Evaluation and clinical application of a bracketing calibration-based isotope dilution liquid chromatography-tandem mass spectrometry candidate reference measurement procedure for serum theophylline.

A candidate reference measurement procedure (RMP) for serum theophylline via isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. With a single-step precipitation pretreatment and a 6-min gradient elution, the method achieved baseline separation of theophylline and its analogs on a C18-packed column. A bracketing calibration method was used to ensure repeatable signal intensity and high measurement precision. The intra-assay and inter-assay imprecisions were 1.06%, 0.84%, 0.72% and 0.47%, 0.41%, 0.25% at concentrations of 4.22 µg/mL (23.40 µmol/L), 8.45 µg/mL (46.90 µmol/L), and 15.21 µg/mL (84.43 µmol/L), respectively. Recoveries ranged from 99.35 to 102.34%. The limit of detection (LoD) was 2 ng/mL, and the lowest limit of quantification (LLoQ) was 5 ng/mL. The linearity range extended from 0.47 to 60 µg/mL (2.61-333.04 µmol/L). No ion suppression and carry-over (< 0.68%) were observed. The relative bias for this candidate RMP that participated in 2023 External Quality Control for Reference Laboratories (RELA) conducted by the International Federation of Clinical Chemistry (IFCC) was within a range of 0.17 to 0.93%. Furthermore, two clinical immunoassay systems were compared with this candidate RMP, demonstrating good correlations. The results of the Trueness Verification Plan indicate significant differences among routine systems, highlighting the need for standardization efforts. The developed candidate RMP for serum theophylline serves as a precise reference baseline for standardizing clinical systems and assigning values to reference materials.

An International Study of Factors Affecting Variability of Dosimetry Calculations, Part 3: Contribution from Calculating Absorbed Dose from Time-Integrated Activity.

Image-based dosimetry-guided radiopharmaceutical therapy has the potential to personalize treatment by limiting toxicity to organs at risk and maximizing the therapeutic effect. The 177Lu dosimetry challenge of the Society of Nuclear Medicine and Molecular Imaging consisted of 5 tasks assessing the variability in the dosimetry workflow. The fifth task investigated the variability associated with the last step, dose conversion, of the dosimetry workflow on which this study is based. Methods: Reference variability was assessed by 2 medical physicists using different software, methods, and all possible combinations of input segmentation formats and time points as provided in the challenge. General descriptive statistics for absorbed dose values from the global submissions from participants were calculated, and variability was measured using the quartile coefficient of dispersion. Results: For the liver, which included lesions with high uptake, variabilities of up to 36% were found. The baseline analysis showed a variability of 29% in absorbed dose results for the liver from datasets where lesions included and excluded were grouped, indicating that variation in how lesions in normal liver were treated was a significant source of variability. For other organs and lesions, variability was within 7%, independently of software used except for the local deposition method. Conclusion: The choice of dosimetry method or software had a small contribution to the overall variability of dose estimates.

Roadmap towards safe and sustainable advanced and innovative materials. (Outlook for 2024-2030).

The adoption of innovative advanced materials holds vast potential, contingent upon addressing safety and sustainability concerns. The European Commission advocates the integration of Safe and Sustainable by Design (SSbD) principles early in the innovation process to streamline market introduction and mitigate costs. Within this framework, encompassing ecological, social, and economic factors is paramount. The NanoSafety Cluster (NSC) delineates key safety and sustainability areas, pinpointing unresolved issues and research gaps to steer the development of safe(r) materials. Leveraging FAIR data management and integration, alongside the alignment of regulatory aspects, fosters informed decision-making and innovation. Integrating circularity and sustainability mandates clear guidance, ensuring responsible innovation at every stage. Collaboration among stakeholders, anticipation of regulatory demands, and a commitment to sustainability are pivotal for translating SSbD into tangible advancements. Harmonizing standards and test guidelines, along with regulatory preparedness through an exchange platform, is imperative for governance and market readiness. By adhering to these principles, the effective and sustainable deployment of innovative materials can be realized, propelling positive transformation and societal acceptance.

Unified calibration of D-dimer can improve the uniformity of different detection systems.

