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Disease progression (PD) at neoadjuvant chemotherapy for patients with colorectal liver metastases (CLMs) is considered a contraindication to hepatic resection. Our aim was to estimate the overall survival (OS) in patients undergoing surgery compared with those treated exclusively with chemotherapy in cases of PD. Patients from a single centre with PD were analyzed and subdivided into two groups: hepatectomy (HEP) versus chemotherapy (CHT). An Inverse Probability Weighting (IPW) was run to balance the baseline differences between the two groups. A Cox regression was carried out on identifying factors predicting mortality. From 2010 to 2020, 105 patients in PD to at least one line of chemotherapy were analyzed. Of these, 27 (25.7%) underwent hepatic resection. After a median follow-up of 30 (IQR 14–46) months, 61.9% were dead. The OS values at 1 and 3 years were 54.4 and 10.6% for CHT, and 95 and 46.8% for HEP (p < 0.001). After IPW, two balanced pseudopopulations were obtained: HEP = 85 and CHT = 103. The OS values at 1 and 3 years were 54.4 and 10.6% for CHT, and 97.8 and 49.3% for HEP (HR 0.256, 95%CI: 0.08–0.78, p = 0.033). After IPW, in the multivariate model, surgery resulted in the only protective variable (HR 0.198, 95%CI: 0.08–0.48, p = 0.0016). Our results show that hepatic resection could offer a chance of a longer OS than the prosecution of chemotherapy only in originally resectable patients.

There is myriad of strategies that can be employed in the classroom. One of these is the Cooperative Learning. Because cooperative learning is a common strategy, it will just be used in different topics without considering its effectiveness in a particular topic. Thus, little attention is given to test how effective this strategy is. This study endeavored to assess if cooperative learning can make the discussion of pie chart an engaging one. The study used Quasi-Experimental research design in fulfilling its objectives. The respondents are grade 6 learners studying at Langin Elementary School in Ronda, Cebu, Philippines. There are 30 respondents in total in both control (15) and experimental (15). The experimental group garnered the mean of 11.47 and the control group mean with 9 in the pretest. While in the posttest, the experimental group garnered 19.33 and the control group landed on 17.60. With the 0.05 significance level, the results between the pretest and posttest of the two groups were found to be significant (p-value= 0.00). This is a realization that strategies can possibly constitute a significant difference. In this study, both the traditional way of teaching the topic and the one that is being introduced marked significantly. Thus, it is recommended to have this strategy tested in different topics in Mathematics and other subjects wherein the findings of this study can be verified.

Pinot blanc is a leading grapevine variety in South Tyrol (Italy) for wine production. The high quality of its wines derives from a typical aroma of elegant apple notes and lively acidity. The typicity of the final wine depends on the origin of the vine, the soil, the oenological practices and time of harvest. The South Tyrolean mountainous areas meet the cold climatic requirements of Pinot blanc, which guarantee its sweet-acidic harmony obtained when organic acids are in balance with the other components of the wine. However, increasing temperatures in valley sites during the berry development period boost the activity of malic acid (MA) enzymes, which negatively affect the final sugar/acid ratio. Researchers are currently focused on understanding acid dynamics in wines, and there are no references for the best sugar/acid ratio for Pinot blanc. Moreover, the contribution of individual acids to the sensory profile of this wine has not yet been studied. In this study we address the effect of different climate conditions and site elevations on the sugar/acid ratio in developmental grapevine berries, and we evaluate the effect on wine bouquet. Even if different models and indices have been proposed for predicting sugar content, no predictive models exist for MA in white grapes. In a three-year study (2017, 2018 and 2019) that involved eight vineyards in four different location in South Tyrol at various elevations ranging from 223 to 730 m a.s.l., the relationships between bioclimatic indices, such as growing-degree day (GDD) and grapevine sugar ripeness (GSR) and grapevine berry content were investigated. The analysis reveals that GDD may potentially predict MA dynamics in Pinot blanc; hence, a GDD-based model was used to determine the GDD to reach target MA concentrations (3.5, 3.0, 2.5, 2.0 g/L). This simple model was improved with additional temperature-based parameters by feature selection, and the best three advanced models were selected and evaluated by 5-fold cross-validation. These models could be used to support location and harvest date choice to produce high-quality Pinot blanc wines.

Resumo A infecao da area genital pelo virus do papiloma humano (HPV) e muito frequente. Estima‐se que 50% dos individuos sexualmente ativos sao infetados pelo menos uma vez ao longo da vida. O diagnostico e essencialmente clinico, toda a area genital deve ser inspecionada cuidadosamente. A sua apresentacao pode dividir‐se em manifestacoes benignas (condilomas acuminados ou verrugas genitais) e em manifestacoes pre‐malignas e malignas (neoplasia intraepitelial e neoplasias invasivas). Faz‐se uma revisao das recomendacoes diagnosticas da infecao pelo HPV no homem, na mulher, no casal e no hospedeiro imunocomprometido, assim como uma atualizacao dos conceitos anatomopatologicos.

O presente estudo visa compreender o uso da comunicação através das redes sociais e plataformas online como uma ferramenta fundamental na promoção de um hotel, no ponto de vista hoteleiro e do cliente. Para atingir o objetivo proposto, foi utilizado o método misto (quantitativo e qualitativo). O método quantitativo, através da aplicação de inquérito por questionário aos hóspedes, por forma a saber se estes utilizam as redes sociais na sua decisão de escolha do hotel e, entrevista ao gestor do hotel acerca do que motiva a utilização de redes sociais. O resultado alcançado nesta investigação confirma que o uso da comunicação através das redes sociais e plataformas online como uma ferramenta fundamental na promoção de um hotel, no ponto de vista hoteleiro e do cliente, são importantes, uma vez que cada vez mais as redes sociais/plataformas digitais fazem parte do funcionamento dos hotéis e da vida dos hóspedes. Com as plataformas online os estabelecimentos hoteleiros rapidamente conseguem estar a par de tudo sobre os seus clientes, assim como os hóspedes conseguem ter informações de modo a ajudar na tomada de decisão sobre o hotel a escolher. Tornam-se ainda mais importantes, principalmente neste momento, devido à situação pandémica que atravessa o mundo, Covid-19. Assim as redes sociais e as plataformas digitais revelam-se o meio mais utilizado para procurar informação e efetuar reservas.

