Toward common mechanisms for risk factors in Alzheimer's syndrome

The global strategic goal of reducing health care cost, especially the prospects for massive increases due to expanding markets for health care services demanded by aging populations and/or people with a wide range of chronic disorders-disabilities, is a complex and formidable challenge with many facets. Current projection s predict marked increases in the demand for health driven by both the exponential climb in the prevalence of chronic disabilities and the increases in the absolute numbers of people in need of some form of health care. Thus, the looming predicament for the economics of health care systems worldwide mandates the formulation of a strategic goal to foster significant expansion of global R & D efforts to discover and develop wide-ranging interventions to delay and/or prevent the onset of chronic disabling conditions. The rationale for adopting such a tactical objective is based on the premise that the costs and prevalence of chronic disabling conditions will be reduced by half even if a modest delay of 5 years in the onset of disability is obtained by a highly focused multinational research initiative. Because of the recent history of many failures in drug trials, the central thesis of this paper is to argue for the exploration-adoption of novel mechanistic ideas, theories, and paradigms for developing wide range and/or types of interventions. Although the primary focus of our discussion has been on biological approaches to therapy, we recognize the importance of emerging knowledge on nonpharmacological interventions and their potential impact in reducing health care costs. Although we may not find a drug to cure or prevent dementia for a long time, research is starting to demonstrate the potential contributes of nonpharmacological interventions toward the economics of health care in terms of rehabilitation, promoting autonomy, and potential to delay institutionalization, thus promoting healthy aging and reductions in the cost of care

Current management of patients hospitalized with community-acquired pneumonia across Europe: outcomes from REACH

Background: Data describing real-life management and treatment of community-acquired pneumonia (CAP) in Europe are limited. REACH (http://NCT01293435 webcite) was a retrospective, observational study collecting data on the management of EU patients hospitalized with CAP. The purpose of this study was to understand patient and disease characteristics in patients hospitalized with CAP and to review current clinical practices and outcomes. Methods: Patients were aged ≥18 years, hospitalized with CAP between March 2010 and February 2011, and requiring in-hospital treatment with intravenous antibiotics. An electronic Case Report Form was used to collect patient, disease and treatment variables, including type of CAP, medical history, treatment setting, antibiotics administered and clinical outcomes. Results: Patients (N = 2,039) were recruited from 128 centres in ten EU countries (Belgium, France, Germany, Greece, Italy, the Netherlands, Portugal, Spain, Turkey, UK). The majority of patients were aged ≥65 years (56.4%) and had CAP only (78.8%). Initial antibiotic treatment modification occurred in 28.9% of patients and was more likely in certain groups (patients with comorbidities; more severely ill patients; patients with healthcare-associated pneumonia, immunosuppression or recurrent episodes of CAP). Streamlining (de-escalation) of therapy occurred in 5.1% of patients. Mean length of hospital stay was 12.6 days and overall mortality was 7.2%. Conclusion: These data provide a current overview of clinical practice in patients with CAP in EU hospitals, revealing high rates of initial antibiotic treatment modification. The findings may precipitate reassessment of optimal management regimens for hospitalized CAP patients

Coalescent-based species delimitation in the sand lizards of the Liolaemus wiegmannii complex (Squamata: Liolaemidae)

