Microplastic pollution was studied in surface waters of Isfjorden, Svalbard in July 2021 as a part of an international regional harmonisation exercise. Surface microplastics (0.5-5 mm) were sampled with a neuston net in triplicate per study site in several branches of Isfjorden, covering populated and unpopulated fjords. High spatial variability of microplastic abundance (0-32,700 items/km2) was observed within a single fjord resulting from the hydrodynamic pattern formed through the interaction of surface currents, freshwater runoff, and wind conditions. Maximum microplastic abundance was not correlated with the distance from the local source and was instead defined by local small-scale hydrodynamics. Future recommendations for correct assessment of surface microplastics concentration in estuarine environments are presented.

BACKGROUND: Pooling data from different sources will advance mental health research by providing larger sample sizes and allowing cross-study comparisons; however, the heterogeneity in how variables are measured across studies poses a challenge to this process.
METHODS: This study explored the potential of using natural language processing (NLP) to harmonise different mental health questionnaires by matching individual questions based on their semantic content. Using the Sentence-BERT model, we calculated the semantic similarity (cosine index) between 741 pairs of questions from five questionnaires. Drawing on data from a representative UK sample of adults (N = 2,058), we calculated a Spearman rank correlation for each of the same pairs of items, and then estimated the correlation between the cosine values and Spearman coefficients. We also used network analysis to explore the model\'s ability to uncover structures within the data and metadata.
RESULTS: We found a moderate overall correlation (r = .48, p < .001) between the two indices. In a holdout sample, the cosine scores predicted the real-world correlations with a small degree of error (MAE = 0.05, MedAE = 0.04, RMSE = 0.064) suggesting the utility of NLP in identifying similar items for cross-study data pooling. Our NLP model could detect more complex patterns in our data, however it required manual rules to decide which edges to include in the network.
CONCLUSIONS: This research shows that it is possible to quantify the semantic similarity between pairs of questionnaire items from their meta-data, and these similarity indices correlate with how participants would answer the same two items. This highlights the potential of NLP to facilitate cross-study data pooling in mental health research. Nevertheless, researchers are cautioned to verify the psychometric equivalence of matched items.

The harmonization of laboratory biomarkers is pivotal in ensuring consistent and reliable diagnostic outcomes across different clinical settings. This systematic review examines the harmonization of C-Reactive Protein (CRP) and N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) measurements, both of which are jointly utilized in the diagnosis and management of cardiovascular diseases. To identify relevant studies, we searched the PubMed electronic database using specific medical subject headings and keywords such as C-Reactive Protein, CRP, high sensitivity C-Reactive Protein (hs-CRP), N-terminal pro B-type natriuretic peptide, and NT-proBNP, focusing on publications from June 1 to September 26, 2021. The query filtered studies to include only those in English involving human subjects. From our search, 97 articles met the inclusion criteria and were included for in-depth analysis. Despite their widespread use, significant variability remains in the measurements of CRP and NT-proBNP due to a lack of standardized pre-analytical, analytical, and post-analytical practices. This review highlights the consequences of this variability on clinical decision-making and patient outcomes and emphasizes the need for international standards and guidelines to achieve better harmonization. Our findings advocate for the establishment of universal protocols to enhance the reliability of these biomarker measurements across different clinical environments, ensuring improved healthcare delivery.

