Testing strategies and follow-up for coeliac disease in a general internal medicine outpatient department from 2000 to 2005

PRINCIPLES: Coeliac disease (gluten sensitive enteropathy) is a genetically determined disorder with an incidence in the general population that is comparable to type 2 diabetes mellitus. Awareness of this fact and of the often atypical and oligosymptomatic manifestations is only now gaining ground in the medical profession. A high index of suspicion is important in order to minimise diagnostic and therapeutic delay. METHODS: Testing patterns and follow-up for coeliac disease in our institution have been analysed retrospectively for the past five years. The current literature was reviewed with respect to recommendations for clinical practice. RESULTS: A total of 271 patients were tested for coeliac disease over a period of five years. Only in 24 patients were positive results found; after further work-up, the final number of cases with certain or presumed coeliac disease was four. Followup was often difficult, many patients being lost after a single visit. CONCLUSIONS: This study showed that the number of tests ordered in our institution, more often for abdominal than atypical symptoms, has started to increase in the past two years. It also showed that screening tests have found their place in general clinical practice, while the final choice of tests needs to be determined in accordance with available guidelines and local resources. Upper endoscopy with small bowel biopsy remains the gold standard for diagnosis, but its place in follow-up is less certain. Coeliac disease is a disorder for which there is a definite treatment (gluten free diet); if it is left untreated diminished quality of life and potentially serious complications may ensue. Further education of the medical profession regarding coeliac disease, its incidence, presentation and treatment, is clearly indicated..

The use of mechanisms and modes of toxic action in integrated testing strategies: the report and recommendations of a workshop held as part of the European Union OSIRIS Integrated Project

This report on The Potential of Mode of Action (MoA) Information Derived from Non-testing and Screening Methodologies to Support Informed Hazard Assessment, resulted from a workshop organised within OSIRIS (Optimised Strategies for Risk Assessment of Industrial Chemicals through Integration of Non-test and Test Information), a project partly funded by the EU Commission within the Sixth Framework Programme. The workshop was held in Liverpool, UK, on 30 October 2008, with 35 attendees. The goal of the OSIRIS project is to develop integrated testing strategies (ITS) fit for use in the REACH system, that would enable a significant increase in the use of non-testing information for regulatory decision making, and thus minimise the need for animal testing. One way to improve the evaluation of chemicals may be through categorisation by way of mechanisms or modes of toxic action. Defining such groups can enhance read-across possibilities and priority settings for certain toxic modes or chemical structures responsible for these toxic modes. Overall, this may result in a reduction of in vivo testing on organisms, through combining available data on mode of action and a focus on the potentially most-toxic groups. In this report, the possibilities of a mechanistic approach to assist in and guide ITS are explored, and the differences between human health and environmental areas are summarised.

Testing consumption optimality using aggregate data

This paper tests the optimality of consumption decisions at the aggregate level taking into account popular deviations from the canonical constant-relative-risk-aversion (CRRA) utility function model-rule of thumb and habit. First, based on the critique in Carroll (2001) and Weber (2002) of the linearization and testing strategies using euler equations for consumption, we provide extensive empirical evidence of their inappropriateness - a drawback for standard rule- of-thumb tests. Second, we propose a novel approach to test for consumption optimality in this context: nonlinear estimation coupled with return aggregation, where rule-of-thumb behavior and habit are special cases of an all encompassing model. We estimated 48 euler equations using GMM. At the 5% level, we only rejected optimality twice out of 48 times. Moreover, out of 24 regressions, we found the rule-of-thumb parameter to be statistically significant only twice. Hence, lack of optimality in consumption decisions represent the exception, not the rule. Finally, we found the habit parameter to be statistically significant on four occasions out of 24.

