Clinical and testing protocols for the analysis of epidermal growth factor receptor mutations in East Asian patients with non-small cell lung cancer:a combined clinical-molecular pathological approach

Several randomized phase III studies in advanced stage non-small cell lung cancer (NSCLC) confirmed the superior response rate and progression-free survival of using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor as first-line therapy compared with chemotherapy in patients with activating EGFR mutations. Despite the need for EGFR mutation tests to guide first-line therapy in East Asian NSCLC, there are no current standard clinical and testing protocols.

Heterozygous ATM mutations do not contribute to early onset of breast cancer

Ataxia telangiectasia (AT) is a recessive syndrome, including cerebellar degeneration, immunologic defects and cancer predisposition, attributed to mutations in the recently isolated ATM (ataxia telangiectasia, mutated) gene. AT is diagnosed in 1/40,000 to 1/100,000 live births, with carriers calculated to comprise approximately 1% of the population. Studies of AT families have suggested that female relatives presumed to be carriers have a 5 to 8-fold increased risk for developing breast cancer, raising the possibility that germline ATM mutations may account for approximately 5% of all breast cancer cases. The increased risk for breast cancer reported for AT family members has been most evident among younger women, leading to an age-specific relative risk model predicting that 8% of breast cancer in women under age 40 arises in AT carriers, compared with 2% of cases between 40-59 years. To test this hypothesis, we undertook a germ-line mutational analysis of the ATM gene in a population of women with early onset of breast cancer, using a protein truncation (PTT) assay to detect chain-terminating mutations, which account for 90% of mutations identified in children with AT. We detected a heterozygous ATM mutation in 2/202 (1%) controls, consistent with the frequency of AT carriers predicted from epidemiologic studies. ATM mutations were present in only 2/401 (0.5%) women with early onset of breast cancer (P = 0.6). We conclude that heterozygous ATM mutations do not confer genetic predisposition to early onset of breast cancer.

A behavioral intervention in a cohort of Japanese-Brazilians at high cardiometabolic risk

OBJECTIVE: To assess the effect of a health promotion program on cardiometabolic risk profile in Japanese-Brazilians. METHODS: A total of 466 subjects from a study on diabetes prevalence conducted in the city of Bauru, southeastern Brazil, in 2000 completed a 1-year intervention program (2005-2006) based on healthy diet counseling and physical activity. Changes in blood pressure and metabolic parameters in the 2005-2006 period were compared with annual changes in these same variables in the 2000-2005 period. RESULTS: During the intervention, there were greater annual reductions in mean (SD) waist circumference [-0.5(3.8) vs. 1.2(1.2) cm per year, p<0.001], systolic blood pressure [-4.6(17.9) vs. 1.8(4.3) mmHg per year, p<0.001], 2-hour plasma glucose [-1.2(2.1) vs. -0.2(0.6) mmol/L per year, p<0.001], LDL-cholesterol [-0.3(0.9) vs. -0.1(0.2) mmol/L per year, p<0.001] and Framingham coronary heart disease risk score [-0.25(3.03) vs. 0.11(0.66) per year, p=0.02] but not in triglycerides [0.2(1.6) vs. 0.1(0.42) mmol/L per year, p<0.001], and fasting insulin level [1.2(5.8) vs. -0.7(2.2) IU/mL per year, p<0.001] compared with the pre-intervention period. Significant reductions in the prevalence of impaired fasting glucose/impaired glucose tolerance and diabetes were seen during the intervention (from 58.4% to 35.4%, p<0.001; and from 30.1% to 21.7%, p= 0.004, respectively). CONCLUSIONS: A one-year community-based health promotion program brings cardiometabolic benefits in a high-risk population of Japanese-Brazilians.

Cancer among blacks and other minorities : statistical profiles /

"National Cancer Institute, Division of Cancer Prevention and Control."

IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population

Background: IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not. Aims: To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry. Methods: rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers. Results: IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 x 10(-5)). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/ relapse (NR/R) (P = 8.00 x 10(-3)). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 x 10(-3)), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 x 10(-3) and P = 2.16 x 10(-2) respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 x 10(-3)); Amerindian and European ancestry genetic contribution were greater in the SVR group. Conclusion: IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy.

Europe's continental regionalism. CEPS Working Document No. 375, February 2013

This paper reviews the multiple forms of European continental regionalism, which takes the overall shape of a complex set of concentric circles, with a substructure of a core group within the EU based on the euro and Schengen areas, and several rings of neighbours outside, including the European Economic Area, the regions of the EU’s neighbourhood policy and finally some pan-European organisations. While all world regions have their own unique features, the European case offers some important lessons that should be of interest to other world regions. The first is what appears to be a relatively robust model for single market integration. The second consists of the lessons currently being learned on the hazards on monetary integration without adequate fiscal and political integration. The third lesson is another warning, over the difficulties of anticipating the political dynamics of integration processes once set in motion, often described in Europe as a ‘journey to an unknown destination’. The fourth consists of the EU’s current efforts to develop a comprehensive neighbourhood policy, which is encountering difficult issues of matching ambitious objectives with incentives of adequate weight. Nevertheless, the policy sees a landscape of positive and constructive relations between the EU and its neighbours, in marked contrast to some ugly conflictual or coercive features seen in the cases of other continental hegemons – the three BRIC states of China, India and Russia, but not the fourth one, Brazil.

