Heart rate distribution in dogs with third degree atrioventricular block and rate responsive pacemakers.

INTRODUCTION: In dogs, single lead ventricular pacing, ventricular sensing, inhibition response, rate adaptive (VVIR) pacemakers are routinely used to treat third degree atrioventricular block. The objectives of this study were to investigate the heart rate distribution in dogs with VVIR pacemakers, and report changes when activity settings were adjusted. ANIMALS: Eighteen client-owned dogs with VVIR pacemakers for third degree atrioventricular block. MATERIALS AND METHODS: This observational study consisted of a review of medical records of dogs with VVIR pacemakers. For dogs with >50% of paced beats at the lower pacing rate, the activity daily living (ADL) and exertion responses were increased. Re-evaluations were performed after 6-12 months. RESULTS: Heart rate distribution similar to healthy dogs was absent for all dogs. In nine dogs, the ADL and exertion responses were increased to the highest level. Of these, three dogs showed no improvement in heart rate distribution; for two dogs, one with an epicardial pacemaker, several activity settings were adjusted and pacing at higher heart rates was observed at re-evaluation. Four dogs died or were lost to follow-up. Clinical signs had resolved for all dogs after pacemaker implantation. CONCLUSION: Default activity settings of VVIR pacemakers do not result in heart rate distribution equivalent to healthy dogs. Increasing the ADL and exertion response settings to the highest levels did not improve the pacemaker rate response. Further investigations into the role of dog size, generator positioning, pacemaker settings, and whether rate responsiveness is required for dogs' quality and quantity of life are warranted.

Study of the effect of anaesthesia on the canine ultrasonographic optic nerve sheath diameter.

OBJECTIVES: To investigate the effects of anaesthetic duration and serial anaesthetic events on optic nerve sheath diameter in a population of dogs without intracranial disease using point-of-care ultrasonography. MATERIALS AND METHODS: Client-owned dogs requiring advanced head imaging were prospectively enrolled. Exclusion criteria included signs of elevated intracranial pressure, glaucoma and optic nerve disease. Using a transpalpebral technique, two optic nerve sheath diameter measurements were recorded for each eye at three timepoints: following premedication, after induction within 7 minutes and before discontinuing isoflurane. Mixed model analysis was used to characterise optic nerve sheath diameter behaviour and investigate the effects of anaesthetic duration, bodyweight and anaesthetic protocol, age and sex. RESULTS: Fourteen dogs of various ages, breeds and bodyweights were enrolled. A positive linear relationship was detected between body weight and optic nerve sheath diameter. In 12 of 14 dogs, the optic nerve sheath diameter increased from measurements taken after premedication when compared to measurements taken after induction within 7 minutes. In a subset of patients, measurements subsequently decreased when anaesthetic duration exceeded 120 minutes. Age, side, sex, final body temperature, blood pressure and anaesthetic protocol did not significantly affect optic nerve sheath diameter. No significant association was noted between optic nerve sheath diameter and end-tidal carbon dioxide after induction and before discontinuing isoflurane. CLINICAL SIGNIFICANCE: When using point-of-care ultrasound, a transient increase in optic nerve sheath diameter occurs between premedication and within 7 minutes following induction, regardless of bodyweight. This should be taken into consideration when serial monitoring is performed.

Endotoxin-induced cytokine, chemokine and white blood cell profiles of variable stress-responding sheep.

Individual variation of the hypothalamic-pituitary-adrenal (HPA) axis response to stress could contribute to variable stress resiliency of livestock. During stress events, the innate immune system can also become activated and work in concert with the neuroendocrine system to restore homeostasis, while minimizing tissue damage. The purpose of this study was to assess immune function in variable stress-responding sheep in response to bacterial lipopolysaccharide (LPS) endotoxin immune-challenge. High (HSR, n = 12), middle (MSR, n = 12), and low-stress responders (LSR, n = 12) were selected from a population of 112 female lambs and classified based on serum cortisol concentration after receiving an intravenous bolus of LPS (400 ng/kg). Blood was collected from the jugular vein at 0 and 4 hrs post-LPS challenge to monitor changes in serum pro- and anti-inflammatory cytokines and chemokines, and white blood cell populations. Rectal temperature was recorded hourly to monitor fever. HSR had the greatest increase in rectal temperature and strongest pro-inflammatory IL-6 and IFN-γ cytokine responses compared to MSR and LSR. HSR and MSR had stronger anti-inflammatory IL-10 cytokine and CCL2 chemokine responses than LSR. White blood cell counts changed between 0 and 4 h; however, no differences were detected among the variable stress response groups. The distinct inflammatory response in variable stress responding sheep could contribute to individual differences in stress resiliency and this warrants investigation in the context of other types of stress.