Mensuração de estratégias de estudo e aprendizagem de alunos universitários: learning and study strategies inventory (lassi) adaptação e validação para o Brasil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A Design Methodology for Computer Security Testing

The field of "computer security" is often considered something in between Art and Science. This is partly due to the lack of widely agreed and standardized methodologies to evaluate the degree of the security of a system. This dissertation intends to contribute to this area by investigating the most common security testing strategies applied nowadays and by proposing an enhanced methodology that may be effectively applied to different threat scenarios with the same degree of effectiveness. Security testing methodologies are the first step towards standardized security evaluation processes and understanding of how the security threats evolve over time. This dissertation analyzes some of the most used identifying differences and commonalities, useful to compare them and assess their quality. The dissertation then proposes a new enhanced methodology built by keeping the best of every analyzed methodology. The designed methodology is tested over different systems with very effective results, which is the main evidence that it could really be applied in practical cases. Most of the dissertation discusses and proves how the presented testing methodology could be applied to such different systems and even to evade security measures by inverting goals and scopes. Real cases are often hard to find in methodology' documents, in contrary this dissertation wants to show real and practical cases offering technical details about how to apply it. Electronic voting systems are the first field test considered, and Pvote and Scantegrity are the two tested electronic voting systems. The usability and effectiveness of the designed methodology for electronic voting systems is proved thanks to this field cases analysis. Furthermore reputation and anti virus engines have also be analyzed with similar results. The dissertation concludes by presenting some general guidelines to build a coordination-based approach of electronic voting systems to improve the security without decreasing the system modularity.

Integrated testing strategy (ITS) for bioaccumulation assessment under REACH

REACH (registration, evaluation, authorisation and restriction of chemicals) regulation requires that all the chemicals produced or imported in Europe above 1 tonne/year are registered. To register a chemical, physicochemical, toxicological and ecotoxicological information needs to be reported in a dossier. REACH promotes the use of alternative methods to replace, refine and reduce the use of animal (eco)toxicity testing. Within the EU OSIRIS project, integrated testing strategies (ITSs) have been developed for the rational use of non-animal testing approaches in chemical hazard assessment. Here we present an ITS for evaluating the bioaccumulation potential of organic chemicals. The scheme includes the use of all available data (also the non-optimal ones), waiving schemes, analysis of physicochemical properties related to the end point and alternative methods (both in silico and in vitro). In vivo methods are used only as last resort. Using the ITS, in vivo testing could be waived for about 67% of the examined compounds, but bioaccumulation potential could be estimated on the basis of non-animal methods. The presented ITS is freely available through a web tool.

Optimizing the aquatic toxicity assessment under REACH through an integrated testing strategy (ITS).

To satisfy REACH requirements a high number of data on chemical of interest should be supplied to the European Chemicals Agency. To organize the various kinds of information and help the registrants to choose the best strategy to obtain the needed information limiting at the minimum the use of animal testing, integrated testing strategies (ITSs) schemes can be used. The present work deals with regulatory data requirements for assessing the hazards of chemicals to the aquatic pelagic environment. We present an ITS scheme for organizing and using the complex existing data available for aquatic toxicity assessment. An ITS to optimize the choice of the correct prediction strategy for aquatic pelagic toxicity is described. All existing information (like physico-chemical information), and all the alternative methods (like in silico, in vitro or the acute-to-chronic ratio) are considered. Moreover the weight of evidence approach to combine the available data is included.

Accuracy of diagnostic testing in primary ciliary dyskinesia.

Diagnosis of primary ciliary dyskinesia (PCD) lacks a "gold standard" test and is therefore based on combinations of tests including nasal nitric oxide (nNO), high-speed video microscopy analysis (HSVMA), genotyping and transmission electron microscopy (TEM). There are few published data on the accuracy of this approach.Using prospectively collected data from 654 consecutive patients referred for PCD diagnostics we calculated sensitivity and specificity for individual and combination testing strategies. Not all patients underwent all tests.HSVMA had excellent sensitivity and specificity (100% and 93%, respectively). TEM was 100% specific, but 21% of PCD patients had normal ultrastructure. nNO (30 nL·min(-1) cut-off) had good sensitivity and specificity (91% and 96%, respectively). Simultaneous testing using HSVMA and TEM was 100% sensitive and 92% specific.In conclusion, combination testing was found to be a highly accurate approach for diagnosing PCD. HSVMA alone has excellent accuracy, but requires significant expertise, and repeated sampling or cell culture is often needed. TEM alone is specific but misses 21% of cases. nNO (≤30 nL·min(-1)) contributes well to the diagnostic process. In isolation nNO screening at this cut-off would miss ∼10% of cases, but in combination with HSVMA could reduce unnecessary further testing. Standardisation of testing between centres is a future priority.

