Uterine cancer restaging according to the updated 2023 FIGO Guidelines does not uniformly affect prognosis: An institutional retrospective cohort study.

OBJECTIVE: Efforts have been made to better risk stratify patients given the rise in incidence of endometrial cancer (EC). The 2023 FIGO staging now incorporates histologic subtype and molecular classification into determination of EC stage. We sought to elucidate if the new staging system demonstrated prognostic differences compared to the 2009 staging system. METHODS: A retrospective chart review was performed on women treated for EC at our institution from September 2013 to May 2023 and combined with the publicly available TCGA Nature 2013 dataset. Detailed clinical information was captured. Patients were restaged according to the 2023 guidelines. Survival estimates were obtained using Kaplan-Meier method, and the log-rank test was used to compare survival curves for progression-free survival (PFS). RESULTS: 919 patients were included in our analysis. The datasets were comparable regarding histologic grade, stage, and age at diagnosis. 175 (31.5%) of patients in the institution dataset and 115 (31.6%) patients in the TCGA dataset experienced a stage change. Most patients whose stage changed were upstaged (275/290; 94.8%). 3-year PFS estimates for stage IA patients with no stage change versus those upstaged were 92.3% (95% CI: 87.2, 95.4) v. 72.0% (95% CI: 68.4, 84.9), p = 0.002. No significant differences in survival difference were seen in other stage subsets. CONCLUSION: Modest survival differences exist in patients with EC originally staged as IA who underwent upstaging. No significant survival difference is observed in patients who are restaged to stage II or III subsets. Improved risk stratification is needed in assessing prognosis and adjuvant therapy for patients with endometrial cancer.

Voting restrictions associated with health inequities in teenage birth rates.

OBJECTIVES: Since the Landmark Shelby V. Holder Supreme Court Ruling, the number of laws in the United States that make it difficult to vote has increased dramatically. This may lead to legislation that limits access to health care, including options for family planning services. We determine whether voting restrictions are associated with county-level teenage birth rates. STUDY DESIGN: This is an ecological study. METHODS: The Cost of Voting Index, a state-level measure of barriers to voting during US elections from 1996 to 2016, was used as a proxy for access to voting. County-level teenage birth rates were obtained from the County Health Rankings data. We used multilevel modeling to determine whether restrictive voting laws were associated with county-level teenage birth rates. We tested whether associations varied across racial and socio-economic groups. RESULTS: When confounders were included, a significant association was observed between increasing voting restrictions and teenage birth rates (ß = 1.72, 95% confidence interval: 0.54, 2.89). A Cost of Voting Index-median income interaction term was tested and was statistically significant (ß = -1.00, 95% confidence interval: -1.36, -0.64), indicating that the observed relationship was particularly strong among lower-income counties. The number of reproductive health clinics per capita within each state is a potential mediator. CONCLUSION: Restrictive voting laws were associated with higher teenage birth rates, particularly for low-income counties. Future work should use methods in which a causal relation can be identified.

"Important but risky": attitudes of global thought leaders towards cost and value research in health professions education.

Studies of cost and value can inform educational decision making, yet our understanding of the barriers to such research is incomplete. To address this gap, our aim was to explore the attitudes of global thought leaders in HPE towards cost and value research. This was a qualitative virtual interview study underpinned by social constructionism. In telephone or videoconference interviews in 2018-2019, we asked global healthcare professional thought leaders their views regarding HPE cost and value research, outstanding research questions in this area and why addressing these questions was important. Analysis was inductive and thematic, and incorporated review and comments from the original interviewees (member checking). We interviewed 11 thought leaders, nine of whom gave later feedback on our data interpretation (member checking). We identified four themes: Cost research is really important but potentially risky (quantifying and reporting costs provides evidence for decision-making but could lead to increased accountability and loss of autonomy); I don't have the knowledge and skills (lack of economic literacy); it's not what I went into education research to do (professional identity); and it's difficult to generate generalizable findings (the importance of context). This study contributes to a wider conversation in the literature about cost and value research by bringing in the views of global HPE thought leaders. Our findings provide insight to inform how best to engage and empower educators and researchers in the processes of asking and answering meaningful, acceptable and relevant cost and value questions in HPE.

