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Detecting the use of bisphosphonates (BPs) in equine athletes is of interest to regulators and laboratories due to the threat to welfare issues for the potential to provide analgesic effects and manipulating bone structure. The detection of BPs in biological matrices is challenging due to erratic biological elimination and inconsistent analytical recoveries. Therefore, complementary approaches are needed to provide evidence of their misuse in racehorses. BPs have two sub-classes: nitrogenous and non-nitrogenous. This study investigated plasma elimination following administration of one example from each sub-class, together with changes in endogenous eicosanoid and corticosteroids. Zoledronic acid (ZA) and tiludronic acid (TA) were administered by IV infusion to 8 thoroughbred horses with an 11-month washout period between each administration. Sample preparation for quantification of BPs by liquid chromatography-tandem mass spectrometry (LC-MS/MS) utilised a two-step solid phase extraction (SPE) consisting of polymeric reversed-phase followed by weak anion exchange prior to derivatisation using trimethyl orthoacetate. Endogenous biomarkers were analysed after protein precipitation and SPE with polymeric reversed-phase prior to liquid chromatography-high resolution mass spectrometry (LC-HRMS) using data independent acquisition. The LC-MS/MS analysis showed ZA was undetectable after 8 h post-administration while TA was detected up to the final collection point of 28 days post-administration. The LC-HRMS analysis utilised targeted (i.e., prior inclusion list of compounds) approaches to monitor level changes of eicosanoid and corticosteroid biomarkers. Putative biomarkers were identified and now subject to validation for translation into routine sample analysis for improved retrospectivity to detecting BP misuse in equine plasma., (© 2024 The Author(s). Drug Testing and Analysis published by John Wiley & Sons Ltd.)

We report results from an analysis aimed at detecting the trispectrum of the kinematic Sunyaev-Zel'dovich (kSZ) effect by combining data from the South Pole Telescope (SPT) and Herschel-SPIRE experiments over a 100  deg^{2} field. The SPT observations combine data from the previous and current surveys, namely SPTpol and SPT-3G, to achieve depths of 4.5, 3, and 16  μK-arcmin in bands centered at 95, 150, and 220 GHz. For SPIRE, we include data from the 600 and 857 GHz bands. We reconstruct the velocity-induced large-scale correlation of the small-scale kSZ signal with a quadratic estimator that uses two cosmic microwave background (CMB) temperature maps, constructed by optimally combining data from all the frequency bands. We reject the null hypothesis of a zero trispectrum at 10.3σ level. However, the measured trispectrum contains contributions from both the kSZ and other undesired components, such as CMB lensing and astrophysical foregrounds, with kSZ being sub-dominant. We use the agora simulations to estimate the expected signal from CMB lensing and astrophysical foregrounds. After accounting for the contributions from CMB lensing and foreground signals, we do not detect an excess kSZ-only trispectrum and use this nondetection to set constraints on reionization. By applying a prior based on observations of the Gunn-Peterson trough, we obtain an upper limit on the duration of reionization of Δz&#95;{re,50}<4.5 (95% confidence level). We find these constraints are fairly robust to foregrounds assumptions. This trispectrum measurement is independent of, but consistent with, Planck's optical depth measurement. This result is the first constraint on the epoch of reionization using the non-Gaussian nature of the kSZ signal.

Our intersectional research explored food insecurity and job insecurity as predictors of healthcare insecurity and mental health challenges among households living in economic instability since the COVID19 pandemic began. The New York City COVID19 Research Team adapted a validated, web based, anonymous survey questionnaire using a Social Determinants of Health Framework. The study oversampled underserved populations with a total of 2,099 participants. We report strong associations between food insecurity and job insecurity among healthcare insecure households, and significant mental health challenges among food insecure and healthcare insecure households. This underscores the need for integrated social policies to protect underserved urban populations.

Background: Plantar warts, or verrucae plantaris, are common lesions causing considerable pain during weightbearing activity. Although current treatment modalities have low success rates, microwave therapy has been introduced as a promising intervention. This study aimed to determine the effectiveness of microwave therapy for the treatment of plantar warts and to determine the clinical factors associated with plantar wart resolution., Methods: A retrospective analysis of 150 plantar warts from 45 patients treated with microwave therapy was undertaken. Binomial regression was conducted to explore clinical characteristics (age, gender, immunosuppression, impaired healing, multiple vs single wart, location of lesion, lesion diameter) associated with lesion resolution., Results: Of the total 150 plantar warts treated with microwave therapy, 125 (83.3%) warts resolved and 25 (17%) warts did not resolve. The mean (SD) total treatment sessions for resolved lesions was 2.8 (1.0). Decreasing age (P = 0.046) was the only clinical characteristic associated with resolution., Conclusions: This retrospective study has shown that plantar warts may be resolved with two to three sessions of microwave therapy, which may be more successful in younger populations., (© 2023. The Author(s).)

