Steroid 21-hydroxylase is a major autoantigen involved in adult onset autoimmune Addison's disease

AbstractAn adrenal-specific protein reacting with autoantibodies in the sera of patients with adult onset Addison's disease has been purified from human adrenal glands. The protein, mol.wt. 55K, has the biochemical characteristics of steroid 21-hydroxylase and reacts on Western blots with rabbit antibodies to recombinant 21-hydroxylase. Absorption of the native human 55K adrenal protein with human adrenal autoantibodies prevented the subsequent reaction of the 55K protein with rabbit antibodies to 21-hydroxylase in Western blot analysis. In addition, human adrenal autoantibodies reacted with recombinant 21-hydroxylase expressed in yeast. These data indicate that the adrenal specific enzyme steroid 21-hydroxylase is a major autoantigen involved in adult onset autoimmune Addison's disease

Advanced code-division multiplexers for superconducting detector arrays

Multiplexers based on the modulation of superconducting quantum interference devices are now regularly used in multi-kilopixel arrays of superconducting detectors for astrophysics, cosmology, and materials analysis. Over the next decade, much larger arrays will be needed. These larger arrays require new modulation techniques and compact multiplexer elements that fit within each pixel. We present a new in-focal-plane code-division multiplexer that provides multiplexing elements with the required scalability. This code-division multiplexer uses compact lithographic modulation elements that simultaneously multiplex both signal outputs and superconducting transition-edge sensor (TES) detector bias voltages. It eliminates the shunt resistor used to voltage bias TES detectors, greatly reduces power dissipation, allows different dc bias voltages for each TES, and makes all elements sufficiently compact to fit inside the detector pixel area. These in-focal-plane code-division multiplexers can be combined with multi-gigahertz readout based on superconducting microresonators to scale to even larger arrays.Comment: 8 pages, 3 figures, presented at the 14th International Workshop on Low Temperature Detectors, Heidelberg University, August 1-5, 2011, proceedings to be published in the Journal of Low Temperature Physic

Modular Assessment of Rainfall-Runoff Models Toolbox (MARRMoT) v1.2:an open-source, extendable framework providing implementations of 46 conceptual hydrologic models as continuous state-space formulations

This paper presents the Modular Assessment of Rainfall-Runoff Models Toolbox (MARRMoT): A modular open-source toolbox containing documentation and model code based on 46 existing conceptual hydrologic models. The toolbox is developed in MATLAB and works with Octave. MARRMoT models are based solely on traceable published material and model documentation, not on already-existing computer code. Models are implemented following several good practices of model development: The definition of model equations (the mathematical model) is kept separate from the numerical methods used to solve these equations (the numerical model) to generate clean code that is easy to adjust and debug; the implicit Euler time-stepping scheme is provided as the default option to numerically approximate each model's ordinary differential equations in a more robust way than (common) explicit schemes would; threshold equations are smoothed to avoid discontinuities in the model's objective function space; and the model equations are solved simultaneously, avoiding the physically unrealistic sequential solving of fluxes. Generalized parameter ranges are provided to assist with model inter-comparison studies. In addition to this paper and its Supplement, a user manual is provided together with several workflow scripts that show basic example applications of the toolbox. The toolbox and user manual are available from span classCombining double low line"uri"https://github.com/wknoben/MARRMoT/span (last access: 30 May 2019; a hrefCombining double low line"https://doi.org/10.5281/zenodo.3235664"https://doi.org/10.5281/zenodo.3235664). Our main scientific objective in developing this toolbox is to facilitate the inter-comparison of conceptual hydrological model structures which are in widespread use in order to ultimately reduce the uncertainty in model structure selection

Making community-supported agriculture accessible to low-income families: Findings from the Farm Fresh Foods for Healthy Kids process evaluation

