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PURPOSE Access to knowledge-based treatment plan quality control has been hindered by the complexity of developing models and integration with different treatment planning systems (TPS). Online Real-time Benchmarking Information Technology for RadioTherapy (ORBIT-RT) provides a free, web-based platform for knowledge-based dose estimation that can be used by clinicians worldwide to benchmark the quality of their radiotherapy plans. MATERIALS AND METHODS The ORBIT-RT platform was developed to satisfy four primary design criteria: web-based access, TPS independence, Health Insurance Portability and Accountability Act compliance, and autonomous operation. ORBIT-RT uses a cloud-based server to automatically anonymize a user's Digital Imaging and Communications in Medicine for RadioTherapy (DICOM-RT) file before upload and processing of the case. From there, ORBIT-RT uses established knowledge-based dose-volume histogram (DVH) estimation methods to autonomously create DVH estimations for the uploaded DICOM-RT. ORBIT-RT performance was evaluated with an independent validation set of 45 volumetric modulated arc therapy prostate plans with two key metrics: (i) accuracy of the DVH estimations, as quantified by their error, DVHclinical − DVHprediction and (ii) time to process and display the DVH estimations on the ORBIT-RT platform. RESULTS ORBIT-RT organ DVH predictions show < 1% bias and 3% error uncertainty at doses > 80% of prescription for the prostate validation set. The ORBIT-RT extensions require 3.0 seconds per organ to analyze. The DICOM upload, data transfer, and DVH output display extend the entire system workflow to 2.5-3 minutes. CONCLUSION ORBIT-RT demonstrated fast and fully autonomous knowledge-based feedback on a web-based platform that takes only anonymized DICOM-RT as input. The ORBIT-RT system can be used for real-time quality control feedback that provides users with objective comparisons for final plan DVHs.

PURPOSEWe report the results from a Foundation for the National Institutes of Health Biomarkers Consortium project to address the absence of well-validated quality control materials (QCMs) for circulating tumor DNA (ctDNA) testing. This absence is considered a cause of variance and inconsistencies in translating ctDNA results into clinical actions.METHODSIn this phase I study, QCMs with 14 clinically relevant mutations representing single nucleotide variants, insertions or deletions (indels), translocations, and copy number variants were sourced from three commercial manufacturers with variant allele frequencies (VAFs) of 5%, 2.5%, 1%, 0.1%, and 0%. Four laboratories tested samples in quadruplicate using two allele-specific droplet digital polymerase chain reaction and three (amplicon and hybrid capture) next-generation sequencing (NGS) panels.RESULTSThe two droplet digital polymerase chain reaction assays reported VAF values very close to the manufacturers’ claimed concentrations for all QCMs. NGS assays reported most single nucleotide variants and indels, but not translocations, close to the expected VAF values. Notably, two NGS assays reported lower VAF than expected for all translocations in all QCM mixtures, possibly related to technical challenges detecting these variants. The ability to call ERBB2 copy number amplifications varied across assays. All three QCMs provided valuable insight into assay precision. Each assay across all variant types demonstrated dropouts at 0.1%, suggesting that the QCM can serve for testing of an assay’s limit of detection with confidence claims for specific variants.CONCLUSIONThese results support the utility of the QCM in testing ctDNA assay analytical performance. However, unique designs and manufacturing methods for the QCM, and variations in a laboratory’s testing configuration, may require testing of multiple QCMs to find the best reagents for accurate result interpretation.

The Connectivity Map (CMap) is a popular resource designed for data-driven drug repositioning using a large transcriptomic compendium. However, evaluations of its performance are limited. We used two iterations of CMap (CMap 1 and 2) to assess their comparability and reliability. We queried CMap 2 with CMap 1-derived signatures, expecting CMap 2 would highly prioritize the queried compounds; the success rate was 17%. Analysis of previously published prioritizations yielded similar results. Low recall is caused by low differential expression (DE) reproducibility both between CMaps and within each CMap. DE strength was predictive of reproducibility, and is influenced by compound concentration and cell-line responsiveness. Reproducibility of CMap 2 sample expression levels was also lower than expected. We attempted to identify the “better” CMap by comparison with a third dataset, but they were mutually discordant. Our findings have implications for CMap usage and we suggest steps for investigators to limit false positives.

Background There are limited data regarding the quality of patient‐reported outcome (PRO) data in immune checkpoint inhibitor (ICI) clinical trial publications. Methods A systematic search of citations from various databases was conducted to identify prospective clinical trials involving ICI in advanced tumors from 2003 to 2020. A 30‐point score was adapted from the CONSORT PRO extension statement to assess adherence to CONSORT PRO reporting. Linear regression was used to identify factors associated with quality reporting. Results After the review of 8058 articles, 33 trials were included with ICIs as either monotherapy (91%) or part of a combination regimen (9%). The median score was 23.5 points (range 15–29). In the majority of cases (82%), PROs were reported in a separate publication from the original study. Most of the trials were conducted in the metastatic setting and predominantly in melanoma, lung, and renal cell carcinoma (RCC) (73%). Univariate analysis revealed that trials with greater than 250 patients were associated with a higher score. The score was more likely to be lower in disease sites other than melanoma, lung, and RCC and was higher in the KEYNOTE than in the CHECKMATE trial series. There was no significant correlation between the score and whether a trial met its primary end‐point or if the trial improved or worsened the quality of life. In the multivariate analysis, the number of patients enrolled to the trial, disease site, and trial series remained significant. Conclusions The quality of reporting of PROs in ICI phase II and III clinical trials is heterogeneous across various cancer sites. As PRO data are increasingly used to counsel patients and complement clinical decision making, innovative and collaborative efforts are required to improve the reporting of these essential data., There are limited data regarding the quality of patient‐reported outcome data in immune checkpoint inhibitor clinical trial publications. A systematic review was conducted of published clinical trials to assess the quality of reporting.

The development and performance of molecular genetic assays has required increasingly complex quality assurance in recent years and continues to pose new challenges. Quality management officers, as well as academic and technical personnel are confronted with new molecular genetic parameters, methods, changing regulatory environments, questions regarding appropriate validation, and quality control for these innovative assays that are increasingly applying quantification and/or multiplex formats. Yet, quality assurance and quality control guidelines are still not widely available or in some circumstances have become outdated. For these reasons, the need for solutions to provide test confidence continues to grow. In order to integrate new test procedures into existing quality assurance measures, the ISO 15189 guideline can serve as an orientation. The ISO 15189 guideline describes requirements for medical laboratories and thus includes those performing molecular diagnostics. This article gives an overview of the possibilities and challenges in quality assurance of molecular parameters and shows possible solutions.

