Electric-Field Manipulation of Magnetic Chirality in a Homo-Ferro-Rotational Helimagnet.

Ferro-rotational (FR) materials, renowned for their distinctive material functionalities, present challenges in the growth of homo-FR crystals (i.e., single FR domain). This study explores a cost-effective approach to growing homo-FR helimagnetic RbFe(SO4)2 (RFSO) crystals by lowering the crystal growth temperature below the TFR threshold using the high-pressure hydrothermal method. Through polarized neutron diffraction experiments, it is observed that nearly 86% of RFSO crystals consist of a homo-FR domain. Notably, RFSO displays remarkable stability in the FR phase, with an exceptionally high TFR of ≈573 K. Furthermore, RFSO exhibits a chiral helical magnetic structure with switchable ferroelectric polarization below 4 K. Importantly, external electric fields can induce a single magnetic domain state and manipulate its magnetic chirality. The findings suggest that the search for new FR magnets with outstanding material properties should consider magnetic sulfates as promising candidates.

In vitro competition between two transmissible cancers and potential implications for their host, the Tasmanian devil.

Since the emergence of a transmissible cancer, devil facial tumour disease (DFT1), in the 1980s, wild Tasmanian devil populations have been in decline. In 2016, a second, independently evolved transmissible cancer (DFT2) was discovered raising concerns for survival of the host species. Here, we applied experimental and modelling frameworks to examine competition dynamics between the two transmissible cancers in vitro. Using representative cell lines for DFT1 and DFT2, we have found that in monoculture, DFT2 grows twice as fast as DFT1 but reaches lower maximum cell densities. Using co-cultures, we demonstrate that DFT2 outcompetes DFT1: the number of DFT1 cells decreasing over time, never reaching exponential growth. This phenomenon could not be replicated when cells were grown separated by a semi-permeable membrane, consistent with exertion of mechanical stress on DFT1 cells by DFT2. A logistic model and a Lotka-Volterra competition model were used to interrogate monoculture and co-culture growth curves, respectively, suggesting DFT2 is a better competitor than DFT1, but also showing that competition outcomes might depend on the initial number of cells, at least in the laboratory. We provide theories how the in vitro results could be translated to observations in the wild and propose that these results may indicate that although DFT2 is currently in a smaller geographic area than DFT1, it could have the potential to outcompete DFT1. Furthermore, we provide a framework for improving the parameterization of epidemiological models applied to these cancer lineages, which will inform future disease management.

Coherent Interactions between Silicon-Vacancy Centers in Diamond.

We report tunable excitation-induced dipole-dipole interactions between silicon-vacancy color centers in diamond at cryogenic temperatures. These interactions couple centers into collective states, and excitation-induced shifts tag the excitation level of these collective states against the background of excited single centers. By characterizing the phase and amplitude of the spectrally resolved interaction-induced signal, we observe oscillations in the interaction strength and population state of the collective states as a function of excitation pulse area. Our results demonstrate that excitation-induced dipole-dipole interactions between color centers provide a route to manipulating collective intercenter states in the context of a congested, inhomogeneous ensemble.

The differentiation state of the Schwann cell progenitor drives phenotypic variation between two contagious cancers.

Contagious cancers are a rare pathogenic phenomenon in which cancer cells gain the ability to spread between genetically distinct hosts. Nine examples have been identified across marine bivalves, dogs and Tasmanian devils, but the Tasmanian devil is the only mammalian species known to have given rise to two distinct lineages of contagious cancer, termed Devil Facial Tumour 1 (DFT1) and 2 (DFT2). Remarkably, DFT1 and DFT2 arose independently from the same cell type, a Schwann cell, and while their ultra-structural features are highly similar they exhibit variation in their mutational signatures and infection dynamics. As such, DFT1 and DFT2 provide a unique framework for investigating how a common progenitor cell can give rise to distinct contagious cancers. Using a proteomics approach, we show that DFT1 and DFT2 are derived from Schwann cells in different differentiation states, with DFT2 carrying a molecular signature of a less well differentiated Schwann cell. Under inflammatory signals DFT1 and DFT2 have different gene expression profiles, most notably involving Schwann cell markers of differentiation, reflecting the influence of their distinct origins. Further, DFT2 cells express immune cell markers typically expressed during nerve repair, consistent with an ability to manipulate their extracellular environment, facilitating the cell's ability to transmit between individuals. The emergence of two contagious cancers in the Tasmanian devil suggests that the inherent plasticity of Schwann cells confers a vulnerability to the formation of contagious cancers.

