Changes in the Pollen Seasons of the Early Flowering Trees Alnus spp. and Corylus spp. in Worcester United Kingdom 1996-2005

Previous work on Betula spp. (birch) in the UK and at five sites in Europe has shown that pollen seasons for this taxon have tended to become earlier by about 5–10 days per decade in most regions investigated over the last 30 years. This pattern has been linked to the trend to warmer winters and springs in recent years. However, little work has been done to investigate the changes in the pollen seasons for the early flowering trees. Several of these, such as Alnus spp. and Corylus spp., have allergens, which cross-react with those of Betula spp., and so have a priming effect on allergic people. This paper investigates pollen seasons for Alnus spp. and Corylus spp. for the years 1996–2005 at Worcester, in the West Midlands, United Kingdom. Pollen data for daily average counts were collected using a Burkard volumetric trap sited on the exposed roof of a three-storey building. The climate is western maritime. Meteorological data for daily temperatures (maximum and minimum) and rainfall were obtained from the local monitoring sites. The local area up to approximately 10 km surrounding the site is mostly level terrain with some undulating hills and valleys. The local vegetation is mixed farmland and deciduous woodland. The pollen seasons for the two taxa investigated are typically late December or early January to late March. Various ways of defining the start and end of the pollen seasons were considered for these taxa, but the most useful was the 1% method whereby the season is deemed to have started when 1% of the total catch is achieved and to have ended when 99% is reached. The cumulative catches (in grains/m3) for Alnus spp. varied from 698 (2001) to 3,467 (2004). For Corylus spp., they varied from 65 (2001) to 4,933 (2004). The start dates for Alnus spp. showed 39 days difference in the 10 years (earliest 2000 day 21, latest 1996 day 60). The end dates differed by 26 days and the length of season differed by 15 days. The last 4 years in the set had notably higher cumulative counts than the first 2, but there was no trend towards earlier starts. For Corylus spp. start days also differed by 39 days (earliest 1999 day 5, latest 1996 day 44). The end date differed by 35 days and length of season by 26 days. Cumulative counts and lengths of season showed a distinct pattern of alternative high (long) and low (short) years. There is some evidence of a synchronous pattern for Alnus spp.. These patterns show some significant correlations with temperature and rainfall through the autumn, winter and early spring, and some relationships with growth degree 4s and chill units, but the series is too short to discern trends. The analysis has provided insight to the variation in the seasons for these early flowering trees and will form a basis for future work on building predictive models for these taxa.

Calcium, vitamin D, casein and whey protein intakes and periodontitis among Danish adults

Objective: To investigate whether intakes of Ca, vitamin D, casein and whey are associated with periodontitis and to investigate the possibility of interactions between them. Design: Cross-sectional study. An Internet-based, 267-item FFQ was used to assess dietary intake. Intakes of casein (32·0 g/d), whey proteins (9·6 g/d) and vitamin D (5·8 μg/d) were classified as within v. above the 50th percentile. Ca intake was classified as within v. below age-specific recommendations. Severe periodontitis was defined as having ≥2 inter-proximal sites with clinical attachment loss ≥6 mm (not on the same tooth) and ≥1 inter-proximal site with pocket depth ≥5 mm. Since vitamin D influences Ca absorption, models were stratified by lower and higher (<5·8 v. ≥5·8 µg/d) vitamin D intake. Setting Danish Health Examination Survey (DANHES) 2007–2008. Subjects Adult participants (n 3287) in the oral health study of DANHES 2007–2008. Results Intakes of Ca within recommendations (OR=0·76; 95 % CI 0·58, 0·99), whey ≥9·6 g/d (OR=0·75; 95 % CI 0·58, 0·97) and casein ≥32 g/d (OR=0·75 95 % CI 0·58, 0·97) were associated with lower likelihood of severe periodontitis after adjustment for age, gender, education, smoking, sucrose intake, alcohol consumption, number of teeth, daily brushing, regular visits to the dentist and chronic illness, irrespective of vitamin D intake levels. Intake of vitamin D alone was not associated severe with periodontitis. Conclusions Intakes of Ca, casein and whey protein were inversely associated with periodontitis. Consumption of foods rich in Ca, casein and whey (e.g. dairy foods) should be promoted, as they may contribute to the prevention of periodontitis. Further longitudinal studies are required to confirm these associations.

