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Glioblastoma, a deadly brain tumor, shows limited response to standard therapies like temozolomide (TMZ). Recent findings from the REGOMA trial underscore a significant survival improvement offered by Regorafenib (REGO) in recurrent glioblastoma. Our study aimed to propose a 3D ex vivo drug response precision medicine approach to investigate recurrent glioblastoma sensitivity to REGO and elucidate the underlying molecular mechanisms involved in tumor resistance or responsiveness to treatment. Three-dimensional glioblastoma organoids (GB-EXPs) obtained from 18 patients' resected recurrent glioblastoma tumors were treated with TMZ and REGO. Drug responses were evaluated using NAD(P)H FLIM, stratifying tumors as responders (Resp) or non-responders (NRs). Whole-exome sequencing was performed on 16 tissue samples, and whole-transcriptome analysis on 13 GB-EXPs treated and untreated. We found 35% (n = 9) and 77% (n = 20) of tumors responded to TMZ and REGO, respectively, with no instances of TMZ-Resp being REGO-NRs. Exome analysis revealed a unique mutational profile in REGO-Resp tumors compared to NR tumors. Transcriptome analysis identified distinct expression patterns in Resp and NR tumors, impacting Rho GTPase and NOTCH signaling, known to be involved in drug response. In conclusion, recurrent glioblastoma tumors were more responsive to REGO compared to TMZ treatment. Importantly, our approach enables a comprehensive longitudinal exploration of the molecular changes induced by treatment, unveiling promising biomarkers indicative of drug response. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) are one of the most important causes of tumor recurrence and distant metastases. Glioblastoma (GBM) has been considered restricted to the brain for many years. Nevertheless, in the past years, several pieces of evidence indicate that hematogenous dissemination is a reality, and this is also in the caseof GBM. Our aim was to optimize CTCs' detection in GBM and define the genetic background of single CTCs compared to the primary GBM tumor and its recurrence to demonstrate that CTCs are indeed derived from the parental tumor. We collected blood samples from a recurrent IDH wt GBM patient. We genotyped the parental recurrent tumor tissue and the respective primary GBM tissue. CTCs were analyzed using the DEPArray system. CTCs Copy Number Alterations (CNAs) and sequencing analyses were performed to compare CTCs' genetic background with the same patient's primary and recurrent GBM tissues. We identified 210 common mutations in the primary and recurrent tumors. Among these, three somatic high-frequency mutations (in PRKCB, TBX1, and COG5 genes) were selected to investigate their presence in CTCs. Almost all sorted CTCs (9/13) had at least one of the mutations tested. The presence of TERT promoter mutations was also investigated and C228T variation was found in parental tumors and CTCs (C228T heterozygous and homozygous, respectively). We were able to isolate and genotype CTCs from a patient with GBM. We found common mutations but also exclusive molecular characteristics. [ABSTRACT FROM AUTHOR]

Forest compartments are usually delineated according to artificial or natural boundaries and usually include portions of different strata. While volume estimation of each stratum can be performed from field plots located within each stratum, volume estimation in portions of the stratum may be problematic owing to the small number (or even the absence) of plots falling in those portions. If upper canopy heights from airborne laser scanning are available at the pixel level for the whole survey area, these data are used as auxiliary information. A ratio model presuming a proportional relationship between transformed heights (e.g., power of heights) and volumes at the pixel level is adopted to guide estimation. From this model, the volume within any portion of the survey area is estimated as the proportionality factor estimate multiplied by the total of transformed heights in that portion. This estimator is considered from the model-based, design-based, and hybrid perspectives. Variances and their estimators are derived under the three approaches together with the corresponding confidence intervals. The volume estimator and the variance estimators are checked from the design-based point of view by a simulation study performed on a real forest in northwestern Italy. An application to a public forest estate in the same zone is performed. Key words: forest management planning, plot sampling, auxiliary information, airborne laser scanning, ratio model, simulation study. Les compartiments de foret sont souvent