Are functional and genetic components of platelets linked to coronary artery disease: A case-control study

Coronary artery disease (CAD) is a multifactorial disease process involving behavioral, inflammatory, clinical, thrombotic, and genetic components. Previous epidemiologic studies focused on identifying behavioral and demographic risk factors of CAD, but none focused on platelets. Current platelet literature lacks the known effects of platelet function and platelet receptor polymorphisms on CAD. This case-control analysis addressed these issues by analyzing data collected for a previous study. Cases were individuals who had undergone CABG and thus had been diagnosed with CAD, while the controls were volunteers presumed to be CAD free. The platelet function variables analyzed included fibrinogen Von Willebrand Factor activity (VWF), shear-induced platelet aggregation (SIPA), sCD40L, and mean platelet volume; and the platelet polymorphisms studied included PIA, α2 807, Ko, Kozak, and VNTR. Univariate analysis found fibrinogen, VWF, SIPA, and PIA to be independent risk factors of CAD. Logistic regression was used to build a predictive model for CAD using the platelet function and platelet polymorphism data adjusted for age, sex, race, and current smoking status. A model containing only platelet polymorphisms and their respective receptor densities, found polymorphisms within GPIbα to be associated with CAD, yielding an 86% (95% C.I. 0.97–3.55) increased risk with the presence of at least 1 polymorphism in Ko, Kozak, or VNTR. Another model included both platelet function and platelet polymorphism data. Fibrinogen, the receptor density of GPIbα, and the polymorphism in GPIa-IIa (α2 807) were all associated with CAD with odds ratios of 1.10, 1.04, and 2.30 for fibrinogen (10mg/dl increase), GPIbα receptors (1 MFI increase), and GPIa-IIa, respectively. In addition, risk estimates and 99% confidence intervals adjusted for race were calculated to determine if the presence of a platelet receptor polymorphism was associated with CAD. The results were as follows: PIA (1.64, 0.74–3.65); α2 807 (1.35, 0.77–2.37); Ko (1.71, 0.70–4.16); Kozak (1.17, 0.54–2.52); and VNTR (1.24, 0.52–2.91). Although not statistically significant, all platelet polymorphisms were associated with an increased risk for CAD. These exploratory findings indicate that platelets do appear to have a role in atherosclerosis and that anti-platelet drugs targeting GPI-IIa and GPIbα may be better treatment candidates for individuals with CAD. ^

Molecular markers of human papillomavirus (HPV) infection and epidemiologic risk factors for squamous intraepithelial lesions (SIL) of the cervix

Infection with certain types of HPV is a necessary event in the development of cervical carcinoma; however, not all women who become infected will progress. While much is known about the molecular influence of HPV E6 and E7 proteins on the malignant transformation, little is known about the additional factors needed to drive the process. Currently, conventional cervical screening is insufficient at identifying women who are likely to progress from premalignant lesions to carcinoma. Aneuploidy and chromatin texture from image cytometry have been suggested as quantitative measures of nuclear damage in premalignant lesions and cancer, and traditional epidemiologic studies have identified potential factors to aid in the discrimination of those lesions likely to progress. ^ In the current study, real-time PCR was used to quantitate mRNA expression of the E7 gene in women exhibiting normal epithelium, LSIL, and HSIL. Quantitative cytometry was used to gather information about the DNA index and chromatin features of cells from the same women. Logistic regression modeling was used to establish predictor variables for histologic grade based on the traditional epidemiologic risk factors and molecular markers. ^ Prevalence of mRNA transcripts was lower among women with normal histology (27%) than for women with LSIL (40%) and HSIL (37%) with mean levels ranging from 2.0 to 4.2. The transcriptional activity of HPV 18 was higher than that of HPV 16 and increased with increasing level of dysplasia, reinforcing the more aggressive nature of HPV 18. DNA index and mRNA level increased with increasing histological grade. Chromatin score was not correlated with histology but was higher for HPV 18 samples and those with both HPV 18 and HPV 16. However, chromatin score and DNA index were not correlated with mRNA levels. The most predictive variables in the regression modeling were mRNA level, DNA index, parity, and age, and the ROC curves for LSIL and HSIL indicated excellent discrimination. ^ Real-time PCR of viral transcripts could provide a more efficient method to analyze the oncogenic potential within cells from cervical swabs. Epidemiological modeling of malignant progression in the cervix should include molecular markers, as well as the traditional epidemiological risk factors. ^

Evaluation of the association between cryptosporidiosis outbreaks and two interactive water fountain parks: Epidemiologic analysis and implications for public health

