Suchergebnisse

BACKGROUND: As healthcare reimbursement shifts from being volume to value-focused, new delivery models aim to coordinate care and improve quality. The patient-centered medical home (PCMH) model is one such model that aims to deliver coordinated, accessible healthcare to improve outcomes and decrease costs. It is unclear how the types of delivery systems in which PCMHs operate differentially impact outcomes. We aim to describe economic, utilization, quality, clinical, and patient satisfaction outcomes resulting from PCMH interventions operating within integrated delivery and finance systems (IDFS), government systems including Veterans Administration, and non-integrated delivery systems. METHODS: We searched PubMed, the Cochrane Library, and Embase from 2004 to 2017. Observational studies and clinical trials occurring within the USA that met PCMH criteria (as defined by the Agency for Healthcare Research and Quality), addressed ambulatory adults, and reported utilization, economic, clinical, processes and quality of care, or patient satisfaction outcomes. RESULTS: Sixty-four studies were included. Twenty-four percent were within IDFS, 29% were within government systems, and 47% were within non-IDFS. IDFS studies reported decreased emergency department use, primary care use, and cost relative to other systems after PCMH implementation. Government systems reported increased primary care use relative to other systems after PCMH implementation. Clinical outcomes, processes and quality of care, and patient satisfaction were assessed heterogeneously or infrequently. DISCUSSION: Published articles assessing PCMH interventions generally report improved outcomes related to utilization and cost. IDFS and government systems exhibit different outcomes relative to non-integrated systems, demonstrating that different health systems and populations may be particularly sensitive to PCMH interventions. Both the definition of PCMH interventions and outcomes measured are heterogeneous, limiting the ability to perform direct ...

Collisions between the DNA replication machinery and co-transcriptional R-loops can impede DNA synthesis and are a major source of genomic instability in cancer cells. How cancer cells deal with R-loops to proliferate is poorly understood. Here we show that the ATP-dependent chromatin remodelling INO80 complex promotes resolution of R-loops to prevent replication-associated DNA damage in cancer cells. Depletion of INO80 in prostate cancer PC3 cells leads to increased R-loops. Overexpression of the RNA:DNA endonuclease RNAse H1 rescues the DNA synthesis defects and suppresses DNA damage caused by INO80 depletion. R-loops co-localize with and promote recruitment of INO80 to chromatin. Artificial tethering of INO80 to a LacO locus enabled turnover of R-loops in cis. Finally, counteracting R-loops by INO80 promotes proliferation and averts DNA damage-induced death in cancer cells. Our work suggests that INO80-dependent resolution of R-loops promotes DNA replication in the presence of transcription, thus enabling unlimited proliferation in cancers. ; Work in MPC lab is supported by Liverpool University, Newcastle University and a Wellcome Institutional Support Fund Award. Work done in A.G.'s lab was supported by Bulgarian National Science Fund grant # DN11/17. Work in the PP lab is supported by grants from the Agence Nationale pour la Recherche (ANR), the Ligue Contre le Cancer (équipe labellisée), SIRIC Montpellier Cancer (INCa Inserm DGOS 12553) and the MSDAvenir fund. ULM was funded by the Royal Society RG170342. IHL was funded from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 754510. Work in the DR lab is supported by a Wellcome Trust Seed Award in Science (206103/Z/17/Z). Work of JMGH was funded by a Wellcome Trust Investigator Award [106951/Z/15/Z] and a Royal Society Wolfson Research Merit Award

Identities on the Move questions the postmodernist concept of identity by looking into more progressive views of identity and difference, addressing post-positivist interpretations of key identity markers such as sex, gender, race, and agency.