Avaliação económica de programas de Reabilitação Respiratória em doentes respiratórios crónicos: impacto no Serviço Nacional de Saúde

Em Portugal, as doenças respiratórias crónicas, em particular a doença pulmonar obstrutiva cronica (DPOC), tem uma expressão significativa no quadro de doenças diagnosticadas. Face à escassez de recursos e ao aumento crescente das necessidades da população, a pressão sobre os serviços de saúde tem aumentado significativamente, pelo que se torna premente uma utilização eficiente dos recursos disponíveis para que, a custos razoáveis, seja possível obter verdadeiros ganhos em saúde. Assim, perceber qual o verdadeiro impacto económico no SNS decorrente da utilização eficiente de recursos no tratamento da DPOC, mais especificamente, a implementação de programas de reabilitação respiratória, é deveras relevante. De modo a proceder à avaliação económica deste tipo de programas, recorreu-se a modelos de simulação de Markov e análise custo-efectividade, onde para diferentes cenários hipotetizados foram relacionados os custos decorrentes destes programas com a sua efectividade, número de internamentos evitados, comparando com a terapêutica convencional. Através da análise de rácios incrementais custo-efectividade, verificou-se que os cenários hipotetizados são custo-efectivos, por apesar de apresentarem mais custos apresentarem também mais benefícios. No entanto, ao comparar o custo por internamento evitado com o custo de um internamento, este valor é bastante superior mesmo para o melhor cenário (9791,50€ vs. 4258,78€). Ao aumentar a eficácia da terapêutica estes rácios tornam-se mais aceitáveis, sendo para o melhor cenário, menores que o custo de internamento de um doente no estadio mais grave. Esta avaliação atende apenas ao impacto nos internamentos evitados, pelo que o real impacto da reabilitação respiratória se encontra subestimado, podendo ser avaliada à luz dessa mesma medida de efectividade.In Portugal, the burden of respiratory diseases, in particular the chronic obstructive respiratory disease, have a huge expression on the number of diagnosed diseases. Due to the lack of resourses and the increase of healthcare needs by the citzens, the pressure over the healthcare services has been significantly higher, so the need for an efficient use of the available resourses, at reasonable prices it’s urgent, in a way that it’s possible to obtain real health gains. Realize the true economic impact to the NHS, by the eficiente use of the resources in the treatment of COPD, more specificly the respiratory rehabilitation programs, is very importante. In order to procced with the eveluation of this health programs, were used Markov simulation models and cost-effectiveness analysis, in which for different scenarios, the costs of these programs were related to their effectivenesses, hospital admissions avoided, when compared to the convencional therapy. Through the analysis of the incremental cost-effectiveness ratios, it was foud that the hypothesized scenarios are cost-effective, because, although presenting more costs also present more benefits. However, when comparing the cost per hospital admisson avoided with the cost of an hospital admission, this figure is significantly higher, even for the best case scenario (9791,50€ vs. 4258,78€). By increasing the eficacy of the therapy, this rácios become more acceptable, and for the best case scenario, lower than an hospital admisson of a patient in the most severe stage. This evaluation only addresses the impact on avoided hospital admissions, so the real impact of respiratory rehebilitation programs are underestimated, and can only be assessed in light of that same measure of effectiveness

Tet2 Rescues Age-Related Regenerative Decline and Enhances Cognitive Function in the Adult Mouse Brain.

Restoring adult stem cell function provides an exciting approach for rejuvenating the aging brain. However, molecular mechanisms mediating neurogenic rejuvenation remain elusive. Here we report that the enzyme ten eleven translocation methylcytosine dioxygenase 2 (Tet2), which catalyzes the production of 5-hydroxymethylcytosine (5hmC), rescues age-related decline in adult neurogenesis and enhances cognition in mice. We detected a decrease in Tet2 expression and 5hmC levels in the aged hippocampus associated with adult neurogenesis. Mimicking an aged condition in young adults by abrogating Tet2 expression within the hippocampal neurogenic niche, or adult neural stem cells, decreased neurogenesis and impaired learning and memory. In a heterochronic parabiosis rejuvenation model, hippocampal Tet2 expression was restored. Overexpressing Tet2 in the hippocampal neurogenic niche of mature adults increased 5hmC associated with neurogenic processes, offset the precipitous age-related decline in neurogenesis, and enhanced learning and memory. Our data identify Tet2 as a key molecular mediator of neurogenic rejuvenation

Systematic Identification of cis-Regulatory Sequences Active in Mouse and Human Embryonic Stem Cells