In this paper we examine how human-machine interaction in the legal sector is suggested to be regulated in the EU’s recently proposed Artificial Intelligence Act. First, we provide a brief background and overview of the proposal. Then we turn towards the assessment of high-risk AI systems for the legal tasks as well as the obligations for such AI systems in terms of human-machine interaction. We argue that whereas the proposed definition of AI system is broad, the concrete high-risk area of ‘administration of justice and democratic processes’, despite coming with considerable legal uncertainty, is narrow and unlikely to extent into many uses of legal AI and IA systems. Nonetheless, these regulatory developments may be of great relevance for current and future legal AI and IA systems.

We show that molecular precursors, combining six given segment types, can produce all carbon nanotubes of chiralities larger than (9,0).

Tecnimed S.r.l. v Artsana S.p.A.; with Case note by Letizia Tomada

Relatório de estágio de mestrado em Ensino do Inglês no 1.º Ciclo do Ensino Básico, No âmbito do Mestrado em Ensino do Inglês no 1º ciclo do Ensino Básico, o presente relatório de estágio apresenta o projeto de intervenção pedagógica supervisionada, assente na investigação-ação, que desenvolvi durante a prática pedagógica, intitulado “ All together now! O potencial educativo da música no ensino de inglês a crianças”. O projeto foi desenvolvido numa turma de 4º ano do 1º Ciclo do Ensino Básico, numa escola primária pertencente a um agrupamento de escolas situado na cidade de Braga, e tinha como objetivos: conhecer perceções e atitudes das crianças relativas à aprendizagem da língua inglesa e ao uso da música nas aulas de inglês; potenciar os níveis de motivação e atenção dos alunos nas aulas de inglês através do uso da música; associar o inglês a sentimentos de diversão, potenciando uma boa relação entre os alunos e a língua e promovendo a aprendizagem; promover a competência de aprender a aprender com foco na autorregulação; avaliar o potencial do uso da música na aprendizagem. Durante o seu desenvolvimento, o projeto passou por três fases distintas, nomeadamente, análise do contexto de intervenção, desenvolvimento das atividades do projeto e avaliação do projeto perante os objetivos inicialmente propostos. As principais estratégias de intervenção utilizadas foram: observação de aulas e registos reflexivos no portefólio de estágio; questionário inicial às crianças; diálogos com as crianças; atividades didáticas com recurso a músicas, seguidas de momentos de autorregulação da aprendizagem. A avaliação do projeto, com base na informação recolhida durante o estágio, permite concluir que os seus objetivos foram globalmente cumpridos e que a música contribuiu para que as crianças aprendessem inglês de uma forma divertida e menos formal. A principal dificuldade sentida prendeu-se com a seleção de canções para ensinar os conteúdos propostos, dada a necessidade de estas cumprirem vários critérios por forma a irem ao encontro dos objetivos do projeto. Contudo, esta dificuldade não coloca em causa o potencial educativo da música quando colocada ao serviço do ensino de inglês a crianças., Within the Master in Teaching English for Primary School, this practicum report presents the supervised pedagogical intervention project based on action research that I developed in my teaching practice, entitled “All together now! The educational potential of music in teaching English to young learners”. The project was developed in a 4º grade class in a primary school located in the city of Braga, and had the following objectives: identifying children’s perceptions and attitudes towards learning the English language and the use of music in English lessons; boosting student’s motivation and attention levels through music; associating English learning with feelings of fun, thus creating a good relationship between the students and the language and improving learning; developing the learning to learn competence with a focus on self-regulation; assessing the potential of music in learning. During its development, the project went through three distinct phases, namely, context analysis, development of project activities, and project evaluation concerning the objectives initially set. The main intervention strategies used were: lesson observation resulting in reflective records kept in the practicum portfolio; initial questionnaire to children; conversations with children; didactic activities with the use of songs, followed by self-regulation moments. The information gathered during the practicum shows that the objectives for this project were globally attained and that music contributed for the children’s learning of English in a fun and less formal way. The main difficulty felt in project development had to do with finding the right songs to take to the classroom, due to the need to comply with criteria I considered essential in order to reach the objectives of the project. Nevertheless, this difficulty does not invalidate the educational potential of music in the teaching of English to young learners.

Downy mildew, caused by Plasmopara viticola, is a highly significant grapevine disease causing severe yield losses and affecting wine quality. Disease control mainly relies on use of copper and synthetic fungicides. Today there is a growing interest in developing microbial biopesticides for downy mildew control in integrated and organic viticulture. Here, the bacterial biocontrol agent Lysobacter capsici AZ78 (AZ78) was tested following a holistic approach including in planta efficacy test (large-scale trial) combined with bioassays aiming to assess potential adverse effects on non-target organisms: beneficial arthropods (Aphidius rhopalosiphi and Typhlodromus pyri), the crustacean Daphnia magna, the algae Selenastrum capricornutum and soil organisms [earthworm Eisenia (Ei.) fetida and worm Enchytraeid (En.) albidus]. Moreover, side effects of AZ78 treatments on grape quality and wine-making process were assessed. The results showed that AZ78 was equally effective to reference fungicide (Kocide®2000) in controlling downy mildew on leaves and bunches. AZ78 had no significant effect on the mortality of the indicator arthropod species at a Limit test Rate, which was equal to four times the recommended field rate. Additionally, no significant effects (mortality, growth rate or reproduction) were observed on D. magna, Ei. albidus, En. fetida and S. capricornutum, indicating AZ78 low toxicity on non-target organisms. Likewise, the yeast population dynamics in fermenting musts was not affected, without compromising the fermentation processes and wine quality. Overall, this study provides new insights into the characterisation of the biocontrol agent AZ78 showing that this bacterium has the potential to be further developed as a commercial biopesticide.