Prevalence of chronic ocular diseases in a genetic isolate : the Norfolk Island Eye Study (NIES)

Purpose: Over 40% of the permanent population of Norfolk Island possesses a unique genetic admixture dating to Pitcairn Island in the late 18 th century, with descendents having varying degrees of combined Polynesian and European ancestry. We conducted a population-based study to determine the prevalence and causes of blindness and low vision on Norfolk Island. Methods: All permanent residents of Norfolk Island aged ≥ 15 years were invited to participate. Participants completed a structured questionnaire/interview and underwent a comprehensive ophthalmic examination including slit-lamp biomicroscopy. Results: We recruited 781 people aged ≥ 15, equal to 62% of the permanent population, 44% of whom could trace their ancestry to Pitcairn Island. No one was bilaterally blind. Prevalence of unilateral blindness (visual acuity [VA] < 6/60) in those aged ≥ 40 was 1.5%. Blindness was more common in females (P=0.049) and less common in people with Pitcairn Island ancestry (P<0.001). The most common causes of unilateral blindness were age-related macular degeneration (AMD), amblyopia, and glaucoma. Five people had low vision (Best-Corrected VA < 6/18 in better eye), with 4 (80%) due to AMD. People with Pitcairn Island ancestry had a lower prevalence of AMD (P<0.001) but a similar prevalence of glaucoma to those without Pitcairn Island ancestry. Conclusions: The prevalence of blindness and visual impairment in this isolated Australian territory is low, especially amongst those with Pitcairn Island ancestry. AMD was the most common cause of unilateral blindness and low vision. The distribution of chronic ocular diseases on Norfolk Island is similar to mainland Australian estimates.

Dynamics of air–sea CO2 fluxes in the northwestern European shelf based on voluntary observing ship and satellite observations

From January 2011 to December 2013, we constructed a comprehensive pCO2 data set based on voluntary observing ship (VOS) measurements in the western English Channel (WEC). We subsequently estimated surface pCO2 and air–sea CO2 fluxes in northwestern European continental shelf waters using multiple linear regressions (MLRs) from remotely sensed sea surface temperature (SST), chlorophyll a concentration (Chl a), wind speed (WND), photosynthetically active radiation (PAR) and modeled mixed layer depth (MLD). We developed specific MLRs for the seasonally stratified northern WEC (nWEC) and the permanently well-mixed southern WEC (sWEC) and calculated surface pCO2 with uncertainties of 17 and 16 μatm, respectively. We extrapolated the relationships obtained for the WEC based on the 2011–2013 data set (1) temporally over a decade and (2) spatially in the adjacent Celtic and Irish seas (CS and IS), two regions which exhibit hydrographical and biogeochemical characteristics similar to those of WEC waters. We validated these extrapolations with pCO2 data from the SOCAT and LDEO databases and obtained good agreement between modeled and observed data. On an annual scale, seasonally stratified systems acted as a sink of CO2 from the atmosphere of −0.6 ± 0.3, −0.9 ± 0.3 and −0.5 ± 0.3 mol C m−2 yr−1 in the northern Celtic Sea, southern Celtic sea and nWEC, respectively, whereas permanently well-mixed systems acted as source of CO2 to the atmosphere of 0.2 ± 0.2 and 0.3 ± 0.2 mol C m−2 yr−1 in the sWEC and IS, respectively. Air–sea CO2 fluxes showed important inter-annual variability resulting in significant differences in the intensity and/or direction of annual fluxes. We scaled the mean annual fluxes over these provinces for the last decade and obtained the first annual average uptake of −1.11 ± 0.32 Tg C yr−1 for this part of the northwestern European continental shelf. Our study showed that combining VOS data with satellite observations can be a powerful tool to estimate and extrapolate air–sea CO2 fluxes in sparsely sampled area.

Rural Development Group Politics. A hidden cost?

