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While it has been hypothesized that brown adipocytes responsible for mammalian thermogenesis are absent in birds, the existence of beige fat has yet to be studied directly. The present study tests the hypothesis that beige fat emerges in birds as a mechanism of physiological adaptation to cold environments. Subcutaneous neck adipose tissue from cold-acclimated or triiodothyronine (T3)-treated chickens exhibited increases in the expression of avian uncoupling protein (avUCP, an ortholog of mammalian UCP2 and UCP3) gene and some known mammalian beige adipocyte-specific markers. Morphological characteristics of white adipose tissues of treated chickens showed increased numbers of both small and larger clusters of multilocular fat cells within the tissues. Increases in protein levels of avUCP and mitochondrial marker protein, voltage-dependent anion channel, and immunohistochemical analysis for subcutaneous neck fat revealed the presence of potentially thermogenic mitochondria-rich cells. This is the first evidence that the capacity for thermogenesis may be acquired by differentiating adipose tissue into beige-like fat for maintaining temperature homeostasis in the subcutaneous fat ‘neck warmer’ in chickens exposed to a cold environment. Supplementary Information The online version contains supplementary material available at 10.1007/s00726-021-02953-5.

Objective: To compare the sensitivity of current field triage practices for identifying high-risk trauma patients to strict guideline adherence, including changes in triage specificity, ambulance transport patterns, and trauma center volumes. Methods: This was a pre-planned secondary analysis of an out-of-hospital prospective cohort of injured children and adults transported by 44 EMS agencies to 28 trauma and non-trauma hospitals in 7 Northwest U.S. counties from January 1, 2011 through December 31, 2011. Outcomes included Injury Severity Score (ISS) ≥16 (primary) and early critical resource use. Strict adherence of the triage guidelines was based on evidence in the EMS chart for patients meeting any current field triage criteria, calculated with and without strict interpretation of the age criterion (55 years). Due to the probability sampling nature of the cohort, strata and weights were included in all analyses. Results: 17,633 injured patients were transported by EMS (weighted to represent 53,487 transported patients), including 3.1% with ISS ≥16 and 1.7% requiring early critical resources. Field triage sensitivity for identifying patients with ISS ≥16 increased from the current 66.2% (95% CI 60.2–71.7%) to 87.3% (95% CI 81.9–91.2%) for strict adherence without age and to 91.0% (95% CI 86.4–94.2%) for strict adherence with age. Specificity decreased with increasing adherence, from 87.8% (current) to 47.6% (strict adherence without age) and 35.8% (strict adherence with age). Areas under the curve (AUC) were 0.78, 0.73, and 0.72, respectively. Results were similar for patients requiring early critical resources. We estimate the number of triage-positive patients transported each year by EMS to an individual major trauma center (on average) to increase from 1,331 (current) to 5,139 (strict adherence without age) and to 6,256 (strict adherence with age). Conclusions: The low sensitivity of current triage practices would be expected to improve with strict adherence to current triage guidelines, with a commensurate decrease in triage specificity and an increase in the number of triage-positive patients transported to major trauma centers.

Author(s): Hansen, MD, MCR, Matthew; Loker, MD, William; Warden, MD, MPH, MS, Craig | Abstract: Introduction: The association between geographic factors, including transport distance, and pediatricemergency medical services (EMS) run clustering on out-of-hospital pediatric endotracheal intubation isunclear. The objective of this study was to determine if endotracheal intubation procedures are more likely tooccur at greater distances from the hospital and near clusters of pediatric calls.Methods: This was a retrospective observational study including all EMS runs for patients less than 18years of age from 2008 to 2014 in a geographically large and diverse Oregon county that includes denselypopulated urban areas near Portland and remote rural areas. We geocoded scene addresses using theautomated address locator created in the cloud-based mapping platform ArcGIS, supplemented with manualaddress geocoding for remaining cases. We then use the Getis-Ord Gi spatial statistic feature in ArcGIS tomap statistically significant spatial clusters (hot spots) of pediatric EMS runs throughout the county. We thensuperimposed all intubation procedures performed during the study period on maps of pediatric EMS-runhot spots, pediatric population density, fire stations, and hospitals. We also performed multivariable logisticregression to determine if distance traveled to the hospital was associated with intubation after controlling forseveral confounding variables.Results: We identified a total of 7,797 pediatric EMS runs during the study period and 38 endotrachealintubations. In univariate analysis we found that patients who were intubated were similar to those who werenot in gender and whether or not they were transported to a children’s hospital. Intubated patients tendedto be transported shorter distances and were older than non-intubated patients. Increased distance fromthe hospital was associated with reduced odds of intubation after controlling for age, sex, scene location,and trauma system entry status in a multivariate logistic regression. The locations of intubations weresuperimposed on hot spots of all pediatric EMS runs. This map demonstrates that most of the intubationsoccurred within areas where pediatric EMS calls were highly clustered. By mapping the intubationprocedures and pediatric population density, we found that intubation procedures were not clustered in asimilar distribution to the pediatric population in the county.Conclusion: In this geographically diverse county the location of intubation procedures was similar to theclustering of pediatric EMS calls, and increased distance from the hospital was associated with reducedodds of intubation after controlling for several potential confounding variables. [West J Emerg Med.2016;17(5)656-661.]

Airway management is an important component of resuscitation from out-of-hospital cardiac arrest (OHCA). The optimal approach to advanced airway management is unknown. The Pragmatic Airway Resuscitation Trial (PART) will compare the effectiveness of endotracheal intubation (ETI) and Laryngeal Tube (LT) insertion upon 72-hour survival in adult OHCA. Encompassing United States Emergency Medical Services agencies affiliated with the Resuscitation Outcomes Consortium (ROC), PART will use a cluster-crossover randomized design. Participating subjects will include adult, non-traumatic OHCA requiring bag-valve-mask ventilation. Trial interventions will include 1) initial airway management with ETI and 2) initial airway management with LT. The primary and secondary trial outcomes are 72-hour survival and return of spontaneous circulation. Additional clinical outcomes will include airway management process and adverse events. The trial will enroll a total of 3,000 subjects. Results of PART may guide the selection of advanced airway management strategies in OHCA.