Monitoring cell-mediated immune responses in AAV gene therapy clinical trials using a validated IFN-γ ELISpot method.

Adeno-associated virus (AAV)-based gene therapies have recently shown promise as a novel treatment for hereditary diseases. Due to the viral origin of the vector capsid, however, cellular immune response may be elicited that could eliminate transduced target cells. To monitor cellular immune responses in clinical trials, we optimized and bioanalytically validated a sensitive, robust, and reliable interferon-γ (IFN-γ) enzyme-linked immunospot (ELISpot) assay. For method performance validation, human peripheral blood mononuclear cells (PBMCs) were stimulated with peptides derived from AAV5 capsid proteins and the encoded transgene product, human blood clotting factor VIII (FVIII), in addition to positive controls, such as peptides from the 65-kDa phosphoprotein of cytomegalovirus. We statistically assessed the limit of detection and confirmatory cutpoint, evaluated precision and linearity, and confirmed specificity using HIV peptides. Robustness parameter ranges and sample stability periods were established. The validated IFN-γ ELISpot assay was then implemented in an AAV5-FVIII gene therapy clinical trial. Cellular immune responses against the AAV5 capsid were observed in most participants as soon as 2 weeks following dose administration; only limited responses against the transgene product were detected. These data underscore the value of using validated methods for monitoring cellular immunity in AAV gene therapy trials.

The immunopeptidomes of two transmissible cancers and their host have a common, dominant peptide motif.

Transmissible cancers are malignant cells that can spread between individuals of a population, akin to both a parasite and a mobile graft. The survival of the Tasmanian devil, the largest remaining marsupial carnivore, is threatened by the remarkable emergence of two independent lineages of transmissible cancer, devil facial tumour (DFT) 1 and devil facial tumour 2 (DFT2). To aid the development of a vaccine and to interrogate how histocompatibility barriers can be overcome, we analysed the peptides bound to major histocompatibility complex class I (MHC-I) molecules from Tasmanian devil cells and representative cell lines of each transmissible cancer. Here, we show that DFT1 + IFN-γ and DFT2 cell lines express a restricted repertoire of MHC-I allotypes compared with fibroblast cells, potentially reducing the breadth of peptide presentation. Comparison of the peptidomes from DFT1 + IFNγ, DFT2 and host fibroblast cells demonstrates a dominant motif, despite differences in MHC-I allotypes between the cell lines, with preference for a hydrophobic leucine residue at position 3 and position Ω of peptides. DFT1 and DFT2 both present peptides derived from neural proteins, which reflects a shared cellular origin that could be exploited for vaccine design. These results suggest that polymorphisms in MHC-I molecules between tumours and host can be 'hidden' by a common peptide motif, providing the potential for permissive passage of infectious cells and demonstrating complexity in mammalian histocompatibility barriers.

The ecology and evolution of wildlife cancers: Applications for management and conservation.