LAY SUMMARYAcute inflammation was studied in sheep stress-phenotyped using bacterial lipopolysaccharide. Sheep selected based on stress responsiveness (i.e. serum cortisol concentration) have different immune responses to bacterial stress. Specifically, high-stress responders have a more pronounced inflammatory response than low-stress responders.

Accuracy of a point-of-care major crossmatch test and risk factors for major crossmatch incompatibility in cats.

Major crossmatch testing can help identify immunologic incompatibilities between blood donors and recipients; however, there are limited studies describing the accuracy of point-of-care crossmatch tests. The first aim of this study was to determine if a gel-based, point-of-care major crossmatch method (GEL-CM), without antiglobulin-enhancement, could accurately detect compatible and incompatible donor-recipient pairings, using an antiglobulin-enhanced laboratory-based major crossmatch method (LAB-CM) as the reference standard. The second aim was to describe the incidence of, and risk factors for, major crossmatch incompatibility in cats. Nineteen previously-transfused cats and 32 transfusion-naïve cats, representing 132 unique donor-recipient pairings, were included in this study. Both LAB-CM and GEL-CM tests were performed for most parings. There was poor agreement between the LAB-CM and GEL-CM results (kappa = 0.111; 95% confidence interval [CI], -0.093 to 0.314). Transfusion-naïve cats had incompatibility rates of 3% and 6% using LAB-CM and GEL-CM, respectively; previously-transfused cats had incompatibility rates of 32% and 26% using LAB-CM and GEL-CM, respectively. History of previous transfusion was the only identified cat risk factor for an incompatible LAB-CM (odds ratio [OR], 31.0; 95% CI, 3.77-254.98; P = 0.0019) and GEL-CM (OR, 5.7; 95% CI, 1.72-19.20; P = 0.0054). Further studies are needed to determine if GEL-CM can detect clinically-relevant immunologic incompatibilities that would result in transfusion reactions. Major crossmatch testing is of greater importance in cats that have previously received a transfusion.

Characteristics and outcomes of cats with and without pacemaker placement for high-grade atrioventricular block.

INTRODUCTION: Available information on characteristics and outcome in cats with high-grade atrioventricular block (AVB) that receive a pacemaker is limited. ANIMALS: Twenty-two privately owned cats presenting with high-grade AVB. MATERIALS AND METHODS: Medical records were retrospectively examined. Cats were grouped as having received a pacemaker (PACE group) or not having received a pacemaker (non-PACE group). Clinical characteristics and outcomes of groups were evaluated. RESULTS: There were 10 cats in the PACE group and 12 cats in the non-PACE group. At presentation, syncope or seizure-like behavior (p = 0.004) and bradycardia (p = 0.043) were more common in the PACE than the non-PACE group. Historical lethargy (p = 0.015) and dull mentation (p = 0.045) were more common in the non-PACE group, as was clinically relevant systemic disease. Pacemaker placement improved syncope or seizure-like behavior in 100% of cats. The degree of AVB at presentation was not associated with pacemaker placement nor the future degree of AVB. The major complication rate of pacemaker placement was 40%. Intergroup survival was not significantly different (PACE group 1278 days, 95% confidence interval: 0-2145 days; non-PACE group 213 days, confidence interval: 1-not available, p = 0.77). CONCLUSIONS: Pacemaker placement improved clinical signs in cats with high-grade AVB. A difference in survival time could not be demonstrated between cats that received and did not receive a pacemaker in this retrospective study. High-grade AVB can be transient and accompanied by systemic disease in some cats.

Echocardiographic parameters for the assessment of congestive heart failure in dogs with myxomatous mitral valve disease and moderate to severe mitral regurgitation.

