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Volunteer Computing is a type of large-scale distributed system formed aggregating computers voluntarily donated by volunteers. These computers are usually off-the-self heterogeneous resources belonging to different administrative authorities (users) that have an uncertain behavior regarding connectivity and failure. Thus, the resource allocation methods in such systems are highly dependent on the availability of resources. On one hand, resources tend to be scarce, but on the other hand, computers exhibiting low availability patterns – which are the most frequent type – are discarded or used at a high cost only when high available nodes are crowded. This paper presents the Complementary Low-Availability Resource-Allocation (CLARA) mechanism, a novel clustering-based resource allocation mechanism that takes advantage of complementarities between nodes with low availability patterns. The combination of them into complementary nodes offers an availability level equivalent to the level offered by a single high-available node. These groups of complementary nodes are maintained using a lazy reassignment algorithm. Consequently, a significant number of nodes with low-availability patterns are considered by the resource allocation mechanism for service placement. Our method has been validated over a simulation environment of a real volunteer network. The analysis of the results shows how our mechanism maximizes the use of poor quality computational resources to satisfy the user quality requirements while minimizes the number of USs replicas reassignments between nodes. As well, the capacity of the system for providing user services is highly increased while the load of the high-available nodes is remarkably reduced.

PURPOSE To evaluate the outcomes and safety of retropupillary iris-claw intraocular lens implantation and associated pars plana vitrectomy. METHODS Multicenter, national audit of 325 eyes (325 patients). Demographics, surgical details, and complications are described. Visual acuity, intraocular pressure, and central retinal thickness assessed by optical coherence tomography were collected at 1, 3, 6, and 12 months after surgery. Kaplan-Meier curves were created to assess the cumulative probability of postoperative visual acuity and intraocular pressure levels, macular edema development, and corneal decompensation. RESULTS The cumulative probability of the final visual acuity ≤0.3 logarithm of the minimum angle of resolution (≥20/40 Snellen) was 75.6% at 12-month follow-up. The probability of intraocular pressure >21, ≥25, and ≥30 mmHg was 48.1%, 33.1%, and 19.0%, and the probability of intraocular pressure-lowering drops was 50.9% at 12 months. Glaucoma surgery was required in 4.3% of the eyes (14/325). The cumulative probability of macular edema was 20.5% at 12 months and was greater in complicated cataract surgery than in intraocular lens-luxation eyes (26% vs. 16.7%, P = 0.04). Corneal transplantation was required in 2.8% of the eyes (9/325). CONCLUSION This study on 325 eyes with aphakia or intraocular lens dislocation managed with the retropupillary iris-claw intraocular lens technique provides clinical outcomes in a real-world scenario, reporting relevant data for patient counseling and preoperative discussions.

The autism spectrum disorder (ASD) is a neurodevelopmental condition, frequently accompanied by medical and psychiatric pathology. One of the most commonly found problems associated with ASD is sleep disturbances, which are estimated to affect approximately 80% of the people with ASD, not only during childhood but also in the adolescence and adult stages. Nevertheless, the relationship of these sleep difficulties with autism severity, as well as other associated impairments such as executive functioning and psychiatric disorders (eg, depression), has not yet been widely studied. The main objective of the present study was to explore the relationship between sleep disturbances, subjective measures of executive function, and psychiatric pathology in the ASD population. To reach that goal, a group of 89 participants with ASD (44 children/adolescents and 45 adults) was recruited and evaluated with self-reported measures of executive function performance and psychiatric pathology tests. Multivariate analysis showed a significant association between sleep disturbances and psychiatric symptoms in both ASD groups, with greater sleep disturbances predicting more severe psychiatric pathology. No significant association was found with executive function in any group. Limitations included a small sample size and lack of objective measures. Sleep problems seem to be associated with the severity of psychiatric pathology throughout the lifespan, increasing the chance of developing psychiatric symptoms when they were present. Improving sleep quality in ASD at all ages may result in preventing and/or decreasing psychiatric pathology in this population.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has gained relevance in recent years as an alternative treatment for neuropsychiatric conditions. The aim of this study is to conduct a systematic review of the use of tDCS in Autism Spectrum Disorder (ASD). Both electronic and manual searches were conducted to identify studies published in peer-reviewed scientific journals addressing the use of tDCS in ASD population. A total of 16 studies fulfilled the criteria to be included in the review. Studies were conducted both in child and adult population. Anodal stimulation on the left dorsolateral prefrontal cortex was the most commonly chosen methodology. Outcomes addressed ASD symptoms and neuropsychological functions. Meta-analytic synthesis identified improvements in social, health, and behavioral problem domains of the Autism Treatment Evaluation Checklist. Limitations included high heterogeneity in the methodology and low-efficacy study designs (pre-post and single-case studies). Recent controlled trials shed promising results for the use of tDCS in ASD. A standardized stimulation protocol and a consensus in the measures used in the evaluation of the efficacy are imperative.

OBJECTIVE: To describe the role of local anaesthetic blocks as a potential cause of paracentral acute middle maculopathy (PAMM) after uneventful ocular surgery. METHODS: Retrospective, observational, international, multicentre case series. Nine cases of PAMM with associated visual loss following uneventful ocular surgery with local anaesthetic blocks were observed in a 9-year period (2011–2020). Demographic, ocular and systemic data, anaesthetic data and surgical details were collected. Visual acuity (VA), fundus photography, fluorescein angiography, optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images were reviewed. RESULTS: All nine cases were associated with decreased VA at 24 h postoperative check (ranging from hand movement to 20/200). A hyperreflective band within the middle retinal layers was observed in the structural OCT in the acute phase, evolving to thinning and atrophy of the inner retinal layers in sequential follow-up scans performed. Fluorescein angiography showed delayed perfusion in early arterial phase with normal perfusion in late venous phases. OCTA showed decreased perfusion in the deep capillary plexus. Visual recovery was variable between cases during follow-up (ranging from count fingers to 20/20). CONCLUSIONS: A combination of a vasoconstrictive effect of the anaesthetic agent, an intraocular pressure spike and a mechanical effect of the volume of anaesthetic injected may result in decreased retinal artery perfusion and be evidenced as PAMM in OCT scans. PAMM may present as a potential complication of local anaesthetic blocks in cases of unexpected visual loss after uneventful ocular surgery.

Pathogenic mutations in NDUFAF4 have been reported in very few cases. Here we present new data to further delineate the phenotypic spectrum of NDUFAF4 deficiency. We describe two siblings presenting with facial dysmorphia and lactic acidosis in the neonatal period. Later on, they developed fatal early encephalopathy with apneic episodes, irritability, central hypoventilation, liver involvement and hyperammonemia. Abnormality of the cerebral white matter was demonstrated in one case, and cardiomyopathy in the other. Urine organic acid profile showed an increased excretion of lactate, Krebs cycle metabolites and 3-methylglutaconate. Whole-exome sequencing identified a novel homozygous nonsense mutation in NDUFAF4 (c.478G > T; p.Glu160Ter), encoding a mitochondrial complex I assembly factor. The disruptive effect of the mutation was corroborated by the absence of NDUFAF4 expression in patient fibroblasts. OXPHOS assembly studies demonstrated almost undetectable levels of fully assembled complex I and complex I–containing supercomplexes and an abnormal accumulation of SCIII2IV1 supercomplexes. Morphologically, fibroblasts showed rounder mitochondria and a diminished degree of branching of the mitochondrial network. Cellular respiratory capacity in fibroblasts was also markedly reduced. In sum, we provide insights into the physiopathological mechanisms underlying NDUFAF4 deficiency and expand the knowledge about the clinical and biochemical spectrum of this disorder.

Diseases of the spinal cord often have devastating consequences and imaging studies are indispensable for their diagnosis. The fundamental imaging technique to evaluate these diseases is magnetic resonance imaging of the spine. The diagnostic approach must be based on the clinical context, the time elapsed since the onset of symptoms and signs, and the imaging findings; for this reason, it sometimes necessary to broaden the study to include the brain. The first step in the diagnostic algorithm is to rule out spinal cord compression before evaluating other causes of myelopathy, which sometimes has multiple causes. This paper includes a broad review of the different diseases that can cause myelopathy, their imaging manifestations, their differential diagnoses, and diagnostic algorithms. Using an appropriate radiological approach will result in better management and prognosis of these patients.