Raman spectroscopy is an analytical method to identify medical samples of bacteria. Because Raman spectroscopy detects the biochemical properties of a cell, there are many factors that can influence and modify the Raman spectra of bacteria. One possible influence is a proper method for isolation of the bacteria. Medical samples in particular never occur in purified form, so a Raman-compatible isolation method is needed which does not affect the bacteria and thus the resulting spectra. In this study, we present a Raman-compatible method for isolation of bacteria from bronchoalveolar lavage (BAL) fluid using density gradient centrifugation. In addition to measuring the bacteria from a patient sample, the yield and the spectral influence of the isolation on the bacteria were investigated. Bacteria isolated from BAL fluid show additional peaks in comparison to pure culture bacteria, which can be attributed to components in the BAL sample. The isolation gradient itself has no effect on the spectra, and with a yield of 63% and 78%, the method is suitable for isolation of low concentrations of bacteria from a complex matrix. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s00216-021-03488-0.

Objectives. To examine age and temporal trends in the proportion of COVID-19 deaths occurring out of hospital or in the emergency department and the proportion of all noninjury deaths assigned ill-defined causes in 2020. Methods. We analyzed newly released (March 2021) provisional COVID-19 death tabulations for the entire United States. Results. Children (younger than 18 years) were most likely (30.5%) and elders aged 64 to 74 years were least likely (10.4%) to die out of hospital or in the emergency department. In parallel, among all noninjury deaths, younger people had the highest proportions coded to symptoms, signs, and ill-defined conditions, and percentage symptoms, signs, and ill-defined conditions increased from 2019 to 2020 in all age–race/ethnicity groups. The majority of young COVID-19 decedents were racial/ethnic minorities. Conclusions. The high proportions of all noninjury deaths among children, adolescents, and young adults that were coded to ill-defined causes in 2020 suggest that some COVID-19 deaths were missed because of systemic failures in timely access to medical care for vulnerable young people. Public Health Implications. Increasing both availability of and access to the best hospital care for young people severely ill with COVID-19 will save lives and improve case fatality rates.

Deriving reliable information about the structural and functional architecture of the brain in vivo is critical for the clinical and basic neurosciences. In the new era of large population‐based datasets, when multiple brain imaging modalities and contrasts are combined in order to reveal latent brain structural patterns and associations with genetic, demographic and clinical information, automated and stringent quality control (QC) procedures are important. Diffusion magnetic resonance imaging (dMRI) is a fertile imaging technique for probing and visualising brain tissue microstructure in vivo, and has been included in most standard imaging protocols in large‐scale studies. Due to its sensitivity to subject motion and technical artefacts, automated QC procedures prior to scalar diffusion metrics estimation are required in order to minimise the influence of noise and artefacts. However, the QC procedures performed on raw diffusion data cannot guarantee an absence of distorted maps among the derived diffusion metrics. Thus, robust and efficient QC methods for diffusion scalar metrics are needed. Here, we introduce Fast qualitY conTrol meThod foR derIved diffUsion Metrics (YTTRIUM), a computationally efficient QC method utilising structural similarity to evaluate diffusion map quality and mean diffusion metrics. As an example, we applied YTTRIUM in the context of tract‐based spatial statistics to assess associations between age and kurtosis imaging and white matter tract integrity maps in U.K. Biobank data (n = 18,608). To assess the influence of outliers on results obtained using machine learning (ML) approaches, we tested the effects of applying YTTRIUM on brain age prediction. We demonstrated that the proposed QC pipeline represents an efficient approach for identifying poor quality datasets and artefacts and increases the accuracy of ML based brain age prediction., Accurate quality control of diffusion scalar maps in big data. Influence of outliers on brain age gap estimation.

Diagnostic imaging plays a key role in the evaluation of non-accidental consequences of injuries in childhood. Fractures are the second most common consequence of child abuse, after skin lesions such as abrasions or bleeding. With the evidence of radiological criteria, non-accidental fractures can be differentiated from accidental fractures. Special types of fractures such as the classic metaphyseal lesion can only be differentiated if the image quality is high.The goal of this prospective study was to assess adherence to guidelines and quality assurance of radiological diagnostics in the event of suspected abuse in Germany. For this purpose, the quantity and diagnostic quality in university and non-university hospitals as well as the existence of a pediatric radiology department were analyzed.In all, 958 X‑ray examinations of 114 suspected abuse cases (46 girls, 68 boys) were evaluated; 42 cases from university, 42 from maximum care and 30 from regular care clinics with a median age of 6 months (3 weeks-3 years of age) were assessed as DICOM data by 3 pediatric radiologists in a consensus procedure with regard to adherence to guidelines and various quality parameters. An accompanying questionnaire was used to compare the theoretical knowledge with the respective practical implementation.A mean of 8.4 X‑rays (range 1-22) were made per case. In 12 of 114 assessed cases (10%) there was a complete skeletal status according to the S1 guideline. A babygram was performed in 13 cases (10.5%). Departments with focus on pediatric radiology produced significantly more X‑rays per skeletal status than facilities without this specialization (p 0.04). Significantly higher qualitative implementation was recorded in university hospitals (p 0.001). Regardless of the type of institution, there was only marginal agreement between the questionnaire response and the available image material.In Germany, a guideline-compliant procedure in the event of suspected child abuse is largely lacking. It remains to be seen whether this will change in the future with the broader implementation of child protection groups and the S3+ child protection guideline adopted in 2019 (AWMF register 027-069). The establishment of reference centers for a second diagnosis and recommendations for imaging technology can also improve the quality of care over the long term.HINTERGRUND: Die bildgebende Diagnostik nimmt in der Evaluation nichtakzidentieller Verletzungsfolgen im Kindesalter eine Schlüsselrolle ein. Frakturen sind nach Hautläsionen wie Abschürfungen oder Hämatomen die zweithäufigste Folge körperlicher Kindesmisshandlung. Mit Hilfe radiologischer Kriterien können nichtakzidentielle von akzidentiellen Frakturen differenziert werden. Spezielle Frakturtypen wie die klassische metaphysäre Läsion können nur bei hoher Bildqualität differenziert werden.In einer prospektiven Analyse sollten Leitlinientreue und Qualitätssicherung der radiologischen Diagnostik bei Misshandlungsverdacht in Deutschland erfasst werden. Dazu wurden Quantität und diagnostische Qualität in der universitären und nichtuniversitären Versorgung sowie in Abhängigkeit einer vorhandenen kinderradiologischen Fachabteilung analysiert.Es wurden 958 Röntgenuntersuchungen von 114 vermuteten Misshandlungsfällen (46 Mädchen, 68 Jungen) bewertet. Insgesamt 42 Fälle aus universitären, 42 aus maximalversorgenden und 30 aus regelversorgenden Kliniken mit einem medianen Alter von 6 Monaten (3 Wochen – 3. Lebensjahr) wurden als DICOM-Daten von 3 Kinderradiologen im Konsensverfahren hinsichtlich Leitlinientreue und verschiedener Qualitätsparameter beurteilt. Ein Begleitfragebogen sollte die theoretischen Kenntnisse mit der jeweiligen praktischen Umsetzung vergleichen.Je Fall wurden im Mittel 8,4 Röntgenaufnahmen (1–22) angefertigt. In 12 von 114 beurteilten Fällen (10 %) lag ein vollständiger Skelettstatus nach S1-Leitlinie GPR vor. In 13 Fällen (10,5 %) wurde ein Babygramm durchgeführt. Abteilungen mit kinderradiologischem Schwerpunkt fertigten signifikant mehr Röntgenaufnahmen je Skelettstatus an als Einrichtungen ohne Schwerpunkt (p 0,05). Eine signifikant höhere qualitative Umsetzung wurde in Universitätskliniken verzeichnet (p 0,001). Eine Übereinstimmung von Fragebogenantwort und vorliegendem Bildmaterial zeigte sich unabhängig der Institutionsart nur marginal.In Deutschland fehlt bislang mehrheitlich ein leitliniengerechtes Vorgehen bei Misshandlungsverdacht. Es bleibt abzuwarten, ob sich dies mit der breiteren Implementierung von Kinderschutzgruppen und der 2019 verabschiedeten S3-Kinderschutzleitlinie (AWMF-Registrierungsnummer: 027-069) zukünftig ändern wird. Die Etablierung von Referenzzentren für Zweitbefundung und Empfehlungen zur Aufnahmetechnik können zusätzlich die Versorgungsqualität nachhaltig verbessern.

