Internationalization process of TUBOFURO

The central objective of this case study was to formulate the strategy of internationalization of Tubofuro®, discriminating relevant points from its design to its implementation. This is a company located in Leiria, Ortigosa parish, which operates, among others, in the Portuguese PVC pipes industry for which currently the domestic market is clearly insufficient, given the oversupply compared to demand. Being Tubofuro® an exporting company since 2004, the work here developed specifically intended to increase sales to the foreign market, with this representing 45% of total company's business in 2018 increasing of the number of markets through new partners to enable the positioning of Tubofuro® among the main players in each market, particularly in South American markets, North African and European. To achieve the above objectives presented a case study was applied, centred on Tubofuro® company, target of the internationalization strategy. The search carried out for the formulation of the strategy has been supported on a thorough analysis of the external environment and internal characteristics of the company, for which were crossed different types of data, quantitative, qualitative, secondary data and primary data. From this work resulted the development of internationalization and international marketing plan for the next three years, whose objectives are based on entrance and consequent growth in new markets, including the market Chilean, Peruvian, Mexican, Argentine, Algerian and German, as well growth in the presence and turnover in the markets for which Tubofuro® already exports regularly, for example Spain, France, Tunisia and Morocco. Based on the production capacity of Tubofuro® company, which will not suffer any kind of investment for incrementing but only to update, it is expected that the appropriate response capacity for the company is 8 regular markets, and could eventually arise sporadic exports to other markets not interfering with the normal production capacity of the company. The suggestion of the presented markets resulted from the study of the final price based on the one that local customers purchase a product equal or similar to Tubofuro® and the number of potential existing customers in each market. The internationalization model known as Uppsala Model corresponds to the strategy adopted by the company to its internationalization process, taking into account the philosophy of senior management and the risk aversion of them. The sales team Tubofuro® demand for each market, export a full container registering customer feedback, including quality and flow capacity in the market in order to seek a partnership agreement with a local distributor, which allows the Tubofuro® go to step two above mentioned model. The partnership agreement is based on mutual commitment to technical cooperation and trade between the Tubofuro® and partner, in order to increase the performance capacity among local customers. Only if the market presents a greater demand to our supply capacity and be justified by cost / benefit ratio, the entry into this market through a joint venture or subsidiary is that the decision will be taken. Although this is a case study, which means that is adjusted to the concrete case Tubofuro® preventing generalization of findings, we believe that this work can be a useful example for other companies in the internationalization process or the methodology adopted in formulating strategy or the outputs and conclusions drawn.

Grape and Wine Metabolites: Biotechnological Approaches to Improve Wine Quality

Grape metabolites can be affected by many extrinsic and intrinsic factors, such as grape variety, ripening stage, growing regions, vineyard management practices, and edaphoclimatic conditions. However, there is still much about the in vivo formation of grape metabolites that need to be investigated. The winemaking process also can create distinct wines. Nowadays, wine fermentations are driven mostly by single-strain inoculations, allowing greater control of fermentation. Pure cultures of selected yeast strains, mostly Saccharomyces cerevisiae, are added to grape must, leading to more predictable outcomes and decreasing the risk of spoilage. Besides yeasts, lactic acid bacteria also play an important role, in the final wine quality. Thus, this chapter attempts to present an overview of grape berry physiology and metabolome to provide a deep understanding of the primary and secondary metabolites accumulated in the grape berries and their potential impact in wine quality. In addition, biotechnological approaches for wine quality practiced during wine alcoholic and malolactic fermentation will also be discussed.

Cystatin C and cardiovascular disease : A mendelian randomization study

BACKGROUND: Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES: The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n ¼ 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n ¼ 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS: Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p ¼ 2.12 1014). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p ¼ 5.95 10211), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence for a causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p ¼ 0.994), which was statistically different from the observational estimate (p ¼ 1.6 105 ). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS: Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD. 

