Population pharmacokinetic meta-analysis of five beta-lactams antibiotics to support dosing regimens in dogs for surgical antimicrobial prophylaxis.

The Pharmacokinetic/Pharmacodynamic (PK/PD) relationship of antimicrobial drugs (AMD) for surgical prophylaxis has been poorly studied, hampering evidence-based decision making around AMD dosing and timing. Our objective is to use PK/PD principles to inform (1) the timing of administration and (2) the interval for re-administration of AMD used peri-operatively in dogs. Raw plasma concentrations of cefazolin, cefuroxime, cefalexin, amoxicillin and ampicillin were retrieved from original intravenous studies performed in dogs. E. coli and methicillin-susceptible staphylococci were identified as possible intraoperative contaminants and their epidemiological cut-offs (ECOFF) were retrieved from the EUCAST database. Individual PK data were refitted with non-linear mixed effect models (Phoenix®). We performed Monte Carlo simulation to compute i) the 95th percentile of time of peak concentration in the peripheral compartment (informing timing between administration and first incision) and ii) the duration for which at least 90% of dogs maintain a free plasma concentration above ECOFF (informing timing of re-administration: 1.5-4 h). Cefazolin (22-25 mg/kg), cefuroxime (20 mg/kg), cefalexin (15 mg/kg) and amoxicillin (16.7 mg/kg) reached peak peripheral concentrations within 30 min, but ampicillin (20 mg/kg) required 82 min, respectively. For methicillin-susceptible staphylococci, cefazolin and cefuroxime require re-administration every 2 h, whereas cefalexin and both amoxicillin and ampicillin can be readministered every 3 and 4 h, respectively. For E. coli, only cefazolin provided adequate perioperative coverage with 2-hourly administration, where cefuroxime and cefalexin failed uniformly. Alternatively, ampicillin and amoxicillin (critically ill dogs) may cover E. coli contaminations, but only if readministered every 1.5 h. These PK-derived conclusions provide a rationale for perioperative AMD administration timing.

Antimicrobial prophylaxis in companion animal surgery: A scoping review for European Network for Optimization of Antimicrobial Therapy (ENOVAT) guidelines.

Surgical antimicrobial prophylaxis (SAP) is widely used to reduce the risk of surgical site infections (SSI), but there is uncertainty as to what the proportion of SSI reduction is. Therefore, it is difficult for surgeons to properly weigh the costs, risks and benefits for individual patients when deciding on the use of SAP, making it challenging to promote antimicrobial stewardship in primary practice settings. The objective of this study was to map the veterinary evidence focused on assessing the effect of SAP on SSI development and in order to identify surgical procedures with some research evidence and possible knowledge gaps. In October 2021 and December 2022, Scopus, CAB Abstracts, Web of Science Core Collection, Embase and MEDLINE were systematically searched. Double blinded screening of records was performed to identify studies in companion animals that reported on the use of SAP and SSI rates. Comparative data were available from 34 out of 39123 records screened including: eight randomised controlled trials (RCT), 23 cohort studies (seven prospective and 16 retrospective) and three retrospective case series representing 12476 dogs and cats in total. Extracted data described peri- or post-operative SAP in nine, and 25 studies, respectively. In the eight RCTs evaluating SAP in companion animals, surgical procedure coverage was skewed towards orthopaedic stifle surgeries in referral settings and there was large variation in SAP protocols, SSI definitions and follow-up periods. More standardized data collection and agreement of SSI definitions is needed to build stronger evidence for optimized patient care.

Association between anticoagulant therapy, exacerbations and mortality in a Danish cohort of patients with Chronic Obstructive Pulmonary Disease.

OBJECTIVES: Pulmonary Embolism has been frequently reported in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AE-COPD). The study aimed to determine whether COPD patients who receive anticoagulant (AC) therapy have a reduced risk of hospitalization due to AE-COPD and death. METHODS: This nationwide population-based study was based on data from the Danish Register of COPD (DrCOPD), which contains complete data on COPD outpatients between 1st January 2010 and 31st December 2018. National registers were used to obtain information regarding comorbidities and vital status. Propensity-score matching and Cox proportional hazards models were used to assess AE-COPD and death after one year. RESULTS: The study cohort consisted of 58,067 patients with COPD. Of these, 5194 patients were on AC therapy. The population was matched 1:1 based on clinical confounders and AC therapy, resulting in two groups of 5180 patients. We found no association between AC therapy and AE-COPD or all-cause mortality in the propensity-score matched population (HR 1.03, 95% CI 0.96-1.10, p = 0.37). These findings were confirmed in a competing risk analysis. In the sensitivity analysis, we performed an adjusted analysis of the complete cohort and found a slightly increased risk of AE-COPD or death in patients treated with AC therapy. This study found a low incidence of pulmonary embolisms and deep venous thrombosis in both groups. CONCLUSIONS: AC therapy was not associated with the risk of hospitalization due to AE-COPD or all-cause mortality.