Ecological and evolutionary concepts have been widely adopted to understand host-pathogen dynamics, and more recently, integrated into wildlife disease management. Cancer is a ubiquitous disease that affects most metazoan species; however, the role of oncogenic phenomena in eco-evolutionary processes and its implications for wildlife management and conservation remains undeveloped. Despite the pervasive nature of cancer across taxa, our ability to detect its occurrence, progression and prevalence in wildlife populations is constrained due to logistic and diagnostic limitations, which suggests that most cancers in the wild are unreported and understudied. Nevertheless, an increasing number of virus-associated and directly transmissible cancers in terrestrial and aquatic environments have been detected. Furthermore, anthropogenic activities and sudden environmental changes are increasingly associated with cancer incidence in wildlife. This highlights the need to upscale surveillance efforts, collection of critical data and developing novel approaches for studying the emergence and evolution of cancers in the wild. Here, we discuss the relevance of malignant cells as important agents of selection and offer a holistic framework to understand the interplay of ecological, epidemiological and evolutionary dynamics of cancer in wildlife. We use a directly transmissible cancer (devil facial tumour disease) as a model system to reveal the potential evolutionary dynamics and broader ecological effects of cancer epidemics in wildlife. We provide further examples of tumour-host interactions and trade-offs that may lead to changes in life histories, and epidemiological and population dynamics. Within this framework, we explore immunological strategies at the individual level as well as transgenerational adaptations at the population level. Then, we highlight the need to integrate multiple disciplines to undertake comparative cancer research at the human-domestic-wildlife interface and their environments. Finally, we suggest strategies for screening cancer incidence in wildlife and discuss how to integrate ecological and evolutionary concepts in the management of current and future cancer epizootics.

Devil Facial Tumours: Towards a Vaccine.

The Tasmanian devil is the only mammalian species to harbour two independent lineages of contagious cancer. Devil facial tumour 1 (DFT1) emerged in the 1990s and has caused significant population declines. Devil facial tumour 2 (DFT2) was identified in 2014, and evidence indicates that this new tumour has emerged independently of DFT1. While DFT1 is widespread across Tasmania, DFT2 is currently found only on the Channel Peninsula in south east Tasmania. Allograft transmission of cancer cells should be prevented by major histocompatibility complex (MHC) molecules. DFT1 avoids immune detection by downregulating MHC class I expression, which can be reversed by treatment with interferon-gamma (IFNγ), while DFT2 currently circulates in hosts with a similar MHC class I genotype to the tumour. Wild Tasmanian devil numbers have not recovered from the emergence of DFT1, and it is feared that widespread transmission of DFT2 will be devastating to the remaining wild population. A preventative solution for the management of the disease is needed. Here, we review the current research on immune responses to devil facial tumours and vaccine strategies against DFT1 and outline our plans moving forward to develop a specific, effective vaccine to support the wild Tasmanian devil population against the threat of these two transmissible tumours.

The newly-arisen Devil facial tumour disease 2 (DFT2) reveals a mechanism for the emergence of a contagious cancer.

Devil Facial Tumour 2 (DFT2) is a recently discovered contagious cancer circulating in the Tasmanian devil (Sarcophilus harrisii), a species which already harbours a more widespread contagious cancer, Devil Facial Tumour 1 (DFT1). Here we show that in contrast to DFT1, DFT2 cells express major histocompatibility complex (MHC) class I molecules, demonstrating that loss of MHC is not necessary for the emergence of a contagious cancer. However, the most highly expressed MHC class I alleles in DFT2 cells are common among host devils or non-polymorphic, reducing immunogenicity in a population sharing these alleles. In parallel, MHC class I loss is emerging in vivo, thus DFT2 may be mimicking the evolutionary trajectory of DFT1. Based on these results we propose that contagious cancers may exploit partial histocompatibility between the tumour and host, but that loss of allogeneic antigens could facilitate widespread transmission of DFT2.

The effect of clinical nursing instructors on student self-efficacy.

Clinical practicum experiences for nursing students provides the students an opportunity to apply concepts learned in class, practice skills learned in lab, and interact with patients, families, and other nurses. Although students look forward to these experiences, they often feel intimated and anxious about them. Clinical instructors play an important role in this experience and can either help or hinder student learning and self-efficacy. Using Bandura's Social Learning Theory as foundation, this descriptive study examined the relationship between perceived instructor effectiveness and student self-efficacy. Data were collected from a BSN school of nursing at a Midwestern USA comprehensive masters university. The instruments used were the Nursing Clinical Teacher Effectiveness Inventory (NCTEI) and the student self-efficacy (SSE) questionnaire. Participants (n = 236) were from a traditional nursing program with 86% female and 14% male. Data was analyzed using Pearson's correlation and MANCOVA. Results indicated: Out of the five areas of attributes, one area showed significant (p < .01) difference between the lower and higher self-efficacy groups and with specific teacher behaviors within the Evaluation category. Students with high self-efficacy reported faculty who suggested ways to improve, identified strengths and weaknesses, observed frequently, communicated expectations, gives positive reinforcement ad corrects without belittling. This can help faculty develop behaviors that increases student learning and student self-efficacy.