Background. A community-wide outbreak of cryptosporidiosis occurred in Dallas County during the summer of 2008. A subset of cases occurring with onset of illness within a 2 week interval was epidemiologically linked to 2 neighborhood interactive water fountain parks. ^ Methods. A case control study was conducted to evaluate risk factors associated with developing illness with cryptosporidiosis from the fountain parks. Cases were selected from a line list from the epidemiological study. The selection for the controls was either healthy family members or a daycare center nearby. Cases and controls were not matched. ^ Results. Interviews were completed for 44 fountain park attendees who met case definition and 54 community controls. Twenty-seven percent (27.3%) of the cases and 13.0% of the controls were between the ages of 0–4 years. Thirty-nine percent (38.6%) of the cases and 24.1% of the controls were between the ages of 5–13 years. Fourteen percent (13.6%) of the cases and 33.3% of the controls were between the ages of 14–31 years. Twenty percent (20.5%) of the cases and 29.6% of the controls were between the ages of 32–63 years. 47.7% of the cases and 42.6% of the controls were males. Fountain park attendees who reported having been splashed in the face with water were 10 times more likely to become ill than controls (OR = 10.0, 95% CI = 2.8–35.1). Persons who reported having swallowed water from the interactive fountains were 34 times more likely to become ill than controls (OR = 34.3, 95%CI = 9.3–125.7). ^ Conclusion. Prompt reporting of cases, identification of outbreak sources, and immediate implementation of remediation measures were critical in curtailing further transmission from these particular sites through the remainder of the season. This investigation underscores the potential for cryptosporidiosis outbreaks to occur in interactive fountain parks, and the need for enhanced preventive measures in these settings. Education of the public regarding avoidance of behaviors such as drinking water from interactive fountains is also an important component of public health prevention efforts. ^

Seroprevalence of toxoplasmosis and current thinking regarding screening in pregnancy: A review of the literature and case study discussion

The approach to the diagnosis and treatment of congenital toxoplasmosis has been one of flux and debate, fueled by lack of knowledge, lack of consensus, different methods of screening and different national policies for screening in different parts of the world. Countries with higher prevalence of disease such as in Europe and South America have a heightened awareness of the need to screen and treat for this parasitic infection during pregnancy. In contrast, in the United States, it is a condition scarcely discussed and has been largely ignored except in some large centers and by a few researchers. Policies and research strategies for any condition should start with obtaining good data. The aims of this thesis included a review of prevalence studies conducted in the United States, focused on the past 20 years, combined with a description of original research conducted by the author several years ago. The latter was a cross-sectional study performed in Houston, one of the largest American cities with a great ethnic mix. The study analyzed prevalence rates of Toxoplasma gondii IgG antibody in sera of women of reproductive age. Overall seroprevalence was 12.3%. In keeping with other studies, higher prevalence correlated with lower socioeconomic status, Black and Hispanic and Asian ethnicities, and increasing age. A literature search revealed only three prevalence studies performed in the United States over the past 20 years, with another four studies only referred to as personal communications or within a textbook, without further study detail available. The literature review also revealed a lack of consensus on whether or not to screen for toxoplasmosis in pregnancy, and even whether or not treatment in utero is worthwhile.^ Proponents of screening and treatment in pregnancy site studies both in the United States and France, emphasize that treatment reduces disease manifestations in infants. Opponents cite other studies that show only marginal benefits, together with potential side effects of medication regimens and generation of anxiety in parents. What is agreed on so far is the value of educating pregnant women on how to avoid contracting toxoplasmosis, and educating physicians on making the best use of reference laboratories before major treatment decisions are made. Further research to reevaluate the literature critically, review new treatment regimens and examine costs and benefits of screening and treatment of toxoplasmosis in pregnancy, bringing together European and American researchers, is needed.^

Ethnographic and epidemiologic approaches for the programming of prenatal and birth services in Mesa los Hornos, Mexico

The investigator conducted an action-oriented investigation of pregnancy and birth among the women of Mesa los Hornos, an urban squatter slum in Mexico City. Three aims guided the project: (1) To obtain information for improving prenatal and maternity service utilization; (2) To examine the utility of rapid ethnographic and epidemiologic assessment methodologies; (3) To cultivate community involvement in health development.^ Viewing service utilization as a culturally-bound decision, the study included a qualitative phase to explore women's cognition of pregnancy and birth, their perceived needs during pregnancy, and their criteria of service acceptability. A probability-based community survey delineated parameters of service utilization and pregnancy health events, and probed reasons for decisions to use medical services, lay midwives, or other sources of prenatal and labor and delivery assistance. Qualitative survey of service providers at relevant clinics, hospitals, and practices contributed information on service availability and access, and on coordination among private, social security, and public assistance health service sectors. The ethnographic approach to exploring the rationale for use or non-use of services provided a necessary complement to conventional barrier-based assessment, to inform planning of culturally appropriate interventions.^ Information collection and interpretation was conducted under the aegis of an advisory committee of community residents and service agency representatives; the residents' committee formulated recommendations for action based on findings, and forwarded the mandate to governmental social and urban development offices. Recommendations were designed to inform and develop community participation in health care decision-making.^ Rapid research methods are powerful tools for achieving community-based empowerment toward investigation and resolution of local health problems. But while ethnography works well in synergy with quantitative assessment approaches to strengthen the validity and richness of short-term field work, the author strongly urges caution in application of Rapid Ethnographic Assessments. An ethnographic sensibility is essential to the research enterprise for the development of an active and cooperative community base, the design and use of quantitative instruments, the appropriate use of qualitative techniques, and the interpretation of culturally-oriented information. However, prescribed and standardized Rapid Ethnographic Assessment techniques are counter-productive if used as research short-cuts before locale- and subject-specific cultural understanding is achieved. ^