TLR5 Activation Exacerbates Airway Inflammation in Asthma.

INTRODUCTION: Innate immune activation through exposure to indoor and outdoor pollutants is emerging as an important determinant of asthma severity. For example, household levels of the bacterial product lipopolysaccharide (LPS) are associated with increased asthma severity. We hypothesized that activation of the innate immune receptor TLR5 by its bacterial ligand flagellin will exacerbate airway inflammation and asthma symptoms. METHODS: We determined the effect of flagellin co-exposure with ovalbumin in a murine model of allergic asthma. We evaluated the presence of flagellin activity in house dust of asthma patients. Finally, we analyzed the association of a dominant-negative polymorphism in TLR5 (rs5744168) with asthma symptoms in patients with asthma. RESULTS: We showed that bacterial flagellin can be found in the house dust of patients with asthma and that this bacterial product exacerbates allergic airway inflammation in an allergen-specific mouse model of asthma. Furthermore, a dominant-negative genetic polymorphism in TLR5, the receptor for flagellin, is associated with decreased symptoms in patients with asthma. CONCLUSION: Together, our results reveal a novel genetic protective factor (TLR5 deficiency) and a novel environmental pollutant (microbial flagellin) that influence asthma severity. (Clinical trials NCT01688986 and NCT01087307).

Whole-genome sequencing reveals a large deletion in the MITF gene in horses with white spotted coat colour and increased risk of deafness.

White spotting phenotypes in horses are highly valued in some breeds. They are quite variable and may range from the common white markings up to completely white horses. EDNRB, KIT, MITF, PAX3 and TRPM1 represent known candidate genes for white spotting phenotypes in horses. For the present study, we investigated an American Paint Horse family segregating a phenotype involving white spotting and blue eyes. Six of eight horses with the white-spotting phenotype were deaf. We obtained whole-genome sequence data from an affected horse and specifically searched for structural variants in the known candidate genes. This analysis revealed a heterozygous ~63-kb deletion spanning exons 6-9 of the MITF gene (chr16:21 503 211-21 566 617). We confirmed the breakpoints of the deletion by PCR and Sanger sequencing. PCR-based genotyping revealed that all eight available affected horses from the family carried the deletion. The finding of an MITF variant fits well with the syndromic phenotype involving both depigmentation and an increased risk for deafness and corresponds to human Waardenburg syndrome type 2A. Our findings will enable more precise genetic testing for depigmentation phenotypes in horses.

A candidate gene approach identifies variants in SLC45A2 that explain dilute phenotypes, pearl and sunshine, in compound heterozygote horses.

Variations in the SLC45A2 gene are responsible for the dilution phenotypes cream and pearl in domestic horses. Cream dilution is inherited in an incomplete dominant manner, diluting only red in the heterozygous state but both red and black pigments when two alleles are present. The pearl dilution is recessive and dilutes only the red and black pigment in the homozygous state or when paired with a cream allele. Horses that inherit one copy of pearl (Cprl ) and one copy of the dominant cream allele (CC r ) display a dilution phenotype similar to that of homozygous cream, suggesting that pearl is the result of a different variation in the same gene responsible for cream. We sequenced SLC45A2 in two 'false double dilute' horses that appeared phenotypically homozygous cream but tested as possessing only a single CC r allele. We also sequenced one known pearl carrier to screen for putative causal variants. The missense variant ECA21:SLC45A2:c.985G>A; p.Ala329Thr (Cprl ) was present in one false double dilute and the pearl carrier and was also genotyped in an additional 126 horses for statistical evaluation. The genotype matched the expected phenotype in all horses (P-value = 6.5 × 10-41 ) and is identical to a pearl variant found previously. The second false double dilute horse and one non-dilute offspring genotyped as heterozygous for a novel missense variant ECA21:SLC45A2:c.568G>A (p.Gly190Arg), the proposed Csun variant (for the name of the horse). This variant produces a recessive dilution similar to pearl and indicates that multiple alleles of SLC45A2 result in dilution phenotypes in the domestic horse.