Coalescent-based algorithms coupled with the access to genome-wide data have become powerful tools forassessing questions on recent or rapid diversification, as well as delineating species boundaries in the absence of reciprocal monophyly. In southern South America, the diversification of Liolaemus lizards during the Pleistocene is well documented and has been attributed to the climatic changes that characterized this recent period of time. Past climatic changes had harsh effects at extreme latitudes, including Patagonia, but habitat changes at intermediate latitudes of South America have also been recorded, including expansion of sand fields over northern Patagonia and Pampas). In this work, we apply a coalescent-based approach to study the diversification of the Liolaemus wiegmannii species complex, a morphologically conservative clade that inhabits sandy soils across northwest and south-central Argentina, and the south shores of Uruguay. Using four standard sequence markers (mitochondrial DNA and three nuclear loci) along with ddRADseq data we inferred species limits and a time calibrated species tree for the L. wiegmannii complex in order to evaluate the influence of Quaternary sand expansion/retraction cycles on diversification. We also evaluated the evolutionary independence of the recently described L. gardeli and inferred its phylogenetic position relative to L. wiegmannii. We find strong evidence for six allopatric candidate species within L. wiegmannii, which diversified during the Pleistocene. The Great Patagonian Glaciation (∼1 million years before present) likely split the species complex into two main groups: one composed of lineages associated with sub-Andean sedimentary formations, and the other mostly related to sand fields in the Pampas and northern Patagonia. We hypothesize that early speciation within L. wiegmannii was influenced by the expansion of sand dunes throughout central Argentina and Pampas. Finally, L. gardeli is supported as a distinct lineage nested within the L. wiegmannii complex.Fil: Villamil, Joaquín. Universidad de la República. Facultad de Ciencias; UruguayFil: Avila, Luciano Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; ArgentinaFil: Morando, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; ArgentinaFil: Sites, Jack W.. University Brigham Young; Estados UnidosFil: Leaché, Adam D.. University of Washington; Estados UnidosFil: Maneyro, Raúl. Universidad de la República. Facultad de Ciencias; UruguayFil: Camargo Bentaberry, Arley. Universidad de la República; Urugua

A revised geographical range for Liolaemus elongates Koslowsky, 1896 (Squamata: Liolaemini) in Argentina: review of reported and new-data based distribution with new localities

Estimating the effective geographical ranges of species is central to species-oriented conservation and management. In this paper, we review the geographical distribution of Liolaemus elongatus Koslowsky, 1896 with three new records for northern Chubut and southern Río Negro provinces, Argentina. Based on detailed locality records pooled from multiple data sources, including new records obtained for this study, we revise the range of L. elongatus sensu stricto and provide geographical distribution maps comparing the previously recognized range to that proposed herein. Our results show that L. elongatus possesses a much more limited geographic distribution than previously thought, being restricted to areas south of 38°S latitude; the newly proposed range is merely half the species formerly recognized geographical distribution

The RELAMPAGO Lightning Mapping Array: Preliminary Scientific Results and Application to GLM Calibration and Validation

During November 2018 through April 2019, an 11-station NASA lightning mapping array (LMA) was installed in the Cordoba region of Argentina, in support of GOES-16 Geostationary Lightning Mapper (GLM) calibration and validation, as well as the Remote sensing of Electrification, Lightning, And Mesoscale/microscale Processes with Adaptive Ground Observations (RELAMPAGO) field campaign. This region of Argentina is well known for frequent, intense thunderstorms and severe weather. The LMA was monitored remotely via the Internet throughout its deployment, but due to bandwidth limitations no real-time data were available. Custom GOES-16 imagery provided by NASA SPoRT assisted with monitoring of thunderstorm cases. Occasional site visits were done to obtain data disks, perform routine maintenance, and troubleshoot problems. During the deployment the network captured lightning in a variety of storm modes, including ordinary and severe multicells, supercells, and mesoscale convective systems. Many examples of normal-polarity thunderstorms, as well as a few examples of anomalously charged thunderstorms, were observed. Long (100+ km) horizontally stratified lightning flashes, as well as lightning in overshooting tops, also were frequently observed. Supporting research radar observations were available through January 2019, with operational radar coverage available after that time. Some cases featured supporting ABI meso scanning. This presentation will report on the LMA deployment in context with the RELAMPAGO field campaign, show results from some representative case studies, and will provide initial comparisons to GLM observations

Walking for transportation in large Latin American cities: walking-only trips and total walking events and their sociodemographic correlates.

Walking for transportation is a common and accessible means of achieving recommended physical activity levels, while providing important social and environmental co-benefits. Even though walking in rapidly growing urban areas has become especially challenging given the increasing dependence on motorised transportation, walking remains a major mode of transportation in Latin American cities. In this paper we aimed to quantify self-reported walking for transportation in Mexico City, Bogota, Santiago de Chile, Sao Paulo, and Buenos Aires, by identifying both walking trips that are conducted entirely on foot and walking events involved in trips mainly conducted on other means of transportation (e.g. private vehicle, public transit) among individuals ≥5-years old. We show how walking-only trips account for approximately 30% trips in the analysed cities, and we evidence how the pedestrian dimension of mobility is largely underestimated if walking that is incidental to other transportation modes is not accounted for: when considering all walking events, we observed an increase between 73% and 217% in daily walking time. As a result, we estimated that between 19% and 25% of residents in these cities meet the WHO physical activity guidelines solely from walking for transportation. The results of the study also suggest that the promotion of public transportation in large Latin American cities can especially help certain population groups achieve the daily recommended levels of physical activity, while among low-income groups accessibility and safety seem to be the key challenges to be addressed