Approximately 25.5 million pediatric patients are treated in Emergency Departments around the United States annually. Roughly 7% of these patients are transported by ambulance; of these, approximately 7% arrive in ambulances running red lights and sirens (RLS). Compared to those transporting without RLS, emergency vehicles employing RLS are involved in more accidents and are associated with more fatalities.To characterize the use of RLS in pediatric transports and identify factors associated with unnecessary use of RLS.As part of the Children's Safety Initiative (CSI-EMS), a large, multi-phased National Institutes of Health-funded study, we conducted a medical record review of all pediatric RLS transports in an urban EMS system over a 4-year period (2008-11). A standardized chart abstraction tool was adapted for the out-of-hospital setting and pilot tested. Charts were independently reviewed by physicians and paramedics, with disagreements arbitrated by a pediatric emergency physician. Reviewers were asked to judge whether RLS transport was necessary and to provide comments justifying their position. Descriptive statistics were used to measure the frequency of unnecessary transports and logistic regression analysis was employed to identify factors associated with unnecessary use of RLS.Of 490 RLS transports, experts identified 96 (19.6%) as unnecessary use of RLS. Necessary and unnecessary RLS transports had similar patient sex and duration of transport, though unnecessary use of RLS tended to increase with patient age. The call reasons that represented the largest proportion of unnecessary RLS transports were trauma (49.0%), respiratory distress (16.7%), and seizure/altered mental status (11.5%). Compared with necessary RLS transports, unnecessary RLS transports were less likely to require resuscitation, airway management, or medication administration. Univariate analysis revealed that patient vital signs within normal limits were associated with increased risk of unnecessary RLS transport, with the most pronounced effect seen in the normal GCS score group (odds ratio 7.74, p-value 0.001).This analysis identified patient and transport characteristics associated with unnecessary use of RLS. Our results could help serve as the basis for designing and prospectively evaluating protocols for use of RLS, potentially mitigating the risk associated with transport in pediatric patients.

All multicellular organisms benefit from their own microbiota, which play important roles in maintaining the host nutritional health and immunity. Recently, the number of studies on the microbiota of animals, fish, and plants of economic importance is rapidly expanding and there are increasing expectations that productivity and sustainability in agricultural management can be improved by microbiota manipulation. However, optimizing microbiota is still a challenging task because of the lack of knowledge on the dominant microorganisms or significant variations between microbiota, reflecting sampling biases, different agricultural management as well as breeding backgrounds. To offer a more generalized view on microbiota in agriculture, which can be used for defining criteria of “optimal microbiota” as the goal of manipulation, we summarize here current knowledge on microbiota on animals, fish, and plants with emphasis on bacterial community structure and metabolic functions, and how microbiota can be affected by domestication, conventional agricultural practices, and use of antimicrobial agents. Finally, we discuss future tasks for defining “optimal microbiota,” which can improve host growth, nutrition, and immunity and reduce the use of antimicrobial agents in agriculture.

Introduction Outdoor education (OE) expeditions travel far from definitive care and have unique epidemiology. Most OE expedition studies have examined a single organization and results may not generalize. This study examines the injuries, illnesses, medical evacuations, and nonmedical incidents of the Northwest Outward Bound School (NWOBS) to broaden our understanding and demonstrate commonalities within the field. Methods This retrospective database review examined incidents and evacuations on NWOBS expeditions from June 1, 2014 through October 31, 2016. Incident rates, evacuation rates, and incident type frequencies were calculated. Frequencies of incidents during different expedition time periods were compared with a 1-sample χ2 test. The odds ratio that each type of incident would require evacuation was calculated and compared with other incident types using Fisher exact test. Results The study period included 59,058 program days, 277 incidents, 143 medical incidents, 75 medical evacuations, and no fatalities. Injuries occurred at a rate of 1.64 per 1000 program days and illnesses at a rate of 0.78 per 1000 program days. The most common injuries were strains, sprains, and trauma or infection of the skin and soft tissue. Most injuries occurred while backpacking, hiking, or moving around camp. The most common illnesses were nausea, vomiting, diarrhea, abdominal pain, asthma, respiratory infections, and urinary tract infections. The medical incidents with the highest odds of evacuation were fractures, urinary tract infections, abdominal pain, and asthma. Conclusions Results from the NWOBS database are consistent with those from other expeditionary OE programs. These findings should guide risk-management strategies and staff medical training.

Objective The objective of this study was to characterize pediatric out-of-hospital airway management interventions, success rates, and complications in the United States using the 2012 National Emergency Medical Services Information System (NEMSIS) dataset. Methods In 2012, NEMSIS collected data from Emergency Medical Services (EMS) encounters in 40 states. We included all patients less than 18 years of age and identified all patients who had airway interventions including endotracheal intubation (ETI), bag-valve-mask ventilation (BVM), continuous positive airway pressure/bilevel positive airway pressure (CPAP/BiPAP) and alternate airways (Combitube, King LT, Laryngeal Mask Airway (LMA), esophageal obturator airway, and cricothyroidotomy). Success and complication rates were analyzed and compared across pediatric age groups, by race, ethnicity, clinical condition, and geographic region. Results We identified a total of 949,301 pediatric patient care events in the NEMSIS 2012 dataset. 4.5% had airway management procedures (42,936 events). Invasive airway management or ventilation (ETI, cricothyroidotomy, alternate airway, CPAP/BiPAP, BVM and other ventilation) took place in 1.5% of patient care events (14,107). Of those who had invasive airway management, 29.9% were less than 1 year of age, 58.1% were male, 42.3% were white, and 83.6% were in urban areas. ETI occurred in 3124 of patient care events (329 per 100,000; 95% CI 318–341). Overall success of ETI was 81.1% (95% CI 79.7–82.6). Lower success was noted in patients with cardiac arrest (75.5%, 95% CI 72.6–78.3) and those aged 1–12 months (72.1%, 95% CI 68.3–75.6). Conclusions Out-of-hospital pediatric advanced airway procedures were infrequently performed. Success rates are lowest in patients aged 1–12 months.

