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Background Diagnosis performances of case-identifying algorithms developed in healthcare database are usually assessed by comparing identified cases with an external data source. When this is not feasible, intra-database validation can present an appropriate alternative. Objectives To illustrate through two practical examples how to perform intra-database validations of case-identifying algorithms using reconstituted Electronic Health Records (rEHRs). Methods Patients with 1) multiple sclerosis (MS) relapses and 2) metastatic castration-resistant prostate cancer (mCRPC) were identified in the French nationwide healthcare database (SNDS) using two case-identifying algorithms. A validation study was then conducted to estimate diagnostic performances of these algorithms through the calculation of their positive predictive value (PPV) and negative predictive value (NPV). To that end, anonymized rEHRs were generated based on the overall information captured in the SNDS over time (e.g. procedure, hospital stays, drug dispensing, medical visits) for a random selection of patients identified as cases or non-cases according to the predefined algorithms. For each disease, an independent validation committee reviewed the rEHRs of 100 cases and 100 non-cases in order to adjudicate on the status of the selected patients (true case/ true non-case), blinded with respect to the result of the corresponding algorithm. Results Algorithm for relapses identification in MS showed a 95% PPV and 100% NPV. Algorithm for mCRPC identification showed a 97% PPV and 99% NPV. Conclusion The use of rEHRs to conduct an intra-database validation appears to be a valuable tool to estimate the performances of a case-identifying algorithm and assess its validity, in the absence of alternative.

Introduction Surgery is the standard of care for eligible patients with localized or stage IIIA locally advanced non-small cell lung cancer (NSCLC) current guidelines recommend the most conservative surgeries possible. The aim of this study was to bring new real-world data on resected NSCLC epidemiology, management, and survival outcomes in patients with resected non-metastatic NSCLC. Materials and methods This is a descriptive, non-interventional, national, retrospective claims study using data from the French National Hospitalization Database (PMSI) describing the management of patients with non-metastatic NSCLC who underwent a first lung resection (LR) between 2015 and 2019. Patients with LR performed in 2015 were followed from LR until the last registered hospital care or in-hospital death. Five-year disease-free survival (DFS [i.e., time from LR to first recurrence or death]) and overall survival (OS) were assessed. Results The rate of patients with non-metastatic NSCLC and a first LR between 2015 and 2019 increased by an average of 4.5% per year (8,688 in 2015 vs. 10,330 in 2019). Lobectomy (79.8% vs. 84.9%) and video-assisted thoracoscopic surgery (29.6% vs. 46.4%) became more frequent. Five-year DFS was 33.7% [95%CI 29.8-37.6%] following infralobar resection, 52.3% [51.0-53.5%] after lobectomy, 42.3% [36.9-47.5%] after bilobectomy, and 33.6% [30.0-37.2%] after pneumonectomy. Respective five-year OS from LR were 58.4% [54.1–62.4], 70.2% [69.0-71.3], 59.3% [53.7–64.4], and 46.3% [42.3–50.2]. Conclusions This study highlights the increasing trend toward conservative and less invasive surgeries in resected NSCLC. Type of LR can be used as an indirect marker of disease expansion, with poorer survival outcomes in case of extensive surgeries.

PurposeTo describe the incidence, management, and survival outcomes of patients with muscle-invasive urothelial carcinoma (MIUC) undergoing radical surgery (RS) in France.MethodsWe relied on a non-interventional real-world retrospective study based on French National Hospitalization Database. Adults with MIUC with a first RS between 2015 and 2020 were selected. Subpopulations of patients with RS performed in 2015 and 2019 (pre-COVID-19) were extracted, according to cancer site: muscle-invasive bladder cancer (MIBC) or upper tract urothelial carcinoma (UTUC). Disease-free and overall survival (DFS, OS – Kaplan–Meier) were assessed on the 2015 subpopulation.ResultsBetween 2015 and 2020, 21,295 MIUC patients underwent a first RS. Of them, 68.9% had MIBC, 28.9% UTUC, and 2.2% both cancers. Apart from fewer men among UTUC (70.2%) than MIBC patients (90.1%), patients’ demographic (mean age ~ 73 years) and clinical characteristics were similar whatever the cancer site or year of first RS. In 2019, RS alone was the most frequent treatment, occurring in 72.3% and 92.6% in MIBC and UTUC, respectively. Between 2015 and 2019, neoadjuvant use rate increased from 13.8% to 22.2% in MIBC, and adjuvant use rate increased from 3.7% to 6.3% in UTUC. Finally, median [95% confidence interval] DFS times were 16.0 [14.0–18.0] and 27.0 [23.0–32.0] months among MIBC and UTUC, respectively.ConclusionAmong patients with resected MIUC annually, RS alone remained the main treatment. Neoadjuvant and adjuvant use increased between 2015 and 2019. Nonetheless, MIUC remains of poor prognosis, highlighting an unmet medical need, notably among patients at high risk of recurrence.

