This paper presents a novel method to delineate metropolitan areas – or functional urban areas (FUAs) – in the entire world and assesses their population trends. According to the definition developed ...by the OECD and the European Union, FUAs are composed of high-density urban centres with at least 50 thousand people plus their surrounding commuting zones. The latter represent the urban centres’ areas of influence in terms of labour market flows. The proposed method combines a functional and a morphological approach to overcome the dependency on travel-to-work data to define commuting zones and allow a global delineation. It relies on a probabilistic approach and the use of population and travel impedance gridded data across the globe. Results show that around 3.9 billion people, making up 53% of the world population, live in 8,790 FUAs, out of which 17% live in their commuting zones. Between 2000 and 2015, population growth was higher in larger FUAs, highlighting a general trend toward higher concentration of the metropolitan population. Commuting zones grew faster than urban centres, though with heterogeneous patterns across world regions, income levels and metropolitan size.
Minimization of immunosuppression and administration of antiretrovirals have been recommended for kidney transplant recipients (KTRs) with coronavirus disease 2019 (COVID‐19). However, outcomes ...remain poor. Given the likely benefit of cyclosporine because of its antiviral and immunomodulatory effect, we have been using it as a strategy in KTRs diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). We studied 29 kidney transplant recipients (KTRs) who were admitted to our institution with COVID‐19 between March 15and April, 24, 2020. Mycophenolate and/or mammalian target of rapamycin inhibitors (mTORi) were discontinued in all patients. Two therapeutic strategies were compared: Group 1, minimization of calcineurin inhibitors (N = 6); and Group 2, cyclosporine‐based therapy (N = 23), with 15 patients switched from tacrolimus. Hydroxychloroquine was considered in both strategies but antivirals in none. Six patients died after respiratory distress (20.6%). Five required mechanical ventilation (17.2%), and 3 could be weaned. Nineteen patients had an uneventful recovery (65.5%). In group 1, 3 of 6 patients died (50%) and 1 of 6 required invasive mechanical ventilation (16.7%). In group 2, 3 of 23 patients died (12.5%). Renal function did not deteriorate and signs of rejection were not observed in any patient on the second treatment regime. In conclusion, immunosuppressant treatment based on cyclosporine could be safe and effective for KTRs diagnosed with COVID‐19.
Immunosuppression reduction alone, compared to immunosuppression reduction and maintenance of or conversion to low‐dose cyclosporine, was associated with less aggressive COVID‐19 disease in kidney transplant recipients.
Despite good long-term outcomes of kidney transplants from controlled donation after circulatory death (DCD) donors, there are few uncontrolled DCD (uDCD) programs. This longitudinal study compares ...outcomes for all uDCD (N = 774) and all donation after brain death (DBD) (N = 613) kidney transplants performed from 1996 to 2015 at our center. DBD transplants were divided into those from standard-criteria (SCD) (N = 366) and expanded-criteria (N = 247) brain-dead donors (ECD). One-, 5-, and 10-year graft survival rates were 91.7%, 85.7%, and 80.6% for SCD; 86.0%, 75.8%, and 61.4% for ECD; and 85.1%, 78.1%, and 72.2% for uDCD, respectively. Graft survival was worse in recipients of uDCD kidneys than of SCD (P = .004) but better than in transplants from ECD (P = .021). The main cause of graft loss in the uDCD transplants was primary nonfunction. Through logistic regression, donor death due to pulmonary embolism (OR 4.31, 95% CI 1.65-11.23), extrahospital CPR time ≥75 minutes (OR1.94, 95%CI 1.18-3.22), and in-hospital CPR time ≥50 minutes (OR 1.79, 95% CI 1.09-2.93) emerged as predictive factors of primary nonunction. According to the outcomes of our long-standing kidney transplantation program, uDCD could help expand the kidney donor pool.
Urban scaling and Zipf's law are two fundamental paradigms for the science of cities. These laws have mostly been investigated independently and are often perceived as disassociated matters. Here we ...present a large scale investigation about the connection between these two laws using population and GDP data from almost five thousand consistently-defined cities in 96 countries. We empirically demonstrate that both laws are tied to each other and derive an expression relating the urban scaling and Zipf exponents. This expression captures the average tendency of the empirical relation between both exponents, and simulations yield very similar results to the real data after accounting for random variations. We find that while the vast majority of countries exhibit increasing returns to scale of urban GDP, this effect is less pronounced in countries with fewer small cities and more metropolises (small Zipf exponent) than in countries with a more uneven number of small and large cities (large Zipf exponent). Our research puts forward the idea that urban scaling does not solely emerge from intra-city processes, as population distribution and scaling of urban GDP are correlated to each other.