Recombinant antibodies (Abs) are an integral modality for the treatment of multiple tumour malignancies. Since the Food and Drug Administration (FDA) approval of rituximab as the first monoclonal antibody (mAb) for cancer treatment, several mAbs and antibody (Ab)-based therapies have been approved for the treatment of solid tumour malignancies and other cancers. These Abs function by either blocking oncogenic pathways or angiogenesis, modulating immune response, or by delivering a conjugated drug. The use of Ab-based therapy in cancer patients who could benefit from the treatment, however, is still limited by associated toxicity profiles which may stem from biological features and processes related to target binding, alongside biochemical and/or biophysical characteristics of the therapeutic Ab. A significant immune-related adverse event (irAE) associated with Ab-based therapies is cytokine release syndrome (CRS), characterized by the development of fever, rash and even marked, life-threatening hypotension, and acute inflammation with secondary to systemic uncontrolled increase in a range of pro-inflammatory cytokines. Here, we review irAEs associated with specific classes of approved, Ab-based novel cancer immunotherapeutics, namely immune checkpoint (IC)-targeting Abs, bispecific Abs (BsAbs) and Ab-drug-conjugates (ADCs), highlighting the significance of harmonization in preclinical assay development for safety assessment of Ab-based biotherapeutics as an approach to support and refine clinical translation.

Permitted Daily Exposure Limits (PDEs) are set for Active Pharmaceutical Ingredients (APIs) to control cross-contamination when manufacturing medicinal products in shared facilities. With the lack of official PDE lists for pharmaceuticals, PDEs have to be set by each company separately. Although general rules and guidelines for the setting of PDEs exist, inter-company variations in the setting of PDEs occur and are considered acceptable within a certain range. To evaluate the robustness of the PDE approach between different pharmaceutical companies, data on PDE setting of five marketed APIs (amlodipine, hydrochlorothiazide, metformin, morphine, and omeprazole) were collected and compared. Findings show that the variability between PDE values is within acceptable ranges (below 10-fold) for all compounds, with the highest difference for morphine due to different Point of Departures (PODs) and Adjustment Factors (AFs). Factors of PDE variability identified and further discussed are: (1) availability of data, (2) selection of POD, (3) assignment of AFs, (4) route-to-route extrapolation, and (5) expert judgement and differences in company policies. We conclude that the investigated PDE methods and calculations are robust and scientifically defensible. Additionally, we provide further recommendations to harmonize PDE calculation approaches across the pharmaceutical industry.

Foods are analysed for their vitamin content to support the verification of regulatory compliance or to generate food composition data. Many international reference methods for the analysis of vitamins in foods originate from the 1990s. Advances in nutrition science and analytical technology and the continuing evolution of statutory regulations necessitate the need of new or supplementary regulatory standards. We have evaluated recent developments in these areas and conclude that most current international reference methods are no longer fit-for-purpose to accurately determine vitamin content in foods and food supplements. We have made recommendations to consider new and/or updated reference methods and regulatory standards for the analysis of vitamins A, D, E, K, B1, B2, B3, B5, B6, B7, B9, B12, C and carotenoids in foods and food supplements. This area of nutrients may benefit from globally harmonised definitions specifying what compounds to include or exclude for analysis, and applicable bioactivity factors.

UNASSIGNED: Electronic healthcare records (EHRs) are an important resource for health research that can be used to improve patient outcomes in chronic respiratory diseases. However, consistent approaches in the analysis of these datasets are needed for coherent messaging, and when undertaking comparative studies across different populations.
UNASSIGNED: We developed a harmonised curation approach to generate comparable patient cohorts for asthma, chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) using datasets from within Clinical Practice Research Datalink (CPRD; for England), Secure Anonymised Information Linkage (SAIL; for Wales) and DataLoch (for Scotland) by defining commonly derived variables consistently between the datasets. By working in parallel on the curation methodology used for CPRD, SAIL and DataLoch for asthma, COPD and ILD, we were able to highlight key differences in coding and recording between the databases and identify solutions to enable valid comparisons.
UNASSIGNED: Codelists and metadata generated have been made available to help re-create the asthma, COPD and ILD cohorts in CPRD, SAIL and DataLoch for different time periods, and provide a starting point for the curation of respiratory datasets in other EHR databases, expediting further comparable respiratory research.