Sepsis represents a global health priority because of its high mortality and morbidity. The key to improving prognosis remains an early diagnosis to initiate appropriate antibiotic treatment. Procalcitonin (PCT) is a recognized biomarker for the early indication of bacterial infections and a valuable tool to guide and individualize antibiotic treatment. To meet the increasing demand for PCT testing, numerous PCT immunoassays have been developed and commercialized, but results have been questioned. Many comparison studies have been carried out to evaluate analytical performance and comparability of results provided by the different commercially available immunoassays for PCT, but results are conflicting. External Quality Assessment Schemes (EQAS) for PCT constitute another way to evaluate results comparability. However, when making this comparison, it must be taken into account that the variety of EQA materials consist of different matrices, the commutability of which has not yet been investigated. The present study gathers results from all published comparison studies and results from 137 EQAS surveys to describe the current state-of-the-art harmonization of PCT results. Comparison studies globally highlight a significant variability of measurement results that nonetheless seem to have a moderate impact on medical decision-making. For their part, EQAS for PCT provides highly discrepant estimates of the interlaboratory CV. Due to differences in commutability of the EQA materials, the results from different peer groups could not be compared. To improve the informative value of the EQA data, the existing limitations such as non-harmonized conditions and suboptimal and/or unknown commutability of the EQA materials have to be overcome. The study highlights the need for commutable reference materials that could be used to properly evaluate result comparability and possibly standardize calibration, if necessary. Such an initiative would further improve the safe use of PCT in clinical routine.

Snakebite envenomation is a public health problem of high impact, particularly for the developing world. Antivenom, which contains whole or protease-digested immunoglobulin G, purified from the plasma of hyper-immunized animals (mainly horses), is the mainstay for the treatment of snakebite envenomation. The success of antivenom therapy depends upon its ability to abrogate or reduce the local and systemic toxicity of envenomation. In addition, antivenom administration must be safe for the patients. Therefore, antivenom manufacturers must ensure that these products are effective and safe in the treatment of envenomations. Antivenom efficacy and safety are determined by the physicochemical characteristics of formulations, purity of the immunoglobulin fragments and antibodies, presence of protein aggregates, endotoxin burden, preservative load, and batch to batch variation, as well as on the ability to neutralize the most important toxins of the venoms against which the antivenom is designed. In this context, recent studies have shown that laboratory-based simple analytical techniques, for example, size exclusion chromatography, sodium dodecyl sulphate polyacrylamide gel electrophoresis, mass spectrometry, immunological profiling including immuno-turbidimetry and enzyme-linked immunosorbent assays, Western blotting, immune-chromatographic technique coupled to mass spectrometry analysis, reverse-phase high performance liquid chromatography, spectrofluorometric analysis, in vitro neutralization of venom enzymatic activities, and other methodologies, can be applied for the assessment of antivenom quality, safety, stability, and efficacy. This article reviews the usefulness of different analytical techniques for the quality assessment of commercial antivenoms. It is suggested that these tests should be applied for screening the quality of commercial antivenoms before their preclinical and clinical assessment.

The proliferation of synthetic data in artificial intelligence for medicine and healthcare raises concerns about the vulnerabilities of the software and the challenges of current policy.

The aim of the study is to assess the effectiveness of quality control of transport environments in accordance with the requirements of domestic and international standards using aerobic and optional anaerobic microorganisms. The results of a comparative assessment of the survival of 10 strains of aerobic and optional anaerobic microorganisms after storage in the semi-liquid transport environment of Ames for 24 and 48 hours at temperatures (4-8)0 C and (20-25)0 C in accordance with the requirements of domestic and international standards are presented. The methodology described in ICC 4.2.2316 causes a number of technical difficulties leading to non-reproducible results. The survival rate of microorganisms in semi-liquid transport environments under ISO 11133-2016 is of high quality. The quantitative assessment is based on two Swab Elution and Roll Plate methods recommended by the CLSI M40-A2 standard.

Purpose: The real-time tumor tracking radiotherapy (RTRT) system requires periodic quality assurance (QA) and quality control. The goal of this study is to propose QA procedures from the viewpoint of imaging devices in the RTRT system. Methods: Tracking by the RTRT system (equips two sets of colored image intensifiers (colored I.I.s) fluoroscopy units) for the moving gold-marker (diameter 2.0 mm) in a rotating phantom were performed under various X-ray conditions. To analyze the relationship between fluoroscopic image quality and precision of gold marker coordinate calculation, the standard deviation of the 3D coordinate (sigma 3D [mm]) of the gold marker, the mean of the pattern recognition score (PRS) and the standard deviation of the distance between rays (DBR) (sigma DBR [mm]) were evaluated. Results: When tracking with speed of 10-60 mm/s, sigma DBR increased, though the mean PRS did not change significantly (p>0.05). On the contrary, the mean PRS increased depending on the integral noise equivalent quanta (integral NEQ) that is an indicator of image quality calculated from the modulation transfer function (MTF) as an indicator of spatial resolution and the noise power spectrum (NPS) as an indicator of noise characteristic. Conclusion: The indicators of NEQ, MTF, and NPS were useful for managing the tracking accuracy of the RTRT system. We propose observing the change of these indicators as additional QA procedures for each imaging device from the commissioning baseline.

Digital pathology provides a possibility for computational analysis of histological slides and automatization of routine pathological tasks. Histological slides are very heterogeneous concerning staining, sections' thickness, and artifacts arising during tissue processing, cutting, staining, and digitization. In this study, we digitally reproduce major types of artifacts. Using six datasets from four different institutions digitized by different scanner systems, we systematically explore artifacts' influence on the accuracy of the pre-trained, validated, deep learning-based model for prostate cancer detection in histological slides. We provide evidence that any histological artifact dependent on severity can lead to a substantial loss in model performance. Strategies for the prevention of diagnostic model accuracy losses in the context of artifacts are warranted. Stress-testing of diagnostic models using synthetically generated artifacts might be an essential step during clinical validation of deep learning-based algorithms.

