A genomic prediction model for racecourse starts in the Thoroughbred horse.

Durability traits in Thoroughbred horses are heritable, economically valuable and may affect horse welfare. The aims of this study were to test the hypotheses that (i) durability traits are heritable and (ii) genetic data may be used to predict a horse's potential to have a racecourse start. Heritability for the phenotype 'number of 2- and 3-year-old starts' was estimated to be h m 2  = 0.11 ± 0.02 (n = 4499). A genome-wide association study identified SNP contributions to the trait. The neurotrimin (NTM), opioid-binding protein/cell adhesion molecule like (OPCML) and prolylcarboxypeptidase (PRCP) genes were identified as candidate genes associated with the trait. NTM functions in brain development and has been shown to have been selected during the domestication of the horse. PRCP is an established expression quantitative trait locus involved in the interaction between voluntary exercise and body composition in mice. We hypothesise that variation at these loci contributes to the motivation of the horse to exercise, which may influence its response to the demands of the training and racing environment. A random forest with mixed effects (RFME) model identified a set of SNPs that contributed to 24.7% of the heritable variation in the trait. In an independent validation set (n = 528 horses), the cohort with high genetic potential for a racecourse start had significantly fewer unraced horses (16% unraced) than did low (27% unraced) potential horses and had more favourable race outcomes among those that raced. Therefore, the information from SNPs included in the model may be used to predict horses with a greater chance of a racecourse start.

Analysis of genetic variation contributing to measured speed in Thoroughbreds identifies genomic regions involved in the transcriptional response to exercise.

Despite strong selection for athletic traits in Thoroughbred horses, there is marked variation in speed and aptitude for racing performance within the breed. Using global positioning system monitoring during exercise training, we measured speed variables and temporal changes in speed with age to derive phenotypes for GWAS. The aim of the study was to test the hypothesis that genetic variation contributes to variation in end-point physiological traits, in this case galloping speed measured during field exercise tests. Standardisation of field-measured phenotypes was attempted by assessing horses exercised on the same gallop track and managed under similar conditions by a single trainer. PCA of six key speed indices captured 73.9% of the variation with principal component 1 (PC1). Verifying the utility of the phenotype, we observed that PC1 (median) in 2-year-old horses was significantly different among elite, non-elite and unraced horses (P < 0.001) and the temporal change with age in PC1 varied among horses with different myostatin (MSTN) g.66493737C>T SNP genotypes. A GWAS for PC1 in 2-year-old horses (n = 122) identified four SNPs reaching the suggestive threshold for association (P < 4.80 × 10-5 ), defining a 1.09 Mb candidate region on ECA8 containing the myosin XVIIIB (MYO18B) gene. In a GWAS for temporal change in PC1 with age (n = 168), five SNPs reached the suggestive threshold for association and defined candidate regions on ECA2 and ECA11. Both regions contained genes that are significantly differentially expressed in equine skeletal muscle in response to acute exercise and training stimuli, including MYO18A. As MYO18A plays a regulatory role in the skeletal muscle response to exercise, the identified genomic variation proximal to the myosin family genes may be important for the regulation of the response to exercise and training.

Genetic contributions to precocity traits in racing Thoroughbreds.

Adaptation to early training and racing (i.e. precocity), which is highly variable in racing Thoroughbreds, has implications for the selection and training of horses. We hypothesised that precocity in Thoroughbred racehorses is heritable. Age at first sprint training session (work day), age at first race and age at best race were used as phenotypes to quantify precocity. Using high-density SNP array data, additive SNP heritability (hSNP2) was estimated to be 0.17, 0.14 and 0.17 for the three traits respectively. In genome-wide association studies (GWAS) for age at first race and age at best race, a 1.98-Mb region on equine chromosome 18 (ECA18) was identified. The most significant association was with the myostatin (MSTN) g.66493737C>T SNP (P = 5.46 × 10-12 and P = 1.89 × 10-14 respectively). In addition, two SNPs on ECA1 (g.37770220G>A and g.37770305T>C) within the first intron of the serotonin receptor gene HTR7 were significantly associated with age at first race and age at best race. Although no significant associations were identified for age at first work day, the MSTN:g.66493737C>T SNP was among the top 20 SNPs in the GWAS (P = 3.98 × 10-5 ). Here we have identified variants with potential roles in early adaptation to training. Although there was an overlap in genes associated with precocity and distance aptitude (i.e. MSTN), the HTR7 variants were more strongly associated with precocity than with distance. Because HTR7 is closely related to the HTR1A gene, previously implicated in tractability in young Thoroughbreds, this suggests that behavioural traits may influence precocity.