We present a benchmark suite of four datasets for evaluating the fairness of pre-trained language models and the techniques used to fine-tune them for downstream tasks. Our benchmarks cover four jurisdictions (European Council, USA, Switzerland, and China), five languages (English, German, French, Italian and Chinese) and fairness across five attributes (gender, age, region, language, and legal area). In our experiments, we evaluate pre-trained language models using several group-robust fine-tuning techniques and show that performance group disparities are vibrant in many cases, while none of these techniques guarantee fairness, nor consistently mitigate group disparities. Furthermore, we provide a quantitative and qualitative analysis of our results, highlighting open challenges in the development of robustness methods in legal NLP., Comment: 9 pages, long paper at ACL 2022 proceedings

The molecular mechanisms responsible for the high immunosuppressive capacity of CD4(+) Tregs in tumors are not well known. High-dimensional single-cell profiling of T cells from chemotherapy-naive individuals with non–small-cell lung cancer identified the transcription factor IRF4 as specifically expressed by a subset of intratumoral CD4(+) effector Tregs with superior suppressive activity. In contrast to the IRF4(–) counterparts, IRF4(+) Tregs expressed a vast array of suppressive molecules, and their presence correlated with multiple exhausted subpopulations of T cells. Integration of transcriptomic and epigenomic data revealed that IRF4, either alone or in combination with its partner BATF, directly controlled a molecular program responsible for immunosuppression in tumors. Accordingly, deletion of Irf4 exclusively in Tregs resulted in delayed tumor growth in mice while the abundance of IRF4(+) Tregs correlated with poor prognosis in patients with multiple human cancers. Thus, a common mechanism underlies immunosuppression in the tumor microenvironment irrespective of the tumor type.

To obtain the therapeutic effect of biological medicines, such as proteins and nucleic acids, these medicines must achieve their intracellular target, such as the cytoplasm, and pass through biological membrane barriers. Endocytosis is an attractive route for the intracellular delivery of such drugs, and various endocytosis inhibitors have been used as tools to study the involvement of endocytosis in the cell internalization of delivery carriers. However, the specificity of these inhibitors has been insufficiently studied, and our preliminary tests could not detect the expected effect of the well-known endocytosis inhibitors. Therefore, the present study aimed to optimize the experimental conditions to precisely analyze cellular internalization via endocytosis. We first found that incubation of model molecules, such as transferrin (Tf) and cholera toxin subunit B (CTB), in cell culture medium (DMEM) could efficiently induce their internalization to HeLa cells compared to that in transport buffer (HBSS). Moreover, we clarified that cell surface wash with glycine-hydrochloric acid buffer before confocal microscopy and flow cytometry strengthened the intracellular fluorescence of Tf, CTB, and dextran tagged with fluorescent probes possibly via the neutralization of endosomal pH. Even under the optimized condition, however, the specificity of endocytosis inhibitors was disputable. The present study suggested the importance of the optimization of the study design with endocytosis inhibitors in analyzing cellular internalization.

The chirality-controlled synthesis of single-walled carbon nanotubes (SWCNTs) is a major challenge facing current nanomaterials science. The surface-assisted bottom-up fabrication from unimolecular CNT seeds (precursors), which unambiguously predefine the chirality of the tube during the growth, appears to be the most promising approach. This strategy opens a venue towards controlled synthesis of CNTs of virtually any possible chirality by applying properly designed precursor molecules. However, synthetic access to the required precursor molecules remains practically unexplored because of their complex structure. Here, we report a general strategy for the synthesis of molecular seeds for the controlled growth of SWCNTs possessing virtually any desired chirality by combinatorial multi-segmental assembly. The suggested combinatorial approach allows facile assembly of complex CNT precursors (with up to 100 carbon atoms immobilized at strictly predefined positions) just in one single step from complementary segments. The feasibility of the approach is demonstrated on the synthesis of the precursor molecules for 21 different SWCNT chiralities utilizing just three relatively simple building blocks., Bottom-up synthesis from rationally designed precursor molecules is one of the most promising routes to single-walled carbon nanotubes of any desired chirality. Here, the authors present a combinatorial approach to easily assemble a variety of these complex nanotube precursors from simple complementary segments.

In an era of growing international competition in modern viticulture, the study and implementation of innovative technologies to increase the production of high-quality grapes and wines are of critical importance. In this study, the non-destructive portable sensor Multiplex, based on fluorescence sensing technique, was applied to evaluate grape maturity parameters and flavonol content of the understudied Pinot blanc variety. The effects of environmental and agronomical factors on flavonol content of Pinot blanc grapes were investigated in eight vineyards characterised by different microclimatic and agronomic conditions. Furthermore, the direct impact of canopy management treatment on the flavonol dynamics of the grapes oriented in the four cardinal directions was assessed. Results highlight the positive role of moderate temperatures and direct sunlight exposure on Pinot blanc flavonol content; however, no direct vineyard-elevation effect was observed. The ability to modulate and evaluate the flavonol content in field represent crucial factors because of their potential effect on flavonoids-dependent wine characteristics, such as stability and ageing. In the present study, for the first time, two calibration curves were reported for pre- and post-veraison periods between flavonol indices and the berry skin flavonol content and a good correlation was observed between Multiplex measurement and the total polyphenolic content of grape juice. Moreover, the strong correlation between the chlorophyll index with grape juice sugar content and titratable acidity revealed the practical application of non-destructive sensors to predict the optimal harvest time for Pinot blanc grapes. In conclusion, the non-destructive fluorescence sensor Multiplex is a high-potential tool for innovative viticulture, for evaluating grape skin composition variables in white grape varieties.

In this paper we examine how human-machine interaction in thelegal sector is suggested to be regulated in the EU’s recentlyproposed Artificial Intelligence Act. First, we provide a briefbackground and overview of the proposal. Then we turn towards the assessment of high-risk AI systems for the legal tasks as well as the obligations for such AI systems in terms of human-machine interaction. We argue that whereas the proposed definition of AI system is broad, the concrete high-risk area of ‘administration of justice and democratic processes’, despite coming with considerable legal uncertainty, is narrow and unlikely to extent into many uses of legal AI and IA systems. Nonetheless, these regulatory developments may be of great relevance for current and future legal AI and IA systems.