Understanding the transcriptional regulation of pluripotent cells is of fundamental interest and will greatly inform efforts aimed at directing differentiation of embryonic stem (ES) cells or reprogramming somatic cells. We first analyzed the transcriptional profiles of mouse ES cells and primordial germ cells and identified genes upregulated in pluripotent cells both in vitro and in vivo. These genes are enriched for roles in transcription, chromatin remodeling, cell cycle, and DNA repair. We developed a novel computational algorithm, CompMoby, which combines analyses of sequences both aligned and non-aligned between different genomes with a probabilistic segmentation model to systematically predict short DNA motifs that regulate gene expression. CompMoby was used to identify conserved overrepresented motifs in genes upregulated in pluripotent cells. We show that the motifs are preferentially active in undifferentiated mouse ES and embryonic germ cells in a sequence-specific manner, and that they can act as enhancers in the context of an endogenous promoter. Importantly, the activity of the motifs is conserved in human ES cells. We further show that the transcription factor NF-Y specifically binds to one of the motifs, is differentially expressed during ES cell differentiation, and is required for ES cell proliferation. This study provides novel insights into the transcriptional regulatory networks of pluripotent cells. Our results suggest that this systematic approach can be broadly applied to understanding transcriptional networks in mammalian species

A heterogeneous computer vision architecture: implementation issues

The prototype of a heterogeneous architecture is currently being built. The architecture is aimed at video-rate computing and is based on a message passing MIMD topology at the top level-transputer based-and on VLSI associative processor arrays (APA, SIMD structure) for low level image processing tasks. The APA structure is implemented through a set of 4 VLSI chips (GLiTCH) containing 64 1-bit processing elements each. This communication addresses some issues concerning the implementation of the first prototype, namely those related to: • the design and integration of the APA controller unit, which provides the required interface between the APA, the MIMD topology and the video image interface: • the evaluation of the GLiTCH chip through an emulator based on transputers and fast programmable devices; the emulator was designed to be flexible enough to evaluate later modifications to the GLiTCH design; • the design of an integrated set of software development tools containing a structured editor-syntax oriented, with a visual interface/programming interface-and a cross compiler and debugger

CompMoby: Comparative MobyDick for detection of cis-regulatory motifs

<p>Abstract</p> <p>Background</p> <p>The regulation of gene expression is complex and occurs at many levels, including transcriptional and post-transcriptional, in metazoans. Transcriptional regulation is mainly determined by sequence elements within the promoter regions of genes while sequence elements within the 3' untranslated regions of mRNAs play important roles in post-transcriptional regulation such as mRNA stability and translation efficiency. Identifying cis-regulatory elements, or motifs, in multicellular eukaryotes is more difficult compared to unicellular eukaryotes due to the larger intergenic sequence space and the increased complexity in regulation. Experimental techniques for discovering functional elements are often time consuming and not easily applied on a genome level. Consequently, computational methods are advantageous for genome-wide cis-regulatory motif detection. To decrease the search space in metazoans, many algorithms use cross-species alignment, although studies have demonstrated that a large portion of the binding sites for the same trans-acting factor do not reside in alignable regions. Therefore, a computational algorithm should account for both conserved and nonconserved cis-regulatory elements in metazoans.</p> <p>Results</p> <p>We present CompMoby (Comparative MobyDick), software developed to identify cis-regulatory binding sites at both the transcriptional and post-transcriptional levels in metazoans without prior knowledge of the trans-acting factors. The CompMoby algorithm was previously shown to identify cis-regulatory binding sites in upstream regions of genes co-regulated in embryonic stem cells. In this paper, we extend the software to identify putative cis-regulatory motifs in 3' UTR sequences and verify our results using experimentally validated data sets in mouse and human. We also detail the implementation of CompMoby into a user-friendly tool that includes a web interface to a streamlined analysis. Our software allows detection of motifs in the following three categories: one, those that are alignable and conserved; two, those that are conserved but not alignable; three, those that are species specific. One of the output files from CompMoby gives the user the option to decide what category of cis-regulatory element to experimentally pursue based on their biological problem. Using experimentally validated biological datasets, we demonstrate that CompMoby is successful in detecting cis-regulatory target sites of known and novel trans-acting factors at the transcriptional and post-transcriptional levels.</p> <p>Conclusion</p> <p>CompMoby is a powerful software tool for systematic <it>de novo </it>discovery of evolutionarily conserved and nonconserved cis-regulatory sequences involved in transcriptional or post-transcriptional regulation in metazoans. This software is freely available to users at <url>http://genome.ucsf.edu/compmoby/</url>.</p