Leukemia and occupational exposure to electromagnetic fields: An incident case-control study

The existence of an association between leukemia and electromagnetic fields (EMF) is still controversial. The results of epidemiologic studies of leukemia in occupational groups with exposure to EMF are inconsistent. Weak associations have been seen in a few studies. EMF assessment is lacking in precision. Reported dose-response relationships have been based on qualitative levels of exposure to EMF without regard to duration of employment or EMF intensity on the jobs. Furthermore, potential confounding factors in the associations were not often well controlled. The current study is an analysis of the data collected from an incident case-control study. The primary objective was to test the hypothesis that occupational exposure to EMF is associated with leukemia, including total leukemia (TL), myelogenous leukemia (MYELOG) and acute non-lymphoid leukemia (ANLL). Potential confounding factors: occupational exposure to benzene, age, smoking, alcohol consumption, and previous medical radiation exposures were controlled in multivariate logistic regression models. Dose-response relationships were estimated by cumulative occupational exposure to EMF, taking into account duration of employment and EMF intensity on the jobs. In order to overcome weaknesses of most previous studies, special efforts were made to improve the precision of EMF assessment. Two definitions of EMF were used and result discrepancies using the two definitions were observed. These difference raised a question as to whether the workers at jobs with low EMF exposure should be considered as non-exposed in future studies. In addition, the current study suggested use of lifetime cumulative EMF exposure estimates to determine dose-response relationship. The analyses of the current study suggest an association between ANLL and employment at selected jobs with high EMF exposure. The existence of an association between three types of leukemia and broader categories of occupational EMF exposure, is still undetermined. If an association does exist between occupational EMF exposure and leukemia, the results of the current study suggest that EMF might only be a potential factor in the promotion of leukemia, but not its initiation. ^

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. ^

EPIDEMIOLOGIC TRENDS OF LUNG DISEASE DUE TO MYCOBACTERIA KANSASII AND AVIUM-INTRACELLULARE IN TEXAS, 1977-1983

This study compared the reported isolations of Mycobacterium kansasii (MK) and Myobacterium avium-intracellulare (MAI) with Mycobacterium tuberculosis (MTB) between 1977-1983 in Texas. A total of 15,395 mycobacterial cases were identified of which 1,352 (8.8%) were MK or MAI. The incidence of MK was higher in urban areas than nonurban areas (p < .005). The incidence of MAI has increased in the Dallas metroplex from 34 cases to 251 for the same time period. Although the number of MK cases previously reported has always exceeded those of MAI, the numbers were equal in the last year (1983) of the study.^ More than 75% of patients with MK or MAI were Caucasians compared to only 18% of patients with MTB. Male to female ratios for MK and MAI are 3:1 and 3:2, respectively. The age distribution of MK patients were an average of 5 years younger than patients with MAI, a finding which concurs with previous studies. MK and MAI pulmonary infections continue to be absent among children and relatively absent among Hispanics.^ MK appears to be associated with occupations in construction, whereas MAI is more often associated with farm work. ^

AN INVESTIGATION OF THE RELIABILITY AND VALIDITY OF THE CENTER FOR EPIDEMIOLOGIC STUDIES DEPRESSION SCALE IN THREE ETHNIC GROUPS

Epidemiologic studies of mental disorder have called attention to the need for identifying untreated cases and to the inadequacies of the instruments available for this purpose. Accurate case ascertainment devices are the basis of sound epidemiology. Without these, neither case classification nor analytic studies of risk factors is possible.^ The purpose of this research was to examine the reliability and validity of an instrument designed to measure depressive symptoms in community populations--the Center for Epidemiologic Studies Depression Scale (CES-D Scale). Two particular foci of the study were whether or not the scale had the same statistical structure across three ethnic groups and whether or not the magnitude and pattern of rates of symptoms for these groups were affected by one source of response error, that due to response tendencies. The effects of age and education on the pattern and magnitude of rates also were examined. In addition, the reliability and validity of the measures of response tendencies were assessed.^ The study population consisted of residents of Alameda County, California. A stratified sample of approximately 700 whites, blacks and Mexican-Americans was interviewed in the summer and fall of 1978.^ The results of the analysis indicated that the scale was reliable and measured a similar content domain across the three ethnic groups. The unadjusted sex- and ethnic-specific rates of depressive symptoms showed an ethnic pattern for both sexes: rates for whites were lowest, those for Mexican-Americans were highest, and those for blacks were intermediate. Measures of response tendencies--need for social approval, trait desirability, and acquiescence--affected the magnitude of the rates for most comparisons. Likewise, the pattern of rates changed somewhat from that originally observed. The one fairly consistent observation was that rates for Mexican-American women were higher than those for the other two female subgroups in most of the comparisons. These results must be considered in the context of the reliability and validity assessment of the measures of response tendencies which indicated the tenuousness of these measures.^ Age affected the ethnic pattern of rates for men in an inconsistent way; for women, Mexican-Americans continued to have higher rates than whites or blacks in all age categories. Education affected the magnitude of rates for women but not for men. For both men and women, Mexican-Americans had higher rates in all educational strata. Rates for women showed an inverse association with education while those for men did not. ^