There are longstanding questions about the origins and ancestry of the Picts of early medieval Scotland (ca. 300-900 CE), prompted in part by exotic medieval origin myths, their enigmatic symbols and inscriptions, and the meagre textual evidence. The Picts, first mentioned in the late 3rd century CE resisted the Romans and went on to form a powerful kingdom that ruled over a large territory in northern Britain. In the 9th and 10th centuries Gaelic language, culture and identity became dominant, transforming the Pictish realm into Alba, the precursor to the medieval kingdom of Scotland. To date, no comprehensive analysis of Pictish genomes has been published, and questions about their biological relationships to other cultural groups living in Britain remain unanswered. Here we present two high-quality Pictish genomes (2.4 and 16.5X coverage) from central and northern Scotland dated from the 5th-7th century which we impute and co-analyse with >8,300 previously published ancient and modern genomes. Using allele frequency and haplotype-based approaches, we can firmly place the genomes within the Iron Age gene pool in Britain and demonstrate regional biological affinity. We also demonstrate the presence of population structure within Pictish groups, with Orcadian Picts being genetically distinct from their mainland contemporaries. When investigating Identity-By-Descent (IBD) with present-day genomes, we observe broad affinities between the mainland Pictish genomes and the present-day people living in western Scotland, Wales, Northern Ireland and Northumbria, but less with the rest of England, the Orkney islands and eastern Scotland-where the political centres of Pictland were located. The pre-Viking Age Orcadian Picts evidence a high degree of IBD sharing across modern Scotland, Wales, Northern Ireland, and the Orkney islands, demonstrating substantial genetic continuity in Orkney for the last ~2,000 years. Analysis of mitochondrial DNA diversity at the Pictish cemetery of Lundin Links (n = 7) reveals absence of direct common female ancestors, with implications for broader social organisation. Overall, our study provides novel insights into the genetic affinities and population structure of the Picts and direct relationships between ancient and present-day groups of the UK., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Morez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The use of catechol-O-methyltransferase inhibitors may mask doping agents, primarily levodopa, administered to racehorses and prolong the stimulating effects of dopaminergic compounds such as dopamine. It is known that 3-methoxytyramine is a metabolite of dopamine and 3-methoxytyrosine is a metabolite of levodopa thus these compounds are proposed to be potential biomarkers of interest. Previous research established a urinary threshold of 4,000 ng/mL for 3-methoxytyramine to monitor misuse of dopaminergic agents. However, there is no equivalent biomarker in plasma. To address this deficiency a rapid protein precipitation method was developed and validated to isolate target compounds from 100 µL equine plasma. A liquid chromatography-high resolution accurate mass (LC-HRAM) method using an IMTAKT Intrada amino acid column provided quantitative analysis of 3-methoxytyrosine (3-MTyr) with lower limit of quantification of 5 ng/mL. Reference population profiling (n = 1129) investigated the expected basal concentrations for raceday samples from equine athletes and showed a right-skewed distribution (skewness = 2.39, kurtosis = 10.65) which resulted from large variation (RSD = 71%) within the data. Logarithmic transformation of the data provided a normal distribution (skewness = 0.26, kurtosis = 3.23) resulting in the proposal of a conservative threshold for plasma 3-MTyr of 1,000 ng/mL at a 99.995% confidence level. A 12-horse administration study of Stalevo® (800 mg L-DOPA, 200 mg carbidopa, 1600 mg entacapone) revealed elevated 3-MTyr concentrations for 24-hours post-administration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The feeding value for ruminants of green hemp biomass, from the low Δ 9 -tetrahydrocannabinol (Δ 9 -THC) variety of Cannabis sativa L., is unknown. Twelve Merino ewes were individually penned and randomly allocated on a stratified liveweight basis to one of two pelleted dietary treatments, control (0% hemp, n = 6) or hemp (42% green hemp biomass, n = 6) that delivered a diet meeting the nutrient requirements of the animals. The experimental period consisted of 17 d dietary and housing adaptation, followed by 7 d total urine and feces collection for determination of apparent nutrient digestibility. A ruminal fluid sample was collected on day 27 and assessed for pH, ammonia, volatile fatty acid (VFA), and cannabinoid concentrations. A blood sample from the jugular vein and incisional subcutaneous fat biopsy from an area around the base of the tail were collected on day 28 with additional fat biopsies taken 35 d and 140 d post-feeding to measure cannabinoids. The dry matter (DM), organic matter (OM), and crude protein (CP) digestibilities, along with total VFA concentration did not differ ( P = 0.713) between the two diets; however, acid detergent fiber (ADF) and neutral detergent fiber (NDF) digestibilities ( P < 0.001), water intake ( P = 0.023), and fecal water output ( P < 0.001) were significantly lower for the sheep-fed Hemp. Rumen pH did not vary ( P = 0.256) between diets, but ruminal ammonia concentration was significantly lower ( P = 0.024) for sheep consuming Hemp. Sheep-fed Hemp had significantly greater molar proportions of butyric ( P = 0.039) and hexanoic ( P = 0.012) acids and lower molar proportions of propionic acid ( P = 0.003). There were no differences between diets for N intake ( P = 0.175), fecal N output ( P = 0.253), and N balance ( P = 0.695), with all sheep in positive N balance; however, there was significantly lower ( P = 0.001) urinary N output for sheep-fed Hemp. Cannabidiolic acid (CBDA) and tetrahydrocannabinolic acid (THCA) were detected in plasma of all sheep-fed Hemp. ∆ 9 -tetrahydrocannabinol was present in the subcutaneous fat of four of the six sheep on the final day of being fed Hemp, and in all (six) sheep 35 d post-feeding and one sheep 140 d post-feeding Hemp. No cannabinoids were detected in the corresponding samples taken from the sheep-fed Control. Thus, despite green hemp biomass being nutritionally a suitable feed for ruminants, under current Food Standards in Australia, the presence of these cannabinoid residues restricts its use in ruminant diets., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Background: Fifty-watt radiofrequency applications have proven to be safe and efficient for pulmonary vein isolation (PVI). However, as PV reconnection still occurs and ablation catheter instability significantly contributes to suboptimal lesion formation, a new ablation catheter capable of delivering 90 W for 4 seconds only has been developed with the aim of improving PVI outcomes. In this setting, we sought to determine whether 90 W applications create transmural lesions without collateral damage experimentally and whether they can safely improve PVI procedures clinically compared with 50 W settings., Methods: Experimentally, individual lesions were created in vivo in the right atrium of 6 swine with 90 W-4 seconds applications using the SmartTouch-SF catheter in a power-controlled mode (3 animals) or the QDOT-MICRO catheter in a temperature-controlled mode (3 animals). Clinically, PVI was performed in a homogenous population of 150 consecutive paroxysmal atrial fibrillation patients using CARTO and the QDOT-MICRO catheter in a temperature-controlled mode (75 patients 50 W-ablation index-guided and 75 patients 90 W-4 seconds)., Results: Mostly, (94.9%) experimental lesions were transmural in the thin-walled right atrium of swine. However, collateral damage was observed with both catheters in 17.9% of lesions. Clinically, 90 W procedures had a lower first-pass PVI rate (49% versus 81%, P <10 -4 ) and a higher acute PV reconnection rate (21% versus 5%, P =0.004) than 50 W procedures, whereas total procedural duration (62 versus 66 minutes, P =0.09), 1-year sinus rhythm maintenance (88% versus 90%, P =0.6) and safety (1 tamponade per group) were similar in both groups., Conclusions: Experimentally, using the QDOT-MICRO catheter, 90 W-4 seconds lesions are mostly transmural in the thin-walled right atrium of swine (median depth 1.87 mm) with a moderate lesion diameter of 6.62 mm but retain the potential for collateral damage. Clinically, 90 W-4 seconds applications are associated with a lower first-pass PVI rate and a higher acute PV reconnection rate than 50 W applications but similar safety outcomes and effectiveness at 1 year.

Purpose: Important implications exist for ophthalmologists when considering possible early surgical intervention for potential amblyogenic anatomical abnormalities. The authors discuss the risks and benefits from an ophthalmological perspective of different interventions and review the genetic testing that confirmed the diagnosis., Observations: The authors describe the findings and management of an infant with Freeman Sheldon syndrome presenting with blepharophimosis of both eyelids resulting in inability to open both eyes during the first several days of life. Although the mode of inheritance for Freeman Sheldon syndrome (formerly known as Whistling Face Syndrome) is often autosomal dominant, our patient had no known family history of congenital abnormalities or consanguinity. However, genetic testing confirmed a heterozygous variant in MYH3 , consistent with autosomal dominant Freeman Sheldon Syndrome. When our patient required gastrostomy (G-tube&#95;placement, we performed an exam under anesthesia (EUA)). As is typical for Freeman Sheldon syndrome patients, intubation was difficult and complicated by pneumothorax. Eye-opening improved slightly after several weeks of life; however, the decision was made to proceed with eyelid surgery to prevent deprivation amblyopia. Surgery is scheduled for a future date. Additionally, the patient had congenital nasolacrimal duct obstruction of the left eye; however, a probing and irrigation failed because of obstruction from the abnormal facial anatomy., Conclusions and Importance: Patients with Freeman Sheldon syndrome are at increased risk for complications from anesthesia and surgery. Risks and benefits should be strongly considered and discussed with parent(s)/guardian(s) prior to any surgical intervention. Genetic testing of the MYH3 gene can confirm the diagnosis.

In 1885, while working at the University of Pennsylvania, Eadweard Muybridge and Francis Dercum used nascent photographic technology to perform the first-ever motion picture study of neurologic patients. To date, our clinical understanding of the Muybridge-Dercum project has been limited to those clinical details included in a handful of contemporaneous publications by Dercum et al. In this study, recently rediscovered clinical notebooks from the Hospital of the University of Pennsylvania's Dispensary for Nervous Diseases were reviewed and found to contain the original clinical records of 9 of Muybridge and Dercum's photographic subjects. These records add new clinical insights into our understanding of this historic photographic study and revive the zeitgeist of a foundational period in the development of neurology as a medical subspecialty in the United States., (© 2021 American Academy of Neurology.)

Background: Intrathecal baclofen (ITB) is traditionally reserved for non-ambulatory patients., Objective: To investigate outcomes of ITB in ambulatory multiple sclerosis (MS) patients., Methods: Changes in outcome measures were estimated by a mixed effect model, while the complication rate was calculated using a logistic regression. Predictors of non-ambulatory status were identified by Cox model., Results: In all, 256 patients received an ITB test injection and 170 underwent ITB surgery. Aggregate Modified Ashworth Scale (MAS) scores for the ambulatory ITB cohort decreased from 13.5 ± 6.96 to 4.54 ± 4.18 at 5 years ( p  < 0.001). There was no significant change in walking speed 1 year post ITB surgery (0.45 m/second ± 0.30 vs 0.38 m/second ± 0.39, p  = 0.80) with 77.8% of patients remaining ambulatory which decreased to 41.7% at year 5. Longer MS disease duration (hazard ratio (HR): 1.04; 95% confidence interval (CI): 1.01-1.07; p  = 0.018) and lower hip flexor strength (HR: 0.40; 95% CI: 0.27-0.57; p  < 0.001) predicted non-ambulatory status after surgery. Complications were more likely in the ambulatory cohort (odds ratio (OR): 3.30, 95% CI: 2.17-5.02; p  = 0.017)., Conclusion: ITB is effective for ambulatory MS patients without compromising short-term walking speed, although a higher complication rate was observed in this cohort.

We present two prescriptions for broadband ($ {\sim} 77 - 252\;{\rm GHz} $), millimeter-wave antireflection coatings for cryogenic, sintered polycrystalline aluminum oxide optics: one for large-format (700 mm diameter) planar and plano-convex elements, the other for densely packed arrays of quasi-optical elements-in our case, 5 mm diameter half-spheres (called "lenslets"). The coatings comprise three layers of commercially available, polytetrafluoroethylene-based, dielectric sheet material. The lenslet coating is molded to fit the 150 mm diameter arrays directly, while the large-diameter lenses are coated using a tiled approach. We review the fabrication processes for both prescriptions, then discuss laboratory measurements of their transmittance and reflectance. In addition, we present the inferred refractive indices and loss tangents for the coating materials and the aluminum oxide substrate. We find that at 150 GHz and 300 K the large-format coating sample achieves $ (97 \pm 2)\% $ transmittance, and the lenslet coating sample achieves $ (94 \pm 3)\% $ transmittance.