The objective of this study was to evaluate the influence of congestive heart failure (CHF) on echocardiographic variables in dogs with moderate or severe mitral valve regurgitation (MR) secondary to myxomatous mitral valve disease (MMVD). The secondary objective was to investigate the preliminary use of left ventricular early inflow-outflow index (LVEIO) and L-waves as indicators of CHF. Forty-five dogs with moderate or severe MR without (n = 23) or with (n = 22) CHF were retrospectively included. Echocardiographic variables of elevated left ventricular (LV) filling pressures and cardiac function, LVEIO and the presence of L-waves were obtained and statistically compared between the two groups. On general linear model analysis, mitral inflow peak E-wave velocity, E:A ratio, ratio of E to isovolumic relaxation time (IVRT) and LVEIO were increased, while left atrium (LA) fractional shortening was reduced, in dogs with CHF. Peak E-wave velocity, peak A-wave velocity, E:A ratio, LA minimum diameter, LA diameter before the P-wave, LA fractional shortening and LVEIO were found to be predictive of CHF. The absence of L-waves indicated a reduced risk of CHF. Several echocardiographic variables may be useful in identifying elevated LV filling pressures, consistent with CHF, in dogs with moderate and severe MR. Left ventricular early inflow-outflow index and L-waves might be of interest as clinical and prognostic markers in dogs with MMVD and require further investigation.

Short communication: Characterizing ovine serum stress biomarkers during endotoxemia.

Breeding stress-resilient livestock is a potential strategy to help mitigate the negative effect of environmental and pathogenic stressors. The hypothalamic-pituitary-adrenal axis and immune system are activated during stress events and release mediators into the circulation that help restore physiological homeostasis. The purpose of this study was to assess a comprehensive set of circulatory mediators released in response to an acute immune stress challenge to identify candidate biomarkers that can be used for the selection of stress-resilient animals. Fifteen female lambs were stress challenged with an intravenous bolus of lipopolysaccharide (LPS; 400 ng/kg), and blood was collected from the jugular vein at 0, 2, 4, and 6 h after LPS challenge to identify and monitor candidate stress biomarkers; temperature was also recorded over time. Biomarker responses were evaluated with a repeated-measures model to compare time points with baseline values. As expected, all sheep had a monophasic febrile response to LPS challenge, and cortisol increased and returned to baseline by 6 h. The cytokines tumor necrosis factor-α, IL-6, IFN-γ (proinflammatory), and IL-10 (anti-inflammatory) increased, but only tumor necrosis factor-α returned to baseline during the monitoring period. The cytokines IL-1α, IL-1ß, IL-17α (proinflammatory), and IL-4 (anti-inflammatory) did not respond to LPS challenge. All chemokines (CCL2, CCL3, CCL4, CXCL10, and IL-8) responded to LPS challenge; however, only CCL2, CCL3, CCL4, and CXCL10 increased over time, and only CCL3, CCL4, and CXCL10 returned to baseline during the monitoring period. MicroRNA (miR-145, miR-233, and miR-1246) also increased and remained elevated during the study. In summary, the LPS challenge induced a strong stress response in Rideau-Dorset sheep that could be monitored with a distinct profile of circulatory biomarkers.

Heart-fatty acid binding protein in dogs with degenerative valvular disease and dilated cardiomyopathy.

The study objective was to investigate heart-fatty acid binding protein (HFABP) concentrations in dogs with degenerative valvular disease (MVD) and dilated cardiomyopathy (DCM), and its potential as a prognostic factor. Plasma HFABP, N-terminal pro brain natriuretic peptide (NTproBNP) and serum cardiac troponin I (cTnI) levels were measured in 21 control dogs, 23 dogs with MVD and 13 dogs with DCM, with repeated sampling at 1 and 3 months after initial presentation. All dogs were followed up after 6 and 12 months to verify survival. Heart-fatty acid binding protein concentrations were significantly higher in dogs with MVD and DCM than controls at initial presentation, and after 1 month in dogs with MVD. For dogs with DCM, a significant reduction in HFABP levels over time was observed. Comparing ACVIM stages, highest HFABP concentrations were detected in ACVIM stage C dogs compared to stage B, with the lowest levels seen in controls, and a reduction over time in stage C dogs was present. Similarly, cTnI concentrations were higher in DCM and stage C in comparison to control dogs and reduced over time, while NTproBNP concentrations were only higher in diseased dogs at 1 month. Heart-fatty acid binding protein and cTnI levels at initial presentation and ACVIM disease stage were independent predictors of survival in a univariate analysis. The elevation of HFABP in dogs with MVD and DCM in comparison to controls, its association with disease severity, and its potential in predicting reduced survival, suggest that HFABP might be useful as marker for canine MVD and DCM.