AN EPIDEMIOLOGIC DESCRIPTION AND ANALYSIS OF LOST WORKDAY OCCUPATIONAL BURN INJURIES

Background research consisted of a hospital case series of all adult burn patients (n = 162) admitted to John Sealy Hospital's burn unit from January 1978 to June 1979. Comparisons between occupationally and nonoccupationally burned adults demonstrated that occupationally burned adults were significantly more likely to have been active in the burn injury event and to have changed jobs during the prior year. They were significantly less likely to have physical or mental problems which contributed to sustaining the burn injury. Comparisons between occupational and nonoccupational burn injury events concluded that occupational burn injury events were significantly more likely to involve multiple sources of energy, sparks as the source of ignition and gases as the source of combustion. Other salient characteristics of occupational burn injuries indicated that subsequent research should focus upon lost workday occupational burns and other injuries sustained by blue-collar petrochemical workers employed in Galveston County, Texas.^ Subsequent research consisted of a historical cohort study of occupational injuries sustained in 1979 by a cohort of blue-collar petrochemical workers (n = 1771) who belonged to O.C.A.W. Local 4-449 in Texas City, Texas. Specific cohort injury rates included 15.08 occupational injuries per 100 person work-years, 11.98 lost workday occupational injuries per 100 person work-years, and 1.64 lost workday occupational burn injuries per 100 person work-years. Salient results from this study indicate that burn injuries are a very important type (in terms of both frequency and severity) of occupational injury sustained by blue-collar petrochemical workers, pipefitters are at greatest risk of lost workday injuries and lost workday burn injuries, company-specific experiences are comparable for lost workday occupational injuries, differences among company-specific nonlost workday occupational injury experiences may not be "safety-related", and minimal job-specific experience may not place employees at greater risk of lost workday burn injuries.^

A case-comparison interview study of brain tumors and employment in occupations with presumed electric and magnetic field exposures

Results from epidemiologic studies suggest that persons working in occupations with presumed electric and magnetic field (EMF) exposures are at increased risk of brain cancer. This study utilized data from a completed, population-based, interview case-control study of central nervous system (CNS) tumors and employment in the petrochemical industry to test the hypothesis that employment in EMF-related occupations increases CNS tumor risk. A total of 375 male residents of the Texas-Louisiana Gulf Coast Area, age 20 to 79, with primary neuroglial CNS tumors diagnosed during the period 1980-84 were identified. A population-based comparison group of 450 age, race and geographically matched males was selected. Occupational histories and potential risk factor data were collected via personal interviews with study subjects or their next-of-kin.^ Adjusted odds ratios were less than 1.0 for persons ever employed in an electrical occupation (OR = 0.65; 95% CI = 0.40-1.09) or whose usual occupation was electrical (OR = 0.76; 95% CI = 0.33-1.73). Relative risk estimates did not increase significantly as time since first employment or duration of employment increased. Examination of CNS tumor risk by high (OR = 0.80), medium (OR = 0.88) and low (OR = 0.45) exposure categories for persons whose usual occupation was electrical did not indicate a dose-response pattern. In addition, the mean age of exposed cases was not significantly younger than that for unexposed cases. Analysis of risk by probability of exposure to EMFs showed non-significant elevations in the adjusted odds ratio for definite exposed workers defined by their usual occupation (OR = 1.78; 95% CI = 0.70-4.51) and ever/never employed status (OR = 1.54; 95% CI = 0.17-4.91).^ These findings suggest that employment in occupations with presumed EMF exposures does not increase CNS tumor risk as was suggested by previous investigations. The results of this study also do not support the EMF-tumor promotion hypothesis. ^

Desintegración vertical en la industria del automóvil en España: un caso de estudio = Vertical disintegration in the automotive industry in Spain: a case study