We report the first detection of gravitational lensing due to galaxy clusters using only the polarization of the cosmic microwave background (CMB). The lensing signal is obtained using a new estimator that extracts the lensing dipole signature from stacked images formed by rotating the cluster-centered Stokes QU map cutouts along the direction of the locally measured background CMB polarization gradient. Using data from the SPTpol 500  deg^{2} survey at the locations of roughly 18 000 clusters with richness λ≥10 from the Dark Energy Survey (DES) Year-3 full galaxy cluster catalog, we detect lensing at 4.8σ. The mean stacked mass of the selected sample is found to be (1.43±0.40)×10^{14}M&#95;{⊙} which is in good agreement with optical weak lensing based estimates using DES data and CMB-lensing based estimates using SPTpol temperature data. This measurement is a key first step for cluster cosmology with future low-noise CMB surveys, like CMB-S4, for which CMB polarization will be the primary channel for cluster lensing measurements.

Paleogenomic and archaeological studies show that Neolithic lifeways spread from the Fertile Crescent into Europe around 9000 BCE, reaching northwestern Europe by 4000 BCE. Starting around 4500 BCE, a new phenomenon of constructing megalithic monuments, particularly for funerary practices, emerged along the Atlantic façade. While it has been suggested that the emergence of megaliths was associated with the territories of farming communities, the origin and social structure of the groups that erected them has remained largely unknown. We generated genome sequence data from human remains, corresponding to 24 individuals from five megalithic burial sites, encompassing the widespread tradition of megalithic construction in northern and western Europe, and analyzed our results in relation to the existing European paleogenomic data. The various individuals buried in megaliths show genetic affinities with local farming groups within their different chronological contexts. Individuals buried in megaliths display (past) admixture with local hunter-gatherers, similar to that seen in other Neolithic individuals in Europe. In relation to the tomb populations, we find significantly more males than females buried in the megaliths of the British Isles. The genetic data show close kin relationships among the individuals buried within the megaliths, and for the Irish megaliths, we found a kin relation between individuals buried in different megaliths. We also see paternal continuity through time, including the same Y-chromosome haplotypes reoccurring. These observations suggest that the investigated funerary monuments were associated with patrilineal kindred groups. Our genomic investigation provides insight into the people associated with this long-standing megalith funerary tradition, including their social dynamics., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Background: A significant proportion of international students at UK universities are from regions with medium to high hepatitis B prevalence rates. Understanding the perception of students regarding hepatitis B infection is crucial for the development of appropriate information and services for this population group., Methods: Twenty semi-structured interviews were conducted with students from the University of Aberdeen. The following key areas were covered: knowledge, awareness, practices including testing, cultural and social aspects and general attitudes to health information and services. Interviews were transcribed verbatim and coded using a framework analysis approach., Results: The participants acknowledged hepatitis B to be a serious disease yet did not consider themselves to be at risk. They felt able to go to their General Practitioner if concerned about hepatitis B but emphasised that there was no indication that this was required. There was a general lack of knowledge about the disease including confusion over other types of hepatitis. This was linked to the perceived lack of attention given to hepatitis B in, for example, sexual health education and disease awareness raising campaigns. The participants expressed a desire for information on hepatitis B to be relevant to the student population, easy to understand, socially acceptable and easily accessible on student portals and social media platforms., Conclusions: Our study suggests that students in Aberdeen, North East Scotland lack knowledge and awareness of hepatitis B and do not perceive themselves as being at risk of hepatitis B infection. There is a need for more tailored hepatitis B messages to be incorporated into a range of contexts with clearer risk communication for the student population.

The use of testosterone and its pro-drugs, such as dehydroepiandrosterone (DHEA), is currently regulated in horseracing by the application of international testosterone thresholds. However, additional steroidomic approaches, such as steroid ratios, to distinguish overall adrenal stimulation from drug administrations and an equine biological passport for longitudinal steroid profiling of individual animals could be advantageous in equine doping testing. Thus, DHEA concentrations and related ratios (testosterone [T] to DHEA and DHEA to epitestosterone [E]) were assessed in the reference population by quantitative analysis of 200 post-race gelding urine samples using liquid chromatography-tandem mass spectrometry. DHEA concentrations ranged between 0.9 and 136.6 ng/mL (mean 12.8 ng/mL), T:DHEA ratios between 0.06 and 1.85 (mean 0.43), and DHEA:E ratios between 0.21 and 13.56 (mean 2.20). Based on the reference population statistical upper limits of 5.4 for T:DHEA ratio and 48.1 for DHEA:E ratio are proposed with a risk of 1 in 10 000 for a normal outlier exceeding the value. Analysis of post-administration urine samples collected following administrations of DHEA, Equi-Bolic® (a mix of DHEA and pregnenolone) and testosterone propionate to geldings showed that the upper limit for T:DHEA ratio was exceeded following testosterone propionate administration and DHEA:E ratio following DHEA administrations and thus these ratios could be used as additional biomarkers when determining the cause of an atypical testosterone concentration. Additionally, DHEA concentrations and ratios can be used as a starting point to establish reference ranges for an equine biological passport., (Copyright © 2018 John Wiley & Sons, Ltd.)