A randomized trial of Farm Fresh Foods for Healthy Kids (F3HK) was initiated across 4 states and 12 farms to test whether cost-offset community-supported agriculture (CO-CSA) could improve diet quality among children in low-income families. Intervention households purchased a 50% subsidized share of local produce and were invited to nine complimentary nutrition classes. The purpose of this study was to assess F3HK reach, dose, and fidelity via a mixed methods process evaluation. Screening and enrollment records indicated reach; study records and postlesson educator surveys tracked dose delivered; CSA pickup logs, lesson sign-in sheets, postseason participant surveys, and postlesson caregiver surveys assessed dose received; and coordinator audits and educator surveys tracked fidelity. Educator interviews contextualized findings. The results of this study were as follows. Reach: enrolled caregivers (n = 305) were older (p =. 005) than eligible nonenrollees (n = 243) and more likely to be female (p <. 001). Dose: mean CSA season was 21 weeks (interquartile range [IQR]: 19-23). Median CSA pickup was 88% of the weeks (IQR: 40-100). All sites offered each class at least once. Most adults (77%) and children (54%) attended at least one class; few attended all. Eighty-two percent of caregivers indicated that their household consumed most or all produce. Median lesson activity ratings were 5/5 ("very useful"). Fidelity: CSA locations functioned with integrity to project standards. Educators taught 92% of activities but frequently modified lesson order. This study demonstrates the feasibility of pairing a CO-CSA intervention with nutrition education across geographically dispersed sites. Greater integration of intervention elements and clearer allowance for site-level modifications, particularly for educational elements, may improve intervention dose and, ultimately, impact

Recruitment of the exotic weakfish at its southernmost limit in Europe: a preliminary assessment.

Since its first record in Europe as an exotic species back in 2009 at the Schelde estuary (Belgium), the weakfish Cynoscion regalis -native from North America East coast- has increased its presence in the Iberian Peninsula waters. Identified for the first time in the Guadalquivir River estuary (2011) and later in the Sado estuary (2014), C. regalis population is increasing in the Gulf of Cadiz and is becoming a fisheries resource. Its introduction into Europe probably occurred through maritime transatlantic trade. Morais et al (2017) suggested that weakfish could have been introduced through multiple independent ballast water release events. The Guadalquivir, Sado and Schelde estuaries show similar transoceanic ship traffic to upstream important commercial ports, supporting multiple direct or secondary transatlantic introductions among European ports. The first genetic studies suggest that C. regalis populations in southern European estuaries are connected and come from a single transoceanic commercial route. Currently, the Gulf of Cadiz maintains a well-established population with frequent catches by artisanal fishing, especially in coastal waters and the estuary, where it is sold in local markets of the surrounding cities. The population in the area is constituted by mature specimens (ranging from 234 to 453 mm) that are using the estuary as a spawning area, where larvae and juvenile have also been found. In recent years, an increase in the abundance of larvae and juvenile has been observed through monthly samplings in the estuary, which indicates the culmination of the complete life cycle in the Gulf of Cadiz. These findings represent new evidence that the Guadalquivir estuary constitutes a remarkable nursery habitat for this species. This could have effects on native fauna and the ecosystem, which is why it is currently under study and evaluation (EcoInvadiz project) for helping the local Administration to establish, if needed, an appropriate management program

Stellar structure and compact objects before 1940: Towards relativistic astrophysics

Since the mid-1920s, different strands of research used stars as "physics laboratories" for investigating the nature of matter under extreme densities and pressures, impossible to realize on Earth. To trace this process this paper is following the evolution of the concept of a dense core in stars, which was important both for an understanding of stellar evolution and as a testing ground for the fast-evolving field of nuclear physics. In spite of the divide between physicists and astrophysicists, some key actors working in the cross-fertilized soil of overlapping but different scientific cultures formulated models and tentative theories that gradually evolved into more realistic and structured astrophysical objects. These investigations culminated in the first contact with general relativity in 1939, when J. Robert Oppenheimer and his students George Volkoff and Hartland Snyder systematically applied the theory to the dense core of a collapsing neutron star. This pioneering application of Einstein's theory to an astrophysical compact object can be regarded as a milestone in the path eventually leading to the emergence of relativistic astrophysics in the early 1960s.Comment: 83 pages, 4 figures, submitted to the European Physical Journal

Community supported agriculture plus nutrition education improves skills, self-efficacy, and eating behaviors among low-income caregivers but not their children: a randomized controlled trial

