Determining risk preferences for pain

The QALY concept is the commonly used approach in research to evaluate the efficiency of therapies in cost utility analysis. We investigate the risk neutrality assumption for time of the QALY concept: can time be included as a linear factor? Various studies show that this assumption does not hold empirically. However, the results are based on hypothetical questionnaires rather than decisions with real consequences. Experimental economists argue that experiments are necessary to avoid hypothetical bias. Our study provides the first experimental analysis of health related decision making. Using the cold pressor test we can analyze decisions when subjects face real consequences. Analog to the hypothetical studies, our experimental results of real decisions provide no linear time preferences. In conclusion, the QALY concept needs to be modified by a weighting factor for time

Do people have a preference for increasing or decreasing pain? An experimental comparison of psychological and economic measures in health related decision making

This paper investigates preferences for different health profiles, especially sequences of increasing and decreasing pain. We test conflicting predictions in terms of preferences over two painful sequences. The QALY concept relevant for the determination of different levels of health-related quality of life implies indifference, whereas behavioral theories find preferences related to ordering, following the peak-end-rule. Using an experimental design with real consequences we generate decisions about painful sequences induced by the cold pressor test. The results are compared with hypothetical choice data elicited using standard methods. We find that hypothetical methods reveal decisions in line with the peak-end-rule. However when it comes to real consequences of their decisions, subjects are on average not willing to pay for that preference

Determining risk preferences for pain

The QALY concept is the commonly used approach in research to evaluate the efficiency of therapies in cost utility analysis. We investigate the risk neutrality assumption for time of the QALY concept: can time be included as a linear factor? Various studies show that this assumption does not hold empirically. However, the results are based on hypothetical questionnaires rather than decisions with real consequences. Experimental economists argue that experiments are necessary to avoid hypothetical bias. Our study provides the first experimental analysis of health related decision making. Using the cold pressor test we can analyze decisions when subjects face real consequences. Analog to the hypothetical studies, our experimental results of real decisions provide no linear time preferences. In conclusion, the QALY concept needs to be modified by a weighting factor for time.

Análise comparativa de metodologias hidrológicas para obtenção de vazões ecológicas e outorgáveis, considerando os critérios anual e mensal para o rio Doce, Brasil

Grant is the National Water Resources Policy legal instrument responsible for guaranteeing water to meet human needs and maintain aquatic life. However, attention should be paid to the method used to obtain grantable volumes, as they are determined through minimum flows on an annual basis studies. This study aims to comparatively analyze methodologies for determining grantable and ecological flows and, seasonality influence in obtaining them for Doce river water regime, Southeast Brazil. Seasonal component was identified by frequency analysis. Log-Pearson type III distribution was the one that best fit the data. Considering 50% of the monthly Q7,10, it is possible to increase the grantable volume in every month, while, for 50% of Q90 and 70% of Q95 criteria, there is a decrease in the volume subject to granting between July and October. The currently method adopted in the basin, 70% of the annual Q95, presents ecological flows lowest values and, in September month, allows granting a volume 21% greater when compared to the monthly basis. It is concluded that ecological and grantable flows determination considering seasonal characteristic allows a better management of the studied watercourse.A outorga é o instrumento legal da Política Nacional de Recursos hídricos responsável pela garantia de água para atendimento das necessidades humanas e manutenção da vida aquática. Porém, deve-se ter atenção quanto ao método empregado na obtenção dos volumes outorgáveis, visto que são determinados através de estudos de vazões mínimas na base anual. Este estudo teve como objetivo analisar, comparativamente, metodologias para determinação de vazões ecológicas e outorgáveis e a influência da sazonalidade em sua obtenção para o regime hídrico do Rio Doce, Sudeste do Brasil. A componente sazonal foi identificada por análise de frequências. A distribuição Log-Pearson tipo III foi a que melhor se ajustou aos dados. Considerando 50% da Q7,10 mensal, é possível aumentar o volume outorgável em todos os meses, enquanto que, para os critérios 50% da Q90 e 70% da Q95, há diminuição do volume passível de outorga entre os meses de julho e outubro. O método adotado atualmente na bacia, 70% da Q95 anual, apresenta os menores valores de vazões ecológicas e, no mês de setembro, permite outorgar um volume 21% maior quando comparado à base mensal. Conclui-se que a determinação de vazões ecológicas e outorgáveis considerando a característica sazonal permite uma melhor gestão do curso d’água estudado

Prospective, open, multi-centre phase I/II trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and oxaliplatin in patients with adenocarcinoma of the oesophagogastric junction

