Performance analysis of persistence technologies for cloud repositories of models

The growing adoption of Model Driven Development (MDD) in companies during last decade arises some model interchange problems. Companies need support to interchange models and reuse parts of them for developing new projects. Traditional tools for model edition and model interchange have different performance issues related to the models storage. There are mainly two styles to organize the persistence of models into repositories: a complex and large model or a large amount of small models. This last approach is common in companies that generate software from models. In this paper, we analyse performance properties of different persistence technologies to store small/medium-scale models, the analysis results should be considered in the design of model repositories in the cloud. With this aim, we have designed and developed a generic architecture to evaluate each persistence technology under similar situations

Are Passages Enough? The MIRACLE Team Participation at QA@CLEF2009

Preceedins of: 10th Workshop of the Cross-Language Evaluation Forum, CLEF 2009.Took place September 30 - October 2, 2009,in Corfu, Greece. The event Web site is http://www.clef-campaign.org/2009.htmlThis paper summarizes the participation of the MIRACLE team in the Multilingual Question Answering Track at CLEF 2009. In this campaign, we took part in the monolingual Spanish task at ResPubliQA and submitted two runs. We have adapted our QA system to the new JRC-Acquis collection and the legal domain. We tested the use of answer filtering and ranking techniques against a baseline system using passage retrieval with no success. The run using question analysis and passage retrieval obtained a global accuracy of 0.33, while the addition of an answer filtering resulted in 0.29. We provide an analy-sis of the results for different questions types to investigate why it is difficult to leverage previous QA techniques. Another task of our work has been the appli-cation of temporal management to QA. Finally we include some discussion of the problems found with the new collection and the complexities of the domain.This work has been partially supported by the Research Network MAVIR (S-0505/TIC/000267) and by the project BRAVO (TIN2007- 67407-C3-01).Publicad

Leishmaniasis and tumor necrosis factor alpha antagonists in the mediterranean basin. A switch in clinical expression

TNF-α blockers therapy; Leishmaniasis; Retrospective observational studyTerapia con bloqueadores de TNF-α; Leishmaniasis; Estudio observacional retrospectivoTeràpia bloquejadora de TNF-α; Leishmaniosi; Estudi observacional retrospectiuBACKGROUND: Tumor necrosis factor alpha (TNF-α) blockers are recognized as a risk factor for reactivation of granulomatous infections. Leishmaniasis has been associated with the use of these drugs, although few cases have been reported. METHODOLOGY: We performed a retrospective observational study including patients with confirmed leishmaniasis acquired in the Mediterranean basin that were under TNF-α blockers therapy at the moment of the diagnosis. Patients diagnosed in our hospital from 2008 to 2018 were included. Moreover, a systematic review of the literature was performed and cases fulfilling the inclusion criteria were also included. PRINCIPAL FINDINGS: Forty-nine patients were analyzed including nine cases from our series. Twenty-seven (55.1%) cases were male and median age was 55 years. Twenty-five (51%) patients were under infliximab treatment, 20 (40.8%) were receiving adalimumab, 2 (4.1%) etanercept, one (2%) golimumab and one (2%) a non-specified TNF-α blocker. Regarding clinical presentation, 28 (57.1%) presented as cutaneous leishmaniasis (CL), 16 (32.6%) as visceral leishmaniasis (VL) and 5 (10.2%) as mucocutaneous leishmaniasis (MCL). All VL and MCL patients were treated with systemic therapies. Among CL patients, 13 (46.4%) were treated with a systemic drug (11 received L-AmB, one intramuscular antimonials and one miltefosine) while 14 (50%) patients were given local treatment (13 received intralesional pentavalent antimonials, and one excisional surgery). TNF-α blockers were interrupted in 32 patients (65.3%). After treatment 5 patients (10.2%) relapsed. Four patients with a CL (3 initially treated with local therapy maintaining TNF-α blockers and one treated with miltefosine) and one patient with VL treated with L-AmB maintaining TNF-α blockers. CONCLUSIONS: This data supports the assumption that the blockage of TNF-α modifies clinical expression of leishmaniasis in endemic population modulating the expression of the disease leading to atypical presentations. According to the cases reported, the best treatment strategy would be a systemic drug and the discontinuation of the TNF-α blockers therapy until clinical resolution

