Variabilité spatiale de la teneur en eau de surface des sols nus par mesures in situ et imagerie radar

National audienceOn présente l'analyse géostatistique de la teneur en eau de surface (0-6 cm de profondeur) collectée les 12 et 13 Mars 2009, sur une quinzaine de parcelles de sol nu d'un petit bassin péri-urbain proche de Lyon. Les mesures in situ, ont été collectées à deux échelles : une échelle locale sur des croix de longueur 20m et un pas d'espace de 1m et une échelle parcellaire sur 3 transects avec un pas de 20m environ. Les résultats montrent une corrélation de quelques m à échelle fine et de 20 à 50m à l'échelle de la parcelle. Après correction du bruit, calibration radiométrique et correction des effets géométriques et de pente, la comparaison des moyennes par parcelles issues de l'image radar TerraSAR-X et des mesures in situ est satisfaisante (R2=0.43) mais l'analyse intra-parcellaire reste à affiner. / This paper presents the geostatistical analysis of surface soil water content (0-6 cm depth), collected on March 12-13 2009, in about 15 bare soil fields located in a small suburban catchment close to Lyon. In situ data were sampled at two scales : a local scale on 20m-long crosses with a space step of about 1m; a field scale, with 3 transects and a space scale of about 20m. The results show a correlation of a few meters at the local scale and of about 20-50m at the field scale. After correction of the noise, radiometric calibration, geometric and slope effect correction, the comparison of the field averages derived from the TerraSAR-X image and of in situ data is satisfactory (R2=0.43), but the intra-field variability should be studied in more details

Physical resolution of tubal ectopic pregnancy on ultrasound imaging following successful expectant management

RESEARCH QUESTION What is the time required for complete physical resolution of tubal ectopic pregnancies diagnosed on ultrasound imaging in women undergoing successful expectant management? DESIGN A prospective observational cohort study of 177 women who had successful expectant management of tubal ectopic pregnancy, who attended a single Early Pregnancy Unit between January 2014 and December 2018. All participants were monitored until their serum β-hCG dropped to non-pregnant levels and with two-weekly follow-up ultrasound scans until resolution of the pregnancy. RESULTS 112/177 (63.8%, 95% CI 56.3-70.9) of tubal ectopic pregnancies were indiscernible on ultrasound 2 weeks after serum β-hCG had returned to non-pregnant levels. In 8/177 (4.5%, 95% CI 2.0-8.7) physical resolution took longer than 78 days. There was a positive correlation between biochemical and physical resolution of tubal ectopic pregnancy (r=0.21, p=0.006). CONCLUSIONS Physical resolution of tubal ectopic pregnancy is often prolonged and is positively correlated with initial and maximum β-hCG levels. Our results indicate that β-hCG resolution cannot be used as the end-point of expectant management of tubal ectopic pregnancy, which should be considered when counselling women and planning for future pregnancies. KEY MESSAGE In a significant proportion, physical resolution of tubal ectopic pregnancy takes several weeks following the return of serum β-hCG to non-pregnant levels. Women should be advised to delay trying for another pregnancy for three months, to avoid resolving pregnancies being misdiagnosed as new ones and to reduce the theoretical risk of recurrent ectopic, due to temporary tubal blockage by the resolving trophoblast

Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colorectal cancer at high risk for the development of peritoneal metastases. A matched case-control study

n/

Neoadjuvant eribulin mesylate following anthracycline and taxane in triple negative breast cancer: Results from the HOPE study

Background Eribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy. Methods Patients with primary triple negative breast cancer 2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.4 mg/m2 x 4 cycles. Primary endpoint was pathological complete response (pCR) rate; secondary and explorative endpoints included clinical/metabolic response rates and safety, and biomarker analysis, respectively. Using a two-stage Simon design, 43 patients were to be included provided that 4 of 13 patients had achieved pCR in the first stage of the study. Results In stage I of the study 13 women were enrolled, median age 43 years, tumor size 2–5 cm in 9/13 (69%), positive nodal status in 8/13 (61%). Main grade 3 adverse event was neutropenia (related to AT and E in 4 and 2 cases, respectively). AT followed by E induced clinical complete + partial responses in 11/13 patients (85%), pCR in 3/13 (23%). Median measurements of maximum standardized uptake value (SUVmax) resulted 13, 3, and 1.9 at baseline, after AT and E, respectively. Complete metabolic response (CMR) occurred after AT and after E in 2 and 3 cases, respectively. Notably, 2 of the 5 (40%) patients with CMR achieved pCR at surgery. Immunostaining of paired pre-/post-treatment tumor specimens showed a reduction of β-catenin, CyclinD1, Zeb-1, and c-myc expression, in the absence of N-cadherin modulation. The study was interrupted at stage I due to the lack of the required patients with pCR. Conclusions Despite the early study closure, preoperative E following AT showed clinical and biological activity in triple negative breast cancer patients. Furthermore, the modulation of β-catenin pathway core proteins, supposedly outside the domain of epithelial–mesenchymal transition, claims for further investigation. Trial registration EU Clinical Trial Register, EudraCT number 2012-004956-12