Ultrasound Core Laboratories (UCL) are used in multicenter trials to assess imaging biomarkers to define robust phenotypes, to reduce imaging variability and to allow blinded independent review with the purpose of optimizing endpoint measurement precision. The Household Air Pollution Intervention Network, a multicountry randomized controlled trial (Guatemala, Peru, India and Rwanda), evaluates the effects of reducing household air pollution on health outcomes. Field studies using portable ultrasound evaluate fetal, lung and vascular imaging endpoints. The objective of this report is to describe administrative methods and training of a centralized clinical research UCL. A comprehensive administrative protocol and training curriculum included standard operating procedures, didactics, practical scanning and written/practical assessments of general ultrasound principles and specific imaging protocols. After initial online training, 18 sonographers (three or four per country and five from the UCL) participated in a 2 wk on-site training program. Written and practical testing evaluated ultrasound topic knowledge and scanning skills, and surveys evaluated the overall course. The UCL developed comprehensive standard operating procedures for image acquisition with a portable ultrasound system, digital image upload to cloud-based storage, off-line analysis and quality control. Pre- and post-training tests showed significant improvements (fetal ultrasound: 71% ± 13% vs. 93% ± 7%, p < 0.0001; vascular lung ultrasound: 60% ± 8% vs. 84% ± 10%, p < 0.0001). Qualitative and quantitative feedback showed high satisfaction with training (mean, 4.9 ± 0.1; scale: 1 = worst, 5 = best). The UCL oversees all stages: training, standardization, performance monitoring, image quality control and consistency of measurements. Sonographers who failed to meet minimum allowable performance were identified for retraining. In conclusion, a UCL was established to ensure accurate and reproducible ultrasound measurements in clinical research. Standardized operating procedures and training are aimed at reducing variability and enhancing measurement precision from study sites, representing a model for use of portable digital ultrasound for multicenter field studies.

MicroRNA can be found in various body fluids, including breast milk. MicroRNA may be transferred from mother to infant via breast milk and potentially regulate the development of the infants immune system on a post-transcriptional level. This study aimed to determine the microRNA extraction efficiency of five RNA extraction kits from human skim milk samples. Their efficiency was determined by comparing microRNA concentrations, total RNA yield and purity. Furthermore, hsa-miR-148a-3p expression and the recovery of an exogenous control, cel-miR-39-3p, were quantified using qPCR. Each kit extracted different amounts of microRNA and total RNA, with one kit tending to isolate the highest amount of both RNA species. Based on these results, the extraction kit ReliaPrep (TM) miRNA Cell and Tissue Miniprep System from Promega was found to be the most appropriate kit for microRNA extraction from human skim milk. Moreover, further research is needed to establish a standardized protocol for microRNA extraction from breast milk. Funding Agencies|Lisa och Johan Gronbergs Stiftelse

The study presents a historical analysis of the problems of standardization of methods for determining ESR. The modern approaches to the automation of ESR research are presented. It is shown that the solution to the problems of standardization of methods for determining ESR lies in the plane of regular intra-laboratory quality control. In accordance with the principles of evidence-based medicine, recommendations are given on the use of methods for determining ESR in clinical practice.

The community-driven initiative Quality Assessment and Reproducibility for Instruments & Images in Light Microscopy (QUAREP-LiMi) wants to improve reproducibility for light microscopy image data through quality control (QC) management of instruments and images. It aims for a common set of QC guidelines for hardware calibration and image acquisition, management and analysis.

OBJECTIVE Myelomeningocele (MMC) is frequently complicated by symptomatic hydrocephalus, necessitating early permanent CSF diversion and revision surgeries. Shunt infections are a common cause of shunt malfunction. This study aims to characterize long-term shunt-related outcomes of patients undergoing MMC closure. METHODS A total of 170 patients undergoing MMC closure between the years of 1995 and 2017 were identified from a retrospective review of a prospectively populated surgical database at the Children’s Hospital of Pittsburgh. Patients who underwent MMC closure and required ventriculoperitoneal (VP) shunt insertion met criteria and were included in the primary study analysis. Analysis with a Fisher exact test was performed for categorical variables, and Mann-Whitney U-tests were utilized for numerical data. RESULTS Of the 158 total patients undergoing MMC closure and meeting inclusion criteria, 137 (87%) required VP shunt insertion. These 137 patients demonstrated a shunt revision rate of 21.1% per person-year and a shunt infection rate of 2.1% per person-year over a mean follow-up of 10.8 years. Patients had a mean of 3.4 ± 0.6 shunt surgeries prior to their first infection. Patients undergoing immediate shunt removal, external ventricular drain placement, or shunt replacement after clearing the infection had lower rates of subsequent infections than patients who initially were managed with shunt externalization (p < 0.001). Placement of a shunt at the time of MMC closure was not found to be a risk factor for infection. Of patients with initial shunt placement after the implementation of the Hydrocephalus Clinical Research Network protocol in 2011, the authors’ institution has had a shunt infection rate of 4.2% per person-year and a revision rate of 35.7% per person-year. CONCLUSIONS This study describes long-term outcomes of shunted MMC patients and factors associated with shunt infections. Most patients underwent multiple revisions prior to the first shunt infection. Shunt externalization may be ineffective at clearing the infection and should be avoided in favor of early shunt removal and external ventricular drainage, followed by shunt replacement once infection is demonstrated to have cleared.

The outbreak of COVID-19 has posed a huge threat to global health and economy. Countermeasures have revolutionized norms for working, socializing, learning, and travel. Importantly, vaccines have been considered as most effective tools to combat with COVID-19. As of the beginning of 2021, >200 COVID-19 vaccine candidates, covering nearly all existing technologies and platforms, are being research and development (R&D) by multiple manufacturers worldwide. This has posed a huge obstacle to the quality control and evaluation of those candidate vaccines, especially in China, where five vaccine platforms are deployed in parallel. To accelerate the R&D progress of COVID-19 vaccines, the guidances on R&D of COVID-19 vaccine have been issued by National Regulatory Authorities or organizations worldwide. The Center for Drug Evaluation and national quality control laboratory in China have played a leading role in launching the research on quality control and evaluation in collaboration with relevant laboratories involved in the vaccine R&D, which greatly supported the progression of vaccines R&D, and accelerated the approval for emergency use and conditional marketing of currently vaccine candidates. In this paper, the progress and experience gained in quality control and evaluation of COVID-19 vaccines developed in China are summarized, which might provide references for the R&D of current and next generation of COVID-19 vaccines worldwide.

Proteins and peptides are amongst the most widely used research reagents but often their quality is inadequate and can result in poor data reproducibility. Here we propose a simple set of guidelines that, when correctly applied to protein reagents should provide more reliable experimental data.