Background: D-dimer at a low level is important evidence for excluding the onset and progression of thrombosis. It is readily detectable and yields rapid results, although significant variability exists among different detection systems. Our study aims to enhance the consistency across various detection systems. Methods: Twelve detection systems were included in our study. We sought to address this inconsistency by using various calibrators (two supplied by manufacturers and two comprising pooled human plasma diluted with different diluents) to standardize D-dimer measurements. We categorized the data into three groups according to D-dimer concentration levels: low (≤0.5 mg/L), medium (>0.5 mg/L - <3 mg/L), and high (≥3 mg/L). We then analyzed the data focusing on range, consistency, comparability, negative coincidence rate, and false negative rate. Results: Calibrating with pooled human plasma led to narrower result ranges in the low and medium groups (P < 0.05). In the low group, consistency improved from weak to strong (ICC 0.4-0.7, P﹤0.05), while it remained excellent in the other groups and overall (ICCï¹¥0.75, P﹤0.05). The percentage of pairwise comparability increased in both the low and high groups. Additionally, there was an increase in the negative coincidence rate. Conclusion: These findings demonstrate that uniform calibration of D-dimer can significantly enhance the consistency of results across different detection systems.

The shape of and applied weight on skin prick lancets critically affect the wheal size in the skin prick test.

The global application of the skin prick test (SPT) is attributed to the low costs, easy execution, and in vivo approach. Still, the healthcare professionals' technique and the lancet shape may challenge the standardization of the method. Thus, we investigated the influence of the shape of the lancet and the applied weight on the wheal size of SPT. Two allergic and one non-allergic individual were tested with allergens (Dermatophagoides pteronyssinus and Phleum pratense) and histamine solution (positive control), respectively. Horizontally (HS) and diagonally (DS) shouldered lancets with the same tip length (1 mm) were tested under two different conditions: either 60 g or 120 g weight pressure. The wheal size induced by the 4 different combinations was measured. The higher-weight device (120 g) induced a significantly larger and less variable wheal response with the tested allergens and histamine. However, the shape of the lancet affected the wheal size more than the applied weight. The least variable response was measured to histamine for the horizontal-shouldered lancet combined with the higher weight, whereas the same lancet with the lower weight resulted in a significant number of false negative results.

State of the Art and Science of Immunocytochemistry.

BACKGROUND: Immunocytochemistry (ICC) is a widely available and extensively used ancillary method in diagnostic cytopathology with great variability in all test phases and a low level of adequate quality management. The non-standardized ICC landscape is now challenged with the introduction of the new European (EU) In Vitro Diagnostic Medical Devices Regulation (IVDR). According to this regulation, ICC on cytological slides falls under the category of Laboratory-Developed Tests (LDT), which requires rigorous standardization, validation, and thorough quality management. SUMMARY: Complete standardization of pre-analytical and analytical steps in ICC is impossible due to the complexity of the method and the constantly evolving antibodies, detection systems, and platforms. However, similar to the approach in immunohistochemistry, improving and standardizing "best practices" in quality management will result in high-quality, correct, accurate, and reliable ICC results. In this review, the current challenges of ICC in diagnostic cytopathology will be discussed, along with practical insights into ICC standardization and validation. KEY MESSAGES: Control slides prepared in the same manner as the patient samples, optimized ICC protocols, and participation in external quality control for ICC are the pillars of good quality management and essential to ensure safe and reliable patient diagnostics.

[Implant anchorage: In vivo and in vitro analyses : Clusters for implant anchorage and safety]. / Implantatverankerung: In-vivo- und In-vitro-Analysen : Cluster Implantatverankerung und -sicherheit.

Aseptic implant loosening is the primary cause of revisions in arthroplasty. Various in vitro and in vivo methods are available for assessing implant fixation and stability. The aim of the Musculoskeletal Biomechanics Research Network (MSB-NET) is to continuously improve or develop these methods. In vitro analyses are often conducted using static and dynamic ISO and ASTM standards, while RSA, DXA, and EBRA analyses are established in vivo methods for evaluating implant fixation. Primary stability analyses, as well as acoustical methods, provide additional opportunities to detect loosening early and precisely evaluate implant stability. The cluster serves as a link between basic research, clinical practice, and end users to promote in vitro and in vivo methods to improve implant safety.

Development and standardization of an enzyme-linked inmunosorbent for the detection of orthohantavirus infection in Argentina based on its bacterial-expressed nucleocapside protein.

We conducted a development and standardization of an IgG ELISA assay for serological detection of human orthohantavirus infections using the recombinant antigen rLECH13 produced in bacterial and derived from the LECHV. The evaluation and standardization were carried out by analyzing serum samples from a total of 50 patients with confirmed Hantavirus Pulmonary Syndrome (HPS) diagnosis through the reference technique, 50 negative sera, and 53 patients with other medical conditions. The data from the assay analysis showed a diagnostic sensitivity value of 95% and a diagnostic specificity of 80%. The high sensitivity of this novel assay leads us to conclude that rLECH13 is a feasible option for use in the immunodiagnostic of orthohantavirus infection. Additionally, it is crucial to have an antigen that can be produced under conditions that do not require highly complex laboratories. Furthermore, the new assay is cost-effective, reproducible, and demonstrates excellent performance.