delimites par des frontieres artificielles ou naturelles et incluent habituellement des parties de differentes strates. Bien que le volume de chaque strate puisse etre estime a partir de placettes situees a l'interieur de ces strates, l'estimation du volume dans certaines parties d'une strate peut etre problematique etant donne le petit nombre, ou meme l'absence, de placettes dans ces parties. Si la hauteur de la strate superieure du couvert forestier obtenue par balayage laser aeroporte est disponible a l'echelle du pixel dans toute la zone inventoriee, ces donnees sont utilisees comme information auxiliaire. Assumant qu'il existe une relation proportionnelle entre la hauteur transformee (p. ex. puissance de la hauteur) et le volume a l'echelle du pixel, un modele de ratio est adopte pour guider l'estimation. A partir de ce modele, le volume dans n'importe quelle partie de la zone inventoriee est estime en multipliant le facteur de proportionnalite estime par le total des hauteurs estimees dans cette partie. Cet estimateur est envisage dans une perspective fondee soit sur le modele de ratio, soit sur le plan de sondage ou dans une perspective hybride. Les variances et leurs estimateurs sont derives selon les trois approches avec des intervalles de confiance correspondants. L'estimateur du volume et les estimateurs de la variance sont verifies en fonction du plan de sondage au moyen d'une etude de simulation qui porte sur une foret reelle du nord-ouest de l'ltalie. Le modele est aussi applique a une foret publique dans la meme region. [Traduit par la Redaction] Mots-cles: planification de l'amenagement forestier, inventaire par placettes, information auxiliaire, balayage laser aeroporte, etude de simulation., 1. Introduction Information about state and changes of forest stands is fundamental for environmental and wood production assessments at various levels of forest management planning (e.g., Schreuder et al. 1993). [...]

Nonresponse is often a problem in forest inventories. It may arise when sample plots are inaccessible because of hazardous terrain. To account for this problem, the use of nonresponse calibration weighting is considered in a complete design-based framework, i.e., both nonresponse and survey variables are viewed as fixed characteristics of the plots. Information derived from remotely sensed data is exploited to compensate for the missing plots. Calibration is performed adopting canopy height from airborne laser scanning as an auxiliary variable. Conditions for approximate unbiasedness of the calibration estimator in two-phase inventories are derived, and some estimators of the sampling variance are proposed. Results from one-phase inventories are achieved as a particular case. Dummy variables are introduced in the presence of different forest types. Monte Carlo results support the validity of the procedure. An application to a forest survey carried out in Central Italy is performed. Key words: auxiliary information, nonresponse calibration weighting, unbiasedness, variance estimation, Monte Carlo study. La non-reponse est souvent un probleme en inventaire forestier. Cela se produit lorsque des placettes- echantillons sont inaccessibles en raison de conditions de terrain perilleuses. Pour tenir compte de ce probleme, l'utilisation de la ponderation par calage fait partie d'un plan d'echantillonnage complet, c'est-a-dire qu'a la fois les variables de non-reponse et les variables d'inventaire sont considerees comme des caracteristiques fixes des placettes. L'information qui provient de donnees de teledetection est utilisee afin de compenser pour les placettes manquantes. L'etalonnage est fait en utilisant la hauteur du couvert forestier, obtenue avec un laser a balayage aeroporte, comme variable auxiliaire. Les conditions pour une absence approximative de biais de l'estimateur par calage dans un echantillonnage a deux phases sont demontrees et certains estimateurs de la variance d'echantillonnage sont proposes. Les resultats d'un echantillonnage a une seule phase sont consideres comme un cas particulier. Des variables nominales sont introduites pour representer differents types forestiers. Les resultats d'une simulation Monte-Carlo demontrent la validite de la methode. La methode est appliquee a un inventaire forestier realise en Italie centrale. [Traduit par la Redaction] Mots-cles : information auxiliaire, ponderation de la non-reponse par calage, absence de biais, estimation de la variance, analyse Monte-Carlo., 1. Introduction Many forest surveys performed over large scales involve two phases of sampling. Relevant examples are the national forest inventories (NFI) of Canada (Gillis 2001), the USA (Scott et [...]