© 2017 Warden et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Our objective is to identify genes that influence the development of any phenotypes of type 2 diabetes (T2D) or kidney disease in obese animals. We use the reproductively isolated UC Davis fatty Zucker strain rat model in which the defective chromosome 4 leptin receptor (LeprfaSte/faSte) results in fatty obesity. We previously produced a congenic strain with the distal half of chromosome 1 from the Brown Norway strain (BN) on a Zucker (ZUC) background (BN.ZUC-D1Rat183–D1Rat90). Previously published studies in males showed that the BN congenic donor region protects from some phenotypes of renal dysfunction and T2D. We now expand our studies to include females and expand phenotyping to gene expression. We performed diabetes and kidney disease phenotyping in chow-fed females of the BN.ZUC-D1Rat183-D1Rat90 congenic strain to determine the specific characteristics of the UC Davis model. Fatty LeprfaSte/faSteanimals of both BN and ZUC genotype in the congenic donor region had prediabetic levels of fasting blood glucose and blood glucose 2 hours after a glucose tolerance test. We observed significant congenic strain chromosome 1 genotype effects of the BN donor region in fatty females that resulted in decreased food intake, urine volume, glucose area under the curve during glucose tolerance test, plasma triglyceride levels, and urine glucose excretion per day. In fatty females, there were significant congenic strain BN genotype effects on non-fasted plasma urea nitrogen, triglyceride, and creatinine. Congenic region genotype effects were observed by quantitative PCR of mRNA from the kidney for six genes, all located in the chromosome 1 BN donor region, with potential effects on T2D or kidney function. The results are consistent with the hypothesis that the BN genotype chromosome 1 congenic region influences traits of both type 2 diabetes and kidney function in fatty UC Davis ZUC females and that there are many positional candidate genes.

Most genetic human obesity is due to multiple genes interacting with each other and with environment. Sequencing exomes, genome-wide associations with single nucleotide polymorphisms, sequencing methylations, and sequencing genomic DNA have revealed hundreds of obesity-causing polymorphisms that all together account for a small percent of total heritability. Pathway analyses reveal that most body mass index genes are expressed in the brain whereas most waist-to-hip ratio fat distribution genes are expressed in adipose tissue. Most mouse obesity genes are also human obesity genes and vice versa. Studies in mice demonstrate that quantitating fat mass, individual fat depots, responses of individual fat depots to dieting and exercise, and parental effects will reveal many new obesity genes. These topics have been explored superficially or not at all in studies of humans. Genetic and randomized controlled diet data are presently inadequate for development of personalized obesity therapy.

Importance Despite a large rural US population, there are potential differences between rural and urban regions in the processes and outcomes following trauma. Objectives To describe and evaluate rural vs urban processes of care, injury severity, and mortality among injured patients served by 9-1-1 emergency medical services (EMS). Design, Setting, and Participants This was a preplanned secondary analysis of a prospective cohort enrolled from January 1 through December 31, 2011, and followed up through hospitalization. The study included 44 EMS agencies transporting to 28 hospitals in 2 rural and 5 urban counties in Oregon and Washington. A population-based, consecutive sample of 67 047 injured children and adults served by EMS (1971 rural and 65 076 urban) was enrolled. Among the 53 487 patients transported by EMS, a stratified probability sample of 17 633 patients (1438 rural and 16 195 urban) was created to track hospital outcomes (78.9% with in-hospital follow-up). Data analysis was performed from June 12, 2015, to May 20, 2016. Exposures Rural was defined at the county level by 60 minutes or more driving proximity to the nearest level I or II trauma center and/or rural designation in the Centers for Medicare & Medicaid Services ambulance fee schedule by zip code. Main Outcomes and Measures Mortality (out-of-hospital and in-hospital), need for early critical resources, and transfer rates. Results Of the 53 487 injured patients transported by EMS (17 633 patients in the probability sample), 27 535 were women (51.5%); mean (SD) age was 51.6 (26.1) years. Rural vs urban sensitivity of field triage for identifying patients requiring early critical resources was 65.2% vs 80.5%, and only 29.4% of rural patients needing critical resources were initially transported to major trauma centers vs 88.7% of urban patients. After accounting for transfers, 39.8% of rural patients requiring critical resources were cared for in major trauma centers vs 88.7% of urban patients. Overall mortality did not differ between rural and urban regions (1.44% vs 0.89%; P = .09); however, 89.6% of rural deaths occurred within 24 hours compared with 64% of urban deaths. Rural regions had higher transfer rates (3.2% vs 2.7%) and longer transfer distances (median, 97.4 km; interquartile range [IQR], 51.7-394.5 km; range, 47.8-398.6 km vs 22.5 km; IQR, 11.6-24.6 km; range, 3.5-97.4 km). Conclusions and Relevance Most high-risk trauma patients injured in rural areas were cared for outside of major trauma centers and most rural trauma deaths occurred early, although overall mortality did not differ between regions. There are opportunities for improved timeliness and access to major trauma care among patients injured in rural regions.

