Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies.

OBJECTIVES: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. METHODS: We conducted a multicentre, international, retrospective cohort study. RESULTS: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. CONCLUSIONS: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

The population genomics of archaeological transition in west Iberia: Investigation of ancient substructure using imputation and haplotype-based methods.

We analyse new genomic data (0.05-2.95x) from 14 ancient individuals from Portugal distributed from the Middle Neolithic (4200-3500 BC) to the Middle Bronze Age (1740-1430 BC) and impute genomewide diploid genotypes in these together with published ancient Eurasians. While discontinuity is evident in the transition to agriculture across the region, sensitive haplotype-based analyses suggest a significant degree of local hunter-gatherer contribution to later Iberian Neolithic populations. A more subtle genetic influx is also apparent in the Bronze Age, detectable from analyses including haplotype sharing with both ancient and modern genomes, D-statistics and Y-chromosome lineages. However, the limited nature of this introgression contrasts with the major Steppe migration turnovers within third Millennium northern Europe and echoes the survival of non-Indo-European language in Iberia. Changes in genomic estimates of individual height across Europe are also associated with these major cultural transitions, and ancestral components continue to correlate with modern differences in stature.

Anthracological study of a Chalcolithic funerary deposit from Perdigões (Alentejo, Portugal): A new analytical methodology to establish the wood burning temperature.

Anthracological analyses of charcoal samples retrieved from Pit 16 of Perdigões (Reguengos de Monsaraz, Portugal), a secondary deposition of cremated human remains dated back to the middle of the 3rd millennium BC, enabled the identification of 7 different taxa: Olea europaea, Quercus spp. (evergreen), Pinus pinaster, Fraxinus cf. angustifolia, Arbutus unedo, Cistus sp. and Fabaceae. All taxa are characteristic of both deciduous and evergreen Mediterranean vegetation, and this data might indicate that the gathering of woods employed for the human cremation/s occurred either on site, or in its vicinity. However, considering both the large distribution of the identified taxa and data about human mobility, it is not possible to conclusively determine the origin of the wood used in the cremation(s). Chemometric analysis were carried out to estimate the absolute burning temperature of woods employed for the human cremation/s. An in-lab charcoal reference collection was created by burning sound wood samples of the three main taxa identified from Pit 16, Olea europaea var. sylvestris, Quercus suber (evergreen type) and Pinus pinaster, at temperatures between 350 and 600 °C. The archaeological charcoal samples and the charcoal reference collection were chemically characterized by using mid-infrared (MIR) spectroscopy in the 1800-400 cm-1 range, and Partial Least Squares (PLS) regression method was used to build calibration models to predict the absolute combustion temperature of the archaeological woods. Results showed successful PLS forecasting of burn temperature for each taxon (significant (P <0.05) cross validation coefficients). The anthracological and chemometric analysis evidenced differences between the taxa coming from the two stratigraphic units within the Pit, SUs 72 and 74, suggesting that they may come from two different pyres or two different depositional moments.

Mandibular morphology and the Mesolithic-Neolithic transition in Westernmost Iberia.

Neolithic farming and animal husbandry were first developed in the Near East ~ 10,000 BCE and expanded westwards, reaching westernmost Iberia no later than 5500 BCE. It resulted in major social, cultural, economic and dietary changes. Yet, the impact of this change on human mandibular morphology in Iberia is yet to be assessed, which is regrettable because mandible form is impacted by population history and diet. In this study we used Mesolithic to Chalcolithic Iberian samples to examine the impact of this transition on mandibular morphology. We also compared these samples with a Southern Levantine Chalcolithic population to assess their relationship. Lastly, we assessed dental wear to determine if the morphological differences identified were related to the material properties of the diet. We found differences between samples in mandibular shape but not size, which we attribute to contrasting population histories between Mesolithic and later populations. Some differences in the severity of dental wear were also found between Mesolithic and later Iberian samples, and smaller between the Mesolithic Iberians and southern Levantines. Little relationship was found between wear magnitude and mandibular shape. Altogether, our results show that the Mesolithic-Neolithic Iberian transition resulted in a meaningful change in mandibular morphology, which was likely driven more by population history than by dietary change.

