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This article presents the results of CO 2 /brine two-phase flow experiments in rocks at reservoir conditions. X-ray CT scanning is used to determine CO 2 saturation at a fine scale with a resolution of a few pore volumes and provide 3D porosity and saturation maps that can be use to correlate CO 2 saturations and rock properties. The study highlights the strong influence of sub-core scale heterogeneities on the spatial distribution of CO 2 at steady state and provides useful relative permeability data on a sample originated from an actual storage site (CO2CRC-Otway project, Victoria, South-West Australia). Two different samples tested, although different in nature, present strong heterogeneities, but differ in the detail of the connectivity of high porosity layers. In both samples, the results of the investigations show that sub-core scale heterogeneities control the sweep efficiency and may cause channeling through the porous medium. In one of the samples, CO 2 saturation appears uncorrelated to porosity close to the outlet end of the core. This observation is understood as a result of the position and the orientation of high porosity layers with respect to the inlet face of the core. Finally, in the operating conditions of the two experiments, the saturation maps demonstrate that gravity does not play a major role since no detectable buoyancy driven flow is observed.

In this single-group, phase 2 study, the use of trastuzumab deruxtecan resulted in a response in 60% of women with HER2-positive advanced breast cancer who had received a median of six previous lines of therapy. The drug was associated with myelosuppression and gastrointestinal toxicity; interstitial lung disease was reported in 13.6% of the patients.

Background Benefit of early awake prone positioning for COVID-19 patients hospitalised in medical wards and who need oxygen therapy remains to be demonstrated. The question was considered at the time of COVID-19 pandemic to avoid overloading the intensive care units. We aimed to determine whether prone position plus usual care could reduce the rate of non-invasive ventilation (NIV) or intubation or death as compared to usual care alone. Methods In this multicentre randomised clinical trial, 268 patients were randomly assigned to awake prone position plus usual care ( N  = 135) or usual care alone ( N  = 132). The primary outcome was the proportion of patients who underwent NIV or intubation or died within 28 days. Main secondary outcomes included the rates of NIV, of intubation or death, within 28 days. Results Median time spent each day in the prone position within 72 h of randomisation was 90 min (IQR 30–133). The proportion of NIV or intubation or death within 28 days was 14.1% (19/135) in the prone position group and 12.9% (17/132) in the usual care group [odds ratio adjusted for stratification (aOR) 0.43; 95% confidence interval (CI) 0.14–1.35]. The probability of intubation, or intubation or death (secondary outcomes) was lower in the prone position group than in the usual care group (aOR 0.11; 95% CI 0.01–0.89 and aOR 0.09; 95% CI 0.01–0.76, respectively) in the whole study population and in the prespecified subgroup of patients with SpO 2  ≥ 95% on inclusion (aOR 0.11; 95% CI 0.01–0.90, and aOR 0.09; 95% CI 0.03–0.27, respectively). Conclusions Awake prone position plus usual care in COVID-19 patients in medical wards did not decrease the composite outcome of need for NIV or intubation or death. Trial registration ClinicalTrials.gov Identifier: NCT04363463 . Registered 27 April 2020.

Background The initial management of patients with sarcoma is a critical issue. We used the nationwide French National Cancer Institute -funded prospective sarcoma database NETSARC to report the management and oncologic outcomes in adolescents and young adults (AYAs) patients with sarcoma at the national level. Patients and methods NETSARC database gathers regularly monitored and updated data from patients with sarcoma. NETSARC was queried for patients (15–30 years) with sarcoma diagnosed from 2010 to 2017 for whom tumor resection had been performed. We reported management, locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) in AYA treated in French reference sarcoma centers (RSC) and outside RSC (non-RSC) and conducted multivariable survival analyses adjusted for classical prognostic factors. Results Among 3,227 patients aged 15–30 years with sarcoma diagnosed between 2010 and 2017, the study included 2,227 patients with surgery data available, among whom 1,290 AYAs had been operated in RSC, and 937 AYAs in non-RSC. Significant differences in compliance to guidelines were observed including pre-treatment biopsy (RSC: 85.9%; non-RSC 48.1%), pre-treatment imaging (RSC: 86.8%; non-RSC: 56.5%) and R0 margins (RSC 57.6%; non-RSC: 20.2%) ( p  < 0.001). 3y-OS rates were 81.1% (95%CI 78.3–83.6) in AYA in RSC and 82.7% (95%CI 79.4–85.5) in AYA in non-RSC, respectively. Whereas no significant differences in OS was observed in AYAs treated in RSC and in non-RSC, LRFS and PFS were improved in AYAs treated in RSC compared to AYAs treated in non-RSC (Hazard Ratios (HR): 0.58 and 0.83, respectively). Conclusions This study highlights the importance for AYA patients with sarcoma to be managed in national sarcoma reference centers involving multidisciplinary medical teams with paediatric and adult oncologists.

