Relationships Between Chemoreflex Responses, Sleep Quality, and Hematocrit in Andean Men and Women.

Andean highlanders are challenged by chronic hypoxia and many exhibit elevated hematocrit (Hct) and blunted ventilation compared to other high-altitude populations. While many Andeans develop Chronic Mountain Sickness (CMS) and excessive erythrocytosis, Hct varies markedly within Andean men and women and may be driven by individual differences in ventilatory control and/or sleep events which exacerbate hypoxemia. To test this hypothesis, we quantified relationships between resting ventilation and ventilatory chemoreflexes, sleep desaturation, breathing disturbance, and Hct in Andean men and women. Ventilatory measures were made in 109 individuals (n = 63 men; n = 46 women), and sleep measures in 45 of these participants (n = 22 men; n = 23 women). In both men and women, high Hct was associated with low daytime SpO2 (p < 0.001 and p < 0.002, respectively) and decreased sleep SpO2 (mean, nadir, and time <80%; all p < 0.02). In men, high Hct was also associated with increased end-tidal PCO2 (p < 0.009). While ventilatory responses to hypoxia and hypercapnia did not predict Hct, decreased hypoxic ventilatory responses were associated with lower daytime SpO2 in men (p < 0.01) and women (p < 0.009) and with lower nadir sleep SpO2 in women (p < 0.02). Decreased ventilatory responses to CO2 were associated with more time below 80% SpO2 during sleep in men (p < 0.05). The obstructive apnea index and apnea-hypopnea index also predicted Hct and CMS scores in men after accounting for age, BMI, and SpO2 during sleep. Finally, heart rate response to hypoxia was lower in men with higher Hct (p < 0.0001). These data support the idea that hypoventilation and decreased ventilatory sensitivity to hypoxia are associated with decreased day time and nighttime SpO2 levels that may exacerbate the stimulus for erythropoiesis in Andean men and women. However, interventional and longitudinal studies are required to establish the causal relationships between these associations

Twisting gauged non-linear sigma-models

We consider gauged sigma-models from a Riemann surface into a Kaehler and hamiltonian G-manifold X. The supersymmetric N=2 theory can always be twisted to produce a gauged A-model. This model localizes to the moduli space of solutions of the vortex equations and computes the Hamiltonian Gromov-Witten invariants. When the target is equivariantly Calabi-Yau, i.e. when its first G-equivariant Chern class vanishes, the supersymmetric theory can also be twisted into a gauged B-model. This model localizes to the Kaehler quotient X//G.Comment: 33 pages; v2: small additions, published versio

Status and challenges for the concept design development of the EU DEMO Plant Electrical System

The EU DEMO Plant Electrical System (PES) main scopes are to supply all the plant electrical loads and to deliver to the Power Transmission Grid (PTG) the net electrical power generated. The studies on the PES during the Pre-Concept Design (PCD) Phase were mainly addressed to understand the possible issues, related to the special features both of the power generated, with respect to a power plant of the same size, and of the power to be supplied to the electrical loads. For this purpose, the approach was to start the design of the different PES components adopting technologies already utilized in fusion experiments and in Nuclear Power Plants (NPP) to verify their applicability and identify possible limits when scaled to the DEMO size and applied to the specific pulsed operating conditions. This work is not completed, however several issues have been already identified related to the pulsed operation of the turbine generator, the large amount of recirculation power, the very high peaks of active power required for the plasma formation and control, the huge reactive power demand, if thyristor converter technology was adopted to supply the superconducting coils, etc.. The paper gives an overview on the features and scope of the PES and its subsystems, on the main achievements during the Pre-Concept Design (PCD) Phase, on the challenges for the development of the conceptual design in the next framework program and on the plan to face them