Advocacy for maintaining and expanding Emergency Medical Services for Children is needed on many fronts. Pediatric emergency medicine (PEM) physicians are uniquely qualified to serve this role due to their expertise in the acute care of sick or injured pediatric patients. Given this, in addition to maintaining the highest standards in the emergency departments in which they work, PEM physicians also have responsibilities in the education, training, and practice of emergency medical services providers in their region. These providers are also well positioned to advocate for Emergency Medical Services for Children on a policy level at local, regional, and state governments and in organizations that deal with the care of children in both the prehospital and hospital arenas. Greater engagement by PEM physicians in such activities is required to optimize pediatric care across the spectrum of emergency services.

To derive and validate a model that accurately predicts ambulance arrival time that could be implemented as a Google Maps web application.This was a retrospective study of all scene transports in Multnomah County, Oregon, from January 1 through December 31, 2008. Scene and destination hospital addresses were converted to coordinates. ArcGIS Network Analyst was used to estimate transport times based on street network speed limits. We then created a linear regression model to improve the accuracy of these street network estimates using weather, patient characteristics, use of lights and sirens, daylight, and rush-hour intervals. The model was derived from a 50% sample and validated on the remainder. Significance of the covariates was determined by p0.05 for a t-test of the model coefficients. Accuracy was quantified by the proportion of estimates that were within 5 minutes of the actual transport times recorded by computer-aided dispatch. We then built a Google Maps-based web application to demonstrate application in real-world EMS operations.There were 48,308 included transports. Street network estimates of transport time were accurate within 5 minutes of actual transport time less than 16% of the time. Actual transport times were longer during daylight and rush-hour intervals and shorter with use of lights and sirens. Age under 18 years, gender, wet weather, and trauma system entry were not significant predictors of transport time. Our model predicted arrival time within 5 minutes 73% of the time. For lights and sirens transports, accuracy was within 5 minutes 77% of the time. Accuracy was identical in the validation dataset. Lights and sirens saved an average of 3.1 minutes for transports under 8.8 minutes, and 5.3 minutes for longer transports.An estimate of transport time based only on a street network significantly underestimated transport times. A simple model incorporating few variables can predict ambulance time of arrival to the emergency department with good accuracy. This model could be linked to global positioning system data and an automated Google Maps web application to optimize emergency department resource use. Use of lights and sirens had a significant effect on transport times.

Outcomes for pediatric out-of-hospital cardiac arrest (OHCA) are poor. Our objective was to determine temporal trends in incidence and mortality for pediatric OHCA.Adjusted incidence and hospital mortality rates of pediatric non-traumatic OHCA patients from 2007-2012 were analyzed using the 9 region Resuscitation Outcomes Consortium-Epidemiological Registry (ROC-Epistry) database. Children were divided into 4 age groups: perinatal (3 days), infants (3days-1year), children (1-11 years), and adolescents (12-19 years). ROC regions were analyzed post-hoc.We studied 1738 children with OHCA. The age- and sex-adjusted incidence rate of OHCA was 8.3 per 100,000 person-years (75.3 for infants vs. 3.7 for children and 6.3 for adolescents, per 100,000 person-years, p0.001). Incidence rates differed by year (p0.001) without overall linear trend. Annual survival rates ranged from 6.7-10.2%. Survival was highest in the perinatal (25%) and adolescent (17.3%) groups. Stratified by age group, survival rates over time were unchanged (all p0.05) but there was a non-significant linear trend (1.3% increase) in infants. In the multivariable logistic regression analysis, infants, unwitnessed event, initial rhythm of asystole, and region were associated with worse survival, all p0.001. Survival by region ranged from 2.6-14.7%. Regions with the highest survival had more cases of EMS-witnessed OHCA, bystander CPR, and increased EMS-defibrillation (all p0.05).Overall incidence and survival of children with OHCA in ROC regions did not significantly change over a recent 5year period. Regional variation represents an opportunity for further study to improve outcomes.

Linkage mapping in a backcross of {Brown Norway [BN/Crl (BN)] × ZUC- LeprfaSte(ZUC)} × ZUC identified a male-specific quantitative trait locus (QTL) for urinary albumin excretion (UAE) on rat chromosome 1. A homozygous ZUC.BN-( D1Rat42- D1Rat90)/Ste congenic was produced containing BN donor alleles from 135 to 276 Mb from chromosome 1 on the ZUC background. We observed threefold higher urinary albumin-to-creatinine ratios (ACR) in 15-wk-old Zucker background strain males than in same sex and age congenic animals when both strains are also homozygous for the ZUC leptin receptor fatty mutation ( LeprfaSte) ( P < 0.0001). We then linkage mapped within the donor region without confounded effects from other chromosomes. Phenotypes were collected in 248 F2 male rats in a population made by crossing parents heterozygous for both the BN donor region and ZUC LeprfaSte. Significant interactions were observed between the Lepr genotype and chromosome 1 QTL for six renal traits: urine volume, UAE at 10 and 15 wk, ACR, right kidney weight, and plasma urea nitrogen. A few traits, such as UAE and ACR, exhibit a second peak at the distal end of the chromosome. Hydronephrosis exhibited one or two QTLs contingent on adjustment for body weight. The results now demonstrate at least two sets of coincident traits with different correlations to kidney function.

Improving survival rates for out of hospital cardiac arrest (OHCA) at the neighborhood level is increasingly seen as priority in US cities. Since wide disparities exist in OHCA rates at the neighborhood level, it is necessary to locate neighborhoods where people are at elevated risk for cardiac arrest and target these for educational outreach and other mitigation strategies. This paper describes a GIS-based methodology that was used to identify communities with high risk for cardiac arrests in Franklin County, Ohio during the period 2004-2009. Prior work in this area used a single criterion, i.e., the density of OHCA events, to define the high-risk areas, and a single analytical technique, i.e., kernel density analysis, to identify the high-risk communities. In this paper, two criteria are used to identify the high-risk communities, the rate of OHCA incidents and the level of bystander CPR participation. We also used Local Moran's I combined with traditional map overlay techniques to add robustness to the methodology for identifying high-risk communities for OHCA. Based on the criteria established for this study, we successfully identified several communities that were at higher risk for OHCA than neighboring communities. These communities had incidence rates of OHCA that were significantly higher than neighboring communities and bystander rates that were significantly lower than neighboring communities. Other risk factors for OHCA were also high in the selected communities. The methodology employed in this study provides for a measurement conceptualization of OHCA clusters that is much broader than what has been previously offered. It is also statistically reliable and can be easily executed using a GIS.