Conversions of Relief: on the perception of depth in drawings

Of the many ways in which depth can be intimated in drawings, perspective has undoubtedly been one of the most frequently examined. But there is also an equally rich history associated with other forms of pictorial representation. Alternatives to perspective became particularly significant in the early twentieth century as artists and architects, intent on throwing off the conventions of their predecessors, looked to new ways of depicting depth. In architecture, this tendency was exemplified by Modernism’s preference for parallel projection – most notably axonometric and oblique. The use of these techniques gave architects the opportunity to convey a new and uniquely modern form of spatial expression. At once shallow and yet expansive, a key feature of these drawings was their ability to support perceptual ambiguity. This paper will consider the philosophy and science of vision, out of which these preoccupations emerged. In this context, the nineteenth-century discovery of stereopsis and the invention of the stereoscope will be used to illustrate the way in which attempts to test the limits of spatial perception led to an opening up of visual experience; and provided a definition of visual experience that could encompass the representational ambiguities later exploited by the early twentieth-century avant-garde.

Relatório de Projecto apresentado ao Instituto Superior de Contabilidade e Administração do Porto para a obtenção do Grau de Mestre em Tradução e Interpretação Especializadas

Orientado pela Doutora Dalila Maria Cerqueira Pereira da Silva Lopes

Electroanalytical study of the antidepressant sertraline

Aflowinjection squarewave cathodic stripping voltammetric method has been developed for the determination of sertraline in a pharmaceutical preparation. The method shows linearity between peak current intensity and sertraline concentration for the interval between 0.20×10−6 and 1.20×10−6 mol L−1. Limits of detection and quantification were found to be 1.5×10−7 and 5.0×10−7 mol L−1, respectively. Up to 70 samples per hour can be analysed with a good precision (R.S.D. = 2.5%). The proposed method was successfully applied to the determination of sertraline in a commercial product. In the voltammetric determination of sertraline in flow, a high sample rate is obtained at reduced costs, opening the possibility to compete with the chromatographic methods generally used for this analysis.

Trace metals in size-fractionated particulate matter in a Portuguese hospital: exposure risks assessment and comparisons with other countries

Hospitals are considered as a special and important type of indoor public place where air quality has significant impacts on potential health outcomes. Information on indoor air quality of these environments, concerning exposures to particulate matter (PM) and related toxicity, is limited though. This work aims to evaluate risks associated with inhalation exposure to ten toxic metals and chlorine (As, Ni, Cr, Cd, Pb, Mn, Se, Ba, Al, Si, and Cl) in coarse (PM2.5–10) and fine (PM2.5) particles in a Portuguese hospital in comparison with studies representative of other countries. Samples were collected during 1 month in one urban hospital; elemental PM characterization was determined by proton-induced X-ray emission. Noncarcinogenic and carcinogenic risks were assessed according to the methodology provided by the United States Environmental Protection Agency (USEPA; Region III Risk-Based Concentration Table) for three different age categories of hospital personnel (adults, >20, and <65 years) and patients (considering nine different age groups, i.e., children of 1–3 years to seniors of >65 years). The estimated noncarcinogenic risks due to occupational inhalation exposure to PM2.5-bound metals ranged from 5.88×10−6 for Se (adults, 55–64 years) to 9.35×10−1 for As (adults, 20–24 years) with total noncarcinogenic risks (sum of all metals) above the safe level for all three age categories. As and Cl (the latter due to its high abundances) were the most important contributors (approximately 90 %) to noncarcinogenic risks. For PM2.5–10, noncarcinogenic risks of all metals were acceptable to all age groups. Concerning carcinogenic risks, for Ni and Pb, they were negligible (<1×10−6) in both PM fractions for all age groups of hospital personnel; potential risks were observed for As and Cr with values in PM2.5 exceeding (up to 62 and 5 times, respectively) USEPA guideline across all age groups; for PM2.5–10, increased excess risks of As and Cr were observed particularly for long-term exposures (adults, 55–64 years). Total carcinogenic risks highly (up to 67 times) exceeded the recommended level for all age groups, thus clearly showing that occupational exposure to metals in fine particles pose significant risks. If the extensive working hours of hospital medical staff were considered, the respective noncarcinogenic and carcinogenic risks were increased, the latter for PM2.5 exceeding the USEPA cumulative guideline of 10−4. For adult patients, the estimated noncarcinogenic and carcinogenic risks were approximately three times higher than for personnel, with particular concerns observed for children and adolescents.