The recent appearance of the SARS-CoV-2 pandemic has had a significant impact on the general population. Patients on renal replacement therapy (RRT) have not been unaware of this situation, and due to their characteristics, they are especially vulnerable. We present the results of the analysis of the COVID-19 Registry of the Spanish Society of Nephrology. This online registry began operating on March 18, 2020. It collects epidemiological variables, contagion and diagnosis data, signs and symptoms, treatments, and outcomes. Patients were diagnosed with SARS-CoV-2 infection based on the results of the PCR of the virus, carried out both in patients who had manifested compatible symptoms or had suspicious signs and in those who had undergone screening after contact with another patient. As of July 18, the registry had data on 1748 patients, from all the autonomous communities. The most represented form of RRT is in-center hemodialysis (HDC), followed by transplant patients. Only 55 (4%) were on peritoneal dialysis (PD). PD patients’ symptoms are similar to those of the general population. A very high percentage (93%) required hospital admission, but none in intensive care units. The most used treatments were hydroxychloroquine, lopinavir–ritonavir, and steroids. Mortality is high and reaches 18%. Age and pneumonia were independently associated with the risk of death. We also found a beneficial effect of PD over HDC. As conclusions, SARS-CoV-2 infection already affects a significant number of Spanish patients on RRT, mainly those on HDC. The proportion of infected patients on PD is significantly lower. Hospitalization rates are very high, and mortality is high; age and the development of pneumonia are factors associated with mortality, while those on PD had lower mortality., Bulletin de la Dialyse à Domicile, Vol. 3 No 3 (2020): Bulletin de la Dialyse à Domicile

Refractoriness to induction therapy and relapse after complete remission are the leading causes of death in patients with acute myeloid leukaemia (AML). This study focussed on the prediction of response to standard induction therapy and outcome of patients with AML using a combined strategy of mutational profiling by next-generation sequencing (NGS, n = 190) and ex vivo PharmaFlow testing (n = 74) for the 10 most widely used drugs for AML induction therapy, in a cohort of adult patients uniformly treated according to Spanish PETHEMA guidelines. We identified an adverse mutational profile (EZH2, KMT2A, U2AF1 and/or TP53 mutations) that carries a greater risk of death [hazard ratio (HR): 3·29, P < 0·0001]. A high correlation was found between the ex vivo PharmaFlow results and clinical induction response (69%). Clinical correlation analysis showed that the pattern of multiresistance revealed by ex vivo PharmaFlow identified patients with a high risk of death (HR: 2·58). Patients with mutation status also ran a high risk (HR 4·19), and the risk was increased further in patients with both adverse profiles (HR 4·82). We have developed a new score based on NGS and ex vivo drug testing for AML patients that improves upon current prognostic risk stratification and allows clinicians to tailor treatments to minimise drug resistance.

Background Granular cell astrocytoma is a rare and aggressive subtype of astrocytoma that is histopathologically well defined in the literature. It is formed by polygonal cells with granular cytoplasm mixed with neoplastic astrocytes and usually a perivascular infiltrate of lymphocytes. Despite its unusual histologic appearance, relevant radiologic features have not yet been described. Case Description We report 2 middle-aged patients with neurologic symptoms secondary to a newly diagnosed brain tumor. The absence of central tumor necrosis as well as the presence of an atypical pattern of enhancement and areas of intense diffusion restriction on magnetic resonance imaging in both cases led to the diagnosis of primary central nervous system lymphoma. Histopathologic findings in both tumors showed an aggressive astrocytoma with a prominent granular cell population and perivascular lymphocytic cuffing in tissue, corresponding to a granular cell astrocytoma. Despite the favorable prognostic factors, including World Health Organization grades II and III astrocytomas and IDH mutations, the outcome was poor. Conclusions Granular cell astrocytomas can show unusual aggressive radiologic features that do not correspond to their histopathologic grade of malignancy. The presence of perivascular lymphocytic infiltrate may alter the typical radiologic appearance of common astrocytomas.

O estudo teve como objetivo conhecer o perfil do serviço de atendimento prestado pela disciplina de Periodontia II da Faculdade de Odontologia da Universidade Federal do Rio de Janeiro, por meio de levantamento de dados dos atendimentos realizados em um período de 10 anos (2007 a 2016). Foram analisados o protocolo de atendimento, número total de procedimentos realizados por semestre e por estudante de graduação, número de exames periodontais, profilaxias, instruções de higiene oral, procedimentos de raspagem supragengivais, procedimentos de raspagem subgengival e alisamento radicular realizados por semestre. As informações relacionadas ao perfil dos usuários foram coletadas a partir do prontuário e incluíram dados sociodemográficos, diagnóstico das condições periodontais e condições sistêmicas associadas. No período estudado foram realizados 13.810 procedimentos clínicos, em média 690,5 por semestre. Em amostragem de 715 usuários a idade variou entre 12 e 85 anos, sendo a faixa etária predominante entre 45 e 64 anos, equivalente a 55,38% da amostra. Na amostra, 14,55% foram diagnosticados com gengivite e 85,45% com periodontite, sendo 93,94% dos casos periodontite crônica e 6,06% periodontite agressiva. Foram identificadas condições sistêmicas de saúde associadas aos quadros de doença periodontal. As condições mais relevantes informadas pelos pacientes foram hipertensão arterial (25,87%), doenças respiratórias como sinusite e rinite alérgica (13,29%), diabetes mellitus (10,35%) e tabagismo (7,70%). Foi possível conhecer em detalhes o funcionamento da clínica da disciplina de Periodontia II da FO/UFRJ e os resultados foram utilizados como base para melhorias no serviço. O perfil de saúde apresentado pelos usuários do serviço apontou para a necessidade de abordagem interprofissional.

Purpose Describe a time-sparing technique to measure disc-foveal angle (DFA), determine normal values and its role when analyzing paired fundus photographs. Methods DFA was analysed using the software program Keynote V 6.2.2 on 440 fundus photographs (3D OCT 2000, Topcon) of 20 individuals. The 11 different head positions were determined with the cervical range of motion device (CROM, Performance Attainment Associates). A reproducibility and correlation study between two fundus cameras (OCT 3D-2000 and TRC-50EX, Topcon) was performed. Results Mean DFA of the right and left eye was 5.5 ± 3.4° and 8.6 ± 2.9°, with a difference of 3.1° (p = 0.001 Wilcoxon signed-rank test) in the upright head position. Mean absolute difference in DFA between eyes was 3.5 ± 2.6°; an increase was seen with increasing head tilt (p = 0.000 Wilcoxon signed-rank test). Mean sum of DFA in both eyes was 14.1 ± 5.4°. On head-tilt of 20° and 40° to the right, mean ocular counterrolling (OCR) was 7.1° and 12.2° in right eye and 7.7° and 12.1° in left eye. On head-tilt of 20° and 40° to the left, OCR was 4.4° and 8° in right eye and 4.2° and 8.7° in left eye (p = 0.000 Wilcoxon signed-rank test). The two cameras showed strong correlation and high reproducibility. Conclusions Our DFA measurement technique is time-sparing and reproducible. Left eye shows higher disc-foveal angle than right eye. OCR occurs only in the roll plane. Absolute difference in disc-foveal angle between eyes changes according to head tilt, this information is of value when analyzing paired fundus photographs.

