Validation of p53 Immunohistochemistry (PAb240 Clone) in Canine Tumors with Next-Generation Sequencing (NGS) Analysis

In human medicine, p53 immunohistochemistry (IHC) is a common method that is used for the identification of tumors with TP53 mutations. In veterinary medicine, several studies have performed IHC for p53 in canine tumors, but it is not known how well it actually predicts the mutation. The aim of this study was to estimate the accuracy of the IHC method for p53 (clone PAb240) using a lab-developed NGS panel to analyze TP53 mutations in a subset of malignant tumors in dogs. A total of 176 tumors were analyzed with IHC and then 41 were subjected to NGS analysis; among them, 15 were IHC positive and 26 were negative, and 16 out of 41 (39%) were found to be inadequate for NGS analysis. Excluding the non-evaluable cases at NGS, of the remaining eight IHC-positive cases, six were mutants and two were wild-type. Among the 17 IHC-negative cases, 13 were wild type, and 4 were mutants. The sensitivity was 60%, specificity was 86.7%, and the accuracy was 76%. These results suggest that when using IHC for p53 with this specific antibody to predict mutation, up to 25% wrong predictions can be expected

Foal weaning in Italy: management and factors associated with the development of abnormal behaviours

The increase of stress at weaning may affect foal welfare and lead to the development of abnormal behaviours (AB). Among them, weaving, box walking, wind suckling and wood chewing, due to their repetitiveness, are considered stereotypic behaviours. An online survey was carried out with 22 questions concerning husbandry methods and behaviour of both foals and mares. Mares are defined dominant, middle or low ranking based on the number of threats given and received in the herd. Horses with dominant behaviour are commonly considered less willing to learn in some disciplines, whereas dominant stallions in dressage eventing obtain generally higher scores than others. Therefore, causes, which could affect dominant attitude in foals, were analysed as well. Data from 74 breeders of Central-Northern Italy, describing 148 horses, were analysed to identify husbandry techniques and management risk factors associated with development of AB. Data were compared with surveys in other countries: higher percentage of Italian foals (16.2%) and mares (10.9%) showing AB (vs an average of 5.2% of other studies) and a higher age average at weaning (7vs 5-6 months) were observed. No effect of breed, feeding, paddock size or housing resulted in this study. Taming period was critical for the onset of AB for 4 foals out of 12 presenting AB. Generally, oral-ingestive AB were more frequent (65%) than other AB. Among them, wood chewing was the most frequent (35%). Expression of foal’s normal behaviour is negatively affected by dam aggressiveness toward humans (P<0.05, chi square test). Following observations showed a trend (P<0.1): development of AB in foals may be in relation to AB in mares; foal dominant behaviour may be related with mare’s dominant attitude in the herd and negatively associated with early handling, which seems favourable for normal behaviour expression. The sample may be biased (respondents may be only breeders interested in improving welfare) however this is an inherent problem with all similar studies. Main difference with North Europe countries is lower competence of the Italian equine sector. Despite the low number of animal sample, the survey can give some indications on the origin of AB in horses

Using Geographic Information Systems (GIS) for Targeted National Recruitment of Community-Dwelling Caregivers Managing Dementia-Related Behavioral and Psychological Symptoms: A Recruitment Approach for a Randomized Clinical Trial.

Over 16 million caregivers of people living with dementia require support in a range of issues, including self-care, disease education, and guidance for how to manage behavioral and psychological symptoms of dementia (BPSD). Non-pharmacological interventions are needed to address these areas, and online applications have been shown to be safe and effective. To ensure the efficacy of such interventions, racially, ethnically, geographically, and socioeconomically diverse participants must be recruited to increase the generalizability of study outcomes. This protocol paper describes a recruitment plan using Geographic Information Systems (GIS) to reach a representative sample of caregivers across the United States for a national Phase III clinical study. Using publicly available census data from the American Community Survey (ACS), combined with location data for local aging resources such as Area Agencies on Aging (AAA), recruitment will be derived from data analysis conducted in ESRI ArcGIS v10.7.1. Datasets including age, gender, income, and education will be assessed nationally at the county and census tract spatial scale in a nine-step process to develop recruitment priority areas containing high concentrations of eligible participants living in the community. Overall, the current protocol will demonstrate the value of GIS in tailoring targeted outreach strategies to recruit community-dwelling populations through local resource institutions. This novel approach may have far-reaching implications in future recruitment initiatives and help to secure racially/ethnically diverse samples

Influence of nonlinear modeling on capacity assessment of RC framed structures

Many existing buildings in the world present serious seismic deficiencies and need to be retrofitted. However, the basis for an effective seismic retrofit intervention is a reliable assessment of the structure. To this end, nowadays structural engineers can simulate the response of structures subjected to earthquake excitation by nonlinear numerical models. These models consider explicitly the mechanical nonlinearities of the structural members, identify the parts of the structure where yielding takes place, quantify the demand of plastic deformation and force. Furthermore, a number of models is available to carry out the nonlinear analysis of structures. All these models are able to provide a detailed representation of the seismic response of the structure. However, they are controlled by many parameters that need to be properly set to obtain an accurate prediction of the response. Based on the framework depicted above, the target of the Reinforced Concrete Work Package 2 of the ReLUIS 2018 project was to examine and compare different nonlinear modelling techniques used to evaluate the response of structures by pushover analysis. To this end, a case study building is analysed by the eight research units involved in the project by different nonlinear numerical models. The building presents very different lateral stiffness and strength in the longitudinal and transverse directions. Each numerical model is run two times including and not including the masonry infills. Furthermore, pushover analysis is run two times with forces in the longitudinal and transverse directions. Finally, the results are compared to illustrate advantages and limitations of each nonlinear modelling techniqu

Descriptive analysis of the French NS-Park registry: Towards a nation-wide Parkinson's disease cohort?

International audienceIntroduction: Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's. The French clinical research network for PD (NS-Park) has created a national patient registry to i)report medical activity of Parkinson Expert Centers (PECs) to the Ministry of Health, ii)facilitate PD patients pre-screening for clinical trials, iii) provide a source for pharmaco-epidemiology studies.Objective: Assess the French Parkinsonian population at a nation-wide level and discover new clinical characteristics.Methods: In this feasibility study, PECs prospectively collected clinical data in a standardized manner. The population main clinical characteristics are described, focusing on motor and non-motor symptoms and treatments, assessing its representativeness. By using an unbiased clustering with multiple correspondence analysis (MCA), we also investigate potential relationships between multiple variables like symptoms and treatments, as clues for future studies.Results: Between 2012 and 2016, among 11,157 included parkinsonian syndromes, 9454 (85%) had PD. MCA identified various profiles depending on disease duration. Occurrences of motor complications, axial signs, cognitive disorders and Levodopa use increase over time. Neurovegetative symptoms, psychiatric disorders, sleep disturbances and impulse control disorders (ICDs) seem stable over time. As expected, ICDs were associated to dopaminergic agonist use but other associations, such as ICDs and sleep disturbances for instance, or anxiety and depression, were found.Conclusions: Our results report one of the biggest PD registries ever reported and demonstrate the feasibility of implementing a nation-wide registry of PD patients in France, a potent tool for future longitudinal studies and clinical trials' population selection, and for pharmaco-epidemiology and cost-effectiveness studies