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OBJECTIVES: Bone void fillers are increasingly being used for dead space management in arthroplasty revision surgery. The aim of this study was to investigate the influence of calcium sulphate bone void filler (CS-BVF) on the damage and wear of total knee arthroplasty using experimental wear simulation. METHODS: A total of 18 fixed-bearing U2 total knee arthroplasty system implants (United Orthopedic Corp., Hsinchu, Taiwan) were used. Implants challenged with CS-BVF were compared with new implants (negative controls) and those intentionally scratched with a diamond stylus (positive controls) representative of severe surface damage (n = 6 for each experimental group). Three million cycles (MC) of experimental simulation were carried out to simulate a walking gait cycle. Wear of the ultra-high-molecular-weight polyethylene (UHMWPE) tibial inserts was measured gravimetrically, and damage to articulating surfaces was assessed using profilometry. RESULTS: There was no significant difference (p > 0.05) between the wear rate of implants challenged with CS-BVF (3.3 mm3/MC (95% confidence interval (CI) 1.8 to 4.8)) and the wear rate of those not challenged (2.8 mm3/MC (95% CI 1.3 to 4.3)). However, scratching the cobalt-chrome (CoCr) significantly (p < 0.001) increased the wear rate (20.6 mm3/MC (95% CI 15.5 to 25.7)). The mean surface roughness of implants challenged with CS-BVF was equivalent to negative controls both after damage simulation (p = 0.98) and at the conclusion of the study (p = 0.28). CONCLUSION: When used close to articulating surfaces, a low-hardness, high-purity CS-BVF had no influence on wear. When trapped between the articulating surfaces of a total knee arthroplasty, CS-BVF did not scratch the surface of CoCr femoral components, nor did it increase the wear of UHMWPE tibial inserts compared with undamaged negative controls.Cite this article: R. M. Cowie, S. S. Aiken, J. J. Cooper, L. M. Jennings. The influence of a calcium sulphate bone void filler on the third-body damage and polyethylene wear of total knee arthroplasty. Bone Joint Res 2019;8:65-72. DOI: 10.1302/2046-3758.82.BJR-2018-0146.R1.

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The aim of this study was to characterise the elution profiles of antibiotics in combination with pharmaceutical grade calcium sulphate beads in phosphate buffered saline and other physiological solutions which more closely mimic the in vivo environment. Synthetic recrystallised calcium sulphate was combined with vancomycin hydrochloride powder and tobramycin sulphate solution and the paste was formed into 3 mm diameter hemispherical beads. Then 2 g of beads were immersed in 2 ml of either phosphate buffered saline, Dulbecco's Modified Eagle Medium or Hartmann's solution and incubated at 37℃ for up to 21 days. At a range of time points, eluent was removed for analysis by liquid chromatography-mass spectrometry (LC-MS). Tobramycin sulphate and vancomycin hydrochloride release was successfully quantified against standard curves from solutions eluted in all three physiological media (phosphate buffered saline, Dulbecco's Modified Eagle Medium and Hartmann's solution) during incubation with calcium sulphate beads. One hour eluate concentrations were high, up to 2602 µg/ml for tobramycin in phosphate buffered saline and 7417 µg/ml for vancomycin, whereas in DMEM, the levels of tobramycin were 2458 µg/ml and 4401 µg/ml for vancomycin. The levels in HRT were 2354 µg/ml for tobramycin and 5948 µg/ml for vancomycin. The results show highest levels of antibiotic elution over the first 24 h, which gradually diminish over the following 21 days.

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Periprosthetic infection (PI) causes significant morbidity and mortality after fixation and joint arthroplasty and has been extensively linked to the formation of bacterial biofilms. Poly(methyl methacrylate) (PMMA), as a cement or as beads, is commonly used for antibiotic release to the site of infection but displays variable elution kinetics and also represents a potential nidus for infection, therefore requiring surgical removal once antibiotics have eluted. Absorbable cements have shown improved elution of a wider range of antibiotics and, crucially, complete biodegradation, but limited data exist as to their antimicrobial and antibiofilm efficacy. Synthetic calcium sulfate beads loaded with tobramycin, vancomycin, or vancomycin-tobramycin dual treatment (in a 1:0.24 [wt/wt] ratio) were assessed for their abilities to eradicate planktonic methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis relative to that of PMMA beads. The ability of the calcium sulfate beads to prevent biofilm formation over multiple days and to eradicate preformed biofilms was studied using a combination of viable cell counts, confocal microscopy, and scanning electron microscopy of the bead surface. Biofilm bacteria displayed a greater tolerance to the antibiotics than their planktonic counterparts. Antibiotic-loaded beads were able to kill planktonic cultures of 10(6) CFU/ml, prevent bacterial colonization, and significantly reduce biofilm formation over multiple days. However, established biofilms were harder to eradicate. These data further demonstrate the difficulty in clearing established biofilms; therefore, early preventive measures are key to reducing the risk of PI. Synthetic calcium sulfate loaded with antibiotics has the potential to reduce or eliminate biofilm formation on adjacent periprosthetic tissue and prosthesis material and, thus, to reduce the rates of periprosthetic infection.

