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OBJECTIVE: In the Netherlands, out-of-hours General Practice Cooperatives (GPCs) increasingly collaborate with Emergency Departments (EDs) to form an Emergency Care Access Point (ECAP). ECAPs aim to decrease the number of low-urgent ED attendances, of which many compromise minor traumatic injuries. In this study, we evaluated the impact of ECAP implementation on the incidence of minor traumatic injuries in the ED.METHODS: We evaluated a total of 2772 ED patients who presented with a minor traumatic injury (categorized into traumatic wounds and isolated extremity injuries) 1 year before and 1 year after ECAP implementation. We compared patient characteristics, throughput, diagnosis, treatment and follow-up before and after ECAP implementation.RESULTS: ECAP implementation was associated with a reduction in ED volume for minor traumatic injuries: -12.4% for isolated extremity injuries (1249 vs. 1094) and -74.6% for traumatic wounds (342 vs. 87). Multivariable logistic regression analysis controlling for patient characteristics showed that ECAP implementation was associated with higher rates of substantial injuries in the ED (OR 1.20, 95% CI = 1.01-1.43), and more patients requiring outpatient follow-up.CONCLUSION: Implementation of an ECAP was associated with a reduction of ED utilization by patients with minor traumatic injuries, traumatic wounds in particular. This healthcare intervention may therefore help to reduce ED utilization for low-urgent complaints.

Serum creatinine (SCr) in humans has proven to be a reliable biomarker of body protein breakdown and/or muscle mass change. This study set out to investigate the potential of SCr to indicate a loss in sow muscle mass over lactation, validated against 3 methyl histidine (3MH) and blood urea nitrogen (BUN), markers of dietary and/or body protein breakdown. A total of 40 sows were allocated to four treatment groups aimed to induce body weight changes by restrictively feeding sows using a stepwise percentage reduction model. Data were pooled and reallocated into three groups representing the 25th , 50th and 75th percentiles based on body weight change over lactation in the range -22.3 to -4.1% (treatment 25), -4.0 to 6.2% (Treatment 50), and 6.3-15.2% (Treatment 75). Indirect measures for the prediction of protein (3MH, BUN) or fat change (caliper, P2) were taken on entry into the farrowing house, day 5 of lactation, and at weaning. Serum was collected on these days, and SCr, 3MH and BUN were analysed. Piglet weaning weight and average daily feed intake did not differ between treatments (p > .05). There were no changes (p > .05) in indirect measures of body composition (sow caliper score, P2) and analytes (SCr, 3MH, BUN) over lactation. By day 20, those sows in treatment 25 had higher (p .05) and did not correlate with SCr change (p > .05) but were highly correlated to BUN change (R2 = 0.691, p < .001). The data suggested that concentrations of SCr and BUN may have been the result of dietary and/or body protein breakdown and/or changes in muscle mass. In the current testing conditions, SCr was not a reliable marker of changes in muscle mass.

Knowledge of soil microtopography and its changes in space and over time is important to the understanding of how tillage influences infiltration, runoff generation and erosion. In this study, the use of a terrestrial laser scanner (TLS) is assessed for its ability to quantify small changes in the soil surface at high spatial resolutions for a relatively large surface area (100 m2). Changes in soil surface morphology during snow cover and melt are driven by frost heave, slaking, pressure exertion by the snowpack and overland flow (erosion and deposition). An attempt is undertaken to link these processes to observed changes at the soil surface. A new algorithm for soil surface roughness is introduced to make optimal use of the raw point cloud. This algorithm is less scale dependent than several commonly used roughness calculations. The results of this study show that TLSs can be used for multitemporal scanning of large surfaces and that small changes in surface elevation and roughness can be detected. Statistical analysis of the observed changes against terrain indices did not yield significant evidence for process differentiation.

Three decades of government budget cuts have placed significant financial pressure on Australia's cultural institutions. Institutions are increasingly trying to attract non-government funding to fulfil their legislative mandates to collect, maintain, and exhibit Australian and international art, to educate and inform the public, and preserve Australia's political, social, and cultural history. Evidence suggests that, despite these efforts, sources of funding have not changed significantly. Budget cuts are impacting a range of areas including acquisitions, preservation, digitisation, as well as limiting access to researchers and the public. This paper concludes that a public review of the roles played by cultural institutions is required, including consideration of the level of public funding provided. To do otherwise is to ignore the importance of Australia's cultural heritage.

The quantification of pulse energy during cardiopulmonary bypass (CPB) post-oxygenator is required prior to the evaluation of the possible beneficial effects of pulsatile flow on patient outcome. We therefore, evaluated the impact of three distinctive oxygenators on the energy indicators energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE) in an adult CPB model under both pulsatile and laminar flow conditions. The pre- and post-oxygenator pressure and flow were measured at room temperature using a 40% glycerin-water mixture at flow rates of 1, 2, 3, 4, 5, and 6 L/min. The pulse settings at frequencies of 40, 50, 60, 70, and 80 beats per minute were according to the internal algorithm of the Sorin CP5 centrifugal pump. The EEP is equal to the mean pressure, hence no SHE is present under laminar flow conditions. The Quadrox-i Adult oxygenator was associated with the highest preservation of pulsatile energy irrespective of flow rates. The low pressure drop-high compliant Quadrox-i Adult oxygenator shows the best SHE performance at flow rates of 5 and 6 L/min, while the intermediate pressure drop-low compliant Fusion oxygenator and the high pressure drop-low compliant Inspire 8F oxygenator behave optimally at flow rates of 5 L/min and up to 4 L/min, respectively. In conclusion, our findings contributed to studies focusing on SHE values post-oxygenator as well as post-cannula in clinical practice. In addition, our findings may give guidance to the clinical perfusionist for oxygenator selection prior to pulsatile CPB based on the calculated flow rate for the individual patient.