En los años recientes se ha producido un rápido crecimiento del comercio internacional en productos semielaborados que son diseñados, producidos y ensamblados en diferentes localizaciones a lo largo de diferentes países, debido principalmente a los siguientes motivos: el desarrollo de las tecnologías de la información, la reducción de los costes de transporte, la liberalización de los mercados de capitales, la armonización de factores institucionales, la integración económica regional que implica la reducción y la eliminación de las barreras al comercio, el desarrollo económico de los países emergentes, el uso de economías de escala, así como una desregulación del comercio internacional. Todo ello ha incrementado la competencia a nivel mundial en los mercados y ha posibilitado a las compañías tener más facilidad de acceso a potenciales mercados, así como a la adquisición de capacidades y conocimientos en otros países y a la realización de alianzas estratégicas internacionales con terceros, creando un entorno con mayor incertidumbre y más exigente para las compañías que componen una industria, y que tiene consecuencias directas en las operaciones de las compañías y en la organización de su producción. Las compañías, para adaptarse, ser competitivas y beneficiarse de este nuevo escenario globalizado y más competitivo, han externalizado partes del proceso productivo hacia proveedores especializados, creando un nuevo mercado intermedio que divide el proceso productivo, anteriormente integrado en las compañías que conforman una industria, entre dos conjuntos de empresas especializadas en esa industria. Dicho proceso suele ocurrir conservando la industria en que tiene lugar, los mismos servicios y productos, la tecnología empleada y las compañías originales que la conformaban previamente a la desintegración vertical. Todo ello es así debido a que es beneficioso tanto para las compañías originales de la industria como para las nuevas compañías de este mercado intermedio por diversos motivos. La desintegración vertical en una industria tiene unas consecuencias que la transforman completamente, así como la forma de operar de las compañías que la integran, incluso para aquellas que permanecen verticalmente integradas. Una de las características más importantes de esta desintegración vertical en una industria es la posibilidad que tiene una compañía de adquirir a una tercera la primera parte del proceso productivo o un bien semielaborado, que posteriormente será finalizado por la compañía adquiriente con la práctica del outsourcing; así mismo, una compañía puede realizar la primera parte del proceso productivo o un bien semielaborado, que posteriormente será finalizado por una tercera compañía con la práctica de la fragmentación. El principal objetivo de la presente investigación es el estudio de los motivos, los facilitadores, los efectos, las consecuencias y los principales factores significativos, microeconómicos y macroeconómicos, que desencadenan o incrementan la práctica de la desintegración vertical en una industria; para ello, la investigación se divide en dos líneas completamente diferenciadas: el estudio de la práctica del outsourcing y, por otro lado, el estudio de la fragmentación por parte de las compañías que componen la industria del automóvil en España, puesto que se trata de una de las industrias más desintegradas verticalmente y fragmentadas, y este sector posee una gran importancia en la economía del país. En primer lugar, se hace una revisión de la literatura existente relativa a los siguientes aspectos: desintegración vertical, outsourcing, fragmentación, teoría del comercio internacional, historia de la industria del automóvil en España y el uso de las aglomeraciones geográficas y las tecnologías de la información en el sector del automóvil. La metodología empleada en cada uno de ellos ha sido diferente en función de la disponibilidad de los datos y del enfoque de investigación: los factores microeconómicos, utilizando el outsourcing, y los factores macroeconómicos, empleando la fragmentación. En el estudio del outsourcing, se usa un índice basado en las compras externas sobre el valor total de la producción. Así mismo, se estudia su correlación y significación con las variables económicas más importantes que definen a una compañía del sector del automóvil, utilizando la técnica estadística de regresión lineal. Aquellas variables relacionadas con la competencia en el mercado, la externalización de las actividades de menor valor añadido y el incremento de la modularización de las actividades de la cadena de valor, han resultado significativas con la práctica del outsourcing. En el estudio de la fragmentación se seleccionan un conjunto de factores macroeconómicos, comúnmente usados en este tipo de investigaciones, relacionados con las principales magnitudes económicas de un país, y un conjunto de factores macroeconómicos, no comúnmente usados en este tipo de investigaciones, relacionados con la libertad económica y el comercio internacional de un país. Se emplea un modelo de regresión logística para identificar qué factores son significativos en la práctica de la fragmentación. De entre todos los factores usados en el modelo, los relacionados con las economías de escala y los costes de servicio han resultado significativos. Los resultados obtenidos de los test estadísticos realizados en el modelo de regresión logística han resultado satisfactorios; por ello, el modelo propuesto de regresión logística puede ser considerado sólido, fiable y versátil; además, acorde con la realidad. De los resultados obtenidos en el estudio del outsourcing y de la fragmentación, combinados conjuntamente con el estado del arte, se concluye que el principal factor que desencadena la desintegración vertical en la industria del automóvil es la competencia en el mercado de vehículos. Cuanto mayor es la demanda de vehículos, más se reducen los beneficios y la rentabilidad para sus fabricantes. Estos, para ser competitivos, diferencian sus productos de la competencia centrándose en las actividades que mayor valor añadido aportan al producto final, externalizando las actividades de menor valor añadido a proveedores especializados, e incrementando la modularidad de las actividades de la cadena de valor. Las compañías de la industria del automóvil se especializan en alguna o varias de estas actividades modularizadas que, combinadas con el uso de factores facilitadores como las economías de escala, las tecnologías de la información, las ventajas de la globalización económica y la aglomeración geográfica de una industria, incrementan y motivan la desintegración vertical en la industria del automóvil, desencadenando la coespecialización en dos sectores claramente diferenciados: el sector de fabricantes de vehículos y el sector de proveedores especializados. Cada uno de ellos se especializa en unas actividades y en unos productos o servicios específicos de la cadena de valor, lo cual genera las siguientes consecuencias en la industria del automóvil: se reducen los costes de transacción en los productos o servicios intercambiados; se incrementan la relación de dependencia entre fabricantes de vehículos y proveedores especializados, provocando un aumento en la cooperación y la coordinación, acelerando el proceso de aprendizaje, posibilitando a ambos adquirir nuevas capacidades, conocimientos y recursos, y creando nuevas ventajas competitivas para ambos; por último, las barreras de entrada a la industria del automóvil y el número de compañías se ven alteradas cambiando su estructura. Como futura línea de investigación, los fabricantes de vehículos tenderán a centrarse en investigar, diseñar y comercializar el producto o servicio, delegando el ensamblaje en manos de nuevos especialistas en la materia, el contract manufacturer; por ello, sería conveniente investigar qué factores motivantes o facilitadores existen y qué consecuencias tendría la implantación de los contract manufacturer en la industria del automóvil. 