Background: This phase I/II-trial assessed the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of neoadjuvant radiochemotherapy (RCT) with docetaxel and oxaliplatin in patients with locally advanced adenocarcinoma of the oesophagogastric junction. Methods: Patients received neoadjuvant radiotherapy (50.4 Gy) together with weekly docetaxel (20 mg/m2 at dose level (DL) 1 and 2, 25 mg/m2 at DL 3) and oxaliplatin (40 mg/m2 at DL 1, 50 mg/m2 at DL 2 and 3) over 5 weeks. The primary endpoint was the DLT and the MTD of the RCT regimen. Secondary endpoints included overall response rate (ORR) and progression-free survival (PFS). Results: A total of 24 patients were included. Four patients were treated at DL 1, 13 patients at DL 2 and 7 patients at DL 3. The MTD of the RCT was considered DL 2 with docetaxel 20 mg/m2 and oxaliplatin 50 mg/m2. Objective response (CR/PR) was observed in 32% (7/22) of patients. Eighteen patients (75%) underwent surgery after RCT. The median PFS for all patients (n = 24) was 6.5 months. The median overall survival for all patients (n = 24) was 16.3 months. Patients treated at DL 2 had a median overall survival of 29.5 months. Conclusion: Neoadjuvant RCT with docetaxel 20 mg/m2 and oxaliplatin 50 mg/m2 was effective and showed a good toxicity profile. Future studies should consider the addition of targeted therapies to current neoadjuvant therapy regimens to further improve the outcome of patients with advanced cancer of the oesophagogastric junction. Trial Registration: NCT0037498

Adjuvante Therapie des Kolonkarzinoms

Adjuvant Therapy in Colon Cancer The goal of improving adjuvant treatment can be reached in two ways: firstly, by developing more effective drugs and protocols and, secondly, by selecting suitable patients on the basis of clinical and molecular factors. In UICC (Union internationale contre le cancer) stage II, microsatellite instability (MSI) is a strong prognostic factor. Whether it can also be used as a predictive marker is currently a matter of controversy because the available data are contradictory. The question whether or not the MSI status should be checked before treatment decisions are made in stage II patients can therefore not be clearly answered at present. For adjuvant treatment in stage III, with capecitabine/oxaliplatin (XELOX) there is now a new protocol available that is based on the orally administered prodrug capecitabine. With regard to the question of how much older patients in this stage may also benefit from a combination chemotherapy, new - and contradictory - data have emerged recently: firstly, preliminary results of two new studies have given rise to safety concerns and, secondly, an analysis by the `ACCENT Collaborative Group' indicated lower efficacy of the `newer' adjuvant protocols in older people. These findings, however, have now been called into question as a result of a new subgroup analysis from the XELOXA study. The expert group therefore recommended that the decision whether to treat patients older than 70 years with an ( oral) fluoropyrimidine alone or in combination with oxaliplatin should be based on clinical parameters such as biological age and comorbidities

“FRUSTRANTE E ANIMADOR”: IDENTIDADE, PENSAMENTO COMPUTACIONAL E O PROFESSOR NA FORMAÇÃO CONTINUADA

Technologies transformed the way of producing and acquiring knowledge. The pandemic proved that now they ought to be a part of the classroom. However, it is still needed that the teacher experiences using such technologies to, then, work with them. Starting from the notion that it is necessary to develop new abilities in order to be digitally literate (KARCHMER-KLEIN; SHINAS, 2012), and considering that identities are shaped by experience (IVANIC, 1998), this paper aims to understand how five students of a Graduate Program in Applied Linguistics, already experienced teachers, while writing, build their identities and reflect upon technology’s relation with the school. Therefore, it was analyzed the journals produced during a class focused on digital literacy, in which the students had to read the theory and experiment with a digital tool. It is concluded that curiosity is one of the key elements to developing digital literacy and computational thinking, and that it is through attempting that the educator improves their knowledge and acquires confidence to incorporate new digital tools in the classroom.As tecnologias digitais transformaram a forma de produzir e adquirir conhecimento. Com a pandemia, fez-se evidente a urgência de utilizá-las mais significativamente no ambiente escolar. Mas ainda é preciso que o professor passe pela experiência de utilizar tais tecnologias para, então, trabalhar com elas. Partindo da noção de que é necessário desenvolver novas habilidades para ser letrado digitalmente (KARCHMER-KLEIN; SHINAS, 2012), e considerando as identidades como sendo moldadas pela experiência (IVANIC, 1998), este artigo busca entender como cinco alunos de um programa de Pós Graduação em Linguística Aplicada, já professores experientes, ao escreverem, constroem suas identidades e refletem sobre a relação das tecnologias digitais com a escola. Para tanto, foram analisados os diários produzidos durante uma aula destinada ao letramento digital, na qual os alunos liam a teoria e experimentavam uma ferramenta digital. Conclui-se que a curiosidade é um dos elementos fundamentais para desenvolver o letramento digital e o pensamento computacional, e que é através das tentativas que o educador aprimora seus conhecimentos e adquire confiança para incorporar novas ferramentas digitais em sala de aula

