The funerary phenomenon in the Cantabrian Iron Age. A new ritual space in the necropolis of Monte Bernorio (excavations from 2007 and 2008)

La necrópolis del oppidum de Monte Bernorio fue uno de los primeros cementerios de la Edad del Hierro excavados en España. No obstante, la atención a los excepcionales materiales metálicos descubiertos en ella, unido a la escasez de restos relacionados con los rituales, ha impedido conocer hasta este momento qué tipo de ceremonias funerarias se desarrollaron en ella. En este trabajo se presentan los diversos estudios y análisis realizados sobre las evidencias recuperadas en las excavaciones de las campañas de 2007 y 2008, así como los resultados obtenidos y las interpretaciones que de estos hemos realizado. El resultado es la identificación de un tipo de ritual que invisibiliza los restos y que implica un uso diferente de los espacios funerarios.The necropolis of the oppidum of Monte Bernorio was one of the first Iron Age cemeteries excavated in Spain. However, the focus of previous studies on the exceptional metal objects discovered, plus the scarcity of human remains, prevented us from establishing the type of funerary ceremonies that took place at the site. This work presents the interpretation of the outcome of the different studies and analyses made on the material evidence recovered during the excavations carried out in 2007 and 2008. As a result, a funerary ritual that obscures the presence of human remains and implies an different use of funerary spaces has been identified

Reversions of QuantiFERON-TB Gold Plus in tuberculosis contact investigation: A prospective multicentre cohort study

Background: Interferon-y Release Assays (IGRA) reversions have been reported in different clinical scenarios for the diagnosis of tuberculosis (TB) infection. This study aimed to determine the rate of QuantiFERON-TB Gold Plus (QFT-Plus) reversions during contact investigation as a potential strategy to reduce the number of preventive treatments. Methods: Prospective, multicentre cohort study of immunocompetent adult contacts of patients with pulmonary TB tested with QFT-Plus. Contacts with an initial positive QFT-Plus (QFT-i) underwent a second test within 4 weeks (QFT-1), and if negative, underwent a repeat test 4 weeks later (QFT-2). Based on the QFT-2 result, we classified cases as sustained reversion if they remained negative and as temporary reversion if they turned positive. Results: We included 415 contacts, of whom 96 (23.1%) had an initial positive test (QFT-i). Following this, 10 had negative QFT-1 results and 4 (4.2%) of these persisted with a negative result in the QFT-2 (sustained reversions). All four sustained reversions occurred in contacts with IFN-γ concentrations between ≥0.35 and ≤0.99 IU•mL-1 in one or both QFT-i tubes. Conclusion: In this study, TB contact investigations rarely reveal QFT-Plus reversion. These results do not support retesting cases with an initial positive result to reduce the number of preventive treatments

Climate change facilitated the early colonization of the Azores Archipelago during medieval times

Humans have made such dramatic and permanent changes to Earth's landscapes that much of it is now substantially and irreversibly altered from its preanthropogenic state. Remote islands, until recently isolated from humans, offer insights into how these landscapes evolved in response to human-induced perturbations. However, little is known about when and how remote systems were colonized because archaeological data and historical records are scarce and incomplete. Here, we use a multiproxy approach to reconstruct the initial colonization and subsequent environmental impacts on the Azores Archipelago. Our reconstructions provide unambiguous evidence for widespread human disturbance of this archipelago starting between 700 -60/+50 and 850 -60/+60 Common Era (CE), ca. 700 y earlier than historical records suggest the onset of Portuguese settlement of the islands. Settlement proceeded in three phases, during which human pressure on the terrestrial and aquatic ecosystems grew steadily (i.e., through livestock introductions, logging, and fire), resulting in irreversible changes. Our climate models suggest that the initial colonization at the end of the early Middle Ages (500 to 900 CE) occurred in conjunction with anomalous northeasterly winds and warmer Northern Hemisphere temperatures. These climate conditions likelyinhibited exploration from southern Europe and facilitated human settlers from the northeast Atlantic. These results are consistent with recent archaeological and genetic data suggesting that the Norse were most likely the earliest settlers on the islands

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Building Standardized and Secure Mobile Health Services Based on Social Media

Mobile devices and social media have been used to create empowering healthcare services. However, privacy and security concerns remain. Furthermore, the integration of interoperability biomedical standards is a strategic feature. Thus, the objective of this paper is to build enhanced healthcare services by merging all these components. Methodologically, the current mobile health telemonitoring architectures and their limitations are described, leading to the identification of new potentialities for a novel architecture. As a result, a standardized, secure/private, social-media-based mobile health architecture has been proposed and discussed. Additionally, a technical proof-of-concept (two Android applications) has been developed by selecting a social media (Twitter), a security envelope (open Pretty Good Privacy (openPGP)), a standard (Health Level 7 (HL7)) and an information-embedding algorithm (modifying the transparency channel, with two versions). The tests performed included a small-scale and a boundary scenario. For the former, two sizes of images were tested; for the latter, the two versions of the embedding algorithm were tested. The results show that the system is fast enough (less than 1 s) for most mHealth telemonitoring services. The architecture provides users with friendly (images shared via social media), straightforward (fast and inexpensive), secure/private and interoperable mHealth services

The ISO/EN 13606 Standard for the Interoperable Exchange of Electronic Health Records

The standardization of Electronic Health Records (EHR) is a crucial factor for ensuring interoperable sharing of health data. During recent decades, a plethora of initiatives - driven by international organizations - has emerged to define the required models describing the exchange of information between EHRs. These models cover different essential characteristics for building interoperable EHRs, such as architecture, methodology, communication, safety or terminology, among others. In this context, the European reference frame for the standardized exchange of EHR is the recently approved ISO/EN 13606 standard. This multi-part standard provides the syntactic and semantic capabilities (through a dual model approach) as well as terminology, security and interface considerations for the standardized exchange of EHR. This paper provides (a) an introduction to the different standardization efforts related to the interoperable exchange of EHR around the world, and (b) a description of how the ISO/EN 13606 standard provides interoperable sharing of clinical information

Design and evaluation of a wireless decision-support system for heart rate variability study in haemodialysis follow-up procedures

In this paper a new wireless decision-support system for haemodialysis patients using heart rate variability (HRV) is presented. The telemedicine system provides connectivity to three participant sites: the general practitioner or nurse at the point of care in the dialysis unit, the remote information and processing server and the cardiologist. At the clinical point of care, the nurse acquires the electrocardiogram (ECG) by using a tailored mobile telecardiology system as well as other relevant physiological information during the clinical procedure, and sends it to the information server. The received information is stored in a secure file server, linked to the patient database and the ECG signal is automatically analyzed by using advanced signal processing tools in the processing server, where a complete clinical results report is generated. The cardiologist can then be linked by means of a web browser to the information server to analyze these results for further clinical diagnosis support. The system has been applied to study HRV in patients undergoing haemodialysis. The clinical report consisted of trends for time- and frequency-domain HRV indexes and other supplementary information automatically calculated, which show the response of the electrical activity of the heart to the dialysis process and that can be helpful for the follow-up of these patients. The telecardiology framework has been successfully evaluated both by the patients and the hospital personnel showing a high compliance with the system. The design and implementation of the telecardiology system have followed the most recent advances in web technologies, biomedical information and storage standards and signal processing techniques. The presented system can be used as a telemedicine tool for clinical diagnosis support and could also be used in other clinical settings