Volume da Aurícula Esquerda: um "Velho" Cálculo Ecocardiográfico com uma Importância Prognóstica Renovada. Um Estudo em Doentes com Miocardiopatia Dilatada

Recentemente, surgiram alguns trabalhos que ressaltaram a importância do cálculo do volume da aurícula esquerda (VAE) como um marcador de eventos cardíacos adversos. Foi objectivo deste estudo avaliar a importância prognóstica deste parâmetro em doentes (dts) com deficiente função ventricular esquerda e correlacioná-lo com outros parâmetros clássicos de prognóstico – consumo de O2 (VO2 max) e pro-BNP (pBNP). Métodos: Analisou-se o volume da aurícula esquerda (VAE) por método de Simpson, numa população de 35 dts com cardiopatia dilatada (idiopática e isquémica) com fracção de ejecção (FE) 31±9,6% doentes (dts) eram de sexo masculino e a média de idades foi de 50,5±10,5 anos. Toda a população efectuou estudos de ecocardiografia convencional (incluindo avaliação por M-mode, bidimensional e Doppler), prova cardiorespiratória (VO2max) e doseamento de pro-BNP. O tempo médio de seguimento foi de 24 ± 4 meses, tendo-se considerado como eventos cardíacos (EC): internamento por insuficiência cardíaca, transplante e morte. Resultados: Dos parâmetros da ecocardiografia - o diâmetro da AE foi de 46,6±5,7mm, as dimensões do VE em diástole – 73,5±10mm e em sístole -58,9±11mm, a média da fracção de ejecção foi de 31±9,6%, o VAE foi de 78,6±33 ml, os volumes do VE foram de 214±82ml em diástole e de 153±75ml em sístole, 15 dts tinham padrão restritivo de enchimento ventricular (E/A>2), a média da área (Doppler cor) da insuficiência mitral foi de 4±3,3cm2, 14 dts tinham E/E’>15. O VO2 max médio foi de 20±5,8ml/kg/min e o pro-BNP de 3146±4629pg/mL. Para além da correlação de outros parâmetros clássicos ecocardiográficos com o prognóstico (volumes VE, FE e E/E’), o VAE e o volume indexado da AE (VAE/SC) mostraram uma correlação com o prognóstico (EC) com r=0,4 (p=0,02) que não se verificou para o diâmetro da AE (p=ns). Em relação à tolerância ao esforço, houve uma correlação inversa entre o diâmetro, o volume e o volume indexado da AE e o VO2max, com maior significado estatístico para o VAE e VAE/SC com r=-0,48, p=0,008. Quanto ao pro-BNP, quer o diâmetro, quer o VAE (ou volume indexado) tiverem o mesmo nível de significado estatístico (r=0,43; p=0,02). O valor predictivo de eventos (curvas ROC) para o VAE foi de 70ml e de 37ml/m2 para o VAE/m2. Conclusão: O volume da aurícula esquerda/volume indexado é um parâmetro ecocardiográfico com significado prognóstico em dts com deficiente função ventricular esquerda, correlacionando-se com a tolerância ao esforço e pro-BNP.

“Green Electrodes” Modified with Au Nanoparticles Synthesized in Glycerol, as Electrochemical Nitrite Sensor

A new environmentally friendly Au nanoparticles (Au NPs) synthesis in glycerol by using ultraviolet irradiation and without extra-added stabilizers is described. The synthesis proposed in this work may impact on the non-polluting production of noble nanoparticles with simple chemicals normally found in standard laboratories. These Au NPs were used to modify a carbon paste electrode (CPE) without having to separate them from the reaction medium. This green electrode was used as an electrochemical sensor for the nitrite detection in water. At the optimum conditions the green sensor presented a linear response in the 2.0×10−7–1.5×10−5 M concentration range, a good detection sensitivity (0.268 A L mol−1), and a low detection limit of 2.0×10−7 M of nitrite. The proposed modified green CPE was used to determine nitrite in tap water samples.

