Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?

Individualising biologic disease-modifying anti-rheumatic drugs (bDMARDs) to maximise outcomes and deliver safe and cost-effective care is a key goal in the management of rheumatoid arthritis (RA). Investigation to identify predictive tools of bDMARD response is a highly active and prolific area of research. In addition to clinical phenotyping, cellular and molecular characterisation of synovial tissue and blood in patients with RA, using different technologies, can facilitate predictive testing. This narrative review will summarise the literature for the available bDMARD classes and focus on where progress has been made. We will also look ahead and consider the increasing use of ‘omics’ technologies, the potential they hold as well as the challenges, and what is needed in the future to fully realise our ambition of personalised bDMARD treatment

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Strategy for large???scale monolithic Perovskite/Silicon tandem solar cell: A review of recent progress

For any solar cell technology to reach the final mass-production/commercialization stage, it must meet all technological, economic, and social criteria such as high efficiency, large-area scalability, long-term stability, price competitiveness, and environmental friendliness of constituent materials. Until now, various solar cell technologies have been proposed and investigated, but only crystalline silicon, CdTe, and CIGS technologies have overcome the threshold of mass-production/commercialization. Recently, a perovskite/silicon (PVK/Si) tandem solar cell technology with high efficiency of 29.1% has been reported, which exceeds the theoretical limit of single-junction solar cells as well as the efficiency of stand-alone silicon or perovskite solar cells. The International Technology Roadmap for Photovoltaics (ITRPV) predicts that silicon-based tandem solar cells will account for about 5% market share in 2029 and among various candidates, the combination of silicon and perovskite is the most likely scenario. Here, we classify and review the PVK/Si tandem solar cell technology in terms of homo- and hetero-junction silicon solar cells, the doping type of the bottom silicon cell, and the corresponding so-called normal and inverted structure of the top perovskite cell, along with mechanical and monolithic tandemization schemes. In particular, we review and discuss the recent advances in manufacturing top perovskite cells using solution and vacuum deposition technology for large-area scalability and specific issues of recombination layers and top transparent electrodes for large-area PVK/Si tandem solar cells, which are indispensable for the final commercialization of tandem solar cells

Análise da implantação do sistema de atendimento pré-hospitalar móvel em cinco capitais brasileiras Analysis of the implementation of a mobile pre-hospital treatment system in five Brazilian state capitals

Apresentamos descrição e análise da implantação do sistema de atendimento pré-hospitalar móvel (Serviço de Atendimento Móvel de Urgência - SAMU). O texto é parte de uma pesquisa denominada Análise Diagnóstica de Implantação da Política Nacional de Redução de Acidentes e Violências. Estudamos a história recente da implantação, organização, recursos humanos, materiais e equipamentos do SAMU em cinco capitais (Curitiba - Paraná; Recife - Pernambuco; Brasília - Distrito Federal; Manaus - Amazonas; Rio de Janeiro) que apresentam elevadas taxas de morbimortalidade por causas externas. Trabalhamos em quatro fases, cada qual agregando ciclos exploratórios, de trabalho de campo e de análise, triangulando dados quantitativos e qualitativos. Os resultados mostram que a implantação do SAMU constitui, hoje, um avanço do setor saúde e da sociedade. É preciso ainda completar a implantação de várias portarias quanto a veículos, pessoal e equipamentos; intensificar a articulação do pré-hospitalar móvel com as unidades de saúde; enfatizar informações geradas nesse subsistema visando ao melhor planejamento das ações; manter e promover a alta qualificação dos profissionais do SAMU. Este serviço veio oficializar, padronizar e regular um subsistema fundamental para salvar vidas.<br>The article presents a description and analysis of the implementation of a pre-hospital treatment system (SAMU) as part of the research project Diagnostic Analysis of the Implementation of a National Policy for the Reduction of Violence and Accidents. Implementation and organization of the SAMU service, together with the related materials, human resources, and equipment, was studied in five Brazilian State capitals with high morbidity and mortality rates from external causes: Curitiba (Paraná), Recife (Pernambuco), Brasília (Federal District), Rio de Janeiro, and Manaus (Amazonas). The study involved four phases, each developing exploratory and analytical cycles, combined with fieldwork, triangulating quantitative and qualitative data. Implementation of the pre-hospital treatment system is now a key health sector asset. Further necessary steps include: comprehensive legislation covering vehicles, personnel, and equipment; closer networking between mobile units and healthcare facilities; focus on information generated in this sub-system, thus facilitating planning; and maintaining and upgrading high qualifications for SAMU crews. The service is officially establishing, standardizing, and regulating a sub-system that is crucial for saving lives

Fatores associados ao uso de serviço de atenção pré-hospitalar por vítimas de acidentes de trânsito Factors associated with pre-hospital care in victims of traffic accidents