Objective: The aim of this study was to evaluate the effects of deep brain stimulation of the subthalamic nucleus (DBS-SN) on cognitive function in patients with Parkinson's disease (PD) 5 years after surgery. Material and methods: We conducted a prospective study including 50 patients with PD who underwent DBS-SN (62.5% were men; mean age of 62.2 ± 8.2 years; mean progression time of 14.1 ± 6.3 years). All patients were assessed before the procedure and at one year after surgery; 40 patients were further followed up until the 5-year mark. Follow-up assessments included the following neuropsychological tests: Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale (MDRS), letter-number sequencing of the WAIS-III (WAIS-III-LN), clock-drawing test, Rey auditory verbal learning test (RAVLT), Benton Visual Retention Test (BVRT), Judgment of Line Orientation (JLO) test, FAS Phonemic Verbal Fluency Test, Stroop test, and the Montgomery–Asberg Depression Rating Scale (MADRS). Results: Patients were found to score lower on the MMSE (−0.89%), clock-drawing test (−2.61%), MDRS (−1.72%), and especially phonemic (−13.28%) and sematic verbal fluency tests (−12.40%) at one year after surgery. Delayed recall on the RAVLT worsened one year after the procedure (−10.12%). At 5 years, impairment affected mainly verbal fluency; scores decreased an additional 16.10% and 16.60% in semantic and phonemic verbal fluency, respectively. Moderate decreases were observed in immediate recall (−16.87%), WAIS-III-LN (−16.67%), and JLO test (−11.56%). Discussion: In our sample, DBS-SN did not result in global cognitive impairment 5 years after surgery. Verbal function was found to be significantly impaired one year after the procedure. Impaired learning and visuospatial function may be attributed to degeneration associated with PD. Resumen: Objetivo: El objetivo es evaluar los efectos de la estimulación cerebral profunda del núcleo subtalámico bilateral (STN-DBS) sobre el estado cognitivo de los pacientes con enfermedad de Parkinson 5 años después de la cirugía. Materiales y métodos: En este estudio prospectivo se incluyeron 50 pacientes con enfermedad de Parkinson (62,5% hombres, edad media 62,2 ± 8,2 años y duración de la enfermedad 14,1 ± 6,3 años) sometidos a STN-DBS. Todos los pacientes fueron evaluados preoperatoriamente y un año después de la cirugía, y 40 pacientes fueron seguidos hasta 5 años. En cada visita se realizaron las siguientes evaluaciones neuropsicológicas: Mini-Mental State Examination, Mattis Dementia Rating Scale (MDRS), test de secuencias números-letras de WAIS III-LN, Prueba de dibujo de reloj, Prueba de aprendizaje verbal auditivo Rey, la Prueba de retención visual de Benton, la Prueba de juicio de orientación de línea de Benton, la fluidez verbal fonética y semántica, la Prueba Stroop y la Escala de clasificación de depresión de Montgomery-Asberg. Resultados: Anualmente se observaron reducciones en la puntación de Mini-Mental State Examination (−0,89%), Prueba del dibujo de reloj (−2,61%) y MDRS (−1,72%), fueron más marcados tanto para la fluidez verbal fonética (−13,28%) como semántica (−12,40%). Para la Prueba de aprendizaje verbal auditivo Rey observamos un deterioro en la capacidad de recuerdo diferido (−10,12%) un año después de la cirugía. A los 5 años la mayor parte del deterioro se produjo en la fluidez verbal, con reducciones adicionales de 16,10% y 16,60% para la fluidez verbal semántica y fonética, respectivamente. Se observó un empeoramiento más moderado del recuerdo inmediato (−16,87%), WAIS III-LN (−16,67%) y de la prueba de orientación lineal de Benton (−11,56%). Discusión: La STN-DBS no condujo a deterioro cognitivo global a los 5 años de la cirugía. Hubo un deterioro significativo en la función verbal desde el primer año de la cirugía. El deterioro de la capacidad de aprendizaje y de las funciones visuoespaciales podría atribuirse al propio proceso degenerativo de la enfermedad. Keywords: Cognitive impairment, Deep brain stimulation, Depression, Parkinson's disease, Quality of life, Subthalamic nucleus, Palabras clave: Deterioro cognitivo, Estimulación cerebral profunda, Depresión, Enfermedad de Parkinson, Calidad de vida, Núcleo subtalámico

Introduction: Microvascular decompression (MVD) is accepted as the only aetiological surgical treatment for refractory classic trigeminal neuralgia (TN). There is therefore increasing interest in establishing the diagnostic and prognostic value of identifying neurovascular compressions (NVC) using preoperative high-resolution three-dimensional magnetic resonance (MRI) in patients with classic TN who are candidates for surgery. Methods: This observational study includes a series of 74 consecutive patients with classic TN treated with MVD. All patients underwent a preoperative three-dimensional high-resolution MRI with DRIVE sequences to diagnose presence of NVC, as well as the degree, cause, and location of compressions. MRI results were analysed by doctors blinded to surgical findings and subsequently compared to those findings. After a minimum follow-up time of six months, we assessed the surgical outcome and graded it on the Barrow Neurological Institute pain intensity score (BNI score). The prognostic value of the preoperative MRI was estimated using binary logistic regression. Results: Preoperative DRIVE MRI sequences showed a sensitivity of 95% and a specificity of 87%, with a 98% positive predictive value and a 70% negative predictive value. Moreover, Cohen's kappa (CK) indicated a good level of agreement between radiological and surgical findings regarding presence of NVC (CK 0.75), type of compression (CK 0.74) and the site of compression (CK 0.72), with only moderate agreement as to the degree of compression (CK 0.48).After a mean follow-up of 29 months (range, 6-100 months), 81% of the patients reported pain control with or without medication (BNI score I–III). Patients with an excellent surgical outcome, i.e. without pain and off medication (BNI score I), made up 66% of the total at the end of follow-up. Univariate analysis using binary logistic regression showed that a diagnosis of NVC on the preoperative MRI was a favourable prognostic factor that significantly increased the odds of obtaining an excellent outcome (OR 0.17, 95% CI 0.04-0.72; P = .02) or an acceptable outcome (OR 0.16, 95% CI 0.04-0.68; P = .01) after MVD. Conclusions: DRIVE MRI shows high sensitivity and specificity for diagnosing NVC in patients with refractory classic TN and who are candidates for MVD. The finding of NVC on preoperative MRI is a good prognostic factor for long-term pain relief with MVD. Resumen: Introducción: La descompresión microvascular (DMV) es aceptada como único tratamiento quirúrgico etiológico para la neuralgia del trigémino (NT) clásica refractaria al tratamiento médico. Por ello existe un creciente interés por establecer el valor diagnóstico y pronóstico de la identificación de compresiones neurovasculares (CNV) mediante resonancia magnética (RM) con secuencias tridimensionales de alta resolución en pacientes con NT clásica candidatos a cirugía. Métodos: Este estudio observacional incluye una serie consecutiva de 74 pacientes con NT clásica refractaria intervenidos mediante DMV. En todos los pacientes se realizó una RM tridimensional de alta resolución con secuencias DRIVE preoperatoria para diagnosticar la existencia de una CNV, así como su grado, origen y localización. Los resultados de la RM fueron analizados de forma «ciega» para los hallazgos de la exploración quirúrgica y posteriormente comparados con estos. Se realizó un seguimiento mínimo de 6 meses para comprobar los resultados quirúrgicos, que se clasificaron según la escala de dolor facial del Barrow Neurological Institute (BNI score). El valour pronóstico de la RM preoperatoria se analizó mediante una regresión logística binaria. Resultados: La RM preoperatoria con secuencias DRIVE demostró una sensibilidad del 95% y una especificidad del 87%, con un valor predictivo positivo del 98% y un valor predictivo negativo del 70%. Además se evidenció un buen grado de concordancia mediante el coeficiente kappa (CK) entre los hallazgos radiológicos y quirúrgicos respecto a la existencia de CNV (CK 0,75), al tipo de compresión (CK 0,74) y a la localización (CK 0,72), siendo del grado de concordancia moderado para el grado de compresión (CK 0,48).Tras un seguimiento medio de 29 meses (rango 6-100 meses), el 81% de los pacientes presentaban un control del dolor sin o con medicación (BNI score I-III). Los pacientes con un resultado excelente del tratamiento, es decir aquellos sin dolor trigeminal y sin medicación (BNI score I) fueron el 66% al final del seguimiento. El análisis univariante mediante regresión logística binaria demostró que el diagnóstico de una CNV en la RM preoperatoria era un factor pronóstico favorable que incrementaba significativamente la probabilidad de obtener un resultado excelente (OR 0,17, IC del 95%, 0,04-0,72; p 0,02) o aceptable (OR 0,16, IC del 95%, 0,04-0,68; p 0,01) tras la DMV. Conclusiones: La RM DRIVE presenta una elevada sensibilidad y especificidad para el diagnóstico preoperatorio de CNV en pacientes con NT clásica refractaria candidatos a tratamiento mediante DMV. El hallazgo de una CNV en el estudio de RM preoperatorio es un factor de buen pronóstico para la obtención de alivio del dolor a largo plazo con la DMV. Keywords: Trigeminal neuralgia, Microvascular decompression, Magnetic resonance, DRIVE, Sensibility, Predictive value, Palabras clave: Neuralgia del trigémino, Descompresión microvascular, Resonancia magnética, DRIVE, Sensibilidad, Valor predictivo

This work evaluates the thermal and natural ventilation behaviour in an underground construction and explains the passive behavior of the building components (tunnel, chimney and cave) in different periods of the year. The CFD models developed take into account the temperature gradients of the terrain, which allows a more realistic simulation of the natural ventilation in underground constructions. The role of the building components in the regulation of the indoor environment vary dramatically in each period. Results show that thermal stability with zero energy consumption is reached in the cave despite the extreme outdoor temperatures. Further, the access tunnel is the key element in the ventilation of the underground construction, where the ground temperature plays an essential role in regulating natural ventilation. By contrast, the ventilation chimney plays a less important role due to lower air velocities. The approach and adjustments of CFD models presented here could be useful as a reference for other underground projects as a decision-making in the design of optimized ventilation and energy management systems.

Spain has a large heritage in vernacular architecture among which the underground constructions can be highlighted. On many occasions these constructions were excavated hundreds of years ago and there is lack of technical information about their geometry or visual characteristics. Among the existing survey techniques, the terrestrial laser scanning technology seems one of the most appropriate and effective for these constructions. Given the high underground heritage in Spain and the lack of graphic documentation with good quality, there is a need to establish a quick and effective methodology aiming to classify these constructions in order to be included in the national heritage registers. To do so, the first step was to assess how aspects such as the scanner resolution, color and meshing strategy (post-processing phase) affect the quality of the graphic results generated. Then, the most adequate survey strategy was selected (based on a reference case study) and was further applied in seven representative underground constructions in order to validate the methodology and verify its effectiveness. Results indicate that a higher density of points is not always associated with a higher graphic quality in both the digital model and graphic information. The type of mesh used in the post-processing stage affects insignificantly the meshing surface, the graphic quality and the processing time of the digital model. On the contrary, it helps to filter unnecessary points in the cloud and thus obtain less heavy digital models. The resolution strategy can considerably increase the processing time of the models, however a lower resolution strategy combined with a higher number of shots is recommended to improve the graphic quality of the results.

