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Background: Advancements in genomic technologies are rapidly evolving, with the potential to transform laboratory diagnostics by enabling high-throughput analysis of complex biological data, such as microbiome data. Large Language Models (LLMs) have shown significant promise in extracting actionable insights from vast datasets, but their application in generating microbiome findings reports with clinical interpretations and lifestyle recommendations has not been explored yet. Methods: This article introduces an innovative framework that utilizes LLMs to automate the generation of findings reports in the context of microbiome diagnostics. The proposed model integrates LLMs within an event-driven, workflow-based architecture, designed to enhance scalability and adaptability in clinical laboratory environments. Special focus is given to aligning the model with clinical standards and regulatory guidelines such as the In-Vitro Diagnostic Regulation (IVDR) and the guidelines published by the High-Level Expert Group on Artificial Intelligence (HLEG AI). The implementation of this model was demonstrated through a prototype called “MicroFlow”. Results: The implementation of MicroFlow indicates the viability of automating findings report generation using LLMs. Initial evaluation by laboratory expert users indicated that the integration of LLMs is promising, with the generated reports being plausible and useful, although further testing on real-world data is necessary to assess the model’s accuracy and reliability. Conclusions: This work presents a potential approach for using LLMs to support the generation of findings reports in microbiome diagnostics. While the initial results seem promising, further evaluation and refinement are needed to ensure the model’s effectiveness and adherence to clinical standards. Future efforts will focus on improvements based on feedback from laboratory experts and comprehensive testing on real patient data.

Genomics-based diagnostic data (GBDD) are becoming increasingly important for laboratory diagnostics. Due to the large quantity of data and their heterogeneity, GBDD poses a big data challenge. Current analysis tools for GBDD are primarily designed for research and do not meet the requirements of laboratory diagnostics for automation, reliability, transparency, reproducibility, robustness, and accessibility. This makes it difficult for laboratories to use these tools in tests that need to be validated according to regulatory frameworks and to execute tests in a time- and cost-efficient manner. In order to better address these requirements, we propose an event-driven workflow-based architecture as the basis for a processing platform that is highly scalable using container technologies and microservices. A prototype implementation of this approach, called GenomicInsights, has been developed and evaluated to demonstrate its feasibility and suitability for laboratory diagnostics.

Mitochondrial DNA (mtDNA) damage is closely associated with typical diseases of aging, such as Alzheimer’s or Parkinson’s disease, and other health conditions, such as infertility. This damage manifests in reduced mitochondrial copy number and deletion mutations in mtDNA. Consequently, the analysis of mitochondrial damage by determining the parameters copy number and deletion ratio using quantitative real-time PCR (qPCR) is of interest for clinical diagnostics. To bring the findings from research into laboratory practice, a suitable and reliable process is needed, which must be thoroughly validated. This process includes the software used for the analysis, which must meet extensive regulatory and process requirements. Existing software does not adequately implement the requirements of laboratories and, in particular, does not provide direct support for the calculation of the aforementioned mtDNA parameters. The paper discusses the development of a new software-based analysis workflow that is designed specifically for laboratories to help with the calculation of mtDNA parameters. The software was developed using the User-Centered Design method and is based on the recently introduced prototype, “PlateFlow”. Initial user tests provide positive feedback. In the future, this workflow could form the basis for validations of mitochondrial tests in medical laboratories.

Manual labeling and categorization are extremely time-consuming and, thus, costly. AI and ML-supported information systems can bridge this gap and support labor-intensive digital activities. Since it requires categorization, coding-based analysis, such as qualitative content analysis, reaches its limits with large amounts of data and could benefit from AI and ML-based support. Empirical social research, its application domain, benefits from Big Data’s ability to create more extensive human behavior and development models. A range of applications are available for statistical analysis to serve this purpose. This paper aims to implement an information system that supports researchers in empirical social research in performing AI-supported qualitative content analysis. AI2VIS4BigData is a reference model that standardizes use cases and artifacts for Big Data information systems that integrate AI and ML for user empowerment. Thus, this work’s concepts and implementations try to achieve an AI2VIS4BigData-compliant information system that supports social researchers in categorizing text data and creating insightful dashboards. Thereby, the text categorization is based on an existing ML component. Furthermore, it presents two evaluations that were conducted for these concepts and implementations: a qualitative cognitive walkthrough assessing the system’s usability and a quantitative user study with 18 participants revealed that though the users perceive AI support as more efficient, they need more time to reflect on the recommendations. The research revealed that AI support increased the correctness of the users’ categorizations but also slowed down their decision-making. The assumption that this is due to the UI design and additional information for processing requires follow-up research.

Indirect questioning techniques are widely discussed and used as methods to avoid or reduce the effects of social desirability in interview situations on sensitive topics. Nevertheless, current evaluation studies suggest that indirect questioning techniques have a bigger compliance problem than evaluation studies based on the "more is-better" principle would suggest. In our study, we investigate the extent to which question compliance problems can be identified for a variant of the Randomized Response Technique, for the Crosswise Model and Triangular Model. By means of an aggregate and an individual level validation, we examine the response patterns of the participants. Contrary to the actual empirical application context of sensitive topics, we use a non-sensitive question that cannot be distorted by social desirability bias. The resulting "same-is-best" rationale differs from most evaluation studies to date, which work according to the "more" or "less-is-better" principle. Our analyses are based on the data of a convenience sample of 1277 students in the form of an online survey experiment. The results suggest that the indirect questioning techniques show substantial weaknesses in terms of compliance and encourage further individual level evaluations.

Abstract Aims Heart failure (HF) is frequent in patients with acute ischaemic stroke (AIS) and associated with higher morbidity and mortality. Assessment of cardiac function in AIS patients using cardiovascular MRI (CMR) may help to detect HF. We report the rate of systolic and diastolic dysfunction in a cohort of patients with AIS using CMR and compare cine real‐time (CRT) sequences with the reference of segmented cine steady‐state free precession sequences. Methods and results Patients with AIS without known atrial fibrillation were prospectively enrolled in the HEart and BRain Interfaces in Acute Ischemic Stroke (HEBRAS) study (NCT 02142413) and underwent CMR at 3 Tesla within 7 days after AIS. Validity of CRT sequences was determined in 50 patients. A total of 229 patients were included in the analysis (mean age 66 years; 35% women; HF 2%). Evaluation of cardiac function was successful in 172 (75%) patients. Median time from stroke onset to CMR was 82 h (interquartile range 56–111) and 54 h (interquartile range 31–78) from cerebral MRI to CMR. Systolic dysfunction was observed in 43 (25%) and diastolic dysfunction in 102 (59%) patients. Diagnostic yield was similar using CRT or segmented cine imaging (no significant difference in left ventricular ejection fraction, myocardial mass, time to peak filling rate, and peak filling rate ratio E/A). Intraobserver and interobserver agreement was high (κ = 0.78–1.0 for all modalities). Conclusions Cardiovascular MRI at 3 Tesla is an appropriate method for the evaluation of cardiac function in a selected cohort of patients with AIS. Systolic and diastolic dysfunction is frequent in these patients. CRT imaging allows reliable assessment of systolic and diastolic function.

Abstract Background For multicenter clinical studies, PET/CT and SPECT/CT scanners need to be validated to ensure comparability between various scanner types and brands. This validation is usually performed using hollow phantoms filled with radioactive liquids. In recent years, 3D printing technology has gained increasing popularity for manufacturing of phantoms, as it is cost-efficient and allows preparation of phantoms of almost any shape. So far, however, direct 3D printing with radioactive building materials has not yet been reported. The aim of this work was to develop a procedure for preparation of 99mTc-containing building materials and demonstrate successful application of this material for 3D printing of several test objects. Method The desired activity of a [99mTc]pertechnetate solution eluted from a 99Mo/99mTc-generator was added to the liquid 3D building material, followed by a minute amount of trioctylphosphine. The resulting two-phase mixture was thoroughly mixed. Following separation of the phases and chemical removal of traces of water, the radioactive building material was diluted with the required volume of non-radioactive building material and directly used for 3D printing. Results Using our optimized extraction protocol with trioctylphosphine as complex-forming phase transfer agent, technetium-99m was efficiently transferred from the aqueous 99Mo/99mTc-generator eluate into the organic liquid resin monomer. The observed radioactivity concentration ratio between the organic phase and the water phase was > 2000:1. The radioactivity was homogeneously distributed in the liquid resin monomer. We did not note differences in the 3D printing behavior of the radiolabeled and the unlabeled organic liquid resin monomers. Radio-TLC and SPECT studies showed homogenous 2D and 3D distribution of radioactivity throughout the printed phantoms. The radioactivity was stably bound in the resin, apart from a small amount of surface-extractable radioactivity under harsh conditions (ethanol at 50 °C). Conclusions 3D printing of radioactive phantoms using 99mTc-containing building materials is feasible. Compared to the classical fillable phantoms, 3D printing with radioactive building materials allows manufacturing of phantoms without cold walls and in almost any shape. Related procedures with longer-lived radionuclides will enable production of phantoms for scanner validation and quality control.