Assessment of CXC ligand 12-mediated calcium signalling and its regulators in basal-like breast cancer cells.

CXC ligand (L)12 is a chemokine implicated in the migration, invasion and metastasis of cancer cells via interaction with its receptors CXC chemokine receptor (CXCR)4 and CXCR7. In the present study, CXCL12-mediated Ca2+ signalling was compared with two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which demonstrate distinct metastatic potential. CXCL12 treatment induced Ca2+ responses in the more metastatic MDA-MB-231 cells but not in the less metastatic MDA-MB-468 cells. Assessment of mRNA levels of CXCL12 receptors and their potential modulators in both cell lines revealed that CXCR4 and CXCR7 levels were increased in MDA-MB-231 cells compared with MDA-MB-468 cells. Cluster of differentiation (CD)24, the negative regulator of CXCL12 responses, demonstrated increased expression in MDA-MB-468 cells compared with MDA-MB-231 cells, and the two cell lines expressed comparable levels of hypoxia-inducible factor (HIF)2α, a CXCR4 regulator. Induction of epithelial-mesenchymal transition (EMT) by epidermal growth factor exhibited opposite effects on CXCR4 mRNA levels compared with hypoxia-induced EMT. Neither EMT inducer exhibited an effect on CXCR7 expression, however hypoxia increased HIF2α expression levels in MDA-MB-468 cells. Analysis of the gene expression profiles of breast tumours revealed that the highest expression levels of CXCR4 and CXCR7 were in the Claudin-Low molecular subtype, which is markedly associated with EMT features.

Diagnostic Utility of Wireless Video-Electroencephalography in Unsedated Dogs.

BACKGROUND: Poor agreement between observers on whether an unusual event is a seizure drives the need for a specific diagnostic tool provided by video-electroencephalography (video-EEG) in human pediatric epileptology. OBJECTIVE: That successful classification of events would be positively associated with increasing EEG recording length and higher event frequency reported before video-EEG evaluation; that a novel wireless video-EEG technique would clarify whether unusual behavioral events were seizures in unsedated dogs. ANIMALS: Eighty-one client-owned dogs of various breeds undergoing investigation of unusual behavioral events at 4 institutions. METHODS: Retrospective case series: evaluation of wireless video-EEG recordings in unsedated dogs performed at 4 institutions. RESULTS: Electroencephalography achieved/excluded diagnosis of epilepsy in 58 dogs (72%); 25 dogs confirmed with epileptic seizures based on ictal/interictal epileptiform discharges, and 33 dogs with no EEG abnormalities associated with their target events. As reported frequency of the target events decreased (annually, monthly, weekly, daily, hourly, minutes, seconds), EEG was less likely to achieve diagnosis (P < 0.001). Every increase in event frequency increased the odds of achieving diagnosis by 2.315 (95% confidence interval: 1.36-4.34). EEG recording length (mean = 3.69 hours, range: 0.17-22.5) was not associated (P = 0.2) with the likelihood of achieving a diagnosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Wireless video-EEG in unsedated dogs had a high success for diagnosis of unusual behavioral events. This technique offered a reliable clinical tool to investigate the epileptic origin of behavioral events in dogs.

Oncosis and apoptosis induction by activation of an overexpressed ion channel in breast cancer cells.

The critical role of calcium signalling in processes related to cancer cell proliferation and invasion has seen a focus on pharmacological inhibition of overexpressed ion channels in specific cancer subtypes as a potential therapeutic approach. However, despite the critical role of calcium in cell death pathways, pharmacological activation of overexpressed ion channels has not been extensively evaluated in breast cancer. Here we define the overexpression of transient receptor potential vanilloid 4 (TRPV4) in a subgroup of breast cancers of the basal molecular subtype. We also report that pharmacological activation of TRPV4 with GSK1016790A reduced viability of two basal breast cancer cell lines with pronounced endogenous overexpression of TRPV4, MDA-MB-468 and HCC1569. Pharmacological activation of TRPV4 produced pronounced cell death through two mechanisms: apoptosis and oncosis in MDA-MB-468 cells. Apoptosis was associated with PARP-1 cleavage and oncosis was associated with a rapid decline in intracellular ATP levels, which was a consequence of, rather than the cause of, the intracellular ion increase. TRPV4 activation also resulted in reduced tumour growth in vivo. These studies define a novel therapeutic strategy for breast cancers that overexpress specific calcium permeable plasmalemmal ion channels with available selective pharmacological activators.

