A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown. METHODS AND FINDINGS The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was considered statistically significant. In multivariable-adjusted conditional logistic regression models with BMI used to define adiposity, compared with metabolically healthy/normal weight individuals, we observed a higher colorectal cancer risk among metabolically unhealthy/normal weight (odds ratio [OR] = 1.59, 95% CI 1.10-2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI 1.01-1.94) participants, but not among metabolically healthy/overweight individuals (OR = 0.96, 95% CI 0.65-1.42). Among the overweight individuals, lower colorectal cancer risk was observed for metabolically healthy/overweight individuals compared with metabolically unhealthy/overweight individuals (OR = 0.69, 95% CI 0.49-0.96). These associations were generally consistent when waist circumference was used as the measure of adiposity. To our knowledge, there is no universally accepted clinical definition for using C-peptide level as an indication of hyperinsulinaemia. Therefore, a possible limitation of our analysis was that the classification of individuals as being hyperinsulinaemic-based on their C-peptide level-was arbitrary. However, when we used quartiles or the median of C-peptide, instead of tertiles, as the cut-point of hyperinsulinaemia, a similar pattern of associations was observed. CONCLUSIONS These results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.

Understanding the hierarchy governance choice of some wineries in Brazil - case study of 3 Brazilian wineries

ABSTRACT This study aims to contribute towards understanding the multiple factors, which influence firm's governance decisions. To identify some of these factors, three cases in the Brazilian wine industry were analyzed: Miolo located in Vale dos Vinhedos (South of Brazil) and in Vale do Rio São Francisco (Northeast of Brazil); Don Laurindo located in Vale dos Vinhedos; and ViniBrasil located in Vale do Rio São Francisco. For the most part, all three firms procure the grapes they use for their wine production in-house. Only Miolo purchases an insignificant amount of grapes outside of its production. By Brazilian standards, these regions have a long tradition of grape production and it is not difficult to purchase sufficient quantity of grapes to produce wine. However, the wineries are concerned also about the quality of the grapes they use and purchasing high-quality grapes might be critical issue. On the other hand, the quality of grapes is easily measured and the cost to buy in the market is cheaper than producing in-house. Furthermore, also the level of asset specificity present in the grape-grower-wine-producer transaction seems, by itself, insufficient to justify the use of hierarchical governance forms. Then, the aim of the article is to analyze the reasons why these wineries largely rely on hierarchy governance forms to procure their grape-inputs. What explains their use of hierarchy governance, given that both asset specificity and measurement problems appear to be relatively low?

A case of suicide by ingestion of caffeine

Summary Intentional or unintentional caffeine abuse due to excessive intake of beverages or energy drinks containing caffeine is relatively frequent. However, death due to caffeine intoxication is rare and case reports of fatalities from caffeine toxicity are relatively infrequent. In this report, we describe an autopsy case involving a 31 year-old man who intentionally took a large amount of caffeine tablets in the form of a weight loss supplement as part of a suicide plan. Caffeine femoral blood concentration (170 mg/l) was within the toxic and potentially lethal ranges reported in the literature in similar cases. Postmortem biochemistry results suggested depressed glomerular filtration rate and prerenal failure at the time of death and failed to reveal myoglobinuria, glycosuria, ketonuria or ketonemia. Based on the absence of pathological findings at autopsy and the high blood caffeine level, death was attributed to acute caffeine toxicity. The case emphasizes the usefulness of performing exhaustive toxicology and searching for all potentially relevant information in order to formulate appropriate hypotheses concerning the cause and manner of death.

Risk assessment of recurrence in sporadic retinoblastoma using a molecular-based algorithm.

PURPOSE: Most RB1 mutations are unique and distributed throughout the RB1 gene. Their detection can be time-consuming and the yield especially low in cases of conservatively-treated sporadic unilateral retinoblastoma (Rb) patients. In order to identify patients with true risk of developing Rb, and to reduce the number of unnecessary examinations under anesthesia in all other cases, we developed a universal sensitive, efficient and cost-effective strategy based on intragenic haplotype analysis. METHODS: This algorithm allows the calculation of the a posteriori risk of developing Rb and takes into account (a) RB1 loss of heterozygosity in tumors, (b) preferential paternal origin of new germline mutations, (c) a priori risk derived from empirical data by Vogel, and (d) disease penetrance of 90% in most cases. We report the occurrence of Rb in first degree relatives of patients with sporadic Rb who visited the Jules Gonin Eye Hospital, Lausanne, Switzerland, from January 1994 to December 2006 compared to expected new cases of Rb using our algorithm. RESULTS: A total of 134 families with sporadic Rb were enrolled; testing was performed in 570 individuals and 99 patients younger than 4 years old were identified. We observed one new case of Rb. Using our algorithm, the cumulated total a posteriori risk of recurrence was 1.77. CONCLUSIONS: This is the first time that linkage analysis has been validated to monitor the risk of recurrence in sporadic Rb. This should be a useful tool in genetic counseling, especially when direct RB1 screening for mutations leaves a negative result or is unavailable.