Summary Whole-genome sequencing (WGS), a powerful tool for detecting novel coding and non-coding disease-causing variants, has largely been applied to clinical diagnosis of inherited disorders. Here we leveraged WGS data in up to 62,653 ethnically diverse participants from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and assessed statistical association of variants with seven red blood cell (RBC) quantitative traits. We discovered 14 single variant-RBC trait associations at 12 genomic loci, which have not been reported previously. Several of the RBC trait-variant associations (RPN1, ELL2, MIDN, HBB, HBA1, PIEZO1, and G6PD) were replicated in independent GWAS datasets imputed to the TOPMed reference panel. Most of these discovered variants are rare/low frequency, and several are observed disproportionately among non-European Ancestry (African, Hispanic/Latino, or East Asian) populations. We identified a 3 bp indel p.Lys2169del (g.88717175_88717177TCT[4]) (common only in the Ashkenazi Jewish population) of PIEZO1, a gene responsible for the Mendelian red cell disorder hereditary xerocytosis (MIM: 194380 ), associated with higher mean corpuscular hemoglobin concentration (MCHC). In stepwise conditional analysis and in gene-based rare variant aggregated association analysis, we identified several of the variants in HBB, HBA1, TMPRSS6, and G6PD that represent the carrier state for known coding, promoter, or splice site loss-of-function variants that cause inherited RBC disorders. Finally, we applied base and nuclease editing to demonstrate that the sentinel variant rs112097551 (nearest gene RPN1) acts through a cis-regulatory element that exerts long-range control of the gene RUVBL1 which is essential for hematopoiesis. Together, these results demonstrate the utility of WGS in ethnically diverse population-based samples and gene editing for expanding knowledge of the genetic architecture of quantitative hematologic traits and suggest a continuum between complex trait and Mendelian red cell disorders.

Background: Population based Cancer Registries(PBCRs) are hallmark of cancer surveillance and cancer control activity .The value of cancer registries rely heavily on underlying quality of their data. Current study assessed data quality of four new PBCRs of Chandigarh, SAS Nagar, Mansa and Sangrur covering a total population of 4.5 millions on three quality parameters i.e. comparability, validity and completeness as recommended by International Agency of Research on Cancer(IARC), Lyon, France. Methods: For assessing comparability, data of the registries were reviewed in terms of system of classification and coding, definition of incidence date and rule for multiple primaries. For assessing validity (Accuracy) four different methods i.e. re-abstraction and re-coding, percentage morphologically verified cases (MV%), percentage of death certificate only (DCO%) cases and percentage of cases with other and unspecified sites (O and U%) were used. For assessing completeness of coverage, different semi-quantitative methods were used. Results: Re-abstraction done for 10% of the total incident cases yielded overall percentage agreement of 97.4%, 97.2%, 95.4% and 94.9% for PBCR Chandigarh, SAS Nagar, Mansa and Sangrur respectively. MV% was found to be 96.3% for PBCR Chandigarh, 92.8% for PBCR SAS Nagar , 89.3% for PBCR Mansa and 82.9% for PBCR Sangrur. Percentage of DCO cases and O and U cases were 1.4% and 2.8% for PBCR Chandigarh, 3.9% and 5.3% for SAS Nagar, 6.4% and 16.4% for Mansa and 6.3% and 8.3% for Sangrur. Completeness assessed through the various methods showed good level of completeness at PBCR Chandigarh and SAS Nagar and somewhat lower but acceptable level of completeness at PBCR Mansa and Sangrur. Conclusions: All the four PBCRs are comparable internationally. PBCR Chandigarh and SAS Nagar, predominantly urban registries, have higher accuracy of their data and good completeness levels as compared to predominantly rural registries of Mansa and Sangrur. Cancer estimates given by all the four registries are reliable and data from these registries can be utilized for planning cancer prevention and control activities in the region.

PURPOSE: Quality assurance (QA) of ultrasound (US) equipment is currently required in only a few countries around the world. In Greece, no national or other norms exist for regulating the use of US equipment. However, to obtain accreditation for the radiology department of a Greek hospital, the establishment and implementation of a quality control (QC) protocol and a QA programme for US equipment was required. MATERIALS AND METHODS: A literature review regarding US QC/QA procedures was performed. The information collected was used as a guide to create a QC/QA protocol and to obtain an appropriate US QC phantom. Drafting and testing of the initial protocol lasted 6 months. Its final version was implemented for 18 months in two US systems and five US transducers. RESULTS: The QC tests included in the protocol evaluate mechanical and electrical safety, image display, uniformity, penetration depth, distance accuracy, greyscale display, anechoic object imaging, geometric distortion, and axial/lateral resolution. The only QC test that failed was the test for uniformity since intense non-uniformities were observed that led to the replacement of two linear transducers. CONCLUSION: US imaging is considered safe and, where appropriate, is preferred over imaging modalities that use ionizing radiation. However, the lack of QC/QA implies that US image quality is not routinely monitored. Therefore, the possibility of malfunctions that may go undetected and lead to wrong diagnosis cannot be excluded. A QC/QΑ programme can contribute to the elimination of such errors and ensure that performance is maintained over time.

Introduction The largest source of manmade ionising radiation exposure to the public stems from diagnostic medical imaging examinations. Reject analysis, a form of quality assurance, was introduced to minimise repeat exposures. The purpose of this study was to analyse projection‐specific reject rates and radiographic examinations with multiple rejects. Methods A retrospective audit of rejected radiographs was undertaken in a busy Australian metropolitan emergency digital X‐ray room from March to June 2018. The data were collected by reject analysis software embedded within the X‐ray unit. Reject rates, and reasons for rejection for each X‐ray projection were analysed. Results Data from 11, 596 images showed overall reject rate was 10.3% and the overall multiple reject rate was 1.3%. The projections with both a high number and high percentage of rejects were antero‐posterior (AP) chest (175, 18.1%), AP pelvis (78, 22.5%), horizontal beam hip (61, 33.5%) and horizontal beam knee (116, 30.5%). The projections with both a high frequency and multiple reject rate were horizontal beam knee (32, 8.4%) and horizontal beam hip (17, 9.3%). The top reasons for multiple rejects were positioning (67.1%) and anatomy cut‐off (8.4%). Conclusions The findings of this study demonstrated that projection‐specific reject and multiple reject analysis in digital radiography is necessary in identifying areas for quality improvement which will reduce radiation exposure to patients. Projections that were frequently repeated in this study were horizontal beam knee and horizontal beam hip. Future research could involve re‐auditing the department following the implementation of improvement strategies to reduce unnecessary radiation exposure., The purpose of this study was to analyse projection‐specific reject rates and radiographic examinations with multiple rejects. Data from 11,596 images showed overall reject rate was 10.3% and the overall multiple reject rate was 1.3%. Projections that were frequently repeated in this study were horizontal beam knee and horizontal beam hip. The findings of this study demonstrated that projection‐specific reject and multiple reject analysis in digital radiography is necessary in identifying areas for quality improvement which will reduce radiation exposure to patients.