Expression of microRNAs miR-21 and miR-181c in cerebrospinal fluid and serum in canine meningoencephalomyelitis of unknown origin.

The potential of microRNAs (miRNAs) as biomarkers for canine meningoencephalomyelitis of unknown origin (MUO) was investigated by using quantitative real-time (qRT)-PCR to determine the expression of microRNA-21 (miR-21) and microRNA-181c (miR-181c) in the cerebrospinal fluid (CSF) of dogs. Dogs with MUO (n = 10) had higher levels of expression of miR-21 and miR-181c in the CSF than dogs with non-inflammatory neurological diseases (n = 8). There was a positive correlation between CSF cellularity and expression of miRNAs in the CSF, particularly for miR-21 in the MUO group.

Calcium influx pathways in breast cancer: opportunities for pharmacological intervention.

Ca(2+) influx through Ca(2+) permeable ion channels is a key trigger and regulator of a diverse set of cellular events, such as neurotransmitter release and muscle contraction. Ca(2+) influx is also a regulator of processes relevant to cancer, including cellular proliferation and migration. This review focuses on calcium influx in breast cancer cells as well as the potential for pharmacological modulators of specific Ca(2+) influx channels to represent future agents for breast cancer therapy. Altered expression of specific calcium permeable ion channels is present in some breast cancers. In some cases, such changes can be related to breast cancer subtype and even prognosis. In vitro and in vivo models have now helped identify specific Ca(2+) channels that play important roles in the proliferation and invasiveness of breast cancer cells. However, some aspects of our understanding of Ca(2+) influx in breast cancer still require further study. These include identifying the mechanisms responsible for altered expression and the most effective therapeutic strategy to target breast cancer cells through specific Ca(2+) channels. The role of Ca(2+) influx in processes beyond breast cancer cell proliferation and migration should become the focus of studies in the next decade.

Induction of epithelial-mesenchymal transition (EMT) in breast cancer cells is calcium signal dependent.

Signals from the tumor microenvironment trigger cancer cells to adopt an invasive phenotype through epithelial-mesenchymal transition (EMT). Relatively little is known regarding key signal transduction pathways that serve as cytosolic bridges between cell surface receptors and nuclear transcription factors to induce EMT. A better understanding of these early EMT events may identify potential targets for the control of metastasis. One rapid intracellular signaling pathway that has not yet been explored during EMT induction is calcium. Here we show that stimuli used to induce EMT produce a transient increase in cytosolic calcium levels in human breast cancer cells. Attenuation of the calcium signal by intracellular calcium chelation significantly reduced epidermal growth factor (EGF)- and hypoxia-induced EMT. Intracellular calcium chelation also inhibited EGF-induced activation of signal transducer and activator of transcription 3 (STAT3), while preserving other signal transduction pathways such as Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. To identify calcium-permeable channels that may regulate EMT induction in breast cancer cells, we performed a targeted siRNA-based screen. We found that transient receptor potential-melastatin-like 7 (TRPM7) channel expression regulated EGF-induced STAT3 phosphorylation and expression of the EMT marker vimentin. Although intracellular calcium chelation almost completely blocked the induction of many EMT markers, including vimentin, Twist and N-cadherin, the effect of TRPM7 silencing was specific for vimentin protein expression and STAT3 phosphorylation. These results indicate that TRPM7 is a partial regulator of EMT in breast cancer cells, and that other calcium-permeable ion channels are also involved in calcium-dependent EMT induction. In summary, this work establishes an important role for the intracellular calcium signal in the induction of EMT in human breast cancer cells. Manipulation of calcium-signaling pathways controlling EMT induction in cancer cells may therefore be an important therapeutic strategy for preventing metastases.

The precision and repeatability of a custom-made pointer device for determination of virtual landmarks in canine three-dimensional kinematics.

