Interoperability and governance in the European Health Data Space regulation

The proposal for a regulation on the European Health Data Space (EHDS) is a much-awaited project. It aspires to create a harmonised framework – a common European data space – for the administration of health data (primary use) across Member States and the promotion of healthcare research and innovation (by establishing rules for the secondary use of health data). As such, although the EHDS proposal is a legal document, in its essence, it includes provisions that introduce not only legal, but also institutional, and technical-infrastructural changes. Overall, together with the Regulation 2017/745 on medical devices, the Data Governance Act (DGA), the Data Act, the AI Act, and the General Data Protection Regulation (GDPR), the EHDS proposal will complete the regulatory canvas for the use of health data in the European Union. Although we are supportive of the EHDS initiative, there are aspects of the proposal that require further debate, reconsideration, and amendments. Following previous work on potential power asymmetries encapsulated in the Proposal, in this commentary, we focus on the provisions of/for interoperability of the Electronic Health Record (EHR) systems (Ar. 14–32) as well as the provisions on the structure of Health Data Access bodies and their cross-border organisation (section 3). We recommend a series of amendments to orientate the EHDS project better to its constitutive goals: the promotion of public health research and respect for the rights of the individuals

Validating animal models for preclinical research: a scientific and ethical discussion

The use of animals to model humans in biomedical research relies on the notion that basic processes are sufficiently similar across species to allow extrapolation. Animal model validity is discussed in terms of the similarity between the model and human condition it is intended to model, but no formal validation of models is applied. There is a stark contrast here with non-animal alternatives in toxicology and safety studies, for which an extensive validation is required. In the present paper we discuss the potential and limitations of validating preclinical animal models for proof-of-concept studies using an approach similar to that applied to alternative non-animal methods in toxicology and safety testing. A major challenge in devising a validation system for animal models is the lack of a clear gold standard to compare results with. While a complete adoption of the validation approach for alternative methods is probably inappropriate for research animal models, key feature such as making data available for external validation and defining a strategy to run experiments in a way that permits meaningful retrospective analysis remain relevant

Paediatric endoscopy in Nigeria humble beginning

Introduction: Paediatric gastroenterology has become an established subspecialty in the last five decades in developed and some developing countries. Endoscopy is the cornerstone of this sub-specialty. In Nigeria, it is still at its infancy stage, though with increasing local interest. This is a report of the first Paediatric Endoscopy Workshop in Nigeria organized as a pre -conference by the Paediatric Association of Nigeria (PAN) and the Nigerian Society of Paediatric Gastroenterology, Hepatology and Nutrition (NISPGHAN).Aim: The aim of the conference was to promote and create awareness on paediatric gastroenterology as a subspecialty and introduce participants to the practice of paediatric endoscopy.Method: This was a two day preconference workshop. Paediatricians, paediatric resisdents and nurses were in attendance. One International and three National resource persons were on ground to impart the needed knowledge and skills. Training involved didactic lectures, hands-on sessions using manikins and three live sessions involving the upper gastrointestinal tract.Results: There were 40 attendees on day 1: 22 (55%) paediatric residents, 12 (30%) consultant paediatricians and six (15%) nurses. Day 2: 22 (52%) paediatric residents, 12 (29%) consultant paediatricians and eight (19%) nurses. Three children (two females and one male) had upper GI endoscopy (with biopsy done in two cases) during the pre-conference workshop as live sessions. They were aged eight, nine and 16 years. Indications for endoscopy were recurrent haematemesis in an eight year old female patient and recurrent upper abdominal pain in the other two patients (a male and a female). Gastritis was found in the two patients and this was confirmed histologically in one of the patients.Conclusion: The training stirred up participant’s interest in this subspecialty of paediatrics. It brought to fore the need for paediatric endoscopy to be developed in Nigeria. The procedure should be performed at tertiary centres at this stage of our development and the cost of it covered by the National Health Insurance Scheme. Four training centres to aid interested paediatricians and paediatric trained nurses acquire the needed skills are recommended.Keywords: Paediatric endoscopy, Calabar, Nigeria

Fatigue crack propagation in HSLA steel specimens subjected to unordered and ordered load spectra

Prediction of fatigue crack propagation in metallic structures subjected to dynamic random load spectra, containing variable overloads and underloads, is challenging because of possible retardation and acceleration effects. In this paper, fatigue crack growth behaviour under random spectrum load is investigated on ESE(T) specimens made of DNV 460 steel, which is an HSLA steel widely used in the offshore industry. A reference spectrum composed of a sequence of random loads is transferred into various reduced and ordered spectra. Reduced spectra have been defined based on a peak-valley segmentation algorithm and on the deletion of non-damaging events. Ordered spectra consist of block loading sequences determined by rainflow counting methods. Specific control software has been developed that allows to execute the K (stress intensity factor) controlled experimental program and perform on-line crack growth measurement using a material compliance method. The different spectra are compared in terms of total crack extension and retardation in crack growth rate. Algorithms for crack growth simulation have been implemented in Abaqus using both existing and adapted plastic zone models. Numerical results are critically compared to the experimental data

