Acute phase protein levels in dogs with mast cell tumours and sarcomas

<p><b>Context:</b> The acute phase protein response is part of a non-specific and complex host response to inflammation. It occurs shortly after tissue injury and may be induced by a range of different causes, including infectious, inflammatory, neoplastic, traumatic or immunological disease. Although it was conventionally believed that APPs were exclusively hepatocyte derived, there is increasing evidence to support extra-hepatic generation in neoplastic and other disease states. In people, C-reactive protein (CRP) has been shown to be of value in identifying metastatic disease from primary renal tumours as well as showing promise for monitoring rejection of renal transplants. Serum CRP correlates with survival in colorectal cancer and oesophageal squamous cell carcinoma while serum amyloid A (SAA) concentrations correlate with cancer activity, stage and prognosis in gastric tumours. Recent immunohistochemical studies in people with oesophageal carcinoma suggest that tumour tissue may itself elaborate APP with a poorer survival and outcome associated with tumours elaborating higher levels of CRP. A similar association has been seen between alpha-1 acid glycoprotein (AGP) and colorectal tumours and ovarian carcinoma.</p> <p>As yet, studies regarding APP values in neoplastic conditions in dogs are limited, and many are non-specific. In veterinary patients, elevated levels of AGP have been identified in dogs with a range of tumours with localisation to liver and splenic tissue in one study. Another study found higher levels of AGP in dogs with non-specific tumours of grade III-IV based on the WHO Tumour Node Metastasis (TNM) scale and elevated serum AGP has been documented in non-specific tumour-bearing cats. Elevated CRP levels have been documented in both dogs and cats with lymphoma and serum CRP may be used as an indicator of complete remission status in dogs with multicentric lymphoma. Elevated levels of CRP, Haptoglobin (Hp) and SAA have been identified in dogs with mammary tumours, with significant increases over normal in the presence of metastatic disease, primary tumours greater than 5cm in diameter and those with ulceration.</p> <p>In this study we evaluated an APP profile using four APPs (CRP, Hp, SAA and AGP), in dogs with mast cell tumours (MCTs) and sarcomas to assess whether the APP profile would change in reflection of tumour presence; whether the extent of any change would correlate with tumour grade; and whether the changes would differ with tumour type.</p> <p><b>Approach:</b> Patients with naturally occurring MCTs and sarcomas presenting for staging and treatment were included if they met the study criteria. Criteria for inclusion were that the patient was not currently being treated with steroids, did not have a recent history of infectious or inflammatory disease other than the tumour, a definitive histological diagnosis was available and a full staging procedure was completed prior to surgery using standard oncological protocols to identify metastatic disease where present. Following surgical resection each tumour was submitted for full histological evaluation and grading to include assessment of the margins of excision. Cases were only enrolled in the study if blood sampling formed part of the clinical investigation and/or treatment, and where residual blood was available after diagnostic sampling which would otherwise have been disposed of as clinical waste. In brief, the CRP levels were determined by immunoturbidometric assay and Hp by means of haemoglobin binding capacity assay. SAA was measured with a commercial canine ELISA kit (TriDelta Development, Dublin, Ireland) and AGP was measured with a commercial radial immunodiffusion assay (J-Path Inc, Tokyo, Japan).</p> <p><b>Results:</b> All comparisons using continuous data were checked for normality and equality of variances and appropriate statistical tests were employed (student’s t test operationalised as a two-sample Welch’s test for samples of unequal sizes and variances, Mann-Whitney, Chi-square and Fishers exact tests as appropriate). In MCTs, the CRP and AGP were elevated above reference ranges, Hp showed no significant change and SAA dropped relative to the reference range. In sarcoma patients CRP, Hp and AGP were all elevated above reference ranges. None of the tumour grade differences were significant apart from SAA in sarcoma patients where values in grade 2 sarcoma were significantly higher than those in grade 1.</p> <p><b>Interpretation and notes of caution:</b> The numbers in our groups were small which compromises the validity of statistical evaluation so our results must be interpreted with caution. However some interesting relationships have emerged from the initial evaluation which suggests that APP profiles may have potential for screening in patients with neoplastic disease. For patients with MCTs, CRP and AGP levels would be expected to increase, with a concurrent drop in SAA levels. In sarcoma patients CRP, AGP and Hp can all be expected to increase. These initial results need to be evaluated in larger numbers of cases with naturally occurring disease to validate the findings, to assess whether the presence and extent of metastatic disease has a significant effect, and also to confirm whether the values alter after surgical resection of the primary tumour.</p> <p><b>Significance of findings:</b> If there are consistent and specific changes in APP profiles associated with different tumour types in dogs, as is the case with a wide range of cancers in humans, then there may be potential for APP profiles on routine blood samples to be used as indicators of disease, or where monitoring for recurrence. Whether they could also have potential for assessment of the presence of metastatic disease and prognosis as in people is unknown as yet.</p&gt