The effect of urine storage temperature and boric acid preservation on quantitative bacterial culture for diagnosing canine urinary tract infection.

BACKGROUND: Quantitative bacterial culture (QBC) is the gold standard for diagnosing canine urinary tract infection. Current guidelines recommend QBC within 24 h of urine collection and that unpreserved urine is refrigerated until culture. However, temperature-controlled transport is rarely feasible, indicating a need for alternative storage during transport of urine from primary veterinary practices to the microbiology laboratory. The objective was to investigate the effect of storage temperature and boric acid sponge-preservation on quantitative bacterial culture of canine urine. RESULTS: Significant bacteriuria was detected in 72 out of 179 samples (40%) collected from 141 dogs. Overall accuracy was 94-98% for both storage conditions and time points. Non-inferiority (15% margin) to reference quantitative bacterial culture was evident for sensitivity, specificity and predictive values for both storage methods and time points, except for the negative predictive value for 48 h boric acid preservation (NPV: 89, 95% CI [79;95]). There was no significant difference between the sensitivity and specificity for either of the time-points (p-value = 0.07-1). CONCLUSIONS: Boric acid sponge-preservation using Uriswab™ is a useful alternative to refrigeration of urine samples during transport. Reliable quantitative bacterial culture results can be obtained from canine urine up to 48 h after collection if urine is refrigerated, and for at least 24 h if urine is stored using a boric acid-containing urine transport system.

Pre-test probability of urinary tract infection in dogs with clinical signs of lower urinary tract disease.

Clinical signs of lower urinary tract disease in dogs are characteristic but non-specific for infection. It has been hypothesized that age, sex and neuter status influences the prevalence of urinary tract infection (UTI), but the predictive value of the combined clinical presentation has not been explored in dogs. The aim of the study was to assess clinical predictors (sex/neuter status, age, dysuria/stranguria, pollakiuria, macroscopic hematuria, malodorous urine and history of recurrent UTI) for bacterial cystitis, and to develop a clinical decision rule. Data was retrieved from medical records (retrospective cases) or from standardized recording sheets (prospective cases). Bacterial cystitis was defined as significant bacteriuria on quantitative bacterial culture in dogs with compatible clinical signs of urinary tract disease. Dogs of any breed, sex and age were included. A total of 1727 microbiology records were screened and 424 samples were included in the analysis. Bacterial cystitis was confirmed in 46% of the cases. Four variables predicted bacterial cystitis: sex/neuter status, age, pollakiuria and hematuria. A score was designated to each variable and a clinical rule was constructed. This rule attained an AUC of 0.75 and had sensitivity of 83% and specificity of 55% at its optimal cut-off (score ≥2.0). A score cut-off of ≥3.0 had a positive predictive value of 70%. Several factors predicted bacterial cystitis, but the clinical rule had only modest predictive value. Other variables or point-of-care test results should be included in future research to optimize overall precision.

Breastfeeding and later maternal risk of hypertension and cardiovascular disease - The role of overall and abdominal obesity.

