Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals

Methods We performed a detailed analysis of one 15q single nucleotide polymorphism (SNP) (rs16969968) with smoking behaviour and cancer risk in a total of 17 300 subjects from five LC studies and four upper aerodigestive tract (UADT) cancer studies. Results Subjects with one minor allele smoked on average 0.3 cigarettes per day (CPD) more, whereas subjects with the homozygous minor AA genotype smoked on average 1.2 CPD more than subjects with a GG genotype (P < 0.001). The variant was associated with heavy smoking (> 20 CPD) [odds ratio (OR) = 1.13, 95% confidence interval (CI) 0.96-1.34, P = 0.13 for heterozygotes and 1.81, 95% CI 1.39-2.35 for homozygotes, P < 0.0001]. The strong association between the variant and LC risk (OR = 1.30, 95% CI 1.23-1.38, P = 1 x 10(-18)), was virtually unchanged after adjusting for this smoking association (smoking adjusted OR = 1.27, 95% CI 1.19-1.35, P = 5 x 10(-13)). Furthermore, we found an association between the variant allele and an earlier age of LC onset (P = 0.02). The association was also noted in UADT cancers (OR = 1.08, 95% CI 1.01-1.15, P = 0.02). Genome wide association (GWA) analysis of over 300 000 SNPs on 11 219 subjects did not identify any additional variants related to smoking behaviour. Conclusions This study confirms the strong association between 15q gene variants and LC and shows an independent association with smoking quantity, as well as an association with UADT cancers.

Anti-tumoral effect of the non-nucleoside DNMT inhibitor RG108 in human prostate cancer cells

Background: Current therapeutic strategies for advanced prostate cancer (PCa) are largely ineffective. Because aberrant DNA methylation associated with inappropriate gene-silencing is a common feature of PCa, DNA methylation inhibitors might constitute an alternative therapy. In this study we aimed to evaluate the anti-cancer properties of RG108, a novel non-nucleoside inhibitor of DNA methyltransferases (DNMT), in PCa cell lines. Methods: The anti-tumoral impact of RG108 in LNCaP, 22Rv1, DU145 and PC-3 cell lines was assessed through standard cell viability, apoptosis and cell cycle assays. Likewise, DNMT activity, DNMT1 expression and global levels of DNA methylation were evaluated in the same cell lines. The effectiveness of DNA demethylation was further assessed through the determination of promoter methylation and transcript levels of GSTP1, APC and RAR-β2, by quantitative methylation-specific PCR and RT-PCR, respectively. Results: RG108 led to a significant dose and time dependent growth inhibition and apoptosis induction in LNCaP, 22Rv1 and DU145. LNCaP and 22Rv1 also displayed decreased DNMT activity, DNMT1 expression and global DNA methylation. Interestingly, chronic treatment with RG108 significantly decreased GSTP1, APC and RAR-β2 promoter hypermethylation levels, although mRNA re-expression was only attained GSTP1 and APC. Conclusions: RG108 is an effective tumor growth suppressor in most PCa cell lines tested. This effect is likely mediated by reversion of aberrant DNA methylation affecting cancer related-genes epigenetically silenced in PCa. However, additional mechanism might underlie the anti-tumor effects of RG108. In vivo studies are now mandatory to confirm these promising results and evaluate the potential of this compound for PCa therapy.

Paridades de poder de compra: estudo dos índices binários e multilaterais e sua aplicação no cálculo dos índices de custo de vida

Relatório de Estágio apresentado como requisito parcial para a obtenção do grau de Mestre em Estatística e Gestão de Informação

Une vision systémique de la formation continue universitaire

Res-Systemica, Volume N°5, Numéro Spécial

Lighting conditions and optical filters effects on visual performance of speleologists exposed to cave environments

The aim of this study is to evaluate lighting conditions and speleologists’ visual performance using optical filters when exposed to the lighting conditions of cave environments. A crosssectional study was conducted. Twenty-three speleologists were submitted to an evaluation of visual function in a clinical lab. An examination of visual acuity, contrast sensitivity, stereoacuity and flashlight illuminance levels was also performed in 16 of the 23 speleologists at two caves deprived of natural lightning. Two organic filters (450 nm and 550 nm) were used to compare visual function with and without filters. The mean age of the speleologists was 40.65 (± 10.93) years. We detected 26.1% participants with visual impairment of which refractive error (17.4%) was the major cause. In the cave environment the majority of the speleologists used a head flashlight with a mean illuminance of 451.0 ± 305.7 lux. Binocular visual acuity (BVA) was -0.05 ± 0.15 LogMAR (20/18). BVA for distance without filter was not statistically different from BVA with 550 nm or 450 nm filters (p = 0.093). Significant improved contrast sensitivity was observed with 450 nm filters for 6 cpd (p = 0.034) and 18 cpd (p = 0.026) spatial frequencies. There were no signs and symptoms of visual pathologies related to cave exposure. Illuminance levels were adequate to the majority of the activities performed. The enhancement in contrast sensitivity with filters could potentially improve tasks related with the activities performed in the cave.