AMEE Guide No. 123 - How to read studies of educational costs.

Healthcare and health professions education share many of the same problems in decision making. In both cases, there is a finite amount of resources, and so choices need to be made between alternatives. To navigate the options available requires effective decision making. Choosing one option requires consideration of its opportunity cost - the benefit forgone of the other competing options. The purpose of this abridged AMEE guide is to introduce educational decision-makers to the economic concept of cost, and how to read studies about educational costs to inform effective cost-conscious decision-making. This guide leads with a brief review of study designs commonly utilized in this field of research, followed by an overview of how study findings are commonly presented. The tutorial will then offer a four-step model for appraising and considering the results of an economic evaluation. It asks the questions: (1) Can I trust the results? (2) What are the results telling me? (3) Could the results be transferred to my context? (4) Should I change my practice?

Natural Variation in the Distribution and Abundance of Transposable Elements Across the Caenorhabditis elegans Species.

Transposons are mobile DNA elements that generate both adaptive and deleterious phenotypic variation thereby driving genome evolution. For these reasons, genomes have mechanisms to regulate transposable element (TE) activity. Approximately 12-16% of the Caenorhabditis elegans genome is composed of TEs, of which the majority are likely inactive. However, most studies of TE activity have been conducted in the laboratory strain N2, which limits our knowledge of the effects of these mobile elements across natural populations. We analyzed the distribution and abundance of TEs in 208 wild C. elegans strains to better understand how transposons contribute to variation in natural populations. We identified 3,397 TEs as compared with the reference strain, of which 2,771 are novel insertions and 241 are TEs that have been excised in at least one wild strain. Likely because of their hypothesized deleterious effects, we find that TEs are found at low allele frequencies throughout the population, and we predict functional effects of TE insertions. The abundances of TEs reflect their activities, and these data allowed us to perform both genome-wide association mappings and rare variant correlations to reveal several candidate genes that impact TE regulation, including small regulatory piwi-interacting RNAs and chromatin factors. Because TE variation in natural populations could underlie phenotypic variation for organismal and behavioral traits, the transposons that we identified and their regulatory mechanisms can be used in future studies to explore the genomics of complex traits and evolutionary changes.

Patterns of childhood body mass index (BMI), overweight and obesity in South Asian and black participants in the English National child measurement programme: effect of applying BMI adjustments standardising for ethnic differences in BMI-body fatness associations.

BACKGROUND: The National Child Measurement Programme (NCMP) records weight and height and assesses overweight-obesity patterns in English children using body mass index (BMI), which tends to underestimate body fatness in South Asian children and overestimate body fatness in Black children of presumed African ethnicity. Using BMI adjustments to ensure that adjusted BMI was similarly related to body fatness in South Asian, Black and White children, we reassessed population overweight and obesity patterns in these ethnic groups in NCMP. METHODS: Analyses were based on 2012-2013 NCMP data in 582 899 children aged 4-5 years and 485 362 children aged 10-11 years. Standard centile-based approaches defined weight status in each age group before and after applying BMI adjustments for English South Asian and Black children derived from previous studies using the deuterium dilution method. FINDINGS: Among White children, overweight-obesity prevalences (boys, girls) were 23% and 21%, respectively, in 4-5 year olds and 33% and 30%, respectively, in 10-11 year olds. Before adjustment, South Asian children had lower overweight-obesity prevalences at 4-5 years (19%, 19%) and slightly higher prevalences at 10-11 years (42%, 34%), whereas Black children had higher overweight-obesity prevalences both at 4-5 years (31%, 29%) and 10-11 years (42%, 45%). Following adjustment, overweight-obesity prevalences were markedly higher in South Asian children both at 4-5 years (39%, 35%) and at 10-11 years (52%, 44%), whereas Black children had lower prevalences at 4-5 years (11%, 12%); at 10-11 years, prevalences were slightly lower in boys (32%) but higher in girls (35%). INTERPRETATION: BMI adjustments revealed extremely high overweight-obesity prevalences among South Asian children in England, which were not apparent in unadjusted data. In contrast, after adjustment, Black children had lower overweight-obesity prevalences except among older girls. FUNDING: British Heart Foundation, NIHR CLAHRC (South London), NIHR CLAHRC (North Thames).

