Discrepancy of p16 immunohistochemical expression and HPV RNA in penile cancer. A multiplex in situ hybridization/immunohistochemistry approach study

Background: The high-risk human papillomavirus (HPV) infection represents one of the main etiologic pathways of penile carcinogenesis in approximately 30–50 % of cases. Several techniques for the detection of HPV are currently available including Polymerase chain reaction-based techniques, DNA and RNA in situ hybridization (ISH), p16 immunohistochemistry (IHC). The multiplex HPV RNA ISH/p16 IHC is a novel technique for the simultaneous detection of HPV E6/E7 transcripts and p16INK4a overexpression on the same slide in a single assay. The main aim of this study was to evaluate the discrepancy of p16 IHC expression relatively to HPV RNA ISH in penile cancer tissue. Methods: We collected a series of 60 PCs. HPV has been analysed through the RNA ISH, p16 IHC and the multiplex HPV RNA ISH/p16 IHC. Results: The multiplex HPV RNA ISH /p16 IHC results in the series were in complete agreement with the previous results obtained through the classic p16 IHC and HPV RNA scope carried out on two different slides. The multiplex HPV RNA ISH /p16 IHC showed that HPV positivity in our series is more frequently in usual squamous cell carcinoma than in special histotypes (19 out of 60 − 15 %- versus 6 out of 60 − 10 %-), in high-grade than in moderate/low grade carcinomas (6 out of 60 − 10 %- versus 4 out of 60 − 6.7 %-). In addition, our data revealed that in 5 out of 20 cases with p16 high intensity expression is not associated with HPV RNA ISH positivity. Conclusions: Our findings emphasize that the use of p16 as a surrogate of HPV positivity was unsuccessful in approximatively 8 % of cases analysed in our series. Indeed, p16 IHC showed a sensitivity of 100 % and a specificity of 71 %, with a positive predictive value (PPV) of 54 % and a negative predictive value of 100 %; when considering high intensity, p16 IHC showed a sensitivity of 100 %, a specificity of 89 %, with a PPV of 75 % and NPV of 100 %. Since HPV positivity could represent a relevant prognostic and predictive value, the correct characterization offered by this approach appears to be of paramount importance

Calda sulfocálcica, óleo mineral e extrato de alho na superação da dormência de quivizeiro

This study aimed to examine the effect of lime sulphur (LS), mineral oil (MO) and garlic extract (GE) on budbreak of 'Bruno' kiwifruit. In the experiment with lime sulphur, 16 treatments in factorial design 4 x 4 (budbreak solutions x bud position) were tested. The solutions were: MO 6%; MO 6% + LS 10%; MO 6% + LS 20% and MO 6% + LS 30%. In the experiment with garlic extract, 28 treatments in factorial design 7 x 4 (budbreak solutions x bud position) were tested. The solutions were: control; MO 4%; MO 4% + GE 2%; MO 4% + GE 4%; MO 4% + GE 6%; MO 4% + GE 8% and MO 4% + GE 10%. Four buds at the shoot apical position were examined at different dates in both experiments. All buds with one visible leaf or more advanced phenological stages were considered like bud burst. Apical bud always showed the greatest percentage of bud sprouting in both experiments, forming a decreased scale until low buds. Lime sulphur did not promote budbreak of kiwifruit, showing the same effect presented by the treatment with only mineral oil. Garlic extract showed effect on budbreak of kiwifruit. The MO 4% + GE 10% treatment was superior to the others, but it was not different from MO 4% + GE 6% and MO 4% + GE 8%. This superiority was a consequence of higher lateral buds sprouting, because apical buds sprouting were the same, averaging 93.33%. In conclusion, the lime sulphur until 30% of concentration combined with mineral oil 6% had no effect to budbreak of Bruno Kiwifruit. Conversely, the garlic extract at 10% of concentration combined with mineral oil 4% enhanced the percentage of lateral buds sprouting, but not in satisfactory levels.Este trabalho teve por objetivo testar o efeito da calda sulfocálcica (CS), do óleo mineral (OM) e do extrato de alho (EA) na superação da dormência de quivizeiro 'Bruno'. No experimento com calda sulfocálcica foram testados 16 tratamentos em esquema fatorial 4 x 4 (soluções para superação da dormência x posição das gemas). As soluções foram: OM 6%; OM 6% + CS 10%; OM 6% + CS 20% e OM 6% + CS 30%. No experimento com extrato de alho foram testados 28 tratamentos em esquema fatorial 7 x 4 (soluções para superação da dormência x posição das gemas). As soluções foram: testemunha; OM 4%; OM 4% + EA 2%; OM 4% + EA 4%; OM 4% + EA 6%; OM 4% + EA 8% e OM 4% + EA 10%. Em ambos experimentos foram avaliadas as quatro gemas da porção apical dos ramos em quatro avaliações. Foram consideradas gemas brotadas todas as que se encontravam com uma folha visível ou em estádios fenológicos mais avançados. Em ambos experimentos, a gema apical sempre apresentou a maior porcentagem de brotação, formando um gradiente decrescente até as gemas inferiores. A calda sulfocálcica não apresentou efeito na superação da dormência de gemas de quivizeiro, apresentando-se semelhante ao tratamento apenas com óleo mineral. O extrato de alho apresentou efeito na superação da dormência das gemas do quivizeiro. O tratamento com OM 4% + EA 10% foi superior aos demais, mas não diferiu dos tratamentos com OM 4% + EA 6% e OM 4% + EA 8%. Essa superioridade é consequência da maior brotação das gemas laterais inferiores, já que a brotação das gemas apicais foi praticamente a mesma, em média 93,33%. Conclui-se que, para superação da dormência de gemas de quivizeiro 'Bruno', a calda sulfocálcica até a concentração de 30% em combinação com óleo mineral 6% não é eficiente e o extrato de alho na concentração de 10% em combinação com óleo mineral 4% eleva a porcentagem de brotação das gemas laterais, mas não em níveis satisfatórios

