To report updated long-term efficacy and safety from the double-blind, placebo-controlled, phase 3 PRIMA/ENGOT-OV26/GOG-3012 study (NCT02655016).
Patients with newly diagnosed advanced ovarian cancer ...with complete or partial response (CR or PR) to first-line platinum-based chemotherapy received niraparib or placebo once daily (2:1 ratio). Stratification factors were best response to first-line chemotherapy regimen (CR/PR), receipt of neoadjuvant chemotherapy (yes/no), and homologous recombination deficiency (HRD) status (deficient HRd/proficient HRp or not determined). Updated (ad hoc) progression-free survival (PFS) data (as of November 17, 2021) by investigator assessment (INV) are reported.
In 733 randomised patients (niraparib, 487; placebo, 246), median PFS follow-up was 3.5years. Median INV-PFS was 24.5 versus 11.2months (hazard ratio, 0.52; 95% confidence interval CI, 0.40–0.68) in the HRd population and 13.8 versus 8.2months (hazard ratio, 0.66; 95% CI, 0.56–0.79) in the overall population for niraparib and placebo, respectively. In the HRp population, median INV-PFS was 8.4 versus 5.4months (hazard ratio, 0.65; 95% CI, 0.49–0.87), respectively. Results were concordant with the primary analysis. Niraparib-treated patients were more likely to be free of progression or death at 4years than placebo-treated patients (HRd, 38% versus 17%; overall, 24% versus 14%). The most common grade ≥ 3 treatment-emergent adverse events in niraparib patients were thrombocytopenia (39.7%), anaemia (31.6%), and neutropenia (21.3%). Myelodysplastic syndromes/acute myeloid leukaemia incidence rate (1.2%) was the same for niraparib- and placebo-treated patients. Overall survival remained immature.
Niraparib maintained clinically significant improvements in PFS with 3.5years of follow-up in patients with newly diagnosed advanced ovarian cancer at high risk of progression irrespective of HRD status. No new safety signals were identified.
•Updated long-term efficacy and safety data from PRIMA/ENGOT-OV26/GOG-3012 study.•Niraparib first-line maintenance therapy extended progression-free survival (PFS).•Durable PFS benefit observed in overall population and across biomarker subgroups.•The most common grade ≥ 3 adverse events in niraparib patients were haematologic.•No new safety signals were identified.
A Co nanolayer is used as a local probe to evaluate the vertical inhomogeneous distribution of the electromagnetic (EM) field within a resonant metallic nanodisk. Taking advantage of the direct ...relation between the magneto‐optical activity and the electromagnetic field intensity in the Co layer, it is shown that the nonuniform EM distribution within the nanodisk under plasmon resonant conditions has maximum values close to the upper and lower flat faces, and a minimum value in the middle.
Magnetoplasmonic Au/Co/Au nanodisks are fabricated by hole mask colloidal lithography, thermal evaporation, and sputtering with different positions of the Co layer in the vertical direction. The Magneto‐optical activity as a function of the Co layer position gives a direct picture of the internal electromagnetic field distribution within the nanodisk when the localized surface plasmon resonance is excited. Theoretical calculations confirm these experimental findings.
We study how the magneto-optical activity in polar configuration of continuous Au/Co/Au trilayers is affected by the excitation of localized plasmon resonances of an array of Au nanodiscs fabricated ...on top of them over a dielectric SiO(2) spacer. We show that the effect of the nanodiscs array is twofold. First, it optimizes the absorption of light at specific photon energies corresponding to the localized surface plasmon excitation of the array, modifying the reflectivity of the system (we define this effect as the purely optical contribution). Second, upon localized plasmon resonance excitation, the electromagnetic field in the whole system is redistributed, and an enhanced magneto-optical activity occurs at those energies where the electromagnetic field in the magnetic layer is increased (this effect is identified as the purely magneto-optical contribution of the nanodiscs array).
Road maintenance is crucial for ensuring safety and government compliance, but manual measurement methods can be time-consuming and hazardous. This work proposes an automated approach for road ...inventory using a deep learning model and a 3D point cloud acquired by a low-cost mobile mapping system. The road inventory includes the road width, number of lanes, individual lane widths, superelevation, and safety barrier height. The results are compared with a ground truth on a 1.5 km subset of road, showing an overall intersection-over-union score of 84% for point cloud segmentation and centimetric errors for road inventory parameters. The number of lanes is correctly estimated in 81% of cases. This proposed method offers a safer and more automated approach to road inventory tasks and can be extended to more complex objects and rules for road maintenance and digitalization. The proposed approach has the potential to pave the way for building digital models from as-built infrastructure acquired by mobile mapping systems, making the road inventory process more efficient and accurate.
Purpose
The alterations of the Subjective visual vertical test are related to vestibular pathology. Our previously validated method to distinguish between healthy and pathological individuals ...measures the deviation from the Subjective visual vertical using a mobile application installed on a smartphone fixed to a turntable anchored to the wall. The aim of this study was evaluating the intra-observer reliability of our method in individuals with or without vestibular pathology.
Methods
Participants were recruited consecutively. In each individual two measurements with an interval of 2 h were made. Both tests were performed by the same examiner. A total of 91 patients were included in this study, of which 25 were healthy and 66 diseased. Intra-observer reliability was evaluated using the intraclass correlation coefficient (ICC). To assess the clinical accuracy of the measurement, we calculated the standard error of the measurement (SEM) and the minimum detectable change (MDC) with a 95% confidence interval.
