Preliminary assessment of cognitive impairments in canine idiopathic epilepsy

In humans, epilepsy can induce or accelerate cognitive impairment (CI). There is emerging evidence of CI in dogs with idiopathic epilepsy (IE) from recent epidemiological studies. The aim of our study was to assess CI in dogs with IE using two tests of cognitive dysfunction designed for use in a clinical setting. Dogs with IE (n=17) were compared against controls (n=18) in their performance in two tasks; a spatial working memory task and a problem-solving task. In addition, owners completed the Canine Cognitive Dysfunction Rating (CCDR) scale for their dog. The groups did not differ statistically with respect to age and breed. Dogs with IE performed significantly worse than controls on the spatial working memory task (P=0.016), but not on the problem solving task (P=0.683). CCDR scores were significantly higher in the IE group (P=0.016); however, no dogs reach the recommended threshold score for CCD diagnosis. Our preliminary data suggest that dogs with IE exhibit impairments in a spatial working memory task. Further research is required to explore the effect of IE on other cognitive abilities in dogs with a larger sample, characterising the age of onset, nature and progression of any impairments and the impact of anti-epileptic drugs

Structural fingerprints of transcription factor binding site regions

Fourier transforms are a powerful tool in the prediction of DNA sequence properties, such as the presence/absence of codons. We have previously compiled a database of the structural properties of all 32,896 unique DNA octamers. In this work we apply Fourier techniques to the analysis of the structural properties of human chromosomes 21 and 22 and also to three sets of transcription factor binding sites within these chromosomes. We find that, for a given structural property, the structural property power spectra of chromosomes 21 and 22 are strikingly similar. We find common peaks in their power spectra for both Sp1 and p53 transcription factor binding sites. We use the power spectra as a structural fingerprint and perform similarity searching in order to find transcription factor binding site regions. This approach provides a new strategy for searching the genome data for information. Although it is difficult to understand the relationship between specific functional properties and the set of structural parameters in our database, our structural fingerprints nevertheless provide a useful tool for searching for function information in sequence data. The power spectrum fingerprints provide a simple, fast method for comparing a set of functional sequences, in this case transcription factor binding site regions, with the sequences of whole chromosomes. On its own, the power spectrum fingerprint does not find all transcription factor binding sites in a chromosome, but the results presented here show that in combination with other approaches, this technique will improve the chances of identifying functional sequences hidden in genomic data

Mechanical assist in cardiac arrest: Optimising circulatory support. Experimental studies.