Evaluation of microRNA expression in plasma and skeletal muscle of thoroughbred racehorses in training.

BACKGROUND: Circulating miRNAs (ci-miRNAs) are endogenous, non-coding RNAs emerging as potential diagnostic biomarkers. Equine miRNAs have been previously identified including subsets of tissue-specific miRNAs. In order to investigate ci-miRNAs as diagnostic tools, normal patterns of expression for different scenarios including responses to exercise need to be identified. Human studies have demonstrated that many ci-miRNAs are up-regulated following exercise with changes in expression patterns in skeletal muscle. However, technical challenges such as haemolysis impact on accurate plasma ci-miRNA quantification, with haemolysis often occurring naturally in horses following moderate-to-intense exercise. The objectives of this study were to identify plasma ci-miRNA profiles and skeletal muscle miRNAs before and after exercise in Thoroughbreds (Tb), and to evaluate for the presence and effect of haemolysis on plasma ci-miRNA determination. Resting and post-exercise plasma ci-miRNA profiles and haemolysis were evaluated in twenty 3 year-old Tbs in sprint training. Resting and post-exercise skeletal muscle miRNA abundance was evaluated in a second cohort of eleven 2 year-old Tbs just entering sprint training. Haemolysis was further quantified in resting blood samples from twelve Tbs in sprint training. A human plasma panel containing 179 miRNAs was used for profiling, with haemolysis assessed spectrophotometrically. Data was analysed using a paired Student's t-test and Pearson's rank correlation. RESULTS: Plasma ci-miRNA data for 13/20 horses and all skeletal muscle miRNA data passed quality control. From plasma, 52/179 miRNAs were detected at both time-points. Haemolysis levels were greater than the threshold for accurate quantification of ci-miRNAs in 18/25 resting and all post-exercise plasma samples. Positive correlations (P < 0.05) between haemolysis and miRNA abundance were detected for all but 4 miRNAs, so exercise-induced changes in plasma ci-miRNA expression could not be quantified. In skeletal muscle samples, 97/179 miRNAs were detected with 5 miRNAs (miR-21-5p, let-7d-3p, let-7d-5p, miR-30b-5p, miR-30e-5p) differentially expressed (DE, P < 0.05) between time-points. CONCLUSIONS: The degree of haemolysis needs to be determined prior to quantifying plasma ci-miRNA expression from horses in high-intensity exercise training. Identification of DE miRNAs in skeletal muscle indicates modification of miRNA expression may contribute to adaptive training responses in Tbs. Using a human plasma panel likely limited detection of equine-specific miRNAs.

A clinical governance framework for blood services.

BACKGROUND AND OBJECTIVES: The elements of clinical governance, which ensure excellence in clinical care, can be applied to blood services. In this survey, their application in a range of blood providers was gauged, with the aim of identifying best practice and producing a generalizable framework. MATERIALS AND METHODS: The Medical Directors of members of the Alliance of Blood Operators surveyed how different elements of clinical governance operated within their organizations and developed recommendations applicable in the blood service environment. RESULTS: The recommendations that emerged highlighted the importance of an organization's culture, with the delivery of optimal clinical governance being a corporate responsibility. Senior management must agree and promote a set of values to ensure that the system operates with the patient and donor at its heart. All staff should understand how their role fits into the 'journey to the patient', and a culture of openness promoted. Thus, reporting of errors and risks should be actively sought and praised, with penalties applied for concealment. Systems should exist to collect, analyse and escalate clinical outcomes, safety data, clinical risk assessments, incident reports and complaints to inform organizational learning. CONCLUSION: Clinical governance principles from general health care can be applied within blood services to complement good manufacturing practice. This requires leadership, accountability, an open culture and a drive for continuous improvement and excellence in clinical care.

Comparison of ventilatory and oxygen consumption measurements of yearling Thoroughbred colts and fillies exercising unridden on an all-weather track.

