Assessment of Risk for Type 1 Diabetes in Children of Affected Families and in the General Population : Role of Immunological and Metabolic Markers

Background and aims. Type 1 diabetes (T1D), an autoimmune disease in which the insulin producing beta cells are gradually destroyed, is preceded by a prodromal phase characterized by appearance of diabetes-associated autoantibodies in circulation. Both the timing of the appearance of autoantibodies and their quality have been used in the prediction of T1D among first-degree relatives of diabetic patients (FDRs). So far, no general strategies for identifying individuals at increased disease risk in the general population have been established, although the majority of new cases originate in this population. The current work aimed at assessing the predictive role of diabetes-associated immunologic and metabolic risk factors in the general population, and comparing these factors with data obtained from studies on FDRs. Subjects and methods. Study subjects in the current work were subcohorts of participants of the Childhood Diabetes in Finland Study (DiMe; n=755), the Cardiovascular Risk in Young Finns Study (LASERI; n=3475), and the Finnish Type 1 Diabetes Prediction and Prevention Study (DIPP) Study subjects (n=7410). These children were observed for signs of beta-cell autoimmunity and progression to T1D, and the results obtained were compared between the FDRs and the general population cohorts. --- Results and conclusions. By combining HLA and autoantibody screening, T1D risks similar to those reported for autoantibody-positive FDRs are observed in the pediatric general population. Progression rate to T1D is high in genetically susceptible children with persistent multipositivity. Measurement of IAA affinity failed in stratifying the risk assessment in young IAA-positive children with HLA-conferred disease susceptibility, among whom affinity of IAA did not increase during the prediabetic period. Young age at seroconversion, increased weight-for-height, decreased early insulin response, and increased IAA and IA-2A levels predict T1D in young children with genetic disease susceptibility and signs of advanced beta-cell autoimmunity. Since the incidence of T1D continues to increase, efforts aimed at preventing T1D are important, and reliable disease prediction is needed both for intervention trials and for effective and safe preventive therapies in the future. Our observations confirmed that combined HLA-based screening and regular autoantibody measurements reveal similar disease risks in pediatric general population as those seen in prediabetic FDRs, and that risk assessment can be stratified further by studying glucose metabolism of prediabetic subjects. As these screening efforts are feasible in practice, the knowledge now obtained can be exploited while designing intervention trials aimed at secondary prevention of T1D.

Status of hilsa (Tenualosa ilisha) management in the Bay of Bengal: an assessment of population risk and data gaps for more effective regional management

Assessment of country status papers on hilsa fisheries presented at the BOBP – IGO Chittagong, Bangladesh 2010. Assessment of status hilsa management in Bangladesh, India and Myanmar. Brief recommendations of potential follow-up activities that could enhance management. Risk assessment of hilsa in each country with Productivity Susceptibility Analysis (PSA). Summary of new approach to assess ecological risk.

A nonlinear model for assessing multiple probabilistic risks: A case study in South five-island of Changdao National Nature Reserve in China

Several methods for estimating the potential impacts caused by multiple probabilistic risks have been suggested. These existing methods mostly rely on the weight sum algorithm to address the need for integrated risk assessment. This paper develops a nonlinear model to perform such an assessment. The joint probability algorithm has been applied to the model development. An application of the developed model in South five-island of Changdao National Nature Reserve, China, combining remote sensing data and a GIS technique, provides a reasonable risk assessment. Based on the case study, we discuss the feasibility of the model. We propose that the model has the potential for use in identifying the regional primary stressor, investigating the most vulnerable habitat, and assessing the integrated impact of multiple stressors. (C) 2006 Elsevier Ltd. All rights reserved.

THE SAAF STUDY: evaluation of the Safeguarding Children Assessment and Analysis Framework (SAAF), compared with management as usual, for improving outcomes for children and young people who have experienced, or are at risk of, maltreatment: study protocol for a randomised controlled trial

Background: Serious case reviews and research studies have indicated weaknesses in risk assessments conducted by child protection social workers. Social workers are adept at gathering information but struggle with analysis and assessment of risk. The Department for Education wants to know if the use of a structured decision-making tool can improve child protection assessments of risk.

Methods/design: This multi-site, cluster-randomised trial will assess the effectiveness of the Safeguarding Children Assessment and Analysis Framework (SAAF). This structured decision-making tool aims to improve social workers' assessments of harm, of future risk and parents' capacity to change. The comparison is management as usual.

Inclusion criteria: Children's Services Departments (CSDs) in England willing to make relevant teams available to be randomised, and willing to meet the trial's training and data collection requirements.

Exclusion criteria: CSDs where there were concerns about performance; where a major organisational restructuring was planned or under way; or where other risk assessment tools were in use.