Prevalencia e incidencia de cáncer en habitantes de Sibaté, y georeferenciación de casos 2010-2014

Introducción: El Cáncer es prevenible en algunos casos, si se evita la exposición a sustancias cancerígenas en el medio ambiente. En Colombia, Cundinamarca es uno de los departamentos con mayores incrementos en la tasa de mortalidad y en el municipio de Sibaté, habitantes han manifestado preocupación por el incremento de la enfermedad. En el campo de la salud ambiental mundial, la georreferenciación aplicada al estudio de fenómenos en salud, ha tenido éxito con resultados válidos. El estudio propuso usar herramientas de información geográfica, para generar análisis de tiempo y espacio que hicieran visible el comportamiento del cáncer en Sibaté y sustentaran hipótesis de influencias ambientales sobre concentraciones de casos. Objetivo: Obtener incidencia y prevalencia de casos de cáncer en habitantes de Sibaté y georreferenciar los casos en un periodo de 5 años, con base en indagación de registros. Metodología: Estudio exploratorio descriptivo de corte transversal,sobre todos los diagnósticos de cáncer entre los años 2010 a 2014, encontrados en los archivos de la Secretaria de Salud municipal. Se incluyeron unicamente quienes tuvieron residencia permanente en el municipio y fueron diagnosticados con cáncer entre los años de 2010 a 2104. Sobre cada caso se obtuvo género, edad, estrato socioeconómico, nivel académico, ocupación y estado civil. Para el análisis de tiempo se usó la fecha de diagnóstico y para el análisis de espacio, la dirección de residencia, tipo de cáncer y coordenada geográfica. Se generaron coordenadas geográficas con un equipo GPS Garmin y se crearon mapas con los puntos de la ubicación de las viviendas de los pacientes. Se proceso la información, con Epi Info 7 Resultados: Se encontraron 107 casos de cáncer registrados en la Secretaria de Salud de Sibaté, 66 mujeres, 41 hombres. Sin división de género, el 30.93% de la población presento cáncer del sistema reproductor, el 18,56% digestivo y el 17,53% tegumentario. Se presentaron 2 grandes casos de agrupaciones espaciales en el territorio estudiado, una en el Barrio Pablo Neruda con 12 (21,05%) casos y en el casco Urbano de Sibaté con 38 (66,67%) casos. Conclusión: Se corroboro que el análisis geográfico con variables espacio temporales y de exposición, puede ser la herramienta para generar hipótesis sobre asociaciones de casos de cáncer con factores ambientales.

Does lamotrigine use in pregnancy increase orofacial cleft risk relative to other malformations?

OBJECTIVE: To investigate whether first trimester exposure to lamotrigine (LTG) monotherapy is specifically associated with an increased risk of orofacial clefts (OCs) relative to other malformations, in response to a signal regarding increased OC risk. METHODS: Population-based case-control study with malformed controls based on EUROCAT congenital anomaly registers. The study population covered 3.9 million births from 19 registries 1995-2005. Registrations included congenital anomaly among livebirths, stillbirths, and terminations of pregnancy following prenatal diagnosis. Cases were 5,511 nonsyndromic OC registrations, of whom 4,571 were isolated, 1,969 were cleft palate (CP), and 1,532 were isolated CP. Controls were 80,052 nonchromosomal, non-OC registrations. We compared first trimester LTG and antiepileptic drug (AED) use vs nonepileptic non-AED use, for mono and polytherapy, adjusting for maternal age. An additional exploratory analysis compared the observed and expected distribution of malformation types associated with LTG use. RESULTS: There were 72 LTG exposed (40 mono- and 32 polytherapy) registrations. The ORs for LTG monotherapy vs no AED use were 0.67 (95% CI 0.10-2.34) for OC relative to other malformations, 0.80 (95% CI 0.11-2.85) for isolated OC, 0.79 (95% CI 0.03-4.35) for CP, and 1.01 (95% CI 0.03-5.57) for isolated CP. ORs for any AED use vs no AED use were 1.43 (95% CI 1.03-1.93) for OC, 1.21 (95% CI 0.82-1.72) for isolated OC, 2.37 (95% CI 1.54-3.43) for CP, and 1.86 (95% CI 1.07-2.94) for isolated CP. The distribution of other nonchromosomal malformation types with LTG exposure was similar to non-AED exposed. CONCLUSION: We find no evidence of a specific increased risk of isolated orofacial clefts relative to other malformations due to lamotrigine (LTG) monotherapy. Our study is not designed to assess whether there is a generalized increased risk of malformations with LTG exposure.