Sex effects on ventilatory and oxygen consumption (V̇O2) measurements during exercise have been identified in humans. This study's aim was to evaluate the hypothesis that there are sex effects on ventilatory and V̇O2 measurements in exercising, untrained yearling Thoroughbreds (Tb). Forty-one Tbs (16 colts, 25 fillies; 19.8 ± 1.4 months old) were recruited. Physiological, ventilatory and exercise data were gathered from horses exercising unridden at high intensity on an all-weather track from a global positioning-heart rate unit and a portable ergospirometry system. Data were analysed with an unpaired Student's t-test and the Benjamini-Hochberg correction for multiple testing (P ≤ 0.05 significant). Mean bodyweight (BW, P = 0.002) and wither height (P = 0.04) were greater for colts than fillies. There were no differences in physiological and exercise data and absolute peak V̇O2 between groups. However, fillies had a higher mass specific peak V̇O2 (P = 0.03) than colts (121.5 ± 21.6 mL/kg.min vs. 111.9 ± 27.4 mL/kg.min). The peak breathing frequency was greater for fillies (P < 0.001) while the peak inspiratory (P < 0.001) and expiratory air flow (P < 0.001), peak expiratory tidal volume (VTE; P < 0.001) and peak minute ventilation (V̇E; P = 0.01) were greater for colts; there were no differences for peak VTE and V̇E when adjusted for BW. Differences in BW explain the differences in mass specific peak V̇O2 between groups. Given their morphological differences, it is likely that lung volumes and airway diameters are smaller for fillies, resulting in greater resistance and lower air flows and volumes. Further research is required to investigate the ventilatory differences and how they may change with maturation and impact performance.

PGC-1α encoded by the PPARGC1A gene regulates oxidative energy metabolism in equine skeletal muscle during exercise.

Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) has emerged as a critical control factor in skeletal muscle adaptation to exercise, acting via transcriptional control of genes responsible for angiogenesis, fatty acid oxidation, oxidative phosphorylation, mitochondrial biogenesis and muscle fibre type composition. In a previous study, we demonstrated a significant increase in mRNA expression for the gene encoding PGC-1α (PPARGC1A) in Thoroughbred horse skeletal muscle following a single bout of endurance exercise. In this study, we investigated mRNA expression changes in genes encoding transcriptional coactivators of PGC-1α and genes that function upstream and downstream of PGC-1α in known canonical pathways. We used linear regression to determine the associations between PPARGC1A mRNA expression and expression of the selected panel of genes. Biopsy samples were obtained from the gluteus medius pre-exercise (T(0) ), immediately post-exercise (T(1) ) and 4 h post-exercise (T(2) ). Significant (P < 0.05) expression fold change differences relative to T(0) were detected for genes functioning in angiogenesis (ANGP2 and VEGFA); Ca(2+) -dependent signalling pathway (PPP3CA); carbohydrate/glucose metabolism (PDK4); fatty acid metabolism/mitochondrial biogenesis (PPPARGC1B); haem biosynthetic process (ALAS1); insulin signalling (FOXO1, PPPARGC1A and SLC2A4); mitogen-activated protein kinase signalling (MAPK14 and MEF2A); and myogenesis (HDAC9). Gene expression associations were identified between PPARGC1A and genes involved in angiogenesis, mitochondrial respiration, glucose transport, insulin signalling and transcriptional regulation. These results suggest that PGC-1α and genes regulated by PGC-1α play significant roles in the skeletal muscle response to exercise and therefore may contribute to performance potential in Thoroughbred horses.

Aerobic fitness and obesity: relationship to cerebral white matter integrity in the brain of active and sedentary older adults.

OBJECTIVE: Aerobic fitness (VO(2) peak) and obesity risk (OR) may impact brain health. This study examined hemispheric and segment specific relationships between VO(2) peak, OR and cerebral white-matter (CWM) integrity in the cingulum brain region in healthy older adults. METHODS: Fifteen subjects (66±6 years) completed VO(2) peak testing and MRI of the brain. OR was determined via body mass index (BMI) and abdominal girth. MRI analysis was performed with a structural 3D T1 MP-Rage and diffusion tensor imaging technique (DTI, 21 directions, repeated four times) on a 3.0 T MR imaging unit. CWM integrity indices, fractional anisotropy (FA) and mean diffusivity (MD), were computed from the tensors. The anterior, middle and posterior cingulum segments were analysed on both sides of the brain. Partial correlations (age and gender controlled) and standard multiple regressions were used to determine significant associations and unique contributions to CWM integrity. RESULTS: VO(2) peak was moderately related to FA in the left middle cingulum segment (r partial=0.573, p=0.041) and explained 28.5% of FA's total variance (p=0.10). Abdominal girth (r partial=-0.764, p=0.002) and BMI (r partial=-0.690, p=0.009) were inversely related to FA in the right posterior cingulum (RPC) segment. Abdominal girth and BMI uniquely explained 53.9% of FA's total variance (p=0.012) and 43.9% (p=0.040), respectively, in the RPC. CONCLUSION: Higher aerobic fitness and lower obesity risk are related to greater CWM integrity but not in the same cingulum segments.

