The contribution of a negative colorectal screening test result to symptom appraisal and help-seeking behaviour among patients subsequently diagnosed with an interval colorectal cancer

Background: Colorectal cancer (CRC) screening programmes using a guaiac faecal occult blood test (gFOBt) reduce CRC mortality. Interval cancers are diagnosed between screening rounds: reassurance from a negative gFOBt has the potential to influence the pathway to diagnosis of an interval colorectal cancer. Methods: Twenty-six semi-structured face-to-face interviews were carried out in Scotland and England, with individuals diagnosed with an interval colorectal cancer following a negative gFOBt result. Results: Participants reported they were reassured by a negative gFOBt, interpreting their result as an "all clear". Therefore, most did not suspect cancer as a possible cause of symptoms and many did not recall their screening result during symptom appraisal. Among those who did consider cancer, and did think about their screening test result, reassurance from a negative gFOBt led some to "downplay" the seriousness of their symptoms with some interviewees explicitly stating that their negative test result contributed to a delayed decision to seek help. Conclusion: Screening participants need to be informed of the limitations of screening and the ongoing risk of developing colorectal cancer even when in receipt of a negative result: the importance of minimizing delay in seeking medical advice for colorectal symptoms should be emphasized

Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation

A role for WNT signalling in gastric carcinogenesis has been suggested due to two major observations. First, patients with germline mutations in adenomatous polyposis coli (APC) are susceptible to stomach polyps and second, in gastric cancer, WNT activation confers a poor prognosis. However, the functional significance of deregulated WNT signalling in gastric homoeostasis and cancer is still unclear. In this study we have addressed this by investigating the immediate effects of WNT signalling activation within the stomach epithelium. We have specifically activated the WNT signalling pathway within the mouse adult gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or APC or via expression of a constitutively active β-catenin protein. WNT pathway deregulation dramatically affects stomach homoeostasis at very short latencies. In the corpus, there is rapid loss of parietal cells with fundic gland polyp (FGP) formation and adenomatous change, which are similar to those observed in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post-WNT activation. Taken together, these data show a pivotal role for WNT signalling in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal cell population and corresponding FGP formation, an early event in gastric carcinogenesis, as well as antral adenoma formation are immediate effects of nuclear β-catenin translocation and WNT target gene expression. Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach

Ovarian steroid cell tumor with biallelic adenomatous polyposis coli inactivation in a patient with familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is an autosomal dominant cancer predisposition syndrome that accounts for approximately 0.5–1% of all colorectal cancer cases. It is caused by germline mutations in the gene encoding the adenomatous polyposis coli ( APC ) tumor suppressor. Somatic APC inactivation due to mutation or loss of heterozygosity (LOH) promotes the development of adenomatous polyps by stabilizing the transcriptional coactivator β‐catenin. Although colorectal cancer is by far the most common malignancy seen in FAP patients, the widespread use of prophylactic colectomy in these patients has increased the clinical importance of extracolonic tumors that are part of the neoplastic spectrum in FAP. Many of these tumors exhibit LOH or somatic APC mutation, strongly supporting a causative role of APC inactivation in their pathogenesis. Here we describe a 47‐year‐old female FAP patient with clinical manifestations of virilization who was found to have an ovarian steroid cell tumor, a rare neoplasm not known to be associated with FAP. Immunohistochemical analysis of the ovarian tumor demonstrated strong nuclear β‐catenin staining consistent with somatic APC inactivation, and molecular analysis confirmed biallelic APC inactivation in the tumor. Our findings provide the first evidence that ovarian steroid cell tumors may be an extracolonic manifestation of FAP and implicate β‐catenin activation as an oncogenic mechanism in ovarian steroid cell tumorigenesis. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90384/1/20953_ftp.pd

Multitargeted Low-Dose GLAD Combination Chemoprevention: A Novel and Promising Approach to Combat Colon Carcinogenesis