Detection of testosterone and/or its pro-drugs in the gelding is currently regulated by the application of an international threshold for urinary testosterone of 20 ng/mL. The use of steroid ratios may provide a useful supplementary approach to aid in differentiating between the administration of these steroids and unusual physiological conditions that may result in atypically high testosterone concentrations. In the current study, an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed to quantify testosterone (T) and epitestosterone (E). The method was used to analyze 200 post-race urine samples from geldings in order to generate the ratios for the reference population. Following statistical analysis of the data, an upper limit of 5 for T:E ratio in geldings is proposed. Samples collected from 15 geldings with atypical urinary testosterone concentrations (>15 ng/mL) but otherwise normal steroid profile, had T:E ratios within those observed for the reference population. The applicability of an upper T:E ratio to detect an administration was demonstrated by the analysis of a selection of incurred samples from testosterone propionate, dehydroepiandrosterone (DHEA), and a mixture of DHEA and pregnenolone (Equi-Bolic®) administrations. These produced testosterone concentrations above the threshold of 20 ng/mL, but also T:E ratios above the proposed limit of 5. In conclusion, consideration of the T:E ratio appears to be a valuable complementary aid to evaluate whether an atypical testosterone concentration could be caused by a natural biological outlier as opposed to the administration of these steroids. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Objectives: Late HIV diagnosis is associated with increased morbidity and mortality, increased risk of transmission, impaired response to antiretroviral therapy and increased health care costs. The aim of this study was to determine the factors associated with late HIV diagnosis in Grampian, North-East Scotland., Study Design: A population based retrospective database analysis., Methods: All newly diagnosed HIV positive individuals in Grampian, North-East Scotland between 2009 and 2014 were included in the study. Participants were classified as having a late diagnosis if the CD4 cell count at presentation was less than 350 cells/mm 3 . Socio-economic and demographic factors were investigated in relation to outcome (late diagnosis) using Chi-squared and Mann-Whitney tests., Results: CD4 cell count results were available for 111 (89.5%) of the 124 newly diagnosed individuals during the study period. The prevalence of late diagnosis was 53.2% (n = 59). Those infected via heterosexual mode of transmission had a 2.83 times higher odds of late diagnosis (OR 2.83 [95% CI: 1.10-7.32]) than men who have sex with men (MSM) and those with no previous HIV testing had a 5.46 increased odds of late diagnosis (OR 5.46 [95% CI: 1.89-15.81]) compared to those who had previously been tested. Missed opportunities for HIV diagnosis were identified in 16.3% (n = 15) of participants., Conclusion: Heterosexual individuals and those with no previous HIV testing were more likely to be diagnosed late. Targeted initiatives to increase perception of HIV risk and uptake of testing in these risk groups are recommended., (Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background Context: Various posterolateral approaches exist to access ventral thoracic spinal canal pathologies. Selecting the optimal surgical approach requires sound understanding of the exposure and working angle afforded by each approach., Purpose: The purpose of this study was to quantify exposure of the ventral spinal canal with various posterolateral thoracic spinal approaches and to determine how regional anatomical differences affect measurements., Study Design: This is a quantitative anatomical cadaveric study., Methods: Four fresh cadaveric C7-L1 specimens were used with a saline infusion model to mimic in vivo thecal sac dimensions. Using stereotactic navigation, we measured exposure (expressed as percentage of total width) and maximum approach angle of the ventral spinal canal without thecal sac retraction after each surgical condition: laminectomy (L), 50% medial facetectomy (MF), transpedicular (TP), costotransversectomy (CTV), and lateral extracavitary (LE). The thoracic spine was divided into four regions (T1-T2, T3-T6, T7-T10, and T9-T12). A two-sided paired t test was used., Results: At T1-T2, visualized exposures were 25.8%, 31.5%, 42.3%, 45.1%, and 46.8%, respectively, after each surgical condition. Costotransversectomy and LE did not provide significant increase in exposure compared with the preceding condition. At T3-T6, exposures were 19.1%, 29.6%, 38.7%, 44.4%, and 44.5%, respectively. Only LE did not provide significant increase in exposure compared with the preceding condition. At T7-T10, visualized exposures were 17.9%, 30.6%, 39.9%, 44.9%, and 53.3%, respectively. All successive surgical conditions provided a significant increase in exposure. At T11-T12, visualized exposures were 14.2%, 25.8%, 43.1%, 47.7%, and 52.7%, respectively. Only LE did not provide a significant increase in exposure compared with the preceding condition. Each successive surgical condition provided a significantly increased lateral approach angle compared with the preceding condition, except LE at T1-T2. Maximum approach angle was more favorable at T1-T2 for L, MF, TP, and CTV compared with other thoracic regions., Conclusions: Medial facetectomy and TP approaches provide significantly increased exposure of the ventral spinal canal at all thoracic regions. Costotransversectomy provided significantly increased exposure compared with TP at T3-T12. Lateral extracavitary only provided significantly increased exposure compared with CTV at T7-T10. The results of this study can be used preoperatively to determine the optimal approach based on quantitative measurements and region-specific anatomical differences., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: It has been experimentally shown that elimination of the negative component of the unipolar atrial electrogram (R morphology completion) during radiofrequency applications reflects transmural lesions creation. Subsequently, it has been clinically suggested that such a transmurality can be either irreversible or reversible. The present study is aimed to determine, at the histological level, whether transmural lesions, assessed by R morphology completion, might indeed be reversible in some circumstances or not., Methods and Results: In 6 Mongrel hound dogs, superior and inferior vena cavae were isolated and individual lesions were created in the right atrium using radiofrequency energy (30 W/48°C/17 mL/min as presettings and 10g of force in average) under CARTO guidance. Five types of lesions were created; R+0: termination of ablation at the time of R morphology completion; R+5, R+10, or R+20: extension of ablation for 5, 10, or 20 seconds, respectively, after R morphology achievement; and conventional: radiofrequency applications lasting 30 seconds irrespective of the atrial electrogram modification. All conventional, R+5, R+10, and R+20 lesions were necrotic and transmural, whereas some R+0 lesions were not (comprising a part of necrosis and a part of reversible cell damage). Interestingly, surrounding organ injuries were observed after conventional, R+10, and R+20 radiofrequency applications but were not observed after R+0 and R+5 applications., Conclusions: Elimination of the negative component of the unipolar atrial electrogram reflects, in general, irreversible transmural necrosis creation. In some cases, however, it translates transmural lesion only (with potential reversibility) likely related to transient cell damage creation., (© 2015 American Heart Association, Inc.)

Background: We hypothesised that in blunt trauma patients with haemodynamic instability and haemoperitoneum on hospital admission, the haemorrhagic source may not be confined to the peritoneum. The purpose of this study was to describe the incidence and location of bleeding source in this population., Methods: The charts of trauma patients admitted consecutively between January 2005 and January 2010 to our level I Regional Trauma Centre were reviewed retrospectively. All hypotensive patients presenting a haemoperitoneum on admission were included. Hypotension was defined by a systolic blood pressure ≤ 90 mmHg. The haemoperitoneum was quantified on CT images or from operative reports as moderate (Federle score<3 or between 200 and 500 ml) or large (Federle score ≥ 3 or >500 ml). Active bleeding (AB) was defined as injury requiring a surgical or radiologic haemostatic procedure, regardless of origin (peritoneal (PAB) or extraperitoneal (EPAB))., Results: Of 1079 patients admitted for severe trauma, 110 patients met the inclusion criteria. Seventy-eight (71%) were male, mean age 35.3 (SD 19) years and mean ISS 36.5 (SD 20.5). Among the 91 patients who had AB, 37 patients (41%) had PAB, 34 (37%) had EPAB and 20 had both (22%). Forty-eight (53%) of them had moderate haemoperitoneum and 43 (47%) had large haemoperitoneum. A large haemoperitoneum had positive predictive value for PAB of 88% (95% CI 75-95%) and negative predictive value of 65% (95% CI 49-79%). The corresponding values in the subgroup of patients with EPAB were 65% (95% CI 38-86%) and 76% (95% CI 59-88%)., Conclusion: Haemoperitoneum was associated with PAB in only 52% of hypotensive blunt trauma patients and 63% of bleeding patients. In contrast, 59% of bleeding patients had at least one EPAB. The screening of a haemoperitoneum as a marker of active haemorrhagic source may be confusing and lead to misdiagnosis and inappropriate strategy. Clinician should exclude carefully the presence of any EPAB explaining haemorrhagic shock, before to decide haemostatic treatment., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Reasons for Performing the Study: As growth hormone increases lean body mass, it could be a therapy for obese horses. However, growth hormone use induces hyperinsulinaemia in some species, so further investigation is warranted., Objectives: To investigate the effects of feeding, exercise and growth hormone therapy on basal insulin concentrations in healthy horses., Study Design: In vivo experimental study., Methods: Blood samples were obtained every 30 min from 12 geldings over 24 h, to establish basal serum insulin concentrations, before they underwent a 3-week exercise programme. Horses were allocated into 2 groups and exercised for another 4 weeks. Group A received daily i.m. injections of recombinant equine growth hormone; 5 mg/day for 5 days, then 12.5 mg/day for 16 days. Blood samples were taken daily before feeding. Insulin vs. time area under curve of Groups A and B were compared using a Student's unpaired t test., Results: Horses demonstrated insulin peaks within 2 h of feeding of 577 ± 108.3 pmol/l at 09.30 h and 342.4 ± 75.7 pmol/l at 17.30 h, despite receiving the same meal. The nadir was between midnight and 07.30 h. Exercise had no effect on basal insulin concentrations prior to equine growth hormone administrations. The equine growth hormone injections increased serum insulin concentrations (P = 0.01) within Group A, from 44.4 ± 15.3 pmol/l initially to 320.9 ± 238.2 pmol/l by Day 12. Exogenous growth hormone caused variable hyperinsulinaemia, which was alleviated once equine growth hormone administration ceased., Conclusions: Single serum samples taken prior to the morning meal provide basal insulin concentrations. Exercise did not change basal insulin concentrations. However, equine growth hormone injections increased basal insulin concentrations, which were not ameliorated by exercise., Potential Relevance: This therapy is not recommended to address obesity in insulin-resistant equids., (© 2013 EVJ Ltd.)