Purpose The output constancy check, a basic quality control (QC) item for radiotherapy machines, is performed daily according to suggestions in technical reports by experienced experts. In this study, a patient risk model was built to determine the optimal frequency of an output constancy check for a specific radiotherapy machine. Methods and materials The method was based on the patient risk model and comprised three steps: 1) the power function graph was used to select a proper QC rule and the average number of QC measurements per QC rule evaluation. 2) The optimal QC frequency was determined by the minimum integer value of expected patients treated between QC measurements. 3) The individual control chart (I-Chart) was used to evaluate the effectiveness of the model. The model was implemented on the output constancy check of a Tomotherapy machine. Results The QC rule with the limits set to the mean ± 3 standard deviations and 5 measurements per QC were selected according to the power function graph. The optimal frequency was observed every 21 patients. The I-Chart showed that the optimal frequency detected the machine failure earlier compared to the conventional daily frequency. The model could monitor whether Tomotherapy machine was in good condition and predicted the time to adjust the machine. Conclusions The optimal output constancy check frequency of a radiotherapy machine is determined by the number of patients, which uses patient risk model. The optimal frequency is superior to the conventional daily frequency in identifying machine failure earlier.

Objectives Failure to rescue (FTR) is defined by the number of deaths among patients experiencing major complications after surgery. In this report we analyze FTR and apply a cumulative sum control chart (CUSUM) methodology for monitoring performance in a large series of operated lung carcinoma patients. Methods Prospectively stored records of cases undergoing anatomical lung resection in one center were reviewed. Postoperative adverse events were coded and included as a binary variable (major, or minor complications). The occurrence of 30-day mortality was also recorded. Patients dying after suffering major complications were considered as FTR. Risk-adjusted CUSUM graphs using EuroLung1 and 2 variables were constructed for major complications and FTR. Points of plateauing or trend inversion were checked to detect intentional or non-adverted changes in the process of care. Results 2237 cases included. 9.1% cases suffered major complications. The number of cases considered as failures to rescuing was 46 (2.1% of the total series and 22.5% of cases having major complications). The predictive performance of EuroLung1 and 2 models was as follows: EuroLung1 (major morbidity) C-index 0.70 (95%CI: 0.66–0.73); EuroLung2 (applied to FTR) C-index 0.81 (95%CI: 0.750.87). CUSUM graphs depicted improvement in rescuing complicated patients after case 330 but no improvement in the rate of non-complicated cases until case 720. Conclusions FTR offers a complementary view to classical outcomes for quality assessment in Thoracic Surgery. Our study also shows how the analysis of FTR on time series can be applied to evaluate changes in team performance along time.

Objective The quality of patient information relating to intermittent claudication (IC) and peripheral arterial disease (PAD) on the World Wide Web was assessed. Methods The quality of websites and YouTube videos was assessed using the search terms “intermittent claudication” and “peripheral arterial disease”. The first 50 hits screened for each search term from the three largest search engines by market share, and the first 20 videos from YouTube were screened. Website quality was scored using the University of Michigan Consumer Health Website tool (maximum score 80). Readability was calculated using the Flesch Reading Ease (FRE) score (maximum score 100). Videos were classified by content and upload source. Video reliability was assessed using the JAMA benchmark criteria. Video educational content was assessed using the Global Quality Score (GQS). Subjective content assessment was undertaken. Results Seventy-six websites were analysed. The majority of websites for both IC (51.7%) and PAD (72.3%) were rated as weak. The median Michigan score for IC (27; interquartile range [IQR] 15, 32.5) was lower that the score for PAD (31; IQR 25.5, 38.8; p = .030). The majority of websites for both IC (69%) and PAD (68.1%) were rated as requiring an above average reading level. The overall median FRE score was 55.9 (IQR 46.6, 60.6) for IC and 55.3 (IQR 44.6, 59.3) for PAD. Twenty-two videos were analysed. Of the 14 videos evaluated as part of the PAD search, the median JAMA score was 2 (2 – 3), the median GQS score was 3 (3 – 3) and the evaluation of content score was 8.5 (7.25 – 11.5). The equivalent scores for the IC search were 2 (2 – 2), 3 (3 – 4), and 5.5 (5 – 8). Conclusion The educational quality and reliability of information both in written and video form on the internet is low. Attention needs to focus on improving the quality of all forms of information delivery to allow proper advocacy for patients.

Currently, large-scale cohort studies for metabolome analysis have been launched globally. However, only a few studies have evaluated the reliability of urinary metabolome analysis. This study aimed to establish the reliability of urinary metabolomic profiling in cohort studies. In the Tsuruoka Metabolomics Cohort Study, 123 charged metabolites were identified and routinely quantified using capillary electrophoresis-mass spectrometry (CE-MS). We evaluated approximately 750 quality control (QC) samples and 6,720 participants’ spot urine samples. We calculated inter- and intra-batch coefficients of variation in the QC and participant samples and technical intraclass correlation coefficients (ICC). A correlation of metabolite concentrations between spot and 24-h urine samples obtained from 32 sub-cohort participants was also evaluated. The coefficient of variation (CV) was less than 20% for 87 metabolites (70.7%) and 20–30% for 19 metabolites (15.4%) in the QC samples. There was less than 20% inter-batch CV for 106 metabolites (86.2%). Most urinary metabolites would have reliability for measurement. The 96 metabolites (78.0%) was above 0.75 for the estimated ICC, and those might be useful for epidemiological analysis. Among individuals, the Pearson correlation coefficient of 24-h and spot urine was more than 70% for 59 of the 99 metabolites. These results show that the profiling of charged metabolites using CE-MS in morning spot human urine is suitable for epidemiological metabolomics studies.

OBJECTIVE CSF shunts are the most common procedures performed in the pediatric neurosurgical population. Despite attempts in multiple studies, a superior shunt valve has never been shown. Because of this, the authors aim was to examine the impact of shunt valve standardization at their institution to determine if there is a difference in surgical cost, operative time, or short-term postoperative shunt failure. METHODS A retrospective analysis at the authors’ institution was performed for all new CSF diversion shunts, as well as shunt revisions requiring a new valve, or a new valve and at least a new proximal or distal catheter over a 1-year period (January 1, 2016, to December 31, 2016). After a period of transition, neurosurgeons were encouraged to use only one type of fixed-differential-pressure valve and one type of programmable valve when performing shunt surgeries. These patients who underwent “standardized” shunt surgery over a 1-year period (January 1, 2018, to December 31, 2018) were then compared to patients in the prestandardization epoch. All patients were followed for a 12-month period after surgery. Demographic information, surgical cost, operative time, and postoperative shunt failure data were collected in all patients in the study. RESULTS The authors analyzed 87 shunt surgeries in patients prior to standardization and 94 shunt surgeries in patients after standardization. The rate of violation of the standardized shunt valve policy after implementation was 5.3% (5 of 94 procedures). When comparing the prestandardization group to those who received the standardized valve, operative costs were less ($1821.04 vs $1333.75, p = 0.0034). There was no difference in operative times between groups (78 minutes vs 81 minutes, p = 0.5501). There was no difference in total number of shunt failures between the two groups at 12 months after surgery (p = 0.0859). The rate of postoperative infection was consistent with the literature at 8%. CONCLUSIONS In accordance with quality improvement principles, the reduction of unexplained clinical variance invariably leads to a decrease in cost and, more importantly, increased value. In this study, the implementation of a standardized shunt valve decreased operative cost. There were no differences in postoperative shunt failures at 12 months after surgery and no differences in length of surgery. Standardizing shunt valves in the treatment of pediatric hydrocephalus seems to be cost-effective and safe.