Identidade Perdida é o nome que atribuí ao presente relatório de estágio, que foi realizado no âmbito do Mestrado em Ensino de Artes Visuais da Universidade do Porto. Este relatório reflete o estágio pedagógico realizado na Escola Secundária Francisco de Holanda, em Guimarães. Uma turma de ensino regular de Artes Visuais do 12.º ano, nas Unidades Curriculares de Desenho A e Oficina de Artes, foi o alvo da minha intervenção. Adicionalmente reflete o acompanhamento de outras turmas de ensino profissional e regular. O objetivo foi o de apresentar e investigar um problema vivido no estágio pedagógico. O problema que investiguei segue em torno da motivação e interesse dos estudantes, sua autonomia e identidade artística. As metodologias de investigação às quais recorri, gradualmente foram aperfeiçoadas. Os métodos de investigação começaram pela participação proativa nas aulas, a observação dos estudantes, professores cooperantes e atividades assistidas e o registo dessas observações no "diário de bordo". Seguiu-se assim para a escrita do relatório, com reflexão da experiência de estágio vivida, apontando os problemas detetados, experiências e práticas dos estudantes. No relatório de estágio consta a sua evolução por acumular de fragmentos, tais como o diálogo com os estudantes e professores, as fotografias da escola e das atividades propostas pelo professor cooperante e fotografias dos desenhos e trabalhos dos estudantes, que culminou na reflexão reservada aos problemas de motivação, identidade, autonomia e método de ensino. Por conseguinte, a sustentação do meu trabalho foi executada a partir da análise e reflexão documental e literária e das situações assistidas no estágio e sessões. Os resultados obtidos são positivos. Durante o estágio, detetei muitas questões e no relatório debrucei-me sobre o problema a que me propus investigar. A relevância desse problema passa pela importância de saber motivar os estudantes para que não haja um divórcio entre eles e o desenho. A sua motivação é relevante para um bom ambiente de aprendizagem. Desta investigação e da minha participação no estágio, consegui concluir que os estudantes tendem a ter um mau relacionamento com as propostas de trabalho e a unidade curricular, quando não lhes é dada a oportunidade de explorarem no desenho o que gostam, o que lhes desperta interesse, o que ambicionam explorar e tendem a desinteressar-se por atividades repetitivas e similares umas às outras.

In 2002, Steve Wilson pioneered new procedures for alternative placement of reservoirs for inflatable prostheses in patients who have suffered damage to the space of Retzius following pelvic surgery or obliteration of the transversalis fascia by mesh hernia repair. Since then, surgical techniques and tools for ectopic reservoir placement have gradually gained acceptance to minimize palpability, and the risk of visceral and vascular lesions for high risk patients has been all but eliminated. Lockout valves and high submuscular placement techniques are now recommended, and reports of vascular, bowel or bladder injuries are uncommonly rare. While surgeons continue their search for safer and more effective placement methods, new skills and instruments are constantly being introduced to make recommendations to minimize complications and provide safety and functionality. Additional studies and comparisons of techniques are needed to achieve a consensus of best practice for reservoir placement solutions.

The prevention of HPV-related diseases is an important healthcare issue due to its increasing incidence. Primary prevention is most important in males as it avoids initial infection and includes the use of condom, circumcision and vaccination. Primary prevention with vaccination is effective in decreasing HPV-related lesions in women up to 45 years old and the existing data for men comes from the experience from vaccinating women. Although it is the only vaccine that prevents cancer, the worldwide rates of vaccination in males is very low due to lack of information related to efficacy and side effects, lack of recommendation from the treating doctor, price and concern about encouragement of sexual promiscuity.

The treatment of condyloma is generally a challenge in clinical practice. Although the spontaneous resolution rate is high, a significant proportion of patients seek treatment, not because of symptomatology, but mainly for aesthetic issues and concerns related to the transmission or worsening of existing lesions. The available treatments should be applied only for clinically evident macroscopic lesions. Ideally, available therapies should have rapid action onset and clearance, resolve symptoms, reduce recurrence rate and viral load, be effective in treating small lesions, and be well tolerated. However, none of the currently available treatments is clearly more effective than the others and there is no ideal treatment for all patients or for all condyloma. Therefore, the therapeutic decision should be based on the clinician's experience, available resources, lesion morphology, size, number and location, primary or recurrent lesions, disease severity, patient preference and expectations, patient's immune competence, convenience, tolerance, cost of treatment and results of previous therapies. The available treatments are divided into three groups: applied by the patient himself (imiquimod 3.75 or 5%, podophyllotoxin .5%, synecatekines 10% or 15%), applied by the health care provider (bi- and tricloacetic acids 80%-90%, intralesional interferon alpha, cryotherapy, surgical removal, electrofulguration, laser ablation) and experimental or alternative therapies (topical cidofovir, intralesional bleomycin, photodynamic therapy). Treatment methodologies can be further divided into their action - ablative or destructive treatment (cryotherapy, electrofulguration, laser ablation, surgical excision), cytotoxic or proapoptotic treatments (podophyllotoxin .5%, 5-fluoruracil, bleomycin) and immunomodulatory treatments (imiquimod 3.75% or 5%, synecatekines 10% or 15%, intralesional interferon alpha). The overall success rate of the various treatments available ranges from 23% to 94%. Only treatments that include cryotherapy or surgical excision are suitable in condyloma with any anatomical location and that have the highest success rate in monotherapy. Recurrences are common regardless of the treatment received. In contrast, immunomodulatory therapies despite having lower initial clearance rates appear to have higher probabilities of cure in the medium term, with low recurrence rates. Some treatments may be combined with each other and the effectiveness of combined therapies appears to be superior to monotherapy (proactive sequential treatment). The consensuses for the treatment of HPV also consider special situations: immunocompromised patients, meatus and intraurethral lesions and treatment of the partner.

Introdução: O Padrão Alimentar Mediterrânico é um modelo alimentar de elevada qualidade e adequação nutricional, que se associa a melhor qualidade de vida. Portugal, embora seja um país com características mediterrânicas, está progressivamente a distanciar-se deste padrão, sobretudo em idades mais jovens, onde a adoção de hábitos alimentares saudáveis é essencial. Objetivos: Avaliar a adesão ao Padrão Alimentar Mediterrânico em crianças e adolescentes, e a sua associação com o seu estado nutricional. Metodologia: Estudo transversal, descritivo e analítico. Foi aplicado o Mediterranean Diet Quality Index in Children and Adolescents (índice KIDMED), a uma amostra de conveniência de crianças e adolescentes, entre os 2 e os 18 anos, seguidos em consulta de vigilância de saúde num hospital privado do norte de Portugal. Para a caracterização do estado nutricional foi calculado o Índice de Massa Corporal e utilizados os critérios da Organização Mundial da Saúde. Foram critérios de exclusão uma idade inferior a 2 anos, qualquer tipo de vegetarianismo e a presença de doenças do comportamento alimentar. Resultados: Dos 153 inquiridos, com uma idade média de 9,9±4,3 anos e uma predominância do sexo feminino (56,2%), 21,6% apresentava excesso de peso, 18,9% obesidade e 9,2% baixo peso/desnutrição. Observou-se alta adesão ao Padrão Alimentar Mediterrânico (81,0%), no entanto, esta era tanto menor quanto maior a idade (r=0,279; p