PCR-based isolation of multigene families: lessons from the avian MHC class IIB.

The amount of sequence data available today highly facilitates the access to genes from many gene families. Primers amplifying the desired genes over a range of species are readily obtained by aligning conserved gene regions, and laborious gene isolation procedures can often be replaced by quicker PCR-based approaches. However, in the case of multigene families, PCR-based approaches bear the often ignored risk of incomplete isolation of family members. This problem is most prominent in gene families with highly variable and thus unpredictable number of gene copies among species, such as in the major histocompatibility complex (MHC). In this study, we (i) report new primers for the isolation of the MHC class IIB (MHCIIB) gene family in birds and (ii) share our experience with isolating MHCIIB genes from an unprecedented number of avian species from all over the avian phylogeny. We report important and usually underappreciated problems encountered during PCR-based multigene family isolation and provide a collection of measures to help significantly improving the chance of successfully isolating complete multigene families using PCR-based approaches.

Kernel-based methods for change detection in remote sensing images

Nowadays, the joint exploitation of images acquired daily by remote sensing instruments and of images available from archives allows a detailed monitoring of the transitions occurring at the surface of the Earth. These modifications of the land cover generate spectral discrepancies that can be detected via the analysis of remote sensing images. Independently from the origin of the images and of type of surface change, a correct processing of such data implies the adoption of flexible, robust and possibly nonlinear method, to correctly account for the complex statistical relationships characterizing the pixels of the images. This Thesis deals with the development and the application of advanced statistical methods for multi-temporal optical remote sensing image processing tasks. Three different families of machine learning models have been explored and fundamental solutions for change detection problems are provided. In the first part, change detection with user supervision has been considered. In a first application, a nonlinear classifier has been applied with the intent of precisely delineating flooded regions from a pair of images. In a second case study, the spatial context of each pixel has been injected into another nonlinear classifier to obtain a precise mapping of new urban structures. In both cases, the user provides the classifier with examples of what he believes has changed or not. In the second part, a completely automatic and unsupervised method for precise binary detection of changes has been proposed. The technique allows a very accurate mapping without any user intervention, resulting particularly useful when readiness and reaction times of the system are a crucial constraint. In the third, the problem of statistical distributions shifting between acquisitions is studied. Two approaches to transform the couple of bi-temporal images and reduce their differences unrelated to changes in land cover are studied. The methods align the distributions of the images, so that the pixel-wise comparison could be carried out with higher accuracy. Furthermore, the second method can deal with images from different sensors, no matter the dimensionality of the data nor the spectral information content. This opens the doors to possible solutions for a crucial problem in the field: detecting changes when the images have been acquired by two different sensors.

Androgen and gonadotropin patterns differ in HIV-1-infected men who develop lipoatrophy during antiretroviral therapy: a case-control study.

OBJECTIVES: We compared androgen and gonadotropin values in HIV-infected men who did and did not develop lipoatrophy on combination antiretroviral therapy (cART). METHODS: From a population of 136 treatment-naïve male Caucasians under successful zidovudine/lamivudine-based cART, the 10 patients developing lipoatrophy (cases) were compared with 87 randomly chosen controls. Plasma levels of free testosterone (fT), dehydroepiandrosterone (DHEA), follicle-stimulating hormone and luteinizing hormone (LH) were measured at baseline and after 2 years of cART. RESULTS: At baseline, 60% of the cases and 71% of the controls showed abnormally low fT values. LH levels were normal or low in 67 and 94% of the patients, respectively, indicating a disturbance of the hypothalamic-pituitary-gonadal axis. fT levels did not significantly change after 2 years of cART. Cases showed a significant increase in LH levels, while controls showed a significant increase in DHEA levels. In a multivariate logistic regression model, lipoatrophy was associated with higher baseline DHEA levels (P=0.04), an increase in LH levels during cART (P=0.001), a lower body mass index and greater age. CONCLUSIONS: Hypogonadism is present in the majority of HIV-infected patients. The development of cART-related lipoatrophy is associated with an increase in LH and a lack of increase in DHEA levels.