AbstractPreclinical studies have shown that gefitinib, licofelone, atorvastatin, and α-difluoromethylornithine (GLAD) are promising colon cancer chemopreventive agents. Because low-dose combination regimens can offer potential additive or synergistic effects without toxicity, GLAD combination was tested for toxicity and chemopreventive efficacy for suppression of intestinal tumorigenesis in adenomatous polyposis coli (APC)Min/+ mice. Six-week-old wild-type and APCMin/+ mice were fed modified American Institute of Nutrition 76A diets with or without GLAD (25 + 50 + 50 + 500 ppm) for 14 weeks. Dietary GLAD caused no signs of toxicity based on organ pathology and liver enzyme profiles. GLAD feeding strongly inhibited (80–83%, P < .0001) total intestinal tumor multiplicity and size in APCMin/+ mice (means ± SEM tumors for control vs GLAD were 67.1 ± 5.4 vs 11.3 ± 1.1 in males and 72.3 ± 8.9 vs 14.5 ± 2.8 in females). Mice fed GLAD had >95% fewer polyps with sizes of >2 mm compared with control mice and showed 75% and 85% inhibition of colonic tumors in males and females, respectively. Molecular analyses of polyps suggested that GLAD exerts efficacy by inhibiting cell proliferation, inducing apoptosis, decreasing β-catenin and caveolin-1 levels, increasing caspase-3 cleavage and p21, and modulating expression profile of inflammatory cytokines. These observations demonstrate that GLAD, a novel cocktail of chemopreventive agents at very low doses, suppresses intestinal tumorigenesis in APCMin/+ mice with no toxicity. This novel strategy to prevent colorectal cancer is an important step in developing agents with high efficacy without unwanted side effects

From Frugality To Exuberance: Architecture And The City In Israel 1923-1977

ABSTRACT This dissertation argues for the emergence of a new materiality in Israeli architecture in the 1950s, 60s and 70s. It examines these decades in an extended historical time frame beginning with the British Mandate for Palestine. Materiality refers to local Israeli socioeconomic and geopolitical conditions. It also reflects the literal use, handling and finishing of materials in architecture. During this period first and second stages are described. The first was shaped by objective circumstances in which architecture operated in response to scarcity and demonstrated a realist attitude, one also embedded in the concept of asceticism. It was manifest in restrained formal gestures, abstention from material extravagance, the use of local materials, and an appeal to rational building procedures. The second stage emerging in the 60s had a different syntax. The analytical, skeletal frame constructions of the 50s turned synthetic, monolithic, and earth-bound. Compositions turned sculptural and exuberant. An appeal to the architect’s expressive ingenuity became a recognized design objective. The issue of banality versus extraordinariness in design surfaced at this point. My analysis of materiality is based on the following disciplinary themes: typology, public space, craft, and topography. These were dimensions of a broader search for a situated architecture undertaken by Israeli architects since the 1930s in which they sought to localize the importation of modern architecture from Europe. Typology offered an opportunity to synthesize modern building practices with vernacular models. It revealed the reciprocal interchange between cultures. Architects and planners perceived public space as a means to consolidate new communities, and represent the collective ethos of the new nation. Public space regained its value as a structural constituent in built fabrics. Building craft and use of local materials made architecture place-specific, of-its-time. Topographical awareness, and the mutual inscription between building and setting represented an ongoing desire to overcome the lack of an unmediated connection between the immigrants and their old/new territorial home. These disciplinary themes address a variety of scales from detail, building, neighborhood, city, and region. They demonstrate how Israeli architects adjusted the modernist appeal to abstraction and universalism with a perceptive recognition of their concrete reality

Avaliação de Cultivares de Arroz de Terras Altas no Município de Humaitá-AM, Safra 2013/2014

O arroz (Oryza sativa L.) é considerado o produto de maior importância econômica em muitos países em desenvolvimento. A elevada produtividade e qualidade de grãos de arroz dependem de procedimentos de manejo aplicados no momento e na quantidade necessária. O presente trabalho tem como objetivo avaliar o comportamento de cultivares de arroz (Oryza sativa L.) de terras altas no município de Humaitá AM, safra 2013/14. O experimento será instalado na Escola Agrícola do Município de Humaitá, localizada na BR 230 Km7, sentido Humaitá-Porto velho, em área de campo natural. A área experimental será composta por 12 cultivares de arroz de terras altas adquiridas junto a EMBRAPA Arroz e Feijão e empresas do ramo, sendo: AN Cambará, BRS Primavera, BRS Sertaneja, BRSMG Curinga, BRS Tropical, BRS Monarca, BRS Pepita, BRS Apinajé, BRSGO Serra Dourada, BRS Esmeralda, BRS Bonança, BRSMG Caravera. O delineamento experimental será de blocos casualizados com quatro repetições. As cultivares serão atribuídas em parcelas, compostas de 9 linhas de 5 m de comprimento, espaçadas 0,20 m entre si. O plantio será realizado manualmente no mês de novembro com a abertura de sulcos seguido da aplicação do fertilizante NPK e posteriormente, a distribuição das sementes de arroz ao longo dos sulcos cobrindo-as com 3 cm de solo. As variáveis avaliadas serão: Incidência de doenças, produtividade de grãos e seus componentes, floração, estatura da planta, acamamento, rendimento industrial. A colheita será efetuada manualmente com o uso de cutelo para o corte das plantas. Os resultados serão submetidos à análise de variância e as médias comparadas pelo teste de Skott-Knott a 5 % de probabilidade.FAPEA