Technical note: A comparison of alkali treatment methods to improve neutral detergent fiber digestibility of corn stover.

The objective of this study was to compare neutral detergent fiber (NDF) digestibility of corn stover that had been treated by 2 alkali treatment methods. Two experiments were conducted to test a sodium hydroxide (NaOH) treatment method that uses an ethanol/water co-solvent (NaOH/ethanol-H2O, United States Patent No. 20140220228) and a calcium hydroxide (CaOH) treatment method, which uses water as a solvent (CaOH/H2O). An in situ trial was conducted to compare NDF digestion kinetics between NaOH/ethanol-H2O-treated stover, CaOH/H2O-treated stover, untreated corn stover, and soy hulls. The digestion rate of potentially digestible NDF (kd) of NaOH/ethanol-H2O-treated corn stover (5.36%/h) was higher than CaOH/H2O-treated stover (2.27%/h), or untreated corn stover (1.76%/h) and similar to the kd of soy hulls (4.93%/h). The indigestible NDF (iNDF) fraction of untreated corn stover (35.1% of NDF) was reduced by CaOH/H2O treatment (27.3% of NDF) and by NaOH/ethanol-H2O treatment (2.8% of NDF). The iNDF fraction in soy hulls (3.6% of NDF) was similar to iNDF of NaOH/ethanol-H2O-treated stover. An in vivo digestibility trial was also conducted to compare fiber digestibility of diets supplemented with untreated corn stover, NaOH/ethanol-H2O-treated corn stover, or soy hulls. Total-tract apparent dry matter (DM) and NDF digestibility were measured with 8 lactating Holstein cows in a replicated 4 × 4 Latin square with four 21-d periods. Apparent DM digestibility (DMD) was improved when supplemental soy hulls were added to the base diet (60.0% DMD) compared with the base diet with no supplemental fiber (57.7% DMD). Apparent DM digestibility was reduced when diets were supplemented with untreated stover (52.4%). Dry matter digestibility of NaOH/ethanol-H2O-treated stover was similar (54.8% DMD) to all other treatments. Digestibility of NDF was lowest when cows were fed the diet with supplemented untreated stover (35.5% of NDF), and improved when soy hulls (40.6% of NDF) or NaOH/ethanol-H2O-treated stover (43.8% of NDF) were added to the diets. The NaOH/ethanol-H2O treatment process improves the DM and NDF digestibility of corn stover to values similar to those of soy hulls.

Efficacy of colostrum replacer versus maternal colostrum on immunological status, health, and growth of preweaned dairy calves.