Science gateways are an integral component of modern collaborative research. They find widespread adoption by research groups to share data, code and tools both amongst collaborators on a project and the broader community. However, not unlike research groups, gateways too, face the vagaries of research funding often resulting in a bleak outlook for their maintenance beyond the original project’s conclusion. We present a sustainability model based on the HUBzero cyberinfrastructure platform that enables multiple research projects to share a single science gateway allowing for their maintenance even after the original funding source has run out. This model brings with it certain other advantages as well; general improvements to the gateway apply to all hosted projects, similar requirements across projects can often be abstracted into new general purpose capabilities for the gateway which feed back into all hosted projects. Such newly developed capabilities can also foster additional research aiding in new funding proposals that can revitalize and jumpstart hosted dormant projects. We describe a specific instance of a HUBzero science gateway, MyGeoHub, that successfully employs this sustainability model to host several geospatial research projects. We also illustrate the specific advantages of this sustainability model in the case of the MyGeoHub gateway that have led to the development of general-purpose data management and visualization software modules that have found use beyond MyGeoHub.

Objective: SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder characterized by progressive retrograde degeneration, or "dying-back" phenomenon, of the corticospinal tract's longest axons. Neuroimaging studies mainly focus on white matter changes and, although previous studies reported cortical thinning in complicated HSP forms, cortical changes remain unclear in SPG4 patients. This work aimed to compare changes in white matter microstructure and cortical thickness between 12 SPG4 patients and 22 healthy age-matched controls. We also explore whether white matter alterations are related to cortical thickness and their correlation with clinical symptoms. Methods: we used fixel-based analysis, an advanced diffusion-weighted imaging technique, and probabilistic tractography of the corticospinal tracts. We also analyzed cortical morphometry using whole-brain surface-based and atlas-based methods in sensorimotor areas. Results: SPG4 patients showed bilateral involvement in the corticospinal tracts; this was more intense in the distal portion than in the upper segments and was associated with the degree of clinical impairment. We found a significant correlation between disease severity and fiber density and cross-section of the corticospinal tracts. Furthermore, corticospinal tract changes were significantly correlated with bilateral cortical thinning in the precentral gyrus in SPG4 patients. Conclusions: Our data point to axonal damage of the corticospinal motor neurons in SPG4 patients might be related to cortical thinning in motor regions.

This manuscript presents findings from the first dichotomous data pooling analysis on clinical trials (CT) regarding the effectiveness of binding potassium. The results emanated from pairwise and network meta-analyses aiming evaluation of response to commercial potassium-binding polymers, that is, to achieve and maintain normal serum potassium (n = 1,722), and the association between this response and an optimal dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) needing individuals affected by heart failure (HF) or resistant hypertension, who may be consuming other hyperkalemia-inducing drugs (HKID) (e.g., b-blockers, heparin, etc.), and frequently are affected by chronic kidney disease (CKD) (n = 1,044): According to the surface under the cumulative ranking area (SUCRA), sodium zirconium cyclosilicate (SZC) (SUCRA >0.78), patiromer (SUCRA >0.58) and sodium polystyrene sulfonate (SPS) (SUCRA 5.1 mEq/L), and, when normokalemia is achieved, patiromer 16.8–25.2 g/day (SUCRA = 0.94) and patiromer 8.4–16.8 g/day (SUCRA = 0.41) can allow to increase the dose of spironolactone up to 50 mg/day in subjects affected by heart failure (HF) or with resistant hypertension needing treatment with other RAASi. The potential of zirconium cyclosilicate should be explored further, as no data exists to assess properly its capacity to optimize dosing of RAASi, contrarily as it occurs with patiromer. More research is also necessary to discern between benefits of binding potassium among all type of hyperkalemic patients, for example, patients with DM who may need treatment for proteinuria, patients with early hypertension, etc. Fil: Lizaraso Soto, Frank. Universidad de Valladolid; España Fil: Gutiérrez Abejón, Eduardo. Universidad de Valladolid; España Fil: Bustamante Munguira, Juan. Universidad de Valladolid; España Fil: Martín García, Débora. Universidad de Valladolid; España Fil: Chimeno, María Montserrat. Hospital Virgen de la Concha; España Fil: Nava Rebollo, Álvaro. Hospital Virgen de la Concha; España Fil: Maurtua Briseño Meiggs, Álvaro. Woodland Medical Practicenhs; Reino Unido Fil: Fernández, Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Universidad Nacional de Cuyo; Argentina. Universidad de Burgos. Departamento de Didácticas Específicas; España Fil: Bustamante Munguira, Elena. Universidad de Valladolid; España Fil: de Paz, Félix Jesús. Universidad de Valladolid; España Fil: Grande Villoria, Jesús. Universidad de Valladolid; España. Universite de Lausanne; Suiza Fil: Ochoa Sangrador, Carlos. Sanidad de Castilla y León; España Fil: Pascual, Manuel. Universite de Lausanne; Suiza Fil: Álvarez, F. Javier. Universidad de Valladolid; España Fil: Herrera Gómez, Francisco. Universite de Lausanne; Suiza. Universidad de Valladolid; España

Cone-beam computed tomography (CBCT) provides images without overlapping anatomical structures, which is important for the diagnosis and assessment of florid cemento-osseous dysplasia. This fibro-osseous lesion that affects the alveolar process without compromising the teeth’ pulp vitality is usually asymptomatic, and bone expansion, cortical disruption, and root resorption are uncommon. Due to its avascular characteristic, surgical procedures are often contraindicated. In this case, a 59-year-old female patient presented with a complaint of pain in the right maxillary central incisor. Panoramic and periapical radiographs showed florid cemento-osseous dysplasia in some regions. The right maxillary central incisor showed an extensive radiolucent image suggestive of root resorption but without fibro- -osseous lesion. For better evaluation and implant planning, CBCT was performed and demonstrated florid cemento-osseous dysplasia adjacent to the right maxillary central incisor, contraindicating implant placement. In other regions, CBCT enabled the identification of the expansive features of this fibro-osseous lesion.

Background Alteration of vitamin B12 metabolism can be genetic or acquired, and can result in anemia, failure to thrive, developmental regression and even irreversible neurologic damage. Therefore, early diagnosis and intervention is critical. Most of the neonatal cases with acquired vitamin B12 deficiency have been detected by clinical symptoms and only few of them trough NBS programs. We aim to assess the usefulness of the second-tier test: methylmalonic acid (MMA), methylcitric acid (MCA) and homocysteine (Hcys) in our newborn screening program and explore the implications on the detection of cobalamin (vitamin B12) related disorders, both genetic and acquired conditions. Methods A screening strategy using the usual primary markers followed by the analysis of MMA, MCA and Hcys as second tier-test in the first dried blood spot (DBS) was developed and evaluated. Results During the period 2015–2018 a total of 258,637 newborns were screened resulting in 130 newborns with acquired vitamin B12 deficiency (incidence 1:1989), 19 with genetic disorders (incidence 1:13,613) and 13 were false positive. No false negatives were notified. Concerning the second-tier test, the percentage of cases with MMA above the cut-off levels, both for genetic and acquired conditions was very similar (58% and 60%, respectively). Interestingly, the percentage of cases with increased levels of Hcys was higher in acquired conditions than in genetic disorders (87% and 47%, respectively). In contrast, MCA was high only in 5% of the acquired conditions versus in 53% of the genetic disorders, and it was always very high in all patients with propionic acidemia. Conclusions When screening for methylmalonic acidemia and homocystinuria, differential diagnosis with acquired vitamin B12 deficiency should be done. The results of our strategy support the inclusion of this acquired condition in the NBS programs, as it is easily detectable and allows the adoption of corrective measures to avoid the consequences of its deficiency.

In the field of laboratory medicine, proficiency testing is a vehicle used to improve the reliability of reported results. When proficiency tests are unavailable for a given analyte, an alternative approach is required to ensure adherence to the International Organization for Standardization (ISO) 15189:2012 standard. In this study, we report the results of a split-sample testing program performed as an alternative to a formal PT. This testing method was based on recommendations provided in the Clinical and Laboratory Standards Institute (CLSI) QMS24 guideline. Two different laboratories measured, in duplicate, the heparan sulfate concentration in five samples using ultra-performance liquid chromatography and tandem mass spectrometry. The data analysis to determine the criterion used for the comparability assessment between the two laboratories was based on Appendix E of the QMS24 guideline. Mean interlaboratory differences fell within the maximum allowable differences calculated from the application of the QMS24 guideline, indicating that the results obtained by the two laboratories were comparable across the concentrations tested. Application of the QMS24 split-sample testing procedure allows laboratories to objectively assess test results, thus providing the evidence needed to face an accreditation audit with confidence. However, due to the limitations of statistical analyses in small samples (participants and/or materials), laboratory specialists should assess whether the maximum allowable differences obtained are suitable for the intended use, and make adjustments if necessary.

