A health systems resilience research agenda: moving from concept to practice.

Health system resilience, known as the ability for health systems to absorb, adapt or transform to maintain essential functions when stressed or shocked, has quickly gained popularity following shocks like COVID-19. The concept is relatively new in health policy and systems research and the existing research remains mostly theoretical. Research to date has viewed resilience as an outcome that can be measured through performance outcomes, as an ability of complex adaptive systems that is derived from dynamic behaviour and interactions, or as both. However, there is little congruence on the theory and the existing frameworks have not been widely used, which as diluted the research applications for health system resilience. A global group of health system researchers were convened in March 2021 to discuss and identify priorities for health system resilience research and implementation based on lessons from COVID-19 and other health emergencies. Five research priority areas were identified: (1) measuring and managing systems dynamic performance, (2) the linkages between societal resilience and health system resilience, (3) the effect of governance on the capacity for resilience, (4) creating legitimacy and (5) the influence of the private sector on health system resilience. A key to filling these research gaps will be longitudinal and comparative case studies that use cocreation and coproduction approaches that go beyond researchers to include policy-makers, practitioners and the public

Calibration of the Logarithmic-Periodic Dipole Antenna (LPDA) Radio Stations at the Pierre Auger Observatory using an Octocopter

An in-situ calibration of a logarithmic periodic dipole antenna with a frequency coverage of 30 MHz to 80 MHz is performed. Such antennas are part of a radio station system used for detection of cosmic ray induced air showers at the Engineering Radio Array of the Pierre Auger Observatory, the so-called Auger Engineering Radio Array (AERA). The directional and frequency characteristics of the broadband antenna are investigated using a remotely piloted aircraft (RPA) carrying a small transmitting antenna. The antenna sensitivity is described by the vector effective length relating the measured voltage with the electric-field components perpendicular to the incoming signal direction. The horizontal and meridional components are determined with an overall uncertainty of 7.4^{+0.9}_{-0.3} % and 10.3^{+2.8}_{-1.7} % respectively. The measurement is used to correct a simulated response of the frequency and directional response of the antenna. In addition, the influence of the ground conductivity and permittivity on the antenna response is simulated. Both have a negligible influence given the ground conditions measured at the detector site. The overall uncertainties of the vector effective length components result in an uncertainty of 8.8^{+2.1}_{-1.3} % in the square root of the energy fluence for incoming signal directions with zenith angles smaller than 60{\deg}.Comment: Published version. Updated online abstract only. Manuscript is unchanged with respect to v2. 39 pages, 15 figures, 2 table

The Role of Robo3 in the Development of Cortical Interneurons

A number of studies in recent years have shown that members of the Roundabout (Robo) receptor family, Robo1 and Robo2, play significant roles in the formation of axonal tracks in the developing forebrain and in the migration and morphological differentiation of cortical interneurons. Here, we investigated the expression and function of Robo3 in the developing cortex. We found that this receptor is strongly expressed in the preplate layer and cortical hem of the early cortex where it colocalizes with markers of Cajal–Retzius cells and interneurons. Analysis of Robo3 mutant mice at early (embryonic day [E] 13.5) and late (E18.5) stages of corticogenesis revealed no significant change in the number of interneurons, but a change in their morphology at E13.5. However, preliminary analysis on a small number of mice that lacked all 3 Robo receptors indicated a marked reduction in the number of cortical interneurons, but only a limited effect on their morphology. These observations and the results of other recent studies suggest a complex interplay between the 3 Robo receptors in regulating the number, migration and morphological differentiation of cortical interneurons

WW Domains of the Yes-Kinase-Associated-Protein (YAP) Transcriptional Regulator Behave as Independent Units with Different Binding Preferences for PPxY Motif-Containing Ligands

YAP is a WW domain-containing effector of the Hippo tumor suppressor pathway, and the object of heightened interest as a potent oncogene and stemness factor. YAP has two major isoforms that differ in the number of WW domains they harbor. Elucidating the degree of co-operation between these WW domains is important for a full understanding of the molecular function of YAP. We present here a detailed biophysical study of the structural stability and binding properties of the two YAP WW domains aimed at investigating the relationship between both domains in terms of structural stability and partner recognition. We have carried out a calorimetric study of the structural stability of the two YAP WW domains, both isolated and in a tandem configuration, and their interaction with a set of functionally relevant ligands derived from PTCH1 and LATS kinases. We find that the two YAP WW domains behave as independent units with different binding preferences, suggesting that the presence of the second WW domain might contribute to modulate target recognition between the two YAP isoforms. Analysis of structural models and phage-display studies indicate that electrostatic interactions play a critical role in binding specificity. Together, these results are relevant to understand of YAP function and open the door to the design of highly specific ligands of interest to delineate the functional role of each WW domain in YAP signaling.This work was supported by the Spanish Ministry of Education and Science [grant BIO2009-13261-CO2], the Spanish Ministry of Economy and Competitivity [grant BIO2012-39922-CO2] including FEDER (European Funds for Regional Development) funds and the Governement of Andalusia [grant CVI-5915]. Marius Sudol was supported by PA Breast Cancer Coalition Grants (#60707 and #920093) plus the Geisinger Clinic