O "Programa Flora" do Brasil - historia e situação atual

Apanhado histórico do PROGRAMA FLORA do Brasil, contendo as razões que levaram o CHPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnológico) a criá-lo, e a situação atual desse projeto. São as seguintes as funções básicas do PROGRAMA FLORA: a) pesquisa fundamental sobre a vegetação e a flora silvestres do Brasil; b) organização de centros de excelência em Botânica em cada Estado e Território do país, especificamente para o desenvolvimento de pesquisas sobre os recursos vegetais silvestres da respectiva região, aqui incluindo a formação de novos botânicos e técnicos auxiliares, em todos os níveis; e c) desenvolvimento de sistemas de informação relacionados ao conhecimento dos recursos vegetais silvestres do Brasil, especialmente a criação e manutenção de bancos de dados com informações as mais completas possíveis sobre esses recursos. Depois de oito anos de funcionamento, e devido à falta de interesse das autoridades competentes, o PROGRAMA FLORA foi implantado em apenas 10 dos 26 Estados e Territórios do Brasil e está, no momento, quase desativado, esperando que o novo governo o reanime, criando núcleos nas demais áreas do pais e continuando a cumprir o projeto inicial, Enquanto o FLORA estava funcionando, ainda que com apenas Ínfimo auxílio governamental, ele proporcionou a contratação de 52 botânicos iniciantes que, sob a orientação de botânicos experimentados, deram grande impulso no estudo das flores de cada região. Os herbários que sediaram núcleos do FLORA foram modernizados, sendo que alguma, como os da Amazônia e do Nordeste, tiveram [zm apenas 5 anos) seus acervos duplicados ou mesmo triplicados. Vários dos botânicos iniciantes ingressaram em cursos de pos-graduação, sendo que alguns já receberam o grau de Mestre e já estão caminhando para a obtenção do grau de Doutor. Na área da Informática, dois técnicos brasileiros foram enviados aos EE.UU., para estágio visando à formação e tratamento de bancas de dados especificamente para o PROGRAMA FLORA. Posteriormente, dois professores norteamericanos vieram ao Brasil, trazendo sistemas de processamento de dados especificamente montados para uso em Botânica Sistemática. Tais sistemas foram implantados no CPD do Centro de Pesquisas Fisicas (CEPF), do CNPq, no Rio de Janeiro. Foram preenchidos mais de 400.000 formulários de coleta de dados nos herbários dos núcleos do FLORA. O SERPRO (Serviço federal de Processamento de Dados) providenciou a digitação dos dados dos formulários, produziu os arquivos, em fitas magnéticas, e o CPD do CBPF organizou e está mantendo o Banco de Dados referente às informações contidas nos herbários levantados.Estes dados dão uma idéia do que poderíamos esperar do PROGRAMA FLORA, se a este tivessem tido dados os indispensáveis recursos e tivesse sido cumprido o programa de ação inicialmente proposto. É, realmente, uma grande pena que as autoridades competentes tenham decidido desativar o PROGRAMA FLORA, justamente quando ele estava precisando ser fortalecido nos núcleos já implantados, e ter novos núcleos criados, cobrindo todo o território do Brasil.

