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INTRODUCTION : L’hyperplasie macronodulaire bilatérale des surrénales (HMBS) GIP-dépendante avec syndrome de Cushing est due à l’expression ectopique du récepteur du GIP (GIPR) dans ces lésions surrénaliennes. Notre objectif était d’identifier la cause moléculaire de cette pathologie. [...]

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The initial STOMP and ORIOLE trial reports suggested that metastasis-directed therapy (MDT) in oligometastatic castration-sensitive prostate cancer (omCSPC) was associated with improved treatment outcomes. Here, we present long-term outcomes of MDT in omCSPC by pooling STOMP and ORIOLE and assess the ability of a high-risk mutational signature to risk stratify outcomes after MDT. The primary end point was progression-free survival (PFS) calculated using the Kaplan-Meier method. High-risk mutations were defined as pathogenic somatic mutations within ATM, BRCA1/2, Rb1, or TP53. The median follow-up for the whole group was 52.5 months. Median PFS was prolonged with MDT compared with observation (pooled hazard ratio [HR], 0.44; 95% CI, 0.29 to 0.66; P value < .001), with the largest benefit of MDT in patients with a high-risk mutation (HR high-risk, 0.05; HR no high-risk, 0.42; P value for interaction: .12). Within the MDT cohort, the PFS was 13.4 months in those without a high-risk mutation, compared with 7.5 months in those with a high-risk mutation (HR, 0.53; 95% CI, 0.25 to 1.11; P = .09). Long-term outcomes from the only two randomized trials in omCSPC suggest a sustained clinical benefit to MDT over observation. A high-risk mutational signature may help risk stratify treatment outcomes after MDT.

Due to complex interactions between social and ecological systems, herbicide resistance has classic features of a “wicked problem”. Herbicide-resistant (HR) Poa annua poses a risk to sustainably managing U.S. turfgrass systems, but there is scant knowledge to guide its management. Six focus groups were conducted throughout the United States to gain understanding of socio-economic barriers to adopting herbicide-resistance management practices. Professionals from major turfgrass sectors (golf courses, sports fields, lawn care, and seed/sod production) were recruited as focus-group participants. Discussions emphasized challenges of the weed management of turfgrass systems as compared to agronomic crops. This included greater time constraints for managing weeds and more limited chemical control options. Lack of understanding about the proper use of compounds with different modes of action was identified as a threat to sustainable weed management. There were significant regional differences in perceptions of the existence, geographic scope, and social and ecological causes of HR in managing Poa annua. Effective resistance management will require tailoring chemical and non-chemical practices to the specific conditions of different turfgrass sectors and regions. Some participants thought it would be helpful to have multi-year resistance management programs that are both sector- and species-specific.

© 2019, Springer Nature Limited. Many symbiotic relationships rely on the acquisition of microbial partners from the environment. However, the mechanisms by which microbial symbionts find and colonize their hosts are often unknown. We propose that the acquisition of environmental symbionts often necessitates active migration and colonization by the symbionts through motility and chemotaxis. The pivotal role of these behaviours in the onset and maintenance of symbiotic interactions is well established in a small number of model systems but remains largely overlooked for the many symbioses that involve the recruitment of microbial partners from the environment. In this Review, we highlight when, where and how chemotaxis and motility can enable symbiont recruitment and propose that these symbiont behaviours are important across a wide range of hosts and environments.

The adult mammalian kidney has a complex, highly-branched collecting duct epithelium that arises as a ureteric bud sidebranch from an epithelial tube known as the nephric duct. Subsequent branching of the ureteric bud to form the collecting duct tree is regulated by subcellular interactions between the epithelium and a population of mesenchymal cells that surround the tips of outgrowing branches. The mesenchymal cells produce glial cell-line derived neurotrophic factor (GDNF), that binds with RET receptors on the surface of the epithelial cells to stimulate several subcellular pathways in the epithelium. Such interactions are known to be a prerequisite for normal branching development, although competing theories exist for their role in morphogenesis. Here we introduce the first agent-based model of ex vivo kidney uretic branching. Through comparison with experimental data, we show that growth factor-regulated growth mechanisms can explain early epithelial cell branching, but only if epithelial cell division depends in a switch-like way on the local growth factor concentration; cell division occurring only if the driving growth factor level exceeds a threshold. We also show how a recently-developed method, "Approximate Approximate Bayesian Computation", can be used to infer key model parameters, and reveal the dependency between the parameters controlling a growth factor-dependent growth switch. These results are consistent with a requirement for signals controlling proliferation and chemotaxis, both of which are previously identified roles for GDNF.