Autism spectrum disorders (ASD) are associated with early disturbances in brain maturation processes and these interferences presumably have their consequences for the progressive emergence of cognitive deficits later in life, as expressed in intelligence profiles. In this study, we addressed the impact of age on cognitive functioning of 6- to 15-year-old children and adolescents with ASD. Intelligence profiles were measured by the Wechsler Intelligence Scale for Children and compared among four consecutive age cohorts (children aged 6.17–8.03 years, 8.04–9.61 years, and 9.68–11.50 years and adolescents aged 11.54–15.85 years) of 237 high-functioning boys with ASD. The results clearly demonstrated that the global intelligence level was lower in children aged 8 years and older, when compared with 6- and 7-year-old children with ASD. This is mostly due to the Freedom From Distractibility factor, suggesting that older children were less able to sustain their attention, they were more distractible, or had more graph motor difficulties. Moreover, an effect of age was also found with respect to the relatively poor performance on the subtest Comprehension when compared with other verbal comprehension subtests, indicating that specifically the impairments in verbal comprehension and social reasoning abilities were more profound in older children when compared with 6- and 7-year-old children with ASD. Findings of this cross-sectional study showed that it is relevant to take age into account when evaluating the impact of cognitive impairments on intelligence in children with ASD, because the impact of these developmental disorders might be different at different ages. Autism Res 2014, 7: 527–534. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.

REASONS FOR PERFORMING STUDY: Equine penile and preputial squamous cell carcinoma (SCC) is a potentially lethal disease of which little is known regarding the relationship between tumour characteristics and prognosis. OBJECTIVES: To assess the relationship between tumour differentiation grade (tumour subtype), presence of papillomaviruses, expression of viral genes (E2, E6, L1), nuclear proteins p53 and Ki67 and metastasis in equine penile and preputial SCC and to assess the relationship of tumour subtype, presence of papillomavirus type 2, p53 and Ki67 with survival. STUDY DESIGN: Retrospective case-control study using archived material. METHODS: Samples (n = 103) from 87 horses with penile and/or preputial intraepithelial neoplasia (PIN), papilloma or SCC and corresponding case files were evaluated. Tumours were graded microscopically and p53 and Ki67 expression evaluated immunohistochemically. Equine papillomavirus (EcPV) types 2 and 3 DNA was detected by conventional PCR. Real-time PCR was used for quantification of E2, E6 and L1 mRNA. RESULTS: Equine papillomavirus type 2 DNA was detected in 89.4% and EcPV3 in 1.5% of horses. No differences in quantitative expression of E2, E6 and L1 oncogenes between subtypes were found. Expression of p53 and occurrence of metastasis were positively correlated to a less differentiated subtype (r = 0.429, P

REASONS FOR PERFORMING STUDY: Multiple in vitro studies assessing articular tissues have indicated that glucosamine and chondroitin sulphate may possess anti-inflammatory effects, but little is known of their clinical effects in vivo. Many old horses have stiff joints, which is likely to be attributable to inflammation and therapy with these nutraceutical compounds could improve joint function. OBJECTIVES: To assess the clinical effects of a mixed supplement on the improvement of stiff gait in aged horses. STUDY DESIGN: Randomised, blinded, placebo-controlled study. METHODS: A group of 24 geriatric equids (age 29 ± 4 years; mean ± s.d.) received either 3 months oral supplementation with a test compound (containing glucosamine, chondroitin sulfate and methyl sulfonyl methane), or a placebo. Kinematic outcome criteria (primary: stride length; secondary: carpal flexion, fore fetlock extension and tarsal range of motion) were objectively quantified on a treadmill at a walk and trot before and after treatment. RESULTS: Stride length did not change significantly in the treated horses at the end of the trial. In the control group, carpal flexion and fore fetlock extension were significantly increased (P

REASONS FOR PERFORMING STUDY: Penile and preputial papilloma and squamous cell carcinoma (SCC) are commonly diagnosed in horses. Papillomas have the potential to progress to potentially lethal SCC. Knowledge of pathogenetic mechanisms may help in prevention and definition of treatment targets. STUDY DESIGN: Retrospective study using archived material. OBJECTIVES: To determine the expression of cyclo-oxygenase 1 (COX-1), cyclo-oxygenase 2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) in penile and preputial normal tissue, papilloma and SCC in horses, and whether expression of these enzymes is influenced by degree of inflammation and differentiation grade. METHODS: Tumour differentiation grade, degree of inflammation and COX-1, COX-2 and mPGES-1 expression in 75 formalin-fixed paraffin embedded samples of penile and preputial papilloma and SCC of 68 horses were investigated by histopathology and immunohistochemistry. RESULTS: Inflammation was more prominent in SCC compared with papilloma. No correlation between expression of COX-1 or COX-2 and inflammation was found. Expression of mPGES-1 was weakly correlated with inflammation. Expression of COX-1, COX-2 and mPGES-1 was found in 42.6%, 50.7% and 96.0% of lesions respectively, but less than 1% of cells were immunopositive for COX-1 and COX-2 in 59.4% and 84.2% of cases respectively. Expression of COX-1 was moderately negatively correlated with differentiation grade, COX-2 was not correlated and mPGES-1 was poorly negatively correlated. CONCLUSIONS: Expression of COX-1 and COX-2 in penile and preputial SCC in the horse is poor and COX inhibitors may thus be of little value for prevention or treatment. Microsomal PGES-1 is more prominently expressed in well-differentiated tissue compared with poorly differentiated tissue. Further research on the role of mPGES-1 in carcinogenesis is needed to assess its potential use as a treatment target. Knowledge of arachidonic pathway enzyme expression and their role in equine penile and preputial carcinogenesis may help in developing preventive and therapeutic strategies.