Objectives Dual platelet inhibition is commonly used for prevention of cardiovascular events in patients undergoing neuroendovascular procedures. Non-responsiveness to platelet inhibitors may be associated with adverse outcomes. The aim of this study was to evaluate the reliability of the platelet function analyzer PFA-100® in comparison to light transmittance aggregometry (LTA) for monitoring clopidogrel and acetylsalicylic acid (ASA) non-responsiveness in a cohort of patients treated for intracranial aneurysm or cranial artery stenosis. Methods Non-responsiveness to clopidogrel and ASA was assessed by LTA using adenosine diphosphate (ADP) and arachidonic acid and by PFA-100® with the ADP/prostaglandin E1 (PGE1) and collagen/epinephrine cartridges, respectively. Results A total of 203 patients (145 females; median age, 57 years) were analyzed. Agreement between the two tests was poor for clopidogrel non-responsiveness (ƙ=0.19) and not better than chance for ASA non-responsiveness (ƙ=0.01). Clopidogrel non-responsiveness by LTA and PFA-100® was associated with higher von Willebrand factor antigen and activity levels. ADP-induced platelet disaggregation was lower in patients with clopidogrel non-responsiveness as assessed by PFA-100®. Clopidogrel non-responsiveness by LTA was associated with a higher prevalence of diabetes and a higher body mass index (BMI). Adverse outcomes (death, thromboembolism, or in-stent thrombosis) occurred in 13% (n=26) of all patients independently of ASA and clopidogrel non-responsiveness as assessed by both devices. Conclusions Our results show that LTA and PFA-100® are not interchangeable in the assessment of ASA and clopidogrel non-responsiveness in patients undergoing neuroendovascular interventions.

Cardiovascular disease risk factors (CVDRF), especially diabetes mellitus (DM), disrupt oxidative stress response. This condition underlies endothelial dysfunction, early manifested in men as erectile dysfunction. The current study is aimed at elucidating the impact of CVDRF in the oxidation responsive AMPK/SIRT1-PGC-1α-SIRT3 pathway and related miRNAs in the human corpus cavernosum. Human penile tissue fragments from individuals submitted to programmed urological surgeries (n = 27), aged 43-63 years, were clustered depending on the presence of CVDRF; the control group included samples from patients without CVDRF, and groups A and B included samples from patients with DM and additional CVDRF, totalizing ≤2 CVDRF (group A) and ≥3 CVDRF (group B). Dual-immunolabelling of SIRT3, SOD2, or GPX1 with α-actin in tissue sections was carried out. The assessment of expression levels of NOX1, phospho-AMPKα, total AMPKα, SIRT1, PGC-1α, SIRT3, SOD2, and GPX1 was performed by western blotting and of miR-200a, miR-34a, miR-421, and miR-206 by real-time PCR. Phospho-AMPKα and SIRT3 expression was found significantly increased in group B relative to other groups, suggesting a marked influence of CVDRF, additional to DM, in the regulation of these enzymes. NOX1 was also increased in group B relative to controls. Only an increasing tendency was observed in the phospho-AMPKα/total AMPKα ratio, SIRT1, and PGC-1α expression in groups A and B when compared with controls. Concerning antioxidant enzymes, GPX1 expression was found incremented in group A, but SOD2 expression was decreased in groups A and B, comparative with controls. Group B presented significantly diminished levels of miR-421 and miR-200a, but only a decreasing trend on miR-34 and miR-206 expression was observed. Taken together, our findings demonstrated that besides DM, additional CVDRF presented a cumulative effect in the cellular response to oxidative unbalance, contributing to AMPK/SIRT1-PGC-1α-SIRT3 pathway activation. SOD2, a major mitochondrial antioxidant defence, did not follow the same variation.

Cardiovascular disease risk factors (CVDRF), especially diabetes mellitus (DM), disrupt oxidative stress response. This condition underlies endothelial dysfunction, early manifested in men as erectile dysfunction. The current study is aimed at elucidating the impact of CVDRF in the oxidation responsive AMPK/SIRT1-PGC-1α-SIRT3 pathway and related miRNAs in the human corpus cavernosum. Human penile tissue fragments from individuals submitted to programmed urological surgeries (n=27), aged 43-63 years, were clustered depending on the presence of CVDRF; the control group included samples from patients without CVDRF, and groups A and B included samples from patients with DM and additional CVDRF, totalizing ≤2 CVDRF (group A) and ≥3 CVDRF (group B). Dual-immunolabelling of SIRT3, SOD2, or GPX1 with α-actin in tissue sections was carried out. The assessment of expression levels of NOX1, phospho-AMPKα, total AMPKα, SIRT1, PGC-1α, SIRT3, SOD2, and GPX1 was performed by western blotting and of miR-200a, miR-34a, miR-421, and miR-206 by real-time PCR. Phospho-AMPKα and SIRT3 expression was found significantly increased in group B relative to other groups, suggesting a marked influence of CVDRF, additional to DM, in the regulation of these enzymes. NOX1 was also increased in group B relative to controls. Only an increasing tendency was observed in the phospho-AMPKα/total AMPKα ratio, SIRT1, and PGC-1α expression in groups A and B when compared with controls. Concerning antioxidant enzymes, GPX1 expression was found incremented in group A, but SOD2 expression was decreased in groups A and B, comparative with controls. Group B presented significantly diminished levels of miR-421 and miR-200a, but only a decreasing trend on miR-34 and miR-206 expression was observed. Taken together, our findings demonstrated that besides DM, additional CVDRF presented a cumulative effect in the cellular response to oxidative unbalance, contributing to AMPK/SIRT1-PGC-1α-SIRT3 pathway activation. SOD2, a major mitochondrial antioxidant defence, did not follow the same variation.