Introduction: Mechanical circulatory support (MCS) may be useful in cardiac arrest (CA), both in- and out- of hospital. However, efficacy and survival benefit has been difficult to evaluate compared to standard cardiopulmonary resuscitation. In three experimental studies we aimed to assess different modes of MCS during CA in providing adequate organ perfusion and systemic circulation and identify predictors of sustainable post-CA heart function. Different theoretical assumptions were the background for analysis in the three study protocols performed as acute experiments in anaesthetized pigs: Paper I: A major limitation to the effectiveness of a LVAD alone during CA is the lack of left ventricular (LV) filling due to minimal pulmonary circulation. We therefore wanted to assess if the combination of a left- and right ventricular assist device (BIVAD/BiPella) was beneficial as circulatory support versus a LVAD alone. Paper II: ECMO has the potential to replace systemic circulation during CA. However, concerns have been voiced regarding retrograde flow-delivery and effect on the myocardium during circulatory collapse. Based on results from Paper I we optimized BiPella support aiming to improve and maintain acceptable coronary perfusion pressure, believing this could potentially rectify the poor outcome of BIVAD/BiPella in Paper I if successful. Thus, in Paper II we compared the efficacy of balanced biventricular circulatory assist with extracorporeal membrane oxygenation (ECMO). Paper III: Pressure build-up in the left ventricle during cardiac arrest may be detrimental during extracorporeal cardiopulmonary resuscitation (ECPR) as indicated in Paper II. Therefore, we wished to investigate if unloading (venting) the left ventricle using add-on LVAD could be of benefit. However, the ideal flow-contributions of each assist device when combining LVAD and ECMO during ECPR in is not known. We therefore wanted to compare ECMO with standard or reduced flow and add-on LVAD versus ECMO alone. Finally, we wished to assess the contribution of add-on LVAD regarding pulmonary flow. Materials and methods: The animal experiments were performed at the Vivarium, University of Bergen, and protocols were approved by the Norwegian Animal Research Authority or by the Norwegian Food Safety Authority. Paper I and II were performed with percutaneous techniques. The final experiment was an open chest model. All protocols followed a similar timeline: 1. Anaesthesia and instrumentation of the pig. 2. Baseline evaluation. 3. Induction of CA by application of a 9V DC battery to the myocardium. 4. Immediate initiation of mechanical circulatory support (MCS). 5. Three attempts of cardioversion at the end of the CA period. 6. If successful return of spontaneous circulation (ROSC) was achieved, unsupported observation (Paper II and Paper III). Comparisons between intervention groups: 1. Haemodynamics (during and after CA). 2. Organ tissue blood flow rate (organ perfusion) and device output as calculated from fluorescent microspheres. 3. Arterial blood gases and biomarkers. 4. ROSC. 5. Sustained cardiac function post-ROSC (Paper II and Paper III). In Paper I, twenty animals were randomized in two groups receiving circulatory support either by the Impella CP alone (LVAD) or in combination with the Impella RP (BIVAD/BiPella) during 30 minutes of CA. In Paper II, twenty pigs were randomized to receive MCS either by BiPella or by extracorporeal membrane oxygenation (ECMO) during 40 minutes of CA. If ROSC was successful, animals were observed for 60 minutes unsupported. In Paper III, twenty-four animals were randomized in three groups. Extracorporeal cardiopulmonary resuscitation (ECPR) in Group 1 was provided by ECMO with standard-flow and add-on Impella CP. In Group 2: ECMO with reduced flow combined with Impella CP. In Group 3, animals were supported by standard-flow ECMO alone. ECPR lasted for 60 minutes. If ROSC was successful, 180 minutes unsupported observation followed. Results: Paper I demonstrated that BIVAD/BiPella provides superior circulatory support and perfusion for peripheral organs (including the brain) related to higher LVAD output and increased central aortic pressure compared to LVAD alone. However, myocardial perfusion was related to the pressure difference between mean aortic pressure and mean left ventricular pressure during cardiac arrest. Myocardial perfusion was inferior with BiPella resulting in significantly fewer ROSC (5/10 vs 10/10, p = 0.033) despite significantly higher etCO2 (p = 0.029). Paper II showed that balancing RVAD and LVAD to ensure acceptable coronary perfusion pressure and concomitant LVAD output was feasible, also sustaining vital organ perfusion. However, ECMO provided a more optimal systemic circulatory support. Device output and mean aortic pressure were increased with subsequent improved peripheral tissue perfusion reflected by reduction of s-lactate. In animals where sufficient myocardial perfusion pressure (mean aortic pressure – mean LV pressure > 10-15 mmHg) could not be achieved, perfusion (ml/min/g) was reduced in the subendo- and midmyocardium, averaging 0.59 ± 0.05 vs. 0.31 ± 0.07, (p = 0.005) and 0.91 ± 0.06 vs 0.65 ± 0.15 (p = 0.085), but not in the subepicardium (1.02 ± 0.07 vs 0.86 ± 0.17, p = 0.30) irrespective of group. These subjects also had inferior post-ROSC cardiac function. Paper III showed that add-on LVAD improved haemodynamics compared with ECMO alone during refractory CA. Add-on LVAD could not substitute a reduced ECMO-flow. Three animals with reduced ECMO flow and adjunctive Impella support did not achieve ROSC. With ECMO alone, ROSC was obtained in all animals. However, 4/8 died post-ROSC due to development of cardiogenic shock. In the remaining 21 animals, 17 animals had sustained cardiac function at study termination 3 h after ROSC. Animals without sustained cardiac function (7/24) had reduced mAP (p < 0.001), CPP (p = 0.002) and mPAf (p = 0.004) during CA and ECPR. Conclusions: Paper I: Biventricular support during cardiac arrest was associated with high intraventricular pressure in the left ventricle resulting in decreased myocardial perfusion pressure, reduced myocardial tissue blood flow rate and subsequent reduction in ROSC. Paper II: Myocardial perfusion and sustained cardiac function were related to myocardial perfusion pressure during VF irrespective of MCS (ECMO and balanced biventricular support). Balanced biventricular support maintained lower intraventricular pressure compared to ECMO. Paper III: Add-on LVAD improved haemodynamics compared to ECMO alone. An add-on Impella could not substitute a reduction in ECMO flow. Increased mean aortic pressure, myocardial perfusion pressure and mean pulmonary artery flow were related to sustained cardiac function and ROSC.Doktorgradsavhandlin