Background This study investigated whether implementation of cell salvage of shed mediastinal and residual blood in all patients undergoing low-to-moderate-risk cardiac surgery reduces the need for allogeneic red blood cell (RBC) transfusion compared to patients not subjected to cell salvage. Study Design and Methods This retrospective cohort study included patients undergoing low-to-moderate-risk cardiac surgery with cardiopulmonary bypass without (control; n = 531) or with cell salvage (n = 433; Autolog, Medtronic). Study endpoints, including 24-hour blood loss and RBC requirements, were evaluated using adjusted logistic regression. Results Baseline characteristics were similar between groups. The cell saver group received 568 ± 267 mL of autologous blood. Median number of allogeneic RBC transfusions was higher in the control group (2 [1-5]) compared with the cell salvage group (1 [0-3]; p < 0.001). There were no clinically relevant differences in postoperative coagulation test results between groups. The relative risk (RR) for postoperative RBC transfusion was reduced to 0.76 (95% confidence interval [CI], 0.70-0.83; p < 0.0001) in the cell salvage group. Moreover, patients in the cell salvage group had a lower chance for myocardial infarction (RR, 0.26; 95% CI, 0.08-0.91; p = 0.035), whereas the cell salvage group was associated with a higher probability for intensive care discharge within 24 hours after surgery (RR, 1.08; 95% CI, 1.02-1.14; p = 0.009). Conclusion The use of cell salvage throughout the entire procedure reduces postoperative blood loss and allogeneic RBC transfusion. These findings advocate implementation of cell salvage in all patients undergoing on-pump cardiac surgery, irrespective of anticipated surgery-related blood loss. © 2013 American Association of Blood Banks.

Terrestrial Laser Scanners (TLS) provide a non-contact method to measure soil microtopography of relatively large surface areas. The appropriateness of the technology in relatation to the derived Digital Elevation Models (DEM) however has not been reported. The suitability of TLS for soil microtopography measurements was tested on-field for three large soil surface areas in agricultural fields. The acquired point clouds were filtered with a custom cloud import algorithm, and converted into digital elevation models (DEM) of different resolutions. To assess DEM quality, point clouds measured from different viewpoints were statistically compared. The statistical fit between point clouds from different viewpoints depends on spatial resolution of the DEM. The best results were obtained at the higher resolutions (0.02 to 0.04?cm), where less than 5 % of the grid cells showed significant differences between one viewpoint and the next (p?

A world-fixed sound presented to a moving head produces changing sound-localization cues, from which the audiomotor system could infer sound movement relative to the head. When appropriately combined with self-motion signals, sound localization remains spatially accurate. Indeed, free-field orienting responses fully incorporate intervening eye-head movements under open-loop localization conditions. Here we investigate the default strategy of the audiomotor system when localizing sounds in the absence of efferent and proprioceptive head-movement signals. Head- and body-restrained listeners made saccades in total darkness toward brief (3, 10 or 100 ms) broadband noise bursts, while being rotated sinusoidally (f=1/9 Hz, V(peak) =112 deg/s) around the vertical body axis. As the loudspeakers were attached to the chair, the 100 ms sounds might be perceived as rotating along with the chair, and localized in head-centred coordinates. During 3 and 10 ms stimuli, however, the amount of chair rotation remained well below the minimum audible movement angle. These brief sounds would therefore be perceived as stationary in space and, as in open-loop gaze orienting, expected to be localized in world-centred coordinates. Analysis of the saccades shows, however, that all stimuli were accurately localized on the basis of imposed acoustic cues, but remained in head-centred coordinates. These results suggest that, in the absence of motor planning, the audio motor system keeps sounds in head-centred coordinates when unsure about sound motion relative to the head. To that end, it ignores vestibular canal signals of passive-induced head rotation, but incorporates intervening eye displacements from vestibular nystagmus during the saccade-reaction time.

Summary Squamous cell carcinoma (SCC) is the most common tumour of the penis and prepuce of the horse and is found mainly in older animals. Reports on breed predilection for penile tumour formation are equivocal but castration, coat colour, poor genital hygiene and various infectious agents have been suggested to predispose to the development of SCC. Careful assessment of the primary tumour is an important first step in the design of an optimal treatment protocol. Tumour size, invasiveness, differentiation grade and presence of metastases are relevant to the decision to pursue additional diagnostic procedures or specific treatment options. Complete elimination of the neoplasm and, therefore, risk of recurrence is highly dependent on the type of therapy chosen. However, the size and histopathological features of the primary tumour are also important factors with respect to prognosis. This review describes the clinical and pathological features of penile and preputial SCC in the horse and proposes a standard staging system.

Penile and preputial tumours are not uncommon in the horse, but can cause discomfort and lead to serious complications. Several types of tumour of the male external genitalia have been described. The most common type is the squamous cell carcinoma (SCC), which is found mainly in older horses. Reports of a breed predilection for penile tumour formation are equivocal, but castration, coat colour, poor hygiene and various infectious agents have all been suggested to predispose to the development of some types of tumour (e.g. SCC, papilloma and melanoma). Careful assessment of the primary tumour is an important first step in the design of an optimal treatment protocol. Invasiveness, differentiation grade, tumour size and presence of metastases are all relevant to the decision to pursue additional diagnostic procedures or specific treatment options. To date, no standard protocol has been reported for the approach to penile tumours in the horse and treatments range from minimally invasive therapies (e.g. topical use of 5-fluorouracil) to radical surgical interventions (e.g. en bloc penile and preputial resection with penile retroversion). Completeness of removal of the neoplasm and therefore risk of recurrence is highly dependent on the type of therapy chosen. However, the size and histopathological features of the primary tumour are also important factors with respect to the likelihood of recurrence. This review describes the most common penile and preputial neoplasms in the horse, and outlines a standard protocol aimed at arriving at a specific diagnosis and tailoring the therapeutic approach accordingly.