Sequence-oriented sensitive analysis for PM2.5 exposure and risk assessment using interactive process mining.

The World Health Organization has estimated that air pollution will be one of the most significant challenges related to the environment in the following years, and air quality monitoring and climate change mitigation actions have been promoted due to the Paris Agreement because of their impact on mortality risk. Thus, generating a methodology that supports experts in making decisions based on exposure data, identifying exposure-related activities, and proposing mitigation scenarios is essential. In this context, the emergence of Interactive Process Mining-a discipline that has progressed in the last years in healthcare-could help to develop a methodology based on human knowledge. For this reason, we propose a new methodology for a sequence-oriented sensitive analysis to identify the best activities and parameters to offer a mitigation policy. This methodology is innovative in the following points: i) we present in this paper the first application of Interactive Process Mining pollution personal exposure mitigation; ii) our solution reduces the computation cost and time of the traditional sensitive analysis; iii) the methodology is human-oriented in the sense that the process should be done with the environmental expert; and iv) our solution has been tested with synthetic data to explore the viability before the move to physical exposure measurements, taking the city of Valencia as the use case, and overcoming the difficulty of performing exposure measurements. This dataset has been generated with a model that considers the city of Valencia's demographic and epidemiological statistics. We have demonstrated that the assessments done using sequence-oriented sensitive analysis can identify target activities. The proposed scenarios can improve the initial KPIs-in the best scenario; we reduce the population exposure by 18% and the relative risk by 12%. Consequently, our proposal could be used with real data in future steps, becoming an innovative point for air pollution mitigation and environmental improvement.

A lunate-triquetral coalition from a commingled funerary context from the Chalcolithic Perdigões ditched enclosures of Portugal.

Carpal coalitions, resulting from a failure of separation of the cartilaginous precursors of the carpal bones during gestation, may be osseous or non-osseous. Even though lunate-triquetral coalitions are the most common of all carpal coalitions there is only one previous palaeopathological report of such a coalition. This study presents a non-osseous lunate-triquetral coalition found amongst the mostly cremated commingled bones from a Chalcolithic pit at Perdigões (Portugal). The cremated bones show evidence of burning at varying but mostly at generally high temperatures. The perfect articulation between these right bones and pinpoint pitting in the lunate-triquetral joint were crucial for the identification of this congenital condition. Carpal coalitions are more frequent in African than European populations. Artifacts produced from ivory of African origin were found in Perdigões, however it is not possible to establish the ancestry of this individual.

Use of Monte Carlo Simulation as a Tool for the Nondestructive Energy Dispersive X-ray Fluorescence (ED-XRF) Spectroscopy Analysis of Archaeological Copper-Based Artifacts from the Chalcolithic Site of Perdigões, Southern Portugal.

This work is part of a broader research line that aims to develop and implement a nondestructive methodology for the chemical characterization of archaeological metals based on a protocol that combines energy dispersive X-ray fluorescence spectrometry (ED-XRF) with a Monte Carlo (MC) simulation algorithm. In this paper, the ED-XRF-MC protocol has been applied to estimate the chemical composition of a selected group of 26 copper-based artifacts and fragments recovered at Perdigões, one of the larger Chalcolithic sites of southwest Iberia. All the analyzed artifacts have a multilayered structure composed of the alloy substrate and of a superficial layer common in each metal buried for hundreds of years and consisting of the patina mixed with soil. Due to the difficulty in determining the quantitative composition of these alloys in the presence of this complex patina/encrustation layer, the spectrometric protocol applied in this paper allows to simulate and to determine the composition of the bulk alloy without any prior removal of the overlying corrosion patina layer and soil-derived crust, even in the presence of rough and irregular surfaces, thus preserving the physical integrity of the artifacts. The overall results obtained with the ED-XRF-MC protocol indicates that the artifacts from Perdigões are almost pure coppers with a low amount of arsenic (<3.0 wt%) and reduced concentration of elements such as Pb, Bi, and Sb, in agreement with the third millennium metallurgy known in southwestern Iberia. Also based on previously theoretical-experimental studies, the data presented in this paper show how the applied analytical methodology can be a fast and completely nondestructive analytical tool reliable for routine and large-scale chemical analysis of archaeological metals, thus representing a major advance to be broadly applied within the field of cultural heritage studies.