Em um estudo de corte transversal foram avaliadas as características das vítimas de acidentes de trânsito ocorridos em Belo Horizonte, Minas Gerais, Brasil, com o objetivo de conhecer as características dos acidentes e das vítimas que usaram o serviço de atendimento pré-hospitalar, e investigar se o uso deste serviço está associado a um menor tempo até o atendimento hospitalar. Participaram do estudo todas as 1.564 vítimas de acidente de trânsito atendidas nos três maiores hospitais públicos de referência para emergência na cidade entre 10 de novembro e 14 de dezembro de 2003. As associações foram investigadas utilizando-se razões de prevalência obtidas por regressão de Poisson. Os resultados mostraram que 49,7% das vítimas usaram o serviço de atendimento pré-hospitalar, sendo a utilização menor entre ocupantes de bicicleta e pedestres. A gravidade (AIS = 2 e AIS <FONT FACE=Symbol>&sup3;</FONT> 3), idade (30-39 anos, 40-49, <FONT FACE=Symbol>&sup3;</FONT> 50 anos), relato de uso de álcool e tempo de admissão hospitalar < 60 minutos estiveram associados ao transporte pelo serviço de atendimento pré-hospitalar. O uso do serviço de atendimento pré-hospitalar foi maior entre vítimas mais graves e esteve associado a um tempo menor de chegada até o hospital, características consideradas essenciais para um serviço de atenção pré-hospitalar.<br>This was a cross-sectional study of all victims of traffic accidents in Belo Horizonte, Minas Gerais State, Brazil, admitted to the three largest public hospitals in the city from November 10 to December 14, 2003, to identify characteristics associated with the use of pre-hospital emergency treatment and investigate whether the time between the accident and hospital admission was shorter among these victims. The association between pre-hospital treatment and target variables was assessed by prevalence ratios obtained from Poisson regression. Among 1,564 victims, 778 (49.7%) were transported in vehicles with pre-hospital treatment. Pre-hospital treatment was less common for bicyclists and pedestrians. The prevalence ratio was higher among victims with more severe injuries (AIS = 2 and AIS <FONT FACE=Symbol>&sup3;</FONT> 3), older victims (30-39 years, 40-49 years, <FONT FACE=Symbol>&sup3;</FONT> 50 years), those who reported alcohol use, and when the time between accident and hospital admission was less than 60 minutes. According to the results, pre-hospital treatment is more frequent among severely injured victims and helps reduce the time between the accident and hospital admission

Elinsiirron saaneen nuoren siirtyminen lasten ja nuorten hoitotyöstä aikuisten terveyspalveluiden käyttäjäksi

Opinnäytetyömme tarkoituksena on kuvata saumaton, hoitoon sitoutumista tukeva hoitopolku nuoren elinsiirtopotilaan siirtyessä lasten ja nuorten hoitotyöstä aikuisten terveyspalvelujen käyttäjäksi. Työmme on osa lasten ja nuorten hoitotyön osaamisen tulevaisuuden hanketta. Hankkeen tarkoituksena on uusien toimintakäytäntöjen luominen, verkostomaisen työskentelyn vahvistaminen, sekä saumattomien hoitopolkujen kehittäminen. Hankkeessa yhteistyökumppaneina ovat HYKS Naisten- ja lastentautien tulosyksikkö, Metropolia ammattikorkeakoulun Hoitotyön koulutusohjelma ja Tampereen yliopiston Hoitotieteen laitos. Työssämme keskitymme potilaan siirtymävaiheen solmukohtiin, kuvaamme nykyisen hoitopolun ja pyrimme löytämään näkökulmia sekä toimintamalleja, jotka antaisivat nuorelle, hänen perheelleen sekä hoitoyksikölle valmiuksia siirtymisprosessin vaiheisiin. Työssämme keskitymme nuorten kehittymishaasteisiin ja pyrimme kartoittamaan nuorten hoitomyönteisyyttä ja vastaanottavaisuutta edistäviä keinoja ja välineitä. Opinnäytetyömme aihe on uusi hoitotieteellisen tutkimuksen kohde ja löytämämme materiaali on luonteeltaan täsmällistä, tuoretta ja vastaa hyvin työmme edistymisen vaateisiin. Käytimme työssämme kvantitatiivista tutkimusmenetelmää. Tutkimustyön tarve sekä prosessin kehittäminen potilaan tarpeita vastaavaksi tällä hoitotyön saralla on erittäin tärkeää. Kansainvälisesti siirtymisessä koetaan haastavimmaksi prosessin alkamisen äkillisyys, riittämätön tiedonkulku lasten ja aikuisten puolen välillä ja tätä kautta hoidon jatkuvuuden kankeus. Toisin sanoen siirtymiseen valmistavien toimintojen aikaistaminen, kirjallinen informaatio ja sujuvampi yhteistyö palveluiden tarjoajien välillä, ovat suurimmat kehittymishaasteet