Denitrification kinetics in biomass- and biochar-amended soils of different landscape positions.

Knowledge of how biochar impacts soil denitrification kinetics as well as the mechanisms of interactions is essential in order to better predict the nitrous oxide (N2O) mitigation capacity of biochar additions. This study had multiple experiments in which the effect of three biochar materials produced from corn stover (Zea mays L.), ponderosa pine wood residue (Pinus ponderosa Douglas ex Lawson and C. Lawson), switchgrass (Panicum virgatum L.), and their corresponding biomass materials (corn stover, ponderosa pine wood residue, and switchgrass) on cumulative N2O emissions and total denitrification in soils from two different landscape positions (crest and footslope) were studied under varying water-filled pore space (40, 70, and 90% WFPS). Cumulative N2O emissions were reduced by 30 to 70% in both crest and footslope soils. The effect of biochars and biomass treatments on cumulative N2O emissions and total denitrification were only observed at ≥40% WFPS. The denitrification enzyme activity (DEA) kinetic parameters, K s (half-saturation constant), and V max (maximum DEA rate) were both significantly reduced by biochar treatments, with reductions of 70-80% in footslope soil and 80-90 % in the crest soil. The activation energy (E a) and enthalpy of activation of DEA (ΔH) were both increased with biochar application. The trends in DEA rate constants (K s and V max) were correlated by the trends of thermodynamic parameters (activation energy E a and enthalpy of activation ΔH) for denitrifying enzyme activity (DEA). The rate constant V max/K s evaluated the capacity of biochars to mitigate the denitrification process. Denitrifying enzyme kinetic parameters can be useful in evaluating the ability of biochars to mitigate N2O gas losses from soil.

Improvement of 2000-m rowing performance with caffeinated carbohydrate-gel ingestion.

PURPOSE: To investigate the effect of ingesting a caffeinated carbohydrate gel (CC) 10 minutes prior on 2000-m rowing performance compared with a carbohydrate-only placebo gel (CP). METHODS: A counterbalanced, single-blind, crossover study design was employed (N=13). All participants completed 1 familiarization trial followed by 2 experimental rowing time trials. The experimental trials were performed 10 min after ingesting CP (21.6 g of carbohydrate, 0 mg caffeine) or CC (21.6 g carbohydrate, 100 mg caffeine), and heart rate (HR), oxygen consumption (VO2), carbon dioxide production, minute ventilation (VE), respiratory-exchange ratio (RER), rating of perceived exertion (RPE), gastrointestinal discomfort (GI), and thirst perception (Thirst) were recorded every 200 m. Blood lactate [La-] was recorded immediately before and after exercise. RESULTS: A pairedsamples t test identified a significant improvement in 2000-m performance of 5.2±3.9 s (1.1%±1.7%; P=.034). Two-way repeated-measures ANOVA revealed no significant treatment effect for HR (177±8 vs 177±9 beats/min, P=.817), VO2 (46.1±6.5 vs 46.6±6.2 mL·kg(-1)·min(-1), P=.590), VE (121.8±14.7 vs 124.8±15.7 L/min, P=.490), RPE, GI, or Thirst for CP and CC, respectively. Paired-samples t tests revealed no treatment effect for postexercise [La-] between CP and CC (11.72±2.69 vs 12.26±3.13 mmol/L, P=.534). CONCLUSION: A relatively low dose of caffeine (1.3±0.1 mg/kg body mass) in an isotonic carbohydrate gel ingested only 10 min before performance improved 2000-m rowing time by 5.2±7.8 s (1.1%±1.7%).