Diagnostics of IgE-mediated occupational allergies: Between reality, requirements, and opportunities.

Occupational skin and respiratory allergies are among the most common occupational diseases in Germany. The identification of the allergy trigger is essential for the recognition of an occupational allergy as well as for effective individual prevention. However, occupational type I allergens are among the "rare" allergens and the possibilities of guideline-compliant diagnosis using quality-tested skin test solutions is becoming increasingly difficult due to the reduction in commercially available test allergens. In order to guarantee meaningful diagnostic workup for all affected insured persons with suspected occupational type I allergies and to ensure this in the future, a durable optimization, standardization, and availability of allergy tests for occupational allergic diseases is urgently required. The need for action has been recognized by the German Social Accident Insurance (DGUV), and steps to eliminate the diagnostic gaps have been initiated by a joint research project at the Institute for Prevention and Occupational Medicine of the DGUV (IPA) and the Paul Ehrlich Institut (PEI). The evaluation of alternative methods for the production of standardized test allergen solutions can also be used for newly emerging allergens in the workplace. New allergen sources at workplaces and thus also sensitization and allergies among employees can be expected as a result of changes in work processes and the introduction of new technologies and/or working materials, which are also introduced in connection with climate change and the concept of sustainability.

Development of a novel phantom for tau PET imaging.

PURPOSE: The cortical uptake of tau positron emission tomography (PET) tracers corresponds to the Braak stage and reflects the distribution and progression of tau neurofibrillary tangles. The present study aimed to develop and validate the basic performance of a novel tau PET phantom, as well as to establish standard test procedures and analytical methods. METHODS: The tau PET phantom consisted of a brain simulation section simulated medial temporal lobe region and resolution and uniformity sections. The brain simulation section and hot rods and uniformity section contained 4 and 2 kBq/mL of 18F, respectively and images were acquired three times for 20 min with a PET/CT scanner. The resolution section was visually assessed with two sets of hot and cold rods. Recovery coefficients (RCs) as a quantitative value and coefficient of variation (CV) as image noise were determined based on the brain simulation and the uniformity section, respectively. RESULTS: Preparation of activity in the phantom was repeatable among three measurements. The quality of images in the brain simulation and uniformity section with the rods was good. The 5- or 6-mm rods were detected separately. The mean RCs calculated based on the VOI template were between 0.75 and 0.83. The CV at the center slice of uniformity section was 5.54%. CONCLUSIONS: We developed a novel tau PET phantom to assess quantitative value, image noise, and detectability and resolution from brain simulation section, uniformity section, and rods, respectively. This phantom will contribute to the standardization and harmonization of tau PET imaging.

Standardization, Collaboration, and Education in the Implementation of Artificial Intelligence in Otolaryngology: The Key to Scalable Impact.

The study delves into the crucial role of standardization, collaboration, and education in the integration of artificial intelligence (AI) in otolaryngology. It emphasizes the necessity of large, diverse datasets for effective AI implementation in health care, particularly in otolaryngology, due to its reliance on medical imagery and diverse instruments. The text identifies current barriers, including siloed work in academia and sparse academic-industrial partnerships, while proposing solutions like forming interdisciplinary teams and aligning incentives. Moreover, it discusses the importance of standardizing AI projects through system reporting and advocates for AI education and literacy among otolaryngology practitioners.

Implementation of a pilot checklist for control standardization on fishery goods consignments at the Livorno border control post.

To standardize control activities, it is necessary to introduce checklists to support the control of consignments entering the European Union through border control posts (BCPs). This study aimed to develop a pilot checklist for the control of fishery consignments, preliminarily identified as the predominant group of goods entering the Livorno (Italy) BCP. The design of the pilot checklist was preceded by i) a revision of the current European and national legislation on the general and specific objectives of border control activities on fishery products and ii) a comparative analysis of two checklists (one of the Ministry of Health and one of the former Livorno border inspection post) developed on the basis of the repealed legislation. This comparison aimed to define the pilot checklist structure, verification objectives, and selection of assessment scores to be included in defining consignment compliance and acceptability. Once developed, the clarity and ease of use of the first draft of the pilot checklist were verified through its use in a field test during the control of 64 fishery product consignments. 22 regulatory sources (18 European and 4 national) were selected as reference legislation. The pilot checklist was structured as a dynamic "read-do" document based on the workflow of control activities described in the current legislation. The field test was useful in improving the clarity of the verification objectives within the documentary, identity, and physical control sections and in facilitating the use of the checklist and the collection of evidence during the control activity. This study, which focused on fishery products, can provide a practical approach for the development of checklists for all the other categories of goods under the responsibility of BCPs.