Increased Framingham Coronary Heart Disease Risk Score in dementia caregivers relative to non-caregiving controls

BACKGROUND: Elderly individuals who provide care to a spouse suffering from dementia bear an increased risk of coronary heart disease (CHD). OBJECTIVE: To test the hypothesis that the Framingham CHD Risk Score would be higher in dementia caregivers relative to non-caregiving controls. METHODS: We investigated 64 caregivers providing in-home care for their spouse with Alzheimer's disease and 41 gender-matched non-caregiving controls. All subjects (mean age 70 +/- 8 years, 75% women, 93% Caucasian) had a negative history of CHD and cerebrovascular disease. The original Framingham CHD Risk Score was computed adding up categorical scores for age, blood lipids, blood pressure, diabetes, and smoking with adjustment made for sex. RESULTS: The average CHD risk score was higher in caregivers than in controls even when co-varying for socioeconomic status, health habits, medication, and psychological distress (8.0 +/- 2.9 vs. 6.3 +/- 3.0 points, p = 0.013). The difference showed a medium effect size (Cohen's d = 0.57). A relatively higher blood pressure in caregivers than in controls made the greatest contribution to this difference. The probability (area under the receiver operator curve) that a randomly selected caregiver had a greater CHD risk score than a randomly selected non-caregiver was 65.5%. CONCLUSIONS: Based on the Framingham CHD Risk Score, the potential to develop overt CHD in the following 10 years was predicted to be greater in dementia caregivers than in non-caregiving controls. The magnitude of the difference in the CHD risk between caregivers and controls appears to be clinically relevant. Clinicians may want to monitor caregiving status as a routine part of standard evaluation of their elderly patients' cardiovascular risk.

Decreasing risk of hepatitis a infection in león, nicaragua: evidence from cross-sectional and longitudinal seroepidemiology studies

BACKGROUND AND OBJECTIVES Nicaragua is highly endemic for hepatitis A. We aimed to provide an estimate of the change in the age-specific risk of hepatitis A virus (HAV) infection based on serological data from cross-sectional and longitudinal samples collected in León, Nicaragua, in 1995/96 (n = 979) and 2003 (n = 494). METHODS The observed age-specific prevalence of anti-HAV antibodies was correlated to the age-specific risk of infection by calculating the probability of freedom from infection at a specific age. RESULTS The proportion of seropositive children aged 1.5 to 6 years was 42% in 2003 compared to 67% in 1995/96. Estimated annual risk of infection for a 3-year old child was 30% (95% CI: 27.0%, 33.1%) in 1995 and 15.5% (95% CI: 12.4%, 19.0%) in 2003. There was good agreement between estimates based on cross-sectional and longitudinal data. The age-specific geometric mean of the quantified anti-HAV antibody levels assessed in 2003 was highest at age 4 and decreased steadily up to age 40. CONCLUSIONS The substantially lower risk of HAV infection in 2003 than in 1995 for young children indicates a beginning transition from high to intermediate endemicity in León, Nicaragua. Consecutive age-stratified serosurveys are useful to assess changes in risk of infection following public health interventions. The decreasing age-specific GMC of anti-HAV antibodies during adulthood in a country with endemic HAV indirectly suggests that ongoing HAV exposure in the community has marginal boosting effect on antibody levels once protective immunity has been established by natural infection.

Relative Energy Balance, CKD, and Risk of Cardiovascular and All-Cause Mortality.

BACKGROUND Mortality risk for people with chronic kidney disease is substantially greater than that for the general population, increasing to a 7-fold greater risk for those on dialysis therapy. Higher body mass index, generally due to higher energy intake, appears protective for people on dialysis therapy, but the relationship between energy intake and survival in those with reduced kidney function is unknown. STUDY DESIGN Prospective cohort study with a median follow-up of 14.5 (IQR, 11.2-15.2) years. SETTING & PARTICIPANTS Blue Mountains Area, west of Sydney, Australia. Participants in the general community enrolled in the Blue Mountains Eye Study (n=2,664) who underwent a detailed interview, food frequency questionnaire, and physical examination including body weight, height, blood pressure, and laboratory tests. PREDICTORS Relative energy intake, food components (carbohydrates, total sugars, fat, protein, and water), and estimated glomerular filtration rate (eGFR). Relative energy intake was dichotomized at 100%, and eGFR, at 60mL/min/1.73m(2). OUTCOMES All-cause and cardiovascular mortality. MEASUREMENTS All-cause and cardiovascular mortality using unadjusted and adjusted Cox proportional regression models. RESULTS 949 people died during follow-up, 318 of cardiovascular events. In people with eGFR<60mL/min/1.73m(2) (n=852), there was an increased risk of all-cause mortality (HR, 1.48; P=0.03), but no increased risk of cardiovascular mortality (HR, 1.59; P=0.1) among those with higher relative energy intake compared with those with lower relative energy intake. Increasing intake of carbohydrates (HR per 100g/d, 1.50; P=0.04) and total sugars (HR per 100g/d, 1.62; P=0.03) was associated significantly with increased risk of cardiovascular mortality. LIMITATIONS Under-reporting of energy intake, baseline laboratory and food intake values only, white population. CONCLUSIONS Increasing relative energy intake was associated with increased all-cause mortality in patients with eGFR<60mL/min/1.73m(2). This effect may be mediated by increasing total sugars intake on subsequent cardiovascular events.