Objective: The aim was to assess the clinical effectiveness of drugs used in hospitalized patients with COVID-19 infection.Method: We conducted a systematic review of randomized clinical trials assessing treatment with remdesivir, chloroquine, hydroxychloroquine, lopinavir, ritonavir, dexamethasone, and convalescent plasma, for hospitalized patients with a diagnosis of SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, duration of ventilation, duration of oxygen support, duration of hospitalization), virological clearance, and severe adverse events.Results: A total of 48 studies were retrieved from the databases. Ten articles were finally included in the data extraction and qualitative synthesis of results. The meta-analysis suggests a benefit of dexamethasone versus standard care in the reduction of risk of mortality at day 28; and the clinical improvement at days 14 and 28 in patients treated with remdesivir.Conclusions: Dexamethasone would have a better result in hospitalized patients, especially in low-resources settings.Significance of results: The analysis of the main treatments proposed for hospitalized patients is of vital importance to reduce mortality in low-income countries; since the COVID-19 pandemic had an economic impact worldwide with the loss of jobs and economic decline in countries with scarce resources.

Distinguishing trauma from heat-induced fractures is a challenge faced by forensic anthropologists and pathologists during medicolegal investigations in which fire has been used by the perpetrators to destroy evidence. This paper aims to validate the provided identification features to distinguish between fire induced alterations and sharp force trauma. A total of 80 cremated adult individuals were used in this paper: 3 recently deceased embalmed cadavers from Cementerio Sur de Madrid for the sharp force trauma experiment in which 55 pre-burning injuries were inflicted using a machete and a serrated knife in different anatomical regions. And 77 cremated individuals from the Forensic Anthropology and Odontology Laboratory osteological collection. Five cremated long bones from this collection were selected, and 10 cuts were manually inflicted using a serrated knife to analyse post-burning trauma. Heat-induced changes and trauma morphologic characteristics were thus documented and analysed. The examination and documentation of morphological traits enabled the production of a heat-induced changes visual guide and a flow-chart. Two intraclass correlation tests were performed to validate the capacity of the observer to distinguish between fire related alterations and toolmarks. The results obtained in the statistical analysis indicate that, even if the toolmarks are visible and recognizable upon macroscopic observation by the observers, some features, such as the step and the transverse fractures can be mistaken with inflicted trauma. The use of the proposed features coupled with careful anthropological examination is recommended and has been found functional for participants with no prior knowledge in the analysis of cremated remains.

Given the variability of previously reported results, this systematic review aims to determine the clinical effectiveness of convalescent plasma employed in the treatment of hospitalized patients with diagnosis of COVID-19.We conducted a systematic review of controlled clinical trials assessing treatment with convalescent plasma for hospitalized patients with a diagnosis of SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, and ventilation requirement.A total of 50 studies were retrieved from the databases. Four articles were finally included in the data extraction, qualitative and quantitative synthesis of results. The meta-analysis suggests that there is no benefit of convalescent plasma compared to standard care or placebo in the reduction of the overall mortality and in the ventilation requirement; but there could be a benefit for the clinical improvement in patients treated with plasma.We can conclude that the convalescent plasma transfusion cannot reduce the mortality or ventilation requirement in hospitalized patients diagnosed with SARS-CoV-2 infection. More controlled clinical trials conducted with methodologies that ensure a low risk of bias are still needed.

Background and Aims The development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life. Methods Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16. Results A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% of patients in remission]. In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at Weeks 24 and 52, respectively; 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at Week 16, 63% at Week 56, and 59% at Week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. Conclusions Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

Newborn screening (NBS) for severe combined immunodeficiency (SCID) started in Catalonia in January-2017, being the first Spanish and European region to universally include this testing. In Spain, a pilot study with 5000 samples was carried out in Seville in 2014, also, a research project with about 35,000 newborns will be carried out in 2021–2022 in the NBS laboratory of Eastern Andalusia. At present, the inclusion of SCID is being evaluated in Spain. The results obtained in the first three and a half years of experience in Catalonia are presented here. All babies born between January-2017 and June-2020 were screened through TREC-quantification in DBS with the Enlite Neonatal TREC-kit from PerkinElmer. A total of 222,857 newborns were screened, of which 48 tested positive. During the study period, three patients were diagnosed with SCID: an incidence of 1 in 74,187 newborns, 17 patients had clinically significant T-cell lymphopenia (non-SCID) with an incidence of 1 in 13,109 newborns who also benefited from the NBS program. The results obtained provide further evidence of the benefits of early diagnosis and curative treatment to justify the inclusion of this disease in NBS programs. A national NBS program is needed, also to define the exact SCID incidence in Spain.

Background: Patients with life threatening diseases may experience anxiety and depression. Aim: To analyze anxiety and depression in Chilean patients with cancer. Material and Methods: The Hospital Anxiety and Depression Scale (HADS) was applied to 623 ambulatory and hospitalized patients with cancer (70% women). Results: A low frequency of clinical anxiety (11,7%) and depression (5,3%) was observed. Depression was more common in women, in patients with mid-level education, in unemployed patients and in older people. Anxiety was more common in young and unemployed patients. Conclusions: The frequency of depression and anxiety was low in this group of cancer patients. Women, educated, uneomployed, and older subjects are risk groups for depression. Young and unemployed subjects experience more anxiety.

SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder characterized by progressive spasticity and weakness of the lower limbs caused by degeneration of the corticospinal tract. In other neurodegenerative motor disorders, the thalamus and basal ganglia are affected, with a considerable impact on disease progression. However, only a few works have studied these brain structures in HSP, mainly in complex forms of this disease. Our research aims to detect potential alterations in the volume and shape of the thalamus and various basal ganglia structures by comparing 12 patients with pure HSP and 18 healthy controls. We used two neuroimaging procedures: automated segmentation of the subcortical structures (thalamus, hippocampus, caudate nucleus, globus pallidus, and putamen) in native space and shape analysis of the structures. We found a significant reduction in thalamic volume bilaterally, as well as an inward deformation, mainly in the sensory-motor thalamic regions in patients with pure HSP and a mutation in SPG4. We also observed a significant negative correlation between the shape of the thalamus and clinical scores (the Spastic Paraplegia Rating Scale score and disease duration). Moreover, we found a ‘Group × Age’ interaction that was closely related to the severity of the disease. No differences in volume or in shape were found in the remaining subcortical structures studied. Our results suggest that changes in structure of the thalamus could be an imaging biomarker of disease progression in pHSP.

