Keskuslaboratorio

Inborn errors of immunity (IEIs) are a heterogeneous group of disorders, genetically diverse but phenotypically overlapping. Over 500 IEI-related genes have been identified. Next generation sequencing (NGS) enables the simultaneous evaluation of a large number of genes in multiple patients in parallel. Since 2017, in our setting, custom IEI panels have been useful mainly for patients displaying clinical phenotypes of immune dysregulation and autoinflammatory disorders. Our aim is to evaluate the performance of targeted NGS panels based on International Union of Immunological Societies (IUIS) gene categories by examining how many patients achieved a conclusive diagnosis. A retrospective analysis was performed on 361 index cases submitted to four chronologically successive targeted NGS custom panels. The first panel included 124 IUIS genes, most of them related to autoimmune and immune dysregulation disease categories. The second panel contained 143 IUIS genes, including defects of innate immunity. The third and fourth, large panels covering 314 and 325 IUIS genes, respectively, included/comprised the majority of IUIS disease categories, with focus on autoinflammatory, immune dysregulation, and intrinsic immunity disease categories. From a total of 361 samples studied, 264 were referred due to clinical suspicion of immune dysregulation, autoinflammatory disease, or defects in innate immunity. Twenty-three percent of them (61/264) achieved a confirmed or highly probable genetic etiology. According to the main IEI IUIS disease categories included in targeted panels, immune dysregulation represented 26% (32/123) of these diagnoses, autoinflammatory disorders 21% (18/85), and defects in innate immunity 19% (11/56). In the remaining patients studied, 42% (41/97) of them achieved a conclusive diagnosis in others IEI IUIS disease categories. The NGS approach demonstrated the expected IEI diagnostic rate. The strategy of designing panels oriented toward IEI disease categories that present the greatest variability in clinical presentations with overlapping phenotypes proved to be effective regarding achievement of conclusive diagnoses in our cohort.

In dense urban environments, traditional GNSS-based navigation for Unmanned Aerial Vehicles (UAVs) suffers from multipath interference and signal obstructions, compromising positioning accuracy and increasing risks of collisions and airspace violations. This paper proposes a novel machine learning-based system architecture for autonomous UAV parcel delivery, leveraging standardized 5G Network Exposure Function (NEF) and CAMARA Device Location API to achieve sub-meter location precision. Our approach integrates dynamic geofencing and predictive rerouting at the network edge, powered by a Random Forest-based collision prediction model that proactively adjusts UAV trajectories to avoid restricted zones in real time. Through simulations of six UAVs navigating dynamically updated no-fly zones, we demonstrate that our system significantly reduces time spent in restricted areas to near zero, compared to GNSS-only and rule-based methods, while limiting path-length inflation to approximately 30% for five of six flights. These results underscore the potential of combining 5G-enabled location services with edge intelligence to enhance safety and compliance in urban UAV operations.

Semisolid extrusion 3D printing is a manufacturing method that has shown promising results in precise production of patient specific dosage forms. Drug nanocrystals, where the particle size of the drug is in the nanometer range, is an attractive formulation strategy for improving the bioavailability of poorly water-soluble drugs. However, because nanocrystals remain suspended in the semisolid extrusion 3D printing formulation, dispensing of the material might be adversely affected by these particles. Currently, the effect of suspended drug nanocrystals on the semisolid extrusion dispensing precision is not well understood. In this study, dispensing precision was evaluated by analysing the weight variation during semisolid extrusion 3D printing. The formulation base, where itraconazole nanocrystals and nanofibrillated cellulose were added, consisted of polyethylene glycol, hydroxypropyl methylcellulose, and water. It was discovered that nanocrystals improved the dispensing precision compared to the nanocrystal free formulation base. Additionally, nanofibrillated cellulose could be combined with nanocrystals to improve the dispensing precision even further. The dispensing precision of the formulations was found to be linked with the viscosity at the high shear rate region. In conclusion, the data suggests that drug nanocrystal containing oral dosage forms can be precisely manufactured using semisolid extrusion 3D printing, without major indication of drug nanocrystals adversely affecting the dispensing process.

ObjectivesAnimal and observational human studies report that delivery of excessive tidal volume (VT) at birth is associated with lung and brain injury.1 2 A respiratory function monitor (RFM) is a potential tool to enhance the appropriateness of positive pressure ventilation (PPV) inflations in the delivery room.3 4 The aim of this study was to assess the impact of using an RFM on neonatal resuscitation performance.MethodsA respiratory function monitor device (Monivent Neo100) was used. The device consists of a face mask with an in-built differential pressure pneumotachograph which provides feedback via an integrated bluetooth sensor module. Continuous real-time feedback of volume delivered, leak (%) and inflation rate (breaths per minute) are displayed on a wireless LED monitor.Following a period of education and familiarisation, participants were asked to provide single person mask PPV to a mannikin model. As per the Resuscitation Council (UK) Newborn Life Support algorithm for newborn resuscitation, participants delivered five inflations (30 cm H2O) over 2–3 seconds followed by 30seconds of ventilation six times to a mannikin model with an estimated weight of 2.5kg. Each alternate round the resuscitators were blinded to the Monivent Neo100 interface.ResultsA total of 2712 inflations from 23 participants were analysed. The level of neonatal resuscitation experience of participants varied from less than one year (n=5), between 1 and 5 years (n=10) and more than 5 years (n=8) of neonatal resuscitation experience. On analysis, there was lower leak (median [IQR]: 14 [5–41]% versus 17 [5–57]; p<0.015) and reduced delivery of excessive tidal volume (median [IQR]: 13.2 [12–16]ml/kg vs 14 [12–20]ml/kg; p <0.001) when participants were unblinded to the results of the Monivent device [table 1]. Participants with less clinical experience (6month-1 year vs 1–5 years vs >5years) achieved lower leak (%) with Monivent usage (median [IQR]: 8 [3–26] versus 14 [5–41] versus 30 [7–66]; p <0.001). 6633 Table 1 Inflation Breaths Ventilation Breaths Blind (n = 83) Unblind (n = 106) Blind (n = 375) Unblind (n = 434) Inflation duration(seconds) 2.3 [1.8–3.0] 2.4 [1.8–2.7] 0.344 1.5 [1.3-1.7] 1.5 [1.3–1.6] 0.057 VTi (ml/kg) 14.9 [12.3-29.7] 12.8 [11.6-16.5] <0.001 13.8[12.2-20.2] 12.7 [11.5-14.9] <0.001 Leakage (%) 26 [7–75] 14 [8–30] 0.045 16 [4–62] 10 [4–32] 0.015 ConclusionIn conclusion, the use of an RFM was associated with superior performance in simulated mannikin resuscitation.Referencesde Medeiros SM, et al. Respiratory function monitoring to improve the outcomes following neonatal resuscitation: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2022;107(6):589–96.Mian Q, et al. Impact of delivered tidal volume on the occurrence of intraventricular haemorrhage in preterm infants during positive pressure ventilation in the delivery room. Arch Dis Child Fetal Neonatal Ed 2019;104(1):F57-f62.van Vonderen JJ, et al. Cardiorespiratory Monitoring during Neonatal Resuscitation for Direct Feedback and Audit. Front Pediatr 2016;4:38.Milner A, et al. Evaluation of respiratory function monitoring at the resuscitation of prematurely born infants. Eur J Pediatr 2015;174(2):205–8.

O artigo tem como foco discutir o direito das/dos estudantes com altas habilidades/superdotação no contexto brasileiro; para tanto apresenta e analisa os principais aportes legais que tratam da inclusão do público-alvo da educação especial. De cunho descritivo analítico, o estudo recorre aos principais encaminhamentos políticos e práticos elucidados nos documentos e nas evidências educacionais, sociais, culturais e identitárias, que apontam para a omissão - quando não violação - dos direitos dessas/desses estudantes em toda sua trajetória, configurando o quanto é real a inexistência do princípio de transversalidade para este público da educação especial, inclusive, naturalizando de sua condição de exclusão.

Civic organisations and progressive campaigns regard digital advertising as an essential method to register to vote lowparticipation groups, such as ethnic minorities, young voters and frequent home movers like private-sector tenants. Digital strategies appear to be promising in countries like the UK, where the registration process can be completed online, usually in less than 5 minutes, using a web link in the advert. But are typical digital campaigns effective in registering voters? To find out, we provide evidence from three randomised controlled trials: two conducted with advocacy organisations and the third run by the research team, carried out in two types of UK elections (general and local) and assigned either at the aggregate (Study 1 and Study 2) or individual (Study 3) level. Despite wide reach and relatively high rates of engagement, we find that the digital ad campaigns trialed across three studies did not affect under-registered groups' voter registrations. These null findings raise questions about commonly-used digital advertising strategies to register marginalised groups. They are consistent with other studies that report either null or minimal effects of digital ads on other types of political behaviour.

One of the key missions of the Polifonia project is to build and interlink knowledge graphs of European musical cultural heritage. These interconnected music knowledge graphs act as a data backbone for the project. This deliverable is centred around one of the ten Polifonia pilots: INTERLINK. The INTERLINK pilot is not bound to a specific institutional dataset, collection or use case; but rather summarises the common needs of all pilots of representing their data as music knowledge graphs, and finding meaningful connections among them. Existing work in the relevant areas of knowledge engineering, knowledge graph construction, and knowledge graph interlinking is promising but presents a number of pitfalls in its direct application to Polifonia from the point of view of achieving this knowledge graph building and interlinking: (a) existing knowledge engineering methodologies do not account for “in-between” knowledge graph construction processes that are not fully distributed nor local; (b) in an integrated vision of European musical cultural heritage through knowledge graphs, both musical content and its ’context’ or metadata need to co-exist; and (c) no current techniques address the issue of finding missing links between different music knowledge graphs at scale, accounting for this co-existence of musical content and context in the same knowledge graph. This deliverable describes our efforts, particularly gathered in Polifonia’s WP2 and Task T2.3, in addressing these challenges, delivering: (a) a scalable methodology for knowledge graph construction that is well suited for the project and sits in-between the two classic extremes of ontology engineering; (b) a music knowledge graph construction framework that leverages modules of the Polifonia Ontology Network and the SPARQL Anything tool; and (c) a music knowledge graph interlinking framework, based on both heuristics and neural network-based link prediction through music knowledge graph embeddings. The latter two are evaluated in two different use-cases, the ChoCo-KG chord annotation knowledge graph, and the MIDI2vec music knowledge graph interlinking method, with encouraging results.

Detailed reporting to safeguard study quality contributes to better translation and reproducibility of preclinical animal studies. In this nationwide study we investigated the reporting prevalence of methodologies and the information’s level of detail. Publications from 2009 and 2018 with at least one affiliation to a Danish university were compared to study possible reporting progress.<br/><br/>A predefined protocol was devised, and a systematic search retrieved all relevant studies. Random sampling of 250 studies from 2009 and 2018 led to evaluation of 500 publications. To identify presence of measures known to impact study results, we applied a two-level scoring “yes/no”. To analyze the reported information’s level of detail, a three-level scoring was conducted.<br/><br/>Reporting prevalence remained low, only minor improvements were noted. Reporting of randomization increased from 24.0% in 2009 to 40.8% in 2018, blinded experiment conduct from 2.4% to 4.4%, blinded outcome assessment from 23.6% to 38.0%, and sample size statements from 3.2% to 14.0%. Details were lacking, e.g., reporting of the method of random allocation to groups being 1.2% in 2009 and 6.0% in 2018, reporting of sample size calculation was respectively 2.4% and 7.6%. Interestingly, conflict-of-interest statements increased from 37.6% to 90.4%.<br/><br/>Reporting of measures to safeguard study quality should be prioritized by all stakeholders. We suggest rigorous teaching in designing, planning, and reporting animal studies and journals should enforce ARRIVE guidelines. Teaching and conduct of systematic reviews could be a good starting point, as the evidence shows this increases motivation and behavior towards quality improvements in science.