In this study, we examined how any, full, and partial breastfeeding durations were associated with maternal risk of hypertension and cardiovascular disease (CVD), and how prepregnancy body mass index (BMI) and waist circumference 7 years postpartum influenced these associations. A total of 63,260 women with live-born singleton infants in the Danish National Birth Cohort (1996-2002) were included. Interviews during pregnancy and 6 and 18 months postpartum provided information on prepregnancy weight, height, and the duration of full and partial breastfeeding. Waist circumference was self-reported 7 years postpartum. Cox regression models were used to estimate hazard ratios of incident hypertension and CVD, registered in the National Patient Register from either 18 months or 7 years postpartum through 15 years postpartum. Any breastfeeding ≥4 months was associated with 20-30% lower risks of hypertension and CVD compared to <4 months in both normal/underweight and overweight/obese women. At follow-up starting 7 years postpartum, similar risk reductions were observed after accounting for waist circumference adjusted for BMI. Partial breastfeeding >2 months compared to ≤2 months, following up to 6 months of full breastfeeding, was associated with 10-25% lower risk of hypertension and CVD. Compared with short breastfeeding duration, additional partial breastfeeding was as important as additional full breastfeeding in reducing risk of hypertension and CVD. Altogether, longer duration of breastfeeding was associated with lower maternal risk of hypertension and CVD irrespective of prepregnancy BMI and abdominal adiposity 7 years after delivery. Both full and partial breastfeeding contributed to an improved cardiovascular health in mothers.

[Relevance of big data for molecular diagnostics]. / Bedeutung von Big Data für die molekulare Diagnostik.

Big data analysis raises the expectation that computerized algorithms may extract new knowledge from otherwise unmanageable vast data sets. What are the algorithms behind the big data discussion? In principle, high throughput technologies in molecular research already introduced big data and the development and application of analysis tools into the field of rheumatology some 15 years ago. This includes especially omics technologies, such as genomics, transcriptomics and cytomics. Some basic methods of data analysis are provided along with the technology, however, functional analysis and interpretation requires adaptation of existing or development of new software tools. For these steps, structuring and evaluating according to the biological context is extremely important and not only a mathematical problem. This aspect has to be considered much more for molecular big data than for those analyzed in health economy or epidemiology. Molecular data are structured in a first order determined by the applied technology and present quantitative characteristics that follow the principles of their biological nature. These biological dependencies have to be integrated into software solutions, which may require networks of molecular big data of the same or even different technologies in order to achieve cross-technology confirmation. More and more extensive recording of molecular processes also in individual patients are generating personal big data and require new strategies for management in order to develop data-driven individualized interpretation concepts. With this perspective in mind, translation of information derived from molecular big data will also require new specifications for education and professional competence.

Effects of Diagnostic Work-Up on Medical Decision-Making for Canine Urinary Tract Infection: An Observational Study in Danish Small Animal Practices.

BACKGROUND: Clinical signs of urinary tract disease in dogs often lead to prescription of antibiotics. Appropriate diagnostic work-up could optimize treatment and reduce the risk of inappropriate use of antibiotics. HYPOTHESIS/OBJECTIVES: To describe and evaluate the impact of diagnostic work-up on decision to treat (DTT) and choice of antibiotic treatment (COT) for dogs presenting with clinical signs of urinary tract disease. ANIMALS: One hundred and fifty-one dogs presenting to 52 Danish veterinary practices. METHODS: Prospective, observational study. Clinical signs, diagnostic work-up, and prescriptions were recorded. Urine samples were submitted to a reference laboratory for quantitative bacterial culture (QBC) and susceptibility testing. The laboratory results were used as reference for assessing the appropriateness of DTT and COT. RESULTS: In the majority of dogs, veterinarians performed dipstick (99%), microscopic examination of urine (80%) and bacterial culture (56%). Fifty-one percent of dogs had urinary tract infection (UTI) based on reference QBC. Appropriate DTT was made for 62% of the dogs, while 36% were over-prescribed and 2% under-prescribed. Inappropriate use of second-line agents was found in 57% of the UTI cases. Performing microscopy-but not culture-significantly impacted DTT (P = 0.039) while no difference was seen in COT (P = 0.67). The accuracy of in-house microscopy and culture were 64.5 and 77%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Over-prescription of antibiotics was common among dogs with suspected UTI, regardless of the diagnostic work-up performed. Test inaccuracy under practice conditions and incoherence between diagnostic test results and decision-making both explained inappropriate and unnecessary use of antibiotics.

Childcare before age 6 and body mass index at age 7 years in a cohort of Danish children.