A comparison is made of the activity of the Ni catalyst and alloys with 5 and 10 at % Cu, in the hydrogenation of benzene. While at low temperatures (< 100°C) Ni is more active, at higher temperatures the situation is reversed; the reason is the presence of side-reactions as hydrogenolysis and coke formation. Alloying of Ni with Cu has a much more pronounced effect on the reactions of CC bonds (side reactions) than of CH bonds.

Mixtures of 2,6- and 2,7-di-t-butylnaphthalene, obtained by the t-butylation of naphthalene, can be conveniently separated making use of the fact that only the 2,6-isomer gives an inclusion compound with thiourea. 1,4- and 1,5-di-t-butylnaphthalene as well as 1,4- and 1,5-diisopropylnaphthalene have been prepared starting from 1,4- and 1,5-naphthalene-dicarboxylic acid, respectively. The NMR spectra of these compounds reveal downfield shifts for the peri protons. 1,8-Diisopropylnaphthalene was synthesized by an eight step synthesis starting from 1,8-naphthalenedicarboxylic anhydride.

The plumbylation of a large number of aromatic compounds is reported and a route for the preparation of the novel compounds ArAr′PbX2 is described. The course of the plumbylation reaction is discussed and its selectivity is explained in terms of differences in reactivity of aryllead(IV) compounds with halogen substituted acetic acids.

Summary Reasons for performing study: Clinical tendon lesions usually enlarge during the first days to weeks after sustaining the injury due to enzymatic and biomechanical influences. Limiting this enlargement would positively influence prognosis related to lesion size. Objectives: To investigate the effect of cyclic loading on the propagation of enzymatically and physically induced tendon lesions and to assess the effect of immobilisation thereon in an ex vivo model. Methods: Equine cadaver limbs with either physically or collagenase-induced SDFT lesions were placed in a pneumatic loading device. Groups consisted of unloaded limbs, cyclically loaded limbs and cyclically loaded limbs with fibreglass cast immobilisation. Lesion size was evaluated ultrasonographically and macroscopically and load at failure was determined for groups where lesions enlarged. Results: Physically induced lesions did not propagate after cyclical loading and were not further investigated. Collagenase-induced lesions propagated significantly more after cyclical loading compared to unloaded limbs. This propagation could effectively be reduced by immobilisation through a lower limb cast. Immobilisation did not influence load at failure. Conclusions: The combination of enzymatic and mechanical stimulation caused the lesions to propagate most. Casting appeared effectively to reduce the enlargement of the original tendon lesions in this ex vivo model, while it did not affect ultimate tendon strength. Potential relevance: As prognosis of tendon injuries is related to lesion size, the outcome of this study warrants further investigations in vivo.

To study the influence of different exercise regimens on the development of locomotion, 40 Warmblood foals aged 1 week were subdivided into 3 groups: box-rest, training and pasture exercise. The box-rest group remained for 24 h a day in a box stall while the training group was housed similarly, but additionally received a 30 min workout with gallop sprints 6 times a week. The pasture group served as a control group and was kept at pasture for 24 h a day. After 5 months, the locomotion pattern at the trot of every foal was recorded overground with a 2-D MacReflex gait analysis system. A randomly selected group of 19 foals was recorded again at age 11 months after they had been kept in an open loose box with access to a small paddock without any specific training for 6 months duration. At 5 months of age the box-rest group moved with a more protracted forelimb, and more extended shoulder and elbow joints than the pasture group. Carpal and fetlock joint kinematics were rather similar in all groups. In the hindlimb, the box-rest foals were significantly different from the other 2 groups, reflected in a more retracted hindlimb, more hip extension, more flexed stifle and tarsal joints, and a larger maximal flexion of hip, stifle, tarsal and fetlock joints. In the simultaneous video recordings this locomotion pattern was visible as a hypermetric movement. The larger protraction in the forelimb and retraction in the hindlimb, as seen in the box-rest group, is opposite to the interlimb coordination of a superior moving horse. The pastured foals had a smaller range of motion of the shoulder and hip joint and less maximal step height of both fore and hind hooves, while the velocity and step length were similar between the 3 groups. Pastured foals could trot the same distance with less joint motion and therefore had a more efficient intralimb coordination. The training group moved in a way comparable with the box-rest group in the similar velocity box-rest foals trot with an abnormal, hypermetric and therefore inefficient and poorer locomotion pattern. When, superimposed on box-rest, exercise is provided in the form of gallop sprints, this will mainly improve the hindlimb locomotion. These induced differences in locomotion pattern of foals can be reversed when the foals afterwards are subjected to the same exercise regimen again.

The trot at 3 m/s of 24 Shetland foals ('ponies') and 24 Dutch Warmblood foals ('horses') was recorded at age 4 months on a treadmill using a modified CODA-3 apparatus to characterise equine locomotion at young age. Locomotor variables of the ponies were qualitatively and, after scaling, quantitatively compared with those of horses. Ponies made shorter strides than horses, evidenced by a shorter stance and swing duration, although their relative stance durations were similar. Neither linear nor dynamic scaling procedures could completely compensate for differences in height at the withers comparing ponies and horses. The patterns of the joint angle-time curves were similar. Ponies had a larger range of pro- and retraction, with a more protracted forelimb and a more retracted hindlimb, therefore demonstrating a more extended trot. The horses trotted with more extended elbow, stifle and tarsal joints and a more flexed hip joint, which is in accordance with the conformation for the Warmblood. The ponies moved with a stiffer trot in contrast to the more supple trot of the horses, which showed a larger maximal fetlock extension during the stance phase. In conclusion, ponies and horses move qualitatively similarly at age 4 months, but characteristic breed differences in conformation and gait quality can already be detected. Scaling methods to compensate for differences in height at the withers cannot be applied when animals move at the same velocity.