Objetivo: Avaliar a prevalência de comportamentos de risco, comportamento sexual e disfunções sexuais (DS) em estudantes de medicina portugueses.Materiais e métodosEstudantes da Faculdade de Medicina do Porto foram divididos em 3 grupos de acordo com o ano académico – grupo 1 (1.°/2.° anos, n = 288), grupo 2 (3.°/4.° anos, n = 267) e grupo 3 (5.°/6.° anos, n = 250) – e convidados a preencher um questionário sobre sexualidade e comportamento de risco. A análise estatística foi efetuada com recurso ao programa SPSS®. Resultados: Responderam ao questionário 258 homens e 547 mulheres, com idade mediana de 20 anos. A idade mediana da primeira experiência sexual dos inquiridos foi 17 anos, no entanto, 33,9% dos estudantes ainda não tinha tido qualquer experiência sexual. Verificou‐se que a prática conjunta de sexo oral e vaginal foi a mais comum (56,2%). A disfunção ejaculatória foi a DS mais referida pelos homens (18,2%), seguida da disfunção erétil (DE) (7,8%), particularmente quando associada ao consumo de drogas ilícitas (22,2%). As mulheres reportaram com maior frequência dispareunia (40,8%), dificuldade em atingir um orgasmo (34,7%) e falta de lubrificação (18,5%). Conclusões: Embora os estudantes de medicina representem uma população jovem saudável, a tensão física, emocional e mental a que estão sujeitos afeta negativamente a sua sexualidade. Além disso, a autoconsciência sexual pode afetar futuras interações com doentes com DS. Este estudo transversal demonstra que esta população em particular é globalmente inexperiente, contudo, são necessários mais estudos de avaliação dos padrões sexuais na população portuguesa para melhor esclarecer o seu perfil relativamente aos restantes jovens., Objective: To assess the prevalence of risk behavior, sexual behavior and sexual dysfunctions in Portuguese medical students. Methods: Students of the Faculty of Medicine of Porto were divided into three groups according to the year they are enrolled: group 1 (1st/2nd year, n = 288), group 2 (3rd/4th year, n = 267) and group 3 (5th/6th year, n = 250). An anonymous questionnaire about sexuality and risk behavior was filled in. Statistical analysis was performed using SPSS®. Results: The questionnaire was answered by 805 students (female = 547; male = 258), with median age of 20 years. The median age of the first sexual experience was 17 years, but 33.9% of the students denied having any sexual experience. The most common sexual practice is the joint practice of oral and vaginal sex (56.2%). Ejaculatory dysfunction was the sexual dysfunction most referred by men (18.2%), followed by erectile dysfunction (7.8%), particularly when associated to illicit drugs consumption (22.2%). The sexual dysfunctions most reported by women were dyspareunia (40.8%), difficulty in attaining an orgasm (34.7%) and lack of lubrication (18.5%). Conclusions: Although medical students represent a healthy young population, the physical, emotional and mental strain they are subjected to affect negatively their sexuality. Furthermore, sexual self-awareness may negatively impact future interactions with patients with sexual dysfunctions. This cross-sectional study is very inclusive, and demonstrated that this population is globally inexperienced. However, more studies of Portuguese population are needed in order to better understand their profile in relation to the other youngsters.

Silicon drift detectors (SDDs) revolutionized spectroscopy in fields as diverse as geology and dentistry. For a subset of experiments at ultra-fast, x-ray free-electron lasers (FELs), SDDs can make substantial contributions. Often the unknown spectrum is interesting, carrying science data, or the background measurement is useful to identify unexpected signals. Many measurements involve only several discrete photon energies known a priori, allowing single event decomposition of pile-up and spectroscopic photon counting. We designed a pulse function and demonstrated that the signal amplitude and rise time are obtained for each pulse by fitting, thus removing the need for pulse shaping. By avoiding pulse shaping, rise times of tens of nanoseconds resulted in reduced pulse pile-up and allowed decomposition of remaining pulse pile-up at photon separation times down to hundreds of nanoseconds while yielding time-of-arrival information with precision of 10 nanoseconds. Waveform fitting yields simultaneously high energy resolution and high counting rates (2 orders of magnitude higher than current digital pulse processors). We showed that pile-up spectrum fitting is relatively simple and preferable to pile-up spectrum deconvolution. We developed a photon pile-up statistical model for constant intensity sources, extended it to variable intensity sources (typical for FELs) and used it to fit a complex pile-up spectrum. We subsequently developed a Bayesian pile-up decomposition method that allows decomposing pile-up of single events with up to 6 photons from 6 monochromatic lines with 99% accuracy. The usefulness of SDDs will continue into the x-ray FEL era of science. Their successors, the ePixS hybrid pixel detectors, already offer hundreds of pixels, each with similar performance to an SDD, in a compact, robust and affordable package, 16 pages, 11 figures, 4 tables

Biological interactions in the microbial communities of the rhizosphere continuously shape the gene expression patterns of each individual microorganism. A dual RNA-Seq approach was applied to obtain a comprehensive overview of the molecular mechanisms activated during the interaction between the biocontrol rhizobacterium Lysobacter capsici AZ78 and the soilborne phytopathogenic oomycete Phytophthora infestans. The RNA-Seq transcriptional profile of L. capsici AZ78 was characterized by up-regulation of genes concerned in the biogenesis of type 4 pilus and lytic enzymes, involved, respectively, in host colonization and subsequent attack of the P. infestans cell wall. The activation of detoxification processes allowed L. capsici AZ78 to overcome the attempted defense processes of P. infestans. Moreover, the genes involved in antibiotic biosynthesis were up-regulated in L. capsici AZ78 and caused cell death in P. infestans, with the activation of putative apoptotic processes. The consequences of P. infestans cell death resulted in the down-regulation of primary metabolic pathways, such as carbohydrates, nucleic acids and protein metabolisms. Overall, the mechanism of action of L. capsici AZ78 was related to parasitism and predatory activities that cause the death of P. infestans.

Phalloplasty can be either performed as a penile reconstructive or phallic constructive procedure, mainly in penile trauma victims or female-to-male gender reassignment. After the introduction of the radial artery-based forearm free flap and with the further awareness of patient desire to void while standing, urethral reconstruction became a standard procedure and a main goal to attain in phalloplasty. Urethroplasty techniques can be broadly split in two main groups: as part of a tube-within-a-tube skin flap or as an independent other-than-skin graft. Urethral complications, such as fistula, stricture, or stones, are common and often recur after treatment. In this review, the main techniques of urethral reconstruction in phalloplasty are reviewed and compared. Urethral complications are also reviewed as well as their management.