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Inferences on mass composition and tests of hadronic interactions from 0.3 to 100 EeV using the water-Cherenkov detectors of the Pierre Auger Observatory

CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO CARLOS CHAGAS FILHO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPWe present a new method for probing the hadronic interaction models at ultrahigh energy and extracting details about mass composition. This is done using the time profiles of the signals recorded with the water-Cherenkov detectors of the Pierre Auger Observatory. The profiles arise from a mix of the muon and electromagnetic components of air showers. Using the risetimes of the recorded signals, we define a new parameter, which we use to compare our observations with predictions from simulations. We find, first, inconsistencies between our data and predictions over a greater energy range and with substantially more events than in previous studies. Second, by calibrating the new parameter with fluorescence measurements from observations made at the Auger Observatory, we can infer the depth of shower maximum X-max for a sample of over 81,000 events extending from 0.3 to over 100 EeV. Above 30 EeV, the sample is nearly 14 times larger than what is currently available from fluorescence measurements and extending the covered energy range by half a decade. The energy dependence of < X-max gt; is compared to simulations and interpreted in terms of the mean of the logarithmic mass. We find good agreement with previous work and extend the measurement of the mean depth of shower maximum to greater energies than before, reducing significantly the statistical uncertainty associated with the inferences about mass composition.9612122CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO CARLOS CHAGAS FILHO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO CARLOS CHAGAS FILHO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPSem informaçãoSem informaçãoSem informação1999/05404-32010/07359-6The successful installation, commissioning, and operation of the Pierre Auger Observatory would not have been possible without the strong commitment and effort from the technical and administrative staff in Malargue. We are very grateful to the following agencies and organizations for financial support: (Argentina) Comision Nacional de Energia Atomica; Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCyT); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Gobierno de la Provincia de Mendoza; Municipalidad de Malargue; and NDM Holdings and Valle Las Lenas in gratitude for their continuing cooperation over land access; (Australia) the Australian Research Council; (Brazil) Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); Financiadora de Estudos e Projetos (FINEP); Fundacao de Amparo a Pesquisa do Estado de Rio de Janeiro (FAPERJ); Sao Paulo Research Foundation (FAPESP) Grants No. 2010/07359-6 and No. 1999/05404-3; Ministerio de Ciencia e Tecnologia (MCT); (Czech Republic) Grants No. MSMT CR LG15014, LO1305, LM2015038, and CZ.02.1.01/0.0/0.0/16\_013/0001402; (France) Centre de Calcul IN2P3/CNRS; Centre National de la Recherche Scientifique (CNRS); Conseil Regional Ile-de-France; Departement Physique Nucleaire et Corpusculaire (PNC-IN2P3/CNRS); Departement Sciences de l'Univers (SDU-INSU/CNRS); Institut Lagrange de Paris (ILP) Grant No. LABEX ANR-10-LABX-63 within the Investissements d'Avenir Programme Grant No. ANR-11-IDEX-0004-02; (Germany) Bundesministerium fur Bildung und Forschung (BMBF); Deutsche Forschungsgemeinschaft (DFG); Finanzministerium Baden-Wurttemberg; Helmholtz Alliance for Astroparticle Physics (HAP); Helmholtz-Gemeinschaft Deutscher Forschungszentren (HGF); Ministerium fur Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen; Ministerium fur Wissenschaft, Forschung und Kunst des Landes Baden-Wurttemberg; (Italy) Istituto Nazionale di Fisica Nucleare (INFN); Istituto Nazionale di Astrofisica (INAF); Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR); CETEMPS Center of Excellence; Ministero degli Affari Esteri (MAE); (Mexico) Consejo Nacional de Ciencia y Tecnologia (CONACYT) Grant No. 167733; Universidad Nacional Autonoma de Mexico (UNAM); PAPIIT DGAPA-UNAM; (Netherlands) Ministerie van Onderwijs, Cultuur en Wetenschap; Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO); Stichting voor Fundamenteel Onderzoek der Materie (FOM); (Poland) National Centre for Research and Development, Grants No. ERA-NET-ASPERA/01/11 and No. ERA-NET-ASPERA/02/11; National Science Centre, Grants No. 2013/08/M/ST9/00322, No. 2013/08/M/ST9/00728, No. HARMONIA 5-2013/10/M/ST9/00062, and No. UMO-2016/22/M/ST9/00198; (Portugal) Portuguese national funds and FEDER funds within Programa Operacional Factores de Competitividade through Fundacao para a Ciencia e a Tecnologia (COMPETE); (Romania) Romanian Authority for Scientific Research ANCS; CNDI-UEFISCDI partnership projects Grants No. 20/2012, No. 194/2012, and No. PN 16 42 01 02; (Slovenia) Slovenian Research Agency; (Spain) Comunidad de Madrid; Fondo Europeo de Desarrollo Regional (FEDER) funds; Ministerio de Economia y Competitividad; Xunta de Galicia; European Community 7th Framework Program Grant No. FP7-PEOPLE-2012-IEF-328826; (USA) Department of Energy, Contracts No. DE-AC02-07CH11359, No. DE-FR02-04ER41300, No. DE-FG02-99ER41107, and No. DE-SC0011689; National Science Foundation, Grant No. 0450696; The Grainger Foundation; Marie Curie-IRSES/EPLANET (European Union); European Particle Physics Latin American Network; European Union 7th Framework Program, Grant No. PIRSES-2009-GA-246806; European Union's Horizon 2020 Research and Innovation Programme (Grant No. 646623); and UNESCO