Low-dose ursodeoxycholic acid prolongs cholesterol nucleation time in gallbladder bile of patients with cholesterol gallstones

The high rate of stone recurrence represents a drawback of non-surgical therapy of cholesterol gallstone disease. Although most studies report that long-term bile acid treatment does not have protective effects, preliminary results suggest that low-dose ursodeoxycholic acid decreases the rate of gallstone recurrence in a subgroup of younger patients. To clarify the underlying mechanism we investigated whether low-dose ursodeoxycholic acid treatment influences biliary cholesterol saturation and/or nucleation time of cholesterol. Ten patients with cholesterol gallstones and functioning gallbladder received 250 mg ursodeoxycholic acid/day at bedtime 6–10 days prior to cholecystectomy. Eleven patients with cholesterol gallstones without treatment served as controls. Cholesterol crystals were present in the gallbladder bile of 7 out of the 10 patients receiving ursodeoxycholic acid and in all control biles. Ursodeoxycholic acid treatment significantly (P < 0.02) decreased the cholesterol saturation index (mean ± S.E.: 0.94 ± 0.05 vs. 1.43 ± 0.18) and led to an approximately 5-fold prolongation (P < 0.005) of the cholesterol nucleation time (mean ± S.E.: 12.0 ± 2,4 vs. 2.3 ± 0.7 days). We conclude that lowdose ursodeoxycholic acid might be effective in the prevention of post-dissolution gallstone recurrence by both decreasing cholesterol saturation and prolonging cholesterol nucieation tim

Generativism: the new hybrid

Generative Artificial Intelligence (GenAI) in Education has in a few short months moved from being the topic of discussion around speculative education futures to a very concrete reality. It is clear that the future of education, as all industries, is collaboration with GenAI. GenAI attributes make it well suited for social and constructivist approaches to learning that value collaboration, community and the construction of knowledge and skills through active learning. This article presents an approach to designing education in collaboration with GenAI, based on digital education frameworks adapted for this new hybrid of the AI age.Comment: 9 pages, 5 figure

Risk and Protection Factors for Substance Use Among Young People

This report presents the results of a study of substance use among young people in Ireland based on information collected in 2008 during face-to-face interviews with 991 people, aged between 15 and 18. The target population comprised school-attending students and young people who, having left school, were attending either a Youthreach centre for education or FÁS Community Training Centre. This latter population is described in this study as “early school-leavers” and represents approximately 12% of the full annual cohort of early school-leavers. This is therefore one of the largest studies ever undertaken on substance use among young people in Ireland, and differs from other studies in two important ways. First, whereas previous studies on substance use in this section of the population focused almost exclusively on young people attending school, this study aims specifically to explore the factors associated with substance use among those who left school early. Secondly, the study aims to identify the risk and protective factors that influence young people’s decisions regarding substance use. The study thus emphasises the underlying conditions for and dynamics of substance use with a view to identifying factors that could be addressed through appropriate policies. In pursuing these two objectives, considerable emphasis is placed on comparing the respective risk and protective factors across the two groups: those who have left school early and are now either attending a Youthreach centre for education or FÁS Community Training Centre, and those who are still attending school. The analysis identifies a limited number of highly significant risk and protective factors that can increase or decrease the risk of using substances among 15 to 18-year-olds in Ireland. When attention is focused on those factors that are amenable to change, the most important conclusion is that both the family (the young person’s parents above all) and the educational institution can have a major impact on this decision

Optimising the Sampling Methodology for CSO Household Surveys

This report assesses alternative sampling designs for CSO household surveys, such as the Quarterly National Household Survey (QNHS), the annual Survey on Income and Living Conditions (SILC) and Household Budget Survey (HBS), as well as considering the design of a potential future General Household Survey. The aim of the report is to provide recommendations in relation to appropriate sampling designs, including considerations in relation to sample size, the degree of clustering, stratification and selection procedures for areas and households

The measurement of social disadvantage and its spatial articulation in the Republic of Ireland

This article contributes to policy research by developing a reliable aggregate measure of social need in small areas and by describing how this index can be used to evaluate public interventions in disadvantaged areas. Spatially-targeted initiatives to combat disadvantage have been implemented in many OECD countries, and the availability of EU funding has encouraged their diffusion. The longitudinal analysis and evaluation of these initiatives is difficult using existing indices, as these do not facilitate comparisons over time. In this article, we describe an alternative approach that relies on Confirmatory Factor Analysis and permits diachronic analyses