We propose a design‐based strategy to exploit pellet group counts performed within plots of a prefixed size using the clearance count technique with the purposes of analyzing habitat selection, mapping the pellet group presence throughout the study area, and estimating the abundance of deer populations. As is customary in design‐based inference, the strategy is free of model assumptions, and the precision and statistical consistency of the proposed estimators are determined by the probabilistic sampling scheme adopted to locate plots. The unique necessary assumptions are the absence of migratory movements during the survey period, the accurate recording of the number of pellet groups deposited within sample plots between the 2 visits, and a precise approximation of the daily defecation rate of the population. In addition to these assumptions, which can be attained by a suitable design of the survey, the statistical soundness of the strategy rests on the use of tessellation stratified sampling, a stratified sampling scheme that ensures an even distribution of plots throughout the study area. The scheme also allows for the estimation of the standard errors and the construction of confidence intervals without involving any other assumptions. We applied this strategy in summer 2019 in a protected area of a Mediterranean coastal region to estimate the density of a fallow deer (Dama dama) population. We estimated the corresponding standard error considering the uncertainty entailed by the estimation of the daily defecation rate, with the purpose of performing reliable monitoring. The proposed strategy provided precise estimates of deer abundance and is readily implementable in the field, standardized, and easily repeatable over time, thus allowing reliable monitoring and comparisons across time and space, which are fundamental attributes for management of deer populations. [ABSTRACT FROM AUTHOR]

A two-stage sampling strategy is proposed to assess small woodlots outside the forests scattered on extensive territories. The first stage is performed to select a sample of small woodlots using fixed-size sampling schemes, and the second stage is performed to sample trees within woodlots selected at first stage. Usually, fixed- or variable-area plots are adopted to sample trees. However, the use of plot sampling in small patches such as woodlots is likely to induce a relevant amount of bias owing to edge effects. In this framework, sector sampling proves to be particularly effective. The present paper investigates the statistical properties of two-stage sampling strategies for estimating forest attributes of woodlot populations when sector sampling is adopted at the second stage. A two-stage estimator of population totals is derived together with a conservative estimator of its sampling variance. By means of a simulation study, the performance of the proposed estimator is checked and compared with that achieved using traditional plot sampling with edge corrections. Simulation results prove the adequacy of sector sampling and provide some guidelines for the effective planning of the strategy. In some countries, the proposed strategy can be performed with few modifications within the framework of large-scale forest inventories. Resume: Une strategie d'echantillonnage en deux etapes est proposee pour evaluer les petits boises situes a l'ecart des forets et disperses sur de vastes territoires. La premiere etape sert a selectionner un echantillon de petits boises en utilisant des plans d'echantillonnage a surface fixe tandis que la deuxieme etape sert a echantillonner les arbres dans les boises selectionnes lors de la premiere etape. Habituellement, des placettes a surface fixe ou variable sont utilisees pour echantillonner les arbres. Cependant, l'utilisation de placettes dans de petits boises est susceptible d'induire un biais appreciable du a l'effet de bordure. Dans ce cas, l'echantillonnage par secteur se revele particulierement efficace. Le present article etudie les proprietes statistiques des strategies d'echantillonnage en deux etapes pour estimer les attributs forestiers de populations de boises lorsque l'echantillonnage par secteur est utilise lors de la deuxieme etape. Un estimateur en deux etapes des totaux de population est derive avec un estimateur conservateur de sa variance d'echantillonnage. La performance de l'estimateur propose est verifiee et comparee par simulation avec celle obtenue par l'echantillonnage traditionnel accompagne d'une correction pour tenir compte de l'effet de bordure. Les resultats de la simulation demontrent que l'echantillonnage par secteur est adequat et fournissent des lignes directrices pour la planification efficace de la strategie d'echantillonnage. Dans certains pays, la strategie proposee peut etre realisee avec peu de modifications dans le cadre de l'inventaire forestier a grande echelle. [Traduit par la Redaction], Introduction Trees outside the forests (TOF) as in small woodlots, windbreaks, and hedgerows play a basic role in biodiversity conservation, protection of soil and water resources, contribution to scenic beauty, [...]