The life history of human foraging: Cross-cultural and individual variation

Human adaptation depends on the integration of slow life history, complex production skills, and extensive sociality. Refining and testing models of the evolution of human life history and cultural learning benefit from increasingly accurate measurement of knowledge, skills, and rates of production with age. We pursue this goal by inferring hunters' increases and declines of skill from approximately 23,000 hunting records generated by more than 1800 individuals at 40 locations. The data reveal an average age of peak productivity between 30 and 35 years of age, although high skill is maintained throughout much of adulthood. In addition, there is substantial variation both among individuals and sites. Within study sites, variation among individuals depends more on heterogeneity in rates of decline than in rates of increase. This analysis sharpens questions about the coevolution of human life history and cultural adaptation

Operations of the Pierre Auger Observatory

The construction of the first stage of the Pierre Auger Observatory, designed for research of ultra-high energy cosmic rays, began in 2001 with a prototype system. The Observatory has been collecting data since early 2004 and was completed in 2008. The Observatory is situated at 1400 m above sea level near Malargüe, (Mendoza province) in western Argentina, covering a vast plain of 3000 km2, known as the Pampa Amarilla. The Observatory consists of a hybrid detector, in which there are 1660 water-Cherenkov stations, forming the Surface Detector (SD) and 27 peripheral atmospheric fluorescence telescopes, comprising the Fluorescence Detector (FD). Over time, the Auger Observatory has been enhanced with different R&amp;D prototypes and is recently being to an important upgrade called AugerPrime. In the present contribution, the general operations of the SD and FD will be described. In particular the FD shift procedure - executable locally in Malargüe or remotely by teams in control rooms abroad within the Collaboration - and the newly SD shifts (operating since 2019) will be explained. Additionally, the SD and FD maintenance campaigns, as well as the data taking and data handling at a basic level, will be reported

A combined fit of energy spectrum, shower depth distribution and arrival directions to constrain astrophysical models of UHECR sources

The combined fit of the measured energy spectrum and distribution of depths of shower maximum of ultra-high-energy cosmic rays is known to constrain the parameters of astrophysical scenarios with homogeneous source distributions. Further measurements show that the cosmic-ray arrival directions agree better with the directions and fluxes of catalogs of starburst galaxies and active galactic nuclei than with isotropy. Here, we present a novel combination of both analyses. For that, a three-dimensional universe model containing a nearby source population and a homogeneous background source distribution is built, and its parameters are adapted using a combined fit of the energy spectrum, depth of shower maximum distribution and energy-dependent arrival directions. The model takes into account a symmetric magnetic field blurring, source evolution and interactions during propagation. We use simulated data, which resemble measurements of the Pierre Auger Observatory, to evaluate the method’s sensitivity. With this, we are able to verify that the source parameters as well as the fraction of events from the nearby source population and the size of the magnetic field blurring are determined correctly, and that the data is described by the fitted model including the catalog sources with their respective fluxes and three-dimensional positions. We demonstrate that by combining all three measurements we reach the sensitivity necessary to discriminate between the catalogs of starburst galaxies and active galactic nuclei