Background: The decision to perform allogeneic haematopoietic stem cell transplantation (alloHSCT) in acute myeloid leukemia (AML) is based on the risk-benefit ratio (non relapse mortality vs reduction of relapse risk). In 2017, the European LeukemiaNet (ELN) proposed a risk score based on cytogenetic and molecular genetic characteristics to facilitate this decision. Despite this improved classification of the genetic landscape of AML, the assessment of risk of relapse should be more precise. However, large cohorts are needed to analyze the clinical outcome of specific genetic alterations. Within the HARMONY alliance, we have now collected harmonized clinical and analytical data for a large number of AML patients. Aims: This study focuses on AML patients who achieved first complete remission (CR1) that, according to ELN risk (low/intermediate) assessment are not classical candidates for alloHSCT as consolidation therapy. The aim of this study is to create a more accurate risk prediction in this setting based on an on-line tool that can visualize the likelihood of relapse and thereby help to determine in which patient alloHSCT should be performed in CR1. Methods: The data included in the HARMONY alliance database was provided by 100 organisations in 18 European countries. In order to be accepted, they passed through quality control, anonymisation and harmonisation processes before being included in the database. Harmonisation is carried out according to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM), which is specially designed to accommodate both administrative claims and medical records, making it possible to bring together all the information from different data sources and to speed up its subsequent analysis. Through the analysis platform, we selected patients from the ~5700 patients available that matched the target population of the study. We filtered out those patients without sufficient information on their clinical course, those who did not achieve complete remission and patients with a poor prognosis (adverse risk according to ELN2017), as the study focuses on patients who a priori did not have an indication for alloHSCT. This process resulted in a sample of 842 patients. In the next steps, variable selection was performed together with the treatment of incomplete cases by imputation. Multiple Machine Learning (ML) techniques, both parametric and non-parametric, were tested for predictions (Random Forest, Weibull distribution), all of them taking into account censored data. Other sets of methods were applied to explain the information handled by the previous models and to present graphically, for each prediction, a breakdown of the influence that each feature had on that prediction. Validation of the results is being performed both by testing by medical specialists and by means of statistical indicators, such as Harrell's index. Results: The study population of 842 AML patients included 47% females and the median age was 49 years. The most frequent mutation was NPM1 (50%), followed by DNMT3A (31%) and NRAS (26%). The tool first displays a panel in which characteristics such as age, gender, and possible mutations and cytogenetic abnormalities are selected from a list based on information in the HARMONY database. Once the desired profile has been selected, graphical results are provided: 1). the probability of Relapse-Free Survival (RFS) over time. In parallel, as a reference, the probability of RFS of patients corresponding to each category of the ELN2017 can be seen. 2). a breakdown of the relative weight of each feature in the model at a specific time point, as well as the positive/negative effect that the presence/absence of these features has on the prognostic factor of relapse, adapting all this information in each individual simulation. This preliminary research tool can integrate new data and be expanded with new tools to provide useful results in a simple and accessible way. Conclusion: Building big data platforms, such as the HARMONY Alliance, are absolutely essential to facilitate the creation of tools to support research and ultimately clinical practice. Big data analysis should be considered a very useful field in disease research and it is necessary to share the results with easy-to-use tools that are available at all times. This new ML tool for AML aims to achieve these goals through its simple design and its implementation in mobile devices. Figure 1 Figure 1. Disclosures Sobas: Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Heckman: Kronos Bio, Inc.: Research Funding; Oncopeptides: Consultancy, Research Funding; Novartis: Research Funding; Orion Pharma: Research Funding; Celgene/BMS: Research Funding. Dombret: Amgen: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Novartis: Research Funding; Pfizer: Honoraria, Research Funding; Servier: Research Funding; Abbvie: Honoraria; BMS-Celgene: Honoraria; Daiichi Sankyo: Honoraria. Sierra: Jazz Pharmaceuticals: Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Other: Educational grant; BMS Celgene: Honoraria, Research Funding; Alexion: Other: Educational grant; Novartis: Honoraria, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Other: Educational grant; Janssen: Other: Educational grant; Pfizer: Honoraria. Mayer: Principia: Research Funding. Voso: Celgene: Consultancy, Research Funding, Speakers Bureau; Novartis: Speakers Bureau. Sanz: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses, Speakers Bureau; Gilead Sciences: Other: Travel, accommodations, and expenses; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Boehringer Ingelheim: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses; Helsinn Healthcare: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses, Research Funding. Calado: Novartis: Current Employment. Döhner: Celgene/BMS: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Other: Advisory Board; Astellas: Research Funding; Jazz Roche: Consultancy, Honoraria; Agios and Astex: Research Funding; Abbvie: Consultancy, Honoraria; Janssen: Honoraria, Other: Advisory Board; Novartis: Consultancy, Honoraria, Research Funding. Gaidzik: Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Speakers Bureau; Janssen: Speakers Bureau. Heuser: Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Research funding for institution; Janssen: Honoraria; Novartis: Consultancy, Honoraria, Other: Research funding for institution; Abbvie: Consultancy; BMS/Celgene: Consultancy; Daiichi Sankyo: Consultancy, Other: Research funding for institution; Pfizer: Consultancy, Other: Research funding for institution; Roche: Consultancy, Other: Research funding for institution; Tolremo: Consultancy; Astellas: Other: Research funding for institution; Bayer Pharma AG: Other: Research funding for institution; BergenBio: Other: Research funding for institution; Karyopharm: Other: Research funding for institution. Haferlach: MLL Munich Leukemia Laboratory: Other: Part ownership. Turki: CSL Behring: Consultancy; MSD: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau. Reinhardt: Astellas Pharma Inc.: Research Funding; Eusa: Other: Advisory board; Novartis: Other: Advisory board; BluebirdBio: Other: Advisory board; Janssen: Other: Advisory board; Abbvie: Other: Advisory board; JAZZ: Other: Advisory board; BMS: Other: Advisory board. Schulze-Rath: Bayer: Current Employment. Dohner: Berlin-Chemie: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; GEMoaB: Honoraria; Gilead: Honoraria; Helsinn: Honoraria; Janssen: Honoraria; Jazz Pharmaceuticals: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Oxford Biomedica: Honoraria; Pfizer: Research Funding; Roche: Honoraria; AstraZeneca: Honoraria; Astex Pharmaceuticals: Honoraria; Astellas: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Agios: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding. Ossenkoppele: Abbvie, AGIOS, BMS/Celgene Astellas,AMGEN, Gilead,Servier,JAZZ,Servier Novartis: Consultancy, Honoraria; Agios: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Jazz: Consultancy, Honoraria. Bullinger: Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Menarini: Consultancy; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Astellas: Honoraria; Sanofi: Honoraria; Seattle Genetics: Honoraria; Bayer: Research Funding; Amgen: Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Gilead: Consultancy; Celgene: Consultancy, Honoraria; Hexal: Consultancy. Hernández-Rivas: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Orthotropic Steel Decks have been used in long-span bridges for several decades because of their high capacity to weight ratio. However, many fatigue related issues have been reported. This paper provides an overview of the main existing fatigue prediction models and discusses their relevance for the fatigue life assessment of Orthotropic Steel Bridge Decks (OSBDs). Several case studies have proven the importance of considering the combined effect of wind and traffic loadings to estimate the fatigue life of long-span bridges. The importance of incorporating welding residual stresses is also well documented while it is often disregarded in design practices. Reliability-based fatigue assessment methods make it possible to quantify how the sources of uncertainty related to loading conditions, welding residual stresses or fabrication defects can affect the fatigue reliability of OSBDs. Monte Carlo simulations are often used to perform probabilistic analyses, but machine-learning algorithms are very promising and computationally efficient. The shortcomings of the Palmgren-Miner rule are discussed and the need for alternative damage accumulation indexes is clear. A number of conclusions are drawn from the analysis of fatigue tests conducted on OSBDs.

Unreinforced masonry (URM) structures are vulnerable to earthquakes; thus, materials and techniques for their strengthening and restoration should be developed. However, the materials used in some of the existing retrofitting technologies for URM and the waste produced at its end-of-life are unsustainable. The production of ordinary Portland cement (OPC) worldwide has enormously contributed to the global carbon footprint, resulting in persistent environmental problems. Replacing OPC with geopolymers, which are more sustainable and environmentally friendly, presents a potential solution to these problems. Geopolymers can replace the OPC component in engineering cementitious composites (ECC), recommended to strengthen and restore URM structures. In the present paper, the state-of-the-art knowledge development on applying geopolymers in URM structures is discussed. The discussion is focused on geopolymers and their components, material characterization, geopolymers as a strengthening and restoration material, and fiber-reinforced geopolymers and their application to URM structures. Based on this review, it was found that the mechanical properties of geopolymers are on par with that of OPC; however, there are few studies on the mentioned applications of geopolymers. The characterization of geopolymers’ mechanical and physical properties as a restoration material for URM structures is still limited. Therefore, other properties such as chemical interaction with the substrate, workability, thixotropic behavior, and aesthetic features of geopolymers need to be investigated for its wide application. The application method of geopolymer-based ECC as a strengthening material for a URM structure is by grouting injection. It is also worth recommending that other application techniques such as deep repointing, jacketing, and cement-plastering be explored.

Objective: To determine the cost-effectiveness of 2 strategies for post-discharge suicide prevention, an Enhanced Contact intervention based on repeated in-person and telephone contacts, and an individual 2-month long problem-solving Psychotherapy program, in comparison to facilitated access to outpatient care following a suicide attempt. Methods: We conducted a cost-effectiveness analysis based on a decision tree between January and December 2019. Comparative effectiveness estimates were obtained from an observational study conducted between 2013 and 2017 in Madrid, Spain. Electronic health care records documented resource use (including extra-hospital emergency care, mortality, inpatient admission, and disability leave). Direct cost data were derived from Madrid’s official list of public health care prices. Indirect cost data were derived from Spain’s National Institute of Statistics. Results: Both augmentation strategies were more cost-effective than a single priority outpatient appointment considering reasonable thresholds of willingness to pay. Under the base-case scenario, Enhanced Contact and Psychotherapy incurred, respectively, €2,340 and 6,260 per averted attempt, compared to a single priority appointment. Deterministic and probabilistic sensitivity analyses showed both augmentation strategies to remain cost-effective under several scenarios. Enhanced Contact was slightly cost minimizing in comparison to Psychotherapy (base-case scenario: €−196 per averted attempt). Conclusions: Two post-discharge suicide prevention strategies based on Enhanced Contact and Psychotherapy were cost-effective in comparison to a single priority appointment. Increasing contacts between suicide attempters and mental health-care providers was slightly cost minimizing compared to psychotherapy.