Lockdown measures and relative changes in the age-specific incidence of SARS-CoV-2 in Spain

During the first months of the SARS-CoV-2 epidemic in 2020, Spain implemented an initial lockdown period on March 15 followed by a strengthened lockdown period on March 30 when only essential workers continued to commute to work. However, little is known about the epidemic dynamics in different age groups during these periods. We used the daily number of COVID-19 cases (by date of symptom onset) reported to the National Epidemiological Surveillance Network (RENAVE) among individuals aged 15-19y through 65-69y. For each age group g, we computed the proportion PrE(g) of individuals in age group g among all reported cases aged 15-69y during the pre-lockdown period (March 1-10, 2020) and the corresponding proportion PrL(g) during two lockdown periods (initial: 25 March-3 April; strengthened: 8-17 April, 2020). For each lockdown period, we computed the proportion ratios PR(g)= PrL(g)/PrE(g). For each pair of age groups g1,g, PR(g)>PR(g) implies a relative increase in the incidence of detected SARS-CoV-2 infection in the age group g compared with g for the lockdown period vs. the pre-lockdown period. For the initial lockdown period, the highest PR values were in age groups 50-54y (PR=1.21; 95% CI: 1.12,1.30) and 55-59y (PR=1.19; 1.11,1.27). For the second lockdown period, the highest PR values were in age groups 15-19y (PR=1.26; 0.95,1.68) and 50-54y (PR=1.20; 1.09,1.31). Our results suggest that different outbreak control measures led to different changes in the relative incidence by age group. During the initial lockdown period, when non-essential work was allowed, individuals aged 40-64y, particularly those aged 50-59y, had a higher relative incidence compared with the pre-lockdown period. Younger adults/older adolescents had an increased relative incidence during the later, strengthened lockdown. The role of different age groups during the epidemic should be considered when implementing future mitigation efforts

Understanding the evolution and spread of chikungunya virus in the Americas using complete genome sequences

Local transmission of chikungunya virus (CHIKV) was first detected in the Americas in December 2013, after which it spread rapidly throughout the Caribbean islands and American mainland, causing a major chikungunya fever epidemic. Previous phylogenetic analysis of CHIKV from a limited number of countries in the Americas suggests that an Asian genotype strain was responsible, except in Brazil where both Asian and East/Central/South African (ECSA) lineage strains were detected. In this study, we sequenced thirty-three complete CHIKV genomes from viruses isolated in 2014 from fourteen Caribbean islands, the Bahamas and two mainland countries in the Americas. Phylogenetic analyses confirmed that they all belonged to the Asian genotype and clustered together with other Caribbean and mainland sequences isolated during the American outbreak, forming an 'Asian/American' lineage defined by two amino acid substitutions, E2 V368A and 6K L20M, and divided into two well-supported clades. This lineage is estimated to be evolving at a mean rate of 5 x 10-4 substitutions per site per year (95% higher probability density, 2.9-7.9 x 10-4) and to have arisen from an ancestor introduced to the Caribbean (most likely from Oceania) in about March 2013, 9 months prior to the first report of CHIKV in the Americas. Estimation of evolutionary rates for individual gene regions and selection analyses indicate that (in contrast to the Indian Ocean Lineage that emerged from the ECSA genotype followed by adaptive evolution and with a significantly higher substitution rate) the evolutionary dynamics of the Asian/American lineage are very similar to the rest of the Asian genotype and natural selection does not appear to have played a major role in its emergence. However, several codon sites with evidence of positive selection were identified within the non-structural regions of Asian genotype sequences outside of the Asian/American lineage