Results
Intra-observer reliability was excellent with an ICC 0.95 (0.92–0.97) in the whole sample, in healthy patients 0.91 (0.80–0.96) and in pathological patients 0.92 (0.87–0.95). The SEM was calculated to be 0.59 for the whole sample (0.26 in the “healthy” group, and 0.67 in the pathological group). Likewise, the sample’s MDC was 1.16, being 0.52 and 1.36 for the healthy and the pathological group, respectively.
Conclusions
Considering the results, our method presents an excellent intraobserver reliability. Furthermore, changes in deviation greater than 0.52 in healthy individuals and 1.36 in pathological individuals can be considered a real change in deviation.
Genetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical ...trials (CTs). Making this treatment available to our patients prompted us to develop a novel CART19 based on our own anti-CD19 antibody (A3B1), followed by CD8 hinge and transmembrane region, 4-1BB- and CD3z-signaling domains. We show that A3B1 CAR T cells are highly cytotoxic and specific against CD19+ cells
, inducing secretion of pro-inflammatory cytokines and CAR T cell proliferation.
, A3B1 CAR T cells are able to fully control disease progression in an NOD.Cg-
/SzJ (NSG) xenograph B-ALL mouse model. Based on the pre-clinical data, we conclude that our CART19 is clearly functional against CD19+ cells, to a level similar to other CAR19s currently being used in the clinic. Concurrently, we describe the implementation of our CAR T cell production system, using lentiviral vector and CliniMACS Prodigy, within a medium-sized academic institution. The results of the validation phase show our system is robust and reproducible, while maintaining a low cost that is affordable for academic institutions. Our model can serve as a paradigm for similar institutions, and it may help to make CAR T cell treatment available to all patients.
The last glacial period (LGP) promoted a loss of genetic diversity in Paleolithic populations of modern humans from diverse regions of the world by range contractions and habitat fragmentation. ...However, this period also provided some currently submersed lands, such as the Sunda shelf in Southeast Asia (SEA), that could have favored the expansion of our species. Concerning the latter, still little is known about the influence of the lowering sea level on the genetic diversity of current SEA populations. Here, we applied approximate Bayesian computation, based on extensive spatially explicit computer simulations, to evaluate the fitting of mtDNA data from diverse SEA populations with alternative evolutionary scenarios that consider and ignore the LGP and migration through long-distance dispersal (LDD). We found that both the LGP and migration through LDD should be taken into consideration to explain the currently observed genetic diversity in these populations and supported a rapid expansion of first populations throughout SEA. We also found that temporarily available lands caused by the low sea level of the LGP provided additional resources and migration corridors that favored genetic diversity. We conclude that migration through LDD and temporarily available lands during the LGP should be considered to properly understand and model the first expansions of modern humans.
Large-pore mesoporous silica supports with different structure and pore sizes distribution have been tested for glyoxyl multipoint covalent immobilization of Pectinex Ultra SP-L, a commercial ...preparation including the enzyme β-galactosidase from Aspergillus aculeatus. The prepared biocatalysts have been assayed in the production of galacto-oligosaccharides (GOS) from lactose as prebiotic functional food, aiming to optimize the yield to the GOS having the highest presumed prebiotic effect, tri- and tetra- GOS (high-GOS). Immobilization of β-galactosidase over glyoxyl-modified silica supports, with pores, large enough to accommodate the enzyme within their structure, led to an enhancement of the enzyme activity in terms of high-GOS production relative to the free enzyme under the same reaction conditions. Remarkably, such an improvement was achieved without previous purification of β-galactosidase from the commercial source. An enhancement of the transgalactosylation activity over the hydrolytic activity, due to the relatively hydrophobic nature of organically modified silica surface of the supports, led to an increase in the selectivity to high-GOS. The best biocatalyst in the series was that based in hexagonal ultra-large-pore SBA-15 (ULP-SBA-15), which presents the most adequate balance between confinement effect within its pore framework and transgalactosylation activity leading to a remarkable yield to high-GOS of 20.2% vs. 11.2% for the enzyme in free conditions. Furthermore, reusability of these silica-based biocatalysts in three consecutive 24 h reaction-cycles has been successfully performed at 50 °C, temperature that minimizes the thermal deactivation of the enzyme.
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•Large-pore mesoporous supports for covalent immobilization of β-galactosidase.•ULP-SBA-15 provides the best catalytic results.•Yield to high-GOS of 20.2% supported enzyme vs. 11.2% with the free enzyme.•Biocatalysts is reusable in three consecutive 24 h-reaction cycles.
Bioko is one of the few islands that exist around Africa, the most genetically diverse continent on the planet. The native Bantu-speaking inhabitants of Bioko, the Bubi, are believed to have ...colonized the island about 2000 years ago. Here, we sequenced the genome of thirteen Bubi individuals at high coverage and analysed their sequences in comparison to mainland populations from the Gulf of Guinea.
We found that, genetically, the closest mainland population to the Bubi are Bantu-speaking groups from Angola instead the geographically closer groups from Cameroon. The Bubi possess a lower proportion of rainforest hunter-gatherer (RHG) ancestry than most other Bantu-speaking groups. However, their RHG component most likely came from the same source and could have reached them by gene flow from the mainland after island settlement. By studying identity by descent (IBD) genomic blocks and runs of homozygosity (ROHs), we found evidence for a significant level of genetic isolation among the Bubi, isolation that can be attributed to the island effect. Additionally, as this population is known to have one of the highest malaria incidence rates in the world we analysed their genome for malaria-resistant alleles. However, we were unable to detect any specific selective sweeps related to this disease.
By describing their dispersal to the Atlantic islands, the genomic characterization of the Bubi contributes to the understanding of the margins of the massive Bantu migration that shaped all Sub-Saharan African populations.
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