Start of SPIDER operation towards ITER neutral beams

Heating Neutral Beam (HNB) Injectors will constitute the main plasma heating and current drive tool both in ITER and JT60-SA, which are the next major experimental steps for demonstrating nuclear fusion as viable energy source. In ITER, in order to achieve the required thermonuclear fusion power gain Q=10 for short pulse operation and Q=5 for long pulse operation (up to 3600s), two HNB injectors will be needed [1], each delivering a total power of about 16.5 MW into the magnetically-confined plasma, by means of neutral hydrogen or deuterium particles having a specific energy of about 1 MeV. Since only negatively charged particles can be efficiently neutralized at such energy, the ITER HNB injectors [2] will be based on negative ions, generated by caesium-catalysed surface conversion of atoms in a radio-frequency driven plasma source. A negative deuterium ion current of more than 40 A will be extracted, accelerated and focused in a multi-aperture, multi-stage electrostatic accelerator, having 1280 apertures (~ 14 mm diam.) and 5 acceleration stages (~200 kV each) [3]. After passing through a narrow gas-cell neutralizer, the residual ions will be deflected and discarded, whereas the neutralized particles will continue their trajectory through a duct into the tokamak vessels to deliver the required heating power to the ITER plasma for a pulse duration of about 3600 s. Although the operating principles and the implementation of the most critical parts of the injector have been tested in different experiments, the ITER NBI requirements have never been simultaneously attained. In order to reduce the risks and to optimize the design and operating procedures of the HNB for ITER, a dedicated Neutral Beam Test Facility (NBTF) [4] has been promoted by the ITER Organization with the contribution of the European Union\u2019s Joint Undertaking for ITER and of the Italian Government, with the participation of the Japanese and Indian Domestic Agencies (JADA and INDA) and of several European laboratories, such as IPP-Garching, KIT-Karlsruhe, CCFE-Culham, CEA-Cadarache. The NBTF, nicknamed PRIMA, has been set up at Consorzio RFX in Padova, Italy [5]. The planned experiments will verify continuous HNB operation for one hour, under stringent requirements for beam divergence (< 7 mrad) and aiming (within 2 mrad). To study and optimise HNB performances, the NBTF includes two experiments: MITICA, full-scale NBI prototype with 1 MeV particle energy and SPIDER, with 100 keV particle energy and 40 A current, aiming at testing and optimizing the full-scale ion source. SPIDER will focus on source uniformity, negative ion current density and beam optics. In June 2018 the experimental operation of SPIDER has started

Assessment of the general public's knowledge about rheumatic diseases: evidence from a Portuguese population-based survey

Background. To identify incorrect beliefs and common knowledge about rheumatic diseases in the general population. Methods. Participants were selected during the follow-up of a representative cohort of adult population of Porto, Portugal; 1626 participants completed a questionnaire that included general knowledge items about rheumatic diseases. Discrete and continuous latent variable models were used to identify knowledge flaws and the target groups. Odds ratios (OR) estimated by multinomial logistic regression, and 95% confidence intervals (95%CI) were computed to evaluate magnitude of associations. Results. A continuous latent variable model identified two dimensions: one related to general beliefs (latent 1) and another concerning characteristics, treatment and impact of rheumatic diseases (latent 2). A 3-class latent variable model refined these results: the first class presented the lowest probabilities of correct answer for items associated with the first latent (mean of 39%), and the second class presented the lowest probabilities of correct answer for items with the second latent (mean of 62%). The third class showed the highest probability of a correct answer for almost all the items (mean of 79%). The age and sex standardized prevalence of the classes was 25.7%, 30.8% and 43.5%. Taking class 2 as reference, class 1 was positively associated with the presence of rheumatic diseases (OR = 2.79; CI95% = (2.10-3.70)), with females (OR = 1.28 CI95% = (0.99-1.67)) and older individuals (OR = 1.04; CI95% = (1.03-1.05)), and was negatively associated with education (OR = 0.84; CI95% = (0.81-0.86)); class 3 was positively associated with education (OR = 1.03; CI95% = (1.00-1.05)) and the presence of rheumatic diseases (OR = 1.29; CI95% = (0.97-1.70)). Conclusions. There are several knowledge flaws about rheumatic diseases in the general public. One out of four participants considered false general beliefs as true and approximately 30% did not have detailed knowledge on rheumatic disease. Higher education and the presence of disease contributed positively to the overall knowledge. These results suggest some degree of effectiveness of patient education, either conducted by health professionals or self-driven. © 2010 Severo et al; licensee BioMed Central Ltd

Indirect calibration between clinical observers - application to the New York Heart Association functional classification system