Commercially available colostrum replacers (CR) are commonly used when maternal colostrum (MC) is unavailable, for managerial convenience, to ensure quality consistency at first feeding, or in disease control and eradication programs. The objective of this study was to determine the efficacy of feeding First Day Formula (Accelerated Genetics, Baraboo, WI) CR versus pooled MC on immunological status, growth, and health of preweaned dairy calves. A total of 1,220 Jersey and Jersey × Holstein calves born on a California Central Valley dairy farm were assigned after birth to receive either CR or MC following a systematic allocation procedure. Calves assigned to MC were tube fed 2.8 L of MC, and calves assigned to CR were tube fed a total of 500 g of CR (150 g of immunoglobulin G; IgG) mixed into 1.9 L of water at 1 h ± 5 min after the calf was born. A subset of calves was selected for passive transfer (n = 592) and growth (n = 268) analyses. Although both coliform count and total bacteria count were low for MC and CR fed to calves during the study, the predicted probability of calves receiving contaminated liquid feed (coliform count >10,000 cfu/mL) at first feeding was reduced for calves fed CR (1.5%) compared with calves fed MC (6.1%). The mean blood concentration of IgG was lower for calves fed CR than for calves fed MC (19.6 vs. 23.4 mg/mL). However, the apparent efficiency of absorption of IgG did not differ between treatments (34.4 and 35.9% for CR and MC, respectively). Total proteins were lower in calves fed CR compared with MC at 24 h (5.16 vs. 5.84 g/dL, respectively). Calves fed CR were 1.5 kg lighter at weaning and gained 0.03 kg less per day (0.30 vs. 0.33 kg/d, respectively) than calves fed MC before weaning. Height at weaning did not differ between the 2 treatment groups. Calves fed CR tended to have a higher predicted probability of not being treated for diarrhea than calves fed MC (0.142 vs. 0.110, respectively). However, when the disease was present, CR had a higher number of treatment days compared with MC (11.6 vs. 10.8 d, respectively). The hazard ratio of dying did not differ between MC and CR; however, CR calves had a numerically higher risk (hazard ratio = 1.347) of dying compared with calves that received MC. In conclusion, IgG absorption and serum concentration of calves were adequate when calves were fed either CR or MC. The CR-fed calves had a lower probability of receiving contaminated liquid feed and performed similar in terms of health compared with calves receiving high-quality MC, although they were slightly lighter at weaning. Therefore, the CR evaluated in this study is a valid alternative to high-quality (>50 mg of IgG/mL) MC.

Effects of group size on school structure and behaviour in yellow-eyed mullet Aldrichetta forsteri.

Schooling behaviour in yellow-eyed mullet Aldrichetta forsteri, a common fish species in New Zealand estuarine habitats, was investigated to identify interaction rules associated with group formation. Tank-based three-dimensional studies of three group sizes (15, 75 and 150 individuals) were carried out to measure the effects of these different group sizes on school structure during control, predation risk and foraging behavioural states. Increased group size positively correlated with nearest-neighbour distance in control and foraging states. Swimming speed was the lowest in all three behavioural states in groups of 15 fish compared with 75 or 150. Immediate behavioural response following visual exposure to a simulated avian predator differed between groups resulting in loss of structure in larger groups. School shape was an oblong-oblate spheroid with a length, breadth and height ratio of 5:2:1 and the area of free space surrounding individual fish was spherical in shape with a high degree of spatial isotropy present in all size groups. These findings challenge traditional theories based on either local or global properties as key drivers of group structure. Instead, our results suggest that a more collaborative approach involving both group size and rules pertaining to nearest-neighbour interactions affects collective behaviours in this species.

Blast-related disinhibition and risk seeking in mice and combat Veterans: Potential role for dysfunctional phasic dopamine release.

Mild traumatic brain injury (mTBI) caused by exposure to high explosives has been called the "signature injury" of the wars in Iraq and Afghanistan. There is a wide array of chronic neurological and behavioral symptoms associated with blast-induced mTBI. However, the underlying mechanisms are not well understood. Here we used a battlefield-relevant mouse model of blast-induced mTBI and in vivo fast-scan cyclic voltammetry (FSCV) to investigate whether the mesolimbic dopamine system contributes to the mechanisms underlying blast-induced behavioral dysfunction. In mice, blast exposure increased novelty seeking, a behavior closely associated with disinhibition and risk for subsequent maladaptive behaviors. In keeping with this, we found that veterans with blast-related mTBI reported greater disinhibition and risk taking on the Frontal Systems Behavior Scale (FrSBe). In addition, in mice we report that blast exposure causes potentiation of evoked phasic dopamine release in the nucleus accumbens. Taken together these findings suggest that blast-induced changes in the dopaminergic system may mediate aspects of the complex array of behavioral dysfunctions reported in blast-exposed veterans.