Placement of markers on anatomical landmarks represents a large source of error in three-dimensional kinematics. Our objectives were to test the accuracy and precision of a custom-made pointer and compare it to conventional skin markers in dogs. The pointer was first assessed by pointing at the surface of a spherical marker of known dimensions and position in space. Secondly, a point located cranio-distally to the lateral epicondyle was marked in 12 canine elbows with a Steinmann pin and reflective markers. Ability to locate a landmark was compared between the pointer and skin-mounted marker. The distance between experimental and true locations was compared between the two methods. A sphere was mathematically fitted through 29 collected points on the spherical marker. Centre, diameter and volume overlap of the fitted sphere were compared to that of the marker. A 0.729 mm bias was found indicating good accuracy. Residual values were small indicating good precision. The average distance between the true and experimental position of the anatomical landmarks were 9.55 ± 4.20 mm and 9.32 ± 3.28 mm for the pointer and the marker respectively. No significant differences were observed between the two methods. The pointer proved to be accurate and reliable for localizing virtual points and was at least equivalent to skin mounted markers for the detection of anatomical landmarks in the dog. It should prove useful in the localization of anatomical landmarks for kinematic analysis.

Effect of the length of the superficial plate on bending stiffness, bending strength and strain distribution in stacked 2.0-2.7 veterinary cuttable plate constructs. An in vitro study.

OBJECTIVES: Use of stacked veterinary cuttable plates (VCP) increases the construct stiffness, but it also increases the stress protection and concentrates the stress at the extremities of the implants. We hypothesized that by shortening the superficial plate, it would not reduce the stiffness of the construct, but that it would reduce the stress concentration at the plate ends. METHODS: A 3 mm fracture gap model was created with copolymer acetal rods, stacked 2.0-2.7 VCP and 2.7 screws. The constructs consisted of an 11-hole VCP bottom plate and a 5-, 7-, 9- or 11-hole VCP superficial plate. Five of each construct were randomly tested for failure in four-point bending and axial loading. Stiffness, load at yield, and area under the curve until contact (AUC) were measured. Strains were recorded during elastic deformation for each configuration. RESULTS: During both testing methods, stiffness, load at yield and AUC progressively decreased when decreasing the length of the superficial plate. No statistically significant differences were obtained for load at yield in four-point bending and AUC in axial loading. The strain within the implant over the gap increased as the length of the superficial plate decreased. CLINICAL SIGNIFICANCE: Shortening the superficial plate reduces the stiffness and strength of the construct, and decreases stress concentration at the implants ends. As the cross section of the implant covering the gap remained constant, friction between the plates may play a role in the mechanical properties of stacked VCP.

The effect of the combination of locking screws and non-locking screws on the torsional properties of a locking-plate construct.

Little is known about the torsional properties of bone-plate constructs when a combination of locking and non-locking screws have been used. Sixty cadaveric canine femurs were divided into three groups. In the first group, the plate was affixed using three non-locking screws. In the second group, only locking screws were used while a combination of one locking and two non-locking screws were used in the third group. All constructs were subjected to torsion until failure. Torque, angle of torsion, and work were all calculated at the maximum failure point, as well as at five degrees of plastic deformation, which was thought to be more representative of clinical failure. At the maximum failure point, the locking group had significantly higher torque, angle, and work values than the non-locking group. The combination group was intermediate to the two other groups, and significantly differed from the non-locking group in torque, and from the locking group in work. At five degrees of plastic deformation, the locking group required significantly higher torque and work than the non-locking group. The combination group required a significantly higher torque than the non-locking group. This study suggests that a construct composed of all locking screws will fail at a greater torque value, and sustain greater work to failure in torsion compared to a construct composed of all non-locking screws. The addition of a single locking screw to an otherwise non-locking construct will increase the torque at the offset failure point and may be of clinical value in constructs subjected to high torsional loads.

The biomechanical properties of the feline femur.