Objective To evaluate surgical outcomes and complications and assess overall patient satisfaction after small intestinal submucosa (SIS) grafting for Peyronie disease. Methods Twenty-eight patients were treated with tunical incision and grafting with SIS. Mean age of the patients was 58 (range: 43-71) years. A preoperative protocol was applied to all patients. Patients were also evaluated at follow-up clinic visits. The International Index of Erectile Function, a modified Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire, postoperative self-reports, and clinical characteristics were used to measure outcomes. Results Hypertension, hypercholesterolemia, and type 2 diabetes were reported in 53,6%, 46,4%, and 28,6% of patients, respectively. Previous penile trauma was reported by 10,7%. The mean operative time was 151 ± 23 minutes. Average follow-up was 18 months (range: 3-36). The only surgical complication was 1 case of infected hematoma treated with surgical drainage. Self-reported complete resolution of curvature was 82,1%. Subjective perception of penile shortening was reported by 71,4% of patients. However, only 4 patients objectively showed postoperative penile shortening. Erectile function was completely preserved in 64,2%. Four patients complained of erectile dysfunction despite medication, even though no objective vascular etiology was shown on postoperative penile Doppler ultrasound. Overall, 82,2% of patients reported high levels of satisfaction. Conclusion Surgical treatment of Peyronie disease using SIS grafting is a safe option, with low rate of major complications. It has good surgical outcomes and high patient satisfaction rates.

Transforming growth factor beta (TGF-ß) plays an important role in the pathogenesis of obesity, influencing the release of inflammation mediators and promoting remodeling and collagen deposition in the adipose tissue (AT). In this context, this work aims to elucidate whether TGF-ß and Smad-dependent or Smad-independent signaling pathways contribute to regional differentiation of AT in high-fat diet (HFD) and energy-restricted (ER) rat models. For this, TGF-ß, TGF-ß receptors I and II, PAI-1 and GLUT4 mRNA levels were quantified by real-time PCR, and western blotting assays allowed the semiquantification of TGF-ß and proteins from Smad3, ERK1/2 and Akt signaling pathways in subcutaneous and visceral (epididymal, retroperitoneal and mesenteric) fat depots from control, HFD and ER-treated rats. HFD was associated to increased levels of TGF-ß and PAI-1 mRNA in epididymal and retroperitoneal visceral fat depots, while ER diet induced a reduction of TGF-ß mRNA levels in mesenteric, but surprisingly an increase in retroperitoneal fat. Regarding the different signaling pathways, contrarily to what was found for Smad3, activation of ERK1/2 and Akt in response to HFD was detected in all the visceral but not in subcutaneous fat depots. ER-treated rats presented a more heterogeneous signaling response, as well as decreased TGF-ß receptors expression, in the different visceral fat depots. In conclusion, subcutaneous and visceral AT respond differently to distinct diet patterns regarding TGF-ß expression and activated signaling pathways. Furthermore, the present study points that visceral AT should not be understood as a homogeneous entity since that response also varied in the different fat depots.

In this chapter the surgical treatment of erectile dysfunction and its historical perspective are reviewed. The standard surgical treatment of erectile dysfunction is the implantation of a penile prothesis, either semirigid or inflatable ones. Penile prothesis materials and design have improved along the last three decades, contributing to a lower rate of mechanical complications and an increased long-term durability. Both penile prothesis hydrophilic- and antibiotic impregnated-coatings, as well as new operative approaches such as the “no touch” approach, have greatly contributed to the lower rate of post-operative infection observed in recent years. Surgeons must be aware of both intra- and post-operative complications of penile prothesis implantation and their management as its prevention is key to success. Penile revascularization still has a minor role in the surgical treatment of erectile dysfunction, although patient selection is key.

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The treatment of condyloma is generally a challenge in clinical practice. Although the spontaneous resolution rate is high, a significant proportion of patients seek treatment, not because of symptomatology, but mainly for aesthetic issues and concerns related to the transmission or worsening of existing lesions. The available treatments should be applied only for clinically evident macroscopic lesions. Ideally, available therapies should have rapid action onset and clearance, resolve symptoms, reduce recurrence rate and viral load, be effective in treating small lesions, and be well tolerated. However, none of the currently available treatments is clearly more effective than the others and there is no ideal treatment for all patients or for all condyloma. Therefore, the therapeutic decision should be based on the clinician's experience, available resources, lesion morphology, size, number and location, primary or recurrent lesions, disease severity, patient preference and expectations, patient's immune competence, convenience, tolerance, cost of treatment and results of previous therapies. The available treatments are divided into three groups: applied by the patient himself (imiquimod 3.75 or 5%, podophyllotoxin .5%, synecatekines 10% or 15%), applied by the health care provider (bi- and tricloacetic acids 80%-90%, intralesional interferon alpha, cryotherapy, surgical removal, electrofulguration, laser ablation) and experimental or alternative therapies (topical cidofovir, intralesional bleomycin, photodynamic therapy). Treatment methodologies can be further divided into their action - ablative or destructive treatment (cryotherapy, electrofulguration, laser ablation, surgical excision), cytotoxic or proapoptotic treatments (podophyllotoxin .5%, 5-fluoruracil, bleomycin) and immunomodulatory treatments (imiquimod 3.75% or 5%, synecatekines 10% or 15%, intralesional interferon alpha). The overall success rate of the various treatments available ranges from 23% to 94%. Only treatments that include cryotherapy or surgical excision are suitable in condyloma with any anatomical location and that have the highest success rate in monotherapy. Recurrences are common regardless of the treatment received. In contrast, immunomodulatory therapies despite having lower initial clearance rates appear to have higher probabilities of cure in the medium term, with low recurrence rates. Some treatments may be combined with each other and the effectiveness of combined therapies appears to be superior to monotherapy (proactive sequential treatment). The consensuses for the treatment of HPV also consider special situations: immunocompromised patients, meatus and intraurethral lesions and treatment of the partner.

HPV infection affects about 50% of sexually active individuals at least once in a lifetime. Diagnosis is made on careful inspection of the genital area and can be divided into benign lesions (genital warts or condyloma acuminatum) and pre-malignant lesions (intraepithelial neoplasia) that can lead to cancer (invasive neoplasia). Diagnostic recommendations are reviewed in Male, Female, Couple and in the immunocompromised host. Recent histological concepts are also discussed.