Two drugs with novel mechanisms of action, the diarylquinoline bedaquiline and the nitroimidazole delamanid—as well as pretomanid from the same class of drugs as delamanid—have recently become available to treat drug-resistant tuberculosis (DR-TB) after many decades of little innovation in the field of DR-TB treatment. Despite evidence of improved efficacy and reduced toxicity of multidrug regimens including the two agents, access to bedaquiline and delamanid has been limited in many settings with a high burden of DR-TB and consistently poor treatment outcomes. Aside from regulatory, logistic and cost barriers at country level, uptake of the novel agents was complicated by gaps in knowledge for optimal use in clinical practice after initial market approval. The main incentives of the current pharmaceutical research and development paradigm are structured around obtaining regulatory approval, which in turn requires efficacy and safety data generated by clinical trials. Recently completed and ongoing clinical trials did not answer critical questions of how to provide shorter, less toxic treatment DR-TB treatment regimens containing bedaquiline and delamanid and improve patient outcomes. Voluntary generation of evidence that is not part of this process—yet essential from a clinical or policy perspective—has been left to non-sponsor partners and researchers, often without collaborative efforts to improve post-regulatory approval access to life-saving drugs. Additionally, these efforts are currently not recognised in the value chain of the research and development process, and there are no incentives to make this critical research happen in a coordinated way.

With the approval of new therapies targeting the PI3K pathway, the detection of PIK3CA mutations has become a key factor in treatment management for HR+/HER2− metastatic breast cancer (MBC). We developed multiplex digital PCR (dPCR) assays to detect and quantify PIK3CA mutations. A first screening assay allows the detection of 21 mutations, with a drop-off system targeting the 542–546 hotspot mutations combined with the simultaneous detection of N345K, C420R, H1047L and H1047R mutations. In the case of a positive result, a sequential strategy based on other assays that we have developped allows for precise mutation identification. Clinical validity was determined by analyzing plasma circulating free DNA (cfDNA) from 213 HR+/HER2− MBC samples, as well as DNA extracted from 97 available matched tumors from 89 patients. Our assays have shown reliable specificity, accuracy and reproducibility, with limits of blank of three and four droplets for the screening assay. Sixty-eight patients (32%) had at least one PIK3CA mutation detectable in their plasma, and we obtained 83.1% agreement between the cfDNA analysis and the corresponding tumors. The high sensitivity and robustness of these new dPCR assays make them well-suited for rapid and cost-effective detection of PIK3CA mutations in the plasma of MBC patients.

Erb‐b2 receptor tyrosine kinase 2 (ERBB2)‐activating mutations are therapeutically actionable alterations found in various cancers, including metastatic breast cancer (MBC). We developed multiplex digital PCR assays to detect and quantify ERBB2 mutations in circulating tumor DNA from liquid biopsies. We studied the plasma from 272 patients with hormone‐receptor‐positive, human epidermal growth factor receptor 2‐negative (HR+/HER2−) MBC to detect 17 ERBB2 mutations using a screening assay. The assay was developed on the three‐color Crystal dPCR™ naica® platform with a two‐step strategy for precise mutation identification. We found that nine patients (3.3%) harbored at least one ERBB2 mutation. The mutation rate was higher in patients with lobular histology (5.9%) compared to invasive breast carcinoma of no special type (2.6%). A total of 12 mutations were found with the following frequencies: L755S (25.00%), V777L (25.00%), S310Y (16.67%), L869R (16.67%), S310F (8.33%), and D769H (8.33%). Matched tumor samples from six patients identified the same mutations with an 83% concordance rate. In summary, our highly sensitive multiplex digital PCR assays are well suited for plasma‐based monitoring of ERBB2 mutational status in patients with MBC. Erb‐b2 receptor tyrosine kinase 2 (ERBB2)‐activating mutations are therapeutically actionable alterations found in various cancers, including metastatic breast cancer (MBC). We developed highly sensitive multiplex digital PCR assays to detect and quantify ERBB2 mutations in circulating tumor DNA from liquid biopsies and found mutations in 3.3% of 272 patients with hormone‐receptor‐positive, human epidermal growth factor receptor 2‐negative (HR+/HER2−) MBC.