Approximation Algorithms for the Two-Watchman Route in a Simple Polygon

The two-watchman route problem is that of computing a pair of closed tours in an environment so that the two tours together see the whole environment and some length measure on the two tours is minimized. Two standard measures are: the minmax measure, where we want the tours where the longest of them has smallest length, and the minsum measure, where we want the tours for which the sum of their lengths is the smallest. It is known that computing a minmax two-watchman route is NP-hard for simple rectilinear polygons and thus also for simple polygons. Also, any c-approximation algorithm for the minmax two-watchman route is automatically a 2c-approximation algorithm for the minsum two-watchman route. We exhibit two constant factor approximation algorithms for computing minmax two-watchman routes in simple polygons with approximation factors 5.969 and 11.939, having running times O(n^8) and O(n^4) respectively, where n is the number of vertices of the polygon. We also use the same techniques to obtain a 6.922-approximation for the fixed two-watchman route problem running in O(n^2) time, i.e., when two starting points of the two tours are given as input.Comment: 36 pages, 14 figure

Visitors’ learning for environmental sustainability: Testing short- and long-term impacts of wildlife tourism experiences using structural equation modelling

Wildlife tourism experiences have the potential to positively impact tourists' awareness, appreciation and actions in relation to the specific wildlife they encounter and the environment in general. This paper investigates the extent of such impact across multiple sites, and uses Structural Equation Modelling to identify factors that best predict positive long-term learning and environmental behaviour change outcomes. Three sets of variables were measured - visitors' entering attributes (including pre-visit environmental orientation and motivation for the visit), salient aspects of the experience, and short- and long-term learning and environmental behaviour change outcomes. Although attributes such as pre-visit commitment and motivation to learn were among the best predictors of the long-term impact of the experience, there was evidence that aspects of the experience were also important. In particular, reflective engagement which involved cognitive and affective processing of the experience was found to be associated with short- and long-term environmental learning outcomes. The implications for wildlife tourism managers are discussed. (C) 2010 Elsevier Ltd. All rights reserved

Transmission dynamics and prospects for the elimination of canine rabies

Rabies has been eliminated from domestic dog populations in Western Europe and North America, but continues to kill many thousands of people throughout Africa and Asia every year. A quantitative understanding of transmission dynamics in domestic dog populations provides critical information to assess whether global elimination of canine rabies is possible. We report extensive observations of individual rabid animals in Tanzania and generate a uniquely detailed analysis of transmission biology, which explains important epidemiological features, including the level of variation in epidemic trajectories. We found that the basic reproductive number for rabies, R&lt;sub&gt;0&lt;/sub&gt;, is very low in our study area in rural Africa (&#8764;1.2) and throughout its historic global range (&#60;2). This finding provides strong support for the feasibility of controlling endemic canine rabies by vaccination, even near wildlife areas with large wild carnivore populations. However, we show that rapid turnover of domestic dog populations has been a major obstacle to successful control in developing countries, thus regular pulse vaccinations will be required to maintain population-level immunity between campaigns. Nonetheless our analyses suggest that with sustained, international commitment, global elimination of rabies from domestic dog populations, the most dangerous vector to humans, is a realistic goal

Tourist experiences of individuals with vision impairments

People with visual disabilities Travel Australia. Tourism Research Australia