Summary To evaluate the effects of uphill trotting on stride characteristics, 6 well trained Dutch Warmblood horses trotted at 4 m/s on a horizontal and on an inclined (6%) treadmill. This was done under 3 different conditions, unloaded, mounted by an experienced 90 kg rider and loaded with 90 kg of lead, to study whether extra weight provoked more or different alterations than the incline per se. In all 3 test situations (unloaded, mounted and lead-loaded), heart rates were significantly higher on the inclined treadmill than on the horizontal treadmill. Stride duration tended to increase on the inclined treadmill. Stance duration increased significantly on a slope, more in the hindlimbs than in the forelimbs. In the unloaded condition, maximal fetlock extension of the forelimb decreased on the incline, whereas maximal fetlock extension of the hindlimb and tarsal range of motion increased significantly on the slope in all 3 conditions. The overall effect was that on an inclined treadmill the hindlimbs seemed to carry more weight (higher maximal fetlock extension), and to provide greater propulsion (higher tarsal flexion and increased pro/retraction).

Summary The forelimb kinematics of 24 Dutch Warmbloods were recorded at the trot on a treadmill (4m/s) at the age of 4, 10, 18 and 26 months using a modified CODA-3 apparatus to study the development of the equine locomotor apparatus. Stride and stance duration increased with age, but swing duration and pro-/retraction angle were consistent. The timing of maximal fetlock extension during the stance phase and carpal flexion during the swing phase did not change significantly as horses grew older. Moreover, individual angle-time and angle-angle diagrams recorded at 4 and 26 months showed a remarkable resemblance, both visually and numerically. From these data it can be concluded that horses seem to have an inherent intralimb coordination pattern.

In this study, the effect of different exercise regimens on proteoglycan metabolism of articular cartilage was examined in 43 newborn foals randomly divided into 3 groups: a) box-rest, b) box-rest with training and c) free pasture exercise. They were subjected to these exercise regimens from ages 1 week to 5 months and at 5 months, 24 foals (8 from each group) were sacrificed to assess short-term exercise effects. The remaining 19 foals were subjected to the same regimen of light exercise for an additional 6 months before being sacrificed to evaluate possible long-term effects. Articular cartilage explants were cultured and proteoglycan synthesis, both ex vivo and after 4 days of serum stimulation, release of endogenous and newly synthesised proteoglycans, and DNA- and GAG contents were measured to determine the metabolic state of the cartilage. Cartilage metabolic parameters in the box-rest group at 5 months indicated a retardation in development of the cartilage but, after an additional 6 months, this retardation had almost completely disappeared. The training regimen induced an increase in proteoglycan synthesis at 5 months in cartilage that was, however, accompanied by an increase in proteoglycan release. In the training group at the long-term, the ability of cartilage to increase proteoglycan synthesis when stimulated was severely reduced. We consider this extra proteoglycan synthesis capacity of great importance to repair small injuries and hence as essential to prevent an early onset of degenerative disorders such as osteoarthritis. Therefore, although extrapolation of in vitro data to the in vivo situation always should be done with the utmost care, it is concluded that pasture exercise is best for the development of healthy cartilage resistant to injury and other exercise protocols may carry harmful long-term effects.

Osteochondrosis (OC) is a disturbance in the process of endochondral ossification, a process in which cartilage is mineralised and transformed into bone. In this process different biochemical events occur, of which the cartilage component has been studied so far almost exclusively. In this study we concentrated on the biochemical characterisation of normal and osteochondrotic subchondral bone, by analysis of enzyme activities, DNA content and phospholipids (PL). In subchondral bone, lysyl oxidase and both total and bone alkaline phosphatase activity were significantly increased in all degrees of OC. DNA content was increased only in the most established grade of OC investigated (grade 4). Furthermore, lactate dehydrogenase activity was significantly lower in grades 2 and 3 OC, but was normal in grade 4 OC, indicating that severe cell damage is not probable. Nonbuffer extractable PL content was substantially higher in osteochondrotic subchondral bone. The phosphatidylethanolamine (PE) to phosphatidylcholine (PC) ratio in both normal and OC subchondral bone was very low (typically 0.21 w/w, PE/PC), which indicates that these PLs were not from cellular origin and could be important in the maturation process of mineralised cartilage into bone and hence in the pathogenesis of OC.

To test the hypothesis that exercise at very young age may influence the eventual molecular composition (and hence the biomechanical properties) of tendon tissue in the horse, 43 Dutch Warmblood foals were allotted to 3 differently exercised groups (box-rest, box-rest with training and pasture exercise). Twenty-four superficial digital flexor tendons (SDFTs) were collected at age 5 months (8 from each exercise group) and the others were obtained at 11 months after an additional period of light exercise that was equal for all remaining foals and was intended to see if any induced changes would be reversible or not. Significant changes in DNA content (cellularity), hyaluronic acid (HA) and polysulphated glycosaminoglycans (PSGAGs) were found after the 5 month period of different exercise regimens. There was a tendency towards an exercise-related effect on hydroxylysine content and number of hydroxylysylpyridinoline (HP) crosslinks. Levels of Cartilage Oligomeric Matrix Protein (COMP), measured by homologous inhibition ELISA, showed significant differences at 5 months and were highest in foals kept at pasture and lowest in foals maintained in a box but given enforced exercise. At 11 months, the biochemical parameters of the tendons from the foals of the former box-rest and pasture groups became similar, indicating the capacity of the immature tendon to recover from a retarded development. However, the ratio of PSGAGs per unit of DNA of the former training group was significantly lower than those from the other groups, suggesting that the training regimen in this study had a lasting negative effect on the tenocytes resulting in a decrease of the production of PSGAGs. Therefore, inappropriate or excessive exercise may damage developing tendon, with limited recovery after normalising the exercise level. These possibly deleterious effects of a training regimen on tendon development may be important for the management of young would-be equine athletes.