<p>Abstract</p> <p>Background</p> <p>Previous studies showed an inter-observer agreement for the NYHA classification of approximately 55%. The aim of this study was to calibrate the New York Heart Association (NYHA) classification system between observers, increasing its reliability.</p> <p>Results</p> <p>Among 1136 community-dwellers in Porto, Portugal, aged ≥ 45 years, 265 reporting breathlessness answered a 4-item questionnaire to characterize symptom severity. The questionnaire was administered by 7 physicians who also classified the subject's functional capacity according to NYHA. Each subject was assessed by one physician. We calibrated NYHA classifications by the concurrent method, using 1-parameter logistic graded response model. Discrepancies between observers were assessed by differences in ability thresholds between NYHA classes I-II and II-III. The ability estimated by the model was used to predict the NYHA classification for each observer.</p> <p>Estimates of the first and second thresholds for each observer ranged from -1.92 to 0.46 and from 1.42 to 2.30, respectively. The agreement between estimated ability and the observers' NYHA classification was 88% (kappa = 0.61).</p> <p>Conclusions</p> <p>The study objectively indicates the main reason why several studies have reported low inter-observer is the existence of discrepant thresholds between observers in the definition of NYHA classes. The concurrent method can be used to minimize the reliability problem of NYHA classification.</p

Advance in the conceptual design of the European DEMO magnet system

The European DEMO, i.e. the demonstration fusion power plant designed in the framework of the Roadmap to Fusion Electricity by the EUROfusion Consortium, is approaching the end of the pre-conceptual design phase, to be accomplished with a Gate Review in 2020, in which all DEMO subsystems will be reviewed by panels of independent experts. The latest 2018 DEMO baseline has major and minor radius of 9.1 m and 2.9 m, plasma current 17.9 MA, toroidal field on the plasma axis 5.2 T, and the peak field in the toroidal-field (TF) conductor 12.0 T. The 900 ton heavy TF coil is prepared in four lowerature-superconductor (LTS) variants, some of them differing slightly, other significantly, from the ITER TF coil design. Two variants of the CS coils are investigated - a purely LTS one resembling the ITER CS, and a hybrid coil, in which the innermost layers made of HTS allow the designers either to increase the magnetic flux, and thus the duration of the fusion pulse, or to reduce the outer radius of the CS coil. An issue presently investigated by mechanical analyzes is the fatigue load. Two variants of the poloidal field coils are being investigated. The magnet and conductor design studies are accompanied by the experimental tests on both LTS and HTS prototype samples, covering a broad range of DC and AC tests. Testing of quench behavior of the 15 kA HTS cables, with size and layout relevant for the fusion magnets and cooled by forced flow helium, is in preparation.</p

Reciprocal Tripartite Interactions between the Aedes aegypti Midgut Microbiota, Innate Immune System and Dengue Virus Influences Vector Competence

Dengue virus is one of the most important arboviral pathogens and the causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. It is transmitted between humans by the mosquitoes Aedes aegypti and Aedes albopictus, and at least 2.5 billion people are at daily risk of infection. During their lifecycle, mosquitoes are exposed to a variety of microbes, some of which are needed for their successful development into adulthood. However, recent studies have suggested that the adult mosquito's midgut microflora is critical in influencing the transmission of human pathogens. In this study we assessed the reciprocal interactions between the mosquito's midgut microbiota and dengue virus infection that are, to a large extent, mediated by the mosquito's innate immune system. We observed a marked decrease in susceptibility to dengue virus infection when mosquitoes harbored certain field-derived bacterial isolates in their midgut. Transcript abundance analysis of selected antimicrobial peptide genes suggested that the mosquito's microbiota elicits a basal immune activity that appears to act against dengue virus infection. Conversely, the elicitation of the mosquito immune response by dengue virus infection itself influences the microbial load of the mosquito midgut. In sum, we show that the mosquito's microbiota influences dengue virus infection of the mosquito, which in turn activates its antibacterial responses

Functional EPAS1/ HIF2A Missense Variant Is Associated With Hematocrit in Andean Highlanders

Hypoxia-inducible factor pathway genes are linked to adaptation in both human and nonhuman highland species. EPAS1, a notable target of hypoxia adaptation, is associated with relatively lower hemoglobin concentration in Tibetans. We provide evidence for an association between an adaptive EPAS1 variant (rs570553380) and the same phenotype of relatively low hematocrit in Andean highlanders. This Andean-specific missense variant is present at a modest frequency in Andeans and absent in other human populations and vertebrate species except the coelacanth. CRISPR-base-edited human cells with this variant exhibit shifts in hypoxia-regulated gene expression, while metabolomic analyses reveal both genotype and phenotype associations and validation in a lowland population. Although this genocopy of relatively lower hematocrit in Andean highlanders parallels well-replicated findings in Tibetans, it likely involves distinct pathway responses based on a protein-coding versus noncoding variants, respectively. These findings illuminate how unique variants at EPAS1 contribute to the same phenotype in Tibetans and a subset of Andean highlanders despite distinct evolutionary trajectories