Stem-cement and cement-bone interfacial failures as well as cement fractures have been noted in cemented total hip arthroplasty (THA) as the cause of aseptic loosening. Attempts to reduce the risk of femoral component loosening include improving the stem-cement interface by various coatings, using a textured or porous coated stem surfaces or by using a tapered stem having a highly-polished surface. The latter approach, often referred to as "force-closed" femoral stem design, would theoretically result in stem stabilization subsequent to debonding and 'taper-lock'. Previous work using three-dimensional finite element analysis has shown a state of stress at the stem-cement interface indicative of 'taper-lock' for the debonded stem and indicated that stem-cement interface friction and bone cement creep played a significant role in the magnitudes of stresses and subsidence of the stem. However, the previous analysis did not include the viscoelastic properties of bone, which has been hypothesized to permit additional expansion of the bone canal and allow additional stem subsidence (Lu and McKellop, 1997). The goal of this study was to investigate the effect of bone viscoelastic behavior on stem subsidence using a 3D finite element analysis. It was hypothesized that the viscoelastic behavior of bone in the hoop direction would allow expansion of the bone reducing the constraint on bone over time and permit additional stem subsidence, which may account for the discrepancies between predicted and clinical subsidence measurements. Analyses were conducted using physiological loads, 'average peak loads' and 'high peak loads' for 'normal patient' and 'active patient' (Bergmann et al., 2010) from which short and long term subsidence was predicted. Results indicated that bone creep does contribute to higher stem subsidence initially and after 10 years of simulated loading. However, it was concluded that the "constraint" upon the cement mantle is not mitigated enough to result in stem subsidence equivalent to that observed clinically., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The pharmacokinetics, efficacy, and safety of meloxicam have been evaluated in adult horses, but not foals. Physiologic differences between neonates and adults might alter drug pharmacokinetics and therapeutic index., Hypotheses: The pharmacokinetics of meloxicam will be different in foals compared with adult horses, and foals could be at increased risk for adverse drug effects., Animals: Twenty lightbreed foals less than 6 weeks of age at commencement of the study., Methods: Single and repeated oral dose pharmacokinetics were determined for meloxicam (0.6 mg/kg) in 10 foals. The safety of the drug was further evaluated in a 2nd group of 10 foals in a randomized blinded prospective study., Results: Plasma concentrations after a single oral dose of meloxicam (0.6 mg/kg) and time to maximum plasma concentration were similar to adult horses. However, drug clearance was much more rapid in foals (elimination half-life 2.48 ± 0.25 hours). Administration of 0.6 mg/kg every 12 hours was well tolerated by foals for up to 3 weeks, with no evidence of drug accumulation in plasma. Adverse effects observed in adult horses at higher dose rates were not observed in foals given 1.8 mg/kg twice daily for 7 days., Conclusions and Clinical Importance: Meloxicam at an oral dose rate of 0.6 mg/kg every 12 hours provided plasma concentrations likely to be therapeutic. In contrast to findings for other NSAIDs, foals appeared more resilient to the adverse effects of this drug than was observed in adult horses., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

We describe the population pharmacokinetics of an acepromazine (ACP) metabolite (2-(1-hydroxyethyl)promazine) (HEPS) in horses for the estimation of likely detection times in plasma and urine. ACP (30 mg) was administered to 12 horses, and blood and urine samples were taken at frequent intervals for chemical analysis. A bayesian hierarchical model was fitted to describe concentration-time data and cumulative urine amounts for HEPS. The metabolite HEPS was modelled separately from the parent ACP as the half-life of the parent was considerably less than that of the metabolite. The clearance (Cl/F(PM)) and volume of distribution (V/F(PM)), scaled by the fraction of parent converted to metabolite, were estimated as 769 L/h and 6874 L, respectively. For a typical horse in the study, after receiving 30 mg of ACP, the upper limit of the detection time was 35 h in plasma and 100 h in urine, assuming an arbitrary limit of detection of 1 lg/L and a small (≈0.01) probability of detection. The model derived allowed the probability of detection to be estimated at the population level. This analysis was conducted on data collected from only 12 horses, but we assume that this is representative of the wider population., (© 2012 Blackwell Publishing Ltd.)

Objective: To determine if postoperative C-reactive protein (CRP) or cortisol concentrations were significantly changed between dogs undergoing ovariohysterectomy by an experienced or inexperienced surgeon. As part of the Charles Sturt University teaching program, 45 bitches from an animal shelter were surgically sterilised between March and October 2010., Methods: The dogs were randomly assigned to surgeons, with 37 sterilised by veterinary undergraduates and 8 by experienced surgeons. Blood samples were collected preoperatively and at 2, 4 and 6 h postoperatively. A standard midline ovariohysterectomy was performed and detailed records kept., Results: The median surgery time for experienced surgeons was 17 min versus 87 min for inexperienced surgeons. Anaesthesia time and blood loss were greater among the inexperienced surgeons. The CRP concentration increased significantly postoperatively for all animals (P < 0.001). Bitches sterilised by inexperienced surgeons had a significantly greater rise in CRP at 4 and 6 h post-surgery (P = 0.046). Serum cortisol concentrations were found to increase significantly over time for all animals (P < 0.001), but were not affected by surgeon experience., Conclusion: The results suggest that inexperienced surgeons affect their patients differently to experienced surgeons, potentially through tissue trauma or anaesthetic duration. The lack of difference in the cortisol concentrations reflects the large number of triggers for cortisol release and, potentially, that there was little difference between the groups in terms of perceived pain in the presence of good analgesia. Serum CRP concentration may be a more sensitive measure than serum cortisol of differences in surgical trauma., (© 2012 The Authors. Australian Veterinary Journal © 2012 Australian Veterinary Association.)

Background: Newer NSAIDs that more selectively target the induced isoform of the cyclooxygenase enzyme (COX2) activity might reduce adverse effects while preserving therapeutic benefits of these drugs., Objectives: To compare the effect of oral administration of multiple dose rates of meloxicam and phenylbutazone (PBZ) on gastric mucosal integrity in horses., Animals: Twenty-five light breed horses., Methods: In vivo toxicity study. Horses were randomly assigned to 5 treatment groups, receiving placebo, PBZ (4.4 mg/kg PO q12h day 1, 2.2 mg/kg PO q12h for 4 days, 2.2 mg/kg PO q24h for 9 days), or 3 dose rates of meloxicam (0.6 mg/kg q24h, 1.8 mg/kg q24h, 3.0 mg/kg q24h) for 14 days. Sucrose permeability testing was performed on Day 0 (before treatment) and on Day 13. All personnel involved with data collection or analysis were blinded to treatment., Results: Administration of PBZ at the above dose rate significantly increased gastric permeability to sucrose, evidenced by increased peak serum sucrose concentrations (280-1,580 pg/μL, P = .001) after treatment. Similar changes were not evident after administration of meloxicam at any dose rate tested, or in control horses (P > .05). Treatment was not associated with significant differences in ulceration of the squamous or glandular mucosa. Peak sucrose concentrations were not correlated with serum total protein or albumin concentrations (R(2) = -0.07, P = .61, R(2) = -0.08, P = .58, respectively)., Conclusion and Clinical Importance: These results suggest that PBZ was associated with greater compromise to gastric mucosal integrity than meloxicam., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Background: A strategy of prophylactic splenic angioembolization using observation failure risk (OFR) computed tomographic (CT) scan criteria has been proposed recently. The main aim of the present study was to evaluate the relevance of the criteria in terms of delayed splenic rupture in patients with blunt splenic injury., Methods: All patients with blunt splenic injuries admitted consecutively between January 2005 and January 2010 to our institution were included. Clinical, CT scan, and angiographic data, initial management, and outcome were noted. Patients managed expectantly were classified according to OFR CT scan criteria (high OFR was defined by at least one of the following CT scan signs: blush, pseudoaneurysm, Organ Injury Scale [OIS] grade III with a large hemoperitoneum, and OIS grade IV or 5). Initial management success was especially studied., Results: Among the 208 patients included, 161 (77%) were treated by observation (35 OIS grade I, 64 OIS grade II, 33 OIS grade III, 18 OIS grade IV, and 11 OIS grade V) and 129 (80%) were men, with a mean (SD) age of 36.1 (18.7) years and a mean (SD) Injury Severity Score of 20.8 (15.4). Forty-nine patients (30%) had high OFR CT scan criteria. Thirteen patients (8%) experienced observation failure. High OFR CT scan criteria (odds ratio, 11; 95% confidence interval, 2.5-47.5) and patients 50 years and older (odds ratio, 33.9; 95% confidence interval, 6.2-185.5) were independent factors related to observation failure. The positive predictive value of OFR CT scan criteria for observation failure was 18%, and the negative predictive value was 96%. The corresponding values were 67% and 90%, respectively, in patients 50 years and older and 3% and 99%, respectively, in patients younger than 50 years., Conclusion: OFR CT scan criteria lack specificity to predict observation failure, mainly in patients younger than 50 years. Age should be considered when identifying patients requiring prophylactic splenic angioembolization., Level of Evidence: Diagnostic study, level III.

This study explores the therapeutic potential of heritage-object handling in nurse-patient encounters with women facing cancer. Ten women participated in an object-focused conversation with a nurse specialist. Sessions were audio-tape recorded and transcribed. Kleinian theory framed the analysis to reveal the individual ways women 'used' the object in the session. Professionally observed heritage-object handling provides an aid to discussion with patients and has potential as an assessment platform for therapeutic work or as an intervention approach in its own right. Further longitudinal controlled trials are needed to evaluate such benefits, particularly given the depth of the talk revealed in this study.