ACADEMIC EMERGENCY MEDICINE 2012; 19:139–146 © 2012 by the Society for Academic Emergency Medicine Abstract Objectives: The objective was to identify high-risk census tracts, defined as those areas that have both a high incidence of out-of-hospital cardiac arrest (OHCA) and a low prevalence of bystander cardiopulmonary resuscitation (CPR), by using three spatial statistical methods. Methods: This was a secondary analysis of two prospectively collected registries in the city of Columbus, Ohio. Consecutive adult (≥18 years) OHCA patients, restricted to those of cardiac etiology and treated by emergency medical services (EMS) from April 1, 2004, to April 30, 2009, were studied. Three different spatial analysis methods (Global Empirical Bayes, Local Moran’s I, and SaTScan’s spatial scan statistic) were used to identify high-risk census tracts. Results: A total of 4,553 arrests in 200 census tracts occurred during the study period, with 1,632 arrests included in the final sample after exclusions for no resuscitation attempt, noncardiac etiology, etc. The overall incidence for OHCA was 0.70 per 1,000 people for the 6-year study period (SD = ±0.52). Bystander CPR occurred in 20.2% (n = 329), with 10.0% (n = 167) surviving to hospital discharge. Five high-risk census tracts were identified by all three analytic methods. Conclusions: The five high-risk census tracts identified may be possible sites for high-yield targeted community-based interventions to improve CPR training and cardiovascular disease education efforts and ultimately improve survival from OHCA.

We previously identified a region of mouse chromosome 7 that influences body fat mass in F2 littermates of congenic × background intercrosses. Current analyses revealed that alleles in the donor region of the subcongenic B6.C- D7Mit318 (318) promoted a twofold increase in adiposity in homozygous lines of 318 compared with background C57BL/6ByJ (B6By) mice. Parent-of-origin effects were discounted through cross-fostering studies and an F1 reciprocal cross. Mapping of the donor region revealed that it has a maximal size of 2.8 Mb (minimum 1.8 Mb) and contains a maximum of eight protein coding genes. Quantitative PCR in whole brain, liver, and gonadal white adipose tissue (GWAT) revealed differential expression between genotypes for three genes in females and two genes in males. Alpha-2,8-sialyltransferase 8B ( St8sia2) showed reduced 318 mRNA levels in brain for females and males and in GWAT for females only. Both sexes of 318 mice had reduced Repulsive guidance molecule-a ( Rgma) expression in GWAT. In brain, Family with sequence similarity 174 member b ( Fam174b) had increased expression in 318 females, whereas Chromodomain helicase DNA binding protein 2 ( Chd2-2) had reduced expression in 318 males. No donor region genes were differentially expressed in liver. Sequence analysis of coding exons for all genes in the 318 donor region revealed only one single nucleotide polymorphism that produced a nonsynonymous missense mutation, Gln7Pro, in Fam174b. Our findings highlight the difficulty of using expression and sequence to identify quantitative trait genes underlying obesity even in small genomic regions.

Crashes on highways frequently cause hazardous material exposure to the public and the environment. We evaluated differences in hazardous materials-related crashes vs. non-hazardous-material-related commercial motor vehicle crashes occurring from 2000 to 2006 on the Oregon state highway network. The two groups were compared for crash characteristics by χ2 analysis, and spatial clustering was tested using Ripley's K-function and kernel density estimator analyses. There were 8,622 total commercial motor vehicle crashes, 232 being hazardous-materials related. Hazardous materials-related crashes were not significantly associated with different road surface conditions, weather conditions or cause of crash. Hazardous materials-related crashes were associated more frequently with late evening/early morning hours and under artificial lights or at dusk. The commercial motor vehicle drivers in hazardous materials-related crashes were less frequently at fault than ones in the non-hazardous materials-related crashes....

Objectives. We sought to identify and characterize areas with high rates of major trauma events in 9 diverse cities and counties in the United States and Canada. Methods. We analyzed a prospective, population-based cohort of injured individuals evaluated by 163 emergency medical service agencies transporting patients to 177 hospitals across the study sites between December 2005 and April 2007. Locations of injuries were geocoded, aggregated by census tract, assessed for geospatial clustering, and matched to sociodemographic measures. Negative binomial models were used to evaluate population measures. Results. Emergency personnel evaluated 8786 major trauma patients, and data on 7326 of these patients were available for analysis. We identified 529 (13.7%) census tracts with a higher than expected incidence of major trauma events. In multivariable models, trauma events were associated with higher unemployment rates, larger percentages of non-White residents, smaller percentages of foreign-born residents, lower educational levels, smaller household sizes, younger age, and lower income levels. Conclusions. Major trauma events tend to cluster in census tracts with distinct population characteristics, suggesting that social and contextual factors may play a role in the occurrence of significant injury events.

