. Findings: After controlling for age, anxiety and depression scores, last alcohol use and how many years spent drinking, there were no significant between-group differences on either the self-reported long-term or short-term PM lapses. However, binge drinkers recalled significantly fewer location-action combinations on the PRVP than non-binge drinkers. Conclusions: The results of the present study suggest that binge drinking in the teenage years leads to impairments in everyday PM.

BACKGROUND:: Properly prepared freeze-dried bone has been used with impunity by orthopedic surgeons since 1992 without a single report of disease transmission. The aim of this study was to evaluate freeze-dried cortical allograft bone for nasal dorsal augmentation. METHODS:: Freeze-dried human cortical bone was obtained from DCI Donor Services, Nashville, Tennessee. Standards recommended by the American Association of Tissue Banks, the U.S. Food and Drug Administration, and the Centers for Disease Control and Prevention were followed. Objective evaluation of the persistence of graft volume was obtained by cephalometric radiography. Vascularization and incorporation of new bone elements within the grafts were demonstrated by using fluorine-18 sodium fluoride positron emission tomographic/computed tomographic scanning. RESULTS:: The average persistence of projection in 18 patients was 87 percent at 6 months. Thereafter, 10 patients showed 100 percent maintenance of projection at 12 to 36 months. Vascularization and incorporation of new bone elements within the grafts were demonstrated by using fluorine-18 sodium fluoride positron emission tomographic/computed tomographic scanning in four patients. CONCLUSIONS:: The initial loss of 13 percent of projection is most likely attributable to resolution of early surgical edema. The authors postulate that there are two pathways based on whether the recipient bed allows vascular access to the graft. The revascularization or inductive pathway involves stem cell conversion to eventual osteoblasts. The scar bed barrier or noninductive pathway involves the preservation of the graft as an unchanged alloimplant. This report is the first of a series that will include a 5-year and a 10-year follow-up.

One of the most difficult National Patient Safety Goals to master is to accurately and completely reconcile medications across the continuum of care. All healthcare providers can agree that reconciliation is valuable, but developing a process that will ensure this is being done at admission, transfer and discharge is difficult. Is there a provider role that should logically take ownership of this process? How can this be seamlessly incorporated into current workflow? As institutions are transitioning to electronic medical records, in a mixed electronic and paper environment, what tools need to be developed to assure that the process is followed consistently? This article will review the process used by a multidisciplinary group to develop a robust medication reconciliation process in an institution which uses a mixed electronic/paper medical record and provides both ambulatory and inpatient care.

OBJECTIVE: To evaluate Hospital at Home (HaH), a substitute for inpatient care, from the perspectives of participating providers. RESEARCH DESIGN: Multivariate general estimating equations regression analyses of a patient-specific survey of providers delivering HaH care in a prospective, nonrandomized clinical trial. SUBJECTS: Eleven physicians and 26 nurses employed in 3 Medicare-Advantage plans and 1 Veterans Administration medical center. MEASURES: Problems with care; benefits; problem-free index. RESULTS: Case response rates were 95% and 82% for physicians and nurses, respectively. The overall problem-free index was high (mean 4.4, median 5, scale 1-5)."Major" problems were cited for 14 of 84 patients (17%), most relating to logistic issues without adverse patient outcomes. Positive effects included quicker patient functional recovery, greater opportunities for patient teaching, and increased communication with family caregivers. In multivariate analysis, the problem-free index was lower for nurses compared with physicians in one site; for patients with cellulitis; and for patients with a higher acuity (APACHE II) score. HaH physicians and nurses differed in their judgments of hours of continuous nursing required by patients. CONCLUSIONS: The health care provider evaluation of substitutive HaH care was positive, providing support for the viability of this innovative model of care. Without provider support, no new model of care will survive. These findings also provide insight into areas to attend to in implementation. Organizations considering adoption of the HaH should monitor provider views to promote quality improvement in HaH.

