Initial trail results of a magnetic biosensor for the rapid detection of Porcine Reproductive and Respiratory Virus (PRRSV) infection

© 2019 The resonant coil magnetometer quantifies paramagnetic particles (PMPs) and has been used to develop magneto-immunoassays in a range of formats. The advantage of magneto-immunoassays is that they are relatively inexpensive, portable, easy to perform and give results in under 5 min. Porcine Reproductive and Respiratory Virus (PRRSV) is an infection of domesticated pigs producing large economic losses in the swine industry current diagnosis is performed using commercially available ELISA kits. Here we describe the development of a competitive magneto-immunoassay (MIA) and pilot study with porcine serum samples. The data show that this technology has the potential for use as a rapid and portable in field system for the detection of antibodies in porcine serum to PRRSV. A range of assay parameters and magnetometer settings were optimised, including the concentration of antibody conjugated PMPs used in the assay and movement of an external magnet to pull particles to a sensor surface. PRRSV positive control serum demonstrated competition with antibody conjugated PMPs with a dose dependent relationship. The magneto-immunoassay developed showed good agreement with the PRRS IDEXX X3 ELISA. The PRRSV magneto-immunoassay demonstrated a sensitivity of 73% and specificity of 100%. The results suggest that a rapid assay using the magnetometer technology detects specific anti-PRRSV antibody in pig serum. The magneto-immunoassay is suitable for use as a rapid ‘on-site’ method for the serological detection of PRRSV infection

Tumor necrosis factor-alpha enhances mRNA expression and secretion of interleukin-6 in cultured human airway smooth muscle cells

Airway smooth muscle (ASM) is considered to be an end-target cell for the effects of mediators released during airway wall inflammation. Several reports suggest that activated ASM may be capable of generating various proinflammatory cytokines. We investigated the effects of tumor necrosis factor (TNF)-alpha, a potent proinflammatory cytokine, on cultured human ASM cells by examining the expression and release of the cytokine interleukin (IL)-6, cell proliferation, and the expression pattern of c-fos and c-jun, two nuclear proto-oncogenes constituting the activator protein-1 transcription factor. Growth-arrested cell monolayers were stimulated with human recombinant TNF-alpha in a concentration- and time-dependent manner. TNF-alpha stimulated the expression of IL-6 messenger RNA (mRNA), which was detected after 15 min, reaching a maximum at 1 h. IL-6 protein was readily detected in ASM cell-conditioned medium after 2 h of TNF-alpha stimulation. Protein levels increased in a time- and concentration-dependent manner. Release of IL-6 elicited by TNF-alpha was significantly inhibited by dexamethasone, cycloheximide, and nordihydroguaiaretic acid (NDGA). TNF-alpha did not alter DNA biosynthesis up to 48 h or cell numbers up to 120 h. Northern blot analysis of proto-oncogene expression revealed that c-fos and c-jun mRNA levels were elevated after 30 min of TNF-alpha incubation with maximum levels at 1 h and 45 min, respectively. Expression of c-fos mRNA was downregulated by NDGA. Four hours of TNF-alpha treatment resulted in translocation of c-jun immunofluorescence from the cytoplasm to the nucleus in human ASM cells. Our results suggest that despite the lack of a mitogenic response to TNF-alpha, upregulation of primary response genes in human ASM cells may account for the induction of proinflammatory cytokines, such as IL-6, in human airways

Seismotectonics of southeast France: from the Jura mountains to Corsica

The analysis of the seismicity catalog (1996 to 2019) covering the region from the Jura mountains to Corsica provides a first-order image of the distribution of earthquakes, highlighting large structures such as the Briançonnais and Piedmontais seismic arcs, the eastward deepening of the focal depths through the Western Alps, several large active faults (e.g. Belledonne, Middle Durance, Ligure). Over this period the magnitudes are moderate and the focal mechanisms of the main events display a diversity of seismic behaviors that can be explained by the complexity of the different geological domains with a more or less strong structural inheritage, by variable rheological characteristics at the scale of the crust and by the joint action of different mechanisms of deformation. The distribution of the historical events is in fairly good agreement with the instrumental seismicity, but several earthquakes of $M >6$ are highlighted since the 14th century until the beginning of the 20th

Seismotectonics of southeast France: from the Jura mountains to Corsica

The analysis of the seismicity catalog (1996 to 2019) covering the region from the Jura mountains to Corsica provides a first-order image of the distribution of earthquakes, highlighting large structures such as the Briançonnais and Piedmontais seismic arcs, the eastward deepening of the focal depths through the Western Alps, several large active faults (e.g. Belledonne, Middle Durance, Ligure). Over this period the magnitudes are moderate and the focal mechanisms of the main events display a diversity of seismic behaviors that can be explained by the complexity of the different geological domains with a more or less strong structural inheritage, by variable rheological characteristics at the scale of the crust and by the joint action of different mechanisms of deformation. The distribution of the historical events is in fairly good agreement with the instrumental seismicity, but several earthquakes of $M >6$ are highlighted since the 14th century until the beginning of the 20th

Assessment of the safety of glucocorticoid regimens in combination with abiraterone acetate for metastatic castration-resistant prostate cancer:a randomized, open-label phase 2 study

Importance: Abiraterone acetate is combined with prednisone, 5 mg, twice daily for metastatic castration-resistant prostate cancer (mCRPC) and with prednisone, 5 mg, once daily for newly diagnosed, high-risk, metastatic castration-sensitive prostate cancer. Understanding the physiological effects of these and other regimens is important. Objective: To evaluate the safety of abiraterone acetate with 4 glucocorticoid regimens. Design, Setting, and Participants: Open-label, randomized clinical trial (1:1:1:1) of 164 men with mCRPC from 22 hospitals in 5 countries who were randomly assigned to 1 of 4 intervention groups between June 2013 and October 2014. Analyses were conducted from August 2017 to June 2018. Interventions: Abiraterone acetate, 1000 mg, once daily with prednisone, 5 mg, twice daily (n = 41), 5 mg once daily (n = 41), 2.5 mg twice daily (n = 40), or dexamethasone, 0.5 mg, once daily (n = 42). Main Outcomes and Measures: Primary end point was no mineralocorticoid excess (grade ≥1 hypokalemia or grade ≥2 hypertension) through 24 weeks (6 cycles) from treatment. Results: Of 164 men (median [range] age, 70 [50-90] years) randomized to receive abiraterone acetate, 1000 mg, daily with prednisone, 5 mg, twice daily, once daily, or 2.5 mg twice daily, or dexamethasone, 0.5 mg, once daily, 24 (70.6%) of 34 patients (95% CI, 53.8%-83.2%), 14 (36.8%) of 38 patients (95% CI, 23.4%-52.7%), 21 (60.0%) of 35 patients (95% CI, 43.6%-74.4%), and 26 (70.3%) of 37 patients (95% CI, 54.2%-82.5%), respectively, had no mineralocorticoid excess. Plasma adrenocorticotrophic hormone and urinary mineralocorticoid metabolites after 8 weeks were higher with prednisone, 2.5 mg, twice daily and 5 mg once daily than with 5 mg twice daily or dexamethasone, 0.5 mg, once daily. The level of urinary glucocorticoid metabolites appeared higher in patients who did not meet the primary end point, regardless of glucocorticoid regimen. Total lean body mass decreased in the prednisone groups and total body fat increased in the prednisone, 5 mg, twice daily and dexamethasone groups. In the dexamethasone group, there was an increase in serum insulin and homeostatic model assessment of insulin resistance, while total bone mineral density decreased. In the prednisone, 5 mg, twice daily, 5 mg once daily, 2.5 mg twice daily, and dexamethasone groups, median radiographic progression-free survival was 18.5, 15.3, 12.8, and 26.6 months, respectively. Conclusions and Relevance: Abiraterone acetate with prednisone, 5 mg, twice daily or dexamethasone, 0.5 mg, once daily met the prespecified threshold for the primary end point (95% CI excluded 50% mineralocorticoid excess); abiraterone acetate with prednisone, 5 mg, once daily or 2.5 mg twice daily did not meet the threshold. Abiraterone acetate in combination with dexamethasone appeared to be particularly active but may be associated with adverse metabolic consequences

Rapid response to the M_w 4.9 earthquake of November 11, 2019 in Le Teil, Lower Rhône Valley, France

On November 11, 2019, a Mw 4.9 earthquake hit the region close to Montelimar (lower Rhône Valley, France), on the eastern margin of the Massif Central close to the external part of the Alps. Occuring in a moderate seismicity area, this earthquake is remarkable for its very shallow focal depth (between 1 and 3 km), its magnitude, and the moderate to large damages it produced in several villages. InSAR interferograms indicated a shallow rupture about 4 km long reaching the surface and the reactivation of the ancient NE-SW La Rouviere normal fault in reverse faulting in agreement with the present-day E-W compressional tectonics. The peculiarity of this earthquake together with a poor coverage of the epicentral region by permanent seismological and geodetic stations triggered the mobilisation of the French post-seismic unit and the broad French scientific community from various institutions, with the deployment of geophysical instruments (seismological and geodesic stations), geological field surveys, and field evaluation of the intensity of the earthquake. Within 7 days after the mainshock, 47 seismological stations were deployed in the epicentral area to improve the Le Teil aftershocks locations relative to the French permanent seismological network (RESIF), monitor the temporal and spatial evolution of microearthquakes close to the fault plane and temporal evolution of the seismic response of 3 damaged historical buildings, and to study suspected site effects and their influence in the distribution of seismic damage. This seismological dataset, completed by data owned by different institutions, was integrated in a homogeneous archive and distributed through FDSN web services by the RESIF data center. This dataset, together with observations of surface rupture evidences, geologic, geodetic and satellite data, will help to unravel the causes and rupture mechanism of this earthquake, and contribute to account in seismic hazard assessment for earthquakes along the major regional Cévenne fault system in a context of present-day compressional tectonics