BACKGROUND: Previous studies show inconsistent associations between childcare and obesity. AIMS: Our prior work demonstrated that childcare in infancy was associated with higher weight in a cohort of Danish children. Here, we extend this work and examine childcare through 6 years and body mass index (BMI) at age 7 years. MATERIALS AND METHODS: We examined 24 714 children in the Danish National Birth Cohort who were also in the Childcare Database. We conducted multivariable linear regressions examining children prior to age 6, overall and by type (daycare, crèche, age-integrated and kindergarten), and BMI z-score at 7 years, stratifying on maternal socio-occupational status. RESULTS: A total of 19 760 (80.0%) children attended childcare before age 6. Childcare prior to age 6 was associated with BMI z-score at 7 years (0.004 units per each additional 6 months of care; 95% CI: 0.001, 0.008; p = 0.01). Childcare in a kindergarten was the only type of care associated with BMI (0.009 units; 95% CI: 0.003, 0.02; p = 0.01). For children of higher socio-occupational status mothers, childcare was associated with a 0.008 unit increase in BMI (95% CI: 0.004, 0.01; p > 0.001). CONCLUSIONS: Childcare was weakly associated with later BMI. This relationship was more pronounced in children from higher socio-occupational status mothers and children in kindergarten care.

Prenatal risk factors influencing childhood BMI and overweight independent of birth weight and infancy BMI: a path analysis within the Danish National Birth Cohort.

BACKGROUND AND OBJECTIVES: Prenatal risk factors for childhood overweight may operate indirectly through development in body size in early life and/or directly independent hereof. We quantified the effects of maternal and paternal body mass index (BMI), maternal age, socioeconomic position (SEP), parity, gestational weight gain, maternal smoking during pregnancy, caesarean section, birth weight, and BMI at 5 and 12 months on BMI and overweight at 7 and 11 years. METHODS: Family triads with information on maternal, paternal and child BMI at ages 7 (n=29 374) and 11 years (n=18 044) were selected from the Danish National Birth Cohort. Information originated from maternal interviews and medical health examinations. Path analysis was used to estimate the direct and indirect effects of prenatal risk factors on childhood BMI z-scores (BMIz per unit score of the risk factor). Logistic regression was used to examine associations with overweight. RESULTS: The strongest direct effects on BMIz at age 7 were found for maternal and paternal BMI (0.19 BMIz and 0.14 BMIz per parental BMIz), low SEP (0.08 BMIz), maternal smoking (0.12 BMIz) and higher BMIz at 5 and 12 months (up to 0.19 BMIz per infant BMIz). For BMIz at age 11 with BMIz at age 7 included in the model, similar effects were found, but the direct effects of BMIz at age 5 and 12 months were mediated through BMI at age 7 (0.62 BMIz per BMIz). Same results were found for overweight. The sum of the direct effects can be translated to approximate absolute measures: 2.4 kg at 7 years, 5.7 kg at 11 years, in a child with average height and BMI. CONCLUSIONS: Parental BMI, low SEP and smoking during pregnancy have persisting, strong and direct effects on child BMI and overweight independent of birth weight and infancy BMI.

The hierarchical response of human corneal collagen to load.

Fibrillar collagen in the human cornea is integral to its function as a transparent lens of precise curvature, and its arrangement is now well-characterised in the literature. While there has been considerable effort to incorporate fibrillar architecture into mechanical models of the cornea, the mechanical response of corneal collagen to small applied loads is not well understood. In this study the fibrillar and molecular response to tensile load was quantified using small and wide angle X-ray scattering (SAXS/WAXS), and digital image correlation (DIC) photography was used to calculate the local strain field that gave rise to the hierarchical changes. A molecular scattering model was used to calculate the tropocollagen tilt relative to the fibril axis and changes associated with applied strain. Changes were measured in the D-period, molecular tilt and the orientation and spacing of the fibrillar and molecular networks. These measurements were summarised into hierarchical deformation mechanisms, which were found to contribute at varying strains. The change in molecular tilt is indicative of a sub-fibrillar "spring-like" deformation mechanism, which was found to account for most of the applied strain under physiological and near-physiological loads. This deformation mechanism may play an important functional role in tissues rich in fibrils of high helical tilt, such as skin and cartilage. STATEMENT OF SIGNIFICANCE: Collagen is the primary mediator of soft tissue biomechanics, and variations in its hierarchical structure convey the varying amounts of structural support necessary for organs to function normally. Here we have examined the structural response of corneal collagen to tensile load using X-rays to probe hierarchies ranging from molecular to fibrillar. We found a previously unreported deformation mechanism whereby molecules, which are helically arranged relative to the axis of their fibril, change in tilt akin to the manner in which a spring stretches. This "spring-like" mechanism accounts for a significant portion of the applied deformation at low strains (<3%). These findings will inform the future design of collagen-based artificial corneas being developed to address world-wide shortages of corneal donor tissue.