1.1. ABSTRACT In recent years there has been a rapid growth of international trade in semi-finished products designed, produced and assembled in different locations across different countries, mainly due to the following reasons: development of information technologies, reduction of transportation costs, liberalisation of capital markets, harmonisation of institutional factors, regional economic integration, which involves the reduction and elimination of trade barriers, economic development of emerging countries, use of economies of scale and deregulation of international trade. All these factors have increased competition in markets at a global level and have allowed companies to gain easier access to potential markets and to the acquisition of skills and knowledge in other countries, as well as to the completion of international strategic alliances with third parties, thus creating a more demanding and uncertain environment for these companies constituting an industry, which has a direct impact on the companies' operations and the organization of their production. In order to adapt, be competitive and benefit from this new and more competitive global scenario, companies have outsourced some parts of their production process to specialist suppliers, generating a new intermediate market which divides the production process, previously integrated in the companies that made up the industry, into two sets of companies specialized in that industry. This process often occurs while preserving the industry where it takes place, its same services and products, the technology used and the original companies that formed it prior to vertical disintegration. This is because it is beneficial for both the industry's original companies and the companies belonging to this new intermediate market, for various reasons. Vertical disintegration has consequences which completely transform the industry where it takes place as well as the modus operandi of the companies that are part of it, even of those who remain vertically integrated. One of the most important features of vertical disintegration of an industry is the possibility for a company to acquire from a third one the first part of the production process or a semi-finished product, which will then be finished by the acquiring company through the practice of outsourcing; also, a company can perform the first part of the production process or a semi-finish product, which will then be completed by a third company through the practice of fragmentation. The main objective of this research is to study the motives, facilitators, effects, consequences and major significant microeconomic and macroeconomic factors that trigger or increase the practice of vertical disintegration in a certain industry; in order to do so, research is divided into two completely differentiated lines: on the one hand, the study of the practise of outsourcing and, on the other, the study of fragmentation by companies constituting the automotive industry in Spain, since this is one of the most vertically disintegrated and fragmented industries and this particular sector is of major significance in this country's economy. First, a review is made of the existing literature, on the following aspects: vertical disintegration, outsourcing, fragmentation, international trade theory, history of the automobile industry in Spain and the use of geographical agglomeration and information technologies in the automotive sector. The methodology used for each of these aspects has been different depending on the availability of data and the research approach: the microeconomic factors, using outsourcing, and the macroeconomic factors, using fragmentation. In the study on outsourcing, an index is used based on external purchases in relation to the total value of production. Likewise, their significance and correlation with the major economic variables that define an automotive company are studied, using the statistical technique of linear regression. Variables related to market competition, outsourcing of lowest value-added activities and increased modularisation of the activities of the value chain have turned out to be significant with the practice of outsourcing. In the study of fragmentation, a set of macroeconomic factors commonly used for this type of research, is selected, related to the main economic indicators of a country, as well as a set of macroeconomic factors, not commonly used for this type of research, which are related to economic freedom and the international trade of a certain country. A logistic regression model is used to identify which factors are significant in the practice of fragmentation. Amongst all factors used in the model, those related to economies of scale and service costs have turned out to be significant. The results obtained from the statistical tests performed on the logistic regression model have been successful; hence, the suggested logistic regression model can be considered to be solid, reliable and versatile; likewise, it is in line with reality. From the results obtained in the study of outsourcing and fragmentation, combined with the state of the art, it is concluded that the main factor that triggers vertical disintegration in the automotive industry is competition within the vehicle market. The greater the vehicle demand, the lower the earnings and profitability for manufacturers. These, in order to be competitive, differentiate their products from the competition by focusing on those activities that contribute with the highest added value to the final product, outsourcing the lower valueadded activities to specialist suppliers, and increasing the modularity of the activities of the value chain. Companies in the automotive industry specialize in one or more of these modularised activities which, combined with the use of enabling factors such as economies of scale, information technologies, the advantages of economic globalisation and the geographical agglomeration of an industry, increase and encourage vertical disintegration in the automotive industry, triggering co-specialization in two clearly distinct sectors: the sector of vehicle manufacturers and the specialist suppliers sector. Each of them specializes in certain activities and specific products or services of the value chain, generating the following consequences in the automotive industry: reduction of transaction costs of the goods or services exchanged; growth of the relationship of dependency between vehicle manufacturers and specialist suppliers, which causes an increase in cooperation and coordination, accelerates the learning process, enables both to acquire new skills, knowledge and resources, and creates new competitive advantages for both; finally, barriers to entry the automotive industry and the number of companies are altered, changing their structure. As a future line of research, vehicle manufacturers will tend to focus on researching, designing and marketing the product or service, delegating the assembly in the hands of new specialists in the field, the contract manufacturer; for this reason, it would be useful to investigate what motivating or facilitating factors exist in this respect and what consequences would the implementation of contract manufacturers have in the automotive industry.