Genome-Wide microRNA Binding Site Variation between Extinct Wild Aurochs and Modern Cattle Identifies Candidate microRNA-Regulated Domestication Genes

peer-reviewedThe domestication of cattle from the now-extinct wild aurochs (Bos primigenius) involved selection for physiological and behavioral traits, with underlying genetic factors that remain largely unknown. Non-coding microRNAs have emerged as key regulators of the spatio-temporal expression of target genes controlling mammalian growth and development, including in livestock species. During the domestication process, selection of mutational changes in miRNAs and/or miRNA binding sites could have provided a mechanism to generate some of the traits that differentiate domesticated cattle from wild aurochs. To investigate this, we analyzed the open reading frame DNA sequence of 19,994 orthologous protein-coding gene pairs from extant Bos taurus genomes and a single extinct B. primigenius genome. We identified miRNA binding site polymorphisms in the 3′ UTRs of 1,620 of these orthologous genes. These 1,620 genes with altered miRNA binding sites between the B. taurus and B. primigenius lineages represent candidate domestication genes. Using a novel Score Site ratio metric we have ranked these miRNA-regulated genes according to the extent of divergence between miRNA binding site presence, frequency and copy number between the orthologous genes from B. taurus and B. primigenius. This provides an unbiased approach to identify cattle genes that have undergone the most changes in miRNA binding (i.e., regulation) between the wild aurochs and modern-day cattle breeds. In addition, we demonstrate that these 1,620 candidate domestication genes are enriched for roles in pigmentation, fertility, neurobiology, metabolism, immunity and production traits (including milk quality and feed efficiency). Our findings suggest that directional selection of miRNA regulatory variants was important in the domestication and subsequent artificial selection that gave rise to modern taurine cattle

Impact of land use on the hydraulic properties of the topsoil in a small French catchment

The hydraulic properties of the topsoil control the partition of rainfall into infiltration and runoff at the soil surface. They must be characterized for distributed hydrological modelling. This study presents the results of a field campaign documenting topsoil hydraulic properties in a small French suburban catchment (7 km2) located near Lyon, France. Two types of infiltration tests were performed: single ring infiltration tests under positive head and tension disk infiltration using a mini-disk. Both categories were processed using the BEST Beerkan Estimation of Soil Transfer parameters- method to derive parameters describing the retention and hydraulic conductivity curves. Dry bulk density and particle size data were also sampled. Almost all the topsoils were found to belong to the sandy loam soil class. No significant differences in hydraulic properties were found in terms of pedologic units, but the results showed a high impact of land use on these properties. The lowest dry bulk density values were obtained in forested soils with the highest organic matter content. Permanent pasture soils showed intermediate values, whereas the highest values were encountered in cultivated lands. For saturated hydraulic conductivity, the highest values were found in broad leaved forests and small woods. The complementary use of tension disk and positive head infiltration tests highlighted a sharp increase of hydraulic conductivity between near saturation and saturated conditions, attributed to macroporosity effect. The ratio of median saturated hydraulic conductivity to median hydraulic conductivity at a pressure of -20 mm of water, was about 50. The study suggests that soil texture, such as used in most pedo-transfer functions, might not be sufficient to properly map the variability of soil hydraulic properties. Land use information should be considered in the parameterizations of topsoil within hydrological models to better represent in situ conditions, as illustrated in the paper

Should clinicians always administer dexamethasone beyond 24 h after chemotherapy to control delayed nausea and vomiting caused by moderately emetogenic regimens? : insight from the re-evaluation of two randomized studies

Purpose Data from two noninferiority trials of a dexamethasone-sparing regimen were assessed for the impact of acute nausea and vomiting on delayed outcome in patients undergoing moderately emetogenic chemotherapy (MEC) or anthracycline plus cyclophosphamide (AC). Methods Chemo-naive patients were randomized to receive palonosetron (0.25 mg IV) plus dexamethasone (8 mg IV) on day 1 of chemotherapy, or the same regimen followed by oral dexamethasone on days 2 and 3 in the MEC (n = 237) and AC (n = 380) cohorts. Patients were divided into two groups according to whether or not they experienced vomiting and/or moderate-to-severe nausea during the acute phase (high- and low-risk groups, respectively). Primary efficacy endpoint was the complete protection (CP) against delayed vomiting and moderate-to-severe nausea. Patient's satisfaction (0-100 mm visual analog scale) was also analyzed. Results Among the 209 low-risk patients undergoing MEC, delayed CP occurred in 82.9 % of those who received single-dose dexamethasone and 89.8 % of those who received 3-day dexamethasone (P = 0.165). Of the 271 low-risk patients undergoing AC, CP was achieved in 71.7 % of those treated with single-dose dexamethasone and 84.2 % treated with 3-day dexamethasone (P = 0.019). In spite of these observations, the patient satisfaction data was not influenced by dexamethasone regimen. In both cohorts, occurrence of acute vomiting or moderate-to-severe nausea was the key independent-predictor for delayed vomiting or nausea, respectively. Conclusions The dexamethasone-sparing regimen provides adequate delayed protection in patients undergoing MEC who are at low risk for delayed symptoms, and can still be discussed for low-risk AC patients as the daily difference in control is modest. Additional dexamethasone doses can be customized on the basis of occurrence or absence of acute symptoms in the first cycle of MEC and even AC

Activity and safety of RAD001 (everolimus) in patients affected by biliary tract cancer progressing after prior chemotherapy: a phase II ITMO study.