Setting the Stage for Standardized Reporting of Clinical and Demographic Information in Laboratory-Based Studies of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a complex inflammatory skin condition affecting 0.1-4% of the population that leads to permanent scarring in the axilla, inframammary region, groin, and buttocks. Its complex pathogenesis involves genetics, innate and adaptive immunity, microbiota, and environmental stimuli. Specific populations have a higher incidence of HS, including females and Black individuals and those with associated comorbidities. HS registries and biobanks have set standards for the documentation of clinical data in the context of clinical trials and outcomes research, but collection, documentation, and reporting of these important clinical and demographic variables are uncommon in HS laboratory research studies. Standardization in the laboratory setting is needed because it helps to elucidate the factors that contribute mechanistically to HS symptoms and pathophysiology. The purpose of this article is to begin to set the stage for standardized reporting in the laboratory setting. We discuss how clinical guidelines can inform laboratory research studies, and we highlight what additional information is necessary for the use of samples in the wet laboratory and interpretation of associated mechanistic data. Through standardized data collection and reporting, data harmonization between research studies will transform our understanding of HS and lead to novel discoveries that will positively impact patient care.

Exploring the Effectiveness of Hatha Yoga as a Complementary Treatment for Adolescent Idiopathic Scoliosis: Clinical Effect and Future Research Directions.

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity that primarily affects adolescents during the key period of growth and development. While traditional treatment methods often involve bracing or surgery, Hatha yoga, a millennia-old practice rooted in Indian tradition, has emerged as a complementary option for AIS cases. This paper explores the potential benefits of Hatha yoga for adolescents with AIS. It also discusses the limitations of existing research, such as the lack of large-scale randomized controlled trials (RCTs), varying yoga protocols, and challenges in blinding participants and researchers. To address these limitations, I propose future research directions, including conducting large-scale RCTs, long-term follow-up studies, standardized yoga protocols, and assessing safety concerns. I also highlight the need for tailored interventions and comparative effectiveness studies to better understand the potential of Hatha yoga in the holistic treatment of AIS in adolescents.

A Standardized Nomenclature Design for Systematic Referencing and Identification of Animal Cellular Material.

The documentation, preservation and rescue of biological diversity increasingly uses living biological samples. Persistent associations between species, biosamples, such as tissues and cell lines, and the accompanying data are indispensable for using, exchanging and benefiting from these valuable materials. Explicit authentication of such biosamples by assigning unique and robust identifiers is therefore required to allow for unambiguous referencing, avoid identification conflicts and maintain reproducibility in research. A predefined nomenclature based on uniform rules would facilitate this process. However, such a nomenclature is currently lacking for animal biological material. We here present a first, standardized, human-readable nomenclature design, which is sufficient to generate unique and stable identifying names for animal cellular material with a focus on wildlife species. A species-specific human- and machine-readable syntax is included in the proposed standard naming scheme, allowing for the traceability of donated material and cultured cells, as well as data FAIRification. Only when it is consistently applied in the public domain, as publications and inter-institutional samples and data are exchanged, distributed and stored centrally, can the risks of misidentification and loss of traceability be mitigated. This innovative globally applicable identification system provides a standard for a sustainable structure for the long-term storage of animal bio-samples in cryobanks and hence facilitates current as well as future species conservation and biomedical research.

Bridging the Gap: Standardizing Orientation to Improve Vacancy and Turnover Rates of Ambulatory Oncology Nurses.

This article describes standardizing ambulatory oncology nursing orientation within an academic comprehensive cancer center to reduce turnover rates. The nursing professional development specialist created a standardized orie.

German adult population norm values of the short Warwick Edinburgh mental well-being scale (SWEMWBS).

