A multifaceted evaluation of the reference model of information assurance & security

The evaluation of a conceptual model, which is an outcome of a qualitative research, is an arduous task due to the lack of a rigorous basis for evaluation. Overcoming this challenge, the paper at hand presents a detailed example of a multifaceted evaluation of a Reference Model of Information Assurance & Security (RMIAS), which summarises the knowledge acquired by the Information Assurance & Security community to date in one all-encompassing model. A combination of analytical and empirical evaluation methods is exploited to evaluate the RMIAS in a sustained way overcoming the limitations of separate methods. The RMIAS is analytically evaluated regarding the quality criteria of conceptual models and compared with existing models. Twenty-six semi-structured interviews with IAS experts are conducted to test the merit of the RMIAS. Three workshops and a case study are carried out to verify the practical value of the model. The paper discusses the evaluation methodology and evaluation results

Human 3D cellular model of hypoxic brain injury of prematurity.

Owing to recent medical and technological advances in neonatal care, infants born extremely premature have increased survival rates1,2. After birth, these infants are at high risk of hypoxic episodes because of lung immaturity, hypotension and lack of cerebral-flow regulation, and can develop a severe condition called encephalopathy of prematurity3. Over 80% of infants born before post-conception week 25 have moderate-to-severe long-term neurodevelopmental impairments4. The susceptible cell types in the cerebral cortex and the molecular mechanisms underlying associated gray-matter defects in premature infants remain unknown. Here we used human three-dimensional brain-region-specific organoids to study the effect of oxygen deprivation on corticogenesis. We identified specific defects in intermediate progenitors, a cortical cell type associated with the expansion of the human cerebral cortex, and showed that these are related to the unfolded protein response and changes. Moreover, we verified these findings in human primary cortical tissue and demonstrated that a small-molecule modulator of the unfolded protein response pathway can prevent the reduction in intermediate progenitors following hypoxia. We anticipate that this human cellular platform will be valuable for studying the environmental and genetic factors underlying injury in the developing human brain

Initial Responses to False Positives in AI-Supported Continuous Interactions: A Colonoscopy Case Study

The use of artificial intelligence (AI) in clinical support systems is increasing. In this article, we focus on AI support for continuous interaction scenarios. A thorough understanding of end-user behaviour during these continuous human-AI interactions, in which user input is sustained over time and during which AI suggestions can appear at any time, is still missing. We present a controlled lab study involving 21 endoscopists and an AI colonoscopy support system. Using a custom-developed application and an off-the-shelf videogame controller, we record participants’ navigation behaviour and clinical assessment across 14 endoscopic videos. Each video is manually annotated to mimic an AI recommendation, being either true positive or false positive in nature. We find that time between AI recommendation and clinical assessment is significantly longer for incorrect assessments. Further, the type of medical content displayed significantly affects decision time. Finally, we discover that the participant’s clinical role plays a large part in the perception of clinical AI support systems. Our study presents a realistic assessment of the effects of imperfect and continuous AI support in a clinical scenario

Use of the Auto-inflammatory Disease Activity Index to monitor disease activity in patients with colchicine-resistant Familial Mediterranean Fever, Mevalonate Kinase Deficiency, and TRAPS treated with canakinumab

To evaluate the feasibility of the autoinflammatory disease activity index (AIDAI) as a tool to assess disease activity in patients with hereditary recurrent fever syndromes (HRFs) treated with canakinumab

Balancing Selection on a Regulatory Region Exhibiting Ancient Variation That Predates Human–Neandertal Divergence

Ancient population structure shaping contemporary genetic variation has been recently appreciated and has important implications regarding our understanding of the structure of modern human genomes. We identified a ∼36-kb DNA segment in the human genome that displays an ancient substructure. The variation at this locus exists primarily as two highly divergent haplogroups. One of these haplogroups (the NE1 haplogroup) aligns with the Neandertal haplotype and contains a 4.6-kb deletion polymorphism in perfect linkage disequilibrium with 12 single nucleotide polymorphisms (SNPs) across diverse populations. The other haplogroup, which does not contain the 4.6-kb deletion, aligns with the chimpanzee haplotype and is likely ancestral. Africans have higher overall pairwise differences with the Neandertal haplotype than Eurasians do for this NE1 locus (p<10−15). Moreover, the nucleotide diversity at this locus is higher in Eurasians than in Africans. These results mimic signatures of recent Neandertal admixture contributing to this locus. However, an in-depth assessment of the variation in this region across multiple populations reveals that African NE1 haplotypes, albeit rare, harbor more sequence variation than NE1 haplotypes found in Europeans, indicating an ancient African origin of this haplogroup and refuting recent Neandertal admixture. Population genetic analyses of the SNPs within each of these haplogroups, along with genome-wide comparisons revealed significant FST (p = 0.00003) and positive Tajima's D (p = 0.00285) statistics, pointing to non-neutral evolution of this locus. The NE1 locus harbors no protein-coding genes, but contains transcribed sequences as well as sequences with putative regulatory function based on bioinformatic predictions and in vitro experiments. We postulate that the variation observed at this locus predates Human–Neandertal divergence and is evolving under balancing selection, especially among European populations