HPV31 and HPV33 incidence in cervical samples from women in Recife, Brazil.

Human papillomavirus (HPV) has been extensively studied concerning genomic structure, infection mechanisms, and diversity of types, as well as disease progression stages and development of vaccines. HPV type prevalence can differ in specific populations in different countries, according to ethnicity. This is the first report of an integrated project to evaluate the incidence of HPV types in different regions in Brazil in order to obtain data for vaccine development. Cervical samples were collected from women seen at a public hospital in Pernambuco, Northeast Brazil, for routine evaluation of genital alterations. Selection of the patients was random. There was a strong prevalence of HPV16 and a high incidence of HPV types 31 and 33. These data foster the discussion about the need to evaluate viral prevalence in each geographic region in order to develop targeted vaccine programs.

Serial evaluation of resting and exercising overground endoscopic examination results in young Thoroughbreds with no treatment intervention.

BACKGROUND: We hypothesised that grade/appearance for upper respiratory tract (URT) disorders identified at the first overground endoscopy (OGE) examination would vary at subsequent examinations. OBJECTIVES: To compare OGE examinations from horses evaluated on at least two occasions under similar exercise conditions without treatment intervention. STUDY DESIGN: Retrospective cohort. METHODS: Pre-exercise and exercising OGE recordings from Thoroughbred horses undergoing multiple examinations under similar exercise conditions were reviewed, with the first two recordings for each horse statistically evaluated. Paired Wilcoxon signed-rank tests were used to assess differences in exercise and physiological parameters between examinations. Z-tests were used to assess the proportion of changes in URT disorder grade/appearance between examinations. A McNemar's test was used to compare the proportion of horses with each disorder at each examination. Test-retest reliability across examinations was assessed using Spearman's ρ, and ordered logistic regression used to explore temporal effects on repeatability. Lattice plots were constructed to view variability in disorders over time. RESULTS: Seventy-eight horses (median age 2.4 years) with 195 resting endoscopic examinations including 72/78 horses with 179 pre-exercise and exercising OGE examinations were evaluated. Median time between examinations was 226.5 days with no differences between exercise and physiological parameters. Grades significantly varied between examinations for all disorders, and in particular for palatal instability (PI) and epiglottic grade at rest. A temporal link between examination interval and disorder grade change was identified for PI and resting arytenoid asymmetry. MAIN LIMITATIONS: OGE re-examinations within a shorter, more consistent time-frame would allow determination of intrahorse variability. The sample size was inadequate to conclusively establish temporal links between disorders and time between examinations. CONCLUSIONS: Variability for most URT abnormalities identified with OGE should be considered when making therapeutic decisions based on a single examination and may partially explain development of additional URT conditions after surgical intervention. The Summary is available in Portuguese - see Supporting Information.

Impact of pharyngeal endoscopic tip placement and water flushing interval on upper respiratory tract disorders in horses undergoing overground endoscopy.