Summary To answer the question whether an experienced rider or a dead weight influences a horse's workload and/or its locomotion, 9 well trained Dutch Warmblood horses, fully accustomed to treadmill exercise, underwent a submaximal standardised treadmill exercise test under 3 different conditions: unloaded, mounted by an experienced rider of 90 kg and loaded with 90 kg of lead. Heart rate was monitored continuously and plasma lactate concentrations were determined in venous jugular blood samples immediately before and 2 and 10 min after exercise. Temporal and angular stride variables were measured in fore- and hindlimbs at the walk (1.7 m/s), trot (4.0 m/s) and canter (7.0 m/s) with a modified CODA-3 computerised kinematic analysis system. Peak heart rates during exercise, and recovery heart rates thereafter were significantly lower in the unloaded horses compared to the mounted and lead-loaded horses. Plasma lactate concentrations immediately and 10 min after exercise were also significantly lower in the unloaded horses than in the mounted and lead-loaded horses. No differences were found in heart rate and plasma lactate concentration between the mounted and lead-loaded horses. Relative stance duration increased comparing the unloaded to the mounted and the lead-loaded horses (P

This study aimed to examine whether biochemical characteristics of juvenile articular cartilage are changing during the first year post partum and whether they can be influenced by exercise at young age. Water, glycosaminoglycan (GAG), DNA, total collagen, hydroxylysine and hydroxylysylpyridinoline (HP) content were measured in articular cartilage of 43 foals that were subdivided into 3 groups (n = 15, 14 and 14) which were subjected to different exercise regimens from one week after birth to age 5 months. At the age of 5 months all foals were weaned and 8 foals were selected randomly from each exercise group and subjected to euthanasia. The remaining foals (n = 19) were grouped and subjected to a similar exercise regimen for an additional 6 months. Differences were tested by student's t test (P

Summary It was hypothesised that imposition of different exercise levels at a young age would lead to differences in bone density in the third tarsal bone and to difference in the prevalence of pathological lesions that might contribute to the development of bone spavin later in life. Furthermore, based on earlier literature, it was hypothesised that such lesions could be classified as a manifestation of osteochondrosis. Changes in bone density in the third tarsal bone and early pathological changes in the articular cartilage of the distal intertarsal joint were studied in the offspring of sires with radiographic evidence of osteochondrosis in either stifle or hock. Twenty-four foals were studied at age 5 months after having been subjected to different exercise programmes (box-rest, box-rest with sprint training, pasture exercise) from age one week. Nineteen other foals that originally belonged to the same exercise groups were studied at age 11 months, after they had been weaned, housed together and subjected to an identical low level exercise regimen for an additional 6 months. Bone density was quantified using a microscopic technique. Histomorphological analysis was performed semiquantitatively and using high detail radiography techniques. At age 5 months, mean ± s.d. bone density in the compact bone of the third tarsal bone was significantly lower in the box-rested foals (37 ± 4%) than in both the trained and pastured foals (48 ± 7% and 52 ± 11%, respectively). After 6 months of identical exercise the previously box-rested foals showed an increase in bone density (53 ± 12%) which became similar to the value found in the formerly pastured foals (52 ± 8%). Major pathological lesions (chondrocyte necrosis, fragmentation and chondrone formation) of the articular cartilage of the third and central tarsal bones were already present at age 5 months, but were significantly more numerous at 11 months. There was no relation between the number of cartilage lesions and the osteochondrosis status of the foals. Only 2 lesions in 11-month-old foals had histological characteristics compatible with osteochondrosis, all other lesions were degenerative in nature. It is concluded that bone density of the compact bone of the subchondral bone plate in the third tarsal bone reacts strongly to variations in exercise at a very young age. Low bone density, caused by lack of exercise, can be compensated for when exercise is later increased. Pathological changes in the distal intertarsal joint are common at 5 months and increase to 11 months. These lesions are degenerative in nature and seem not to be related to osteochondrosis. Although the clinical relevance of these abnormalities is uncertain, they may be relevant for the development of osteoarthritic processes in this region later in life.

Summary Bone mineral density (BMD) and cross-sectional area (CSA), measured using peripheral quantitative computed tomography, were determined in the left third metacarpal bone (MCIII) and left medial proximal sesamoid bone (psb) in 3 differently exercised groups of foals. Groupbox (n = 14) was confined to a box stall from birth to age 5 months, Grouptraining (n = 14) was kept in similar box stalls but additionally given a daily exercise programme consisting of an increasing number of gallop sprints and Grouppasture (n = 15) remained at pasture. At 5 months of age, 8 foals from each group were randomly selected and subjected to euthanasia, the remaining 19 foals were given an identical light exercise regimen for an additional 6 months and were killed at age 11 months. In MCIII CSA increased with age and was also significantly (P