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A new method is described which can be used to determine the setting times of small amounts of high value bone cements. The test was developed to measure how the setting times of a commercially available synthetic calcium sulfate cement (Stimulan, Biocomposites, UK) in two forms (standard and Rapid Cure) varies with the addition of clinically relevant antibiotics. The importance of being able to accurately quantify these setting times is discussed. The results demonstrate that this new method, which is shown to correlate to the Vicat needle, gives reliable and repeatable data with additional benefits expressed in the article. The majority of antibiotics mixed were found to retard the setting reaction of the calcium sulfate cement.

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Choice feeding is often used to investigate an animal's nutritional requirements and dietary preferences. A problem with this approach is that animals with long gut transit times, such as the horse, may find it difficult to associate a chosen food with its nutritional consequence when alternative foods are presented simultaneously. One solution is to present foods singly for a period of time before a simultaneous choice session to allow the development of learned associations. This method was used to determine if horse's voluntary intake and feeding behavior was influenced by the macronutrient composition of the diet. Seven stabled horses, maintained on a low intensity exercise regimen, were allowed, on an ad libitum basis, haylage and 3 isocaloric forage based diets that were rich in 1 of 3 macronutrients (protein, lipid, and hydrolyzable carbohydrate). Initially, diets were presented as a 3-way choice for 5 d (self-selection a [SSa]), then singly (monadic phase) with exposure to each diet for 2 separate periods of 3 d each, and finally again as a choice for 5 d (self-selection b [SSb]). The total amount of trial diet offered differed with trial phase, with 2 to 2.5% of BW during SSa and the monadic phase, increasing to ad libitum access during SSb. To control differences in the total amount of trial diet offered, 2 measurements of voluntary intake were taken at 4 and 22 h postpresentation. Daily macronutrient and energy intakes were estimated from proximate analysis of the trial diets and batches of haylage fed. Feeding behavior was observed over a single 4-h period during both self-selection phases. Horses showed no initial preference after 4 h for any 1 diet during SSa. Following the monadic phase, horses demonstrated a preference for the protein and hydrolyzable carbohydrate rich diets over the lipid rich diet (P < 0.001). Dietary experience modified foraging behavior as the total number of visits to the diets decreased during SSb (P < 0.005). Analysis of 24 -h macronutrient consumption showed that protein and hydrolyzable carbohydrate intake increased during SSb, whereas lipid intake remained constant over both self-selection phases (P < 0.001). These data indicate for perhaps the first time that horses can respond to dietary macronutrient content and that single presentations during choice studies facilitates expression of dietary preferences.

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BACKGROUND: Canine necrotizing meningoencephalitis (NME) is a fatal, noninfectious inflammatory disease of unknown etiology. NME has been reported only in a small number of dog breeds, which has led to the presumption that it is a breed-restricted disorder. HYPOTHESIS/OBJECTIVES: Our objective was to describe histopathologically confirmed NME in dog breeds in which the condition has not been reported previously and to provide preliminary evidence that NME affects a wider spectrum of dog breeds than previously reported. ANIMALS: Four dogs with NME. METHODS: Archives from 3 institutions and from 1 author's (BS) collection were reviewed to identify histopathologically confirmed cases of NME in breeds in which the disease has not been reported previously. Age, sex, breed, survival from onset of clinical signs, and histopathologic findings were evaluated. RESULTS: Necrotizing meningoencephalitis was identified in 4 small dog breeds (Papillon, Shih Tzu, Coton de Tulear, and Brussels Griffon). Median age at clinical evaluation was 2.5 years. Histopathologic abnormalities included 2 or more of the following: lymphoplasmacytic or histiocytic meningoencephalitis or encephalitis, moderate-to-severe cerebrocortical necrosis, variable involvement of other anatomic locations within the brain (cerebellum, brainstem), and absence of detectable infectious agents. CONCLUSIONS AND CLINICAL IMPORTANCE: Until now, NME has only been described in 5 small dog breeds. We document an additional 4 small breeds previously not shown to develop NME. Our cases further illustrate that NME is not a breed-restricted disorder and should be considered in the differential diagnosis for dogs with signalment and clinical signs consistent with inflammatory brain disease.