Maturidade sexual morfológica de Aegla platensis (Crustacea, Decapoda, Anomura) no Lajeado Bonito, norte do estado do Rio Grande do Sul, Brasil

O tamanho da primeira maturação sexual (TPM) em Aegla platensis Schmitt, 1942 foi estimado através das mudanças nas proporções de dimensões corporais dos animais. Para isso, foram realizadas coletas mensais, de julho de 2007 a junho de 2008 no Lajeado Bonito (27º25'27''S, 53º24'39''W), um tributário de primeira ordem do Rio da Várzea, município de Frederico Westphalen, Rio Grande do Sul. Foram utilizados 437 machos com comprimento de cefalotórax (CC) variando de 6,00 mm a 31,75 mm e 368 fêmeas, com tamanhos entre 6,08 mm e 27,92 mm de CC. As seguintes dimensões corporais foram mensuradas em todos os indivíduos coletados: comprimento do cefalotórax (CC), largura do abdome (LA), comprimento do própodo do quelípodo direito (CPD) e comprimento do própodo do quelípodo esquerdo (CPE). Após o registro dessas medidas, os animais foram devolvidos ao mesmo local de captura. As análises de maturidade sexual morfológica foram realizadas com auxílio do software Mature 2, nas quais foram utilizadas as medidas de CC, considerada como variável independente e relacionada com as demais dimensões. As relações que melhor se ajustaram para estas análises, em machos, foram CPD x CC (TPM: CC=18,2 mm) e CPE x CC (TPM: CC=20,1 mm) e LA x CC (TPM: CC=16,5 mm) nas fêmeas.

Transferència d’electrò i protó als intermediaris de reacció de les hemo-catalases

Projecte de recerca elaborat a partir d’una estada a l’University of Pennsylvania, EUA, entre els mesos d’agosta a desembre del 2006. Les hemo-catalases són enzims que protegeixen les cèl•lules dels efectes tòxics del peròxid d'hidrogen. Aquesta reacció té lloc en dues etapes, via l'intermediari Compost I (Cpd I). Tanmateix, el Compost I pot seguir una reacció secundària, a través de l'intermediari Compost II. Hi ha dos tipus d'hemo-catalases: les hemo-b (com la d'Helicobacter pylori, HPC) i les hemo-d catalases (com la de Penicillium vitale, PVC). Experimentalment s'observa que les hemo-b catalases formen Cpd II més fàcilment que les hemo-d. La formació del Cpd II consta de dos processos: la reducció del catió radical porfirínic i la protonació del grup oxoferril. Durant l'estada, es va estudiar el procès de transferència electrònica a la porfirina utilitzant una metodologia desenvolupada recentment. Els resultats mostren que per PVC la reducció és més fàcil que per HPC. Posteriorment hem realitzat una sèrie de optimitzacions de geometria CPMD QM/MM al llarg del camí per la transferència de protó (PT) de la histidina distal a l'oxoferril. Mentre que per HPC aquesta PT és espontània, per PVC l'isòmer hidroxoferrílic és menys estable que el catió imidazoli.

Monitorització d'un centre de processament de dades d'una administració pública, mitjançant Nagios i Centreon

Es mostra la implantació d'un sistema de monitorització d'un CPD en una administració pública amb Nagios i Centreon, i es compara breument amb algunes alternatives.

Modelatge i simulació de quatre centres de processament de dades connectats per WAN

Aquest projecte conté l'estudi de la comunicació entre quatre Centres de Processament de Dades (CPD) per via WAN. L'estudi consisteix en simular aquestes comunicacions en un entorn de proves físic i també en entorn de proves virtual on s'han extret resultats dels protocols de seguretat, d'enrutament, a més dels temps de resposta i limitacions dels equips físics i virtuals.

Adequació de la infraestructura de l'Hospital Universitari Arnau de Vilanova per a la implantació de S.A.P. (System Application & Products)

En aquesta memòria s'explica com, per la implantació de SAP en l'Hospital Universitari Arnau de Vilanova s'ha de realitzar una adequació tant de xarxa, com de parc d'ordinadors i impressores, instal·lació d'un nou cpd. Es fa un anàlisi previ de la situació i s'expliqen quins canvis es fan i perquè.

Effective continuing professional development for translating shared decision making in primary care: A study protocol.

Background: Shared decision making (SDM) is a process by which a healthcare choice is made jointly by the healthcare professional and the patient. SDM is the essential element of patient-centered care, a core concept of primary care. However, SDM is seldom translated into primary practice. Continuing professional development (CPD) is the principal means by which healthcare professionals continue to gain, improve, and broaden the knowledge and skills required for patient-centered care. Our international collaboration seeks to improve the knowledge base of CPD that targets translating SDM into the clinical practice of primary care in diverse healthcare systems. Methods: Funded by the Canadian Institutes of Health Research (CIHR), our project is to form an international, interdisciplinary research team composed of health services researchers, physicians, nurses, psychologists, dietitians, CPD decision makers and others who will study how CPD causes SDM to be practiced in primary care. We will perform an environmental scan to create an inventory of CPD programs and related activities for translating SDM into clinical practice. These programs will be critically assessed and compared according to their strengths and limitations. We will use the empirical data that results from the environmental scan and the critical appraisal to identify knowledge gaps and generate a research agenda during a two-day workshop to be held in Quebec City. We will ask CPD stakeholders to validate these knowledge gaps and the research agenda. Discussion: This project will analyse existing CPD programs and related activities for translating SDM into the practice of primary care. Because this international collaboration will develop and identify various factors influencing SDM, the project could shed new light on how SDM is implemented in primary care.

