How new technologies can promote an active and healthy city. Digital platform to identify areas of informal sport practise in the city of Malaga

La investigación realizada se ha llevado a cabo en el marco de la Cátedra Tecnologías Emergentes para la Ciudadanía, Red de Cátedras Estratégicas del Vicerrectorado de Proyectos Estratégicos, Universidad de Málaga, y el Polo Digital, Ayuntamiento de Málaga.In recent years the urban public space has become the largest casual sports infrastructure in cities and suburbs. WHO establishes a direct relationship between the Active Healthy City, social cohesion of communities and public space. This approach provides a framework for research and work on the design of the city and urban space as support for this sport practice. Moreover, new technologies provide an opportunity to promote the sport in the city. “Malaga Activa” digital platform project is an initiative that wants to promote the informal sport practice on the urban public space (outside the regulated sports facilities) and healthy living in the neighborhoods of the city of Malaga. This paper presents the results of the first phase of the project identifying the active sport areas -those in which physical and casual sport activities take place-. It also includes a methodology and a performance test of the created digital platform, as well as an assessment of the experience and possible improvements to be incorporated in the successive phases of the project.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Indicator system to measure the qualities of urban space affecting urban safety and coexistence

Preprint de los autores enviado a: IOP Conference Series: Materials Science and Engineering. DOI:10.1088/issn.1757-899xUrban space design directly influences its own safety. Sometimes this security is given by urban furniture, lighting or urban facilities, among other aspects. This paper presents a methodology based on the development of a system of indicators that provides the opportunity to assess what qualities of urban space influence street safety. It is important to know what aspects of public space make the citizen consider it a safe place and at the same time, to contrast these data with scientific documents. The first results are shown after applying this methodology to the case study of the city of Malaga, and specifically, to a sample of streets selected based on objective criteria crime rate. For research and obtaining indicators, digital surveys have been carried out on a group of 300 people, using Google Forms and social networks. Likewise, to obtain samples of the streets with the highest and lowest crime rates, registration data has been geolocated by the tolls of the Geographic Information Systems (GIS). The main contribution of this document is focused on defining indicators to characterize and quantify the safety in the streets of the urban public space. These are contrasted with objective data and records of insecurity and crime, and can be applicable to any street in any city. Finally, through these indicators, it is intended to know what are the parameters that influence urban safety for future designs of public spaces, or their renovation, achieving in the future, the existence of streets with a higher level of safety.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Bacteriological and Immunological Profiling of Meconium and Fecal Samples from Preterm Infants : A Two-Year Follow-Up Study

An abnormal colonization pattern of the preterm gut may affect immune maturation and exert a long-term influence on the intestinal bacterial composition and host health. However, follow-up studies assessing the evolution of the fecal microbiota of infants that were born preterm are very scarce. In this work, the bacterial compositions of fecal samples, obtained from sixteen 2-year-old infants were evaluated using a phylogenetic microarray; subsequently, the results were compared with those obtained in a previous study from samples of meconium and feces collected from the same infants while they stayed in the neonatal intensive care unit (NICU). In parallel, the concentration of a wide range of cytokines, chemokines, growth factors and immunoglobulins were determined in meconium and fecal samples. Globally, a higher bacterial diversity and a lower interindividual variability were observed in 2-year-olds' feces, when compared to the samples obtained during their first days of life. Hospital-associated fecal bacteria, that were dominant during the NICU stay, seemed to be replaced, two years later, by genera, which are usually predominant in the healthy adult microbiome. The immune profile of the meconium and fecal samples differed, depending on the sampling time, showing different immune maturation statuses of the gut.Peer reviewe

The role of the land-surface model for climate change projections over the Iberian Peninsula

The importance of land-surface processes within Regional Climate Models for accurately reproducing the present-day climate is well known. However, their role when projecting future climate is still poorly reported. Hence, this work assesses the influence of the land-surface processes, particularly the contribution of soil moisture, when projecting future changes for temperature, precipitation and wind over a complex area as the Iberian Peninsula, which, in addition, shows great sensitivity to climate change. The main signals are found for the summer season, when the results indicate a strengthening in the increases projected for both mean temperature and temperature variability as a consequence of the future intensification of the positive soil moisture-temperature feedback. The more severe warming over the inner dry Iberian Peninsula further implies an intensification of the Iberian thermal low and, thus, of the cyclonic circulation. Furthermore, the land-atmosphere coupling leads to the projection of a wider future daily temperature range, since maximum temperatures are more affected than minima, a feature absent in non-coupled simulations. Regarding variability, the areas where the land-atmosphere coupling introduces larger changes are those where the reduction in the soil moisture content is more dramatic in future simulations, i.e., the so-called transitional zones. As regards precipitation, weaker positive signals for convective precipitation and more intense negative signals for non-convective precipitation are obtained as a result of the soil moisture-atmosphere interactions. These results highlight the crucial contribution of soil moisture to climate change projections and suggest its plausible key role for future projections of extreme events

Bacterial Diversity in Meconium of Preterm Neonates and Evolution of Their Fecal Microbiota during the First Month of Life

Peer reviewe

Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer's Disease Patients: Clinical, Neuroimaging and Neuropathological Findings