Toward a more robust facial expression recognition in occluded images using randomly sampled Gabor based templates

Occlusion is a big challenge for facial expression recognition (FER) in real-world situations. Previous FER efforts to address occlusion suffer from loss of appearance features and are largely limited to a few occlusion types and single testing strategy. This paper presents a robust approach for FER in occluded images and addresses these issues. A set of Gabor based templates is extracted from images in the gallery using a Monte Carlo algorithm. These templates are converted into distance features using template matching. The resulting feature vectors are robust to occlusion. Occluded eyes and mouth regions and randomly places occlusion patches are used for testing. Two testing strategies analyze the effects of these occlusions on the overall recognition performance as well as each facial expression. Experimental results on the Cohn-Kanade database confirm the high robustness of our approach and provide useful insights about the effects of occlusion on FER. Performance is also compared with previous approaches.

Environment characterization as an aid to wheat improvement: interpreting genotype-environment interactions by modelling water-deficit patterns in North-Eastern Australia.

Genotype-environment interactions (GEI) limit genetic gain for complex traits such as tolerance to drought. Characterization of the crop environment is an important step in understanding GEI. A modelling approach is proposed here to characterize broadly (large geographic area, long-term period) and locally (field experiment) drought-related environmental stresses, which enables breeders to analyse their experimental trials with regard to the broad population of environments that they target. Water-deficit patterns experienced by wheat crops were determined for drought-prone north-eastern Australia, using the APSIM crop model to account for the interactions of crops with their environment (e.g. feedback of plant growth on water depletion). Simulations based on more than 100 years of historical climate data were conducted for representative locations, soils, and management systems, for a check cultivar, Hartog. The three main environment types identified differed in their patterns of simulated water stress around flowering and during grain-filling. Over the entire region, the terminal drought-stress pattern was most common (50% of production environments) followed by a flowering stress (24%), although the frequencies of occurrence of the three types varied greatly across regions, years, and management. This environment classification was applied to 16 trials relevant to late stages testing of a breeding programme. The incorporation of the independently-determined environment types in a statistical analysis assisted interpretation of the GEI for yield among the 18 representative genotypes by reducing the relative effect of GEI compared with genotypic variance, and helped to identify opportunities to improve breeding and germplasm-testing strategies for this region.

Defining critical soil nutrient concentrations in soils supporting grains and cotton in Northern NSW and Queensland

This project focussed on the phosphorus (P) and potassium (K) status of northern cropping soils. Stores of P and K have been depleted by crop removal and limited fertiliser application, with depletion most significant in the subsoil. Soil testing strategies are confounded by slowly available mineral reserves with uncertain availability. The utility of new soil tests was assessed to measure these reserves, their availability to plants quantified and a regional sampling strategy undertaken to identify areas of greatest P and K deficit. Fertiliser application strategies for P and K have been tested and the interactions between these and other nutrients have been determined in a large field program.

In vitro/In vivo assessment and mechanisms of toxicity of bioceramic materials and its wear particulates

With the progress in modern technological research, novel biomaterials are being largely developed for various biomedical applications. Over the past two decades, most of the research focuses on the development of a new generation of bioceramics as substitutes for hard tissue replacement. In reference to their application in different anatomical locations of a patient, newly developed bioceramic materials can potentially induce a toxic/harmful effect to the host tissues. Therefore, prior to clinical testing, relevant biochemical screening assays are to be performed at the cellular and molecular level, to address the issues of biocompatibility and long term performance of the implants. Along with testing strategies in the bulk material toxicity, a detailed evaluation should also be conducted to determine the toxicity of the wear products of the potential bioceramics. This is important as the bioceramics are intended to be implanted in patients with longer life expectancy and notwithstanding, the material will eventually release finer (mostly nanosized) sized debris particles due to continuous wear at articulating surfaces in the hostile corrosive environment of the human body. The wear particulates generated from a biocompatible bioceramic may act in a different way, inducing early/late aseptic loosening at the implant site, resulting in osteolysis and inflammation. Hence, a study on the chronic effects of the wear particulates, in terms of local and systemic toxicity becomes the major criteria in the toxicity evaluation of implantable bioceramics. In this broad perspective, this article summarizes some of the currently used techniques and knowledge in assessing the in vitro and in vivo cytotoxicity and genotoxicity of bioceramic implant materials. It also addresses the need to conduct a broad evaluation before claiming the biocompatibility and clinical feasibility of any new biomaterial. This review also emphasizes some of the case studies based on the experimental designs that are currently followed and its importance in the context of clinical applications.