Objectives: In patients with acute ischemic stroke, reduced heart rate variability (HRV) may indicate poor outcome. We tested whether HRV in the acute phase of stroke is associated with higher rates of mortality, recurrent stroke, myocardial infarction (MI) or functional outcome.Materials and Methods: Patients with acute mild to moderate ischemic stroke without known atrial fibrillation were prospectively enrolled to the investigator-initiated Heart and Brain interfaces in Acute Ischemic Stroke (HEBRAS) study (NCT 02142413). HRV parameters were assessed during the in-hospital stay using a 10-min section of each patient's ECG recording at day- and nighttime, calculating time and frequency domain HRV parameters. Frequency of a combined endpoint of recurrent stroke, MI or death of any cause and the respective individual events were assessed 12 months after the index stroke. Patients' functional outcome was measured by the modified Rankin Scale (mRS) at 12 months.Results: We included 308 patients (37% female, median NIHSS = 2 on admission, median age 69 years). Complete follow-up was achieved in 286/308 (93%) patients. At 12 months, 32 (9.5%), 5 (1.7%) and 13 (3.7%) patients had suffered a recurrent stroke, MI or death, respectively. After adjustment for age, sex, stroke severity and vascular risk factors, there was no significant association between HRV and recurrent stroke, MI, death or the combined endpoint. We did not find a significant impact of HRV on a mRS ≥ 2 12 months after the index stroke.Conclusion: HRV did not predict recurrent vascular events in patients with acute mild to moderate ischemic stroke.

The increasing availability of vast quantities of data from various sources significantly impacts the insurance industry, although this industry has always been data driven. It accelerates manual processes and enables new products or business models. On the other hand, it also burdens insurance analysts and other users that need to cope with this development parallel to other global changes. A novel information system (IS) for artificial intelligence (AI)-supported big data analysis, introduced within this paper, shall help to overcome user overload and to empower human data analysts in the insurance industry. The IS research’s focus lies neither in novel algorithms nor datasets but in concepts that combine AI and big data analysis for synergies, such as usability enhancements. For this purpose, this paper systematically designs and implements an AI2VIS4BigData reference model to help information systems conform to automatically detect anomalies and increase its users’ confidence and efficiency. Practical relevance is assured by an interview with an insurance analyst to verify the demand for the developed system and derive all requirements from two insurance industry user stories. A core contribution is the introduction of the IS. Another significant contribution is an extension of the AI2VIS4BigData service-based architecture and user interface (UI) concept on AI and machine learning (ML)-based user empowerment and data transformation. The implemented prototype was applied to synthetic data to enable the evaluation of the system. The quantitative and qualitative evaluations confirm the system’s usability and applicability to the insurance domain yet reveal the need for improvements toward bigger quantities of data and further evaluations with a more extensive user group.

Background: Elevated high-sensitive cardiac troponin (hs-cTn) can be found in more than 50% of the patients with acute ischemic stroke. The observational TRoponin ELevation in Acute ischemic Stroke (TRELAS) study revealed that about 25% of all stroke patients with elevated troponin had a coronary angiography-detected culprit lesion affording immediate intervention, and about 50% of all patients did not have any obstructive coronary artery disease. Given the risk of procedure-related complications, the identification of stroke patients in urgent need of invasive coronary angiography is desirable. Methods: TRELAS patients were prospectively enrolled into this sub-study. In addition to conventional coronary angiography, a cardiac magnetic resonance imaging (MRI) at 3T was performed during the in-hospital stay after acute ischemic stroke to compare the diagnostic value of both imaging modalities. Results:Nine stroke patients (median age 73 years [range 58–87]; four females; median NIH Stroke Severity score on admission 4 [range 0–6] with elevated hs-cTnT [median 74 ng/L, interquartile range 41–247] on admission) completed cardiac MRI and underwent coronary angiography. The absence of MRI-detected wall motion abnormalities and/or late gadolinium enhancement in 5 stroke patients corresponded with the exclusion of culprit lesions or significant coronary artery disease by coronary angiography. Four patients had abnormal MRI findings, whereof 2 showed evidence of myocardial infarction and in whom coronary angiography demonstrated a >70% stenosis of a coronary artery. Conclusions: The TRELAS sub-study indicates that noninvasive cardiac MRI may provide helpful information to identify stroke patients with or without acute coronary syndrome. Our findings might help to select stroke patients in urgent need of coronary angiography.