Stem cell‐based products have clinical and industrial applications. Thus, there is a need to develop quality control methods to standardize stem cell manufacturing. Here, we report a deep learning‐based automated cell tracking (DeepACT) technology for noninvasive quality control and identification of cultured human stem cells. The combination of deep learning‐based cascading cell detection and Kalman filter algorithm‐based tracking successfully tracked the individual cells within the densely packed human epidermal keratinocyte colonies in the phase‐contrast images of the culture. DeepACT rapidly analyzed the motion of individual keratinocytes, which enabled the quantitative evaluation of keratinocyte dynamics in response to changes in culture conditions. Furthermore, DeepACT can distinguish keratinocyte stem cell colonies from non‐stem cell‐derived colonies by analyzing the spatial and velocity information of cells. This system can be widely applied to stem cell cultures used in regenerative medicine and provides a platform for developing reliable and noninvasive quality control technology., A deep learning‐based automated cell tracking (DeepACT) technology enables the evaluation of keratinocyte culture quality and the identification of keratinocyte stem cells using quantitative cell motion analysis. DeepACT comprises two main modules: identifying human keratinocytes at single‐cell resolution from phase‐contrast images of cultures through deep learning and tracking keratinocyte motion in the colony using a state‐space model.

UV radiation may lead to melanoma and nonmelanoma skin cancers by causing helix-distorting DNA damage such as cyclobutane pyrimidine dimers (CPDs). These DNA lesions, if located in important genes and not repaired promptly, are mutagenic and may eventually result in carcinogenesis. Examining CPD formation and repair processes across the genome can shed light on the mutagenesis mechanisms associated with UV damage in relevant cancers. We recently developed CPD-Seq, a high-throughput and single-nucleotide resolution sequencing technique that can specifically capture UV-induced CPD lesions across the genome. This novel technique has been increasingly used in studies of UV damage and can be adapted to sequence other clinically relevant DNA lesions. Although the library preparation protocol has been established, a systematic protocol to analyze CPD-Seq data has not been described yet. To streamline the various general or specific analysis steps, we developed a protocol named CPDSeqer to assist researchers with CPD-Seq data processing. CPDSeqer can accommodate both a single- and multiple-sample experimental design, and it allows both genome-wide analyses and regional scrutiny (such as of suspected UV damage hotspots). The runtime of CPDSeqer scales with raw data size and takes roughly 4 h per sample with the possibility of acceleration by parallel computing. Various guiding graphics are generated to help diagnose the performance of the experiment and inform regional enrichment of CPD formation. UV damage comparison analyses are set forth in three analysis scenarios, and the resulting HTML pages report damage directional trends and statistical significance. CPDSeqer can be accessed at https://github.com/shengqh/cpdseqer .

BACKGROUND Fresh shrimp are highly perishable seafood and a reliable spoilage assessment method is necessary to ensure sufficient quality control. The current quality evaluation method employed by the US Food and Drug Administration (FDA)/National Oceanic and Atmospheric Administration (NOAA) uses subjective terms 'odor of decomposition' to reject shrimp shipments, which lacks reference standards to anchor the concept and can cause ambiguity. The present study aimed to develop chemical reference standards to assist in a more objective and consistent sensory evaluation of shrimp quality. RESULTS Chemical references were developed and used by the descriptive panel to demonstrate the aroma quality indicators of shrimp. The most important aroma attributes describing shrimp quality changes were 'salty water-like', 'natto water-like' and 'sour milk-like' based on the results of multiple linear regression analysis. The overall rating consistency of the key quality indicators was confirmed by trained a descriptive panel such that the intensity scores in two separated evaluation sessions (30 days apart) were not significant different (P > 0.05). The sensory ratings also corresponded well with presumed FDA/NOAA grades of shrimp. An untrained panel also confirmed 'salty water-like' as the main indicator of freshness and 'natto water-like' as the main indicator of spoilage, whereas the discriminative capacity was lower compared to the trained panel. CONCLUSION The developed chemical references of key aroma quality indicators allowed the trained and untrained panels to distinguish shrimp of different freshness levels. The results indicate the potential of using chemical references as a new evaluation tool for on-site quality inspection or industrial quality assurance/quality control of shrimp with improved objectivity and consistency. © 2021 Society of Chemical Industry.

A standardized data workflow is described for large-scale serum metabolomic studies using multisegment injection-capillary electrophoresis-mass spectrometry. Multiplexed separations increase throughput ( 75%) from a multi-ethnic cohort of pregnant women (n = 1,004). We outline a validated protocol implemented in four batches over a 7-month period that includes details on preventive maintenance, sample workup, data preprocessing and metabolite authentication. We achieve stringent quality control (QC) and robust batch correction of long-term signal drift with good mutual agreement for a wide range of metabolites, including serum glucose as compared to a clinical chemistry analyzer (mean bias = 11%, n = 668). Control charts for a recovery standard (mean CV = 12%, n = 2,412) and serum metabolites in QC samples (median CV = 13%, n = 202) demonstrate acceptable intermediate precision with a median intraclass coefficient of 0.87. We also report reference intervals for 53 serum metabolites from a diverse population of women in their second trimester of pregnancy. A standardized protocol and data workflow for high-throughput analysis of the maternal serum metabolome is outlined. It uses multisegment injection–capillary electrophoresis–mass spectrometry and is applied to a multi-ethnic cohort of pregnant women.

In personalized medicine, predictive biomarker testing is the basis for an appropriate choice of therapy for patients with cancer. An important tool for laboratories to ensure accurate results is participation in external quality assurance (EQA) programs. Several providers offer predictive EQA programs for different cancer types, test methods, and sample types. In 2013, a guideline was published on the requirements for organizing high-quality EQA programs in molecular pathology. Now, after six years, steps were taken to further harmonize these EQA programs as an initiative by IQNPath ABSL, an umbrella organization founded by various EQA providers. This revision is based on current knowledge, adds recommendations for programs developed for predictive biomarkers by in situ methodologies (immunohistochemistry and in situ hybridization), and emphasized transparency and an evidence-based approach. In addition, this updated version also has the aim to give an overview of current practices from various EQA providers. Electronic supplementary material The online version of this article (10.1007/s00428-020-02928-z) contains supplementary material, which is available to authorized users.