Chronic mercury exposure in Late Neolithic/Chalcolithic populations in Portugal from the cultural use of cinnabar.

Cinnabar is a natural mercury sulfide (HgS) mineral of volcanic or hydrothermal origin that is found worldwide. It has been mined prehistorically and historically in China, Japan, Europe, and the Americas to extract metallic mercury (Hg(0)) for use in metallurgy, as a medicinal, a preservative, and as a red pigment for body paint and ceramics. Processing cinnabar via combustion releases Hg(0) vapor that can be toxic if inhaled. Mercury from cinnabar can also be absorbed through the gut and skin, where it can accumulate in organs and bone. Here, we report moderate to high levels of total mercury (THg) in human bone from three Late Neolithic/Chalcolithic (5400-4100 B.P.) sites in southern Portugal that were likely caused by cultural use of cinnabar. We use light stable isotope and Hg stable isotope tracking to test three hypotheses on the origin of mercury in this prehistoric human bone. We traced Hg in two individuals to cinnabar deposits near Almadén, Spain, and conclude that use of this mineral likely caused mild to severe mercury poisoning in the prehistoric population. Our methods have applications to bioarchaeological investigations worldwide, and for tracking trade routes and mobility of prehistoric populations where cinnabar use is documented.

Diagnóstico y tratamiento de la retinopatía diabética y edema macular diabético: guía de práctica clínica del Seguro Social de Salud del Perú (EsSalud) / Diagnosis and treatment of diabetic retinopathy and diabetic macular edema: clinical practice guidelines of the Peruvian Health Social Security (EsSalud)

RESUMEN Introducción. El presente artículo resume la guía de práctica clínica (GPC) para el diagnóstico y tratamiento de la retinopatía diabética y el edema macular diabético en el Seguro Social de Salud del Perú (EsSalud). Objetivo. Proveer recomendaciones clínicas basadas en evidencia para el diagnóstico y tratamiento de la retinopatía diabética y el edema macular diabético en EsSalud. Métodos. Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos. El GEG formuló 4 preguntas clínicas a ser respondidas por la presente GPC. Para cada una de estas preguntas se realizó búsquedas de revisiones sistemáticas y de estudios primarios (cuando se consideró pertinente) en PubMed durante el 2018. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones, los puntos de buena práctica clínica y el flujograma de manejo. Resultados. La presente GPC abordó 4 preguntas clínicas sobre el tamizaje, diagnóstico, tratamiento de elección y tratamiento adyuvante. En base a estas preguntas se formularon 6 recomendaciones (4 fuertes y 2 condicionales), 19 puntos de buena práctica clínica y 1 flujograma de manejo. Conclusión. El presente artículo resume la metodología y las conclusiones basadas en evidencias de la GPC para el diagnóstico y tratamiento de la retinopatía diabética y el edema macular diabético en EsSalud.

ABSTRACT Introduction. This article summarizes the clinical practice guidelines (CPG) for the diagnosis and treatment of diabetic retinopathy and diabetic macular edema of the Health Social Security of Peru (EsSalud). Objective. To provide clinical recommendations based on evidence for the diagnosis and treatment of diabetic retinopathy and diabetic macular edema in EsSalud. Methods. A guidelines elaborating group (GEG) was conformed by medical specialists and methodologists. The GEG formulated 4 clinical questions intended to be answered by this CPG. For each of these questions systematic searches of systematic reviews and primary studies (when considered pertinent) were carried out in PubMed during 2018. Evidence was selected in order to reply each of the proposed clinical questions. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. During periodic working meetings, the GEG used the GRADE methodology to review the evidence and formulate the recommendations, points of good clinical practice and the management flowchart. Results. The present CPG addressed 4 clinical questions of four topics: screening, diagnosis, treatment of choice and adjuvant treatment. Based on these questions, 6 recommendations (4 strong and 2 conditional), 19 points of good clinical practice, and 1 management flowchart were formulated. Conclusion. This article summarizes the methodology and conclusions based on evidence from the CPG for the diagnosis and treatment of diabetic retinopathy and diabetic macular edema in EsSalud.