Body mass index adjustments to increase the validity of body fatness assessment in UK Black African and South Asian children.

BACKGROUND/OBJECTIVES: Body mass index (BMI) (weight per height2) is the most widely used marker of childhood obesity and total body fatness (BF). However, its validity is limited, especially in children of South Asian and Black African origins. We aimed to quantify BMI adjustments needed for UK children of Black African and South Asian origins so that adjusted BMI related to BF in the same way as for White European children. METHODS: We used data from four recent UK studies that made deuterium dilution BF measurements in UK children of White European, South Asian and Black African origins. A height-standardized fat mass index (FMI) was derived to represent BF. Linear regression models were then fitted, separately for boys and girls, to quantify ethnic differences in BMI-FMI relationships and to provide ethnic-specific BMI adjustments. RESULTS: We restricted analyses to 4-12 year olds, to whom a single consistent FMI (fat mass per height5) could be applied. BMI consistently underestimated BF in South Asians, requiring positive BMI adjustments of +1.12 kg m-2 (95% confidence interval (CI): 0.83, 1.41 kg m-2; P<0.0001) for boys and +1.07 kg m-2 (95% CI: 0.74, 1.39 kg m-2; P<0.0001) for girls of all age groups and FMI levels. BMI overestimated BF in Black Africans, requiring negative BMI adjustments for Black African children. However, these were complex because there were statistically significant interactions between Black African ethnicity and FMI (P=0.004 boys; P=0.003 girls) and also between FMI and age group (P<0.0001 for boys and girls). BMI adjustments therefore varied by age group and FMI level (and indirectly BMI); the largest adjustments were in younger children with higher unadjusted BMI and the smallest in older children with lower unadjusted BMI. CONCLUSIONS: BMI underestimated BF in South Asians and overestimated BF in Black Africans. Ethnic-specific adjustments, increasing BMI in South Asians and reducing BMI in Black Africans, can improve the accuracy of BF assessment in these children.

Shift in disparities in hepatitis C treatment from interferon to DAA era: A population-based cohort study.

We evaluated the shift in the characteristics of people who received interferon-based hepatitis C virus (HCV) treatments and those who received recently introduced direct-acting antivirals (DAAs) in British Columbia (BC), Canada. The BC Hepatitis Testers Cohort includes 1.5 million individuals tested for HCV or HIV, or reported cases of hepatitis B and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalization, cancer, prescription drugs and mortality data. This analysis included all patients who filled at least one prescription for HCV treatment until 31 July 2015. HCV treatments were classified as older interferon-based treatments including pegylated interferon/ribavirin (PegIFN/RBV) with/without boceprevir or telaprevir, DAAs with RBV or PegIFN/RBV, and newer interferon-free DAAs. Of 11 886 people treated for HCV between 2000 and 2015, 1164 (9.8%) received interferon-free DAAs (ledipasvir/sofosbuvir: n=1075; 92.4%), while 452 (3.8%) received a combination of DAAs and RBV or PegIFN/RBV. Compared to those receiving interferon-based treatment, people with HIV co-infection (adjusted odds ratio [aOR]: 2.96, 95% CI: 2.31-3.81), cirrhosis (aOR: 1.77, 95% CI: 1.45-2.15), decompensated cirrhosis (aOR: 1.72, 95% CI: 1.31-2.28), diabetes (aOR: 1.30, 95% CI: 1.10-1.54), a history of injection drug use (aOR: 1.34, 95% CI: 1.09-1.65) and opioid substitution therapy (aOR: 1.30, 95% CI: 1.01-1.67) were more likely to receive interferon-free DAAs. Socio-economically marginalized individuals were significantly less likely (most deprived vs most privileged: aOR: 0.71, 95% CI: 0.58-0.87) to receive DAAs. In conclusion, there is a shift in prescription of new HCV treatments to previously excluded groups (eg HIV-co-infected), although gaps remain for the socio-economically marginalized populations.