Six CSDs are participating in this study. Social workers in the experimental arm will receive 2 days training in SAAF together with a range of support materials, and access to limited telephone consultation post-training. The primary outcome is child maltreatment. This will be assessed using data collected nationally on two key performance indicators: the first is the number of children in a year who have been subject to a second Child Protection Plan (CPP); the second is the number of re-referrals of children because of related concerns about maltreatment. Secondary outcomes are: i) the quality of assessments judged against a schedule of quality criteria and ii) the relationship between the three assessments required by the structured decision-making tool (level of harm, risk of (re) abuse and prospects for successful intervention).

Discussion: This is the first study to examine the effectiveness of SAAF. It will contribute to a very limited literature on the contribution that structured decision-making tools can make to improving risk assessment and case planning in child protection and on what is involved in their effective implementation.

The SAFE FOODS framework for improved risk analysis of foods

Three main changes to current risk analysis processes are proposed to improve their transparency, openness, and accountability. First, the addition of a formal framing stage would allow interested parties, experts and officials to work together as needed to gain an initial shared understanding of the issue, the objectives of regulatory action, and alternative risk management measures. Second, the scope of the risk assessment is expanded to include the assessment of health and environmental benefits as well as risks, and the explicit consideration of economic- and social-impacts of risk management action and their distribution. Moreover approaches were developed for deriving improved information from genomic, proteomic and metabolomic profiling methods and for probabilistic modelling of health impacts for risk assessment purposes. Third, in an added evaluation stage, interested parties, experts, and officials may compare and weigh the risks, costs, and benefits and their distribution. As part of a set of recommendations on risk communication, we propose that reports on each stage should be made public.

Chronological Monte Carlo-based assessment of distribution system reliability

Regulatory authorities in many countries, in order to maintain an acceptable balance between appropriate customer service qualities and costs, are introducing a performance-based regulation. These regulations impose penalties, and in some cases rewards, which introduce a component of financial risk to an electric power utility due to the uncertainty associated with preserving a specific level of system reliability. In Brazil, for instance, one of the reliability indices receiving special attention by the utilities is the Maximum Continuous Interruption Duration per customer (MCID). This paper describes a chronological Monte Carlo simulation approach to evaluate probability distributions of reliability indices, including the MCID, and the corresponding penalties. In order to get the desired efficiency, modern computational techniques are used for modeling (UML -Unified Modeling Language) as well as for programming (Object- Oriented Programming). Case studies on a simple distribution network and on real Brazilian distribution systems are presented and discussed. © Copyright KTH 2006.

The role of myocardial scintigraphy in the assessment of cardiovascular risk in patients with end-stage chronic kidney disease on the waiting list for renal transplantation

The usefulness of stress myocardial perfusion scintigraphy for cardiovascular (CV) risk stratification in chronic kidney disease remains controversial. We tested the hypothesis that different clinical risk profiles influence the test. We assessed the prognostic value of myocardial scintigraphy in 892 consecutive renal transplant candidates classified into four risk groups: very high (aged epsilon 50 years, diabetes and CV disease), high (two factors), intermediate (one factor) and low (no factor). The incidence of CV events and death was 20 and 18, respectively (median follow-up 22 months). Altered stress testing was associated with an increased probability of cardiovascular events only in intermediate-risk (one risk factor) patients [30.3 versus 10, hazard ratio (HR) 2.37, confidence interval (CI) 1.693.33, P 0.0001]. Low-risk patients did well regardless of scan results. In patients with two or three risk factors, an altered stress test did not add to the already increased CV risk. Myocardial scintigraphy was related to overall mortality only in intermediate-risk patients (HR 2.8, CI 1.55.1, P 0.007). CV risk stratification based on myocardial stress testing is useful only in patients with just one risk factor. Screening may avoid unnecessary testing in 60 of patients, help stratifying for risk of events and provide an explanation for the inconsistent performance of myocardial scintigraphy.

Assessment of cardiovascular risk of patients with arterial hypertension of a public health unit

OBJECTIVE: To assess the cardiovascular risk, using the Framingham risk score, in a sample of hypertensive individuals coming from a public primary care unit. METHODS: The caseload comprised hypertensive individuals according to criteria established by the JNC VII, 2003, of 2003, among 1601 patients followed up in 1999, at the Cardiology and Arterial Hypertension Outpatients Clinic of the Teaching Primary Care Unit, at the Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. The patients were selected by draw, aged over 20 years, both genders, excluding pregnant women. It was a descriptive, cross-sectional, observational study. The Framingham risk score was used to stratify cardiovascular risk of developing coronary artery disease (death or non-fatal acute myocardial infarction). RESULTS: Age range of 27-79 years ( = 63.2 ± 9.58). Out of 382 individuals studied, 270 (70.7%) were female and 139 (36.4%) were characterized as high cardiovascular risk for presenting diabetes mellitus, atherosclerosis documented by event or procedure. Out of 243 stratified patients, 127 (52.3%) had HDL-C < 50 mg/dL; 210 (86.4%) had systolic blood pressure > 120 mmHg; 46 (18.9%) were smokers; 33 (13.6%) had a high cardiovascular risk. Those added to 139 enrolled directly as high cardiovascular risk, totaled up 172 (45%); 77 (20.2%) of medium cardiovascular risk and 133 (34.8%) of low risk. The highest percentage of high cardiovascular risk individuals was aged over 70 years; those of medium risk were aged over 60 years; and the low risk patients were aged 50 to 69 years. CONCLUSION: The significant number of high and medium cardiovascular risk individuals indicates the need to closely follow them up.

Multicentre validation of the Geneva Risk Score for hospitalised medical patients at risk of venous thromboembolism. Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE).

There is a need to validate risk assessment tools for hospitalised medical patients at risk of venous thromboembolism (VTE). We investigated whether a predefined cut-off of the Geneva Risk Score, as compared to the Padua Prediction Score, accurately distinguishes low-risk from high-risk patients regardless of the use of thromboprophylaxis. In the multicentre, prospective Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE) cohort study, 1,478 hospitalised medical patients were enrolled of whom 637 (43%) did not receive thromboprophylaxis. The primary endpoint was symptomatic VTE or VTE-related death at 90 days. The study is registered at ClinicalTrials.gov, number NCT01277536. According to the Geneva Risk Score, the cumulative rate of the primary endpoint was 3.2% (95% confidence interval [CI] 2.2-4.6%) in 962 high-risk vs 0.6% (95% CI 0.2-1.9%) in 516 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.5% vs 0.8% (p=0.029), respectively. In comparison, the Padua Prediction Score yielded a cumulative rate of the primary endpoint of 3.5% (95% CI 2.3-5.3%) in 714 high-risk vs 1.1% (95% CI 0.6-2.3%) in 764 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.2% vs 1.5% (p=0.130), respectively. Negative likelihood ratio was 0.28 (95% CI 0.10-0.83) for the Geneva Risk Score and 0.51 (95% CI 0.28-0.93) for the Padua Prediction Score. In conclusion, among hospitalised medical patients, the Geneva Risk Score predicted VTE and VTE-related mortality and compared favourably with the Padua Prediction Score, particularly for its accuracy to identify low-risk patients who do not require thromboprophylaxis.

A simplified Probabilistic Safety Assesment of a Steam-Methane Reforming Hydrogen Production Plant coupled to a High-Temperature Gas Cooled Nuclear Reactor

A Probabilistic Safety Assessment (PSA) is being developed for a steam-methane reforming hydrogen production plant linked to a High-Temperature Gas Cooled Nuclear Reactor (HTGR). This work is based on the Japan Atomic Energy Research Institute’s (JAERI) High Temperature Test Reactor (HTTR) prototype in Japan. This study has two major objectives: calculate the risk to onsite and offsite individuals, and calculate the frequency of different types of damage to the complex. A simplified HAZOP study was performed to identify initiating events, based on existing studies. The initiating events presented here are methane pipe break, helium pipe break, and PPWC heat exchanger pipe break. Generic data was used for the fault tree analysis and the initiating event frequency. Saphire was used for the PSA analysis. The results show that the average frequency of an accident at this complex is 2.5E-06, which is divided into the various end states. The dominant sequences result in graphite oxidation which does not pose a health risk to the population. The dominant sequences that could affect the population are those that result in a methane explosion and occur 6.6E-8/year, while the other sequences are much less frequent. The health risk presents itself if there are people in the vicinity who could be affected by the explosion. This analysis also demonstrates that an accident in one of the plants has little effect on the other. This is true given the design base distance between the plants, the fact that the reactor is underground, as well as other safety characteristics of the HTGR. Sensitivity studies are being performed in order to determine where additional and improved data is needed.

Precautionary principles: a jurisdiction-free framework for decision-making under risk

Fundamental principles of precaution are legal maxims that ask for preventive actions, perhaps as contingent interim measures while relevant information about causality and harm remains unavailable, to minimize the societal impact of potentially severe or irreversible outcomes. Such principles do not explain how to make choices or how to identify what is protective when incomplete and inconsistent scientific evidence of causation characterizes the potential hazards. Rather, they entrust lower jurisdictions, such as agencies or authorities, to make current decisions while recognizing that future information can contradict the scientific basis that supported the initial decision. After reviewing and synthesizing national and international legal aspects of precautionary principles, this paper addresses the key question: How can society manage potentially severe, irreversible or serious environmental outcomes when variability, uncertainty, and limited causal knowledge characterize their decision-making? A decision-analytic solution is outlined that focuses on risky decisions and accounts for prior states of information and scientific beliefs that can be updated as subsequent information becomes available. As a practical and established approach to causal reasoning and decision-making under risk, inherent to precautionary decision-making, these (Bayesian) methods help decision-makers and stakeholders because they formally account for probabilistic outcomes, new information, and are consistent and replicable. Rational choice of an action from among various alternatives-defined as a choice that makes preferred consequences more likely-requires accounting for costs, benefits and the change in risks associated with each candidate action. Decisions under any form of the precautionary principle reviewed must account for the contingent nature of scientific information, creating a link to the decision-analytic principle of expected value of information (VOI), to show the relevance of new information, relative to the initial ( and smaller) set of data on which the decision was based. We exemplify this seemingly simple situation using risk management of BSE. As an integral aspect of causal analysis under risk, the methods developed in this paper permit the addition of non-linear, hormetic dose-response models to the current set of regulatory defaults such as the linear, non-threshold models. This increase in the number of defaults is an important improvement because most of the variants of the precautionary principle require cost-benefit balancing. Specifically, increasing the set of causal defaults accounts for beneficial effects at very low doses. We also show and conclude that quantitative risk assessment dominates qualitative risk assessment, supporting the extension of the set of default causal models.

Concepts and methods of quantitative assessment of risk to groundwater resources

This work presents a two-dimensional approach of risk assessment method based on the quantification of the probability of the occurrence of contaminant source terms, as well as the assessment of the resultant impacts. The risk is calculated using Monte Carlo simulation methods whereby synthetic contaminant source terms were generated to the same distribution as historically occurring pollution events or a priori potential probability distribution. The spatial and temporal distributions of the generated contaminant concentrations at pre-defined monitoring points within the aquifer were then simulated from repeated realisations using integrated mathematical models. The number of times when user defined ranges of concentration magnitudes were exceeded is quantified as risk. The utilities of the method were demonstrated using hypothetical scenarios, and the risk of pollution from a number of sources all occurring by chance together was evaluated. The results are presented in the form of charts and spatial maps. The generated risk maps show the risk of pollution at each observation borehole, as well as the trends within the study area. This capability to generate synthetic pollution events from numerous potential sources of pollution based on historical frequency of their occurrence proved to be a great asset to the method, and a large benefit over the contemporary methods.

Development of a probabilistic graphical structure from a model of mental health clinical expertise

This thesis explores the process of developing a principled approach for translating a model of mental-health risk expertise into a probabilistic graphical structure. Probabilistic graphical structures can be a combination of graph and probability theory that provide numerous advantages when it comes to the representation of domains involving uncertainty, domains such as the mental health domain. In this thesis the advantages that probabilistic graphical structures offer in representing such domains is built on. The Galatean Risk Screening Tool (GRiST) is a psychological model for mental health risk assessment based on fuzzy sets. In this thesis the knowledge encapsulated in the psychological model was used to develop the structure of the probability graph by exploiting the semantics of the clinical expertise. This thesis describes how a chain graph can be developed from the psychological model to provide a probabilistic evaluation of risk that complements the one generated by GRiST’s clinical expertise by the decomposing of the GRiST knowledge structure in component parts, which were in turned mapped into equivalent probabilistic graphical structures such as Bayesian Belief Nets and Markov Random Fields to produce a composite chain graph that provides a probabilistic classification of risk expertise to complement the expert clinical judgements

A probabilistic approach to assess hydrate formation and design preventive measures

Formation of hydrates is one of the major flow assurance problems faced by the oil and gas industry. Hydrates tend to form in natural gas pipelines with the presence of water and favorable temperature and pressure conditions, generally low temperatures and corresponding high pressures. Agglomeration of hydrates can result in blockage of flowlines and equipment, which can be time consuming to remove in subsea equipment and cause safety issues. Natural gas pipelines are more susceptible to burst and explosion owing to hydrate plugging. Therefore, a rigorous risk-assessment related to hydrate formation is required, which assists in preventing hydrate blockage and ensuring equipment integrity. This thesis presents a novel methodology to assess the probability of hydrate formation and presents a risk-based approach to determine the parameters of winterization schemes to avoid hydrate formation in natural gas pipelines operating in Arctic conditions. It also presents a lab-scale multiphase flow loop to study the effects of geometric and hydrodynamic parameters on hydrate formation and discusses the effects of geometric and hydrodynamic parameters on multiphase development length of a pipeline. Therefore, this study substantially contributes to the assessment of probability of hydrate formation and the decision making process of winterization strategies to prevent hydrate formation in Arctic conditions.