In the last few years, the SORL1 gene has been strongly implicated in the development of Alzheimer’s disease (AD). We performed whole-exome sequencing on 37 patients with early-onset dementia or family history suggestive of autosomal dominant dementia. Data analysis was based on a custom panel that included 46 genes related to AD and dementia. SORL1 variants were present in a high proportion of patients with candidate variants (15%, 3/20). We expand the clinical manifestations associated with the SORL1 gene by reporting detailed clinical and neuroimaging findings of six unrelated patients with AD and SORL1 mutations. We also present for the first time a patient with the homozygous truncating variant c.364C>T (p.R122*) in SORL1, who also had severe cerebral amyloid angiopathy. Furthermore, we report neuropathological findings and immunochemistry assays from one patient with the splicing variant c.4519+5G>A in the SORL1 gene, in which AD was confirmed by neuropathological examination. Our results highlight the heterogeneity of clinical presentation and familial dementia background of SORL1-associated AD and suggest that SORL1 might be contributing to AD development as a risk factor gene rather than as a major autosomal dominant gene.This work was supported by the Instituto de Salud Carlos III (PI17/01067) and AGAUR from the Autonomous Catalan Government (2017SGR1134). Dr. Víctor Antonio Blanco-Palmero is supported by the Instituto de Salud Carlos III (ISCIII, Spanish Biomedical Research Institute) through a “Río Hortega” contract (CM18/0095). Dr. Sara Llamas-Velasco is supported by the Instituto de Salud Carlos III (ISCIII; Spanish Biomedical Research Institute) through a “Juan Rodés” contract (JR 18/00046).S

Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry

Background & aims: Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period. Methods: Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected. Results: A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974-0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994-0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy's law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%).The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional – FEDER (contract numbers: PI19/00883, PI16/01748, PI18/00901, PI18/01804, PI-0285-2016, PI-0274-2016, PI-0310- 2018, PT17/0017/0020) and Agencia Española del Medicamento. CIBERehd and Plataforma ISCIII Ensayos Clinicos are funded by Instituto de Salud Carlos III. MRD holds a Joan Rodes (JR16/ 00015)/Acción B clinicos investigadores (B-0002-2019) and JSC a Rio Hortega (CM17/00243) research contract from ISCIII and Consejería de Salud de Andalucía. The funding sources had no involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the report or in the de- cision to submit the manuscript for publication

Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma

The historical lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) hampers the advance of therapeutic discoveries. To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-κB, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. Fifteen genetically diverse models developed bone marrow (BM) tumors fulfilling MM pathogenesis. Integrative analyses of ∼500 mice and ∼1,000 patients revealed a common MAPK-MYC genetic pathway that accelerated time to progression from precursor states across genetically heterogeneous MM. MYC-dependent time to progression conditioned immune evasion mechanisms that remodeled the BM microenvironment differently. Rapid MYC-driven progressors exhibited a high number of activated/exhausted CD8+ T cells with reduced immunosuppressive regulatory T (Treg) cells, while late MYC acquisition in slow progressors was associated with lower CD8+ T cell infiltration and more abundant Treg cells. Single-cell transcriptomics and functional assays defined a high ratio of CD8+ T cells versus Treg cells as a predictor of response to immune checkpoint blockade (ICB). In clinical series, high CD8+ T/Treg cell ratios underlie early progression in untreated smoldering MM, and correlated with early relapse in newly diagnosed patients with MM under Len/Dex therapy. In ICB-refractory MM models, increasing CD8+ T cell cytotoxicity or depleting Treg cells reversed immunotherapy resistance and yielded prolonged MM control. Our experimental models enable the correlation of MM genetic and immunological traits with preclinical therapy responses, which may inform the next-generation immunotherapy trials

Clinical benefit of lapatinib-based therapy in patients with human epidermal growth factor receptor 2-positive breast tumors coexpressing the truncated p95HER2 receptor

PURPOSE: A subgroup of HER2 overexpressing breast tumors co-expresses p95HER2, a truncated HER2 receptor that retains a highly functional HER2 kinase domain but lacks the extracellular domain and results in intrinsic trastuzumab resistance. We hypothesized that lapatinib, a HER2 tyrosine kinase inhibitor, would be active in these tumors. We have studied the correlation between p95HER2 expression and response to lapatinib, both in preclinical models and in the clinical setting EXPERIMENTAL DESIGN: Two different p95HER2 animal models were used for preclinical studies. Expression of p95HER2 was analyzed in HER2 overexpressing breast primary tumors from a first line lapatinib monotherapy study (EGF20009) and a second line lapatinib in combination with capecitabine study (EGF100151). p95HER2 expression was correlated with overall response rate (complete + partial response), clinical benefit rate (complete response + partial response + stable disease ≥ 24 weeks) and progression-free survival using logistic regression and Cox-proportional hazard models. RESULTS: Lapatinib inhibited tumor growth and HER2 downstream signaling of p95HER2 expressing tumors. A total of 68 and 156 tumors from studies EGF20009 and EGF100151 were evaluable, respectively, for p95HER2 detection. The percentage of p95HER2 positive patients was 20.5% in the EGF20009 study and 28.5% in the EGF100151 study. In both studies there was no statistically significant difference in progression-free survival, clinical benefit rate and overall response rate between p95HER2-positive and p95HER2-negative tumors. CONCLUSIONS: Lapatinib as a monotherapy or in combination with capecitabine appears to be equally effective in patients with p95HER2-positive and p95HER2-negative HER2-positive breast tumors