Definitive surgical treatment of enterocutaneous fistula: outcomes of a 23-year experience.

OBJECTIVE: To analyze postoperative outcomes, morbidity, and mortality following enterocutaneous fistula (ECF) takedown. DESIGN, SETTING, AND PATIENTS: Retrospective review of the complete medical records of patients who presented to a single tertiary care referral center from December 24, 1987, to June 18, 2010, and subsequently underwent definitive surgical treatment for ECF originating from the stomach, small bowel, colon, or rectum. MAIN OUTCOME MEASURES: Postoperative fistula recurrence and mortality. RESULTS: A total of 153 patients received operative intervention for ECF. Most ECFs were referred to us from outside institutions (75.2%), high output (52.3%), originating from the small bowel (88.2%), and iatrogenic in cause (66.7%). Successful ECF closure was ultimately achieved in 128 patients (83.7%). Six patients (3.9%) died within 30 days of surgery, and overall 1-year mortality was 15.0%. Postoperative complications occurred in 134 patients, for an overall morbidity rate of 87.6%. Significant risk factors for fistula recurrence were numerous, but postoperative ventilation for longer than 48 hours, organ space surgical site infection, and blood transfusion within 72 hours of surgery carried the most considerable impact (relative risks, 4.87, 4.07, and 3.91, respectively; P < .05). Risk of 1-year mortality was also associated with multiple risk factors, the most substantial of which were postoperative pulmonary and infectious complications. Closure of abdominal fascia was protective against both recurrent ECF and mortality (relative risks, 0.47 and 0.38, respectively; P < .05). CONCLUSIONS: Understanding risk factors both associated with and protective against ECF recurrence and postoperative morbidity and mortality is imperative for appropriate ECF management. Closure of abdominal fascia is of utmost importance, and preventing postoperative complications must be prioritized to optimize patient outcomes.

Impact of operative duration on postoperative pulmonary complications in laparoscopic versus open colectomy.

BACKGROUND: Prolonged operative duration is associated with increased postoperative morbidity and mortality. Although laparoscopic colectomy (LC) is associated with longer operative duration compared with open colectomy (OC), research shows paradoxically decreased morbidity following LC versus OC. The direct impact of operative duration on postoperative pulmonary complications (PPC) following LC versus OC has not been analyzed. METHODS: We queried the ACS/NSQIP 2009-2010 Public Use File for patients who underwent elective LC and OC. The associations between operative duration and a PPC (pneumonia, intubation >48 h, and unplanned intubation) were evaluated. Multivariable regression models were created to determine the independent effect of operative time on the development of PPC controlling for LC versus OC. RESULTS: A total of 25,419 colectomies (13,741 laparoscopic and 11,678 open) were reviewed; 765 (3 %) patients experienced at least one PPC. Regression modeling demonstrated that for both LC and OC each 60-min increase in operative time up to 480 min was associated with 13 % increased odds of PPC [odds ratio (OR) 1.13; 95 % confidence interval (CI) 1.07-1.19]. Beyond 480 min, each additional 60-min interval was associated with 33 % increased risk of PPC (OR 1.33; 95 % CI 1.12-1.58). Overall, PPCs occurred half as often following LC [270 (2 %) laparoscopic vs. 497 (4.3 %) open; OR 0.45; 95 % CI 0.39-0.53]. CONCLUSIONS: Operative duration is independently associated with increased risk of PPC in patients undergoing LC and OC. However, a laparoscopic approach carries half the absolute risk of PPC and, when safe, should be preferentially utilized despite a potential for prolonged operative duration.

Routine intraoperative frozen section analysis of bronchial margins is of limited utility in lung cancer resection.