Background Well-designed studies assessing the treatment outcome of brain arteriovenous malformations (AVMs) are infrequent and have not consistently included all of the available treatment modalities, making their results not completely generalizable. Moreover, the predictors of poor outcome are not well defined. Methods We performed an observational retrospective study of AVM patients. We included patients with clinical, radiologic, and outcome data, with a minimum follow-up of 1 year. Neurologic outcome was documented using the modified Rankin Scale (mRS) at the AVM diagnosis and 30 days after the treatment. Results There were 117 patients, with equal male/female proportion. The mean follow-up time was 51 months. Treatment distribution in the Spetzler–Martin grades I–III was as follows: 52 (54.6%) surgery, 31 (32.35%) radiosurgery, 2 (0.02%) embolization, and 11 (12%) conservative follow-up. Treatment distribution in Spetzler–Martin grades IV and V was as follows: 4 (20%) surgery, 7 (35%) radiosurgery, and 10 (45%) conservative follow-up. Poor neurologic outcome (mRS ≥ 3) was significantly associated with poor clinical status at diagnosis (Glasgow Coma Scale [GCS] score< 14; odds ratio [OR]: 0.20; 95% confidence interval [CI]: 0.001–0.396; p = 0.010). The rupture of the AVM was associated with poor neurologic outcome. The Lawton–Young Supplementary scale (LYSS) proved to be the most effective in predicting poor outcome. The existence of seizures, treatment-related complications, and conservative treatment was associated with the worsening of the mRS score, whereas the existence of hemorrhage was associated with the likelihood of disability. Conclusion Our results suggest that poor neurologic status at diagnosis, AVM rupture, and conservative treatment were associated with worse outcome. Hemorrhage as initial presentation is related to disability, not with mRS worsening. The LYSS appeared to be the best method to predict outcome.

BackgroundGlobal pandemic SARS-CoV-2 causes a prothrombotic state without fully elucidated effects. This study aims to analyse and quantify the possible retinal microvascular abnormalities.Materials and methodsCase–control study. Patients between 18 and 55 years old with PCR-confirmed SARS-CoV-2 infection within the last 3 months were included. Risk stratification: group 1—mild disease (asymptomatic/paucisymptomatic); group 2—moderate disease (required hospital admission with no acute respiratory distress) and group 3—severe disease (subjects who developed an acute respiratory distress were admitted in the intensive care unit and presented interleukin 6 values above 40 pg/mL). Age-matched volunteers with negative serology tests were enrolled to control group. A colour photograph, an optical coherence tomography (OCT) and an angiography using OCT centred on the fovea were performed.ResultsControl group included 27 subjects: group 1 included 24 patients, group 2 consisted of 24 patients and 21 participants were recruited for group 3. There were no funduscopic lesions, neither in the colour images nor in the structural OCT. Fovea-centred vascular density (VD) was reduced in group 2 and group 3 compared with group 1 and control group (control group vs group 2; 16.92 vs 13.37; p=0.009) (control group vs group 3; 16.92 vs .13.63; p=0.026) (group 1 vs group 2; 17.16 vs 13.37; p=0.006) (group 1 vs group 3; 17.16 vs 13.63 p=0.017).ConclusionPatients with moderate and severe SARS-CoV-2 pneumonia had decreased central retinal VD as compared with that of asymptomatic/paucisymptomatic cases or control subjects.

Background To identify different response patterns to intravitreal dexamethasone implants (IDI) in naïve and previously treated (PT) diabetic macular edema (DME) eyes in a real-life setting. Methods 342 IDI injections (203 DME eyes) were included. Number of IDI injections, percentage (%) of eyes with 1, 2, 3 and ≥ 4 injections, time to reinjections, visual acuity (VA), intraocular pressure (IOP) and central retinal thickness (CRT) were evaluated for naïve and PT DME eyes over 24 months. Results Mean number of injections was significantly lower in naïve vs PT DME eyes (1.40 ± 0.9 vs 1.82 ± 0.9, p p p p = 0.80). Mean time to reinjection was not significantly different between both groups for the second, third and fourth injection (9.6 ± 4.0 vs 10.0 ± 5.5, p = 0.75, 13.2 ± 4.0 vs 16.0 ± 3.5, p = 0.21 and 21.7 ± 3.8 vs 19.7 ± 5.8, p = 0.55). VA scores were consistently better in naïve vs PT DME eyes at all studied timepoints, with no significant differences in CRT reduction or adverse effect rates. Conclusion Naïve DME eyes received lower number of IDI injections and showed better VA levels than PT DME eyes for 24 months in a real-world setting. This data supports the IDI use in early DME stages and provide further evidence of better IDI response when used as first-line therapy.

SummaryObjectiveThe aim was to assess the clinical effectiveness of drugs used in hospitalized patients with COVID-19 infection.MethodWe conducted a systematic review of randomized clinical trials assessing treatment with remdesivir, chloroquine, hydroxychloroquine, lopinavir, ritonavir, dexamethasone, and convalescent plasma, for hospitalized patients with a diagnosis of SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, duration of ventilation, duration of oxygen support, duration of hospitalization), virological clearance, and severe adverse events.ResultsA total of 48 studies were retrieved from the databases. Ten articles were finally included in the data extraction and qualitative synthesis of results. The meta-analysis suggests a benefit of dexamethasone versus standard care in the reduction of risk of mortality at day 28; and the clinical improvement at days 14 and 28 in patients treated with remdesivir.ConclusionsDexamethasone would have a better result in hospitalized patients, especially in low-resources settings.Significance of resultsThe analysis of the main treatments proposed for hospitalized patients is of vital importance to reduce mortality in low-income countries; since the COVID-19 pandemic had an economic impact worldwide with the loss of jobs and economic decline in countries with scarce resources.

Background and Aims: Data from clinical trials suggest that biological drugs may improve the outcomes in Crohn&rsquo, s disease (CD) by reducing the need for surgery or hospitalization. The aim of this study is to evaluate the time-trends of the use of biological drugs and other treatments for CD, and its relationship with outcomes in Catalonia. Materials and Methods: All patients with CD included in the Catalan Health Surveillance System (containing data on a population of more than 7.5 million) from 2011 to 2017 were identified. The exposures to different treatments for inflammatory bowel disease were retrieved from electronic invoicing records. Results: Between 2011 and 2017, the use of salicylates, corticosteroids and immunosuppressive treatment fell from 28.8% to 17.1%, 15.8% to 13.7%, and 32.9% to 29.6%, respectively (p &lt, 0.001). Biological treatment use rose from 15.0% to 18.7% (p &lt, 0.001). Ostomy rates per 1000 patients/year fell from 13.2 in 2011 to 9.8 in 2017 (p = 0.003), and surgical resection rates from 24.1 to 18.0 (p &lt, 0.001). The rate of CD-related hospitalizations per 1000 patients/year also fell, from 92.7 to 72.2 (p &lt, 0.001). Conclusions: Biological drug use rose from 15.0% to 18.7% between 2011 and 2017. During this period, we observed an improvement in the outcomes of CD patients.

During a homicide investigation in which fire has been used to reduce the size of the cadaver and conceal the evidence of injuries, the identification of perimortem trauma presents a challenge, in particular in cases when the perpetrator has dismembered the body followed by burning the remains. It is therefore important to understand the effects which heat causes on fresh bone. The aim of this paper is to perform a pilot study on the survival ratio of toolmarks in different anatomical regions associated with dismemberment, and a descriptive analysis of the variables that may potentially influence the post-burning survival and detection. To achieve this, three donated embalmed cadavers were used to simulate a case in which an attempted dismemberment and burning had occurred. Fifty-five pre-burning injuries were manually induced: 30 using a machete to inflict chopping trauma, and 25 with a serrated bread knife to inflict sharp force trauma, on the thigh, knee, ankle and wrist. The cadavers were cremated in a furnace at Madrid’s Cementerio Sur and the burnt remains were analysed at the Laboratorio de Antropología y Odontología Forense of the Universidad Complutense de Madrid. Not all pre-burning injuries inflicted were visible after the cremation process; only 13% were detected in this experiment. Toolmarks can be masked, modified, destroyed or overlooked from the outset of the procedure due to several factors which influence the post-burning survival and detection of toolmarks and contribute to conceal the evidence of trauma. Additional research should be done to study further variables which affect the post-burning visibility of sharp force trauma.