Background: Diagnosis performances of case-identifying algorithms developed in healthcare database are usually assessed by comparing identified cases with an external data source. When this is not feasible, intra-database validation can present an appropriate alternative. Objectives: To illustrate through two practical examples how to perform intra-database validations of case-identifying algorithms using reconstituted Electronic Health Records (rEHRs). Methods: Patients with 1) multiple sclerosis (MS) relapses and 2) metastatic castration-resistant prostate cancer (mCRPC) were identified in the French nationwide healthcare database (SNDS) using two case-identifying algorithms. A validation study was then conduct to estimate diagnostic performances of these algorithms through the calculation of their positive predictive value (PPV) and negative predictive value (NPV). To that end, anonymized rEHRs were generated based on the overall information captured in the SNDS over time (e.g. procedure, hospital stays, drug dispensing, medical visits) for a random selection of patients identified as cases or non-cases according to the predefined algorithms. For each diseases, an independent validation committee reviewed the rEHRs of 100 cases and 100 non-cases in order to adjudicate on the status of the selected patients (true case/ true non-case), blinded with respect to the result of the corresponding algorithm. Results: Algorithm for relapses identification in MS showed a 95% PPV and 100% NPV and for mCRPC identification, a 97% PPV and 99% NPV. Conclusion: The use of rEHRs to conduct an intra-database validation appears to be a valuable tool to estimate the performances of a case-identifying algorithm and assess its validity, in the absence of alternative.

Environmentally transformative human use of land accelerated with the emergence of agriculture, but the extent, trajectory, and implications of these early changes are not well understood. An empirical global assessment of land use from 10,000 years before the present (yr B.P.) to 1850 CE reveals a planet largely transformed by hunter-gatherers, farmers, and pastoralists by 3000 years ago, considerably earlier than the dates in the land-use reconstructions commonly used by Earth scientists. Synthesis of knowledge contributed by more than 250 archaeologists highlighted gaps in archaeological expertise and data quality, which peaked for 2000 yr B.P. and in traditionally studied and wealthier regions. Archaeological reconstruction of global land-use history illuminates the deep roots of Earth’s transformation and challenges the emerging Anthropocene paradigm that large-scale anthropogenic global environmental change is mostly a recent phenomenon.

Allo-HSCT with CCR5Δ32/Δ32 donor cells is the only curative HIV-1 intervention. We investigated the impact of allo-HSCT on the viral reservoir in PBMCs and post-mortem tissue in two patients. IciS-05 and IciS-11 both received a CCR5Δ32/Δ32 allo-HSCT. Before allo-HSCT, ultrasensitive HIV-1 RNA quantification; HIV-1-DNA quantification; co-receptor tropism analysis; deep-sequencing and viral characterization in PBMCs and bone marrow; and post-allo-HSCT, ultrasensitive RNA and HIV-1-DNA quantification were performed. Proviral quantification, deep sequencing, and viral characterization were done in post-mortem tissue samples. Both patients harbored subtype B CCR5-tropic HIV-1 as determined genotypically and functionally by virus culture. Pre-allo-HSCT, HIV-1-DNA could be detected in both patients in bone marrow, PBMCs, and T-cell subsets. Chimerism correlated with detectable HIV-1-DNA LTR copies in cells and tissues. Post-mortem analysis of IciS-05 revealed proviral DNA in all tissue biopsies, but not in PBMCs. In patient IciS-11, who was transplanted twice, no HIV-1-DNA could be detected in PBMCs at the time of death, whereas HIV-1-DNA was detectable in the lymph node. In conclusion, shortly after CCR5Δ32/Δ32, allo-HSCT HIV-1-DNA became undetectable in PBMCs. However, HIV-1-DNA variants identical to those present before transplantation persisted in post-mortem-obtained tissues, indicating that these tissues play an important role as viral reservoirs.

Due to the difficulty in dispersing some engineered nanomaterials in exposure media, realizing homogeneous distributions of nanoparticles (NP) in soil may pose major challenges. The present study investigated the distribution of zinc oxide (ZnO) NP (30 nm) and non-nano ZnO (200 nm) in natural soil using two different spiking procedures, i.e. as dry powder and as suspension in soil extract. Both spiking procedures showed a good recovery (>85 %) of zinc and based on total zinc concentrations no difference was found between the two spiking methods. Both spiking procedures resulted in a fairly homogeneous distribution of the ZnO particles in soil, as evidenced by the low variation in total zinc concentration between replicate samples (<12 % in most cases). Survival of Folsomia candida in soil spiked at concentrations up to 6,400 mg Zn kg −1 d.w. was not affected for both compounds. Reproduction was reduced in a concentration-dependent manner with EC50 values of 3,159 and 2,914 mg Zn kg −1 d.w. for 30 and 200 nm ZnO spiked as dry powder and 3,593 and 5,633 mg Zn kg −1 d.w. introduced as suspension. Toxicity of ZnO at 30 and 200 nm did not differ. We conclude that the ZnO particle toxicity is not size related and that the spiking of the soil with ZnO as dry powder or as a suspension in soil extract does not affect its toxicity to F. candida .