Methods: Diagnostic 123I-MIBG scans from 249 patients (123 from a European and 126 from the COG cohort) were assessed for metastatic spread in 14 body segments and the form of the lesions: “focal” (clear margins distinguishable from adjacent background) or “diffuse” (indistinct margins, dispersed throughout the body segment). The total numbers of diffuse and focal lesions were recorded. Patients were then categorized as having lesions exclusively focal, lesions more focal than diffuse, lesions more diffuse than focal, or lesions exclusively diffuse.Results: Diffuse lesions affected a median of seven body segments and focal lesions a median of two body segments (P < 0.001, both cohorts). Patients with a focal pattern had a median of 2 affected body segments and those with a diffuse pattern a median of 11 affected body segments (P < 0.001, both cohorts). Thus, two MIBG-avid metastatic patterns emerged: “limited-focal” and “extensive-diffuse”. The median numbers of affected body segments in MYCN-amplified (MNA) tumours were 5 (European cohort) and 4 (COG cohort) compared to 9 and 11, respectively, in single-copy MYCN (MYCNsc) tumours (P < 0.001). Patients with exclusively focal metastases were more likely to have a MNA tumour (60 % and 70 %, respectively) than patients with the other types of metastases (23 % and 28 %, respectively; P < 0.001). In a multivariate Cox regression analysis, focal metastases were associated with a better event-free and overall survival than the other types of metastases in patients with MNA tumours in the COG cohort (P < 0.01).Conclusion: Two metastatic patterns were found: a “limited and focal” pattern found mainly in patients with MNA neuroblastoma that correlated with prognosis, and an “extensive and diffuse” pattern found mainly in patients with MYCNsc neuroblastoma.Purpose: The aim of this study was to find clinically relevant MIBG-avid metastatic patterns in patients with newly diagnosed stage 4 neuroblastoma.

4H-SiC JBS diodes have been manufactured on a Norstel epitaxied N/N + substrate using a JTE as edge termination. A breakdown voltage higherthan 3.5 kV has been measured on 0.16 and 2.56 mm 2 diodes. The leakage current in the 25°C-300°C temperature range depends on the bipolar/Schottky ratio whereas in forward mode its impact is minor. Diodes have been stressed in DC mode to show that the 2.56 mm 2 diodes have a slight forward voltage degradation independently of the layout. In switching mode, the recovery charge is only 20 nC for a 4A current switched at 300°C.

In this paper, AlGaAs/InGaAs pseudomorphic HEMTs have been submitted to DC life-tests in impact ionisation regime with and without thermal stress. Control devices present an identical and steep shape of the on-state breakdown locus while aged devices present a large dispersion of this characteristic. It seems that some slight modification of the surface properties and/or micro-defects located in the gate-drain region affect the on-state breakdown voltage loci measured with a gate current of 0.13mA/mm. After the two life-tests, the temperature evolution of the surface leakage contribution to the reverse gate current has increased while impact ionisation current remains unchanged. This result is confirmed by a weak temperature dependence of the on-state breakdown voltage measured with a gate current of 1mA/mm. These slight modifications of the surface properties do not affect the reliability of this technology.

Epidemiologic studies indicate that prolonged exposure to high pollution levels is associated with increased risk of cancer, especially lung cancer. However, under conditions of moderate or low air pollution, epidemiologic evidence does not permit reliable conclusions. Biomarker-based population studies may serve as complementary tools providing a better understanding of the relative contribution of ambient atmospheric pollution to the overall genotoxic burden suffered by city dwellers. However, past efforts to apply biomarkers to studies of low levels exposure to urban air pollution have given inconclusive results, partly because of the absence of adequate data on personal exposure, covering a time-window which is appropriate for the biomarkers being examined, as well as a battery of biomarkers reflecting different stages of the carcinogenic process. In the present paper, the potential of biomarker-based population studies to aid the assessment of the genotoxic and carcinogenic effects of urban air pollution is reviewed by reference to the achievements and limitations of earlier reported studies. The design and methodology adopted in a recently completed large-scale population study, carried out in the context of the European Union Environment and Climate Programme, known by the short name of AULIS project, The authors worked on behalf of the AULIS project network.1 is discussed and descriptive statistics of the main findings of the project are presented. These findings indicate that for cohorts suffering moderate-to-low exposures to airborne particulate-bound polycyclic aromatic hydrocarbons (PAHs), no simple correlation with biomarkers of genotoxicity existed and suggest that additional factors made a significant contribution to the overall genotoxic burden. © 2001 Elsevier Science B.V. All rights reserved.

The ability of the ID 32E system to identify and discriminate 74 Escherichia coli O157 isolates among 106 E. coli non-O157 isolates was evaluated. The results showed atypical biochemical reactions but accurate identification at the species level and no unique biochemical profile numbers for E. coli O157, although these numbers were distinct from those of other serotypes.

Udgivelsesdato: 1998-Sep-20, The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965-1988 for at least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.

Udgivelsesdato: 1998-null, It has not previously been clear whether cytogenetic biomarkers in healthy subjects will predict cancer. Earlier analyses of a Nordic and an Italian cohort indicated predictivity for chromosomal aberrations (CAS) but not for sister chromatid exchanges (SCES). A pooled analysis of the updated cohorts, forming a joint study base of 5271 subjects, will now be performed, allowing a more solid evaluation. The importance of potential effect modifiers, such as gender, age at testing, and time since testing, will be evaluated using Poisson regression models. Two other potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.