Predicting 10-year risk of fatal cardiovascular disease in Germany: an update based on the SCORE-Deutschland Risk Charts

Estimation of absolute risk of cardiovascular disease (CVD), preferably with population-specific risk charts, has become a cornerstone of CVD primary prevention. Regular recalibration of risk charts may be necessary due to decreasing CVD rates and CVD risk factor levels. The SCORE risk charts for fatal CVD risk assessment were first calibrated for Germany with 1998 risk factor level data and 1999 mortality statistics. We present an update of these risk charts based on the SCORE methodology including estimates of relative risks from SCORE, risk factor levels from the German Health Interview and Examination Survey for Adults 2008-11 (DEGS1) and official mortality statistics from 2012. Competing risks methods were applied and estimates were independently validated. Updated risk charts were calculated based on cholesterol, smoking, systolic blood pressure risk factor levels, sex and 5-year age-groups. The absolute 10-year risk estimates of fatal CVD were lower according to the updated risk charts compared to the first calibration for Germany. In a nationwide sample of 3062 adults aged 40-65 years free of major CVD from DEGS1, the mean 10-year risk of fatal CVD estimated by the updated charts was lower by 29% and the estimated proportion of high risk people (10-year risk > = 5%) by 50% compared to the older risk charts. This recalibration shows a need for regular updates of risk charts according to changes in mortality and risk factor levels in order to sustain the identification of people with a high CVD risk.

Association between ferritin, high sensitivity c-reactive protein (hsCRP) and relative abundance of Hepcidin mRNA with the risk of type 2 diabetes in obese subjects

Obesity and Type 2 diabetes mellitus share a strong pro-inflammatory profile. It has been observed that iron is a risk factor in the development of type 2 diabetes. The aim of this study was to evaluate the relationship between iron nutritional status and inflammation with the risk of type 2 diabetes development in obese subjects. We studied 30 obese men with type 2 diabetes (OBDM); 30 obese subjects without diabetes (OB) and 30 healthy subjects (Cn). We isolated peripheral mononuclear cells (PMCs) and challenged them with high Fe concentrations. Total mRNA was isolated and relative abundance of TNF-αIL-6 and hepcidin were determined by qPCR. Iron status, biochemical, inflammatory and oxidative stress parameters were also characterized. OBDM and OB patients showed increased hsCRP levels compared to the Cn group. OBDM subjects showed higher levels of ferritin than the Cn group. TNF-α and IL-6 mRNA relative abundances were increased in OBDM PMCs treated with high/Fe. Hepcidin mRNA was increased with basal and high iron concentration. We found that the highest quartile of ferritin was associated with an increased risk of type 2 diabetes when it was adjusted to BMI and HOMA-IR; this association was independent of the inflammatory status. The highest level of hepcidin gene expression also showed a trend of increased risk of diabetes, however it was not significant. Levels of hsCRP over 2 mg/L showed a significant trend of increasing the risk of diabetes. In conclusion, iron may stimulate the expression of pro-inflammatory genes (TNF-α and IL-6), and both hepcidin and ferritin gene expression levels could be a risk factor for the development of type 2 diabetes. Subjects that have an increased cardiovascular risk also have a major risk to develop type 2 diabetes, which is independent of the BMI and insulin resistance state.