Summary To study the influence of training on the equine locomotor apparatus, the kinematics of 24 almost two-and-a-half-year-old Dutch Warmbloods were recorded on a treadmill at the trot (4 m/s) using a modified CODA-3 apparatus before and after a period of 70 days. In that period, 12 horses of the group were trained for dressage and jumping, while the other 12 were sent to pasture day and night. After 70 days, the hindlimb of the trained horses showed a decreased stance duration, less limb flexion and it reached its maximal protraction earlier in the stride. The stride duration remained the same in the trained horses, while the protraction and retraction range of the forelimb decreased in this group. In the pastured group, however, the horses increased their total range of forelimb movement in the sagittal plane and had a longer swing and stride duration. These results indicate that the definition of ‘training’ is rather relative. The response in the trained group was in agreement with the observation that the majority of horses from this group were trotting with impulsion ‘on the bit’. The pastured group was trotting in a more relaxed way with a longer stride duration and thus a lower stride frequency. In conclusion, this study proved that horses show different responses in their locomotor apparatus depending on the ‘training’ regime received. Using modern gait analysis equipment these differences could be evaluated objectively.

Summary In osteochondrosis (OC) the process of endochondral ossification is impaired. Proteoglycans form one of the major components of the extracellular matrix of cartilage and are able to bind calcium. For this reason, proteoglycans are thought to play an important role early in the mineralisation process and may, therefore, be important in the pathogenesis of OC. To investigate possible differences in proteoglycan metabolism, normal and osteochondrotic articular-epiphyseal cartilage was harvested from the hock and stifle joints of 43 foals age 5 and 11 months. The samples were cultured as explants in which 35S-[sulphate]-incorporation, release of newly synthesised and endogenous proteoglycans and content of DNA and proteoglycans were measured ex vivo and after a 4 day period of serum stimulation. In osteochondrotic cartilage of foals age both 5 and 11 months synthesis of proteoglycans was less stimulated by serum than in normal cartilage. Furthermore, only in the foals age 11 months, ex vivo proteoglycan production was decreased and an increase in the turnover of newly synthesised proteoglycans was detected in osteochondrotic cartilage, without a change in release of endogenous proteoglycans. The reduced response to serum stimulation in osteochondrotic cartilage indicates that osteochondrotic chondrocytes are less vital. The increase in turnover of newly synthesised proteoglycans reflects a change in composition of the proteoglycan pool. Considering the late changes in proteoglycan synthesis, an aberrant proteoglycan synthesis pattern is more likely to be a sequence than a primary cause of the impaired endochondral ossification of osteochondrotic lesions.

Summary Displacement of skin over the underlying skeletal structures in the proximal parts of the limbs was investigated in four walking Dutch Warmblood horses. Movement of the skin was visualised with self adhesive spot labels whereas that of the skeletal parts was visualised indirectly by means of a plastic strip connected to a transcutaneous Steinmann pin, driven into the bone of interest. Consistent results for all four horses were found. Individual and mean total displacements ranged from 1 to 4 cm (distal scapula) to 13 to 17 cm (caudal part of the greater trochanter of the femur). Displacements of this magnitude are of considerable importance to the interpretation of results of modern gait analysis techniques.

Summary Osteochondrosis (OC) is a multifactorial disorder with endocrinological dysfunction and mineral imbalance having a role in pathogenesis. The present study focused on a possible relationship between insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), parathyroid hormone (PTH), 1,25-dihydroxy-vitamin D (1,25(OH)2D), cortisol, copper, zinc, calcium, ionised calcium, magnesium and phosphorus and 5 different postmortem and radiographical osteochondrosis scores of hock and ***stifle joints in foals age 0–11 months. Osteochondrosis-positive foals showed a significantly lower IGF-I activity than osteochondrosis-negative foals. PTH, 1,25(OH)2D, cortisol, copper, zinc and calcium also showed significant differences between osteochondrosis-positive and osteochondrosis-negative foals.

The repair process of tendon injuries, which are common in both human and equine athletes, is slow and the quality of the repair tissue is often inferior to the original tendon tissue, which frequently leads to re-injury. The relatively poor vascularization of tendons is considered to be one of the reasons for their limited healing potential. Recently, platelet-rich plasma (PRP), an autologous concentrate of platelets, rich in growth factors, has been shown to enhance the repair process of injured tendons. This effect has been ascribed to the high levels of growth factors in PRP, several of which are known to be involved in tendon repair. Among many other growth factors, the vascular endothelial growth factor, a powerful stimulator of angiogenesis, is abundantly present in PRP, suggesting that enhancement of neovascularization might be one of the working mechanisms. In this study, the effect of PRP on neovascularization was studied in experimentally induced tendon injuries using color Doppler ultrasonography and immunological staining of Factor VIII. PRP induced significantly more neovascularization than the placebo treatment until at least 23 weeks after treatment, as detected by both Doppler ultrasonography and Factor VIII staining. Neovascularization might be one of the explanations for the long-lasting effect of a single intratendinous treatment with PRP.

AIM To examine social information processing in children and adolescents with neurofibromatosis type 1 (NF1). METHOD Thirty-two children with NF1 (12 males, 20 females; mean age 12y 4mo, SD 4y) and 32 comparison children (12 males, 20 females; mean age 13y 1mo, SD 3y 11mo) completed face recognition, identification of facial emotions (IFE), and matching facial emotions (MFE) tasks. A series of general linear model analyses of variance were used to compare performance between children with NF1 and comparison children. RESULTS Children with NF1 performed less accurately than comparison children in the face recognition task when faces were presented 'in profile' (p=0.05), when fearful expressions had to be identified in IFE (p=0.017), and across conditions in MFE (p=0.009). When quality of cognitive control (i.e. mean standardized scores on tasks measuring working memory and inhibitory control) was introduced to the analyses, differences in face recognition were no longer significant and differences in MFE were largely reduced (p=0.048). Differences in IFE between the comparison group and children with NF1 remained largely intact (fear: p=0.047). INTERPRETATION Children with NF1 have problems in social information processing, which, in part, appear to be caused by cognitive control deficits. Some of the deficits, however, appear to be caused by deficient bottom-up processing of social signals (e.g. fear recognition).