Effect of Chronic Administration of Resveratrol on Cognitive Performance during Aging Process in Rats

The increase in the elderly population has generated concern to meet health demands. The research efforts to elucidate the mechanisms of damage associated with aging have also been significantly increased, especially in order to avoid the reduction of the cognitive abilities in geriatric patients, resulting from the damage generated mainly at the level of the hippocampus during old age. At present, many studies describe resveratrol as an antiaging component. There are reports that it can activate the Sirt1 gene related to antiaging, emulating the effects obtained by caloric restriction in rodents. The aim of the study was to evaluate the effect of chronic administration of resveratrol (10 mg/kg) on cognitive performance in behavioral tests after 8 months of treatment and on the preservation of cerebral integrity in the cytoarchitecture of regions CA1 and CA2. Results showed that the cytoarchitecture of the CA1 and CA2 regions in the hippocampus retained their integrity over time in rats treated with resveratrol, and the behavioral test performed revealed that chronic resveratrol administration for 8 months showed improvements in cognitive performance. The results indicate that resveratrol may exhibit therapeutic potential for age-related conditions

Identification of the Photoreceptor Transcriptional Co-Repressor SAMD11 as Novel Cause of Autosomal Recessive Retinitis Pigmentosa

Retinitis pigmentosa (RP), the most frequent form of inherited retinal dystrophy is characterized by progressive photoreceptor degeneration. Many genes have been implicated in RP development, but several others remain to be identified. Using a combination of homozygosity mapping, whole-exome and targeted next-generation sequencing, we found a novel homozygous nonsense mutation in SAMD11 in five individuals diagnosed with adult-onset RP from two unrelated consanguineous Spanish families. SAMD11 is ortholog to the mouse major retinal SAM domain (mr-s) protein that is implicated in CRX-mediated transcriptional regulation in the retina. Accordingly, protein-protein network analysis revealed a significant interaction of SAMD11 with CRX. Immunoblotting analysis confirmed strong expression of SAMD11 in human retina. Immunolocalization studies revealed SAMD11 was detected in the three nuclear layers of the human retina and interestingly differential expression between cone and rod photoreceptors was observed. Our study strongly implicates SAMD11 as novel cause of RP playing an important role in the pathogenesis of human degeneration of photoreceptors.This work was supported by several grants from the Spanish Centre for Biomedical Network Research on Rare Diseases (CIBERER)(06/07/0036), Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Health)/FEDER, including FIS (PI013/00226) and RETICS (RD09/0076/00101 and RD12/0034/0010), Ministry of Economy and Competitiveness (MINECO), including FEDER (BFU2012-36845), and BIO2011-27069, Conselleria de Educació of the Valencia Community (PROMETEOII/2014/025), Spanish National Organization of the Blind (ONCE) and the Spanish Fighting Blindness Foundation (FUNDALUCE). M.C. was sponsored by the Miguel Servet Program for Researchers in the Spanish National Health Service (CP12/03256) and RSA by Sara Borrel Postdoctoral Program (CD12/00676), both from the ISCIII/FEDER. A.A-F. was sponsored by CIBERER, RPC is supported by Fundación Conchita Rábago (FCR), L.C is sponsored by RETICS (RD12/0034/0010) from ISCIII and L.d.S. was supported by CAPES Foundation, Ministry of Education of Brazil

Highlights from the Pierre Auger Observatory

The Pierre Auger Observatory is the world's largest cosmic ray observatory. Our current exposure reaches nearly 40,000 km$^2$ str and provides us with an unprecedented quality data set. The performance and stability of the detectors and their enhancements are described. Data analyses have led to a number of major breakthroughs. Among these we discuss the energy spectrum and the searches for large-scale anisotropies. We present analyses of our X$_{max}$ data and show how it can be interpreted in terms of mass composition. We also describe some new analyses that extract mass sensitive parameters from the 100% duty cycle SD data. A coherent interpretation of all these recent results opens new directions. The consequences regarding the cosmic ray composition and the properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray Conference, Rio de Janeiro 201