Near real-time surveillance of the SARS-CoV-2 epidemic with incomplete data

When responding to infectious disease outbreaks, rapid and accurate estimation of the epidemic trajectory is critical. However, two common data collection problems affect the reliability of the epidemiological data in real time: missing information on the time of first symptoms, and retrospective revision of historical information, including right censoring. Here, we propose an approach to construct epidemic curves in near real time that addresses these two challenges by 1) imputation of dates of symptom onset for reported cases using a dynamically-estimated "backward" reporting delay conditional distribution, and 2) adjustment for right censoring using the NobBS software package to nowcast cases by date of symptom onset. This process allows us to obtain an approximation of the time-varying reproduction number (Rt) in real time. We apply this approach to characterize the early SARS-CoV-2 outbreak in two Spanish regions between March and April 2020. We evaluate how these real-time estimates compare with more complete epidemiological data that became available later. We explore the impact of the different assumptions on the estimates, and compare our estimates with those obtained from commonly used surveillance approaches. Our framework can help improve accuracy, quantify uncertainty, and evaluate frequently unstated assumptions when recovering the epidemic curves from limited data obtained from public health systems in other locations.PMD was supported by the fellowship Ramón Areces Foundation. JAH was funded by the National Institute of General Medical Sciences, Award U54GM088558, and the National Institutes of Health Director’s Early Independence, Award DP5-OD028145. ML was supported by the Morris-Singer Fund and by a subcontract from the Carnegie Mellon University under an award from the US Centers for Disease Control and Prevention, Award U01IP001121). MS was supported by the National Institute Of General Medical Sciences, Award R01GM130668-02. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

A combined dietary approach using isotope and dental buccal-microwear analysis of human remains from the Neolithic, Roman and Medieval periods from the archaeological site of Tossal de les Basses (Alicante, Spain)

Stable isotope and dental-microwear analysis aremethods commonly used to reconstruct dietary habits in modern and ancient human populations. However, it is rare that they are both used together in the same study, and here both methods are combined to obtain information on human dietary habits from the site of Tossal de les Basses (Alicante, Spain) through time. Middle Neolithic, Late Roman and Medieval (Islamic) individuals have been analyzed for carbon and nitrogen stable isotope ratios of bone collagen, as well as for buccal-dental microwear. Overall, δ13C and δ15N isotopic values show that for all periods the diet was mainly based on C3 terrestrial resources. However, the isotopic signature suggests a small, but clear amount ofmarine protein consumption during the Neolithic period and possibly also for a few individuals from the Medieval period. When compared to other studies from the region, it is also possible to see that the consumption of C4 resources was much more extensive during Medieval times than in previous periods. Microwear scratch density and length found for teeth fromthe Neolithic and Medieval periods reflect a diet inwhich tough foods predominated, requiring substantial pressure to chew in comparison with what was recorded for the Roman individuals. Combined with the δ15N data, the microwear signature suggests a higher input of marine/gritty resources among the Neolithic and Medieval populations compared to the Romans. Our findings also suggest that dietary patterns might be explained by cultural and technological population factors rather than habitat resource availability

Anti‑inflammatory drugs and uterine cervical cancer cells: Antineoplastic effect of meclofenamic acid