The long-term fate of uranium-contaminated sediments, especially downstream former mining areas, is a widespread environmental challenge. Essential for their management is the proper understanding of uranium (U) immobilization mechanisms in reducing environments. In particular, the long-term behavior of noncrystalline U(IV) species and their possible evolution to more stable phases in subsurface conditions is poorly documented, which limits our ability to predict U long-term geochemical reactivity. Here, we report direct evidence for the evolution of U speciation over 3,300 y in naturally highly U-enriched sediments (350–760 μg · g−1 U) from Lake Nègre (Mercantour Massif, Mediterranean Alps, France) by combining U isotopic data (δ238U and (234U/238U)) with U L₃-edge X-ray absorption fine structure spectroscopy. Constant isotopic ratios over the entire sediment core indicate stable U sources and accumulation modes, allowing for determination of the impact of aging on U speciation. We demonstrate that, after sediment deposition, mononuclear U(IV) species associated with organic matter transformed into authigenic polymeric U(IV)–silica species that might have partially converted to a nanocrystalline coffinite (UIVSiO₄·nH₂O)-like phase. This diagenetic transformation occurred in less than 700 y and is consistent with the high silica availability of sediments in which diatoms are abundant. It also yields consistency with laboratory studies that proposed the formation of colloidal polynuclear U(IV)–silica species, as precursors for coffinite formation. However, the incomplete transformation observed here only slightly reduces the potential lability of U, which could have important implications to evaluate the longterm management of U-contaminated sediments and, by extension, of U-bearing wastes in silica-rich subsurface environments.

The long-term fate of uranium-contaminated sediments, especially downstream former mining areas, is a widespread environmental challenge. Essential for their management is the proper understanding of uranium (U) immobilization mechanisms in reducing environments. In particular, the long-term behavior of noncrystalline U(IV) species and their possible evolution to more stable phases in subsurface conditions is poorly documented, which limits our ability to predict U long-term geochemical reactivity. Here, we report direct evidence for the evolution of U speciation over 3,300 y in naturally highly U-enriched sediments (350–760 µg ⋅ g −1 U) from Lake Nègre (Mercantour Massif, Mediterranean Alps, France) by combining U isotopic data (δ 238 U and ( 234 U/ 238 U)) with U L 3 -edge X-ray absorption fine structure spectroscopy. Constant isotopic ratios over the entire sediment core indicate stable U sources and accumulation modes, allowing for determination of the impact of aging on U speciation. We demonstrate that, after sediment deposition, mononuclear U(IV) species associated with organic matter transformed into authigenic polymeric U(IV)–silica species that might have partially converted to a nanocrystalline coffinite (U IV SiO 4 · n H 2 O)-like phase. This diagenetic transformation occurred in less than 700 y and is consistent with the high silica availability of sediments in which diatoms are abundant. It also yields consistency with laboratory studies that proposed the formation of colloidal polynuclear U(IV)–silica species, as precursors for coffinite formation. However, the incomplete transformation observed here only slightly reduces the potential lability of U, which could have important implications to evaluate the long-term management of U-contaminated sediments and, by extension, of U-bearing wastes in silica-rich subsurface environments.

Larger volumes of sea ice have been thawing in the Central Arctic Ocean (CAO) during the last decades than during the past 800,000 years. Brackish brine (fed by meltwater inside the ice) is an expanding sympagic habitat in summer all over the CAO. We report for the first time the structure of bacterial communities in this brine. They are composed of psychrophilic extremophiles, many of them related to phylotypes known from Arctic and Antarctic regions. Community structure displayed strong habitat segregation between brackish ice brine (IB; salinity 2.4–9.6) and immediate sub-ice seawater (SW; salinity 33.3–34.9), expressed at all taxonomic levels (class to genus), by dominant phylotypes as well as by the rare biosphere, and with specialists dominating IB and generalists SW. The dominant phylotypes in IB were related to Candidatus Aquiluna and Flavobacterium , those in SW to Balneatrix and ZD0405, and those shared between the habitats to Halomonas , Polaribacter and Shewanella . A meta-analysis for the oligotrophic CAO showed a pattern with Flavobacteriia dominating in melt ponds, Flavobacteriia and Gammaproteobacteria in solid ice cores, Flavobacteriia, Gamma- and Betaproteobacteria, and Actinobacteria in brine, and Alphaproteobacteria in SW. Based on our results, we expect that the roles of Actinobacteria and Betaproteobacteria in the CAO will increase with global warming owing to the increased production of meltwater in summer. IB contained three times more phylotypes than SW and may act as an insurance reservoir for bacterial diversity that can act as a recruitment base when environmental conditions change.