Genetic risk scores for body fat distribution attenuate weight loss in women during dietary intervention.

OBJECTIVE: The well-established link between body fat distribution and metabolic health has been suggested to act through an impact on the remodeling capacity of the adipose tissue. Remodeling of the adipose tissue has been shown to affect body fat distribution and might affect the ability to lose weight. We aimed to study the effect of weighted genetic risk scores (GRSs) on weight loss based on single-nucleotide polymorphisms (SNPs) associated with waist-hip-ratio adjusted for body mass index (WHRadjBMI). DESIGN: We included 707 participants (533 women and 174 men) from the NUGENOB multi-center 10-week diet intervention study with weekly weight measurements. We created 3 GRSs, one including all reported WHRadjBMI SNPs (GRStotal), one including only SNPs with genome-wide significance in women or with significantly greater effect in women (GRSwomen), and one excluding SNPs in the GRSwomen (GRSmen). The data were analyzed in a mixed linear model framework. RESULTS: The GRStotal and GRSwomen attenuated weight loss in women. The effect was strongest for the GRSwomen with an effect of 2.21 g per risk allele per day (95% confidence intereval (CI) (0.90;3.52), P=0.0009). Adjustment for WHR, basal metabolic rate or diet compliance did not affect the result. The GRSs had no effect on weight loss in men. The VEGFA rs1358980-T strongly attenuated weight loss in both men and women (ß=15.95 g per risk allele per day, (3.16;26.74), P=0.013) and (ß=15.95 g per risk allele per day, (2.58;13.53), P=0.004), respectively). CONCLUSION: Our findings suggest that genetic variants influencing body fat distribution attenuate weight loss in women independently on the effect on WHR. The stronger effect of the GRSwomen implies heterogenic effects of the WHRadjBMI variants on weight loss. A strong effect of rs1358980-T in the VEGFA locus suggests that angiogenesis plays a role, but this needs confirmation from functional studies.

Should Europe follow the US and declare obesity a disease?: a discussion of the so-called utilitarian argument.

In 2013, the American Medical Association (AMA) decided to recognize obesity as a disease. One of the main arguments presented in favor of this was broadly 'utilitarian': the disease label would, it was claimed, provide more benefits than harms and thereby serve the general good. Several individuals and groups have argued that this reasoning is just as powerful in the European context. Drawing mainly on a review of relevant social science research, we discuss the validity of this argument. Our conclusion is that in a Western European welfare state, defining obesity as a disease will not on balance serve the general good, and that it is therefore more appropriate to continue to treat obesity as a risk factor. The main reasons presented in favor of this conclusion are: It is debatable whether a disease label would lead to better access to care and preventive measures and provide better legal protection in Europe. Medicalization and overtreatment are possible negative effects of a disease label. There is no evidence to support the claim that declaring obesity a disease would reduce discrimination or stigmatization. In fact, the contrary is more likely, since a disease label would categorically define the obese body as deviant.

Body mass index trajectories from 2 to 18 years - exploring differences between European cohorts.

BACKGROUND: In recent decades, there has been an increase in the prevalence of childhood overweight in most high-income countries. Within northern Europe, prevalence tends to be higher in the UK compared with the Scandinavian countries. We aimed to study differences in body mass index (BMI) trajectories between large cohorts of children from UK and Scandinavian populations. METHODS: We compared BMI trajectories in participants from the English Avon Longitudinal Study of Parents and Children born in 1991-1993 (ALSPAC) (N = 6517), the Northern Finland Birth Cohorts born in 1966 (NFBC1966) (N = 3321) and 1986 (NFBC1986) (N = 4764), and the Danish Aarhus Birth Cohort born in 1990-1992 (ABC) (N = 1920). We used multilevel models to estimate BMI trajectories from 2 to 18 years. We explored whether cohort differences were explained by maternal BMI, height, education or smoking during pregnancy and whether differences were attributable to changes in the degree of skew in the BMI distribution. RESULTS: Differences in mean BMI between the cohorts were small but emerged early and persisted in most cases across childhood. Girls in ALSPAC had a higher BMI than all other cohorts throughout childhood, e.g. compared with the NFBC1986 BMI was 2.2-3.5% higher. For boys, the difference emerging over time (comparing the two NFBC's) exceeded the differences across populations (comparing NFBC1986, ABC and ALSPAC). BMI distribution demonstrated increasing right skew with age. CONCLUSION: Population-level differences between cohorts were small, tended to emerge very early, persisted across childhood, and demonstrated an increase in the right-hand tail of the BMI distribution.