Biochemical heterogeneity of cartilage within a joint is well known in mature individuals. It has recently been reported that heterogeneity for proteoglycan content and chondrocyte metabolism in sheep develops postnatally under the influence of loading. No data exist on the collagen network in general or on the specific situation in the horse. The objective of this study was to investigate the alterations in equine articular cartilage biochemistry that occur from birth up to age one year, testing the hypothesis that the molecular composition of equine cartilage matrix is uniform at birth and biochemical heterogeneity is formed postnatally. Water content, DNA content, glycosaminoglycan content (GAG) and biochemical characteristics of the collagen network (collagen content, hydroxylysine content and hydroxylysylpyridinoline [HP] crosslinks) were measured in immature articular cartilage of neonatal (n = 16), 5-month-old foals (n = 16) and yearlings (n = 16) at 2 predefined differently loaded sites within the metacarpophalangeal joint. Statistical differences between sites were analysed by ANOVA (P

Summary In accidental wounds, trauma and infection can result in dehiscence of primarily closed wounds and in sequestrum formation when cortical bone is exposed. In experimental studies, it has been shown that second intention healing is faster and occurs with less complications in ponies than in horses. Also, a greater initial inflammatory response was seen in ponies. Based on these experimental data, it was hypothesised that accidental wounds in ponies would heal with a lower incidence of wound dehiscence and/or sequestrum formation compared to horses. A retrospective study of 89 ponies and 422 horses with traumatic wounds was performed. The animals, wounds and treatments were categorised and related to the success rate of primary closure and to the incidence of sequestrum formation. The ponies and horses were of similar age and sex. The wounds that were treated were comparable for localisation, duration, degree of contamination and depth in both groups of animals, but there were significantly more cases with ruptured extensor tendons in ponies. Antibiotics and NSAIDs were administered significantly less often to ponies. The success rate of primary closure was significantly higher in ponies than in horses, and sequestra were formed significantly less often in ponies. It was concluded that the results of healing were better in ponies although the external conditions were less favourable. This may be associated with the differences in the initial inflammatory response after injury as found in earlier experimental work, which may result in a betterlocal defence against wound infection.

Summary Reasons for performing study: The importance of osteoarthritis (OA) in the horse and the difficulty in its early diagnosis have led to a search for potential biomarkers of joint disease. If the levels of such markers are to be interpreted accurately, clinicians and researchers need to know whether they are influenced by environmental factors and/or interventions such as exercise and repeated arthrocentesis. Objective: To investigate the influence of repeated arthrocentesis and exercise on nitric oxide (NO), prostaglandin E2 (PGE2) and glycosaminoglycan (GAG) concentrations in synovial fluid (SF) from normal equine joints. Methods: SF was collected from the left metacarpophalangeal (MCP), radiocarpal and tarsocrural joints of 16 horses. Half of the horses were exercised and arthrocentesis was repeated 14, 14.5, 17 and 24 days after the start of the exercise programme, in both exercised and control horses. Nitric oxide was determined in SF from the MCP joint only and PGE2 and GAG concentrations were determined in SF from all joints. Results: Repeated arthrocentesis caused an increase in NO concentration in the MCP joint on Day 14.5, in PGE2 concentrations in the radiocarpal and tarsocrural joints on Day 14.5 and the release of GAGs into SF of the MCP and radiocarpal joints on Day 17. Exercise resulted in an increase in PGE2 levels in all joints but did not influence the other parameters measured. Potential relevance: Repeated arthrocentesis is a potential confounding factor for the use of synovial NO, PGE2 and GAG concentrations as markers of joint disease. Based on this study, such a confounding effect can be avoided if one week or more separates arthrocentesis procedures. Moderate exercise causes a transient rise in PGE2 in SF.

The contribution of wound contraction to wound closure determines the speed of second intention wound healing and it has been shown that significant differences exist with regard to both contraction and inflammatory response between horses and ponies and between various areas of the body. In this study, the contraction capacity of fibroblasts from limbs and buttocks of 4 Dutch Warmblood horses and 4 Shetland ponies was studied in vitro, in order to determine whether differences in wound contraction are due to differences in the inherent contraction capacity of the fibroblasts or to differences in tissue environmental factors, such as the inflammatory response. Fibroblasts were harvested from subcutaneous tissue, cultured and then suspended in both floating and anchored collagen gels. Contraction capacity was assessed by measuring the decrease in area of the floating gels and by measuring the microforces generated in the anchored gels using a custom-built measuring device. In the floating gels, no difference existed in the contraction capacity of fibroblasts from horses and ponies, or from limbs and buttocks. In the anchored gels, no differences existed between horse and pony fibroblasts, but the fibroblasts from the limbs started to contract significantly sooner and produced significantly higher forces than those from the buttocks. It is concluded that the in vivo differences in wound contraction between horses and ponies and between different sites of the body are not caused by differences in the inherent contraction capacity of fibroblasts. The in vitro differences between fibroblasts from limbs and buttocks are thought to be due to the lower proliferation rate and the longer culture time of the fibroblasts originating from the limbs, because mature fibroblasts can develop higher contraction forces than immature fibroblasts. This means that tissue environmental factors, such as cytokine profiles during the inflammatory response, determine the extent of contraction during wound healing. Further research should be directed towards the role of the inflammatory response in wound healing.