Individual Recognition in Domestic Cattle (Bos taurus): Evidence from 2D-Images of Heads from Different Breeds

BACKGROUND: In order to maintain cohesion of groups, social animals need to process social information efficiently. Visual individual recognition, which is distinguished from mere visual discrimination, has been studied in only few mammalian species. In addition, most previous studies used either a small number of subjects or a few various views as test stimuli. Dairy cattle, as a domestic species allow the testing of a good sample size and provide a large variety of test stimuli due to the morphological diversity of breeds. Hence cattle are a suitable model for studying individual visual recognition. This study demonstrates that cattle display visual individual recognition and shows the effect of both familiarity and coat diversity in discrimination. [br/]METHODOLOGY/PRINCIPAL FINDINGS: We tested whether 8 Prim'Holstein heifers could recognize 2D-images of heads of one cow (face, profiles, (3/4) views) from those of other cows. Experiments were based on a simultaneous discrimination paradigm through instrumental conditioning using food rewards. In Experiment 1, all images represented familiar cows (belonging to the same social group) from the Prim'Holstein breed. In Experiments 2, 3 and 4, images were from unfamiliar (unknown) individuals either from the same breed or other breeds. All heifers displayed individual recognition of familiar and unfamiliar individuals from their own breed. Subjects reached criterion sooner when recognizing a familiar individual than when recognizing an unfamiliar one (Exp 1: 3.1+/-0.7 vs. Exp 2: 5.2+/-1.2 sessions; Z = 1.99, N = 8, P = 0.046). In addition almost all subjects recognized unknown individuals from different breeds, however with greater difficulty. [br/] CONCLUSIONS/SIGNIFICANCE: Our results demonstrated that cattle have efficient individual recognition based on categorization capacities. Social familiarity improved their performance. The recognition of individuals with very different coat characteristics from the subjects was the most difficult task. These results call for studies exploring the mechanisms involved in face recognition allowing interspecies comparisons, including humans

A modified Delphi study of screening for fetal alcohol spectrum disorders in Australia

Background: There is little reliable information on the prevalence of fetal alcohol spectrum disorders (FASD) in Australia and no coordinated national approach to facilitate case detection. The aim of this study was to identify health professionals’ perceptions about screening for FASD in Australia. Method: A modified Delphi process was used to assess perceptions of the need for, and the process of, screening for FASD in Australia. We recruited a panel of 130 Australian health professionals with experience or expertise in FASD screening or diagnosis. A systematic review of the literature was used to develop Likert statements on screening coverage, components and assessment methods which were administered using an online survey over two survey rounds. Results: Of the panel members surveyed, 95 (73%) responded to the questions on screening in the first survey round and, of these, 81 (85%) responded to the second round. Following two rounds there was consensus agreement on the need for targeted screening at birth (76%) and in childhood (84%). Participants did not reach consensus agreement on the need for universal screening at birth (55%) or in childhood (40%). Support for targeted screening was linked to perceived constraints on service provision and the need to examine the performance, costs and benefits of screening. For targeted screening of high risk groups, we found highest agreement for siblings of known cases of FASD (96%) and children of mothers attending alcohol treatment services (93%). Participants agreed that screening for FASD primarily requires assessment of prenatal alcohol exposure at birth (86%) and in childhood (88%), and that a checklist is needed to identify the components of screening and criteria for referral at birth (84%) and in childhood (90%). Conclusions: There is an agreed need for targeted but not universal screening for FASD in Australia, and sufficient consensus among health professionals to warrant development and evaluation of standardised methods for targeted screening and referral in the Australian context. Participants emphasised the need for locally-appropriate, evidence-based approaches to facilitate case detection, and the importance of ensuring that screening and referral programs are supported by adequate diagnostic and management capacity

International Consortium on Mammographic Density:methodology and population diversity captured across 22 countries

Mammographic density (MD) is a quantitative trait, measurable in all women, and is among the strongest markers of breast cancer risk. The population-based epidemiology of MD has revealed genetic, lifestyle and societal/environmental determinants, but studies have largely been conducted in women with similar westernized lifestyles living in countries with high breast cancer incidence rates. To benefit from the heterogeneity in risk factors and their combinations worldwide, we created an International Consortium on Mammographic Density (ICMD) to pool individual-level epidemiological and MD data from general population studies worldwide. ICMD aims to characterize determinants of MD more precisely, and to evaluate whether they are consistent across populations worldwide. We included 11755 women, from 27 studies in 22 countries, on whom individual-level risk factor data were pooled and original mammographic images were re-read for ICMD to obtain standardized comparable MD data. In the present article, we present (i) the rationale for this consortium; (ii) characteristics of the studies and women included; and (iii) study methodology to obtain comparable MD data from original re-read films. We also highlight the risk factor heterogeneity captured by such an effort and, thus, the unique insight the pooled study promises to offer through wider exposure ranges, different confounding structures and enhanced power for sub-group analyses