I challenge the popular notion of European rural development group dynamics and argue for a better understanding of the role of micro-politics as a means of enhancing the performance of these groups. The views are research based and have relevance to the broader rural development and regeneration sector. Micro-politics involves knowledge, power, trust, perceptions, understanding, social networks, values and traits that arise as a result of individuals interacting within a group whilst working on a shared goal, such as rural development. The monetary and time costs to a community of failing to address micro-politics and nurture positive group relations are considerable. These include time spent in unproductive meetings and poorly prioritized—and ultimately unsuccessful—funding applications as a result of failure to agree priorities. Successful groups rely on individuals interacting in a way that achieves a greater social good. Mutual trust amongst the actors lies at the heart of effective group activity. Effective management of micro-politics requires steps to nurture a culture of mutual trust to ensure that rural development actors co-operate rather than play destructive games with one another. A case study example of a relatively straightforward approach illustrates how this might be done in practice.

Results of a collaborative study of the EDNAP group regarding mitochondrial DNA heteroplasmy and segregation in hair shafts.

A collaborative exercise was carried out by the European DNA Profiling Group (EDNAP) in order to evaluate the distribution of mitochondrial DNA (mtDNA) heteroplasmy amongst the hairs of an individual who displays point heteroplasmy in blood and buccal cells. A second aim of the exercise was to study reproducibility of mtDNA sequencing of hairs between laboratories using differing chemistries, further to the first mtDNA reproducibility study carried out by the EDNAP group. Laboratories were asked to type 2 sections from each of 10 hairs, such that each hair was typed by at least two laboratories. Ten laboratories participated in the study, and a total of 55 hairs were typed. The results showed that the C/T point heteroplasmy observed in blood and buccal cells at position 16234 segregated differentially between hairs, such that some hairs showed only C, others only T and the remainder, C/T heteroplasmy at varying ratios. Additionally, differential segregation of heteroplasmic variants was confirmed in independent extracts at positions 16093 and the poly(C) tract at 302-309, whilst a complete A-G transition was confirmed at position 16129 in one hair. Heteroplasmy was observed at position 16195 on both strands of a single extract from one hair segment, but was not observed in the extracts from any other segment of the same hair. Similarly, heteroplasmy at position 16304 was observed on both strands of a single extract from one hair. Additional variants at positions 73, 249 and the HVII poly(C) region were reported by one laboratory; as these were not confirmed in independent extracts, the possibility of contamination cannot be excluded. Additionally, the electrophoresis and detection equipment used by this laboratory was different to those of the other laboratories, and the discrepancies at position 249 and the HVII poly(C) region appear to be due to reading errors that may be associated with this technology. The results, and their implications for forensic mtDNA typing, are discussed in the light of the biology of hair formation.

The breast cancer related burden of morbidity and mortality in six European coutries

Background: The burden of breast cancer expressed in Disability Adjusted Life Years (DALYs) was compared for six European countries and its sensitivity to different sources of variation examined. Methods: DALYs were calculated using country-specific epidemiological data and European Disability Weights. Epidemiological data for 1996 were obtained for Denmark, England and Wales, France, the Netherlands, Spain and Sweden. Disability weights were empirically derived. Results:  Denmark and the Netherlands lost the largest number of DALYs (approximately 1100 DALYs per 100,000 women). They were followed by England (87% of the Danish burden), France (72%), Sweden (68%) and Spain (67%). 70 to 80% of the burden was caused by mortality. Cross-national variation in disease epidemiology was the largest source of variation in the burden of breast cancer. Variation in disability weights and uncertainty in epidemiological data had smaller effects. Conclusion: To compare the burden of breast cancer and most other types of cancer mortality rates provide sufficient information.

The European Investment Bank and SMEs: key lessons for Latin America and the Caribbean

Incluye Bibliografía

A prática da reportagem radiofônica na Emissora Continental do Rio de Janeiro

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

n-Alkanes and lignin in bottom sediments of the West European Basin (area of the battleship Bismark wreck site)

Three bottom sediment cores were collected from the top, slope, and foot of a small topographic high located near the West European continental rise within the Porcupine abyssal plain at the battleship Bismark wreck site. Using high-efficient gas chromatography technique we determined content and examined molecular composition of n-alkane fraction of hydrocarbons and phenol compounds of lignin. n-Alkane and phenol concentrations in bottom sediments of all three cores were low both in values per unit mass of sediments and in organic matter composition that is typical for pelagic deposits of the World Ocean. They vary from 0.07 to 2.01 µg/g of dry sediment and from 0.0001 to 0.01% of TOC; phenol ranges are from 1.43 to 11.1 µg/g and from 0.03 to 0.6%. Non-uniform supply of terrigenous matter to the bottom under conditions of changes in sedimentation environment in different geological epochs is the principal reason for significant variations in n-alkane and lignin concentrations with depth in the cores. Lignin and its derivatives make the main contribution to formation of organic matter composition of the region in study. With respect to n-alkane and lignin concentrations organic matter of deposits of the West European Basin is composed of remains of higher plants and of autochtonous organic matter of marine flora; they have mixed terrigenous-autochtonous (terrigenous-planktonogenic) origin.