BACKGROUND: Endoscopic tip placement in the pharynx and water flushing interval (FI) may affect exercising upper respiratory tract (URT) endoscopic results. OBJECTIVES: To determine associations between the endoscopic tip position in the pharynx and automated FI with overground endoscopic (OGE) results. STUDY DESIGN: Randomised balanced 2X5 factorial design. METHODS: A total of n = 200 horses undergoing OGE were randomly assigned into 10 groups (n = 20/group) of different automated endoscopic FIs (no flushing, 60, 120, 180, 240 s) with the endoscope tip positioned either rostrally (position A) or caudally (position B) in the pharynx. Endoscopic videos were analysed and all URT abnormalities graded using published scales. Disorders with ≤10% prevalence were excluded from the final analysis with only arytenoid asymmetry at exercise (AAex), vocal fold collapse (VFC), palatal dysfunction (PD) and medial deviation of the aryepiglottic folds (MDAF) included. The association of endoscope position and FI with URT disorders was assessed using ordinal regression models with P≤0.05 significant. RESULTS: Endoscope tip positioning was significantly associated with PD grading (P = 0.002), with 63/100 horses diagnosed with PD in position A and 45/100 in position B. No other significant direct associations between URT disease and endoscope tip position were identified, although interactions between exercise velocity and endoscope position affected MDAF grade. FI was not directly associated with alterations in disorder grading, although interactions between exercise velocity and FI appeared to affect MDAF grade. MAIN LIMITATIONS: The same horse was not evaluated under each test condition potentially resulting in sample bias. Interactions between disorders were not evaluated. The sample size was insufficient to conclusively explore relationships between all factors and disorder grading. CONCLUSIONS: Position of the endoscope tip within the pharynx appears to affect grading of PD during OGE examination. Exercise velocity may affect MDAF grade through interactions with endoscope position and FI.

The contribution of myostatin (MSTN) and additional modifying genetic loci to race distance aptitude in Thoroughbred horses racing in different geographic regions.

BACKGROUND: Race distance aptitude in Thoroughbred horses is highly heritable and is influenced largely by variation at the myostatin gene (MSTN). OBJECTIVES: In addition to MSTN, we hypothesised that other modifying loci contribute to best race distance. STUDY DESIGN: Using 3006 Thoroughbreds, including 835 'elite' horses, which were >3 years old, had race records and were sampled from Europe/Middle-East, Australia/New Zealand, North America and South Africa, we performed genome-wide association (GWA) tests and separately developed a genomic prediction algorithm to comprehensively catalogue additive genetic variation contributing to best race distance. METHODS: 48,896 single-nucleotide polymorphism (SNP) genotypes were generated from high-density SNP genotyping arrays. Heritability estimates, tests of GWA and genomic prediction models were derived for the phenotypes: average race distance, best race distance for elite, nonelite and all winning horses. RESULTS: Heritability estimates were high ( h m 2  = 0.51, best race distance - elite; h m 2  = 0.42, best race distance - nonelite; h m 2  = 0.40, best race distance - all) and most of the variation was attributed to the MSTN gene. MSTN locus SNPs were the most strongly associated with the trait and included BIEC2-438999 (ECA18:66913090; P = 4.51 × 10-110 , average race distance; P = 2.33 × 10-42 , best race distance - elite). The genomic prediction algorithm enabled the inclusion of variation from all SNPs in a model that partitioned horses into short and long cohorts following assignment of MSTN genotype. Additional genes with minor contributions to best race distance were identified. MAIN LIMITATIONS: The nongenetic influence of owner/trainer decisions on placement of horses in suitable races could not be controlled. CONCLUSIONS: MSTN is the single most important genetic contributor to best race distance in the Thoroughbred. Employment of genetic prediction models will lead to more accurate placing of horses in races that are best suited to their inherited genetic potential for distance aptitude.

Exploratory factor analysis of signalment and conformational measurements in Thoroughbred horses with and without recurrent laryngeal neuropathy.

BACKGROUND: Conflicting results have been reported for risk factors for recurrent laryngeal neuropathy (RLN) based on resting endoscopic evaluation and comparison of single conformation traits, with many traits correlated to one another. OBJECTIVES: To simplify identification of signalment and conformation traits (i.e. variables) associated with RLN cases and controls diagnosed with exercising overground endoscopy (OGE) using exploratory factor analysis (EFA). STUDY DESIGN: Prospective cohort. METHODS: Pearson's rank correlation was used to establish significance and association between variables collected from n = 188 Thoroughbreds from one stable by observers blinded to OGE results. Exploratory factor analysis was conducted on nine variables for cases and controls; common elements between variables developed a factor, with variables grouped into three factors for cases and controls respectively. Correlation (loading) between each variable and factor was calculated to rank relationships between variables and cases/controls, with factors retrospectively named based on their underlying correlations with variables. RESULTS: Numerous inter-correlations were present between variables. Most strongly correlated in cases were wither height with body weight (r = 0.70) and ventral neck length (r = 0.68) and in controls body weight with rostral neck circumference (r = 0.58). Wither height (r = 0.61) significantly loaded the top-ranked factor for cases ('heightRLN '), explaining 25% of conformational variance. Ventral neck length (r = 0.69) and age (r = 0.57) significantly loaded the second-ranked factor for cases ('neck lengthRLN '), explaining 16% of conformational variance. Rostral neck circumference (r = 0.86) and body weight (r = 0.6) significantly loaded the top-ranked factor for controls ('body sizeCON '), explaining 19% of the variance. Wither height (r = 0.84) significantly loaded the second-ranked factor for controls ('heightCON '), explaining 13% of the variance. MAIN LIMITATIONS: Horses had not reached skeletal maturity. CONCLUSIONS: Exploratory factor analysis allowed weightings to be determined for each variable. Wither height was the predominant conformational feature associated with RLN. Exploratory factor analysis confirms aggregated conformational differences exist between RLN cases and controls, suitable for future evaluations.