Abstract The Batesian mimetic swallowtail butterfly Papilio dardanus exhibits numerous distinct wing colour morphs whose evolutionary origins require large phenotypic shifts. A phylogenetic framework to study the history of these morphs was established by DNA sequencing of representative subspecies from sub-Saharan Africa and Indian Ocean islands. Two mitochondrial genes and the nuclear internal transcribed spacer marker revealed deeply separated eastern and western African mainland lineages, plus one lineage each on Madagascar and Grande Comore. These markers showed very little polymorphism within lineages. In contrast, markers genetically linked to the mimicry locus H, including the transcription factor invected and two adjacent amplified fragment length polymorphisms-derived sequences, showed high nucleotide diversity but were not geographically structured. Variation in the unlinked wingless gene showed a similar pattern, rejecting the hypothesis that high level of variation in the H region is due to balancing selection exerted by the phenotypes. The separation from a common ancestor with Papilio phorcas estimated at 2.9 Ma coincides with the origin of a mimicry model, Danaus chrysippus. However, the model reached Africa only at the time of the internal splits of P. dardanus mtDNA groups, here estimated at 0.55-0.94 Ma. The nuclear genome shows less geographic structure and may not track recent population differentiation, suggesting that widespread mimicry morphs have arisen early in the evolution of the P. dardanus lineage, although after the male-female dimorphism which is ancestral. The current wide distribution of P. dardanus and population subdivision evident from mtDNA may have been achieved only with the spread of the models across Africa.

Wound healing is delayed in diabetic patients. We developed a diabetic-porcine burn model and compared the healing of partial-thickness burns in normal and diabetic pigs. We hypothesized that wound healing would be delayed in the diabetic swine. Diabetes mellitus was chemically induced in three domestic pigs (25-50 kg) by intravenous injection of streptozotocin 130 mg/kg over 30 minutes. Glucose levels were maintained between 250 and 500 mg/dl by injecting short-acting or long-acting insulin 1 unit/kg daily as needed. Three weeks later, 14 partial-thickness burns were created on the backs and flanks of each of the anesthetized pigs with a 2.5 x 2.5-cm aluminum bar preheated to 80 degrees C and applied for 20 seconds. A similar number of burns were created on three control nondiabetic pigs. The burns were treated with a topical antibiotic, and 3-mm full-thickness biopsies were taken from all wounds at 7, 10, 14, and 21 days for histomorphologic evaluation using hematoxylin and eosin staining by a board-certified dermatopathologist masked to the type of pig. The main outcome was the percentage of the wound in cross section that was reepithelialized. Comparison of outcomes between normal and diabetic pigs was performed with Student's t-tests. The diabetic pigs gained less weight, and their skin was considerably thinner than in the control pigs. Although the absolute depth of the burns was similar, the relative depth was greater in the diabetic pigs. The percentage of wound reepithelialization was lower in diabetic than in normal pigs at 7 days (1.8%[95% CI: 0-5.5] vs 65.0%[95% CI: 54.2-75.9]; P <.001) as well as at 10 days (19.2%[95% CI: 6.0-32.4] vs 76.9%[95% CI: 59.8-94.0]; P <.001) and 14 days (43.9%[95% CI: 30.4-57.4] vs 99.9%[95% CI: 92.6-100]; P <.001). All burns were completely reepithelialized at 21 days, and none of the wounds were infected. Reepithelialization of partial-thickness burns is delayed in streptozotocin-induced diabetic pigs when compared with normal pigs. It is unclear whether the delay in healing is due to the thinner skin or the metabolic consequences of diabetes or their combination.

The aim of this study was to investigate mechanical sensitivity responses at the lateral elbow to repeated weekly bouts of low load exercise in healthy subjects. Thirteen young men (n=6) and women participated in 4 weeks of exercise. Arms were randomly allocated to an eccentric-only exercise protocol (ECC: 5 sets of 20 contractions) or to a concentric-eccentric protocol (CON-ECC: 5 sets of 10 eccentric/10 concentric contractions) performed at 30% maximal wrist extension force. Arms were exercised consecutively within each supervised weekly session. Quantitative measures of pressure pain threshold (PPT) recorded at three sites and maximal force for grip and wrist extension were assessed at baseline, and immediately pre/post exercise at each session. Muscle endurance during 100 maximal grip contractions force was assessed at baseline and one week following the final exercise session. Results showed that regardless of protocol, repeated low load exercise resulted in a time-dependent increase in PPT at all sites post exercise Weeks 3 and 4 and persisting at follow up Week 5 (P<0.02). No significant difference between protocols was evident for any measure. Muscle force and endurance were not significantly augmented compared with baseline. In conclusion mechanical hypoalgesia is induced by repeated low load exercises regardless of exercise mode, and this may prove beneficial if replicated clinically.