Intrauterine exposure to carbamazepine and specific congenital malformations: systematic review and case-control study.

OBJECTIVE: To identify specific major congenital malformations associated with use of carbamazepine in the first trimester of pregnancy. DESIGN: A review of all published cohort studies to identify key indications and a population based case-control study to test these indications. SETTING: Review of PubMed, Web of Science, and Embase for papers about carbamazepine exposure in the first trimester of pregnancy and specific malformations, and the EUROCAT Antiepileptic Study Database, including data from 19 European population based congenital anomaly registries, 1995-2005. PARTICIPANTS: The literature review covered eight cohort studies of 2680 pregnancies with carbamazepine monotherapy exposure, and the EUROCAT dataset included 98 075 registrations of malformations covering over 3.8 million births. MAIN OUTCOME MEASURES: Overall prevalence for a major congenital malformation after exposure to carbamazepine monotherapy in the first trimester. Odds ratios for malformations with exposure to carbamazepine among cases (five types of malformation identified in the literature review) compared with two groups of controls: other non-chromosomal registrations of malformations and chromosomal syndromes. RESULTS: The literature review yielded an overall prevalence for a major congenital malformation of 3.3% (95% confidence interval 2.7 to 4.2) after exposure to carbamazepine monotherapy in the first trimester. In 131 registrations of malformations, the fetus had been exposed to carbamazepine monotherapy. Spina bifida was the only specific major congenital malformation significantly associated with exposure to carbamazepine monotherapy (odds ratio 2.6 (95% confidence interval 1.2 to 5.3) compared with no antiepileptic drug), but the risk was smaller for carbamazepine than for valproic acid (0.2, 0.1 to 0.6). There was no evidence for an association with total anomalous pulmonary venous return (no cases with carbamazepine exposure), cleft lip (with or without palate) (0.2, 0.0 to 1.3), diaphragmatic hernia (0.9, 0.1 to 6.6), or hypospadias (0.7, 0.3 to 1.6) compared with no exposure to antiepileptic drugs. Further exploratory analysis suggested a higher risk of single ventricle and atrioventricular septal defect. CONCLUSION: Carbamazepine teratogenicity is relatively specific to spina bifida, though the risk is less than with valproic acid. Despite the large dataset, there was not enough power to detect moderate risks for some rare major congenital malformations.

Do Nasty and Pleasant Surprises Regarding Tax Revenue Explain Spending Drifts ? : The Case of the Swiss Cantons

This article aims to explain the difference between the expenditure reported in governmental end-of-the-year budgets and the amounts previously forecasted in the approved beginning-of-the-year budgets. We measure how political, financial, and institutional variables affect this spending drift. We focus on two much-debated factors, namely, tax revenue budgeting errors and the stringency of fiscal rules. Our econometric approach uses a panel based on the 26 Swiss cantons covering the period of 1980 to 2011. Results suggest that stringent fiscal rules discourage budget overruns, whereas underestimating tax revenue-i.e., a budgetary "pleasant surprise"-offers the opportunity for some overspending.

Focal dermal hypoplasia (goltz-gorlin syndrome): A new case with a novel variant in the PORCN gene (c.1250T>C:p.F417S) and unusual spinal anomaly.

Focal dermal hypoplasia (FDH; Goltz-Gorlin syndrome; OMIM 305600) is a disorder that features involvement of the skin, skeletal system, and eyes. It is caused by loss-of-function mutations in the PORCN gene. We report a young girl with FDH, microphthalmos associated with colobomatous orbital cyst, dural ectasia and cystic malformation of the spinal cord, and a de novo variant in PORCN. This association has not been previously reported, and based on these observations the phenotypic spectrum of FDH might be broader than previously appreciated. It would be prudent to alter the suggested surveillance for this rare disorder. © 2013 Wiley Periodicals, Inc.