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A wide range of electronic dog training collars (e-collars) is available in the UK, but information enabling purchasers to compare the important characteristics of these collars is not available. In this research, the electrical characteristics of 13 e-collar models were examined, and an approach to ranking the strength of the electrical stimuli was developed. To achieve this, the electrical impedance of dogs' necks were measured so that e-collars could be tested under realistic conditions. This impedance was found to be about 10 kΩ for wet dogs and 640 kΩ for dry dogs. Two replicates of eight e-collar models and single copies of a further five models were then examined. The stimuli generated by these collars comprised sequences of short high-voltage pulses. There were large differences between e-collar models in the energy, peak voltage, number of pulses and duration of the pulses, but little variation between the replicates. The peak voltage varied with the impedance, from 6000V at an impedance of 500 kΩ to 100V at 5 kΩ. The highest voltages were generated for a few millionths of a second. Stimulus energy levels at the maximum strength setting with a 50 kΩ load ranged from 3.3 mJ to 287 mJ. A stimulus strength ranking indicator was then developed to enable the strengths of e-collars with diverse electrical characteristics to be ranked. This ranking shows a wide range in the stimulus strengths of collars, and that the relationships between 'momentary' and 'continuous' stimuli for various models differ significantly.

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A 4-year-old, spayed-female great Dane was referred for surgical treatment of a suspected meningioma, diagnosed on magnetic resonance imaging 10 days prior to presentation. The suspected meningioma was removed via image-guided stereotactic craniotomy. Histopathological diagnosis was severe, locally extensive, chronic meningoencephalitis with an intralesional nematode egg. The egg was morphologically consistent with Eucoleus boehmi, and aberrant migration into the cranial cavity was the presumed cause of this lesion. Three faecal samples were collected and revealed 4+ E. boehmi eggs. Treatment involved 110 mg/kg fenbendazole (Panacur, Intervet) orally twice daily for 14 days. Nematodes including E. boehmi are a previously un-recognised source of intracranial disease in dogs, and should be considered as a differential for mass-like lesions visualised by magnetic resonance imaging.

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By exploiting the correlation properties of ultracold atoms in a multimode interferometer, we show how quantum enhanced measurement precision can be achieved with strong robustness to particle loss. While the potential for enhanced measurement precision is limited for even moderate loss in two-mode schemes, multimode schemes can be more robust. A ring interferometer for sensing rotational motion with noninteracting fermionic atoms can realize an uncertainty scaling of 1/(N√η) for N particles with a fraction η remaining after loss, which undercuts the shot-noise limit of two-mode interferometers. A second scheme with strongly interacting bosons achieves a comparable measurement precision and improved readout.

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1. The study investigated the effects of providing sight barriers in breeding pens on pheasant mortality, feather damage and behaviour. 2. Data were collected from 11 conventional pens (control) and 11 pens with additional sight barriers (barrier) over the course of a ten week breeding season. Each pen contained 8 males and 56 females at the beginning of the season. 3. There was a higher rate of mortality in males (6 x 25%) than females (2 x 11%) that was unaffected by treatment. 4. Feather damage increased over the breeding season and both male and female pheasants showed better feather condition in the pens with barriers at the end of the season. 5. The pheasants spent most of their time walking or standing. Providing barriers increased perching, but reduced preening. 6. The provision of sight barriers had no effect on the incidence of courtship and mating, but did reduce aggressive interactions such as pecking and chasing. 7. The study provides baseline data on the behaviour of breeding pheasants under these husbandry conditions, and suggests that barriers may improve pheasant welfare by reducing potentially harmful aggressive interactions, without affecting activity patterns or reproductive behaviour.

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1. The effects of sight barriers in the pens of breeding ring-necked pheasants were investigated on a commercial game farm over a 10-week laying season. 2. Reproductive performance was recorded as egg production, numbers of eggs rejected for hatching together with measures of fertility, embryonic mortality and hatchability for 11 pens with barriers and 11 pens that were left open and acted as controls. 3. Egg production per pen and the numbers of rejected eggs were not significantly affected by the presence of the barriers. 4. Fertility was significantly higher and persisted for longer in the barrier pens, particularly towards the end of the laying season. 5. Embryonic mortality was unaffected by the presence of the barriers but hatchability was significantly lower in the open pens, which was associated with lower levels of fertility. 6. Establishing sight barriers in breeder pens for commercial pheasants would appear not only to offer improved welfare but also significant commercial advantages.