Evaluation of different sampling methods and criteria for diagnosing canine urinary tract infection by quantitative bacterial culture.

The use of voided urine specimens for bacteriological culture in dogs is discouraged because contamination from external genitalia could lead to misinterpretation of laboratory results. Quantitative culturing and defining significant bacteriuria could increase the usefulness of voided specimens. However, limited evidence exists for the cut-offs currently recommended. The aim of this study was to evaluate the accuracy of current veterinary cut-off values for significant bacteriuria in voided canine urine. A secondary aim was to investigate if accuracy improved when applying qualitative criteria used in humans. Paired urine specimens were collected by both cystocentesis and voiding, and quantitative bacteriological cultures were performed within the same day. Cystocentesis was used as the reference standard with a cut-off for significant bacteriuria of ≥1000 colony forming units (CFU)/mL. Voided specimens were compared to cystocentesis using: (1) the veterinary cut-off of ≥100,000 CFU/mL; and (2) various cut-offs depending on qualitative criteria (sex, clinical signs and complicating factors), adapted from human guidelines. Ninety-four dogs with suspected urinary tract infection (UTI) were included for analysis. The veterinary cut-off yielded an accuracy of 94% with a sensitivity and specificity of 94% (95% confidence intervals [CI] 0.81, 0.99) and 94% (95% CI 0.86, 0.98), respectively. Applying the human guidelines did not improve overall accuracy (89%), and yielded a sensitivity and specificity of 97% (95% CI 0.86, 1.00) and 86% (95% CI 0.77, 0.92), respectively. The veterinary cut-off value of ≥100,000 CFU/mL for voided urine is appropriate for determining significant bacteriuria in the majority of dogs with suspected UTI if specimens are refrigerated and cultured on the day of collection.

Tracking of body mass index from 7 to 69 years of age.

BACKGROUND: Heavy children have an increased risk of being overweight young adults. Whether this risk remains in late adulthood is not well-understood. We investigated body mass index (BMI; kg m(-2)) tracking from childhood to late adulthood. METHODS: From the Copenhagen School Health Records Register, 72 959 men and 25 252 women born between 1930 and 1989 with BMI values at 7 and/or 13 years and as adults were included. Using a meta-regression approach, age- and sex-specific partial correlation analyses and logistic regressions were performed. RESULTS: Correlations between BMI at 7 years and young adult ages (18-19 years) were r=0.55 for men and r=0.55 for women. At late ages (60-69 years) these were r=0.28 for men and r=0.26 for women. The correlations did not differ by birth years. Compared with normal-weight 7-year-olds, overweight children had a higher odds of overweight at 18-19 years; odds ratio (OR)=14.02 (95% confidence interval (CI): 12.14-16.19) for men and 10.46 (95% CI: 4.82-22.70) for women. At ages 60-69 years ORs were 5.46 (95% CI: 0.95-31.36) for men and 1.61 (95% CI: 0.83-3.15) for women. Correlations and ORs were stronger at age 13 years than age 7 years as expected, but the overall patterns were similar. CONCLUSIONS: BMI tracking was weaker at late adult ages than at young adult ages. Although BMI tracks across the life course, childhood BMI is relatively poor at identifying later adult overweight or obesity at ages when chronic diseases generally emerge.

Childhood body mass index and height and risk of histologic subtypes of endometrial cancer.