Fractional Hardy-Sobolev type inequalities for half spaces and John domains

As our main result we prove a variant of the fractional Hardy-Sobolev-Maz'ya inequality for half spaces. This result contains a complete answer to a recent open question by Musina and Nazarov. In the proof we apply a new version of the fractional Hardy-Sobolev inequality that we establish also for more general unbounded John domains than half spaces

PT-CRIS: Um miradouro sobre o universo científico nacional

Reconhecida a importância da ciência, tecnologia, inovação e do conhecimento gerado pela investigação científica, são inúmeros os sistemas de informação criados para dar resposta a necessidades de gestão e disseminação de informação em diferentes domínios. Contudo, a dispersão de informação em vários sistemas, a não adoção de normas/práticas de referência e consequentemente a replicação de informação criam dificuldades às várias entidades que gerem ou consultam informação sobre ciência e respetivos indicadores na capacidade de gestão, execução, avaliação e tomada de decisão relativa a processos de investigação. Surge assim a necessidade de criar um sistema que ofereça uma visão global do universo de ciência e tecnologia, agregando e relacionando informação de suporte à atividade científica desenvolvida em Portugal, i.e., informação sobre investigadores, organizações, programas de financiamento, projetos, resultados de investigação, instalações, equipamentos e serviços. O sistema, ao relacionar e contextualizar a informação científica atualmente dispersa em vários sistemas, permitirá transformar informação em conhecimento, aumentar a visibilidade e difusão da ciência e simplificar processos na gestão da produção científica nacional.Comunicação patrocinada pela KEEP SOLUTION

A LINE1-Nucleolin partnership regulates early development and ESC identity

Transposable elements represent nearly half of mammalian genomes and are generally described as parasites, or "junk DNA." The LINE1 retrotransposon is the most abundant class and is thought to be deleterious for cells, yet it is paradoxically highly expressed during early development. Here, we report that LINE1 plays essential roles in mouse embryonic stem cells (ESCs) and pre-implantation embryos. In ESCs, LINE1 acts as a nuclear RNA scaffold that recruits Nucleolin and Kap1/Trim28 to repress Dux, the master activator of a transcriptional program specific to the 2-cell embryo. In parallel, LINE1 RNA mediates binding of Nucleolin and Kap1 to rDNA, promoting rRNA synthesis and ESC self-renewal. In embryos, LINE1 RNA is required for Dux silencing, synthesis of rRNA, and exit from the 2-cell stage. The results reveal an essential partnership between LINE1 RNA, Nucleolin, Kap1, and peri-nucleolar chromatin in the regulation of transcription, developmental potency, and ESC self-renewal

Detection of tuberculosis drug resistance a comparison by Mycobacterium tuberculosis MLPA assay versus Genotype®MTBDRplus

BACKGROUND: To cope with the emergence of multidrug-resistant tuberculosis (MDR-TB), new molecular methods that can routinely be used to screen for a wide range of drug resistance related genetic markers in the Mycobacterium tuberculosis genome are urgently needed. OBJECTIVE: To evaluate the performance of multiplex ligaton-dependent probe amplification (MLPA) against Genotype® MTBDRplus to detect resistance to isoniazid (INHr) and rifampicin (RIFr). METHOD: 96 culture isolates characterised for identification, drug susceptibility testing (DST) and sequencing of rpoB, katG, and inhA genes were evaluated by the MLPA and Genotype®MTBDRplus assays. RESULTS: With sequencing as a reference standard, sensitivity (SE) to detect INHr was 92.8% and 85.7%, and specificity (SP) was 100% and 97.5%, for MLPA and Genotype®MTBDRplus, respectively. In relation to RIFr, SE was 87.5% and 100%, and SP was 100% and 98.8%, respectively. Kappa value was identical between Genotype®MTBDRplus and MLPA compared with the standard DST and sequencing for detection of INHr [0.83 (0.75-0.91)] and RIFr [0.93 (0.88-0.98)]. CONCLUSION: Compared to Genotype®MTBDRplus, MLPA showed similar sensitivity to detect INH and RIF resistance. The results obtained by the MLPA and Genotype®MTBDRplus assays indicate that both molecular tests can be used for the rapid detection of drug-resistant TB with high accuracy. MLPA has the added value of providing information on the circulating M. tuberculosis lineages.publishersversionpublishe