Multivariate dynamic model for ordinal outcomes

Individual or stand-level biomass is not easy to measure. The current methods employed, based on cutting down a representative sample of plantations, make it possible to assess the biomasses for various compartments (bark, dead branches, leaves, . . .). However, this felling makes individual longitudinal follow-up impossible. In this context, we propose a method to evaluate individual biomasses by compartments when these biomasses are taken as ordinals. Biomass is measured visually and observations are therefore not destructive. The technique is based on a probit model redefined in terms of latent variables. A generalization of the univariate case to the multivariate case is then natural and takes into account the dependency between compartment biomasses. These models are then extended to the longitudinal case by developing a Dynamic Multivariate Ordinal Probit Model. The performance of the MCMC algorithm used for the estimation is illustrated by means of simulations built from known biomass models. The quality of the estimates and the impact of certain parameters, are then discussed

Health-Related Quality of Life with Pembrolizumab in Patients with Locally Advanced or Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: KEYNOTE-629

Advanced squamous cell carcinoma; Immunotherapy; PembrolizumabCarcinoma de cèl·lules escamoses avançat; Immunoteràpia; PembrolizumabCarcinoma de células escamosas avanzado; Inmunoterapia; PembrolizumabIntroduction At first interim analysis of KEYNOTE-629, health-related quality of life (HRQoL) with pembrolizumab was stable or improved over 48 weeks in recurrent or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC). HRQoL results from the second interim analysis in R/M or locally advanced (LA) cSCC are presented. Methods Patients received pembrolizumab 200 mg every 3 weeks for ≤ 2 years. Change in EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EQ-5D-5L scores were exploratory end points. Primary analysis was performed at week 12 to ensure adequate completion/compliance. Descriptive analyses were also conducted through weeks 48 and 75 for the LA and R/M cohorts, respectively. Results At data cutoff (29 July 2020), mean scores in the LA cohort (n = 47) were stable from baseline to week 12 for EORTC QLQ-C30 global health status (GHS)/quality of life (QoL) (−0.27 points [95% confidence interval (CI) −10.93 to 10.39]), physical functioning (−1.29 points [95% CI  −8.77 to 6.19]), and EQ-5D-5L visual analog scale (2.06 [95% CI −7.70 to 11.82]). HRQoL remained stable through week 48 in the LA cohort; 76.6% and 74.5% of patients had improved or stable GHS/QoL and physical functioning scores, respectively. HRQoL continued to show stability or improvement through week 75 in the R/M cohort (n = 99); 71.7% and 64.6% of patients had improved or stable GHS/QoL and physical functioning scores, respectively. Conclusions Pembrolizumab has demonstrated antitumor activity and manageable safety. The current analysis shows pembrolizumab treatment preserved HRQoL. Collectively, these results support pembrolizumab as standard of care for LA or R/M cSCC. Trial Registration ClinicalTrials.gov, NCT03284424—September 15, 2017.Funding for this research and the journal’s Rapid Service Fee was provided by Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA

Photodynamic therapy for actinic keratosis: Is the European consensus protocol for daylight PDT superior to conventional protocol for Aktilite CL 128 PDT?

International audienceBackground: Topical photodynamic therapy (PDT) is an established treatment modality for various dermato-oncologic conditions. In Europe, initially requiring irradiation with red light, PDT of actinic keratosis (AK) can now also be carried out with exposure to daylight that has been clinically proven to be as effective as and less painful than red light. Objectives: In this paper, we propose a comparison between the conventional protocol for Aktilite CL 128 (red light source) PDT and the European consensus protocol for daylight PDT — with the exposure is assumed to be performed during either a clear sunny day or an overcast day — in the treatment of AK with methyl aminolevulinate through a mathematical modeling. Method: This already published modeling that is based on an iterative procedure alternating determination of the local fluence rate and updating of the local optical properties enables to estimate the local damage induced by the therapy. Results: The European consensus protocol for daylight PDT during a sunny day and an overcast day provides, on average, 6.50 and 1.79 times higher PDT local damages at the end 2 of the treatment than those obtained using the conventional protocol for Aktilite CL 128 PDT, respectively. Conclusions: Results analysis shows that, even performed during an overcast day, the European consensus protocol for daylight PDT leads to higher PDT local damages than the efficient conventional protocol for Aktilite CL 128

Antitumour activity of pembrolizumab in advanced mucosal melanoma: a post-hoc analysis of KEYNOTE-001, 002, 006.