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Mycotic meningoencephalitis in dogs may manifest as a primary disease of the central nervous system or as a part of disseminated infection. Fungi belonging to the genus Bipolaris are saprophytic plant pathogens and can cause disease in humans. The authors report a case of Bipolaris infection in a dog with granulomatous meningoencephalitis, nephritis, and vasculitis. The clinical and histological features resembled those of the more common aspergillosis, thus warranting confirmation by molecular methods. Polymerase chain reaction and sequence analysis identified Bipolaris from the brain lesion, indicating its involvement in the disease. To the authors' knowledge, this is the first reported case of meningoencephalitis caused by this fungus in a domestic animal.

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REASONS FOR PERFORMING STUDY: It is unknown if different locomotor activities are equally effective at meeting the stabled horse's need for exercise and if they attenuate unwanted behaviour. HYPOTHESIS: Alternative forms of exercise influence the intensity of locomotor activities during a period of turn-out (the so-called rebound effect) and the occurrence of unwanted or undesirable activities during standard handling situations. METHOD: Twenty-four horses kept in stables were randomly assigned to one of 4 exercise regimes (walker, treadmill, turn-out and riding) for 4 consecutive days. Because these forms of exercise provide additional environmental stimulation, beyond that provided by exercise, each horse served as its own control in 4 corresponding (no exercise) control treatments presented in a balanced order. Unwanted behaviour was tested by taking horses to weighing scales and loading and unloading them onto a 4-horse float by an experienced handler and the rebound effect was tested by releasing them into a large arena for a period of 15 min at the end of the exercise and control treatments. RESULTS: Locomotor activities made up a large part of behaviour in the large arena following control treatments and all exercise regimes were sufficient to reduce the intensity of walking (P < 0.05), trotting (P < 0.01) and cantering (P < 0.001) on release into a large arena. Exercise regime reduced the number of bucks (P < 0.01) and rolling (P < 0.05) during rebound tests suggesting that turn-out was having a stronger effect than the other 3 exercise regimes. Exercise regimes significantly reduced the amount of unwanted behaviour and the number of commands given by the handler during weighing (P < 0.05) but had no effect on these behaviours during loading onto a float. CONCLUSION: Providing stabled horses with one hour/day of exercise on a walker, treadmill, turn-out or by being ridden are all effective at allowing expression of locomotor activities in stabled horses. POTENTIAL RELEVANCE: Providing stabled horses with regular exercise is likely to provide positive effects on horse welfare, training ability and handler safety.

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1. Limited information is available on how changes in horizontal and vertical space within enriched or furnished layer cages (as defined by Directive 1999/74/EC) influence hen behaviour. This study evaluated the effects of varying minimum cage heights and space allowances on the behaviour of laying hens housed in furnished cages. It was conducted on two flocks of medium brown hybrid hens housed in furnished cages with access to perches and nest boxes on a semi-commercial scale at ADAS Gleadthorpe. 2. Flock 1 consisted of two layer strains (ISA Brown and Babcock 380), housed at two minimum cage heights (38 and 45 cm) and 5 stocking densities between 609 and 870 cm2/bird, with 12 replicates of each of the 20 strain/cage height/stocking density treatment combinations. Stocking density was varied by varying the number of birds per cage from 10 to 7 in standard full-width cages or housing 7 hens in a narrower cage. As a consequence stocking density, group size and trough width per bird co-varied for 4 out of 5 stocking density treatments. 3. Behaviour of flock 1 was sampled at 33 to 36, 46 and 68 weeks of age. At each age one top-tier, one middle-tier and one bottom-tier cage was sampled for each treatment. 4. Few behavioural differences due to cage treatments were detected. Hens at 870 cm2 had shorter feeding bouts than hens at 609 and 762 cm2. Yawning was more common in the cages with greater cage height. 5. Video recordings of flock 1 examined cage height effects on hens' use of vertical space and provided additional data on stretching and self-maintenance activities. No differences in behaviour between 38 and 45 cm cages were found except that scratching head was more common in cages with greater cage height. 6. Flock 2 consisted of two layer strains (Shaver Brown and Hy-Line Brown), housed at 38 and 45 cm and 609, 762 and 1016 cm2/bird, with 18 replicates of each of the 12 strain/cage height/stocking density treatment combinations. Stocking density was varied by housing 10, 8 or 6 hens in standard full-width cages. Behaviour of flock 2 was sampled at 30, 48, 60 and 67 weeks from video recordings. Three cages per treatment from middle-tiers only were sampled at each age. 7. Hens housed at 609 cm2/hen had the longest mean feeding bout, greater than for hens at 762 cm2/hen but not hens at 1016 cm2/hen. More unsuccessful attempts to reach the feeder and sideways and backwards displacements from the feeder occurred at 762 and 609 cm2/hen than at 1016 cm2/hen. A maximum of 8 hens were observed feeding synchronously. 8. These results suggest that changes in horizontal and vertical space over the ranges we studied had little effect on behaviour other than feeding behaviour. Specifying a minimum useable trough space per hen, rather than calculating feeder space from total length of feeder per cage, irrespective of accessibility, might help avoid crowding at the feeder and associated disturbance of feeding bouts.