Background: Little is known about the communication of everyday pain between young children and their parents, i.e. when children experience pain resulting from minor injury or illness that occur in everyday life. This study aimed to gain an in-depth understanding of how parents make sense of their young children's expression of everyday pains and how they respond., Methods: Parents (n = 48) of children (1-5 years inclusive) participated in focus group discussions at seven children's centres across England where they were asked to describe their children's communication of everyday pain. Thematic analysis was used to analyse the data., Results: Six main themes were identified in the parents' discourse. Parents described children's pain communication as (1) sharing common elements, but unique to each child; (2) having multifaceted pain and non-pain-related purposes; (3) challenging to interpret; (4) influenced by their own pain-related communication; (5) requiring a variety of pharmacological, psychological and physical strategies to manage. The sixth theme that emerged from the data related to parents' dissatisfaction with health care providers, particularly general practitioners' sometimes quick dismissal of parental concerns about their children's pain and illness complaints., Conclusions: These findings suggest that parents have well developed, although personal, ways of recognizing and responding to their children's communication of pain, but also experience uncertainty in their judgments. Parents would benefit from information about the developmental aspects of pain and should be included as active partners in their children's pain assessment and management., (© 2012 European Federation of International Association for the Study of Pain Chapters.)

Background: Safety of meloxicam, a potent NSAID with selective COX-2 inhibition, has not been evaluated in horses., Objectives: To evaluate pharmacokinetics and safety of single and repeated oral doses of meloxicam in adult horses., Animals: Forty-nine healthy, university-owned adult lightbreed horses., Methods: Study conducted in 2 parts. Part I addressed pharmacokinetics of single oral dose meloxicam (0.6 mg/kg) in 16 horses. Part II, 33 horses were randomly assigned to 5 treatment groups to assess prolonged administration (0.6 mg/kg PO q24h for 6 weeks, n = 7) or higher doses (1.8 mg/kg, n = 7, or 3.0 mg/kg PO q24h, n = 7) of meloxicam for 2 weeks, compared with control horses (placebo, n = 7, or phenylbutazone, 4.4 mg/kg q12h on day 1, 2.2 mg/kg q12h for 4 days, then 2.2 mg/kg q24h for 9 days, n = 5)., Results: Maximum plasma concentration following a single oral dose of meloxicam was 915.1 ± 116.9 ng/mL and elimination half-life 10.2 ± 3.0 hours. Meloxicam (0.6 mg/kg, q24h, PO for 6 weeks) yielded plasma concentrations between 100 and 1000 ng/mL and was well tolerated by healthy adult horses. Administration of 3-5 times the recommended dose of meloxicam was associated with decreased total serum protein and albumin concentrations, gastrointestinal damage, renal damage, or bone marrow dyscrasia. PBZ administration was associated with the development right dorsal colitis, gastric ulceration, and protein losing enteropathy in 2 horses., Conclusions and Clinical Importance: Administration meloxicam at 0.6 mg/kg q24h was well tolerated for 6 weeks, without drug accumulation in plasma. Higher doses were associated with dose-dependent adverse effects typical of class of drugs., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Extensive periosteal stripping (PS) is a risk factor for post-radiation pathologic fracture following surgery for extremity soft tissue tumors. The purpose of this study was to determine the effects of PS on bone structure and mechanical properties. Thirty-one skeletally mature mice underwent PS, with circumferential removal of periosteum from an 8-mm segment of the mid-diaphysis of the left femur. Thirty-one control mice underwent sham surgery in which the femur was isolated without manipulation of the periosteum. At 2, 6, 12, or 26 weeks following surgery, the left femora were examined by micro-CT to quantify cortical thickness (CtTh), cross-sectional area (CSA), bone volume (BV), and polar moment of inertia (PMI). Three-point mechanical bend testing was performed and peak load, stiffness, and energy to failure were determined. PS resulted in significantly decreased CtTh, CSA, BV, and PMI at all time points. Peak load, stiffness, and energy to failure were significantly reduced at 2, 6, and 12 weeks. There were no significant differences in mechanical properties at 26 weeks. In this mouse model, extensive circumferential PS resulted in sustained changes in bone structure that were still evident after 6 months, accompanied by reductions in bone strength that persisted for at least 3 months., (Copyright © 2011 Orthopaedic Research Society.)

Background: Musculoskeletal pain is detrimental to quality of life (QOL) and disruptive to activities of daily living. It also places a major economic burden on healthcare systems and wider society. In 2006, the Welsh Assembly Government (WAG) established a three tiered self-referral Occupational Health Physiotherapy Pilot Project (OHPPP) comprising: 1.) telephone advice and triage, 2.) face-to-face physiotherapy assessment and treatment if required, and 3.) workplace assessment and a return-to-work facilitation package as appropriate. This study aimed to evaluate the feasibility and cost-effectiveness of the pilot service., Methods: A pragmatic cohort study was undertaken, with all OHPPP service users between September 2008 and February 2009 being invited to participate. Participants were assessed on clinical status, yellow flags, sickness absence and work performance at baseline, after treatment and at 3 month follow up. Cost-effectiveness was evaluated from both top-down and bottom-up perspectives and cost per Quality Adjusted Life Year (cost/QALY) was calculated. The cost-effectiveness analysis assessed the increase in service cost that would be necessary before the cost-effectiveness of the service was compromised., Results: A total of 515 patients completed questionnaires at baseline. Of these, 486 were referred for face to face assessment with a physiotherapist and were included in the analysis for the current study. 264 (54.3%) and 199 (40.9%) were retained at end of treatment and 3 month follow up respectively. An improvement was observed at follow up in all the clinical outcomes assessed, as well as a reduction in healthcare resource usage and sickness absence, and improvement in self-reported work performance. Multivariate regression indicated that baseline and current physical health were associated with work-related outcomes at follow up. The costs of the service were £194-£360 per service user depending on the method used, and the health gains contributed to a cost/QALY of £1386-£7760, which would represent value for money according to current UK thresholds. Sensitivity analyses demonstrated that the service would remain cost effective until the service costs were increased to 160% per user., Conclusions: This pragmatic evaluation of the OHPPP indicated that it was likely to be feasible in terms of service usage and could potentially be cost effective in terms of QALYs. Further, the study confirmed that improving physical health status for musculoskeletal pain patients is important in reducing problems with work capacity and related costs. This study suggests that this type of service could be potentially be useful in reducing the burden of pain and should be further investigated, ideally via randomised controlled trials assessing effectiveness and cost-effectiveness.

Infectious respiratory pathogens were the suspected cause of 480 outbreaks investigated by the Centers for Disease Control and Prevention's Epidemic Intelligence Service officers during 1946-2005. All epidemic-assistance investigation reports and associated articles from scientific journals were reviewed. Investigations identified 25 different infectious respiratory pathogens including, most frequently, tuberculosis, influenza, and legionellosis. Other bacterial-, viral-, and fungal-related pathogens also were identified. Epidemic-assistance investigations were notable for first identifying Legionnaires disease and Pontiac fever, hantavirus pulmonary syndrome, and new strains of human and avian influenza, as well as emerging challenges (e.g., multidrug-resistant tuberculosis and pneumococcus). The investigations provided clinical insights into such diseases as pulmonary anthrax and identified high risks of serious respiratory illnesses for persons infected with human immunodeficiency virus, other immunocompromised persons, and persons with diabetes. They identified settings placing persons at high risk of acquiring disease, including nursing homes, prisons, homeless shelters, and hospitals. Travel also placed persons at risk. Key environmental factors related to spread of diseases and occupational risks for brucellosis and psittacosis were identified. The outbreak investigations constitute a wealth of prevention experience and provide the basis for recommendations to mitigate outbreaks and reduce future risks.