The structural features responsible for the activities of hepatic lipase (HL) can be clarified by in vivo comparisons of naturally occurring variants. The coding sequence of HL from C57BL/6J (B6) and SPRET/EiJ (SPRET) mice differs by four amino acids (S106N, A156V, L416V, S480T); however, these changes are not predicted to influence HL function. To test for allelic effects, we generated SPRET-HL transgenics with physiological levels of HL mRNA and HL activity that was parallel in female transgenics and about 70% higher in male transgenics, toward tri-[3H]oleate, compared with B6 controls. We found no correlation between activity levels and plasma lipids. However, significant allelic effects on plasma lipids were observed. Compared with B6-HL, SPRET-HL mediated reductions in total cholesterol (TC) and VLDL-, LDL- and HDL-cholesterol and HDL-triglyceride (TG) in fed males, and SPRET-HL decreased total TG and VLDL- and HDL-TG levels in fasted males. Fasted female transgenics had reduced TC compared with controls. We also found allele and sex effects on lipoprotein particle size. Male transgenic mice had increased VLDL and decreased LDL size, and female transgenic mice had decreased HDL size compared with control animals. These findings demonstrate highly divergent effects of naturally occurring HL coding sequence variants on lipid and lipoprotein metabolism.

To determine clusters of trauma incidents with high injury severity and resource utilization and to test their association with census demographic information.Using "trauma band" unique identifiers and probabilistic linkage for unmatched cases, we matched injury location information collected from a centralized regional trauma communications center to the state trauma system registry for patients directly transported to two level I trauma centers for the years 2001-2003 in a three-county area. The injury locations were aggregated at the census tract level using a geographic information system (GIS). Moran's I analysis was used to determine clusters of census tracts that had a high incidence of either total trauma injuries, Injury Severity Scores (ISSs)15, or high resource use (in-hospital mortality, admission to the intensive care unit, or major nonorthopedic surgery). These clusters were then tested for association with census tract demographics using logistic regression.Eight thousand seven hundred fifty-one injured persons were directly transported from the tricounty area to a trauma center during the study period. The mean (+/- standard deviation) age was 37 +/- 21 years, 67.4% were male, 18.9% had ISSs15, and 29.8% had a high-resource-use indicator. Moran's I analysis demonstrated a single large cluster of incidents for total injuries, ISS15, and occurrence of a high-resource-use indictor that overlapped except for one small census tract. Logistic regression revealed that the high-risk cluster was associated with a higher prevalence of nonwhite population and vacant housing and a lower prevalence of foreign-born residents and family housing.GIS cluster analysis demonstrated high-risk census tracts for trauma incidents and associated population demographics. Geospatial analyses may assist injury prevention interventions and emergency medical services deployment strategies for trauma.

Author(s): Warden, CH; Fisler, JS; Espinal, G; Graham, J; Havel, PJ; Perroud, B | Abstract: BackgroundMaternal genotype has lifetime effects on progeny, but few specific genes, and no proteases, are known to underlie maternal effects. Prolyl endopeptidase (PREP) is a serine protease with putative substrates that regulate appetite or milk production.ObjectiveTo test effects of PREP on obesity phenotypes in mice.DesignMice with a gene trap (GT) of PREP (PREP(gt/gt)) on the C57BL/6J (B6) background were generated. Minimal PREP protein was detected by western blot. In Experiment 1, direct effects of PREP were measured in littermate mice derived from intercrosses of heterozygotes (PREP(WT/gt)). In Experiment 2, maternal effects of PREP were measured in reciprocal crosses of heterozygous (PREP(WT/gt)) and wild-type (WT) (PREP(WT/WT)) males and females. DIETS: Mice were fed either low-fat (LF, Experiments 1 and 2) or high-fat (HF, Experiment 1) defined diets.MeasurementsAdiposity index (AI) was calculated from body weight (BW) and weights of four fat depots measured in 120-day-old mice. Fasting plasma glucose, insulin and leptin were measured. In vivo plasma alpha-MSH levels were measured by targeted quantitative peptidomics.ResultsExperiment 1-In intercross mice, there were significant diet effects, but few genotype effects. There were no genotype effects on BW or AI in males or females on either diet. Experiment 2-In contrast, reciprocal crosses of heterozygous males or females with WT B6 revealed highly significant parent of origin effects on all traits except body length. Progeny (WT and heterozygous genotypes and both sexes) born to female PREP(WT/gt) heterozygotes had fat pads that weighed as much as -twofold more at 120 days old than progeny born to male heterozygotes.ConclusionHeterozygosity for PREP GT results in highly significant maternal effects, whereas homozygosity for the PREP(gt/gt) mutation has a much more limited direct effect.

Objectives: Patients of all ages use emergency departments (EDs) for primary care. Several studies have evaluated patient and system characteristics that influence pediatric ED use. However, the issue of proximity as a predictor of ED use has not been well studied. The authors sought to determine whether ED use by pediatric Medicaid enrollees was associated with the distance to their primary care providers (PCPs), distance to the nearest ED, and distance to the nearest children’s hospital. Methods: This historical cohort study included 26,038 children age 18 and under, assigned to 332 primary care practices affiliated with a Medicaid health maintenance organization (HMO). Predictor variables were distance from the child’s home to his or her PCP site, distance from home to the nearest ED, and distance from home to the nearest children’s hospital. The outcome variable was each child’s ED use. A negative binomial model was used to determine the association between distance variables and ED use, adjusted for age, sex, and race, plus medical and primary care site characteristics previously found to influence ED use. Distance variables were divided into quartiles to test for nonlinear associations. Results: On average, children made 0.31 ED visits/person/year. In the multivariable model, children living greater than 1.19 miles from the nearest ED had 11% lower ED use than those living within 0.5 miles of the nearest ED (risk ratio [RR] = 0.89, 95% CI = 0.81 to 0.99). Children living between 1.54 and 3.13 miles from their PCPs had 13% greater ED use (RR = 1.13, 95% CI = 1.03 to 1.24) than those who lived within 0.7 miles of their PCP. Conclusions: Geographical variables play a significant role in ED utilization in children, confirming the importance of system-level determinants of ED use and creating the opportunity for interventions to reduce geographical barriers to primary care.