Genetics plays an ever-increasing role in medical diagnostics. The requirements for laboratory diagnostics are constantly changing due to new emerging diagnostic procedures, methodologies, devices, and regulatory requirements. Standard software already available for laboratories often cannot keep up with the latest developments or is focused on research rather than process automation. Although the software utilized in diagnostic laboratories is subject to regulatory requirements, there is no well-defined formal procedure for software development. Reference models have been developed to formalize these solutions, but they do not facilitate the initial requirements analysis or the development process itself. A systematic requirements engineering process is however not only essential to ensure the quality of the final product but is also required by regulations such as the European In Vitro Diagnostic Regulation and international standards such as IEC 62304. This paper shows, by example, the systematic requirements analysis of a system for qPCR-based (quantitative polymerase chain reaction) gene expression analysis. Towards this goal, a multi-step research approach was employed, which included literature review, user interviews, and market analysis. Results revealed the complexity of the field with many requirements to be considered for future implementation.

PURPOSE:Image texture is increasingly used to discriminate tissues and lesions in PET/CT. For quantification or in computer-aided diagnosis, textural feature analysis must produce robust and comparable values. Because statistical feature values depend on image count statistics, we investigated in depth the stability of Haralick features values as functions of acquisition duration, and for common image resolutions and reconstructions. METHODS:A homogeneous cylindrical phantom containing 9.6 kBq/ml Ge-68 was repeatedly imaged on a Siemens Biograph mCT, with acquisition durations ranging from three seconds to three hours. Images with 1.5, 2, and 4 mm isometrically spaced voxels were reconstructed with filtered back-projection (FBP), ordered subset expectation maximization (OSEM), and the Siemens TrueX algorithm. We analysed Haralick features derived from differently quantized (3 to 8-bit) grey level co-occurrence matrices (GLCMs) as functions of exposure E, which we defined as the product of activity concentration in a volume of interest (VOI) and acquisition duration. The VOI was a 50 mm wide cube at the centre of the phantom. Feature stability was defined for df/dE → 0. RESULTS:The most stable feature values occurred in low resolution FBPs, whereas some feature values from 1.5 mm TrueX reconstructions ranged over two orders of magnitude. Within the same reconstructions, most feature value-exposure curves reached stable plateaus at similar exposures, regardless of GLCM quantization. With 8-bit GLCM, median time to stability was 16 s and 22 s for FBPs, 18 s and 125 s for OSEM, and 23 s, 45 s, and 76 s for PSF reconstructions, with longer durations for higher resolutions. Stable exposures coincided in OSEM and TrueX reconstructions with image noise distributions converging to a Gaussian. In FBP, the occurrence of stable values coincided the disappearance of negatives image values in the VOI. CONCLUSIONS:Haralick feature values depend strongly on exposure, but invariance exists within defined domains of exposure. Here, we present an easily replicable procedure to identify said stable exposure domains, where image noise does not substantially add to textural feature values. Only by imaging at predetermined feature-invariant exposure levels and by adjusting exposure to expected activity concentrations, can textural features have a quantitative use in PET/CT. The necessary exposure levels are attainable by modern PET/CT systems in clinical routine.