Protocol adherence for continuously titrated interventions in randomized trials: an overview of the current methodology and case study.

BACKGROUND: The standard definition for protocol adherence is the proportion of all scheduled doses that are delivered. In clinical research, this definition has several limitations when evaluating protocol adherence in trials that study interventions requiring continuous titration. DISCUSSION: Building upon a specific case study, we analyzed a recent trial of a continuously titrated intervention to assess the impact of different definitions of protocol deviations on the interpretation of protocol adherence. The OVATION pilot trial was an open-label randomized controlled trial of higher (75-80 mmHg) versus lower (60-65 mmHg) mean arterial pressure (MAP) targets for vasopressor therapy in shock. In this trial, potential protocol deviations were defined as MAP values outside the targeted range for >4 consecutive hours during vasopressor therapy without synchronous and consistent adjustments of vasopressor doses. An adjudication committee reviewed each potential deviation to determine if it was clinically-justified or not. There are four reasons for this contextual measurement and reporting of protocol adherence. First, between-arm separation is a robust measure of adherence to complex protocols. Second, adherence assessed by protocol deviations varies in function of the definition of deviations and the frequency of measurements. Third, distinguishing clinically-justified vs. not clinically-justified protocol deviations acknowledges clinically sensible bedside decision-making and offers a clear terminology before the trial begins. Finally, multiple metrics exist to report protocol deviations, which provides different information but complementary information on protocol adherence. CONCLUSIONS: In trials of interventions requiring continuous titration, metrics used for defining protocol deviations have a considerable impact on the interpretation of protocol adherence. Definitions for protocol deviations should be prespecified and correlated with between-arm separation, if it can be measured.

Single nucleotide polymorphisms for DNA typing in the domestic horse.

Genetic markers are important resources for individual identification and parentage assessment. Although short tandem repeats (STRs) have been the traditional DNA marker, technological advances have led to single nucleotide polymorphisms (SNPs) becoming an attractive alternative. SNPs can be highly multiplexed and automatically scored, which allows for easier standardization and sharing among laboratories. Equine parentage is currently assessed using STRs. We obtained a publicly available SNP dataset of 729 horses representing 32 diverse breeds. A proposed set of 101 SNPs was analyzed for DNA typing suitability. The overall minor allele frequency of the panel was 0.376 (range 0.304-0.419), with per breed probability of identities ranging from 5.6 × 10-35 to 1.86 × 10-42 . When one parent was available, exclusion probabilities ranged from 0.9998 to 0.999996, although when both parents were available, all breeds had exclusion probabilities greater than 0.9999999. A set of 388 horses from 35 breeds was genotyped to evaluate marker performance on known families. The set included 107 parent-offspring pairs and 101 full trios. No horses shared identical genotypes across all markers, indicating that the selected set was sufficient for individual identification. All pairwise comparisons were classified using ISAG rules, with one or two excluding markers considered an accepted parent-offspring pair, two or three excluding markers considered doubtful and four or more excluding markers rejecting parentage. The panel had an overall accuracy of 99.9% for identifying true parent-offspring pairs. Our developed marker set is both present on current generation SNP chips and can be highly multiplexed in standalone panels and thus is a promising resource for SNP-based DNA typing.

