A model for measuring the health burden of classic congenital adrenal hyperplasia in adults

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Aim: Patients with classic Congenital Adrenal Hyperplasia (CAH) have poor health outcomes. In the absence of a comprehensive observational study, this manuscript provides a model to estimate the lifetime disease burden of adults with classic CAH. Methods: The model, built in Excel, comprises sub-domains addressing the health consequences of CAH, and synthesises evidence from clinical and epidemiological studies on health outcomes. Results: The model estimates that adults with classic CAH will implement “sick day rules” (doubling or tripling glucocorticoid and/or use of parenteral therapy) 171 times over their lifetime, and attend hospital for adrenal crisis on 11 occasions. In a population of 1,000, over 200 will die of a condition complicated by adrenal crisis resulting, on average, in a loss of 7 years of life. CAH patients may also suffer from excess CVD events. Treatment with glucocorticoids almost doubles the risk of bone fractures in CAH patients compared to the general population, leading on average to an additional 0.8 fractures per CAH patient over their lifetime. Conclusions: The disease burden model highlights gaps in evidence, particularly regarding intensity of care and adrenal crisis, and the relationship between control of CAH and risks of CVD, osteoporosis, diabetes and infertility. The model can be used for research on the impact of new clinical pathways and therapeutic interventions in terms of clinical events and cost.Funded by: European Commission under the Framework 7 programme. Grant Number: HEALTH-F5-2011-281654Diurnal Limited (UK

Automation and data processing with the immucor Galileo (R) system in a university blood bank

Background: The implementation of automated techniques improves the workflow and quality of immuno-hematological results. The workflows of our university blood bank were reviewed during the implementation of an automated immunohematological testing system. Methods: Work impact of blood grouping and subgrouping, cross- matching and antibody search using the Immucor Galileo system was compared to the previous used standard manual and semi- automated methods. Results: The redesign of our workflow did not achieve a significant reduction of the specimen's working process time, the operator's time however was reduced by 23%. Corresponding results were achieved for blood grouping, Rhesus typing, antibody screen and for autocontrol when changing from two semi- automated to the Galileo system. Because of the higher sensitivity of the Immucor antibody detection system, the rate of the initial positive antibody screens rose from 4 to 6% Conclusion: The Immucor Galileo system automates routine blood bank testing with high reliability, specificity and higher sensitivity compared to our previous used standard manual and semi- automated methods

On The Stability Of Non-Supersymmetric AdS Vacua

We consider two infinite families of Non-Supersymmetric $AdS_4$ vacua, called Type 2) and Type 3) vacua, that arise in massive IIA supergravity with flux. We show that both families are perturbatively stable. We then examine non-perturbative decays of these vacua to other supersymmetric and non-supersymmetric $AdS_4$ vacua mediated by instantons in the thin wall approximation. We find that many decays are ruled out since the tension of the interpolating domain wall is too big compared to the energy difference in AdS units. In fact, within our approximations no decays of Type 2) vacua are allowed, although some decays are only marginally forbidden. This can be understood in terms of a "pairing symmetry" in the landscape which relate Type 2) vacua with supersymmetric ones of the same energy.Comment: 50 pages, Minor changes in section 2.2.

Education can improve the negative perception of a threatened long-lived scavenging bird, the Andean condor

Human-wildlife conflicts currently represent one of the main conservation problems for wildlife species around the world. Vultures have serious conservation concerns, many of which are related to people's adverse perception about them due to the belief that they prey on livestock. Our aim was to assess local perception and the factors influencing people's perception of the largest scavenging bird in South America, the Andean condor. For this, we interviewed 112 people from Valle Fértil, San Juan province, a rural area of central west Argentina. Overall, people in the area mostly have an elementary education, and their most important activity is livestock rearing. The results showed that, in general, most people perceive the Andean condor as an injurious species and, in fact, some people recognize that they still kill condors. We identified two major factors that affect this perception, the education level of villagers and their relationship with livestock ranching. Our study suggests that conservation of condors and other similar scavengers depends on education programs designed to change the negative perception people have about them. Such programs should be particularly focused on ranchers since they are the ones who have the worst perception of these scavengers. We suggest that highlighting the central ecological role of scavengers and recovering their cultural value would be fundamental to reverse their persecution and their negative perception by people.Fil: Cailly Arnulphi, Verónica Beatríz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; ArgentinaFil: Lambertucci, Sergio Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Borghi, Carlos Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; Argentin

In-street wind direction variability in the vicinity of a busy intersection in central London

