12 research outputs found

    Interrogating open issues in cancer precision medicine with patient-derived xenografts

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    Diagenetic paths in the margin of a Triassic Basin: NW zone of the Iberian Chain, Spain

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    Buntsandstein deposits generated in a slowly subsiding basin on the western margin of the Iberian Chain are represented by a stratigraphic succession of fluvial deposits less than 100 m thick (conglomerates, sandstones, and shales). Diagenetic processes in sandstones can be grouped as eodiagenetic, mesodiagenetic, and telodiagenetic. Eodiagenesis can be associated with Muschelkalk, Keuper, and probably early Jurassic times. Mesodiagenesis is probably related to Jurassic times. Diagenetic chemical reactions suggest a maximum burial less than 1.5 km and low temperatures (<120ÂşC). Patterns of porosity reduction by compaction and cementation suggest four diagenetic stages: (1) Loss of primary porosity by early mechanical compaction; (2) early cementation (Kfeldspar and dolomite); (3) dissolution of cements; and (4) framework collapse by re-compaction. These stages are manifested by the presence of two types of sandstone. Type I sandstones present high intergranular volume (mean, 30%). Type II sandstones are characterized by high compactional porosity loss and exhibit low values of intergranular volume (mean, 16.9%). Type II sandstones are associated with the dissolution of cement and later re-compaction of type I sandstones. An intermediate telodiagenetic phase is deduced and related to the sharp unconformity between Lower Cretaceous sediments and the underlying sediments. This suggests that a mechanically unstable framework collapsed during the Cretaceous, generating type II sandstones. The analyzed diagenetic paths have a wide applicability on similar marginal areas of rift basins

    Interrogating open issues in cancer precision medicine with patient-derived xenografts

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    Patient-derived xenografts (PDXs) have emerged as an important platform to elucidate new treatments and biomarkers in oncology. PDX models are used to address clinically relevant questions, including the contribution of tumour heterogeneity to therapeutic responsiveness, the patterns of cancer evolutionary dynamics during tumour progression and under drug pressure, and the mechanisms of resistance to treatment. The ability of PDX models to predict clinical outcomes is being improved through mouse humanization strategies and the implementation of co-clinical trials, within which patients and PDXs reciprocally inform therapeutic decisions. This Opinion article discusses aspects of PDX modelling that are relevant to these questions and highlights the merits of shared PDX resources to advance cancer medicine from the perspective of EurOPDX, an international initiative devoted to PDX-based research.status: publishe

    Improvements in virological control among women conceiving on combination antiretroviral therapy in Western Europe

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    Among 396 HIV-infected women conceiving on combination antiretroviral therapy and enrolled in the European Collaborative Study in 2000-2011, the proportion with virological failure (>200 copies/ml after 65 24 weeks of treatment) declined substantially from 34% in 2000-2001 to 3% in 2010-2011. In adjusted analyses, younger women and those with at least two children were at increased risk of virological failure, highlighting the importance of close monitoring and adherence support

    Insufficient antiretroviral therapy in pregnancy: missed opportunities for prevention of mother-to- child transmission of HIV in Europe

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    BACKGROUND: Although mother-to-child transmission (MTCT) rates are at an all-time low in Western Europe, potentially preventable transmissions continue to occur. Duration of antenatal combination antiretroviral therapy (ART) is strongly associated with MTCT risk. METHODS: Data on pregnant HIV-infected women enrolled in the Western and Central European sites of the European Collaborative Study between January 2000 and July 2009 were analysed. The proportion of women receiving no antenatal ART or 1-13 days of treatment was investigated, and associated factors explored using logistic regression models. RESULTS: Of 2,148 women, 142 (7%) received no antenatal ART, decreasing from 8% in 2000-2003 to 5% in 2004-2009 (\u3c7(2)=8.73; P<0.01). A further 41 (2%) received 1-13 days of ART. One-third (64/171) of women with 'insufficient' (0 or 1-13 days) antenatal ART had a late HIV diagnosis (in the third trimester or intrapartum), but half (85/171) were diagnosed before conception. Pre-term delivery <34 weeks was associated with receipt of no and 1-13 days antenatal ART (adjusted odds ratios [ORs] 2.9 [P<0.01] and 4.5 [P<0.01], respectively). History of injecting drug use was associated with an increased risk of no ART (adjusted OR 2.9; P<0.01) and severe symptomatic HIV disease with a decreased risk (adjusted OR 0.2; P<0.01). MTCT rates were 1.1% (15/1,318) among women with 6514 days antenatal ART and 7.4% (10/136) among those with insufficient ART. CONCLUSIONS: Over the last 10 years, around one in 11 women in this study received insufficient antenatal ART, accounting for 40% of MTCTs. One-half of these women were diagnosed before conception, suggesting disengagement from care

    Interrogating open issues in cancer precision medicine with patient-derived xenografts

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    Patient-derived xenografts (PDXs) have emerged as an important platform to elucidate new treatments and biomarkers in oncology. PDX models are used to address clinically relevant questions, including the contribution of tumour heterogeneity to therapeutic responsiveness, the patterns of cancer evolutionary dynamics during tumour progression and under drug pressure, and the mechanisms of resistance to treatment. The ability of PDX models to predict clinical outcomes is being improved through mouse humanization strategies and the implementation of co-clinical trials, within which patients and PDXs reciprocally inform therapeutic decisions. This Opinion article discusses aspects of PDX modelling that are relevant to these questions and highlights the merits of shared PDX resources to advance cancer medicine from the perspective of EurOPDX, an international initiative devoted to PDX-based research
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