Graph based study of allergen cross-reactivity of plant lipid transfer proteins (LTPs) using microarray in a multicenter study.

The study of cross-reactivity in allergy is key to both understanding. the allergic response of many patients and providing them with a rational treatment In the present study, protein microarrays and a co-sensitization graph approach were used in conjunction with an allergen microarray immunoassay. This enabled us to include a wide number of proteins and a large number of patients, and to study sensitization profiles among members of the LTP family. Fourteen LTPs from the most frequent plant food-induced allergies in the geographical area studied were printed into a microarray specifically designed for this research. 212 patients with fruit allergy and 117 food-tolerant pollen allergic subjects were recruited from seven regions of Spain with different pollen profiles, and their sera were tested with allergen microarray. This approach has proven itself to be a good tool to study cross-reactivity between members of LTP family, and could become a useful strategy to analyze other families of allergens.

The involvement of thaumatin-like proteins in plant food cross-reactivity: a multicenter study using a specific protein microarray.

Cross-reactivity of plant foods is an important phenomenon in allergy, with geographical variations with respect to the number and prevalence of the allergens involved in this process, whose complexity requires detailed studies. We have addressed the role of thaumatin-like proteins (TLPs) in cross-reactivity between fruit and pollen allergies. A representative panel of 16 purified TLPs was printed onto an allergen microarray. The proteins selected belonged to the sources most frequently associated with peach allergy in representative regions of Spain. Sera from two groups of well characterized patients, one with allergy to Rosaceae fruit (FAG) and another against pollens but tolerant to food-plant allergens (PAG), were obtained from seven geographical areas with different environmental pollen profiles. Cross-reactivity between members of this family was demonstrated by inhibition assays. Only 6 out of 16 purified TLPs showed noticeable allergenic activity in the studied populations. Pru p 2.0201, the peach TLP (41%), chestnut TLP (24%) and plane pollen TLP (22%) proved to be allergens of probable relevance to fruit allergy, being mainly associated with pollen sensitization, and strongly linked to specific geographical areas such as Barcelona, Bilbao, the Canary Islands and Madrid. The patients exhibited mayor que50% positive response to Pru p 2.0201 and to chestnut TLP in these specific areas. Therefore, their recognition patterns were associated with the geographical area, suggesting a role for pollen in the sensitization of these allergens. Finally, the co-sensitizations of patients considering pairs of TLP allergens were analyzed by using the co-sensitization graph associated with an allergen microarray immunoassay. Our data indicate that TLPs are significant allergens in plant food allergy and should be considered when diagnosing and treating pollen-food allergy.