Autophagy is a highly coordinated process that is controlled at several levels including transcriptional regulation. Here, we identify the transcription factor NFE2L2/NRF2 (nuclear factor, erythroid ...2 like 2) as a regulator of autophagy gene expression and its relevance in a mouse model of Alzheimer disease (AD) that reproduces impaired APP (amyloid β precursor protein) and human (Hs)MAPT/TAU processing, clearance and aggregation. We screened the chromatin immunoprecipitation database ENCODE for 2 proteins, MAFK and BACH1, that bind the NFE2L2-regulated enhancer antioxidant response element (ARE). Using a script generated from the JASPAR's consensus ARE sequence, we identified 27 putative AREs in 16 autophagy-related genes. Twelve of these sequences were validated as NFE2L2 regulated AREs in 9 autophagy genes by additional ChIP assays and quantitative RT-PCR on human and mouse cells after NFE2L2 activation with sulforaphane. Mouse embryo fibroblasts of nfe2l2-knockout mice exhibited reduced expression of autophagy genes, which was rescued by an NFE2L2 expressing lentivirus, and impaired autophagy flux when exposed to hydrogen peroxide. NFE2L2-deficient mice co-expressing HsAPP
V717I
and HsMAPT
P301L
, exhibited more intracellular aggregates of these proteins and reduced neuronal levels of SQSTM1/p62, CALCOCO2/NDP52, ULK1, ATG5 and GABARAPL1. Also, colocalization of HsAPP
V717I
and HsMAPT
P301L
with the NFE2L2-regulated autophagy marker SQSTM1/p62 was reduced in the absence of NFE2L2. In AD patients, neurons expressing high levels of APP or MAPT also expressed SQSTM1/p62 and nuclear NFE2L2, suggesting their attempt to degrade intraneuronal aggregates through autophagy. This study shows that NFE2L2 modulates autophagy gene expression and suggests a new strategy to combat proteinopathies.
Tumour-associated macrophages (TAMs) have been associated with survival in classic Hodgkin lymphoma (cHL) and other lymphoma types. The maturation and differentiation of tissue macrophages depends ...upon interactions between colony-stimulating factor 1 receptor (CSF1R) and its ligands. There remains, however, a lack of consistent information on CSF1R expression in TAMs. A new monoclonal antibody, FER216, was generated to investigate CSF1R protein distribution in formalin fixed tissue samples from 24 reactive lymphoid tissues and 187 different lymphoma types. We also analysed the distribution of CSF1R+, CD68+ and CD163+ macrophages by double immunostaining, and studied the relationship between CSF1R expression and survival in an independent series of 249 cHL patients. CSF1R+ TAMs were less frequent in B-cell lymphocytic leukaemia and lymphoblastic B-cell lymphoma than in diffuse large B-cell lymphoma, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma and cHL. HRS cells in cHL and, with the exception of three cases of anaplastic large cell lymphoma, the neoplastic cells in NHLs, lacked detectable CSF1R protein. A CSF1R+ enriched microenvironment in cHL was associated with shorter survival in an independent series of 249 cHL patients. CSF1R pathway activation was evident in the cHL and inactivation of this pathway could be a potential therapeutic target in cHL cases.
Mentalization or reflective functioning (RF) is the capacity to interpret oneself or the others in terms of internal mental states. Its failures have been linked to several mental disorders and ...interventions improving RF have a therapeutic effect. Mentalizing capacity of the parents influences the children's attachment. The Reflective Functioning Questionnaire (RFQ-8) is a widely used tool for the assessment of RF. No instrument is available to assess general RF in Spanish-speaking samples. The aim of this study is to develop a Spanish version of the RFQ-8 and to evaluate its reliability and validity in the general population and in individuals with personality disorders.
602 non-clinical and 41 personality disordered participants completed a Spanish translation of the RFQ and a battery of self-reported questionnaires assessing several RF related constructs (alexithymia, perspective taking, identity diffusion and mindfulness), psychopathology (general and specific) and interpersonal problems. Temporal stability was tested in a non-clinical sub-sample of 113 participants.
Exploratory and confirmatory factor analyses suggested a one-factor structure in the Spanish version of the RFQ-8. RFQ-8 understood as a single scale was tested, with low scorings reflecting genuine mentalizing, and high scorings uncertainty. The questionnaire showed good internal consistence in both samples and moderate temporal stability in non-clinical sample. RFQ correlated significantly with identity diffusion, alexithymia, and general psychopathology in both samples; and with mindfulness, perspective taking, and interpersonal problems in clinical sample. Mean values of the scale were significantly higher in the clinical group.
This study provides evidence that the Spanish version of the RFQ-8, understood as a single scale, has an adequate reliability and validity assessing failures in reflective functioning (i.e., hypomentalization) in general population and personality disorders.
The use of solid‐phase microextraction coatings based on gold nanoparticles was investigated, focusing the attention on the preparation of nanoparticles with nonclassical reduction agents of HAuCl4 ...such as gallic acid and H2O2, rather than the conventional sodium citrate. All nanoparticles were characterized by diode array spectroscopy, whereas novel nanoparticles prepared with gallic acid and H2O2 were also characterized by microscopic techniques. Solid‐phase microextraction coatings were prepared with a layer‐by‐layer approach. Gallic acid permitted the preparation of stable nanoparticles with milder experimental conditions (1 min, room temperature) and provided the most uniform coatings (thickness ∼3 μm). Seven organochlorine pesticides were determined in different environmental waters using gas chromatography with electron capture detection. Despite the low thickness of the coatings, limits of detection of the entire method down to 0.13 μg/L were obtained. A comparison with the commercial polyacrylate in terms of the partition coefficients of the analytes to the coatings gave logarithm of the partition coefficient values two times higher with gallic acid than polyacrylate (although the commercial fiber is 28 times thicker). Interfiber relative standard deviation values ranged from 8.67 to 21.3%. Optimum fibers also presented an adequate lifetime (>100 extractions).
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