Characterization of green zero-valent iron nanoparticles produced with tree leaf extracts

In the last decades nanotechnology has become increasingly important because it offers indisputable advantages to almost every area of expertise, including environmental remediation. In this area the synthesis of highly reactive nanomaterials (e.g. zero-valent iron nanoparticles, nZVI) is gaining the attention of the scientific community, service providers and other stakeholders. The synthesis of nZVI by the recently developed green bottom-up method is extremely promising. However, the lack of information about the characteristics of the synthetized particles hinders a wider and more extensive application. This work aims to evaluate the characteristics of nZVI synthesized through the green method using leaves from different trees. Considering the requirements of a product for environmental remediation the following characteristics were studied: size, shape, reactivity and agglomeration tendency. The mulberry and pomegranate leaf extracts produced the smallest nZVIs (5–10 nm), the peach, pear and vine leaf extracts produced the most reactive nZVIs while the ones produced with passion fruit, medlar and cherry extracts did not settle at high nZVI concentrations (931 and 266 ppm). Considering all tests, the nZVIs obtained from medlar and vine leaf extracts are the ones that could present better performances in the environmental remediation. The information gathered in this paper will be useful to choose the most appropriate leaf extracts and operational conditions for the application of the green nZVIs in environmental remediation.

Tradução e validação para Portugal do Patient Activation Measure 13 : em pessoas com Diabetes Mellitus tipo 2

RESUMO - Introdução: A Diabetes Mellitus Tipo 2 (DM2) tem uma elevada prevalência em todo o mundo, com impacto significativo a nível de Saúde Pública, na vida dos doentes e nos custos que lhe são associados. O Patiente Activation Measure 13 (PAM13) é um questionário que possibilita a avaliação das crenças, conhecimentos, motivação e capacidades de uma pessoa em relação à sua saúde; pelo que a sua utilização na DM2 é pertinente. Objetivos: Traduzir o PAM 13, versão curta, para Português de Portugal; Estabelecer as propriedades psicométricas da versão Portuguesa do PAM 13 (PAM13-P); Validar a PAM 13-P num grupo de pessoas com DM2. Material e métodos: O processo de tradução e adaptação cultural do questionário foi composto pelas fases: 1-Tradução, 2-Reconciliação e síntese, 3-Back translation, 4-Rever e sintetizar a Back translation, 5-Harmonização, 6-Revisão do comité de peritos, 7-Cognitive debriefing e 8-Avaliação final. Para validar o PAM13-P realizou-se um estudo observacional transversal analítico com uma amostra de conveniência, de pessoas com DM2, seguidas na Associação Protectora dos Diabéticos de Portugal. O questionário foi de autopreenchimento e foi consultado o processo clínico para obtenção da HbA1c. O tratamento estatístico foi realizado através do SPSS 21® e Winsteps v3.8.1®. Resultados e discussão: O processo de tradução e adaptação cultural foi realizado de acordo com as guidelines. Foram realizados 3 painéis de e-Delphi, com 21 participantes de áreas distintas, tendo-se obtido bons níveis de concordância. As principais modificações realizadas ao questionário foram a simplificação da linguagem e dos itens, obtendo-se as equivalências necessárias. O PAM13-P foi aplicado a 201 pessoas, sendo que a taxa de resposta foi de 83%. Na amostra analisada 57.3% eram homens. Obtiveram-se as médias de idade 67.1 anos e de duração de diabetes 17.3 anos. A média do score do PAM foi 58.5±10.1(41.8-90.5) pontos e 49,7% da amostra estava no nível 3 de ativação. Relativamente aos itens verificou-se que os itens mais difíceis foram o 13(56.1) e o 8(55.4) e o com menor dificuldade foi 4(38.5). As categorias de resposta tiveram um bom ajuste ao Modelo de Rasch. O ajustamento dos itens foi infit entre 0.779-1.177 e outfit entre 0.794-1.315. A fiabilidade dos indivíduos variou entre 0.77(real) e 0.83(modelo) e dos itens foi de 0.97 (real e modelo). O Alfa de Cronbach foi bom (α=0.82). Estas estatísticas foram semelhantes aos da validação do PAM13. Existiu uma relação entre o score do PAM e os itens de validação em 51%. Das variáveis analisadas, existia um relação do nível de ativação com a idade e com a HbA1c. Conclusões: O PAM13-P foi traduzido e adaptado culturalmente para Português e foi validado em pessoas com DM2, sendo as propriedades psicométricas boas.

Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.

Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on (1)H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10(-8)) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10(-44)) and lysine (rs8101881, P = 1.2×10(-33)), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers.

SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease.

Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Aβ1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5×10(-12)). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 × 10(-5)), with the strongest effect being observed in APOE-ε4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 × 10(-3)). Functional microglia experiments showed that SUCLG2 was involved in clearance of Aβ1-42.

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Safety of human immunisation with a live-attenuated Mycobacterium tuberculosis vaccine: a randomised, double-blind, controlled phase I trial.

BACKGROUND: Tuberculosis remains one of the world's deadliest transmissible diseases despite widespread use of the BCG vaccine. MTBVAC is a new live tuberculosis vaccine based on genetically attenuated Mycobacterium tuberculosis that expresses most antigens present in human isolates of M tuberculosis. We aimed to compare the safety of MTBVAC with BCG in healthy adult volunteers. METHODS: We did this single-centre, randomised, double-blind, controlled phase 1 study at the Centre Hospitalier Universitaire Vaudois (CHUV; Lausanne, Switzerland). Volunteers were eligible for inclusion if they were aged 18-45 years, clinically healthy, HIV-negative and tuberculosis-negative, and had no history of active tuberculosis, chemoprophylaxis for tuberculosis, or BCG vaccination. Volunteers fulfilling the inclusion criteria were randomly assigned to three cohorts in a dose-escalation manner. Randomisation was done centrally by the CHUV Pharmacy and treatments were masked from the study team and volunteers. As participants were recruited within each cohort, they were randomly assigned 3:1 to receive MTBVAC or BCG. Of the participants allocated MTBVAC, those in the first cohort received 5 × 10(3) colony forming units (CFU) MTBVAC, those in the second cohort received 5 × 10(4) CFU MTBVAC, and those in the third cohort received 5 × 10(5) CFU MTBVAC. In all cohorts, participants assigned to receive BCG were given 5 × 10(5) CFU BCG. Each participant received a single intradermal injection of their assigned vaccine in 0·1 mL sterile water in their non-dominant arm. The primary outcome was safety in all vaccinated participants. Secondary outcomes included whole blood cell-mediated immune response to live MTBVAC and BCG, and interferon γ release assays (IGRA) of peripheral blood mononuclear cells. This trial is registered with ClinicalTrials.gov, number NCT02013245. FINDINGS: Between Jan 23, 2013, and Nov 6, 2013, we enrolled 36 volunteers into three cohorts, each of which consisted of nine participants who received MTBVAC and three who received BCG. 34 volunteers completed the trial. The safety of vaccination with MTBVAC at all doses was similar to that of BCG, and vaccination did not induce any serious adverse events. All individuals were IGRA negative at the end of follow-up (day 210). After whole blood stimulation with live MTBVAC or BCG, MTBVAC was at least as immunogenic as BCG. At the same dose as BCG (5×10(5) CFU), although no statistical significance could be achieved, there were more responders in the MTBVAC group than in the BCG group, with a greater frequency of polyfunctional CD4+ central memory T cells. INTERPRETATION: To our knowledge, MTBVAC is the first live-attenuated M tuberculosis vaccine to reach clinical assessment, showing similar safety to BCG. MTBVAC seemed to be at least as immunogenic as BCG, but the study was not powered to investigate this outcome. Further plans to use more immunogenicity endpoints in a larger number of volunteers (adults and adolescents) are underway, with the aim to thoroughly characterise and potentially distinguish immunogenicity between MTBVAC and BCG in tuberculosis-endemic countries. Combined with an excellent safety profile, these data support advanced clinical development in high-burden tuberculosis endemic countries. FUNDING: Biofabri and Bill & Melinda Gates Foundation through the TuBerculosis Vaccine Initiative (TBVI).