Validation of masks for determination of V̇O2 max in horses exercising at high intensity.

BACKGROUND: The need for a horse to be ridden while wearing a measurement device that allows unrestricted ventilation and gas exchange has hampered accurate measurement of its maximal oxygen consumption (V̇O2 max) under field conditions. OBJECTIVES: Design and validate a facemask with the potential to measure V̇O2 max accurately in the field. STUDY DESIGN: Experiment with 6 × 6 Latin square design. METHODS: Two variations of a mask and associated electronic control module (ECM) were designed to enable breath-by-breath measurement of airflows through two 7.8 cm diameter pneumotachometers located 7.5 cm in front of each narus. The ECM was comprised of an analogue-to-digital converter and a lithium-ion battery that provided power and signal filtering to the pneumotachometers and an oxygen sensing cell, and powered a pump connected to gas sampling ports between the nares and pneumotachometers. Airflow and oxygen content of inspired and expired gases were recorded through the ECM and electronically transferred to a notebook. V̇O2 was determined from these recordings using a customised software program. Mask B encased the lower jaw. Mask R left the jaw free so the horse could wear a bit if ridden. V̇O2 max and arterial blood gases were measured in 6 horses during multiple treadmill tests. Each mask was worn twice and results compared to those from an established open flow-through system (O) by ANOVA-RM (P<0.05). System utility was evaluated using the intraclass correlation coefficient of 4 independent raters. RESULTS: Blood gases and V̇O2 max (151.9±7.0 [mean±s.d.; O], 151.5±9.6 [B], 149.5±7.5 [R] ml/[kg.min]) were not different between masks. V̇O2 max measures were reproducible for each mask. Intraclass correlation coefficient between raters = 0.99. MAIN LIMITATIONS: Some rebreathing of expired air from mask dead space. CONCLUSION: Masks capable of measuring V̇O2 max during treadmill exercise were developed, tested and found to be accurate. Mask R has potential application to measurement of V̇O2 max under field conditions.

Intra- and interobserver reliability estimates for identification and grading of upper respiratory tract abnormalities recorded in horses at rest and during overground endoscopy.

BACKGROUND: Previous studies support good intra- and interobserver agreements for endoscopic evaluation of various upper respiratory tract (URT) diseases in horses. However, these studies mainly assessed resting endoscopic examination videos and/or focussed on a single URT abnormality. OBJECTIVES: To estimate intra- and interobserver agreement for identification and grading of all URT abnormalities from resting and overground endoscopy (OGE) videos of Thoroughbreds. STUDY DESIGN: Blinded, fully crossed design. METHODS: Resting and OGE URT videos for n = 43 Thoroughbreds were retrospectively chosen based on identification of common URT disorders. The videos were randomly evaluated in duplicate by 4 raters blinded to all information including prior URT disorder(s) diagnosis. Abnormalities were graded using well-described ordinal scales. Intra- and interobserver agreements were estimated using Cohen's weighted κ and Krippendorff's α, respectively. RESULTS: Intraobserver agreement was perfect/nearly perfect for arytenoid symmetry at exercise, epiglottic entrapment and epiglottic retroversion, substantial for arytenoid asymmetry at rest, palatal dysfunction (PD), medial deviation of the aryepiglottic folds (MDAF), pharyngeal mucus and epiglottic grade at exercise and moderate for vocal fold collapse (VFC), ventromedial luxation of the apex of the corniculate process of the arytenoid (VLAC), nasopharyngeal collapse (NPC) and epiglottic grade at rest. Interobserver agreement was substantial for arytenoid symmetry at exercise and PD and moderate for arytenoid asymmetry at rest, MDAF, VLAC and epiglottic entrapment. It was only fair for VFC, epiglottic grade at exercise, epiglottic retroversion, pharyngeal mucus and NPC and poor for epiglottic grade at rest. MAIN LIMITATIONS: Sample size was insufficient to allow assessment of the effect of one abnormality on the grading of another abnormality. CONCLUSIONS: Observers were consistent in grading URT disorders. However, significant disparity in grading existed between observers for some conditions affecting reliability.