Genetic Variants of Diabetes Risk and Incident Cardiovascular Events in Chronic Coronary Artery Disease

Objective: To determine whether information from genetic risk variants for diabetes is associated with cardiovascular events incidence. Methods: From the about 30 known genes associated with diabetes, we genotyped single-nucleotide polymorphisms at the 10 loci most associated with type-2 diabetes in 425 subjects from the MASS-II Study, a randomized study in patients with multi-vessel coronary artery disease. The combined genetic information was evaluated by number of risk alleles for diabetes. Performance of genetic models relative to major cardiovascular events incidence was analyzed through Kaplan-Meier curve comparison and Cox Hazard Models and the discriminatory ability of models was assessed for cardiovascular events by calculating the area under the ROC curve. Results: Genetic information was able to predict 5-year incidence of major cardiovascular events and overall-mortality in non-diabetic individuals, even after adjustment for potential confounders including fasting glycemia. Non-diabetic individuals with high genetic risk had a similar incidence of events then diabetic individuals (cumulative hazard of 33.0 versus 35.1% of diabetic subjects). The addition of combined genetic information to clinical predictors significantly improved the AUC for cardiovascular events incidence (AUC = 0.641 versus 0.610). Conclusions: Combined information of genetic variants for diabetes risk is associated to major cardiovascular events incidence, including overall mortality, in non-diabetic individuals with coronary artery disease.

Evaluating gene by sex and age interactions on cardiovascular risk factors in Brazilian families

Background: In family studies, it is important to evaluate the impact of genes and environmental factors on traits of interest. In particular, the relative influences of both genes and the environment may vary in different strata of the population of interest, such as young and old individuals, or males and females. Methods: In this paper, extensions of the variance components model are used to evaluate heterogeneity in the genetic and environmental variance components due to the effects of sex and age (the cutoff between young and old was 43 yrs). The data analyzed were from 81 Brazilian families (1,675 individuals) of the Baependi Family Heart Study. Results: The models allowing for heterogeneity of variance components by sex suggest that genetic and environmental variances are not different in males and females for diastolic blood pressure, LDL-cholesterol, and HDL-cholesterol, independent of the covariates included in the models. However, for systolic blood pressure, fasting glucose and triglycerides, the evidence for heterogeneity was dependent on the covariates in the model. For instance, in the presence of sex and age covariates, heterogeneity in the genetic variance component was suggested for fasting glucose. But, for systolic blood pressure, there was no evidence of heterogeneity in any of the two variance components. Except for the LDL-cholesterol, models allowing for heterogeneity by age provide evidence of heterogeneity in genetic variance for triglycerides and systolic and diastolic blood pressure. There was evidence of heterogeneity in environmental variance in fasting glucose and HDL-cholesterol. Conclusions: Our results suggest that heterogeneity in trait variances should not be ignored in the design and analyses of gene-finding studies involving these traits, as it may generate additional information about gene effects, and allow the investigation of more sophisticated models such as the model including sex-specific oligogenic variance components.

GIS applied to geotechnical and environmental risk management in a Brazilian oil pipeline

The paper presents the development of a decision support system for the management of geotechnical and environmental risks in oil pipelines using a geographical information system. The system covers a 48.5 km long section of the So Paulo to Brasilia (OSBRA) oil pipeline, which crosses three municipalities in the northeast region of the So Paulo state (Brazil) and represents an area of 205.8 km(2). The spatial database was created using geo-processing procedures, surface and intrusive investigations and geotechnical reports. The risk assessment was based mainly on qualitative models (relative numeric weights and multicriteria decision analysis) and considered pluvial erosion, slope movements, soil corrosion and third party activities. The maps were produced at a scale of 1:10,000.

Speciation and absolute bioavailability: risk assessment of arsenic-contaminated sites in a residential suburb in Canberra

Watson is a fully developed suburb of some 30 years in Canberra (the capital city of Australia), A plunge dip using arsenical pesticides for tick control was operated there between 1946 and 1960, Chemical investigations revealed that many soil samples obtained from the study area contained levels of arsenic exceeding the current health-based investigation levels of 100 mg kg(-1) set by the National Health and Medical Research Council in Australia, For the speciation study, nine composite samples of surface and sub-surface soils and a composite sample of rocks were selected. ICP-MS analysis showed that arsenic levels in these samples ranged from 32 to 1597 mg kg(-1), Chemical speciation of arsenic showed that the arsenite (trivalent) components were 0.32-56% in the soil and 44.8% in the rock composite samples. Using a rat model, the absolute bioavailability of these contaminated soils relative to As3+ or As5+ ranged from 1.02 to 9.87% and 0.26 to 2.98%, respectively, An attempt was made to develop a suitable leachate test as an index of bioavailability. However, the results indicated that there was no significant correlation between the bioavailability and leachates using neutral pH water or 1 M HCl. Our results indicate that speciation is highly significant for the interpretation of bioavailability and risk assessment data; the bioavailable fractions of arsenic in soils from Watson are small and therefore the health impact upon the environment and humans due to this element is limited.