BACKGROUND: Endometrial cancer risk factors include adult obesity and taller stature, but the influence of size earlier in life is incompletely understood. We examined whether childhood body mass index (BMI; kg m(-2)) and height were associated with histologic subtypes of endometrial cancer. METHODS: From the Copenhagen School Health Records Register, 155 505 girls born 1930-1989 with measured weights and heights from 7 to 13 years were linked to health registers. BMI and height were transformed to age-specific z-scores. Hazard ratios (HRs) and 95% confidence intervals were estimated by Cox regressions. RESULTS: A total of 1020 endometrial cancers were recorded. BMI was non-linearly associated with all endometrial cancers, oestrogen-dependent cancers and the subtype of endometrioid adenocarcinomas; associations were statistically significant and positive above a z-score=0 and non-significant below zero. Compared with a 7-year-old girl with a BMI z-score=0, an equally tall girl who was 3.6 kg heavier (BMI z-score=1.5) had a hazard ratio=1.53 (95% confidence interval: 1.29-1.82) for endometrioid adenocarcinoma. BMI was not associated with non-oestrogen-dependent cancers, except at the oldest childhood ages. Height at all ages was statistically significant and positively associated with all endometrial cancers, except non-oestrogen-dependent cancers. At 7 years, per ~5.2 cm (1 z-score), the risk of endometrioid adenocarcinoma was 1.18 (95% confidence interval: 1.09-1.28). Among non-users of unopposed oestrogens, associations between BMI and endometrioid adenocarcinoma strengthened, but no effects on height associations were observed. CONCLUSIONS: Endometrial carcinogenesis is linked to early-life body size, suggesting that childhood BMI and height may be useful indicators for the risk of later development of endometrial cancer and might aid in the early prevention of obesity-related endometrial cancers.

Safety in High School Supervised Agricultural Experiences: Teachers' Training and Students' Injury Awareness.

This research study sought to gather evidence of school-based agriculture teachers' hazard perceptions, safety practices, training experiences, and awareness of student injuries related to supervised agricultural experience (SAE) programs. Teachers agreed that students should follow safety guidelines developed by the National Children's Center for Rural and Agricultural Safety and Health during SAE work. Approximately 66% (f = 153) of teachers reported having general training in first aid, CPR, and AED. Twenty participants (8.6%) indicated having no safety certifications or training. Abrasions, lacerations, bites/stings, and burns accounted for a majority of the student SAE-related injuries that were reported. There were 82 participants (35.5%) who stated that no injuries had been reported or they were not aware of any injuries that occurred. The majority of teachers (66%) had received some form offirst aid or first response training, but fewer teachers had received safety training for ATVs (f = 25, 10.8%), tractors (f = 48, 20.7%), and livestock (f = 39, 16.8%). Results indicated a disparity between required safe work habits and the types of hazardous tasks students should be allowed to complete alone while participating in SAE activities. It appears most responding teachers in this study agreed to allow students to operate equipment and machinery alone. Recommendations for teachers include attending professional development training specific to SAE safety and keeping records of any risk assessments conducted during SAE supervision. Further development of best practices for SAE supervision and safety are needed to assist agricultural education professionals in protecting and shaping our future leaders in agriculture.

Childhood body mass index and risk of schizophrenia in relation to childhood age, sex and age of first contact with schizophrenia.

UNLABELLED: Childhood leanness is associated with an increased risk of schizophrenia, but the effects of gender, age at anthropometric measurements and age at first diagnosis on this relationship are unclear. The present study aimed at elucidating these associations. METHODS: Population-based cohort study with childhood anthropometric measures obtained annually from the age of 7 to 13 years in 253,353 Danes born 1930-1976 and followed to 31 December 2010. During this period, 4936 were registered with schizophrenia. The associations of childhood BMI with risk of schizophrenia were estimated with Cox regression models. RESULTS: Childhood BMI was significantly inversely associated with risk of schizophrenia, however with different patterns among boys and girls. In boys, childhood BMI had an inverse non-linear association with schizophrenia risk dependent on age at diagnosis; in particular, a surprisingly strong association was found between leanness and later onset of schizophrenia. In girls, the risk of schizophrenia decreased linearly with increasing BMI z-score (HR: 0.93; 95% CI: 0.88-0.98). In both boys and girls, birth weight was inversely associated with later risk. In girls, but not in boys, birth weight appeared to significantly modify the associations; there was a somewhat stronger inverse association in the lowest birth weight category. CONCLUSION: Birth weight as well as childhood BMI at ages 7 through 13 years is associated with risk of schizophrenia in both genders, but with a particular high risk of late-onset in lean boys irrespective of birth weight, and in lean girls with low birth weight. If replicated, these observations may inform preventive efforts build on schizophrenia trajectories rooted in early life.