Direct costs of glaucoma and severity of the disease: a multinational long term study of resource utilisation in Europe.

BACKGROUND: Resource utilisation and direct costs associated with glaucoma progression in Europe are unknown. As population progressively ages, the economic impact of the disease will increase. METHODS: From a total of 1655 consecutive cases, the records of 194 patients were selected and stratified by disease severity. Record selection was based on diagnoses of primary open angle glaucoma, glaucoma suspect, ocular hypertension, or normal tension glaucoma; 5 years minimum follow up were required. Glaucoma severity was assessed using a six stage glaucoma staging system based on static threshold visual field parameters. Resource utilisation data were abstracted from the charts and unit costs were applied to estimate direct costs to the payer. Resource utilisation and estimated direct cost of treatment, per person year, were calculated. RESULTS: A statistically significant increasing linear trend (p = 0.018) in direct cost as disease severity worsened was demonstrated. The direct cost of treatment increased by an estimated 86 for each incremental step ranging from 455 euro per person year for stage 0 to 969 euro per person year for stage 4 disease. Medication costs ranged from 42% to 56% of total direct cost for all stages of disease. CONCLUSIONS: These results demonstrate for the first time in Europe that resource utilisation and direct medical costs of glaucoma management increase with worsening disease severity. Based on these findings, managing glaucoma and effectively delaying disease progression would be expected to significantly reduce the economic burden of this disease. These data are relevant to general practitioners and healthcare administrators who have a direct influence on the distribution of resources.

Correlates of anxiety in psychiatrically hospitalized children and their parents.

The authors separated 100 children hospitalized in a child psychiatry service into three groups according to their level of anxiety on the basis of the responses of the children and their parents to diagnostic interviews. Differentiation of the groups of children was validated by independent test instruments. Results of tests administered to the children and their parents revealed significant relationships between anxiety in the adults and in the children. In addition, parents of anxious children reported more SCL-90-R symptoms as well as more negative family relations than parents of nonanxious children and the more severely anxious children had higher rates of dysthymia and negative life events.

Prenatal ethanol exposure alters scotopic and photopic components of adult rat electroretinograms.

Ocular malformations and visual deficits are pathognomic of fetal alcohol syndrome (FAS). However, there are no reports on retinal visual function. To determine if prenatal (human second-trimester equivalent) or prenatal plus 10 days of postnatal (human third-trimester equivalent) ethanol exposure produced scotopic and/or photopic deficits in adult hooded rats, electroretinography (ERG) was used to examine rod and cone, increment threshold, dark adaptation, and paired-flash amplitude recovery functions. The rhodopsin content per eye also was determined. Five main results were found. First, voltage-log intensity and latency-log intensity functions, generated from single-flash ERGs in fully dark-adapted rats, showed increases in absolute threshold and latency and decreases in response amplitude. Second, cone ERGs had latency increases. Third, there were decreases in the scotopic and photopic critical flicker-fusion frequencies, increment threshold functions, and absolute and relative refractory periods. Fourth, rod sensitivity, range, and rate of dark adaptation were decreased. Fifth, rhodopsin content per eye was decreased. These data showed that prenatal ethanol exposure produces long-term deficits in retinal sensitivity, amplitude, light and dark adaptation, temporal processing, and excitability. Larger deficits occurred in the scotopic than photopic system and were produced with an additional 10 days of postnatal ethanol exposure. Alterations in photoreceptors and other cells of the distal retina probably contributed to these deficits. The relevance and applicability of these data to FAS and subclinical alcohol embryopathy have yet to be demonstrated; however, they suggest that similar retinal alterations may occur in human FAS.