BackgroundMucosal melanoma is an aggressive melanoma with poor prognosis. We assessed efficacy of pembrolizumab in patients with advanced mucosal melanoma in KEYNOTE-001 (NCT01295827), -002 (NCT01704287), and -006 (NCT01866319).MethodsPatients received pembrolizumab 2 mg/kg every 3 weeks (Q3W) or 10 mg/kg Q2W or Q3W. Response was assessed by independent central review per RECIST v1.1.Results1567 patients were treated and 84 (5%) had mucosal melanoma. Fifty-one of 84 were ipilimumab-naive. In patients with mucosal melanoma, the objective response rate (ORR) was 19% (95% CI 11-29%), with median duration of response (DOR) of 27.6 months (range 1.1 + to 27.6). Median progression-free survival (PFS) was 2.8 months (95% CI 2.7-2.8), with median overall survival (OS) of 11.3 months (7.7-16.6). ORR was 22% (95% CI 11-35%) and 15% (95% CI 5-32%) in ipilimumab-naive and ipilimumab-treated patients.ConclusionPembrolizumab provides durable antitumour activity in patients with advanced mucosal melanoma regardless of prior ipilimumab

Controling the coupling properties of active ultrahigh-Q WGM microcavities from undercoupling to selective amplification

International audienceUltrahigh-quality (Q) factor microresonators have a lot of applications in the photonics domain ranging from low-threshold nonlinear optics to integrated optical sensors. Glass-based whispering gallery mode (WGM) microresonators are easy to produce by melting techniques, however they suffer from surface contamination which limits their long-term quality factor to a few 10^8 . Here we show that an optical gain provided by erbium ions can compensate for residual losses. Moreover it is possible to control the coupling regime of an ultrahigh Q-factor three port microresonator from undercoupling to spectral selective amplification by changing the pumping rate. The optical characterization method is based on frequency-swept cavity-ring-down- pectroscopy. This method allows the transmission and dispersive properties of perfectly transparent microresonators and intrinsic finesses up to 4.0x10^7 to be measured. Finally we characterize a critically coupled fluoride glass WGM microresonator with a diameter of 220 mm and a loaded Q-factor of 5.3x10^9 is demonstrated

Comparison of 10 efficient protocols for photodynamic therapy of actinic keratosis: How relevant are effective light dose and local damage in predicting the complete response rate at 3 months?

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Modeling Surface Currents in the Eastern Levantine Mediterranean

International audienceWe consider the problem of reconstructing the meso-scale features of the currents in the Eastern Levantine Mediterranean from combining in-situ and satellite altimetry data. Mathematically, this is an inverse problem where the objective is to invert Lagrangian trajectories, which are positions of drifters launched at sea, in order to improve the coarse Eulerian velocity, provided by the altimetric satellite measurements. We shall use a variational assimilation approach, whereby the eulerian velocity correction is obtained by minimizing the distance between the simulated position from a velocity background and actual observations. One important property of our approach is that it is model free, so that it is inexpensive and can be easily cast into real-time oceanic operational products. Our method is first validated with twin experiments, where we conduct sensitivity analysis to parameters such as number of drifters, assimilation time window and spatial filter length. The approach is next validated with past and present data from the Levantine Mediterranean by correcting velocity fields derived from altimetry by assimilating drifters' data. The drifters' data used here were collected in the context of the MedSVP program and more recently by the National Lebanese Marine Center (CNSM) in September 2013. The CNSM with its boat CANA has developed an important activity of data collection along the Lebanese coast so far and this activity will permit it to extend its collaborations further by integrating the modeling and data assimilation methods for reconstructing the surface currents

Evidence that a common arbuscular mycorrhizal network alleviates phosphate shortage in interconnected walnut sapling and maize plants