BACKGROUND: It has been suggested that schizophrenia involves dysconnectivity between functional brain regions and also the white matter structural disorganisation. Thus, diffusion tensor imaging (DTI) has widely been used for studying schizophrenia. However, most previous studies have used the region of interest (ROI) based approach. We, therefore, performed the probabilistic tractography method in this study to reveal the alterations of white matter tracts in the schizophrenia brain.
METHODS: A total of four different datasets consisted of 189 patients with schizophrenia and 213 healthy controls were investigated. We performed retrospective harmonisation of raw diffusion MRI data by dMRIharmonisation and used the FMRIB Software Library (FSL) for probabilistic tractography. The connectivities between different ROIs were then compared between patients and controls. Furthermore, we evaluated the relationship between the connection probabilities and the symptoms and cognitive measures in patients with schizophrenia.
RESULTS: After applying Bonferroni correction for multiple comparisons, 11 different tracts showed significant differences between patients with schizophrenia and healthy controls. Many of these tracts were associated with the basal ganglia or cortico-striatal structures, which aligns with the current literature highlighting striatal dysfunction. Moreover, we found that these tracts demonstrated statistically significant relationships with few cognitive measures related to language, executive function, or processing speed.
CONCLUSIONS: We performed probabilistic tractography using a large, harmonised dataset of diffusion MRI data, which enhanced the statistical power of our study. It is important to note that most of the tracts identified in this study, particularly callosal and cortico-striatal streamlines, have been previously implicated in schizophrenia within the current literature. Further research with harmonised data focusing specifically on these brain regions could be recommended.

Thyroid-stimulating hormone (TSH) is an important clinical marker in the diagnosis and management of thyroid disease. TSH measurements are reported in milli-International Units per Litre (mIU/L), traceable to a World Health Organisation (WHO) reference material. There is a wide variety of commercial immunoassays for TSH measurements available, which have historically been poorly harmonised due to a lack of commutability of the WHO reference materials with patient samples. This led to the recent development of a serum-based reference panel for TSH, traceable to the WHO reference material, available via the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC), aimed at harmonisation of TSH immunoassays. This report describes recent developments in the TSH reference system, including establishment of the 4th WHO International Standard for TSH, and aims to clarify the relationship between the available reference materials and their intended uses. This 4th WHO IS is widely available and defines the unit of TSH activity, therefore its continued existence is of paramount importance, however it continues to show a lack of commutability with patient in many TSH immunoassays. This makes the C-STFT TSH panel, albeit available in restricted numbers, a critical resource to ensure better TSH assay harmonisation.

OBJECTIVE: The Global Dietary Database (GDD) expanded its previous methods to harmonise and publicly disseminate individual-level dietary data from nutrition surveys worldwide.
METHODS: Analysis of cross-sectional data.
METHODS: Global.
METHODS: General population.
METHODS: Comprehensive methods to streamline the harmonisation of primary, individual-level 24-h recall and food record data worldwide were developed. To standardise the varying food descriptions, FoodEx2 was used, a highly detailed food classification and description system developed and adapted for international use by European Food Safety Authority (EFSA). Standardised processes were developed to: identify eligible surveys; contact data owners; screen surveys for inclusion; harmonise data structure, variable definition and unit and food characterisation; perform data checks and publicly disseminate the harmonised datasets. The GDD joined forces with FAO and EFSA, given the shared goal of harmonising individual-level dietary data worldwide.
RESULTS: Of 1500 dietary surveys identified, 600 met the eligibility criteria, and 156 were prioritised and contacted; fifty-five surveys were included for harmonisation and, ultimately, fifty two were harmonised. The included surveys were primarily nationally representative (59 %); included high- (39 %), upper-middle (21 %), lower-middle (27 %) and low- (13 %) income countries; usually collected multiple recalls/ records (64 %) and largely captured both sexes, all ages and both rural and urban areas. Surveys from low- and lower-middle v. high- and upper-middle income countries reported fewer nutrients (median 17 v. 30) and rarely included nutrients relevant to diet-related chronic diseases, such as n-3 fatty acids and Na.
CONCLUSIONS: Diverse 24-h recalls/records can be harmonised to provide highly granular, standardised data, supporting nutrition programming, research and capacity development worldwide.