A Novel Requirement for Janus Kinases as Mediators of Drug Resistance Induced by Fibroblast Growth Factor-2 in Human Cancer Cells

The development of resistance to chemotherapy is a major cause of cancer-related death. Elucidating the mechanisms of drug resistance should thus lead to novel therapeutic strategies. Fibroblast growth factor (FGF)-2 signaling induces the assembly of a multi-protein complex that provides tumor cells with the molecular machinery necessary for drug resistance. This complex, which involves protein kinase C (PKC) ε, v-raf murine sarcoma viral oncogene homolog B1 (B-RAF) and p70 S6 kinase β (S6K2), enhances the selective translation of anti-apoptotic proteins such as B-cell leukaemia/lymphoma-2 (BCL-2) and inhibitors of apoptosis protein (IAP) family members and these are able to protect multiple cancer cell types from chemotherapy-induced cell death. The Janus kinases (JAKs) are most noted for their critical roles in mediating cytokine signaling and immune responses. Here, we show that JAKs have novel functions that support their consideration as new targets in therapies aimed at reducing drug resistance. As an example, we show that the Janus kinase TYK2 is phosphorylated downstream of FGF-2 signaling and required for the full phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Moreover, TYK2 is necessary for the induction of key anti-apoptotic proteins, such as BCL-2 and myeloid cell leukemia sequence (MCL) 1, and for the promotion of cell survival upon FGF-2. Silencing JAK1, JAK2 or TYK2 using RNA interference (RNAi) inhibits FGF2-mediated proliferation and results in the sensitization of tumor cells to chemotherapy-induced killing. These effects are independent of activation of signal transducer and activator of transcription (STAT) 1, STAT3 and STAT5A/B, the normal targets of JAK signaling. Instead, TYK2 associates with the other kinases previously implicated in FGF-2-mediated drug resistance. In light of these findings we hypothesize that TYK2 and other JAKs are important modulators of FGF-2-driven cell survival and that inhibitors of these kinases will likely improve the effectiveness of other cancer therapies

The Effect of Photoinduced Surface Oxygen Vacancies on the Charge Carrier Dynamics in TiO₂ Films

Metal-oxide semiconductors (MOS) are widely utilized for catalytic and photocatalytic applications in which the dynamics of charged carriers (e.g., electrons, holes) play important roles. Under operation conditions, photoinduced surface oxygen vacancies (PI-SOV) can greatly impact the dynamics of charge carriers. However, current knowledge regarding the effect of PI-SOV on the dynamics of hole migration in MOS films, such as titanium dioxide, is solely based upon volume-averaged measurements and/or vacuum conditions. This limits the basic understanding of hole-vacancy interactions, as they are not capable of revealing time-resolved variations during operation. Here, we measured the effect of PI-SOV on the dynamics of hole migration using time-resolved atomic force microscopy. Our findings demonstrate that the time constant associated with hole migration is strongly affected by PI-SOV, in a reversible manner. These results will nucleate an insightful understanding of the physics of hole dynamics and thus enable emerging technologies, facilitated by engineering hole-vacancy interactions

Use of domesticated pigs by Mesolithic hunter-gatherers in northwestern Europe

Acknowledgements We thank the Archaeological State Museum Schleswig-Holstein, the Archaeological State Offices of Brandenburg, Lower Saxony and Saxony and the following individuals who provided sample material: Betty Arndt, Jo¨rg Ewersen, Frederick Feulner, Susanne Hanik, Ru¨diger Krause, Jochen Reinhard, Uwe Reuter, Karl-Heinz Ro¨hrig, Maguerita Scha¨fer, Jo¨rg Schibler, Reinhold Schoon, Regina Smolnik, Thomas Terberger and Ingrid Ulbricht. We are grateful to Ulrich Schmo¨lcke, Michael Forster, Peter Forster and Aikaterini Glykou for their support and comments on the manuscript. We also thank many institutions and individuals that provided sample material and access to collections, especially the curators of the Museum fu¨r Naturkunde, Berlin; Muse´um National d0 Histoire Naturelle, Paris; Smithsonian Institution, National Museum of Natural History, Washington D.C.; Zoologische Staatssammlung, Mu¨nchen; Museum fu¨r Haustierkunde, Halle; the American Museum of Natural History, New-York. This work was funded by the Graduate School ‘Human Development in Landscapes’ at Kiel University (CAU) and supported by NERC project Grant NE/F003382/1. Radiocarbon dating was carried out at the Leibniz Laboratory, CAU. This work is licensed under a Creative Commons AttributionNonCommercial-NoDerivs 3.0 Unported License.Peer reviewedPublisher PD