Patterns of de novo allo B cells and antibody formation in chronic cardiac allograft rejection after alemtuzumab treatment.

Even though the etiology of chronic rejection (CR) is multifactorial, donor specific antibody (DSA) is considered to have a causal effect on CR development. Currently the antibody-mediated mechanisms during CR are poorly understood due to lack of proper animal models and tools. In a clinical setting, we previously demonstrated that induction therapy by lymphocyte depletion, using alemtuzumab (anti-human CD52), is associated with an increased incidence of serum alloantibody, C4d deposition and antibody-mediated rejection in human patients. In this study, the effects of T cell depletion in the development of antibody-mediated rejection were examined using human CD52 transgenic (CD52Tg) mice treated with alemtuzumab. Fully mismatched cardiac allografts were transplanted into alemtuzumab treated CD52Tg mice and showed no acute rejection while untreated recipients acutely rejected their grafts. However, approximately half of long-term recipients showed increased degree of vasculopathy, fibrosis and perivascular C3d depositions at posttransplant day 100. The development of CR correlated with DSA and C3d deposition in the graft. Using novel tracking tools to monitor donor-specific B cells, alloreactive B cells were shown to increase in accordance with DSA detection. The current animal model could provide a means of testing strategies to understand mechanisms and developing therapeutic approaches to prevent chronic rejection.

Application of fractional algorithms in the control of a robotic bird

In this paper, it is studied the dynamics of the robotic bird in terms of time response and robustness. It is analyzed the wing angle of attack and the velocity of the bird, the tail influence, the gliding flight and the flapping flight. The results are positive for the construction of flying robots. The development of computational simulation based on the dynamic of the robotic bird should allow testing strategies and different algorithms of control such as integer and fractional controllers.

Reasons for late presentation to HIV care in Switzerland.

INTRODUCTION: Late presentation to HIV care leads to increased morbidity and mortality. We explored risk factors and reasons for late HIV testing and presentation to care in the nationally representative Swiss HIV Cohort Study (SHCS). METHODS: Adult patients enrolled in the SHCS between July 2009 and June 2012 were included. An initial CD4 count <350 cells/µl or an AIDS-defining illness defined late presentation. Demographic and behavioural characteristics of late presenters (LPs) were compared with those of non-late presenters (NLPs). Information on self-reported, individual barriers to HIV testing and care were obtained during face-to-face interviews. RESULTS: Of 1366 patients included, 680 (49.8%) were LPs. Seventy-two percent of eligible patients took part in the survey. LPs were more likely to be female (p<0.001) or from sub-Saharan Africa (p<0.001) and less likely to be highly educated (p=0.002) or men who have sex with men (p<0.001). LPs were more likely to have their first HIV test following a doctor's suggestion (p=0.01), and NLPs in the context of a regular check-up (p=0.02) or after a specific risk situation (p<0.001). The main reasons for late HIV testing were "did not feel at risk" (72%), "did not feel ill" (65%) and "did not know the symptoms of HIV" (51%). Seventy-one percent of the participants were symptomatic during the year preceding HIV diagnosis and the majority consulted a physician for these symptoms. CONCLUSIONS: In Switzerland, late presentation to care is driven by late HIV testing due to low risk perception and lack of awareness about HIV. Tailored HIV testing strategies and enhanced provider-initiated testing are urgently needed.