Under agroforestry practices, inter-specific facilitation between tree rows and cultivated alleys occurs when plants increase the growth of their neighbors especially under nutrient limitation. Owing to a coarse root architecture limiting soil inorganic phosphate (Pi) uptake, walnut trees (Juglans spp.) exhibit dependency on soil-borne symbiotic arbuscular mycorrhizal fungi that extend extra-radical hyphae beyond the root Pi depletion zone. To investigate the benefits of mycorrhizal walnuts in alley cropping, we experimentally simulated an agroforestry system in which walnut rootstocks RX1 (J. regia x J. microcarpa) were connected or not by a common mycelial network (CMN) to maize plants grown under two contrasting Pi levels. Mycorrhizal colonization parameters showed that the inoculum reservoir formed by inoculated walnut donor saplings allowed the mycorrhization of maize recipient roots. Relative to non-mycorrhizal plants and whatever the Pi supply, CMN enabled walnut saplings to access maize Pi fertilization residues according to significant increases in biomass, stem diameter, and expression of JrPHT1;1 and JrPHT1;2, two mycorrhiza-inducible phosphate transporter candidates here identified by phylogenic inference of orthologs. In the lowest Pi supply, stem height, leaf Pi concentration, and biomass of RX1 were significantly higher than in non-mycorrhizal controls, showing that mycorrhizal connections between walnut and maize roots alleviated Pi deficiency in the mycorrhizal RX1 donor plant. Under Pi limitation, maize recipient plants also benefited from mycorrhization relative to controls, as inferred from larger stem diameter and height, biomass, leaf number, N content, and Pi concentration. Mycorrhization-induced Pi uptake generated a higher carbon cost for donor walnut plants than for maize plants by increasing walnut plant photosynthesis to provide the AM fungus with carbon assimilate. Here, we show that CMN alleviates Pi deficiency in co-cultivated walnut and maize plants, and may therefore contribute to limit the use of chemical P fertilizers in agroforestry systems

Submillimetre surveys: The prospects for Herschel

Using the observed submillimetre source counts, from 250-1200 microns (including the most recent 250, 350 and 500 micron counts from BLAST), we present a model capable of reproducing these results, which is used as a basis to make predictions for upcoming surveys with the SPIRE instrument aboard the Herschel Space Observatory. The model successfully fits both the integral and differential source counts of submillimetre galaxies in all wavebands, predicting that while ultra-luminous infrared galaxies dominate at the brightest flux densities, the bulk of the infrared background is due to the less luminous infrared galaxy population. The model also predicts confusion limits and contributions to the cosmic infrared background that are consistent with the BLAST results. Applying this to SPIRE gives predicted source confusion limits of 19.4, 20.5 and 16.1mJy in the 250, 350 and 500 micron bands respectively. This means the SPIRE surveys should achieve sensitivities 1.5 times deeper than BLAST, revealing a fainter population of infrared-luminous galaxies, and detecting approximately 2600, 1300, and 700 sources per square degree in the SPIRE bands (with one in three sources expected to be a high redshift ultra-luminous source at 500 microns). The model number redshift distributions predict a bimodal distribution of local quiescent galaxies and a high redshift peak corresponding to strongly evolving star-forming galaxies. It suggests the very deepest surveys with Herschel-SPIRE ought to sample the source population responsible for the bulk of the infrared background.Comment: 5 pages, 4 figures, accepted for publication in MNRAS Letter

Scales and dynamics of Submesoscale Coherent Vortices formed by deep convection in the northwestern Mediterranean Sea

Since 2010, an intense effort in the collection of in situ observations has been carried out in the northwestern Mediterranean Sea thanks to gliders, profiling floats, regular cruises, and mooring lines. This integrated observing system enabled a year‐to‐year monitoring of the deep waters formation that occurred in the Gulf of Lions area during four consecutive winters (2010–2013). Vortical structures remnant of wintertime deep vertical mixing events were regularly sampled by the different observing platforms. These are Submesoscale Coherent Vortices (SCVs) characterized by a small radius (∼5–8 km), strong depth‐intensified orbital velocities (∼10–20 cm s−1) with often a weak surface signature, high Rossby (∼0.5) and Burger numbers O(0.5–1). Anticyclones transport convected waters resulting from intermediate (∼300 m) to deep (∼2000 m) vertical mixing. Cyclones are characterized by a 500–1000 m thick layer of weakly stratified deep waters (or bottom waters that cascaded from the shelf of the Gulf of Lions in 2012) extending down to the bottom of the ocean at ∼2500 m. The formation of cyclonic eddies seems to be favored by bottom‐reaching convection occurring during the study period or cascading events reaching the abyssal plain. We confirm the prominent role of anticyclonic SCVs and shed light on the important role of cyclonic SCVs in the spreading of a significant amount (∼30%) of the newly formed deep waters away from the winter mixing areas. Since they can survive until the following winter, they can potentially have a great impact on the mixed layer deepening through a local preconditioning effect