Uterine cervical cancer (UCC) is one of the main causes of cancer-associated mortality in women. Inflammation has been identified as an important component of this neoplasia; in this context, anti-inflammatory drugs represent possible prophylactic and/or therapeutic alternatives that require further investigation. Anti-inflammatory drugs are common and each one may exhibit a different antineoplastic effect. As a result, the present study investigated different anti-inflammatory models of UCC in vitro and in vivo. Celecoxib, sulindac, nimesulide, dexamethasone, meclofenamic acid, flufenamic acid and mefenamic acid were tested in UCC HeLa, VIPA, INBL and SiHa cell lines. The cytotoxicity of the drugs was evaluated in vitro. Celecoxib, sulindac, nimesulide, mefenamic acid and flufenamic acid presented with slight to moderate toxicity (10–40% of cell death corresponding to 100 µM) in certain cell lines, while meclofenamic acid exhibited significant cytotoxicity in all essayed cell lines (50–90% of cell death corresponding to 100 µM). The meclofenamic acid was tested in murine models (immunodeficient and immunocompetent) of UCC, which manifested a significant reduction in tumor growth and increased mouse survival. It was demonstrated that of the evaluated anti-inflammatory drugs, meclofenamic acid was the most cytotoxic, with a significant antitumor effect in murine models. Subsequent studies are necessary to evaluate the clinical utility of this drug

A promising novel formulation for articular cartilage regeneration: Preclinical evaluation of a treatment that produces SOX9 overexpression in human synovial fluid cells

Osteoarthritis (OA) is a chronic disorder of synovial joints, in which there is progressive softening and disintegration of the articular cartilage. OA is the most common form of arthritis, and is the primary cause of disability and impaired quality of life in the elderly. Despite considerable medical necessity, no treatment has yet been proven to act as a disease‑modifying agent that may halt or reverse the structural progression of OA. The replacement of the joint with a prosthesis appears to be the best option in the advanced stages of the disease. A formulation (BIOF2) for cartilage regeneration has been recently developed. The present study evaluated the effects of BIOF2 on gene expression in human cell cultures, followed by efficacy trials in three OA animal models. Human synovial fluid cells that were exposed to the formulation exhibited increased transcription factor SOX‑9 (SOX9; chondrogenic factor) expression, and decreased mimecan (mineralization inducer) and macrophage‑stimulating protein receptor (osteoclastogenic factor) expression. The intra‑articular application of BIOF2 in the animal models significantly increased cartilage thickness from 12 to 31% at 28 days, compared with articular cartilage treated with saline solution. The articular area and number of chondrocytes additionally increased significantly, maintaining an unaltered chondrocyte/mm2 proportion. Evaluation of the histological architecture additionally displayed a decrease in the grade of articular damage in the groups treated with BIOF2. In conclusion, BIOF2 has proven to be effective for treating OA in animal models, most likely due to SOX9 overexpression in articular cells

Adenovirus 5 produces obesity and adverse metabolic, morphological, and functional changes in the long term in animals fed a balanced diet or a high‑fat diet: a study on hamsters

Adenovirus 5 (Ad-5) infection is a common cause of acute respiratory infections and the main vector used in gene therapy. There are few studies on the relationship of Ad-5 to obesity. In the present study, we evaluated the chronic effects of Ad-5 infection on golden (Syrian) hamsters fed either a balanced diet (BD) or a high-fat diet (HFD). After a single inoculation with Ad-5 (1 × 107 pfu), the body weight of the animals was measured weekly. Medium-term (22 weeks) serum biochemical analyses and long-term (44 weeks) liver morphology, adiposity, and locomotive functionality (movement velocity) assessments were carried out. In the animals fed the BD, adenovirus infection produced hyperglycemia and hyperlipidemia. In the long term, it produced a 57% increase in epididymal pad fat and a 30% body weight gain compared with uninoculated animals. In addition, morphological changes related to non-alcoholic fatty liver disease (NAFLD) were observed. The animals fed the HFD had similar but more severe changes. In addition, the hamsters presented an obesity paradox: at the end of the study, the animals that had the most morphological and functional changes (significantly reduced movement velocity) had the lowest body weight. Despite the fact that an HFD appears to be a more harmful factor in the long term than adenovirus infection alone, infection could increase the severity of harmful effects in individuals with an HFD. Epidemiological studies are needed to evaluate the effect of adenovirus as a precursor of chronic liver and cardiovascular diseases, including the chronic effects of gene therapy