Introducción. El uso tradicional de plantas medicinales para tratar diferentes enfermedades, ya sean infecciosas o no, es ampliamente aceptado debido a su bajo costo y sus bajos índices de toxicidad. Estas plantas son frecuentemente usadas en casos que involucran irritaciones de la piel, heridas superficiales, picaduras de insectos y mordeduras de víboras.Objetivo. Recopilar la información disponible sobre los principales usos terapéuticos y los componentes fitoquímicos de Cnidoscolus aconitifolius, una planta conocida popularmente como chaya y que crece en regiones tropicales de México y Centroamérica.Materiales y métodos. Se realizó una revisión de la literatura sobre C. aconitifolius publicada hasta 2017 en las bases de datos BIREME, PubMed/Medline, Elsevier y SciELO. Para la búsqueda se emplearon los descriptores “Cnidoscolus” y “aconitifoloius”, y no se aplicaron filtros de idioma.Resultados. Se identificaron 82 artículos luego de completar la búsqueda inicial. Después de filtrar los estudios por título (presencia de descriptores de búsqueda en el título) y remover duplicados, se incluyeron 18 artículos en la revisión. De acuerdo a la información encontrada, fue posible confirmar que esta planta ofrece diversos beneficios para la salud.Conclusiones. El uso terapéutico tradicional de la chaya está sustentado por evidencia científica, por lo que se sugiere realizar más investigaciones centradas en la identificación de nuevas propiedades fitoquímicas de esta planta y, así, establecer alternativas terapéuticas para distintas afecciones.

To test the hypothesis that periodontitis is associated with AD and search whether periodontal and other variables would negatively impact the oral health-related quality of life (OHRQoL) perception. Oral examinations and interview on self-perceived oral health status (Geriatric Oral Health Assessment Index (GOHAI) questionnaire (higher score corresponds to better perceived oral status)) were carried out and socio-demographic data were collected from outpatients with mild to moderate AD (cases, n = 50) and from their age- and sex-matched family caregivers (controls, n = 52). Full-mouth periodontal examination was performed. Significance of differences between groups was sought by chi-square, Student’s t, or the Mann-Whitney test. The association between the variables periodontitis, probing depth (PD) ≥ 5 mm, and clinical attachment loss (CAL) ≥ 5 mm with the variable group was tested in binary logistic regression models (LRMs). LRMs were used to test the association of oral findings, demographics, and group with GOHAI. Cases had fewer teeth and greater CAL than controls. Cases had a superior percentage of sites with plaque, calculus, and bleeding on probing than controls. Cases had greater GOHAI scores than controls. Periodontitis was a variable most likely associated with AD (OR = 11.08, p < 0.001). None of the oral findings or demographics, but group, was associated with GOHAI (OR = 14.45, p < 0.001). Periodontitis is associated with AD, but not with patients’ OHRQoL. Health care professionals must be aware that AD patients should have a periodic thorough oral examination and preventive intervention aiming at their welfare and maintenance of a pain-free functional dentition.

Objective To evaluate the national general prevalence of postoperative pain and the associated organizational/structural factors related to the provision of health care services. Design and Setting Observational prospective cohort study performed in 46 tertiary hospitals that were randomly selected from the Spanish National Inventory of Hospitals through a two-stage balanced and stratified procedure. Subjects and Methods Nine-hundred surgical patients representing a wide spectrum of surgical procedures and anesthetic methods were recruited. Those suffering moderate or worse pain while in the postanesthesia care unit/surgery ward (PACU/SW) were followed for 72 hours. Site characteristics were also surveyed. Multilevel models were used to evaluate center- and patient-level factors associated with pain and quality of recovery (QoR). Weighted generalized estimating equations were used to analyze the evolution of pain intensity. Results The prevalence while in and at discharge from the PACU/SW was 48.7% (cluster-adjusted 95% confidence interval [CI] = 38.1–59.2%) and 21.6% (95% CI = 15.4–27.8%), respectively. Pain intensity decreased significantly over time. Less than 20% of the patients received systemic patient-controlled analgesia (PCA) or regional analgesic techniques. Age, preexisting pain, type of surgery, use of general anesthesia, and postoperative potent opioids were associated with pain risk and intensity, as were center-level factors such as patient information, protocol availability, and coordination of care. In turn, QoR was related to pain intensity and patient satisfaction with analgesia and side effects. Conclusions Compared with previous reports, the prevalence of moderate/severe postoperative pain has decreased but remains excessive. Organizational improvements to deploy procedure-specific, opioid-sparing analgesic strategies including regional techniques are recommended.

We estimate the impact of the tariffs that U.S. export crops face on farmland rental rates. The estimation of the impact of the localized measure on the rents faces two aggregation problems that lead to identification challenges: a) aggregating tariffs across trading partners to obtain crop-specific tariffs, and b) aggregating the crop-specific tariffs across crops to obtain the localized measure. Utilizing shift-share style approaches, we find that a one percent increase in the localized tariff reduces the rents by about 2.6 - 5.3% point, which implies that the 2018 Chinese retaliatory tariffs would reduce the rents by about 2%.

We estimate the effects of agricultural technological progress on cropland expansion at various geographical resolutions, from the country level to the world as a whole, while formally accounting for the international interdependence of national supply responses. Evidence for these effects has thus far been scant, contributing to polarized perceptions about the potential for improving agricultural technologies as a means to slow down deforestation. We find that, in most countries of the world, growth in total factor productivity (TFP) is either uncorrelated or is positively associated with cropland expansion. Yet worldwide TFP growth have been an important source of global land savings. The divergence between the country-level and the global results is explained by the changes in production patterns as countries interact in international markets. Our preferred point estimate of the elasticity of global cropland to global TFP growth is -0.34. Moreover, we estimate that satisfying food demand from 1991 to 2010 without observed TFP growth would have necessitated an additional 173 million hectares, or close to 10% of the area covered by tropical rain forests.

Purpose To report a case of hypertensive choroidopathy with detailed chorioretinal images obtained using swept source optical coherence tomography. Methods We report the case of a 36-year-old pregnant woman who presented with extensive bilateral exudative retinal detachments (visual acuity of hands movement bilaterally), high blood pressure, and severe alteration of the laboratory test results resulting in the diagnosis of HELLP syndrome. The baby was delivered by emergency cesarean section and the patient was hospitalized in the intensive care unit. Results Two weeks later, exudative retinal detachments improved substantially and bilateral Elschnig spots were present in the posterior fundus. Swept source optical coherence tomography revealed serous retinal detachment, multiple pigmentary epithelial detachments (PEDs), a thickened subfoveal choroid (437 and 466 μm), and fibrinous material between the neurosensory retina and retinal pigment epithelium in the B-scans of both eyes. En face swept source optical coherence tomography allowed a more precise evaluation of the multiple and confluent PEDs. Six weeks later, despite some focal areas of thickened retinal pigment epithelium, the serous retinal detachment, PEDs, and fibrinous material resolved bilaterally and visual acuity and choroidal thickness returned to normal range (361 and 366 μm). En face swept source optical coherence tomography revealed a dramatic improvement of PEDs in terms of extension and distribution. Conclusion Swept source optical coherence tomography detected serous retinal detachment, PEDs, increased subfoveal choroidal thickness, and fibrinous material under the neurosensory retina in the acute phase of hypertensive choroidopathy. En face OCT is useful for monitoring the evolution of confluent PEDs in hypertensive choroidopathy.

Resumen Antecedentes y objetivo El objetivo de este trabajo es evaluar el cambio del diagnostico molecular sobre el histologico de una serie de tumores gliales al revisar el diagnostico con la clasificacion de la OMS de 2016. Materiales y metodos Se realiza un estudio retrospectivo de los tumores gliales (oligodendrogliomas y astrocitomas) tratados en nuestro centro entre enero de 2012 y junio de 2016, y una revision diagnostica segun su estudio molecular. Se lleva a cabo el analisis estadistico de variables epidemiologicas, histologicas y de genetica molecular (mutaciones en IDH y presencia de codelecion 1p19q), variacion en el diagnostico al introducir la nueva clasificacion tumoral e impacto clinico de dicha reclasificacion. Resultados De los 147 casos de tumores gliales revisados, se obtuvo el diagnostico molecular en 74 casos (50,3%). En 23 casos (31%) cambio el diagnostico, predominando en 20 (87%) el diagnostico previo de oligodendroglioma (69,6% grado ii y 17,4% grado iii ). Solo 3 de los 23 casos cambiaron de diagnostico inicial astrocitario al oligodendroglial. Respecto al patron molecular en estos 23 casos, se detecto IDH mutado en 16 (69,6%) y codelecion 1p19q negativa en 20 (87%). Segun la estirpe celular, de los 27 oligodendrogliomas de esta serie, 20 (74%) cambiaron de diagnostico por tener la codelecion negativa, pasando a ser astrocitomas. Se observo una tendencia a un mayor cambio de diagnostico en pacientes jovenes ( Conclusiones Dentro del espectro de tumores astrocitarios y oligodendrogliales en nuestro centro, la clasificacion diagnostica con genetica molecular evidencia importantes cambios respecto al diagnostico morfologico. Estos cambios afectan especialmente a los diagnosticos previos de oligodendrogliomas y a los pacientes jovenes en los casos revisados, y con patrones moleculares de mutacion en la IDH y de ausencia de codelecion 1p19q. Si bien se pueden plantear dudas respecto a la clinica, el pronostico y el tratamiento realizado en estos casos, se requieren estudios especificos en estos aspectos para lograr unas conclusiones apropiadas.