Desenvolvimento sustentável: uma proposta para descarbonização de frotas de veículos

O objetivo deste artigo é propor um modelo para auxiliar a aquisição de frotas de veículos. A proposta baseia-se em utilizar características veiculares, tais como: níveis de emissões de poluentes, consumo energético, categoria veicular, transmissão e motorização. Idealizando um processo avaliativo com base na análise multicritério, que ajude à tomada de decisões no momento da aquisição de veículos considerando vários critérios. Com a finalidade de gerar listas de veículos que apoiam a escolha do consumidor, no que tange a descarbonização de frotas, contribuindo na redução dos impactos resultantes das emissões de gases nas grandes cidades

The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics.

ABSTRACT: A global genome database of all of Earth’s species diversity could be a treasure trove of scientific discoveries. However, regardless of the major advances in genome sequencing technologies, only a tiny fraction of species have genomic information available. To contribute to a more complete planetary genomic database, scientists and institutions across the world have united under the Earth BioGenome Project (EBP), which plans to sequence and assemble high-quality reference genomes for all ∼1.5 million recognized eukaryotic species through a stepwise phased approach. As the initiative transitions into Phase II, where 150,000 species are to be sequenced in just four years, worldwide participation in the project will be fundamental to success. As the European node of the EBP, the European Reference Genome Atlas (ERGA) seeks to implement a new decentralised, accessible, equitable and inclusive model for producing high-quality reference genomes, which will inform EBP as it scales. To embark on this mission, ERGA launched a Pilot Project to establish a network across Europe to develop and test the first infrastructure of its kind for the coordinated and distributed reference genome production on 98 European eukaryotic species from sample providers across 33 European countries. Here we outline the process and challenges faced during the development of a pilot infrastructure for the production of reference genome resources, and explore the effectiveness of this approach in terms of high-quality reference genome production, considering also equity and inclusion. The outcomes and lessons learned during this pilot provide a solid foundation for ERGA while offering key learnings to other transnational and national genomic resource projects.info:eu-repo/semantics/publishedVersio

The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics

A genomic database of all Earth’s eukaryotic species could contribute to many scientific discoveries; however, only a tiny fraction of species have genomic information available. In 2018, scientists across the world united under the Earth BioGenome Project (EBP), aiming to produce a database of high-quality reference genomes containing all ~1.5 million recognized eukaryotic species. As the European node of the EBP, the European Reference Genome Atlas (ERGA) sought to implement a new decentralised, equitable and inclusive model for producing reference genomes. For this, ERGA launched a Pilot Project establishing the first distributed reference genome production infrastructure and testing it on 98 eukaryotic species from 33 European countries. Here we outline the infrastructure and explore its effectiveness for scaling high-quality reference genome production, whilst considering equity and inclusion. The outcomes and lessons learned provide a solid foundation for ERGA while offering key learnings to other transnational, national genomic resource projects and the EBP.info:eu-repo/semantics/publishedVersio

Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older. Methods Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health. Findings Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week. Interpretation Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.Peer reviewe

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder