Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

BackgroundThe PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.MethodsFebrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.FindingsOf 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.InterpretationMost febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.FundingEU Horizon 2020 grant 668303

Paradoxes of European Foreign Policy.Balancing Europe's Eastern and Southern Dimensions

Digitised version produced by the EUI Library and made available online in 2020

Professional perception for the elderly care in the COVID-19 crisis: the Senior Centers of the Ciudad Lineal District of Madrid

La COVID-19 ha desencadenado una crisis sanitaria y social a nivel mundial. En España, las medidas de contención desencadenadas por la crisis han resultado especialmente duras y han generado situaciones sobrevenidas de vulnerabilidad. Los Centros Municipales de Mayores se configuran como equipamientos públicos, no residenciales y destinados a promover la convivencia de las personas mayores. El presente artículo tiene como objetivo conocer la percepción profesional de los Centros Municipales de Mayores en torno a la atención a las necesidades de las personas mayores durante la etapa de confinamiento en el distrito de Ciudad Lineal en Madrid. Para ello, se ha desarrollado un estudio cualitativo y realizado entrevistas semiestructuradas y un grupo focal. Los resultados muestran que el cierre de los Centros ha generado situaciones de vulnerabilidad para las personas mayores, especialmente para aquellas en situación de soledad y/o con mayor grado de dependencia y menores competencias digitales. Los equipos profesionales han visto incrementada su actividad laboral y diversidad de funciones para dar respuesta a las necesidades emergentes. Las aplicaciones en línea han jugado un papel fundamental en el acceso a los servicios prestados en hogares, visibilizándose la brecha digital para aquellas personas con menos accesibilidad y a su uso. Los Centros de Mayores Municipales se configuran como recursos proactivos en prevención de situaciones de soledad y aislamiento, superando el actual carácter de espacios de convivencia.COVID-19 has triggered a worldwide health and social crisis. In Spain, the containment measures unleashed by the crisis have been particularly harsh and have generated situations of vulnerability. The Municipal Centers for the Elderly are configured as public, non-residential facilities designed to promote the coexistence of the elderly. The aim of this article is to know the professional perception of the Municipal Centers for the Elderly regarding the attention to the needs of the elderly during the confinement stage in the district of Ciudad Lineal in Madrid. For this purpose, a qualitative study was carried out and semi-structured interviews and a focus group were conducted. The results show that the closure of the centers has generated situations of vulnerability for the elderly, especially for those in a situation of loneliness and/or with a higher degree of dependence and lower digital skills. The professional teams have seen an increase in their work activity and diversity of functions in order to respond to emerging needs. Online applications have played a fundamental role in the access to services provided in homes, making the digital divide visible for those people with less accessibility to its use. The Municipal Senior Citizen Centers are configured as proactive resources to prevent situations of loneliness and isolation, overcoming the current character of coexistence spaces.Depto. de Trabajo Social y Servicios SocialesFac. de Trabajo SocialTRUEpu

No Higher Risk-Seeking Tendencies or Altered Self-Estimation in a Social Decision-Making Task in Patients with Parkinson's Disease

Background: Parkinson's disease (PD) has been associated with a tendency towards more risky decisions. However, the commonly used paradigms typically neglect the social context. Objective: Here, we investigated social decision-making and self-estimation in a competitive experimental task. Methods: A computerized experimental setting was used in which 86 PD patients (age = 66.5 [50-79], 62.8% male, H&Y= 2 [1.5-3]) and 44 healthy controls (HC; age = 67 [54-79], 54.4% male) in groups of four performed mathematical addition tasks in which they were asked to calculate as many sums as possible in five minutes. Participants had to choose their preferred compensation scheme (piece rate versus tournament) and retrospectively rank their performance in comparison to the suspected performance of the others. A comprehensive neuropsychological test battery was also conducted. Results: No significant difference was found in overall social decision-making and self-estimation between PD patients and HC. However, for those individuals who made inadequate decisions, PD patients engaged in significantly more risk-averse and HC in more risky decisions. Concerning those inadequate decisions, the PD patients made more extreme decisions (severity of social decision-making) in both directions (risk-averse, risk-seeking). Conclusion: Our data indicate that social decision-making behavior and self-estimation are largely intact in PD patients with mild to moderate disease stages and intact global cognition, executive functions, and social cognition. Future studies with more heterogeneous PD samples regarding their neuropsychological profile will have to examine at which state social decision-making may be affected and by which factors this behavior might be influenced

Dopamine replacement modulates oscillatory coupling between premotor and motor cortical areas in Parkinson's disease

Efficient neural communication between premotor and motor cortical areas is critical for manual motor control. Here, we used high-density electroencephalography to study cortical connectivity in patients with Parkinson's disease (PD) and age-matched healthy controls while they performed repetitive movements of the right index finger at maximal repetition rate. Multiple source beamformer analysis and dynamic causal modeling were used to assess oscillatory coupling between the lateral premotor cortex (lPM), supplementary motor area (SMA), and primary motor cortex (M1) in the contralateral hemisphere. Elderly healthy controls showed task-related modulation in connections from lPM to SMA and M1, mainly within the γ-band (>30 Hz). Nonmedicated PD patients also showed task-related γ-γ coupling from lPM to M1, but γ coupling from lPM to SMA was absent. Levodopa reinstated physiological γ-γ coupling from lPM to SMA and significantly strengthened coupling in the feedback connection from M1 to lPM expressed as β-β as well as θ-β coupling. Enhancement in cross-frequency θ-β coupling from M1 to lPM was correlated with levodopa-induced improvement in motor function. The results show that PD is associated with an altered neural communication between premotor and motor cortical areas, which can be modulated by dopamine replacement