The aim of this study was to test the feasibility of a method designed for the rapid counting of bacteria in various kinds of foods i.e. the Direct Epifluorescent Filter Technique (DEFT). With frozen vegetables, total bacteria count found in 103 samples (n = 103) is significantly correlated (r = 0.87) with the standard method (Plate count agar - PCA); with raw meat (n = 14), even if the DEFT seems to overestimate the total bacteria populations, the correlation with PCA is higher (r = 0.99). However, for this last kind of food, an extraction of fat is necessary. When poultry products are examined, the correlation obtained with neck skin samples is unsatisfactory (r = 0.42). As far as the enumeration of more specific bacteria populations is concerned, e.g. the Enterobacteriaceae in frozen spinach (n = 28), a poor correlation is observed with the standard procedure (r = 0.57). However, better results are obtained with the enumeration of Staphylococcus aureus in raw meat (r = 0.8 to 0.95, n = 17). Good agreement is obtained between visual counting (r = 0.95) and semi-automated image analyser counting.

Udgivelsesdato: 1994-Jun-1, Cytogenetic assays in peripheral blood lymphocytes (PBL) have been used extensively to survey the exposure of humans to genotoxic agents. The conceptual basis for this has been the hypothesis that the extent of genetic damage in PBL reflects critical events for carcinogenic processes in target tissues. Until now, no follow-up studies have been performed to assess the predictive value of these methods for subsequent cancer risk. In an ongoing Nordic cohort study of cancer incidence, 3182 subjects were examined between 1970 and 1988 for chromosomal aberrations (CA), sister chromatid exchange or micronuclei in PBL. In order to standardize for the interlaboratory variation, the results were trichotomized for each laboratory into three strata: low (1-33 percentile), medium (34-66 percentile), or high (67-100 percentile). In this second follow-up, a total of 85 cancers were diagnosed during the observation period (1970-1991). There was no significant trend in the standardized incidence ratio with the frequencies of sister chromatid exchange or micronuclei, but the data for these parameters are still too limited to allow firm conclusions. There was a statistically significant linear trend (P = 0.0009) in CA strata with regard to subsequent cancer risk. The point estimates of the standardized incidence ratio in the three CA strata were 0.9, 0.7, and 2.1, respectively. Thus, an increased level of chromosome breakage appears to be a relevant biomarker of future cancer risk.

The objective of this project was to develop and validate a criterion with which the Air Force could reliably evaluate the compatibility of an individual's physical capacities with the physical demands of the various Air Force Specialty Codes (AFSCs). The benefits derived by the Air Force from this capability are a reduction in early discharges due to the inability of the individual to physically qualify for an AFSC after enlistment; a corresponding decrease in training costs, both initial and cross-training, due to a lower probability of an individual's eventual failure in the AFSC; a reduction in injury related costs due to a fewer number of individuals performing physical work at levels near or exceeding their maximum safe capability to work; and a reduction in operating costs by improving the work force capacity relevant to the physical demands of the task.

This report provides a plan which, when executed, will result in an improvement of the Air Force's present capabilities to select and assign personnel to Air Force Specialty Codes (AFSCs). This will be accomplished through the development of a validated objective criterion, as proposed, with which the Air Force can reliably evaluate the compatability of an individual's physical capacities with the physical demands of the various Air Force Specialty Codes. The validity of the criterion will be measured by the individual's ability or inability to successfully perform a selected set of well defined demanding tasks within an Air Force Specialty Code. Phase I is task oriented. In this phase each AFSC is surveyed to identify the tasks which require significant physical demands. Phase II involves the identification of tests which can be used at the Armed Forces Examination and Enlistment Station (AFEES) and Basic Military Training (BMT) Center for predicting the individual's success within jobs having varied degrees of heavy physical demands. Phase III involves the definition, hazard evaluation, and procurement of the equipment needed for task analyses, AFEES and BMT testing, and for testing during the longitudinal validation phase (phase IV). Phase IV involves the finalization and validation of the assignment criteria. Samples of incoming personnel will be tested and categorized according to their tested physical capabilities.

Primary efforts during the first year were focused on the initial job analysis phase of the project. In this phase each Air Force Specialty Code (AFSC) is surveyed to identify the tasks which require significant physical demands. These tasks are quantified, using an appropriate physical unit through the use of task analysis, such that an accurate assessment of demands can be made. From this list of tasks for each AFSC, a set of tasks known as Performance Criteria Tasks (PCTs) will be selected. An individual's performance on these PCTs, then, will determine whether or not the individual is successful or not in performing the physically demanding tasks within the AFSC. This report discusses the questionnaires developed for the field surveys to be conducted, the rationale and sampling scheme used for the selection of tasks, the preliminary questionnaire used in the field survey of the initial 45 AFSCs, and the basic questionnaire to be used on the accompanying follow-up survey.