Most quantitative trait loci (QTL) studies fail to account for the effect that the maternal genotype may have on an individual’s phenotypes, even though maternal effect QTL have been shown to account for considerable variation in growth and obesity traits in mouse models. Moreover, the fetal programming theory suggests that maternal effects influence an offspring’s adult fitness, although the genetic nature of fetal programming remains unclear. Within this context, our study focused on mapping genomic regions associated with maternal effect QTL by analyzing the phenotypes of chromosomes 2 and 7 subcongenic mice from genetically distinct dams. We analyzed 12 chromosome 2 subcongenic strains that spanned from 70 to 180 Mb with CAST/EiJ donor regions on the background of C57BL/6 J, and 14 chromosome 7 subcongenic strains that spanned from 81 to 111 Mb with BALB/cByJ donor regions on C57BL/6ByJ background. Maternal QTL analyses were performed on the basis of overlapping donor regions between subcongenic strains. We identified several highly significant (P

Background— Population-based data for pediatric cardiac arrest are scant and largely from urban areas. The Resuscitation Outcomes Consortium (ROC) Epistry–Cardiac Arrest is a population-based emergency medical services registry of out-of-hospital nontraumatic cardiac arrest (OHCA). This study examined age-stratified incidence and outcomes of pediatric OHCA. We hypothesized that survival to hospital discharge is less frequent from pediatric OHCA than adult OHCA. Methods and Results— This prospective population-based cohort study in 11 US and Canadian ROC sites included persons P =0.03). Unadjusted odds ratio for pediatric survival to discharge compared with adults was 0.71 (95% confidence interval, 0.37 to 1.39) for infants, 2.11 (95% confidence interval, 1.21 to 3.66) for children, and 2.04 (95% confidence interval, 1.24 to 3.38) for adolescents. Conclusions— This study demonstrates that the incidence of OHCA in infants approaches that observed in adults but is lower among children and adolescents. Survival to discharge was more common among children and adolescents than infants or adults.

Summary Study objective For trials involving exception from informed consent, some IRBs require that community members be allowed to “opt out” prior to enrollment. We tested for geospatial clustering of opt-out requests and the associated census tract characteristics in one study region. Methods This was a retrospective study at a single site of a multicenter exception from informed consent resuscitation trial. We collected and geocoded mailing addresses for persons requesting opt-out bracelets over 16 months, then tested for geospatial clustering using geographic information systems (GIS) analysis. Characteristics for tracts with and without bracelet clustering were compared using univariate tests, multivariable regression, and classification and regression tree (CART) analysis. Results We received 395 phone calls requesting 718 bracelets, of which 673 were analyzable. Of 397 census tracts in the region, 208 (52%) had at least one request and 38 (10%) demonstrated clustering. In multivariable models, an increasing proportion of family households (OR .90, 95%CI .85–.93), veterans (OR .91, 95%CI .81–1.02), and renters (OR .96, 95%CI .92–.99) were associated with lower odds of requesting an opt-out bracelet, while census tracts with higher income had higher odds of opting-out (OR 1.07, 95%CI 1.02–1.11). Using CART, the proportion of family households and graduate education identified the majority of opt-out requests by census tracts (cross-validation sensitivity 92%, specificity 56%). Conclusions Opt-out requests for an exception from informed consent trial at one study site were geographically clustered and associated with certain population demographics. These findings may help identify key target groups for community consultation in future trials.

In the present investigation we describe the life span characteristics and phenotypic traits of ad libitum-fed mice that overexpress UCP2/3 (Positive-TG), their non-overexpressing littermates (Negative-TG), mice that do not expression UCP2 (UCP2KO) or UCP3 (UCP3KO), and wild-type C57BL/6J mice (WT-Control). We also included a group of C57BL/6J mice calorie-restricted to 70% of ad libitum-fed mice in order to test partially the hypothesis that UCPs contribute to the life extension properties of CR. Mean survival was slightly, but significantly, greater in Positive-TG, than that observed in Negative-TG or WT-Control; mean life span did not significantly differ from that of the UCP3KO mice. Maximal life span did not differ among the ad libitum-fed groups. Genotype did not significantly affect body weight, food intake, or the type of pathology at time of death. Calorie restriction increased significantly mean and maximal life span, and the expression of UCP2 and UCP3. The lack of difference in maximal life spans among the Positive-TG, Negative-TG, and UCP3KO suggests that UCP3 does not significantly affect longevity in mice.

Gastric bypass surgery is the most commonly performed bariatric surgical procedure in the United States. Variable weight loss following this relatively standardized intervention has been reported. To date, a method for reliable profiling of patients who will successfully sustain weight loss for the long term has not been established. In addition, the mechanisms of action in accomplishing major weight loss as well as the explanation for the variable weight loss have not been established. To examine whether gene expression in perioperative omental adipose is associated with gastric bypass-induced weight loss. Cross-sectional study of gene expression in perisurgical omental adipose tissues taken/available at the time of operation and total excess weight loss (EWL). Fifteen overweight individuals who underwent Roux-en-Y gastric bypass (RYGB) surgery at the University of California Davis Medical Center (BMI: 40.6–72.8 kg/m2). Body weight before and following weight stabilization 18–42 months after surgery. Perioperative omental adipose RNA isolated from 15 subjects was hybridized to Affymetrix HG-U133A chips for 22 283 transcript expression measurements. Downstream analysis identified a set of genes whose expression was significantly correlated with RYGB-induced weight loss. The significant individual genes include acyl-coenzyme A oxidase 1 (ACOX1), phosphodiesterase 3A cGMP-inhibited (PDE3A) and protein kinase, AMP-activated, beta 1 non-catalytic subunit (PRKAB1). Specifically, ACOX1 plays a role in fatty acid metabolism. PDE3A is involved in purine metabolism and hormone-stimulated lipolysis. PRKAB1 is involved in adipocytokine signaling pathway. Gene network analysis revealed that pathways for glycerolipid metabolism, breast cancer and apoptosis were significantly correlated with long-term weight loss. This study demonstrates that RNA expression profiles from perioperative adipose tissue are associated with weight loss outcome following RYGB surgery. Our data suggest that EWL could be predicted from preoperative samples, which would allow for informed decisions about whether or not to proceed to surgery.