The prevention of HPV-related diseases is an important healthcare issue due to its increasing incidence. Primary prevention is most important in males as it avoids initial infection and includes the use of condom, circumcision and vaccination. Primary prevention with vaccination is effective in decreasing HPV-related lesions in women up to 45 years old and the existing data for men comes from the experience from vaccinating women. Although it is the only vaccine that prevents cancer, the worldwide rates of vaccination in males is very low due to lack of information related to efficacy and side effects, lack of recommendation from the treating doctor, price and concern about encouragement of sexual promiscuity.

The Compact Linear Collider (CLIC) is a high-energy high-luminosity linear electron-positron collider under development. It is foreseen to be built and operated in three stages, at centre-of-mass energies of 380 GeV, 1.5 TeV and 3 TeV, respectively. It offers a rich physics program including direct searches as well as the probing of new physics through a broad set of precision measurements of Standard Model processes, particularly in the Higgs-boson and top-quark sectors. The precision required for such measurements and the specific conditions imposed by the beam dimensions and time structure put strict requirements on the detector design and technology. This includes low-mass vertexing and tracking systems with small cells, highly granular imaging calorimeters, as well as a precise hit-time resolution and power-pulsed operation for all subsystems. A conceptual design for the CLIC detector system was published in 2012. Since then, ambitious R&D programmes for silicon vertex and tracking detectors, as well as for calorimeters have been pursued within the CLICdp, CALICE and FCAL collaborations, addressing the challenging detector requirements with innovative technologies. This report introduces the experimental environment and detector requirements at CLIC and reviews the current status and future plans for detector technology R&D., 152 pages, 116 figures; published as CERN Yellow Report Monograph Vol. 1/2019; corresponding editors: Dominik Dannheim, Katja Kr\"uger, Aharon Levy, Andreas N\"urnberg, Eva Sicking

The Compact Linear Collider (CLIC) is a high-energy high-luminosity linear electron-positron collider under development. It is foreseen to be built and operated in three stages, at centre-of-mass energies of 380 GeV, 1.5 TeV and 3 TeV, respectively. It offers a rich physics program including direct searches as well as the probing of new physics through a broad set of precision measurements of Standard Model processes, particularly in the Higgs-boson and top-quark sectors. The precision required for such measurements and the specific conditions imposed by the beam dimensions and time structure put strict requirements on the detector design and technology. This includes low-mass vertexing and tracking systems with small cells, highly granular imaging calorimeters, as well as a precise hit-time resolution and power-pulsed operation for all subsystems. A conceptual design for the CLIC detector system was published in 2012. Since then, ambitious R&D programmes for silicon vertex and tracking detectors, as well as for calorimeters have been pursued within the CLICdp, CALICE and FCAL collaborations, addressing the challenging detector requirements with innovative technologies. This report introduces the experimental environment and detector requirements at CLIC and reviews the current status and future plans for detector technology R&D.

CERN 152 pp. (2019). doi:10.23731/CYRM-2019-001, The Compact Linear Collider (CLIC) is a high-energy high-luminosity linear electron-positron collider under development. It is foreseen to be built and operated in three stages, at centre-of-mass energies of 380 GeV, 1.5 TeV and 3 TeV, respectively. It offers a rich physics program including direct searches as well as the probing of new physics through a broad set of precision measurements of Standard Model processes, particularly in the Higgs-boson and top-quark sectors. The precision required for such measurements and the specific conditions imposed by the beam dimensions and time structure put strict requirements on the detector design and technology. This includes low-mass vertexing and tracking systems with small cells, highly granular imaging calorimeters, as well as a precise hit-time resolution and power-pulsed operation for all subsystems. A conceptual design for the CLIC detector system was published in 2012. Since then, ambitious R&D programmes for silicon vertex and tracking detectors, as well as for calorimeters have been pursued within the CLICdp, CALICE and FCAL collaborations, addressing the challenging detector requirements with innovative technologies. This report introduces the experimental environment and detector requirements at CLIC and reviews the current status and future plans for detector technology R&D., Published by CERN

Why should SMEs entrepreneurs care about Intellectual Property (IP) management? This is the starting point of the book Innovation, Startups and Intellectual Property Management. The authors are lea...

We have fabricated and characterized test devices of a new geometry for cryogenic dark matter search superconducting sensors. The modified design uses the same photolithography masks used to fabricate earlier-generation devices, but with the Al and W films deposited in reverse order. This inverted film geometry (Al over W instead of our conventional W over Al) offers a simplified and robust way to dramatically increase the thickness of Al energy-collecting fins coupled to thin W-TESs—tungsten-transition edge sensors. Data are presented from experiments with inverted geometry test devices exposed to X-rays from a NaCl fluorescence source. The results are compared to data obtained with similar devices fabricated in the standard, non-inverted geometry.

FoxP3 + T regulatory (Treg) cells are central elements of immunologic tolerance. They are abundant in many tumors, where they restrict potentially favorable antitumor responses. We used a three-pronged strategy to identify genes related to the presence and function of Tregs in the tumor microenvironment. Gene expression profiles were generated from tumor-infiltrating Tregs (TITRs) of both human and mouse tumors and were compared with those of Tregs of lymphoid organs or normal tissues from the same individuals. A computational deconvolution of whole-tumor datasets from the Cancer Genome Atlas (TCGA) was performed to identify transcripts specifically associated with Tregs across thousands of tumors from different stages and locations. We identified a set of TITR-differential transcripts with striking reproducibility between tumor types in mice, between mice and humans, and between different human patients spanning tumor stages. Many of the TITR-preferential transcripts were shared with “tissue Tregs” residing in nonlymphoid tissues, but a tumor-preferential segment could be identified. Many of these TITR signature transcripts were confirmed by mining of TCGA datasets, which also brought forth transcript modules likely representing the parenchymal attraction of, or response to, tumor Tregs. Importantly, the TITR signature included several genes encoding effective targets of tumor immunotherapy. A number of other targets were validated by CRISPR-based gene inactivation in mouse Tregs. These results confirm the validity of the signature, generating a wealth of leads for understanding the role of Tregs in tumor progression and identifying potential targets for cancer immunotherapy.