Extracting science from surveys of our Galaxy

Our knowledge of the Galaxy is being revolutionised by a series of photometric, spectroscopic and astrometric surveys. Already an enormous body of data is available from completed surveys, and data of ever increasing quality and richness will accrue at least until the end of this decade. To extract science from these surveys we need a class of models that can give probability density functions in the space of the observables of a survey -- we should not attempt to "invert" the data from the space of observables into the physical space of the Galaxy. Currently just one class of model has the required capability, so-called "torus models". A pilot application of torus models to understanding the structure of the Galaxy's thin and thick discs has already produced two significant results: a major revision of our best estimate of the Sun's velocity with respect to the Local Standard of Rest, and a successful prediction of the way in which the vertical velocity dispersion in the disc varies with distance from the Galactic plane.Comment: 13 pages. Invited review to appear in Pramana - journal of physics (Indian Academy of Sciences

Peritoneal defense in continuous ambulatory versus continuous cyclic peritoneal dialysis

Peritoneal defense in continuous ambulatory peritoneal dialysis versus continuous cyclic peritoneal dialysis. Several centers have reported a lower rate of peritonitis among adult patients on continuous cyclic peritoneal dialysis (CCPD) as compared to those undergoing continuous ambulatory peritoneal dialysis (CAPD). Preliminary results of our ongoing prospective randomized study comparing CAPD-Y with CCPD also suggest a lower peritonitis incidence among CCPD-treated patients. To investigate whether the two dialysis regimens could result in differences in local host defense, we studied peritoneal macrophage (PMO) function and effluent opsonic activity in eight patients established on CAPD-Y matched with eight chronic CCPD patients. Since short and long dwell times are inherent to both dialysis modalities, and we previously found that dwell time has an impact on PMO function and effluent opsonic activity, patients were studied after both a short (4hr) and a long (15hr) dwell time. In both patient groups PMO phagocytic capacity increased significantly with dwell time (39 ± 3.3% at 4hr vs. 58 ± 4.2% at 15hr in CAPD patients, and 40 ± 3.9 vs. 72 ± 3.3% in CCPD patients; P < 0.01), as did PMO peak chemiluminescence response (31 ± 4.9 vs. 77 ± 7.2 counts · min-1/104 cells in CAPD, and 22 ± 3.9 vs. 109 ± 21.2 counts · min-1/104 cells in CCPD; P < 0.01) and effluent opsonic activity (41 ± 7.6 vs. 73 ± 5.8% in CAPD and 39 ± 6.2 vs. 70 ± 5.9% in CCPD; P < 0.01). However, no significant difference was found in either variable between CAPD and CCPD patients when dwell times were equal. In conclusion, no differences were observed in PMO function or effluent opsonic activity between matched CAPD-Y and CCPD patients when dwell times were equal. In both patient groups prolongation of dwell time enhanced PMO function as well as effluent opsonic activity, thereby providing a better host defense. The improvement in peritoneal defenses may, in part, be responsible for the lower peritonitis incidence observed among CCPD-treated patients

A comparison of the illness beliefs of people with angina and their peers: a questionnaire study

BACKGROUND: What people believe about their illness may affect how they cope with it. It has been suggested that such beliefs stem from those commonly held within society . This study compared the beliefs held by people with angina, regarding causation and coping in angina, with the beliefs of their friends who do not suffer from angina. METHODS: Postal survey using the York Angina Beliefs Questionnaire (version 1), which elicits stress attributions and misconceived beliefs about causation and coping. This was administered to 164 people with angina and their non-cohabiting friends matched for age and sex. 132 people with angina and 94 friends completed the questionnaire. RESULTS: Peers are more likely than people with angina to believe that angina is caused by a worn out heart (p <0.01), angina is a small heart attack (p = 0.02), and that it causes permanent damage to the heart (p <0.001). Peers were also more likely to believe that people with angina should take life easy (p <0.01) and avoid exercise (p = 0.04) and excitement (p <0.01). CONCLUSIONS: The beliefs of the peer group about causation and coping in angina run counter to professional advice. Over time this may contribute to a reduction in patient concordance with risk factor reduction, and may help to create cardiac invalids