Prevalence, risk factors, and treatments for post-COVID breathlessness:a systematic review and meta-analysis

Persistent breathlessness >28 days after acute COVID-19 infection has been identified as a highly debilitating post-COVID symptom. However, the prevalence, risk factors, mechanisms and treatments for post-COVID breathlessness remain poorly understood. We systematically searched PubMed and Embase for relevant studies published from 1 January 2020 to 1 November 2021 (PROSPERO registration number: CRD42021285733) and included 119 eligible papers. Random-effects meta-analysis of 42 872 patients with COVID-19 reported in 102 papers found an overall prevalence of post-COVID breathlessness of 26% (95% CI 23-29) when measuring the presence/absence of the symptom, and 41% (95% CI 34-48) when using Medical Research Council (MRC)/modified MRC dyspnoea scale. The pooled prevalence decreased significantly from 1-6 months to 7-12 months post-infection. Post-COVID breathlessness was more common in those with severe/critical acute infection, those who were hospitalised and females, and was less likely to be reported by patients in Asia than those in Europe or North America. Multiple pathophysiological mechanisms have been proposed (including deconditioning, restrictive/obstructive airflow limitation, systemic inflammation, impaired mental health), but the body of evidence remains inconclusive. Seven cohort studies and one randomised controlled trial suggested rehabilitation exercises may reduce post-COVID breathlessness. There is an urgent need for mechanistic research and development of interventions for the prevention and treatment of post-COVID breathlessness

TCT-171 Predicting the Risk of Perforation Requiring Pericardiocentesis in Chronic Total Occlusion Percutaneous Coronary Intervention: The PROGRESS-CTO Pericardiocentesis Score

Background: Estimating the risk for complications facilitates risk-benefit assessment and procedural planning in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Methods: We analyzed the PROGRESS-CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention; NCT02061436) and created a risk score for pericardiocentesis. Patients with histories of coronary artery bypass graft surgery were excluded. Logistic regression prediction modeling was used to identify independently associated variables, and the model was internally validated with bootstrapping. Results: Of the 7,672 CTO PCI cases performed between 2012 and 2022 at 40 centers, 83 (1.1%) required pericardiocentesis. The final prediction model identified predictors of pericardiocentesis: age ≥ 65 years (OR: 2.10; 95% CI: 1.27-3.46), 1 point; female sex (OR: 2.25; 95% CI: 1.39-3.63), 1 point; moderate to severe calcification (OR: 3.28; 95% CI: 1.96-5.49), 1 point; antegrade dissection re-entry (OR: 2.83, 95% CI: 1.45-5.51), 1 point; and retrograde strategy (OR: 3.50; 95% CI: 2.08-5.87), 2 points; with a bootstrap corrected C statistic of 0.78 (95% CI: 0.72-0.83). The calculated risk percentages for pericardiocentesis on the basis of the PROGRESS-CTO mortality score ranged from 0.18% to 8.74% for pericardiocentesis, and 55% of patients had PROGRESS-CTO pericardiocentesis scores of 1 or 2, corresponding to a pericardiocentesis risk of 0.4% to 1.6%. Conclusions: The PROGRESS-CTO pericardiocentesis risk score can facilitate risk-benefit assessment and procedural planning in patients undergoing CTO PCI. Categories: CORONARY: Complex and Higher Risk Procedures for Indicated Patients (CHIP

TCT-113 Predicting the Risk of In-Hospital Major Adverse Cardiovascular Events in Chronic Total Occlusion Percutaneous Coronary Intervention: The PROGRESS-CTO MACE Score

Background: Estimating the risk of complications in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) facilitates risk-benefit assessment and procedural planning. Methods: We analyzed the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO; NCT02061436) and created a risk score for in-hospital major adverse cardiovascular events (MACE). Logistic regression prediction modeling was used to identify independently associated variables and the model was internally validated with bootstrapping. Results: Of the 10,480 CTO PCI cases performed between 2012-2022 at 40 US and non-US centers, in-hospital MACE occurred in 215 (2.05%). The final prediction model identified 5 independent predictors of MACE: age ≥65 years, odds ratio (OR) 1.57, 95% confidence interval (CI) 1.10-2.26, 1 point; female sex, OR 2.46, 95% CI 1.72-3.53, 2 points; moderate to severe calcification, OR 1.71, 95% CI 1.20-2.44, 1 point; Blunt stump, OR 1.63, 95% CI 1.14-2.33, 1 point; and Antegrade dissection re-entry, OR 2.21, 95% CI 1.32-3.72, 1 point; and retrograde strategy, OR 2.86, 95% CI 1.94-4.22, 2 points; with a bootstrap corrected c-statistic of 0.72, 95% CI 0.68-0.76. The calculated risk percentages for MACE based on the PROGRESS-CTO MACE score ranged from 0.4% to 9.4% for MACE; 42% of patients had PROGRESS-CTO MACE score of 2-3, corresponding to a MACE risk of 1.1%-2.0%. Conclusion: The PROGRESS-CTO in-hospital MACE risk score can facilitate risk-benefit assessment and procedural planning in patients undergoing CTO PCI. Categories: CORONARY: Complex and Higher Risk Procedures for Indicated Patients (CHIP