BACKGROUND: Residual disease at the bronchial margin after resection of non-small cell lung cancer (NSCLC) adversely affects survival. To ensure an R0 resection, thoracic surgeons commonly use intraoperative frozen section analysis of the bronchial margin. We hypothesize that frozen section of the bronchial margin is rarely positive and seldom changes intraoperative management. METHODS: Our institutional Society of Thoracic Surgery database was queried for all patients undergoing planned lobectomy for NSCLC from 2009 to 2011. Clinical variables, intraoperative data, and postoperative outcomes were reviewed. Specifically, intraoperative frozen section and final pathology results of all bronchial margins were examined. The frequency that frozen section results affected intraoperative decision making was evaluated. RESULTS: A total of 287 lobectomies for NSCLC were performed. Frozen section of the bronchial margin was performed in 270 patients (94.1%). There were 6 (2.2%) true-positive bronchial margins and 1 (0.4%) false-negative margin. In no cases did a positive frozen section lead to a change in operative management; reasons included unable to tolerate further resection (n = 5) and advanced-stage disease (n = 1). Positive margins were more frequent with open techniques (7%) than in video-assisted thoracoscopic operations (0.05%; p < 0.01). Tumors with positive margins were closer to the bronchial margin (1.0 vs 2.5 cm; p = 0.04). Frozen section was not used in 17 patients (5.9%), and none had positive margins on final pathology. CONCLUSIONS: Frozen section analysis of the bronchial margin rarely yields a positive result and infrequently changes intraoperative management in patients undergoing NSCLC resection. These data support selective use of intraoperative frozen section of bronchial margins during lobectomy for NSCLC.

Pneumonectomy for benign disease: analysis of the early and late outcomes.

OBJECTIVES: To analyse the indications, operative techniques, postoperative morbidity, mortality and long-term outcomes of patients who underwent pneumonectomy for benign lung disease. METHODS: We retrospectively reviewed our institutional database for patients who underwent a pneumonectomy for benign lung disease from January 1991 to June 2010. The data were queried for the indications for surgery, details of operative technique, development of perioperative complications, mortality and long-term survival. RESULTS: There were 32 patients, 19 men (59%) and 13 women, with a mean age of 48 years (17-78). Indications for pneumonectomy included pulmonary tuberculosis in 10 patients (31%), chronic septic lung disease in seven (22%), invasive opportunistic infections in five (16%), fibrosing mediastinitis in four (12%) and other in six (19%). Pneumonectomies were left-sided in 17 (53%) and right-sided in 15 patients; nine (28%) were completion pneumonectomies. Intraoperatively, intrapericardial isolation was performed in 21 (66%) patients and extrapleural dissection in seven (22%); bronchial reinforcement was performed in 25 (78%). Operative mortality occurred in two (6%) patients. Major complications occurred in 12 (38%) patients; no patient developed bronchopleural fistula or postpneumonectomy empyema requiring intervention. Overall 5-year survival was 75% (95% CI 56.2-87.9), with a mean follow-up of 99 months. CONCLUSIONS: Pneumonectomy for benign disease is a high-risk procedure performed for a variety of indications. A detailed operative technique is of the utmost importance to minimize postoperative morbidity and mortality. Despite an increased perioperative risk, the long-term outcomes can be especially satisfactory. Pneumonectomy for benign disease should continue to be a treatment option for carefully selected patients.

Impact of surgical care improvement project inf-9 on postoperative urinary tract infections: do exemptions interfere with quality patient care?