Mucosal integrity may be objectively assessed by determination of the absorption of exogenous substances such as sucrose. Gas chromatography-mass spectrometry (GC/MS) and liquid chromatography-mass spectrometry (LC/MS) have been reported for the accurate quantification of low concentrations of sucrose in serum. LC/MS offered the advantage of high sensitivity and mass selectivity without the need for extensive sample derivatization required for GC/MS methods. However, the high polarity and non-volatile nature of the sucrose molecule renders LC/MS techniques challenging. Previously published reports lacked sufficient detail to permit replication of methodology. Problems encountered with existing protocols included poor peak resolution and weak fragmentation of the parent molecule. This communication describes a LC/MS protocol developed to provide improved resolution and product detection., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)

Determining circulating equine insulin concentrations is becoming increasingly important in equine clinical practice and research. Most available assays are optimized for human medicine, but there is strong equine cross-reactivity because of the highly conserved nature of insulin. To identify an accurate and reliable assay for equine insulin, 6 commercial immunoassays were evaluated for precision, accuracy, and specificity. Only 1 assay initially reached the requisite standard: Mercodia Equine Insulin Enzyme-linked Immunosorbent assay (ELISA). Plasma matrix interferences were identified when the provided assay buffer was used with the Siemens Count-a-Coat Insulin radioimmunoassay (RIA) but not when charcoal-stripped equine plasma was used as the diluent. This modified RIA and the Mercodia Equine Insulin ELISA were evaluated further by directly examining accuracy by comparing their results for 18 equine plasma samples with values obtained using liquid chromatography and high-resolution/high-accuracy mass spectrometry (LC-MS). Compared with LC-MS measurements, the modified Siemens Insulin RIA rendered a moderate Lin's concordance coefficient (ρ(c)) of 0.41, whereas the Mercodia Equine Insulin ELISA rendered a very poor ρ(c) of 0.06. This suggests that the Siemens Insulin RIA is appropriate to use for routine evaluations when LC-MS is not available., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: The objectives of this paper were to (i) identify the behavioural cues used by parents to detect young children's transient pain from minor illnesses or injuries ('everyday pain'); and (ii) perform an initial psychometric evaluation of the Parents' Post-operative Pain Measure (PPPM) in the context of children's everyday pain., Method: Cross-sectional Internet survey., Results: One thousand seven hundred sixteen parents of children (1-6 years) completed the survey. The parents reported more behaviours when children had pain from minor illnesses than from minor injuries (9.6 ± 3.9 vs. 2.5 ± 2.3, P < 0.001). Principal component analysis of the PPPM revealed a two-factor solution for illness-related pain and a three-factor solution for injury-related pain. Behavioural cues varied with characteristics of children (age, gender and prior hospital experience) and parents (gender, age and parenting experience)., Conclusions: The PPPM is a promising tool for parental assessment of children's pain in everyday situations. Further research is needed to determine its utility in facilitating communication between parents and healthcare professionals, and in improving the management of young children's pain., (© 2010 Blackwell Publishing Ltd.)

There are currently two known serotypes of equine adenovirus (EAdV), equine adenovirus type 1 (EAdV1) and equine adenovirus type 2 (EAdV2); EAdV1 is predominantly associated with upper respiratory tract infections while EAdV2 appears to have a higher association with gastrointestinal infection, however, very little is known about the prevalence of these viruses in horse populations in Australia. In this study we tested 122 serum samples obtained from horses in New South Wales, Australia, using a standard serum neutralization (SN) assay and ELISA. Ninety-seven of the 122 sera displayed had moderate to high titers of antibodies to EAdV1 and/or EAdV2. Eighteen of the 122 sera were positive for both EAdV1 and EAdV2. In contrast, only thirty-seven positive samples were detected using the ELISA. These results suggest that EAdV1 and EAdV2 infections are widely prevalent in the horse population tested and that SN is currently the most suitable assay for the detection of EAdV1 and EAdV2 antibodies in equine serum., ((c) 2009 Elsevier B.V. All rights reserved.)

Background: Little is known about the development of language to express pain in the young or how children and parents verbally communicate when young children have everyday minor illnesses and injuries., Methods: UK parents of children between the ages of 1 and 6 were invited to complete an Internet survey on children's pain language during everyday situations of minor illness or injury., Results: Of the 1716 parents completing the survey, 45% reported their child had at least one word to express pain by 17 months of age, increasing to 81% by 23 months of age. Children used different words based on their age and in the contexts of minor illnesses and injuries, with words for expressing pain related to illness emerging slightly later. Children's language was purposeful in describing causes of pain and requesting specific forms of assistance from parents even in the very youngest age groups. Parents' communicated with their children primarily to gain further information about the source and nature of pain and to direct children's behaviour., Conclusions: Children rapidly develop an extensive vocabulary to describe pain between 12 and 30 months of age, with words for pain from injury emerging first and reflecting the development of normal speech acquisition. The differences in verbal expressions in the context of minor illnesses and injuries suggest that children make a cognitive distinction between the origins and sensory aspects of pain. These findings can help parents, childcare and healthcare professionals to appreciate the early communication capabilities of young children and to engage in more effective pain assessment and management for young children.

Objective: To investigate health information needs of users of a health information website for children and young people., Methods: A prospective analysis was conducted of unsolicited information requests to the Children First for Health (www.childrenfirst.nhs.uk) website, an NHS-run health and hospital online information resource for children, young people and families. All specific and general enquiries were recorded prospectively and coded according to health topic, age of the enquirer and web pages accessed., Results: There were 2865 (62%) general health information and 924 (21%) specific enquiries received over an 18-month period (6.3 enquiries per day). More general enquiries were received about adolescent (64%) than children's (36%) health issues. The most common topics were psychosocial issues, hospital and health services, and normal growth and development. Only 1% of requests for information related to smoking, alcohol and drugs., Conclusion: Children and adolescents are active users of the Internet for health information. The results of this study highlight the health topics that are of greatest interest to children and young people., Practice Implications: The findings provide objective data on health information topics of interest to UK children and young people and can be used to guide development of health information aimed at UK youth.

Reason for Performing Study: L-tryptophan is a common ingredient in equine calmative products, but its effectiveness has not been demonstrated in horses., Hypothesis: To determine whether a commercial dose of L-tryptophan increases plasma tryptophan and alters behaviour in horses fed a roughage or concentrate meal., Methods: L-tryptophan (6.3 g) or placebo (water) was administered per os in a cross-over design, to 12 Thoroughbred horses (503 +/- 12.1 kg bwt), just before a meal of lucerne hay or oats. Plasma tryptophan was measured by gas chromatography. Horse behaviour was observed in an empty enclosure, then in the presence of an unfamiliar person and a novel object., Results: Total plasma tryptophan increased 3-fold in both studies, peaking 1.5-2 h after dosing. After the peak, tryptophan remained high for several hours if the horses had been fed hay, but fell sharply if fed oats, consistent with the glycaemic responses to these meals. However, the ratio of tryptophan to 4 large neutral amino acids (phenylalanine, tyrosine, leucine and isoleucine) increased in the tryptophan-treated horses to a similar extent and for a similar duration, with both diets. The presence of a stranger or novel object increased heart rate (P<0.05), but caused no behavioural effects that were altered by tryptophan, regardless of the diet., Conclusions: Plasma tryptophan increases when tryptophan is administered at a dose used in some commercial products, but this is not reflected by marked behavioural changes in the horse., Potential Relevance: Further work is required to refine behavioural tests and identify an effective dose of L-tryptophan in the horse.

Use of the internet to provide health information to young people is a relatively recent development. Few studies have explored young people's views on how they use internet health websites. This study investigated the navigation, design and content preferences of young people using the Children First for Health (CFfH) website. Young people from five secondary schools completed an internet site navigation exercise, website evaluation questionnaire and participated in informal discussions. Of the participants, 45 percent visited the website section aimed at older adolescents within their first two clicks, regardless of their age. There were conflicting preferences for design and strong preference for gender-specific information on topics such as appearance, relationships, fitness and sexual health. The findings indicate the importance of gaining young people's views to ensure that health information websites meet the needs of their intended audience. Cooperation from schools can facilitate the process of gaining young people's views on internet website navigation, design and content.

Insulin-like growth factor-1 could be a useful marker in the horse for diagnostic, selection, or forensic purposes, provided its physiological regulation is well understood. The objective of this study was to investigate factors, such as acute exercise, fitness training, time of day, sex, and age, that may influence serum IGF-1 in normal, healthy horses. Throughout a 9-wk training program, 6 geldings maintained a mean (+/- SEM) IGF-1 concentration of 302 +/- 29 ng/mL. Moderate or high intensity exercise had no effect on IGF-1 concentrations, when pre- and postexercise values were compared. Over a 24-h period, there was some variation in IGF-1 concentrations but no clear diurnal rhythm. Concentrations of IGF-1 were measured in a large population of thoroughbred horses (1,880) on 3 continents. The population deviated slightly from a normal distribution (P < 0.001) because of large IGF-1 concentrations in 10 horses. The global mean IGF-1 concentration was 310 +/- 2.2 ng/mL, with a greater mean value (P < 0.001) in gonad-intact males (336 +/- 5.6 ng/mL) than in females (303 +/- 3.2 ng/mL) or geldings (302 +/- 3.2 ng/mL). However, the greatest IGF-1 concentrations observed for all stallions, mares, and geldings were 627, 676, and 709 ng/mL, respectively. In mares and geldings, IGF-1 concentrations showed a gradual decrease with advancing age (P < 0.001), but the effect was much less marked in stallions. This study confirms that IGF-1 concentrations are stable, compared with GH concentrations, in the horse and that a meaningful measure of IGF-1 status can be obtained from a daily serum sample.