A common biological basis of obesity and nicotine addiction.

Smoking influences body weight such that smokers weigh less than non-smokers and smoking cessation often leads to weight increase. The relationship between body weight and smoking is partly explained by the effect of nicotine on appetite and metabolism. However, the brain reward system is involved in the control of the intake of both food and tobacco. We evaluated the effect of single-nucleotide polymorphisms (SNPs) affecting body mass index (BMI) on smoking behavior, and tested the 32 SNPs identified in a meta-analysis for association with two smoking phenotypes, smoking initiation (SI) and the number of cigarettes smoked per day (CPD) in an Icelandic sample (N=34,216 smokers). Combined according to their effect on BMI, the SNPs correlate with both SI (r=0.019, P=0.00054) and CPD (r=0.032, P=8.0 × 10(-7)). These findings replicate in a second large data set (N=127,274, thereof 76,242 smokers) for both SI (P=1.2 × 10(-5)) and CPD (P=9.3 × 10(-5)). Notably, the variant most strongly associated with BMI (rs1558902-A in FTO) did not associate with smoking behavior. The association with smoking behavior is not due to the effect of the SNPs on BMI. Our results strongly point to a common biological basis of the regulation of our appetite for tobacco and food, and thus the vulnerability to nicotine addiction and obesity.

Remaining rod activity mediates visual behavior in adult Rpe65-/- mice.

Purpose: C57/Bl6, Cpfl1-/- (Cone photoreceptors function loss 1; pure rod function), Gnat1alpha-/- (rod alpha-transducin; pure cone function) and Rpe65-/-;Rho-/- double knock-out mice were studied in order to distinguish the respective contributions of the different photoreceptor (PR) systems that enable light perception and mediate a visual reflex in adult Rpe65-/- mice using a simple behavioural procedure. Methods: Visual function was estimated using a rotating automatized optomotor drum covered with vertical black and white stripes at spatial frequencies of 0.025 to 0.5 cycles per degree (cpd) in both photopic and scotopic conditions. To evaluate the contribution as well as the light intensity threshold of each PR system, we tested the mouse strains with different luminances. Results: Stripe rotation elicits head movements in wild-type (WT) animals in photopic and scotopic conditions depending on the spatial frequency, whereas Cpfl1-/- mice show a reduced activity in the photopic condition and Gnat1alpha-/- mice an almost absent response in the scotopic condition. Interestingly, a robust visual response is obtained with Rpe65-/- knockout mice at 0.075 cpd and 0.1 cpd in the photopic condition. The residual rod function in the Rpe65-/- animals was demonstrated by testing Rpe65-/-;Rho-/- mice that present no response in photopic conditions. Conclusions: The optomotor test is a simple method to estimate the visual function, and to evaluate the respective contributions of rod and cone systems. Using this test, we demonstrate that in Rpe65-/- mice, devoid of functional cones and of detectable 11-cis-retinal protein, rods mimic in part the cone function by mediating vision in photopic conditions.

Contrast sensitivity to radial frequencies modulated by Jn and j n Bessel profiles

We measured human contrast sensitivity to radial frequencies modulated by cylindrical (Jo) and spherical (j o) Bessel profiles. We also measured responses to profiles of j o, j1, j2, j4, j8, and j16. Functions were measured three times by at least three of eight observers using a forced-choice method. The results conform to our expectations that sensitivity would be higher for cylindrical profiles. We also observed that contrast sensitivity is increased with the j n order for n greater than zero, having distinct orderly effects at the low and high frequency ends. For n = 0, 1, 2, and 4 sensitivity tended to occur around 0.8-1.0 cpd while for n = 8 and 16 it seemed to shift gradually to 0.8-3.0 cpd. We interpret these results as being consistent with the possibility that spatial frequency processing by the human visual system can be defined a priori in terms of polar coordinates and discuss its application to study face perception.