The purpose of this study was to determine the biomechanical properties of feline long bone by testing cadaver bone from mature cats in compression, three-point bending, notch sensitivity and screw pull-out strength. The determination of these properties is of clinical relevance with regard to the forces resulting in long bone fractures in cats as well as the behaviour and failure mode of surgical implants utilized for fracture stabilization and repair in the cat. Cadaveric cat femurs were tested in compression, three-point bending and in three-point bending after the addition of a 2.0 mm screw hole. Cortical screws, 2.7 mm in diameter, were inserted in cadaveric cat femur samples for screw pull-out testing. The mean maximum load to failure of mid diaphyseal feline femurs tested in compression was 4201+/-1218 N. Statistical analysis of the parameter of maximum load tested in compression revealed a statistical difference between sides (p=0.02), but not location (p=0.07), or location by side (p=0.12). The maximum strength of mid diaphyseal feline femurs tested in compression was 110.6+/-26.6 MPa. The modulus of elasticity of mid-diaphyseal cat femurs tested in compression was determined to be 5.004+/-0.970 GPa. The mean maximum load to failure of feline femurs tested in three-point bending was 443+/-98 N. The mean maximum load to failure of feline femurs tested in three-point bending after a 2.0 mm diameter hole was drilled in the mid-diaphyseal region of each sample through both cortices was 471+/-52 N. The mean maximum load required for screw pull-out of 2.7 mm cortical screws placed in feline femurs tested in tension was 886+/-221 N. This data should be suitable for investigating fracture biomechanics and the testing of orthopaedic constructs commonly used for fracture stabilization in the feline patient.

Molecular phylogeny and biogeography of the dung beetle genus Temnoplectron Westwood (Scarabaeidae: Scarabaeinae) from Australia's wet tropics.

The landscape of the Australian Wet Tropics can be described as "islands" of montane rainforest surrounded by warmer or more xeric habitats. Historical glaciation cycles have caused expansion and contraction of these rainforest "islands" leading to consistent patterns of genetic divergence within species of vertebrates. To explore whether this dynamic history has promoted speciation in endemic and diverse groups of insects, we used a combination of mtDNA sequencing and morphological characters to estimate relationships and the tempo of divergence among Australian representatives of the dung beetle genus Temnoplectron. This phylogenetic hypothesis shares a number of well-supported clades with a previously published phylogenetic hypothesis based on morphological data, though statistical support for several nodes is weak. Sister species relationships well-supported in both tree topologies, and a tree obtained by combining the two data sets, suggest that speciation has mostly been allopatric. We identify a number of speciation barriers, which coincide with phylogeographic breaks found in vertebrate species. Large sequence divergences between species emphasize that speciation events are ancient (pre-Pleistocene). The flightless, rainforest species appear to have speciated rapidly, but also in the distant past.

Evaluating Australia's National Medicines Policy using geographical mapping.

BACKGROUND: There has been a proliferation of quality use of medicines activities in Australia since the 1990s. However, knowledge of the nature and extent of these activities was lacking. A mechanism was required to map the activities to enable their coordination. AIMS: To develop a geographical mapping facility as an evaluative tool to assist the planning and implementation of Australia's policy on the quality use of medicines. METHODS: A web-based database incorporating geographical mapping software was developed. Quality use of medicines projects implemented across the country was identified from project listings funded by the Quality Use of Medicines Evaluation Program, the National Health and Medical Research Council, Mental Health Strategy, Rural Health Support, Education and Training Program, the Healthy Seniors Initiative, the General Practice Evaluation Program and the Drug Utilisation Evaluation Network. In addition, projects were identified through direct mail to persons working in the field. RESULTS: The Quality Use of Medicines Mapping Project (QUMMP) was developed, providing a Web-based database that can be continuously updated. This database showed the distribution of quality use of medicines activities by: (i) geographical region, (ii) project type, (iii) target group, (iv) stakeholder involvement, (v) funding body and (vi) evaluation method. At September 2001, the database included 901 projects. Sixty-two per cent of projects had been conducted in Australian capital cities, where approximately 63% of the population reside. Distribution of projects varied between States. In Western Australia and Queensland, 36 and 73 projects had been conducted, respectively, representing approximately two projects per 100,000 people. By comparison, in South Australia and Tasmania approximately seven projects per 100,000 people were recorded, with six per 100,000 people in Victoria and three per 100,000 people in New South Wales. Rural and remote areas of the country had more limited project activity. CONCLUSIONS: The mapping of projects by geographical location enabled easy identification of high and low activity areas. Analysis of the types of projects undertaken in each region enabled identification of target groups that had not been involved or services that had not yet been developed. This served as a powerful tool for policy planning and implementation and will be used to support the continued implementation of Australia's policy on the quality use of medicines.