Genotype analysis of the human endostatin variant p.D104N in benign and malignant adrenocortical tumors

OBJECTIVE: Endostatin is a potent endogenous inhibitor of angiogenesis. It is derived from the proteolytic cleavage of collagen XVIII, which is encoded by the COL18A1 gene. A polymorphic COL18A1 allele encoding the functional polymorphism p.D104N impairs the activity of endostatin, resulting in a decreased ability to inhibit angiogenesis. This polymorphism has been previously analyzed in many types of cancer and has been considered a phenotype modulator in some benign and malignant tumors. However, these data are controversial, and different results have been reported for the same tumor types, such as prostate and breast cancer. The purpose of this study was to genotype the p.D104N variant in a cohort of pediatric and adult patients with adrenocortical tumors and to determine its possible association with the biological behavior of adrenocortical tumors. METHODS: DNA samples were obtained from 38 pediatric and 56 adult patients (0.6-75 yrs) with adrenocortical tumors. The DNA samples were obtained from peripheral blood, frozen tissue or paraffin-embedded tumor blocks when blood samples or fresh frozen tissue samples were unavailable. Restriction fragment length polymorphism analysis was used to genotype the patients and 150 controls. The potential associations of the p.D104N polymorphism with clinical and histopathological features and oncologic outcome (age of onset, tumor size, malignant tumor behavior, and clinical syndrome) were analyzed. RESULTS: Both the patient group and the control group were in Hardy-Weinberg equilibrium. The frequencies of the p.D104N polymorphism in the patient group were 81.9% (DD), 15.9% (DN) and 2.2% (NN). In the controls, these frequencies were 80.6%, 17.3% and 2.0%, respectively. We did not observe any association of this variant with clinical or histopathological features or oncologic outcome in our cohort of pediatric and adult patients with adrenocortical tumors

Spezielle Therapiesituationen beim metastasierten kolorektalen Karzinom

Specific Treatment Situations in Metastatic Colorectal Cancer As far as the management of primary resectable liver metastases is concerned, three approaches are currently competing with each other: surgery alone, surgery with pre- and postoperative chemotherapy, and surgery with postoperative chemotherapy alone. The core of the argument for pre- and postoperative chemotherapy in these patients is the European Organisation for Research and Treatment of Cancer (EORTC) 40983 study, which concluded that, in comparison with surgery alone, perioperative chemotherapy improved the 3-year progression-free survival (PFS) by 7 months. In contrast to this, there are two smaller studies - at a somewhat lower strength of evidence - indicating that adjuvant chemotherapy extends PFS by 9.1 months compared with surgery alone. In Germany, the adjuvant approach continues to be favored in many places; this can also be seen in the formulation of the S3 guideline. In patients with unresectable liver metastases - with the associated difficulty of classification due to the lack of clear and definitive criteria preoperative systemic therapy to induce `conversion' is indicated, in order to allow secondary resection. In KRAS wild-type tumors, high response rates ( in terms of a reduction in size of the metastases, such as according to RECIST ( Response Evaluation Criteria in Solid Tumors)) and a high conversion rate are achieved using a cetuximab/chemotherapy combination. Triple chemotherapy combinations with 5-fluorouracil (5-FU), oxaliplatin and irinotecan also produce high response rates. Bevacizumab/chemotherapy combinations have led to a high number of complete and partial pathohistological remissions in phase II studies; these seem to correlate with long survival times. In the absence of long-term survival data, it therefore seems to remain unclear as to what is the best parameter to use in order to assess the success of preoperative treatment. Lung metastases, too, or local peritoneal carcinomatosis can nowadays be operated on in selected patients with a good prospect of long-term remission or even cure. The surgery should, however, generally only be carried out in experienced centers, especially in the case of peritoneal carcinomatosis. For synchronous metastasization, the appropriate management depends on the size and extent of liver metastases and of the primary tumor. Small, peripherally lying and safely resectable liver metastases can be removed before or at the same time as the primary tumor, especially if a hemicolectomy is being carried out. If the metastases are unresectable and there is no bleeding or stenosis, the primary tumor can also be left in situ and systemic chemotherapy can be carried out first. However, it should be borne in mind that, according to current data, palliative resection of the primary tumor combined with systemic therapy leads to longer overall survival than does chemotherapy alone. Whether resection or chemotherapy should be done first therefore depends on the patient's clinical situation