To evaluate the change in nausea scales and incidence of vomiting with the use of ondansetron in the treatment of nausea and vomiting in the prehospital setting.Data were prospectively collected on all emergency medical service patients who received ondansetron for undifferentiated nausea and vomiting during a 6-month study period. Added outcome measures for this study were verbal quantitative (scale of 1-10) and qualitative "nausea scales," incidence of vomiting prior to and after administration of ondansetron, and adverse events. Patients who had this additional data collected and ones who did not were compared. Changes in the "nausea scales" and incidence of vomiting before and after administration and correlation among these measures were also compared. There was no control or placebo group.Ondansetron was administered to 952 patients of 20,054 patients transported during this time period (5%); of these 472 had at least some of the outcome measures documented. There were minimal differences in the two cohorts; 198 patients had paired before and after quantitative "nausea scales" documented: 7.6 +/- 2.4 and 4.6 +/- 3.1, respectively (Delta = 2.9, 95% CI: 2.5-3.4); 447 patients had a qualitative change in nausea level documented: 0.4% "a lot worse," 1.3% "a little worse," 34% "unchanged," 40% "a little better," and 25% "a lot better"; 187 patients had all three measures documented with a Pearson correlation coefficient of 0.63 between the change in the quantitative scale and the qualitative scale (95% CI: 0.14-0.20, R(2) 0.39). In 462 patients, vomiting decreased from 60% to 30% (Wilcoxon signed ranks test p0.001). The Pearson correlation coefficients for the change in vomiting incidence with the qualitative and quantitative "nausea scales" were poor: 0.012 (95% CI: -0.015 to 0.039, R(2) 0.00014) and 0.051 (95% CI: -0.032 to 0.118, R(2) 0.00026), respectively. There were no reported adverse events.Ondansetron appears to be moderately effective in decreasing nausea and vomiting in undifferentiated prehospital patients. Additional controlled trials may be needed to compare it with other antiemetics.

Tumor suppressor candidate 5 (Tusc5, also termed brain endothelial cell derived gene-1 or BEC-1), a CD225 domain-containing, cold-repressed gene identified during brown adipose tissue (BAT) transcriptome analyses was found to be robustly-expressed in mouse white adipose tissue (WAT) and BAT, with similarly high expression in human adipocytes. Tusc5 mRNA was markedly increased from trace levels in pre-adipocytes to significant levels in developing 3T3-L1 adipocytes, coincident with several mature adipocyte markers (phosphoenolpyruvate carboxykinase 1, GLUT4, adipsin, leptin). The Tusc5 transcript levels were increased by the peroxisome proliferator activated receptor- (PPAR) agonist GW1929 (1g/mL, 18 h) by >10-fold (pre-adipocytes) to ∼1.5-fold (mature adipocytes) versus controls (p < 0.0001). Taken together, these results suggest an important role for Tusc5 in maturing adipocytes. Intriguingly, we discovered robust co-expression of the gene in peripheral nerves (primary somatosensory neurons). In light of the marked repression of the gene observed after cold exposure, these findings may point to participation of Tusc5 in shared adipose–nervous system functions linking environmental cues, CNS signals, and WAT–BAT physiology. Characterization of such links is important for clarifying the molecular basis for adipocyte proliferation and could have implications for understanding the biology of metabolic disease-related neuropathies. Published by Elsevier Ireland Ltd.

Background Glutamate carboxypeptidase II (GCPII) encodes for intestinal folate hydrolase and brain N-acetylated alpha-linked acidic dipeptidase. Previous studies provided conflicting results on the effect of the GCPII 1561C-->T polymorphism on folate and total homocysteine (tHcy) concentrations. Objective We aimed to determine the potential effects of 2 polymorphisms of GCPII on plasma folate and tHcy concentrations, cognition, anxiety, and depression in a large aging cohort of Norwegians enrolled in the Hordaland Homocysteine Study. Design DNA samples were genotyped for the GCPII 1561C-->T and 484A-->G polymorphisms, and the results were linked to plasma folate and tHcy concentrations and to scores for cognition, anxiety, and depression. Results The 2 polymorphisms were in linkage disequilibrium and were associated with concentrations of tHcy. After adjustment for covariates, persons in the CT or combined CT and TT groups of the 1561C-->T polymorphism had higher plasma folate concentrations and lower tHcy concentrations than did those in the CC group. Subjects with the TT genotype had lower Symbol Digit Modalities Test (SDMT) scores than did subjects with the CC genotype. Compared with abstainers, moderate alcohol drinkers had higher plasma folate concentrations and higher scores on the Mini Mental State Examination. However, women abstainers with the CT genotype had lower SDMT scores than did abstainers with the CC genotype or moderate drinkers with the CT genotype. Conclusions The 1561C-->T polymorphism is associated with higher plasma folate and lower tHcy concentrations and with lower SDMT cognitive scores in women who abstain from alcohol.

There are many chemical respiratory agents suitable for use by terrorists. They are the oldest chemical agents used and have caused the most casualties throughout the 20th century. Many are available in large quantities for industrial use and are susceptible to potential sabotage. This paper will concentrate on respiratory agents that are readily available and have the potential to cause a large number of casualties and panic. These agents have a lower rate of lethality when compared to other chemical agents but could produce many casualties that may overwhelm the emergency medical system.

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries. © The Authors 2005.