Education, Equity and Distributive Beliefs: Evidences from the Chilean Case

During the year 2011, Chile has been scenario of several student's demonstrations claiming for more equity in the access to the higher education. The high support to the protests by the side of the general population (nearly 89% of approval in public opinion polls) seems to suggest the existence of a large consensus about the weaknesses of the Chilean educative model, a model that would challenge the traditional ideals of meritocracy and social mobility that are at the core of the educational systems in modern societies. In this context, a question that remains open is to what extent these claims are mostly based on consensual equality ideals, or whether they are influenced by individual socio-economic determinants vis-à-vis rational motives. Using data of the social inequality module International Social Survey Program (ISSP) of 2009, this research analyzes perceptions and beliefs about education and the distributive system as well as the influence of income and educational variables, through a structural equation modeling framework. Preliminary results indicate the presence of socioeconomic cleavages in relation to the fairness of the educational system, questioning the assumption about a normative consensus.

Geometry-based demosaicking

Demosaicking is a particular case of interpolation problems where, from a scalar image in which each pixel has either the red, the green or the blue component, we want to interpolate the full-color image. State-of-the-art demosaicking algorithms perform interpolation along edges, but these edges are estimated locally. We propose a level-set-based geometric method to estimate image edges, inspired by the image in-painting literature. This method has a time complexity of O(S) , where S is the number of pixels in the image, and compares favorably with the state-of-the-art algorithms both visually and in most relevant image quality measures.

Discovering the campus together: a mobile and computer-based learning experience

One of the most relevant difficulties faced by first-year undergraduate students is to settle into the educational environment of universities. This paper presents a case study that proposes a computer-assisted collaborative experience designed to help students in their transition from high school to university. This is done by facilitating their first contact with the campus and its services, the university community, methodologies and activities. The experience combines individual and collaborative activities, conducted in and out of the classroom, structured following the Jigsaw Collaborative Learning Flow Pattern. A specific environment including portable technologies with network and computer applications has been developed to support and facilitate the orchestration of a flow of learning activities into a single integrated learning setting. The result is a Computer-Supported Collaborative Blended Learning scenario, which has been evaluated with first-year university students of the degrees of Software and Audiovisual Engineering within the subject Introduction to Information and Communications Technologies. The findings reveal that the scenario improves significantly students’ interest in their studies and their understanding about the campus and services provided. The environment is also an innovative approach to successfully support the heterogeneous activities conducted by both teachers and students during the scenario. This paper introduces the goals and context of the case study, describes how the technology was employed to conduct the learning scenario, the evaluation methods and the main results of the experience.

Leveraging explicitly disclosed location information to understand tourist dynamics: a case study

In recent years, the large deployment of mobile devices has led to a massiveincrease in the volume of records of where people have been and when they were there.The analysis of these spatio-temporal data can supply high-level human behaviorinformation valuable to urban planners, local authorities, and designer of location-basedservices. In this paper, we describe our approach to collect and analyze the history ofphysical presence of tourists from the digital footprints they publicly disclose on the web.Our work takes place in the Province of Florence in Italy, where the insights on thevisitors’ flows and on the nationalities of the tourists who do not sleep in town has beenlimited to information from survey-based hotel and museums frequentation. In fact, mostlocal authorities in the world must face this dearth of data on tourist dynamics. In thiscase study, we used a corpus of geographically referenced photos taken in the provinceby 4280 photographers over a period of 2 years. Based on the disclosure of the locationof the photos, we design geovisualizations to reveal the tourist concentration and spatiotemporalflows. Our initial results provide insights on the density of tourists, the points ofinterests they visit as well as the most common trajectories they follow.

A multicase study for the evaluation of a pattern-based visual design process for collaborative learning

Collage is a pattern-based visual design authoring tool for the creation of collaborative learning scripts computationally modelled with IMS Learning Design (LD). The pattern-based visual approach aims to provide teachers with design ideas that are based on broadly accepted practices. Besides, it seeks hiding the LD notation so that teachers can easily create their own designs. The use of visual representations supports both the understanding of the design ideas and the usability of the authoring tool. This paper presents a multicase study comprising three different cases that evaluate the approach from different perspectives. The first case includes workshops where teachers use Collage. A second case implies the design of a scenario proposed by a third-party using related approaches. The third case analyzes a situation where students follow a design created with Collage. The cross-case analysis provides a global understanding of the possibilities and limitations of the pattern-based visual design approach.