Study of OLSR protocol with Network Simulator 2 over Linux

Until a few years ago, most of the network communications were based in the wire as the physical media, but due to the advances and the maturity of the wireless communications, this is changing. Nowadays wireless communications offers fast, secure, efficient and reliable connections. Mobile communications are in expansion, clearly driven by the use of smart phones and other mobile devices, the use of laptops, etc… Besides that point, the inversion in the installation and maintenance of the physical medium is much lower than in wired communications, not only because the air has no cost, but because the installation and maintenance of the wire require a high economic cost. Besides the economic cost we find that wire is a more vulnerable medium to external threats such as noise, sabotages, etc… There are two different types of wireless networks: those which the structure is part of the network itself and those which have a lack of structure or any centralization, in a way that the devices that form part of the network can connect themselves in a dynamic and random way, handling also the routing of every control and information messages, this kind of networks is known as Ad-hoc. In the present work we will proceed to study one of the multiple wireless protocols that allows mobile communications, it is Optimized Link State Routing, from now on, OLSR, it is an pro-active routing, standard mechanism that works in a distributed in order to stablish the connections among the different nodes that belong to a wireless network. Thanks to this protocol it is possible to get all the routing tables in all the devices correctly updated every moment through the periodical transmission of control messages and on this way allow a complete connectivity among the devices that are part of the network and also, allow access to other external networks such as virtual private networks o Internet. This protocol could be perfectly used in environments such as airports, malls, etc… The update of the routing tables in all the devices is got thanks to the periodical transmission of control messages and finally it will offer connectivity among all the devices and the corresponding external networks. For the study of OLSR protocol we will have the help of the network simulator “Network Simulator 2”, a freeware network simulator programmed in C++ based in discrete events. This simulator is used mainly in educational and research environments and allows a very extensive range of protocols, both, wired networks protocols and wireless network protocols, what is going to be really useful to proceed to the simulation of different configurations of networks and protocols. In the present work we will also study different simulations with Network Simulator 2, in different scenarios with different configurations, wired networks, and Ad-hoc networks, where we will study OLSR Protocol. RESUMEN. Hasta hace pocos años, la mayoría de las comunicaciones de red estaban basadas en el cable como medio físico pero debido al avance y madurez alcanzados en el campo de las comunicaciones inalámbricas esto está cambiando. Hoy día las comunicaciones inalámbricas nos ofrecen conexiones veloces, seguras, eficientes y fiables. Las comunicaciones móviles se encuentran en su momento de máxima expansión, claramente impulsadas por el uso de teléfonos y demás dispositivos móviles, el uso de portátiles, etc… Además la inversión a realizar en la instalación y el mantenimiento del medio físico en las comunicaciones móviles es muchísimo menor que en comunicaciones por cable, ya no sólo porque el aire no tenga coste alguno, sino porque la instalación y mantenimiento del cable precisan de un elevado coste económico por norma. Además del coste económico nos encontramos con que es un medio más vulnerable a amenazas externas tales como el ruido, escuchas no autorizadas, sabotajes, etc… Existen dos tipos de redes inalámbricas: las constituidas por una infraestructura que forma parte más o menos de la misma y las que carecen de estructura o centralización alguna, de modo que los dispositivos que forman parte de ella pueden conectarse de manera dinámica y arbitraria entre ellos, encargándose además del encaminamiento de todos los mensajes de control e información, a este tipo de redes se las conoce como redes Ad-hoc. En el presente Proyecto de Fin de Carrera se procederá al estudio de uno de los múltiples protocolos inalámbricos que permiten comunicaciones móviles, se trata del protocolo inalámbrico Optimized Link State Routing, de ahora en adelante OLSR, un mecanismo estándar de enrutamiento pro-activo, que trabaja de manera distribuida para establecer las conexiones entre los nodos que formen parte de las redes inalámbricas Ad-hoc, las cuales carecen de un nodo central y de una infraestructura pre-existente. Gracias a este protocolo es posible conseguir que todos los equipos mantengan en todo momento las tablas de ruta actualizadas correctamente mediante la transmisión periódica de mensajes de control y así permitir una completa conectividad entre todos los equipos que formen parte de la red y, a su vez, también permitir el acceso a otras redes externas tales como redes privadas virtuales o Internet. Este protocolo sería usado en entornos tales como aeropuertos La actualización de las tablas de enrutamiento de todos los equipos se conseguirá mediante la transmisión periódica de mensajes de control y así finalmente se podrá permitir conectividad entre todos los equipos y con las correspondientes redes externas. Para el estudio del protocolo OLSR contaremos con el simulador de redes Network Simulator 2, un simulador de redes freeware programado en C++ basado en eventos discretos. Este simulador es usado principalmente en ambientes educativos y de investigación y permite la simulación tanto de protocolos unicast como multicast. El campo donde más se utiliza es precisamente en el de la investigación de redes móviles Ad-hoc. El simulador Network Simulator 2 no sólo implementa el protocolo OLSR, sino que éste implementa una amplia gama de protocolos, tanto de redes cableadas como de redes inalámbricas, lo cual va a sernos de gran utilidad para proceder a la simulación de distintas configuraciones de redes y protocolos. En el presente Proyecto de Fin de Carrera se estudiarán también diversas simulaciones con el simulador NS2 en diferentes escenarios con diversas configuraciones; redes cableadas, redes inalámbricas Ad-hoc, donde se estudiará el protocolo antes mencionado: OLSR. Este Proyecto de Fin de Carrera consta de cuatro apartados distintos: Primeramente se realizará el estudio completo del protocolo OLSR, se verán los beneficios y contrapartidas que ofrece este protocolo inalámbrico. También se verán los distintos tipos de mensajes existentes en este protocolo y unos pequeños ejemplos del funcionamiento del protocolo OLSR. Seguidamente se hará una pequeña introducción al simulador de redes Network Simulator 2, veremos la historia de este simulador, y también se hará referencia a la herramienta extra NAM, la cual nos permitirá visualizar el intercambio de paquetes que se produce entre los diferentes dispositivos de nuestras simulaciones de forma intuitiva y amigable. Se hará mención a la plataforma MASIMUM, encargada de facilitar en un entorno académico software y documentación a sus alumnos con el fin de facilitarles la investigación y la simulación de redes y sensores Ad-hoc. Finalmente se verán dos ejemplos, uno en el que se realizará una simulación entre dos PCs en un entorno Ethernet y otro ejemplo en el que se realizará una simulación inalámbrica entre cinco dispositivos móviles mediante el protocolo a estudiar, OLSR.