BACKGROUND: The Surgical Care Improvement Project (SCIP) Inf-9 guideline promotes removal of indwelling urinary catheters (IUCs) within 48 hours of surgery. OBJECTIVES: To determine whether a correlation exists between SCIP Inf-9 compliance and postoperative urinary tract infection (UTI) rates and whether an association exists between UTI rates and SCIP Inf-9 exemption status. DESIGN Retrospective case control study. SETTING: Southeastern academic medical center. PATIENTS: American College of Surgeons National Surgical Quality Improvement Program (NSQIP) and SCIP Inf-9 compliance data were collected prospectively on randomly selected general and vascular surgery inpatients. Monthly UTI rates and SCIP Inf-9 compliance scores were tested for correlation. Complete NSQIP data for all the inpatients with postoperative UTIs were compared with a group of 100 random controls to determine whether an association exists between UTI rates and SCIP Inf-9 exemption status. MAIN OUTCOME MEASURE: Postoperative UTI. RESULTS: In 2459 patients reviewed, SCIP Inf-9 compliance increased over time, but this was not correlated with improved monthly UTI rates. Sixty-one of the 69 UTIs (88.4%) were compliant with SCIP Inf-9; however, 49 (71.0%) of these were considered exempt from the guideline and, therefore, the IUC was not removed within 48 hours of surgery. Retrospective review of 100 random controls showed a similar compliance rate (84.0%, P = .43) but a lower rate of exemption (23.5%, P < .001). The odds of developing a postoperative UTI were 8 times higher in patients deemed exempt from SCIP Inf-9 (odds ratio [OR], 7.99; 95% CI, 3.85-16.61). After controlling for differences between the 2 groups, the adjusted ORs slightly increased (OR, 8.34; 95% CI, 3.70-18.76). CONCLUSIONS: Most UTIs occurred in patients deemed exempt from SCIP Inf-9. Although compliance rates remain high, practices are not actually improving. Surgical Care Improvement Project Inf-9 guidelines should be modified with fewer exemptions to facilitate earlier removal of IUCs.

Risk factors for 30-day hospital readmission among general surgery patients.

BACKGROUND: Hospital readmission within 30 days of an index hospitalization is receiving increased scrutiny as a marker of poor-quality patient care. This study identifies factors associated with 30-day readmission after general surgery procedures. STUDY DESIGN: Using standard National Surgical Quality Improvement Project protocol, preoperative, intraoperative, and postoperative outcomes were collected on patients undergoing inpatient general surgery procedures at a single academic center between 2009 and 2011. Data were merged with our institutional clinical data warehouse to identify unplanned 30-day readmissions. Demographics, comorbidities, type of procedure, postoperative complications, and ICD-9 coding data were reviewed for patients who were readmitted. Univariate and multivariate analysis was used to identify risk factors associated with 30-day readmission. RESULTS: One thousand four hundred and forty-two general surgery patients were reviewed. One hundred and sixty-three (11.3%) were readmitted within 30 days of discharge. The most common reasons for readmission were gastrointestinal problem/complication (27.6%), surgical infection (22.1%), and failure to thrive/malnutrition (10.4%). Comorbidities associated with risk of readmission included disseminated cancer, dyspnea, and preoperative open wound (p < 0.05 for all variables). Surgical procedures associated with higher rates of readmission included pancreatectomy, colectomy, and liver resection. Postoperative occurrences leading to increased risk of readmission were blood transfusion, postoperative pulmonary complication, wound complication, sepsis/shock, urinary tract infection, and vascular complications. Multivariable analysis demonstrates that the most significant independent risk factor for readmission is the occurrence of any postoperative complication (odds ratio = 4.20; 95% CI, 2.89-6.13). CONCLUSIONS: Risk factors for readmission after general surgery procedures are multifactorial, however, postoperative complications appear to drive readmissions in surgical patients. Taking appropriate steps to minimize postoperative complications will decrease postoperative readmissions.

Non-legislative interventions for the promotion of cycle helmet wearing by children.

