Aging pathology in sprague dawley rats : background lesions and comparative study between wild type and transgenic rats with neuronal overexpression of human adenosine A2A receptors

Dissertação de Mestrado Integrado em Medicina VeterináriaAging is a complex phenomenon defined as a time-dependent functional decline, progressive loss of physiological integrity and progressive increase in disease susceptibly. Adenosine A2A receptors (A2AR) are G protein-couple receptors that, upon binding of adenosine, lead to different transducing signals. Although having a protective effect, A2AR also play an important role in neurodegenerative disorders and are upregulated in the brain of Alzheimer and Parkinson patients. Previous studies from our collaborators showed that transgenic rats with neuronal overexpression of human A2AR (Tg (CaMKIIhA2AR)) have depressive-like behavior, impaired hypothalamic-pituitary-adrenal (HPA) axis and, as a result of this, increased levels of circulating corticosteroids. The aim of this work was to evaluate, by histopathology, the impact of the neuronal overexpression of human A2AR in the onset of specific or age-associated lesions in transgenic Sprague Dawley rats. Comprehensive necropsy and histopathology were performed in 37 Wild-type (Wt) and 39 transgenic (Tg) rats, at specific time-points, ranging from 12 to 126 weeks of age. Univariate and multivariate statistical analysis were performed to investigate the association between the phenotype and genotype. Briefly we found that Tg rats are 2.7 times more likely to develop systemic pathology than Wt rats [Odds ratio (OR) 2.745, IC 95% 1.0.07-6.997; (p0.05)]. In blood vessels, mineralization was the most frequent lesion and Tg rats were 5.5 times more likely to develop this lesion than Wt [OR 5.486, IC 95% 1.776- 17.074; (p0.05)]. Regarding adrenal gland pathology, vacuolation of the cortical cells was the most frequent lesion and Tg rats were 4.3 times more likely to develop this pathology than Wt [OR 4.3, IC 95% 1.156-16.248; (p0.05)]. Nos vasos sanguíneos, a lesão mais frequente foi a mineralização da parede, sendo que os ratos Tg foram 5.5 vezes mais suscetíveis a desenvolver esta lesão que os Wt [OR 5.486, IC 95% 1.776- 17.074; (p0.05)]. Relativamente às adrenais, a lesão mais frequente foi a vacuolização das células da cortical e os ratos Tg foram 4.3 vezes mais suscetíveis para o desenvolvimento desta lesão que os Wt [OR 4.3, IC 95% 1.156-16.248; (p<0.05)]. Fibroadenoma mamário foi o tumor mais frequente, tendo sido observado em um rato Wt e cinco ratos Tg. Mesmo em casos onde não foi observada diferença entre ratos Wt e Tg, todas as lesões encontradas neste estudo são lesões muitas vezes associadas ao envelhecimento, típicas desta espécie e a sua incidência correlacionou-se com a idade. Os nossos resultados mostram uma relação clara entre a sobre expressão neuronal de A2AR e envelhecimento acelerado na nossa amostra, e apesar de não termos explorado os mecanismos específicos para tal acontecimento, poderá estar ligado ao facto dos ratos Tg terem disfunção do eixo hipotálamo-hipófise-adrenal e níveis elevados de corticosterona, o que se traduz em stress crónico. A conhecimento dos autores, este é o primeiro estudo a caracterizar as repercussões sistémicas da sobre expressão neuronal de A2AR, que é observada em várias doenças degenerativas durante o envelhecimento.N/

Unlocking Machine Learning Business Value

Machine learning (ML) stands out as one of the most successful advanced analytics for dealing with big data. However, as a quite recent tool amongst organizations, there are some doubts hanging over this technology. Through an original lens, we expect to substantiate how organizations can sustained ML business value. We developed a conceptual model, grounded on the resource-based view, that aims to validate key antecedents of ML business value. Through a positivist approach, we imply ML use, big data analytics maturity, top management support and process complexity enhance ML business value, in terms of firm performance. Due to the pioneering nature of our research model, we expect to support our data analysis with the partial least squares. To the authors’ best knowledge, this represents the first study aiming such findings on the ML discipline

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Assessing the drivers of machine learning business value

Machine learning (ML) is expected to transform the business landscape in the near future completely. Hitherto, some successful ML case-stories have emerged. However, how organizations can derive business value (BV) from ML has not yet been substantiated. We assemble a conceptual model, grounded on the dynamic capabilities theory, to uncover key drivers of ML BV, in terms of financial and strategic performance. The proposed model was assessed by surveying 319 corporations. Our findings are that ML use, big data analytics maturity, platform maturity, top management support, and process complexity are, to some extent, drivers of ML BV. We also find that platform maturity has, to some degree, a moderator influence between ML use and ML BV, and between big data analytics maturity and ML BV. To the best of our knowledge, this is the first research to deliver such findings in the ML field.authorsversionpublishe

Unlocking machine learning business value

Reis, C., Ruivo, P., Oliveira, T., & Faroleiro, P. (2019). Unlocking machine learning business value. In Atas da Conferencia da Associacao Portuguesa de Sistemas de Informacao 2019: Capsi 2019 (Atas da Conferencia da Associacao Portuguesa de Sistemas de Informacao).Machine learning (ML) stands out as one of the most successful advanced analytics for dealing with big data. However, as a quite recent tool amongst organizations, there are some doubts hanging over this technology. Through an original lens, we expect to substantiate how organizations can sustained ML business value. We developed a conceptual model, grounded on the resource-based view, that aims to validate key antecedents of ML business value. Through a positivist approach, we imply ML use, big data analytics maturity, top management support and process complexity enhance ML business value, in terms of firm performance. Due to the pioneering nature of our research model, we expect to support our data analysis with the partial least squares. To the authors’ best knowledge, this represents the first study aiming such findings on the ML discipline.publishersversionpublishe

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AimThe SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery.MethodsThis was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin.ResultsOverall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P ConclusionOne in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery