Genetic epidemiologic methods in risk determination in Li-Fraumeni syndrome

Li-Fraumeni syndrome (LFS) is characterized by a variety of neoplasms occurring at a young age with an apparent autosomal dominant transmission. Individuals in pedigrees with LFS have high incidence of second malignancies. Recently LFS has been found to be associated with germline mutations of a tumor-suppressor gene, p53. Because LFS is rare and indeed not a clear-cut disease, it is not known whether all cases of LFS are attributable to p53 germline mutations and how p53 plays in cancer occurrence in such cancer syndrome families. In the present study, DNAs from constitutive cells of two-hundred and thirty-three family members from ten extended pedigrees were screened for p53 mutations. Six out of the ten LFS families had germline mutations at the p53 locus, including point and deletion mutations. In these six families, 55 out of 146 members were carriers of p53 mutations. Except one, all mutations occurred in exons 5 to 8 (i.e., the "hot spot" region) of the p53 gene. The age-specific penetrance of cancer was estimated after the genotype for each family member at risk was determined. The penetrance was 0.15, 0.29, 0.35, 0.77, and 0.91 by 20, 30, 40, 50 and 60 year-old, respectively, in male carriers; 0.19, 0.44, 0.76, and 0.90 by 20, 30, 40, and 50 year-old, respectively, in female carriers. These results indicated that one cannot escape from tumorigenesis if one inherits a p53 mutant allele; at least ninety percent of p53 carriers will develop cancer by the age of 60. To evaluate the possible bias due to the unexamined blood-relatives in LFS families, I performed a simulation analysis in which a p53 genotype was assigned to each unexamined person based on his cancer status and liability to cancer. The results showed that the penetrance estimates were not biased by the unexamined relatives. I also determined the sex, site, and age-specific penetrance of breast cancer in female carriers and lung cancer in male carriers. The penetrance of breast cancer in female carriers was 0.81 by age 45; the penetrance of lung cancer in male carriers was 0.78 by age 60, indicating that p53 play a key role for tumorigenesis in common cancers. ^

A proposed application of the attributable risk technique in the assessment of unmet need among newly organized populations

In the midst of health care reform, and as health care organizations reorganize to provide more cost-effective healthcare, the population is being shifted into new healthcare delivery systems such as health insurance purchasing alliances, and health maintenance organizations. These new models of delivery are usually organized within resource restricted and data limited environments. Health care planners are faced with the challenge of identifying priorities for preventive and primary care services within these newly organized populations (Medicare HMO, Medicaid HMO, etc.). The author proposes a technique usually employed in epidemiology--attributable risk estimation--as a planning methodology to establish preventive health priorities within newly organized populations. Illustrations of the methodology are provided utilizing the Texas 1992 population. ^

The Relationship of Provincial Economic Level and Child Injury Mortality in Thailand: A Cross-Sectional Analysis in a Middle Income Country

The objective of this cross-sectional study was to examine the relationship of provincial economic development indices with incidences of child injury mortality in Thailand from 1999 - 2001. All injury deaths among children age 1-14 years were included. The independent variables included gross provincial product per capita (GPP/c), poverty and inequality indices, material and social deprivation indices, population in rural/ urban areas, and migration. Due to multicollinearity of such variables, the 76 provinces were categorized by GPP/c quartile, and means of overall injury, drowning, and transport-related mortality rates were compared among quartile groups. Spearman’s rho correlation between GPP/c and injury mortality rates was also performed. Finally, factor analysis was employed to create a set of factors to be treated as uncorrelated variables and stepwise multiple regression was carried out for the effects of the factors on injury mortality rates. A significant direct relationship was observed between GPP/c and overall injury mortality among children age 1-4 years, and 10-14 year-olds of both genders. Drowning was the main cause of this relationship among children age 1-4 years, and transport-related injury was the principle cause among children age 10-14 years. Conversely, provinces with lower GPP/c experienced higher injury mortality rates among school-age children 5-9 years old for both genders, mostly due to drowning. Factor analysis, and multiple regression results confirmed the relationships between economic development and injury mortality rates. These findings revealed that economic development had an adverse impact on injury-related mortality among children 1 to 4 and 10 to14 in Thailand.

Survey and brain storming studies about machines, constructions, human and environmental risk consideration in the careers of the Universidad Politécnica of Madrid

The Universidad Politécnica of Madrid (UPM) includes schools and faculties that were for engineering degrees, architecture and computer science, that are now in a quick EEES Bolonia Plan metamorphosis getting into degrees, masters and doctorate structures. They are focused towards action in machines, constructions, enterprises, that are subjected to machines, human and environment created risks. These are present in actions such as use loads, wind, snow, waves, flows, earthquakes, forces and effects in machines, vehicles behavior, chemical effects, and other environmental factors including effects of crops, cattle and beasts, forests, and varied essential economic and social disturbances. Emphasis is for authors in this session more about risks of natural origin, such as for hail, winds, snow or waves that are not exactly known a priori, but that are often considered with statistical expected distributions giving extreme values for convenient return periods. These distributions are known from measures in time, statistic of extremes and models about hazard scenarios and about responses of man made constructions or devices. In each engineering field theories were built about hazards scenarios and how to cover for important risks. Engineers must get that the systems they handle, such as vehicles, machines, firms or agro lands or forests, obtain production with enough safety for persons and with decent economic results in spite of risks. For that risks must be considered in planning, in realization and in operation, and safety margins must be taken but at a reasonable cost. That is a small level of risks will often remain, due to limitations in costs or because of due to strange hazards, and maybe they will be covered by insurance in cases such as in transport with cars, ships or aircrafts, in agro for hail, or for fire in houses or in forests. These and other decisions about quality, security for men or about business financial risks are sometimes considered with Decision Theories models, using often tools from Statistics or operational Research. The authors have done and are following field surveys about risk consideration in the careers in UPM, making deep analysis of curricula taking into account the new structures of degrees in the EEES Bolonia Plan, and they have considered the risk structures offered by diverse schools of Decision theories. That gives an aspect of the needs and uses, and recommendations about improving in the teaching about risk, that may include special subjects especially oriented for each career, school or faculty, so as to be recommended to be included into the curricula, including an elaboration and presentation format using a multi-criteria decision model.

A multinational SDI-based system to facilitate disaster risk management in the Andean Community

A useful strategy for improving disaster risk management is sharing spatial data across different technical organizations using shared information systems. However, the implementation of this type of system requires a large effort, so it is difficult to find fully implemented and sustainable information systems that facilitate sharing multinational spatial data about disasters, especially in developing countries. In this paper, we describe a pioneer system for sharing spatial information that we developed for the Andean Community. This system, called SIAPAD (Andean Information System for Disaster Prevention and Relief), integrates spatial information from 37 technical organizations in the Andean countries (Bolivia, Colombia, Ecuador, and Peru). SIAPAD was based on the concept of a thematic Spatial Data Infrastructure (SDI) and includes a web application, called GEORiesgo, which helps users to find relevant information with a knowledge-based system. In the paper, we describe the design and implementation of SIAPAD together with general conclusions and future directions which we learned as a result of this work.

Risk analysis for UAV safe operations: a rationalization for an agricultural environment

The road to the automation of the agricultural processes passes through the safe operation of the autonomous vehicles. This requirement is a fact in ground mobile units, but it still has not well defined for the aerial robots (UAVs) mainly because the normative and legislation are quite diffuse or even inexistent. Therefore, to define a common and global policy is the challenge to tackle. This characterization has to be addressed from the field experience. Accordingly, this paper presents the work done in this direction, based on the analysis of the most common sources of hazards when using UAV's for agricultural tasks. The work, based on the ISO 31000 normative, has been carried out by applying a three-step structure that integrates the identification, assessment and reduction procedures. The present paper exposes how this method has been applied to analyze previous accidents and malfunctions during UAV operations in order to obtain real failure causes. It has allowed highlighting common risks and hazardous sources and proposing specific guards and safety measures for the agricultural context.

Environmental risk assessment in open pit blasting operations: compliance with ISO 31010:2010

All activities of an organization involve risks that should be managed. The risk management process aids decision making by taking account of uncertainty and the possibility of future events or circumstances (intended or unintended) and their effects on agreed objectives. With that idea, new ISO Standard has been drawn up. ISO 31010 has been recently issued which provides a structured process that identifies how objectives may be affected, and analyses the risk in term of consequences and their probabilities before deciding on whether further treatment is required. In this lecture, that ISO Standard has been adapted to Open Pit Blasting Operations, focusing in Environmental effects which can be managed properly. Technique used is Fault Tree Analysis (FTA), which is applied in all possible scenarios, providing to Blasting Professionals the tools to identify, analyze and manage environmental effects in blasting operations. Also this lecture can help to minimize each effect, studying each case. This paper also can be useful to Project Managers and Occupational Health and Safety Departments (OH&S) because blasting operations can be evaluated and compared one to each other to determine the risks that should be managed in different case studies. The environmental effects studied are: ground vibrations, flyrock and air overpressure (airblast). Sometimes, blasting operations are carried out near populated areas where environmental effects may impose several limitations on the use of explosives. In those cases, where these factors approach certain limits, National Standards and Regulations have to be applied.

Radar track segmentation with cubic splines for collision risk models in high density terminal areas

This paper presents a method to segment airplane radar tracks in high density terminal areas where the air traffic follows trajectories with several changes in heading, speed and altitude. The radar tracks are modelled with different types of segments, straight lines, cubic spline function and shape preserving cubic function. The longitudinal, lateral and vertical deviations are calculated for terminal manoeuvring area scenarios. The most promising model of the radar tracks resulted from a mixed interpolation using straight lines for linear segments and spline cubic functions for curved segments. A sensitivity analysis is used to optimise the size of the window for the segmentation process.

Social risk factors in Spanish youth and their impact on self-concept construction

This paper presents evidence from a psychosocial framework about the relationship among youth, work, and identity construction. The aims of this research were twofold. The first one was to analyze the working conditions of Spanish youth and their impact on individuals' biographies. The second one was to examine the effect of labor-related variables on construction / change of identity elements in Spanish youth. For this purpose, two research techniques were used: the Delphi method (103 experts sample from several entities and organizations closely related to our topic) and deep interviews (15 interviews with youths classified according to their relationship with the work market). Copyright 2007 by The Spanish Journal of Psychology.

Cancer mortality inequalities in urban areas: a Bayesian small area analysis in Spanish cities

Background: Intra-urban inequalities in mortality have been infrequently analysed in European contexts. The aim of the present study was to analyse patterns of cancer mortality and their relationship with socioeconomic deprivation in small areas in 11 Spanish cities. Methods: It is a cross-sectional ecological design using mortality data (years 1996-2003). Units of analysis were the census tracts. A deprivation index was calculated for each census tract. In order to control the variability in estimating the risk of dying we used Bayesian models. We present the RR of the census tract with the highest deprivation vs. the census tract with the lowest deprivation. Results: In the case of men, socioeconomic inequalities are observed in total cancer mortality in all cities, except in Castellon, Cordoba and Vigo, while Barcelona (RR = 1.53 95%CI 1.42-1.67), Madrid (RR = 1.57 95%CI 1.49-1.65) and Seville (RR = 1.53 95%CI 1.36-1.74) present the greatest inequalities. In general Barcelona and Madrid, present inequalities for most types of cancer. Among women for total cancer mortality, inequalities have only been found in Barcelona and Zaragoza. The excess number of cancer deaths due to socioeconomic deprivation was 16,413 for men and 1,142 for women. Conclusion: This study has analysed inequalities in cancer mortality in small areas of cities in Spain, not only relating this mortality with socioeconomic deprivation, but also calculating the excess mortality which may be attributed to such deprivation. This knowledge is particularly useful to determine which geographical areas in each city need intersectorial policies in order to promote a healthy environment.

Carbon fiber risk analysis.

Item 830-H-10 (microfiche)

Spill risk analysis program : methodology development and demonstration /

Final report, Apr. 1977.

Movable concrete median barrier: risk analysis of deflection into opposing traffic.

Federal Highway Administration, Office of Research, Development, and Technology, Washington, D.C.

Automotive manufacturers' cost/revenue, financial and risk analysis: projected impact of automobile manufacturing on the plastics industry. Final report.

National Highway Traffic Safety Administration, Office of Research and Development, Washington, D.C.

Design risk analysis. Volume I: final report. Final report.

Federal Highway Administration, Office of Safety and Traffic Operations Research and Development, McLean, Va.