Background: Adults and children in the U.S. consume inadequate quantities of fruit and vegetables (FV), in part, due to poor access among households with lower socioeconomic status. One approach to improving access to FV is community supported agriculture (CSA) in which households purchase a ‘share’ of local farm produce throughout the growing season. This study examined the effects of cost-offset (half-price) CSA plus tailored nutrition education for low-income households with children. Methods: The Farm Fresh Foods for Healthy Kids (F3HK) randomized controlled trial in New York, North Carolina, Vermont, and Washington (2016–2018) assigned caregiver-child dyads (n = 305) into cost-offset CSA plus education intervention or control (delayed intervention) groups. Following one growing season of CSA participation, changes in children’s diet quality, body mass index (BMI), and physical activity; caregivers’ nutrition knowledge, attitudes, behaviors, and diet quality; and household food access and security were examined using multiple linear or logistic regression, with adjustment for baseline value within an intent-to-treat (ITT) framework in which missing data were multiply imputed. Results: No significant net effects on children’s dietary intake, BMI, or physical activity were observed. Statistically significant net improvements were observed after one growing season for caregivers’ cooking attitudes, skills, and self-efficacy; FV intake and skin carotenoid levels; and household food security. Changes in attitudes and self-efficacy remained one-year after baseline, but improvements in caregiver diet and household food security did not. The number of weeks that participants picked up a CSA share (but not number of education sessions attended) was associated with improvements in caregiver FV intake and household food security. Conclusions: Cost-offset CSA plus tailored nutrition education for low-income households improved important caregiver and household outcomes within just one season of participation; most notably, both self-reported and objectively measured caregiver FV intake and household food security improved. Households that picked up more shares also reported larger improvements. However, these changes were not maintained after the CSA season ended. These results suggest that cost-offset CSA is a viable approach to improving adult, but not child, FV intake and household food security for low-income families, but the seasonality of most CSAs may limit their potential to improve year-round dietary behavior and food security. Trial registration: ClinicalTrials.gov. NCT02770196. Registered 5 April 2016. Retrospectively registered

Influence of Vancomycin Minimum Inhibitory Concentration on the Outcome of Methicillin-Susceptible Staphylococcus aureus Left-Sided Infective Endocarditis Treated with Anti-staphylococcal Beta-Lactam Antibiotics; a Prospective Cohort Study by the International Collaboration on Endocarditis

Objectives: Left-sided methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis treated with cloxacillin has a poorer prognosis when the vancomycin minimum inhibitory concentration (MIC) is ≥1.5 mg/L. We aimed to validate this using the International Collaboration on Endocarditis cohort and to analyse whether specific genetic characteristics were associated with a high vancomycin MIC (≥1.5 mg/L) phenotype. Methods: All patients with left-sided MSSA infective endocarditis treated with antistaphylococcal β-lactam antibiotics between 2000 and 2006 with available isolates were included. Vancomycin MIC was determined by Etest as either high (≥1.5 mg/L) or low (<1.5 mg/L). Isolates underwent spa typing to infer clonal complexes and multiplex PCR for identifying virulence genes. Univariate analysis was performed to evaluate the association between in-hospital and 1-year mortality, and vancomycin MIC phenotype. Results: Sixty-two cases met the inclusion criteria. Vancomycin MIC was low in 28 cases (45%) and high in 34 cases (55%). No significant differences in patient demographic data or characteristics of infection were observed between patients with infective endocarditis due to high and low vancomycin MIC isolates. Isolates with high and low vancomycin MIC had similar distributions of virulence genes and clonal lineages. In-hospital and 1-year mortality did not differ significantly between the two groups (32% (9/28) vs. 27% (9/34), p 0.780; and 43% (12/28) vs. 29% (10/34), p 0.298, for low and high vancomycin MIC respectively). Conclusions: In this international cohort of patients with left-sided MSSA endocarditis treated with antistaphylococcal β-lactams, vancomycin MIC phenotype was not associated with patient demographics, clinical outcome or virulence gene repertoire

Attentive Learning of Sequential Handwriting Movements: A Neural Network Model

Defense Advanced research Projects Agency and the Office of Naval Research (N00014-95-1-0409, N00014-92-J-1309); National Science Foundation (IRI-97-20333); National Institutes of Health (I-R29-DC02952-01)