Interstellar

A dying massive star ends in a supernova explosion ejecting a large fraction of its mass into the interstellar medium. If this happens nearby, part of the ejecta might end on Solar System bodies and, in fact, radioactive ^{60}Fe has been detected on the Pacific ocean floor in about 2 Ma old layers. Here, we report on the detection of this isotope also in lunar samples, originating presumably from the same event. The concentration of the cosmic ray produced isotope ^{53}Mn, measured in the same samples, proves the supernova origin of the ^{60}Fe. From the ^{60}Fe concentrations found we deduce a reliable value for the local interstellar fluence in the range of 1×10^{8} at/cm^{2}. Thus, we obtain constraints on the recent and nearby supernova(e).

Fruit, vegetable and vitamin C intakes and plasma vitamin C: cross-sectional associations with insulin resistance and glycaemia in 9-10 year-old children.

AIM: To examine whether low circulating vitamin C concentrations and low fruit and vegetable intakes were associated with insulin resistance and other Type 2 diabetes risk markers in childhood. METHODS: We conducted a cross-sectional, school-based study in 2025 UK children aged 9-10 years, predominantly of white European, South-Asian and black African origin. A 24-h dietary recall was used to assess fruit, vegetable and vitamin C intakes. Height, weight and fat mass were measured and a fasting blood sample collected to measure plasma vitamin C concentrations and Type 2 diabetes risk markers. RESULTS: In analyses adjusting for confounding variables (including socio-economic status), a one interquartile range higher plasma vitamin C concentration (30.9 µmol/l) was associated with a 9.6% (95% CI 6.5, 12.6%) lower homeostatic model assessment of insulin resistance value, 0.8% (95% CI 0.4, 1.2%) lower fasting glucose, 4.5% (95% CI 3.2, 5.9%) lower urate and 2.2% (95% CI 0.9, 3.4%) higher HDL cholesterol. HbA1c concentration was 0.6% (95% CI 0.2, 1.0%) higher. Dietary fruit, vegetable and total vitamin C intakes were not associated with any Type 2 diabetes risk markers. Lower plasma vitamin C concentrations in South-Asian and black African-Caribbean children could partly explain their higher insulin resistance. CONCLUSIONS: Lower plasma vitamin C concentrations are associated with insulin resistance and could partly explain ethnic differences in insulin resistance. Experimental studies are needed to establish whether increasing plasma vitamin C can help prevent Type 2 diabetes at an early stage.

Traffic pollution and the incidence of cardiorespiratory outcomes in an adult cohort in London.

OBJECTIVES: The epidemiological evidence for adverse health effects of long-term exposure to air and noise pollution from traffic is not coherent. Further, the relative roles of background versus near traffic pollution concentrations in this process are unclear. We investigated relationships between modelled concentrations of air and noise pollution from traffic and incident cardiorespiratory disease in London. METHODS: Among 211 016 adults aged 40-79 years registered in 75 Greater London practices between 2005 and 2011, the first diagnosis for a range of cardiovascular and respiratory outcomes were identified from primary care and hospital records. Annual baseline concentrations for nitrogen oxide (NOx), particulate matter with a median aerodynamic diameter <2.5 µm (PM2.5) attributable to exhaust and non-exhaust sources, traffic intensity and noise were estimated at 20 m2 resolution from dispersion models, linked to clinical data via residential postcode. HRs were adjusted for confounders including smoking and area deprivation. RESULTS: The largest observed associations were between traffic-related air pollution and heart failure (HR=1.10 for 20 µg/m3 change in NOx, 95% CI 1.01 to 1.21). However, no other outcomes were consistently associated with any of the pollution indicators, including noise. The greater variations in modelled air pollution from traffic between practices, versus within, hampered meaningful fine spatial scale analyses. CONCLUSIONS: The associations observed with heart failure may suggest exacerbatory effects rather than underlying chronic disease. However, the overall failure to observe wider associations with traffic pollution may reflect that exposure estimates based on residence inadequately represent the relevant pattern of personal exposure, and future studies must address this issue.