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Six dogs (Canis familiaris) were trained to sit and come reliably in response to tape-recorded commands. The phonemes within these commands were then changed, and the dogs' behavior in response to these modified commands was recorded. Performance markedly declined in all cases, with the type of alteration affecting response to the modified sit command but not to the modified come command. The results suggest that dogs do not perceive a tape-recorded command as simply a physical sound but that they recognize a relationship between certain sounds.

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The effect of substrate characteristics on primary human bone cell response to mechanical loading was investigated in this study. The substrates comprised organic and inorganic materials with a range of hydrophilic and hydrophobic features. Substrate surface topography varied from smooth to particulate to porous. It was found that hydrophilic substrates such as borosilicate glass facilitated bone cell adhesion, in contrast to hydrophobic substrates such as poly(L-lactic acid), in which clumps of cells grew unevenly across the substrate surface. All primary bone cells cultured in the various collagen-coated substrates were responsive to mechanical stimulation. The study showed that, at a low strain level of 1000 microstrain, mechanical stimulation enhanced bone cell differentiation rather than proliferation. Coating the substrates with collagen type I enhanced cell adhesion and promoted an elongated cell morphology, indicating that the presence of specific binding sites on a substrate may be more important than its hydrophilic properties, regardless of the substrate topography.

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Addressing the behavioral priorities of captive animals and the development of practical, objective measures of the value of environmental resources is a principal objective of animal welfare science. In theory, consumer demand approaches derived from human microeconomics should provide valid measures of the value of environmental resources. In practice, however, a number of empirical and theoretical problems have rendered these measures difficult to interpret in studies with animals. A common approach has been to impose a cost on access to resources and to use time with each resource as a measure of consumption to construct demand curves. This can be recorded easily by automatic means, but in a number of studies, it has been found that animals compensate for increased cost of access with longer visit time. Furthermore, direct observation of the test animals' behavior has shown that resource interaction is more intense once the animals have overcome higher costs. As a consequence, measures based on time with the resource may underestimate resource consumption at higher access costs, and demand curves derived from these measures may not be a true reflection of the value of different resources. An alternative approach to demand curves is reservation price, which is the maximum price individual animals are prepared to pay to gain access to resources. In studies using this approach, farmed mink (Mustela vison) paid higher prices for food and swimming water than for resources such as tunnels, water bowls, pet toys, and empty compartments. This indicates that the mink placed a higher value on food and swimming water than on other resources.

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Increasing evidence suggests that the biology of acute myeloid leukemia (AML) may differ between older and younger patients, with a higher incidence of antecedent myelodysplasia, unfavorable cytogenetic abnormalities, and multidrug resistance seen in the elderly. Abrogation of apoptosis in response to cytotoxic medications is associated with drug resistance in AML, as is expression of bcl-2, an important anti-apoptotic protein. We hypothesized that blasts from elderly (> or = 55 years) and young adult AML patients might have different levels of apoptotic and cell cycle responses to chemotherapeutic agents, as well as different levels of proliferation and of bcl-2 protein expression. Therefore, we cultured bone marrow leukemia samples from previously untreated elderly (n=33) and young (n=21) AML patients for 48 h and then measured apoptosis, bcl-2 protein levels, cell cycle distributions, and expression of a proliferation marker, proliferating cellular nuclear antigen (PCNA) in multi-parametric flow cytometry assays. In some experiments, leukemia samples were exposed to cytarabine (Ara-C) or daunomycin (DNR) for the last 16-18 h of the culture period. In comparison to samples from young patients, cultured samples from elderly AML patients had a higher fraction of viable cells, as measured by Trypan blue exclusion, higher PCNA expression, and significantly less culture-induced and drug-induced apoptosis. The mean apoptosis after culture was 13% for elderly AML samples, versus 20% for young AML samples (P=0.009). Similarly, the mean apoptosis after Ara-C was lower in elderly than in young AML samples, 13 versus 28% (P=0.001), as was the mean apoptosis after DNR, 15 versus 26% (P=0.012). Diminished apoptotic responses in elderly AML cells were not consistently associated with high bcl-2 levels at thaw or bcl-2 levels increased by culture. These data suggest that new therapies should be developed to overcome abrogated apoptosis, particularly in elderly AML patients.

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