Comparing the Frequency, Overlap, Stability, and Predictive Utility of Preclinical Dementia Constructs

Numerous constructs have been proposed to describe the transitional state between normal aging and dementia, but no one set of criteria is consistently referred to as the prodrome to dementia. Although there are many studies of the rates of these constructs, results are hampered by methodological differences. Research examining the overlap and stability of these constructs over time is also lacking, and predictive utility for later dementia remains inconclusive. Moreover, it is unknown whether one construct is superior in predicting later dementia or Alzheimer's disease. The current study addressed these issues using longitudinal clinical and neuropsychological data from a subsample (N=661) of participants in an epidemiological study of aging and dementia, the Cache County Memory Study (CCMS). Results confirmed wide variability in rates of preclinical dementia constructs. Constructs that included measures of functional impairment were the most stable, whereas constructs relying on memory impairment were generally unstable. Using bivariate logistic regression, four of the seven constructs were associated with later dementia, and these constructs either measured multiple cognitive domains or functional impairment. The 'Mild Ambiguous' construct, which includes memory or functional impairment, was statistically superior in predicting later dementia. Although four of the seven constructs were also significant predictors of later AD, no one construct was superior

O contador empreendedor : ações iniciais, desafios, riscos e possibilidades

Orientador : Luiz Rogério FariasMonografia (especialização) - Universidade Federal do Paraná, Setor de Ciências Sociais Aplicadas, Curso de Especialização em ControladoriaInclui referênciasResumo: O trabalho a seguir tem como objetivo demonstrar a percepção do Contador como empreendedor, bem como verificar os quesitos observados no momento da migração para o campo do empreendedorismo, permitindo identificar o perfil necessário e as expectativas possíveis. O contexto atual permite prognósticos favoráveis ao movimento contábil empreendedor, tendo em vista recentes mudanças na Legislação do país, tais quais favoreceram a saída da informalidade para microempreendedores, ampliando então o nicho de atuação para escritórios de contabilidade. Concomitante ao estímulo de regularização aos profissionais, até então, informais, está o aumento de conjuntos residenciais e condomínios, os quais necessitam de serviços contábeis para seu pleno funcionamento; deste modo, entende-se que o mercado para o contador que deseja lograr-se autônomo e possuir o seu próprio negócio encontra-se receptivo. Com base nos preceitos, ora informados, faz-se necessária à pesquisa com profissionais já atuantes no ramo de escritórios contábeis, no intuito de obter informações concisas e que permitam ao profissional recém-graduado, auferir meios para avaliar mais esta possibilidade de carreira profissiona

Modeling and the Use of Surrogate Endpoints:Is This a Valid Approach?

Background: Development of novel colorectal cancer (CRC) screening tests is a dynamic field. Decision analytic modeling based on inputs derived from rigorous prospective studies informs CRC screening guidelines. Exploratory modeling may have a place in early phases of test development. Methods: We explored whether (1) surrogate endpoints for long-term, programmatic effectiveness, and cost-effectiveness could be potentially informative in early stages of test development and (2) whether rapid exploratory modeling with a web-based tool would be feasible. Results: First, based on comparisons with published estimates for reductions in CRC mortality with various screening tests in four established decision analytic models of CRC screening, the surrogate endpoint of the number needed to colonoscope to detect one CRC or advanced precancerous lesion (APL) in round 1 of screening appears to hold promise as a measure of clinical effectiveness. Similarly, based on comparisons with published estimates for cost/quality-adjusted life-year gained with screening in the four models, the surrogate endpoint of cost to detect one CRC or APL in round 1 of screening appears to hold promise as a measure of cost-effectiveness. Second, exploration of the impact of lowering the screening initiation age in Israel from age 50 to 45 with the web-based EU-TOPIA tool, compared with the results of a recently published comprehensive modeling study, suggests that exploratory modeling of programmatic screening may be feasible with relatively low time demand vs. that required for typical full-length modeling publications. Conclusion: Further validation in other models and with a broader set of test performance characteristics is prudent before surrogate endpoints or rapid modeling are incorporated into the novel test development process.</p