Objective: To investigate the hypoalgesic effects of transcutaneous electrical nerve stimulation (TENS) upon low back pain (LBP) in people with multiple sclerosis (MS)., Design: A randomized double-blind placebo controlled clinical pilot study., Subjects and Setting: Fifteen people with MS were recruited and randomly allocated to one of the following groups under double blind conditions (n = 5 per group): TENS 1 (4 Hz, 200 micros), TENS 2 (110 Hz, 200 micros), placebo TENS., Interventions: Treatment was applied for 45 minutes three times a week for six weeks with a four-week follow-up., Outcome Measures: The following outcome measures were taken at weeks 1, 6, and 10: visual analogue scale (VAS) (for current LBP, right leg pain, left leg pain); Leeds Multiple Sclerosis Quality of Life Questionnaire; Roland Morris Disability Questionnaire; Short Form-36 (SF-36) Version 1; and the McGill Pain Questionnaire (MPQ). VAS for current LBP, right and left leg pain were also taken before and after treatment, and once a week during the follow-up period., Results: Analysis showed no statistically significant effects for any of the data. However, both active treatment groups showed a trend of improvement in the majority of the outcome measures., Conclusion: Active TENS was more effective than placebo TENS in decreasing VAS scores following each treatment although results were not statistically significant. Further work in this area is warranted and should include a larger number of participants in the form of a randomized controlled clinical trial to determine the efficacy of this modality.

Background: We prospectively assess if there are any outcome differences between men and women undergoing coronary artery bypass graft surgery., Study Design: This is an eight-year, prospective, hospitalization cohort study. Data were collected on 225 variables concurrently with admission. The main outcome was mortality. In addition, we evaluated 12 morbidity outcomes. To minimize confounding, we controlled for 18 other variables., Results: We analyzed 5,324 patients (1,742 women; 3,582 men). Women were significantly older, with more African Americans and more Medicaid-insured (p < 0.05). Men had significantly higher body surface area, creatinine, tobacco history, prior myocardial infarctions, left ventricular hypertrophy, and cardiac pump time (p < 0.05). Women had significantly more diabetes, hypercholesterolemia, hypertension, previous cerebrovascular disease, urgency of the surgical procedure, fewer arterial grafts, and reduced functional capacity by the New York Heart Association classification (p < 0.05). Using multiple regression analysis there was no difference for mortality, positive bacterial cultures, ICU length of stay, arrhythmias, reoperation for bleeding, pulmonary complications, gastrointestinal complications, and return to the ICU. Women had significantly more intraoperative complications (RR = 2.09, 95% CI 1.35-3.23), length of stay (RR = 1.01, 95% CI 1.002-1.027), and low cardiac output conditions (RR = 1.10, 95% CI 1.01-1.20). Males developed more neurologic complications (RR = 0.85, 95% CI 0.75-0.95)., Conclusions: Women undergoing coronary artery bypass graft surgery have more comorbidities at surgical presentation compared with men. Women have more unadjusted mortality, which is confounded by the difference in age and body surface area. But, even after multiple adjustments, female gender is a predictor of higher morbidity in patients undergoing coronary artery bypass graft., (Copyright 2003 by the American College of Surgeons)

Despite over two decades of clinical use, the neurophysiological and anti-nociceptive effects of transcutaneous electrical nerve stimulation (TENS) have yet to be definitively described. The current study was designed to examine the effect of TENS on the RIII nociceptive reflex elicited in healthy human subjects; the H-reflex was measured concomitantly to monitor changes in alpha-motoneuron excitability. Following approval from the university's ethical committee, 50 healthy human volunteers (25 male and 25 female) participated in the study. The subjects ranged in age from 18 to 30 years (mean 22, SD 3). Subjects were randomly allocated equally to a control group or one of four TENS groups. In the TENS groups, stimulation was applied for a total of 15 min over the sural nerve in the left leg. Ipsilateral RIII and H-reflexes were recorded five times during the 45 min experimental period. In addition, subjects also rated pain associated with the RIII reflex using a computerized visual analogue scale (VAS). Statistical analysis using two-way repeated-measures ANOVA showed no differences between groups for H-reflex, RIII reflex nor VAS data. These results suggest that TENS does not significantly affect either of the two reflexes, at least using the parameters and application time in the current study.

Livers of bullfrogs (Rana catesbeiana) from a polychlorinated biphenyl (PCB) contaminated watershed and hazardous waste site located in Pickens County, South Carolina, contained significantly higher concentrations of PCBs (2.33 and 2.26 ppm, respectively) than those from a reference site (0.05 ppm). Green frogs (R. clamitans) from the two contaminated sites also accumulated higher levels of PCBs (2.37 and 3.88 ppm, respectively) than those from the reference site (0.02 ppm). No temporal variation was observed in PCB concentrations of bullfrogs or green frogs from the contaminated sites between 1992 and 1993. Levels of PCBs in the livers of northern water snakes (Nerodia sipedon) were significantly higher in snakes from the contaminated watershed (13.70 ppm) than in those from the waste site (2.29 ppm) and two reference sites (2.50 and 1.23 ppm). When compared to frogs, significantly higher bioaccumulation occurred in water snakes from the contaminated watershed. No significant differences in PCB levels were found with respect to sex or body size (snout-vent length (SVL) or body mass) for frogs or snakes. PCBs were detected also in eggs of both frogs and snakes. Results of this study provide baseline data and document the bioaccumulation of PCB residues in frog and snake tissues; however, the significance of these tissue residues to reproduction, survival, growth/development, and population dynamics in contaminated habitats is unknown.

Objective: To study the effect of transcutaneous electrical nerve stimulation (TENS) and interferential therapy (IFT) upon the RIII nociceptive reflex and H-reflex., Design: Double-blind conditions., Participants: Seventy healthy subjects were randomly allocated to one of seven groups (n = 10 per group): Control, TENS 1 (5 Hz), TENS 2 (100 Hz), TENS 3 (200 Hz), IFT 1 (5 Hz), IFT 2 (100 Hz), IFT 3 (200 Hz)., Intervention: In the treatment groups, stimulation was applied over the right sural nerve for 15 minutes., Main Outcome Measures: Ipsilateral RIII and H-reflexes were recorded before treatment, immediately after treatment, and subsequently at 25, 35, and 45 minutes. Subjects rated the pain associated with the RIII reflex using a computerized visual analogue scale (VAS)., Results: Statistical analysis using ANOVA showed no significant differences between baseline and posttreatment measurement for RIII reflex, H-reflex, or VAS data., Conclusion: These results suggest that neither type of electrical stimulation (TENS or IFT) affects the RIII or H-reflexes, at least using the parameters and application time in this study.

Background: The purposes of this study were to assess the effects of levobupivacaine on uterine blood flow and fetal well-being and to compare its placental transfer with that of bupivacaine and ropivacaine., Methods: After a control period, pregnant ewes that were fitted with instruments for long-term monitoring were randomized to receive a two-step intravenous infusion of levobupivacaine, bupivacaine, or ropivacaine, in a blinded manner, for 1 h. Maternal and fetal hemodynamics were monitored during the study. Arterial blood samples were drawn at 30 and 60 min of infusion from the mother and fetus to determine the acid-base status (60 min only) and serum drug concentrations. The fetal brain, heart, liver, lungs, adrenal glands, and kidneys were obtained to measure tissue drug levels., Results: Maternal blood pressure, central venous and intraamniotic pressures, acid-base status and uterine blood flow were unaffected by any drug infusion. In contrast to the other two local anesthetics, the infusion of bupivacaine was associated with a small but significant decrease in the ewe's heart rate. At the end of the study, the heart rate in the bupivacaine-treated animals was significantly less than in the animals treated with the other two drugs. All fetuses were in good condition at the start of study, and none of the local anesthetics affected fetal well-being. No significant differences were found among the three drugs in the maternal serum, fetal serum, fetal tissue concentrations, and tissue:serum concentration ratios., Conclusions: Levobupivacaine was similar to bupivacaine and ropivacaine in causing no important hemodynamic changes in the pregnant ewe and fetus. There were no significant differences in the fetal serum and tissue levels of the drugs.