BACKGROUND: Biliary tract cancer (BTC) is a highly lethal disease for which the best available therapy remains undetermined. The mammalian target of rapamycin (mTOR) pathway is up-regulated in several cancers, including BTC, and preclinical evidence indicates that mTOR inhibition may be effective in the treatment of BTC. We sought to evaluate the activity and tolerability of the mTOR inhibitor RAD001-everolimus-in patients with BTC progressing after prior chemotherapy. PATIENTS AND METHODS: This was an open-label, single-arm, phase II study (EUDRACT 2008-007152-94) conducted in eight sites in Italy. Patients with locally advanced, metastatic or recurrent BTC progressing despite previous chemotherapy received a daily oral dose of everolimus 10 mg administered continuously in 28-day cycles. The two primary end points were disease control rate (DCR) and objective response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival (OS) and time-to-progression (TTP). RESULTS: Thirty-nine patients were enrolled. The DCR was 44.7%, and the ORR was 5.1%. One patient showed a partial response at 2 months and one patient showed a complete response sustained up to 8 months. The median (95% confidence interval) PFS was 3.2 (1.8-4.0) months, and the median OS was 7.7 (5.5-13.2) months. The median TTP was 2.0 (1.7-3.7) months. Most common toxicities were asthenia (43.6%), thrombocytopenia (35.9%), pyrexia (30.8%) and erythema, mainly of mild-to-moderate severity. Two patients required dose reduction due to adverse events. CONCLUSION: Everolimus demonstrated a favourable toxicity profile and encouraging anti-tumour activity. Further trials are needed to establish the role of everolimus in the treatment of BTC. EUDRACT 2008-007152-94

Safety of long-term exposure to abiraterone acetate in patients with castration-resistant prostate cancer and concomitant cardiovascular risk factors

Background: We aimed to evaluate the long-term safety profile of abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) with controlled cardiovascular comorbidities or risk factors. Methods: We retrospectively analysed the clinical charts of consecutive mCRPC patients with cardiac disorders/risk factors who had been treated with abiraterone 1000 mg once daily plus prednisone 5 mg twice daily for a median duration of 16 months at an oncology referral centre between April 2011 and July 2015. Patients underwent an electrocardiogram (ECG) and echocardiographic assessments, including measurement of left ventricular ejection fraction (LVEF) at baseline and at the end of treatment. Blood pressure (BP) was measured daily at home. During follow up (median 24 months), all adverse events were recorded. Cardiac events (CEs) were defined, according to Common Terminology Criteria for Adverse Events version 4.0, as the appearance of a symptomatic CE that required medical intervention. Results: A total of 51 patients (median age 71 years) were evaluated. Pre-existing cardiovascular conditions included hypertension (41%), cardiac ischaemia (12%), stroke (9%), dyslipidaemia (18%) and type 2 diabetes mellitus (12%). No CEs were recorded and no changes in LVEF were observed. The most frequently reported adverse events were Grade 1-2 fluid retention (18%), hypertension (16%) and asthenia (16%). No patients permanently discontinued abiraterone due to cardiac events. Conclusions: Long-term abiraterone treatment was well tolerated in mCRPC patients with controlled cardiovascular comorbidities/risk factors, with no apparent worsening of cardiovascular conditions from baseline over an extended observation period

Analysis of Qa-1bPeptide Binding Specificity and the Capacity of Cd94/Nkg2a to Discriminate between Qa-1–Peptide Complexes

The major histocompatibility complex class Ib protein, Qa-1b, serves as a ligand for murine CD94/NKG2A natural killer (NK) cell inhibitory receptors. The Qa-1b peptide-binding site is predominantly occupied by a single nonameric peptide, Qa-1 determinant modifier (Qdm), derived from the leader sequence of H-2D and L molecules. Five anchor residues were identified in this study by measuring the peptide-binding affinities of substituted Qdm peptides in experiments with purified recombinant Qa-1b. A candidate peptide-binding motif was determined by sequence analysis of peptides eluted from Qa-1 that had been folded in the presence of random peptide libraries or pools of Qdm derivatives randomized at specific anchor positions. The results indicate that Qa-1b can bind a diverse repertoire of peptides but that Qdm has an optimal primary structure for binding Qa-1b. Flow cytometry experiments with Qa-1b tetramers and NK target cell lysis assays demonstrated that CD94/NKG2A discriminates between Qa-1b complexes containing peptides with substitutions at nonanchor positions P4, P5, or P8. Our findings suggest that it may be difficult for viruses to generate decoy peptides that mimic Qdm and raise the possibility that competitive replacement of Qdm with other peptides may provide a novel mechanism for activation of NK cells