BACKGROUND: Helmets reduce bicycle-related head injuries, particularly in single vehicle crashes and those where the head strikes the ground. We aimed to identify non-legislative interventions for promoting helmet use among children, so future interventions can be designed on a firm evidence base. OBJECTIVES: To assess the effectiveness of non-legislative interventions in increasing helmet use among children; to identify possible reasons for differences in effectiveness of interventions; to evaluate effectiveness with respect to social group; to identify adverse consequences of interventions. SEARCH METHODS: We searched the following databases: Cochrane Injuries Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; PsycINFO (Ovid); PsycEXTRA (Ovid); CINAHL (EBSCO); ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED); Social Sciences Citation Index (SSCI); Conference Proceedings Citation Index-Science (CPCI-S); and PubMed from inception to April 2009; TRANSPORT to 2007; and manually searched other sources of data. SELECTION CRITERIA: We included RCTs and CBAs. Studies included participants aged 0 to 18 years, described interventions promoting helmet use not requiring enactment of legislation and reported observed helmet wearing, self reported helmet ownership or self reported helmet wearing. DATA COLLECTION AND ANALYSIS: Two independent review authors selected studies for inclusion and extracted data. We used random-effects models to estimate pooled odds ratios (ORs) (with 95% confidence interval (CI)). We explored heterogeneity with subgroup analyses. MAIN RESULTS: We included 29 studies in the review, 21 of which were included in at least one meta-analysis. Non-legislative interventions increased observed helmet wearing (11 studies: OR 2.08, 95% CI 1.29 to 3.34). The effect was most marked amongst community-based interventions (four studies: OR 4.30, 95% 2.24 to 8.25) and those providing free helmets (two studies: OR 4.35, 95% CI 2.13 to 8.89). Significant effects were also found amongst school-based interventions (eight studies: OR 1.73, CI 95% 1.03 to 2.91), with a smaller effect found for interventions providing education only (three studies: OR 1.43, 95% CI 1.09 to 1.88). No significant effect was found for providing subsidised helmets (seven studies: OR 2.02, 95% CI 0.98 to 4.17). Interventions provided to younger children (aged under 12) may be more effective (five studies: OR 2.50, 95% CI 1.17 to 5.37) than those provided to children of all ages (five studies: OR 1.83, 95% CI 0.98 to 3.42).Interventions were only effective in increasing self reported helmet ownership where they provided free helmets (three studies: OR 11.63, 95% CI 2.14 to 63.16).Interventions were effective in increasing self reported helmet wearing (nine studies: OR 3.27, 95% CI 1.56 to 6.87), including those undertaken in schools (six studies: OR 4.21, 95% CI 1.06 to 16.74), providing free helmets (three studies: OR 7.27, 95% CI 1.28 to 41.44), providing education only (seven studies: OR 1.93, 95% CI 1.03 to 3.63) and in healthcare settings (two studies: OR 2.78, 95% CI 1.38 to 5.61). AUTHORS' CONCLUSIONS: Non-legislative interventions appear to be effective in increasing observed helmet use, particularly community-based interventions and those providing free helmets. Those set in schools appear to be effective but possibly less so than community-based interventions. Interventions providing education only are less effective than those providing free helmets. There is insufficient evidence to recommend providing subsidised helmets at present. Interventions may be more effective if provided to younger rather than older children. There is evidence that interventions offered in healthcare settings can increase self reported helmet wearing.Further high-quality studies are needed to explore whether non-legislative interventions increase helmet wearing, and particularly the effect of providing subsided as opposed to free helmets, and of providing interventions in healthcare settings as opposed to in schools or communities. Alternative interventions (e.g. those including peer educators, those aimed at developing safety skills including skills in decision making and resisting peer pressure or those aimed at improving self esteem or self efficacy) need developing and testing, particularly for 11 to 18 year olds. The effect of interventions in countries with existing cycle helmet legislation and in low and middle-income countries also requires investigation.

Insulin signaling to the glomerular podocyte is critical for normal kidney function.

Diabetic nephropathy (DN) is the leading cause of renal failure in the world. It is characterized by albuminuria and abnormal glomerular function and is considered a hyperglycemic "microvascular" complication of diabetes, implying a primary defect in the endothelium. However, we have previously shown that human podocytes have robust responses to insulin. To determine whether insulin signaling in podocytes affects glomerular function in vivo, we generated mice with specific deletion of the insulin receptor from their podocytes. These animals develop significant albuminuria together with histological features that recapitulate DN, but in a normoglycemic environment. Examination of "normal" insulin-responsive podocytes in vivo and in vitro demonstrates that insulin signals through the MAPK and PI3K pathways via the insulin receptor and directly remodels the actin cytoskeleton of this cell. Collectively, this work reveals the critical importance of podocyte insulin sensitivity for kidney function.