PURPOSE: The Warwick-Edinburgh Mental Well-Being Scale represents an internationally established inventory to assess population mental well-being. Particularly the short form (SWEMWBS) is recommended for use in Mental Health Surveillance. In the present study, we present normative data of the SWEMWBS for the German adult population. METHODS: Data from the telephone survey German Health Update (GEDA) in 2022 representative of the German adult population (48.9% women, 18-98 years) was processed to estimate SWEMWBS percentile norm values, T-values, z-values and internationally comparable logit-transformed raw scores for the total sample (N = 5,606) as well as stratified by sex, age group and sex with age group combinations. RESULTS: The average mental well-being was comparable to that of other European countries at M = 27.3 (SD = 4.0; logit-transformed: M = 24.79, SD = 3.73). To provide a benchmark, the cut off for low well-being was set at the 15th percentile (raw score: 23; logit-transformed: 20.73), for high well-being at the 85th percentile (raw score: 32; logit-transformed: 29.31). CONCLUSION: The present study provides SWEMWBS norm values for the German adult population. The normative data can be used for national and international comparisons on a population level to initiate, plan and evaluate mental well-being promotion and prevention measures.

Standardization of the Norwood Procedure Improves Outcomes in a Medium-Sized Volume Center.

The Norwood operation has become common practice to palliate patients with hypoplastic left heart structures. Surgical technique and postoperative care have improved; yet, there remains significant attrition prior to stage II palliation. The objective of this study is to report outcomes before and after standardizing our approach to the Norwood operation. Patients who underwent the Norwood operation at Children's of Alabama were identified, those who underwent hybrid palliation operations were excluded. Pre- (2015-2020) and post- (2020-January 2023) standardization groups were compared and outcomes analyzed. Ninety-one patients were included (pre-standardization 44 (48.3%) and 47 (51.7%) post-standardization). There were no differences in baseline and intraoperative characteristics at Norwood between the pre- and post-standardization groups. Compared with pre-standardization, post-standardization was associated with decreased time to extubation (OR 0.87, 95%CI 0.79-0.96), inotrope duration (OR 0.92, 95%CI 0.86-0.98) and hospital length of stay (OR 0.98, 95%CI 0.96-0.99). There was a trend toward decreased cardiac arrest, reintervention rates, and interstage mortality for the post-standardization group. A standardized approach to complex neonatal cardiac operations such as the Norwood procedure may improve morbidity and decrease hospital resource utilization. We recommend establishing protocols at an institutional level to optimize outcomes in such high-risk patient populations.

Golden spikes, scientific types, and the ma(r)king of deep time.

Chronostratigraphy is the subfield of geology that studies the relative age of rock strata and that aims at producing a hierarchical classification of (global) divisions of the historical time-rock record. The 'golden spike' or 'GSSP' approach is the cornerstone of contemporary chronostratigraphic methodology. It is also perplexing. Chronostratigraphers define each global time-rock boundary extremely locally, often by driving a gold-colored pin into an exposed rock section at a particular level. Moreover, they usually avoid rock sections that show any meaningful sign of paleontological disruption or geological discontinuity: the less obvious the boundary, the better. It has been argued that we can make sense of this practice of marking boundaries by comparing the status and function of golden spikes to that of other concrete, particular reference standards from other sciences: holotypes from biological taxonomy and measurement prototypes from the metrology of weight and measures. Alisa Bokulich (2020b) has argued that these 'scientific types' are in an important sense one of a kind: they have a common status and function. I will argue that this picture of high-level conceptual unity is mistaken and fails to consider the diversity of aims and purposes of standardization and classification across the sciences. I develop an alternative, disunified account of scientific types that shows how differences in ontological attitudes and epistemic aims inform scientists' choices between different kinds of scientific types. This perspective on scientific types helps to make sense of an intriguing mid-twentieth-century debate among chronostratigraphers about the very nature of their enterprise. Should chronostratigraphers conventionally make boundaries by designating golden spikes, or should they attempt to mark pre-existing 'natural' boundaries with the help of a different kind of scientific type?

Visualizing Worldwide Prevalence of Age-Related Dual Sensory Loss.

Objectives: This study aims to create a first visualization of global prevalence of age-related dual sensory loss (DSL), significantly affecting older people's quality of life. Methods: Data from World Health Organization (WHO) regions, particularly African, American, and European, were analyzed. The study focused on DSL onset and prevalence, using adjusted life expectancy for regional comparison. Results: There were notable regional variations in DSL onset and prevalence. The African region showed consistent data, thanks to standardized methods from the World Federation of the Deafblind. However, global patterns varied when adjusted for life expectancy, hinting at possible DSL prevalence stabilization at older ages. Discussion: The study identifies a lack of standardization in DSL prevalence research regarding definitions, methodologies, and reporting. It calls for more uniform and thorough research methods for accurate global DSL understanding. The research highlights the complexity and challenges in determining DSL prevalence worldwide.