Rezensierte Werke: Thomas Glyn Watkin, The Legal History of Wales, Cardiff: University of Wales Press 2007, X, 332 p., ISBN 978-0-7083-2064-8; Legal Wales: its Past, its Future. Essays dedicated to Professor Dafydd Jenkins on his ninetieth birthday, ed. by Thomas Glyn Watkin, Cardiff: Welsh Legal History Society 2001, XI, 181 p., ISBN 0-9541637-0-2; The Trial of Dic Penderyn and other Essays, ed. by Thomas Glyn Watkin, Cardiff: Welsh Legal History Society 2003, X, 196 p., ISBN 0-9541637-1-0; Y Cyfraniad Cymreig – Welsh Contributions to Legal Development, ed. by Thomas Glyn Watkin, Bangor: Welsh Legal History Society 2005, XI, 231 p., ISBN 0-9541637-2-9; Sir William Jones, An Essay of the Law of Bailments, 1781, ed. by David J. Ibbetson, Bangor: Welsh Legal History Society 2007, ISBN 0-9541637-3-7; Tair Colofn Cyfraith = The Three Columns of Law in Medieval Wales: Homicide, Theft and Fire, ed. by T.M. Charles-Edwards and Paul Russell, Bangor: Welsh Legal History Society 2007, ISBN 978-0-9541637-4-7; Sara Elin Roberts, The Legal Triads of Medieval Wales, Cardiff: University of Wales Press 2007, XV, 461 p., ISBN 978-0-7083-2107-2; Richard W. Ireland, A Want of Order…, Cardiff: University of Wales Press 2007, XIII, 302 p., ISBN 978-0-7083-1945-1; Sharon Howard, Law and Disorder in Early Modern Wales: Crime and Authority in the Denbighshire Courts, c. 1660–1730, Cardiff: University of Wales Press 2008, XXII, 295 p., ISBN 978-0-7083-1994-9

Rezensierte Werke: Gerhard Ammerer, Alfred Stefan Weiss (Hg.), Strafe, Disziplin und Besserung. Österreichische Zucht- und Arbeitshäuser von 1750 bis 1850, Frankfurt a. M.: Peter Lang 2006, 287 S., ISBN 3-631-541136-8; Martina Henze, Strafvollzugsreformen im 19. Jahrhundert. Gefängniskundlicher Diskurs und staatliche Praxis in Bayern und Hessen-Darmstadt (Quellen und Forschungen zur hessischen Geschichte 135), Darmstadt, Marburg: Selbstverlag der Hessischen Historischen Kommission Darmstadt und der Historischen Kommision für Hessen 2003, 501 S., ISBN 3-88443-088-2; Lars Hendrik Riemer, Das Netzwerk der »Gefängnisfreunde« (1830–1872). Karl Josef Anton Mittermaiers Briefwechsel mit europäischen Strafvollzugsexperten, 2 Halbbde. (Studien zur euro­päischen Rechtsgeschichte 192.1 u. 192.2), Frankfurt a. M.: Klostermann 2005, XIV, XXX, 1908 S., ISBN 3-465-03405-8; Kai Naumann, Gefängnis und Gesellschaft. Freiheitsentzug in Deutschland in Wissenschaft und Praxis 1920–1960 (Forschungen zur Geschichte der Neuzeit: Marburger Beiträge 9), Berlin: Lit Verlag 2006, 335 S., ISBN 3-8258-9101-1; Nikolaus Wachsmann, Hitler’s Prisons. Legal Terror in Nazi Germany, New Haven, London: Yale University Press 2004, XV, 538 p., ISBN 0-300-10250-X; Nikolaus Wachsmann, Gefangen unter Hitler. Justizterror und Strafvollzug im NS-Staat, München: Siedler Verlag 2006, 622 S., ISBN 3-88680-828-9

This review article discusses studies on the history of crime and the criminal law in England and Ireland published during the last few years. These reflect the ›history of crime and punishment‹ as a more or less established sub-discipline of social history, at least in England, whereas it only really began to flourish in the german-speaking world from the 1990s onwards. By contrast, the legal history of the criminal law and its procedure has a strong, recently revived academic tradition in Germany that does not really have a parallel in the British Isles, whose legal scholars still evidence their traditional reluctance to confront penal subjects.

Background Stroke aetiology remains cryptogenic in a relevant proportion of patients with acute ischaemic stroke (AIS). We assessed whether enhanced diagnostic workup after AIS yields a higher rate of prespecified pathological findings compared with routine diagnostic care in-hospital.Methods Hospitalised patients with AIS were prospectively enrolled in the investigator-initiated observational HEart and BRain Interfaces in Acute Ischaemic Stroke (HEBRAS) study at the Charité, Berlin, Germany. Patients with AIS without known atrial fibrillation (AF) underwent cardiovascular MR imaging (CMR), MR-angiography of the aortic arch and prolonged Holter-ECG monitoring on top of routine diagnostic care.Results Among 356 patients with AIS (mean age 66 years, 37.6% female), enhanced workup yielded a higher rate of prespecified pathological findings compared with routine care (17.7% vs 5.3%; p