A proton-exchange membrane fuel cell (PEMFC) constitutes today one of the preferred technologies to promote hydrogen-based alternative energies. However, the large-scale deployment of PEMFCs is still hampered by insufficient durability and reliability. In particular, the degradation of the polyelectrolyte membrane, caused by harsh mechanical and chemical stresses experienced during fuel cell operation, has been identified as one of the main factors restricting the PEMFC lifetime. An innovative chemical-mechanical ex situ aging device was developed to simultaneously expose the membrane to mechanical fatigue and an oxidizing environment (i.e., free radicals) in order to reproduce conditions close to those encountered in fuel cell systems. A cyclic compressive stress of 5 or 10 MPa was applied during several hours while a degrading solution (H2O2 or a Fenton solution) was circulated in contact with the membrane. The results demonstrated that both composite Nafion™ XL and non-reinforced Nafion™ NR211 membranes are significantly degraded by the conjoint mechanical and chemical stress exposure. The fluoride emission rate (FER) was generally slightly lower with XL than with NR211, which could be attributed to the degradation mitigation strategies developed for composite XL, except when the pressure level or the aging duration were increased, suggesting a limitation of the improved durability of XL.

Background CIC‐rearranged sarcomas (CIC‐RS) represent the most frequent subset of “Ewing‐like” undifferentiated small round cell sarcomas. These tumors tend to be more aggressive than Ewing sarcomas. Moreover, treatment strategy can differ according to teams. The primary aim of this retrospective study was to describe the characteristics, treatments, and outcome for patients with CIC‐RS included in the French NETSARC+ database. Methods Pediatric and adult patients from 13 French centers with a diagnosis of CIC‐RS were registered from October 2008 to March 2021. Patients and tumors characteristics were collected from the national network NETSARC+ database (http://netsarc.sarcomabcb.org). CIC‐RS diagnosis was pathologically and molecularly confirmed with a central review by expert pathologists. Two groups of patients were studied: those treated as classical Ewing sarcomas (cohort EwS) and those treated as high‐grade soft tissue sarcomas (cohort STS) according to ESMO and/or EpSSG guidelines. Survival was calculated using the Kaplan–Meier method and the log‐rank test was used to compare survival. Results Among 79 patients, the male/female sex ratio was 0.7 and the median age at diagnosis was 27 years (range 2–87). With a median follow‐up of 37 months, 39 patients died of the disease. Median overall survival from diagnosis was 18 months, with no significant difference between both cohorts (p = 0.9). Nevertheless, when focusing on patients with metastatic disease at diagnosis (N = 21), all patients from cohort STS died of disease while some patients from cohort EwS were still alive and in complete remission. Conclusion FSG experience confirms the aggressive clinical course of CDS patients regardless of chemotherapy regimen. Two groups characterized by different patterns of care were evaluated in our study. On one hand (cohort 1), patients were treated as Ewing sarcomas, and on the other hand (cohort 2), patients were treated as high‐grade soft tissue sarcomas. Overall, the prognosis was poor and there were no statistical differences in overall survival and relapse‐free survival between the two groups. Nevertheless, a significant proportion of patients with metastatic CDS from cohort 1 achieved very long‐term survival and might be cured.

[...]the WHO has adopted coverage targets for diabetes, which include “100% of people with type 1 diabetes have access to affordable insulin and blood glucose self-monitoring”.11 In assessing availability, the WHO’s Global NCD Action Plan includes both the public and private sectors, providing a ‘holistic’ view as differences in availability in public and private sectors have been shown to vary in different contexts.6 The new global coverage target has the added challenge of measuring the availability and affordability of both insulin, delivery devices and self-monitoring equipment. WHO proposes to measure availability both with facility surveys and population survey data and affordability based on the lowest paid government worker (less than or equal to 1 day’s wage) from different national sources.12 This is similar to the definition proposed by the WHO and Health Action International: “the number of days the lowest paid unskilled government worker would have to work to afford the cost of 30 days of treatment for the chronic condition being analysed”.13 A way forward? Challenges include the burden of data collection and availability of data to monitor these targets. Despite the focus on monitoring availability at facilities,17 the main aim of such measures is to ensure availability for the individual, meaning data collection might need to be done at household levels.