We present results from fast-response wind measurements within and above a busy intersection between two street canyons (Marylebone Road and Gloucester Place) in Westminster, London taken as part of the DAPPLE (Dispersion of Air Pollution and Penetration into the Local Environment; www.dapple.org.uk) 2007 field campaign. The data reported here were collected using ultrasonic anemometers on the roof-top of a building adjacent to the intersection and at two heights on a pair of lamp-posts on opposite sides of the intersection. Site characteristics, data analysis and the variation of intersection flow with the above-roof wind direction (θref) are discussed. Evidence of both flow channelling and recirculation was identified within the canyon, only a few metres from the intersection for along-street and across-street roof-top winds respectively. Results also indicate that for oblique rooftop flows, the intersection flow is a complex combination of bifurcated channelled flows, recirculation and corner vortices. Asymmetries in local building geometry around the intersection and small changes in the background wind direction (changes in 15-min mean θref of 5–10 degrees) were also observed to have profound influences on the behaviour of intersection flow patterns. Consequently, short time-scale variability in the background flow direction can lead to highly scattered in-street mean flow angles masking the true multi-modal features of the flow and thus further complicating modelling challenges

Intersecting Flavor Branes

We consider an instance of the AdS/CFT duality where the bulk theory contains an open string tachyon, and study the instability from the viewpoint of the boundary field theory. We focus on the specific example of the AdS_5 X S^5 background with two probe D7 branes intersecting at general angles. For generic angles supersymmetry is completely broken and there is an open string tachyon between the branes. The field theory action for this system is obtained by coupling to N =4 super Yang-Mills two N =2 hyper multiplets in the fundamental representation of the SU(N) gauge group, but with different choices of embedding of the two N=2 subalgebras into N=4. On the field theory side we find a one-loop Coleman-Weinberg instability in the effective potential for the fundamental scalars. We identify a mesonic operator as the dual of the open string tachyon. By AdS/CFT, we predict the tachyon mass for small 't Hooft coupling (large bulk curvature) and confirm that it violates the AdS stability bound.Comment: 36 page

Discrete Information from CHL Black Holes

AdS_2/CFT_1 correspondence predicts that the logarithm of a Z_N twisted index over states carrying a fixed set of charges grows as 1/N times the entropy of the black hole carrying the same set of charges. In this paper we verify this explicitly by calculating the microscopic Z_N twisted index for a class of states in the CHL models. This demonstrates that black holes carry more information about the microstates than just the total degeneracy.Comment: LaTeX file, 24 pages; v2: references adde

Strategy selection and outcome prediction in sport using dynamic learning for stochastic processes

We study reliability equivalence factors of a system of independent and identical components with exponentiated Weibull lifetimes. The system has n subsystems connected in parallel and subsystem i has mi components connected in series, i=1,…,n. We consider improving the reliability of the system by (a) a reduction method and (b) several duplication methods: (i) hot duplication; (ii) cold duplication with perfect switching; (iii) cold duplication with imperfect switching. We compute two types of reliability equivalence factors: survival equivalence factors and mean equivalence factors. Although our methods adapt to allow for general lifetime models, we use the exponentiated Weibull distribution because it is flexible and enables comparisons with other reliability equivalence studies. The example we present demonstrates the potential for applying these methods to address specific questions that arise when attempting to improve the reliability of simple systems or simple configurations of possibly complex subsystems in many diverse applications

Conjugated bile acids attenuate allergen-induced airway inflammation and hyperresposiveness by inhibiting UPR transducers

© 2019 American Society for Clinical Investigation. Conjugated bile acids (CBAs), such as tauroursodeoxycholic acid (TUDCA), are known to resolve the inflammatory and unfolded protein response (UPR) in inflammatory diseases, such as asthma. Whether CBAs exert their beneficial effects on allergic airway responses via 1 arm or several arms of the UPR, or alternatively through the signaling pathways for conserved bile acid receptor, remains largely unknown. We used a house dust mite-induced (HDM-induced) murine model of asthma to evaluate and compare the effects of 5 CBAs and 1 unconjugated bile acid in attenuating allergen-induced UPR and airway responses. Expression of UPRassociated transcripts was assessed in airway brushings from human patients with asthma and healthy subjects. Here we show that CBAs, such as alanyl β-muricholic acid (AβM) and TUDCA, significantly decreased inflammatory, immune, and cytokine responses; mucus metaplasia; and airway hyperresponsiveness, as compared with other CBAs in a model of allergic airway disease. CBAs predominantly bind to activating transcription factor 6α (ATF6α) compared with the other canonical transducers of the UPR, subsequently decreasing allergen-induced UPR activation and resolving allergic airway disease, without significant activation of the bile acid receptors. TUDCA and AβM also attenuated other HDM-induced ER stress markers in the lungs of allergic mice. Quantitative mRNA analysis of airway epithelial brushings from human subjects demonstrated that several ATF6α-related transcripts were significantly upregulated in patients with asthma compared with healthy subjects. Collectively, these results demonstrate that CBA-based therapy potently inhibits the allergen-induced UPR and allergic airway disease in mice via preferential binding of the canonical transducer of the UPR, ATF6α. These results potentially suggest a novel avenue to treat allergic asthma using select CBAs