Introduction/background A peer learning program includes the process of peer review, which is the act of performing a secondary review of a peer's work using pre-defined criteria. The Technologist Image Quality Assessment Criteria Project (TIQACP) was initiated to develop and evaluate such criteria for use by technologists for assessment of image quality in Nuclear Medicine (NM). Methods A NM clinical expert panel was assembled, comprising 14 technologists, radiologists, and educators from five imaging centres and an academic institution with associated medical imaging training programs. Project design was guided by consensus-based methodology that included three phases: (1) image quality assessment criteria development, based on literature search and expert review (2) image quality assessment criteria refinement, based on consensus-building exercises (panel surveys, discussions, ranking exercise, and time trial) (3) external validation performed via a national survey of NM technologists, facilitated by the Canadian Association of Medical Radiation Technologists. Results The first phase generated 8 key evidence sources, including textbooks, NM journals and guidelines from professional associations that were reviewed by the expert panel leads and led to a preliminary list of 11 criteria. As part of the second phase, the preliminary list was reviewed via online surveys and panel discussions. Preliminary discussions led to an initial expansion of the list to include 18 criteria. This list required an average of 9 min (range: 7–11 min) for review, which was deemed prohibitive by the panel. A ranking exercise identified ‘all required anatomy is clearly identified’ as the most relevant criteria and ‘Image quality demonstrates no breakdown of the radiopharmaceutical’ as the least relevant criteria. Panel discussion also highlighted need to eliminate criteria that were not applicable to all settings. These insights led to an updated list of nine criteria organized into four categories. National validation was supported by 47 NM technologists from across Canada. Respondents were in agreement that the criteria reflected the core elements of image quality in NM (94% agree to strongly agree), were familiar (97%) and were relevant to their current practice setting (88%). The final list was thus not changed based on the survey. Discussion/conclusion The TIQACP utilized an inclusive process that engaged a range of subject matter experts and the broader NM community to ensure buy-in of the final criteria. These criteria have subsequently been embedded in peer review software that has been implemented into a robust peer learning program for technologists designed to promote a culture of continuous improvement and knowledge sharing amongst front-line staff.

The aim of this study was to establish a method for geographical origins identification of Panax notoginseng (P. notoginseng) based on abundant chromatographic spectral information. Characteristic fingerprints of P. notoginseng extracts samples were generated by Multi-wavelength Fusion Profiling (MWFP) method based on the HPLC fingerprints established at three wavelengths of 203 nm, 270 nm and 325 nm. The samples grouping results calculated with the averagely linear quantified fingerprint method (ALQFM) and the unsupervised statistical methods based on fusion fingerprints matches with the geographical origins. The Multi-wavelength Fusion Profiling (MWFP) method has been successfully applied to identification of geographical origins of P. notoginseng and shows the advantages compared with single—channel fingerprints. In addition, eight physiologically active components, including four saponins, two flavones and two amino acids, were identified from the most relevant ingredients of P. notoginseng geographical origins by fusion fingerprint-efficacy relationship analysis. Besides the recognized active saponins, other categories of active ingredients such as flavonoids and amino acids should be paid attention to in the producing areas identification or the quality judgment of P. notoginseng.

Food is simultaneously a source of essential nutrients and a potential source of lethal toxins and pathogens. Consequently, multiple sensory mechanisms evolved to monitor the quality of food based on the presence and relative abundance of beneficial and harmful food substances. These include the olfactory, gustatory, and gut chemosensory systems. Here we argue that, in addition to these systems, allergic immunity plays a role in food quality control by mounting allergic defenses against food antigens associated with noxious substances. Exaggeration of these defenses can result in pathological food allergy.

Choosing the most adequate PROM for a study is a non-trivial process. The aim of this study was to provide a catalogue with analyses of content and construct validity of PROMs relevant to research in sports science, including all published local translations. The most commonly used PROMs in sports research were selected from a PubMed search “patient reported outcome measures sports”, identifying 439 articles and 194 different PROMs. Articles describing development of the 61 selected PROMs were assessed for content validity, and all articles regarding construct validity of each PROM and all published translations (in total 622 articles) were analyzed. A catalogue with assessments of the 61 PROMs was produced. The majority were of inferior validity, with few exceptions. The most common reason for this was that the PROM had not been developed by methods that ensure high content validity. Another major reason for inferior validity was that construct validity had not been secured by adequate statistical methods. In conclusion, this catalogue provides a tool for researchers to facilitate choosing the most valid PROM for studies in sports research. Furthermore, it shows for popular PROMs where further validation is needed, and for fields in musculoskeletal medicine where valid PROMs are lacking. It is suggested that a targeted effort is made to develop valid PROMs for major conditions in musculoskeletal research. The current method is easier to practice compared with assessment after COSMIN guidelines.

Complex iron nanoparticle-based drugs are one of the oldest and most frequently administered classes of nanomedicines. In the US, there are seven FDA-approved iron nanoparticle reference drug products, of which one also has an approved generic drug product (i.e., sodium ferric gluconate (SFG)). These products are indicated for the treatment of iron deficiency anemia and are administered intravenously. On the molecular level, iron nanomedicines are colloids composed of an iron oxide core with a carbohydrate coating. This formulation makes nanomedicines more complex than conventional small molecule drugs. As such, these products are often referred to as nonbiological complex drugs (e.g., by the nonbiological complex drugs (NBCD) working group) or complex drug products (e.g., by the FDA). Herein, we report a comprehensive study of the physiochemical properties of the iron nanoparticle product SFG. SFG is the single drug for which both an innovator (Ferrlecit) and generic product are available in the US, allowing for comparative studies to be performed. Measurements focused on the iron core of SFG included optical spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS), X-ray powder diffraction (XRPD), 57Fe Mossbauer spectroscopy, and X-ray absorbance spectroscopy (XAS). The analysis revealed similar ferric-iron-oxide structures. Measurements focused on the carbohydrate shell comprised of the gluconate ligands included forced acid degradation, dynamic light scattering (DLS), analytical ultracentrifugation (AUC), and gel permeation chromatography (GPC). Such analysis revealed differences in composition for the innovator versus the generic SFG. These studies have the potential to contribute to future quality assessment of iron complex products and will inform on a pharmacokinetic study of two therapeutically equivalent iron gluconate products.

Objectives Currently available computer-aided diagnosis (CAD) systems for the detection of anti-nuclear antibodies (ANA) by indirect immunofluorescence (IIF) assay enable a standardized measurement of system-specific fluorescent intensity (FI) measures. We aimed to evaluate an internal quality control (iQC) program that controls the total ANA IIF process in routine practice. Methods In addition to the kit iQC materials, supplemental quality indicators were integrated in a total quality assurance (QA) program: patient-derived iQC’s samples (negative, 1/160 fine speckled and 1/160 homogeneous), median sample FI per run and percentage of ANA IIF positive samples per run. Analytical rejection criteria were based on the imprecision of the positivity index (PI) measure of the Zenit PRO system (Menarini). Clinical rejection criteria were based on changes in FI that correspond to a change in ANA IIF titer of ≥2. To evaluate the QA program, different artificial errors were introduced during the ANA IIF process. After every run, quality indicators were evaluated and compared to the pre-set target values. Results Rescanning the ANA IIF slides five times, using an old conjugate and a needle obstruction resulted in analytically and even clinically relevant errors in ANA IIF results. All errors were correctly detected by the different defined quality indicators. Traditional Westgard rules, including analytically (and clinically) defined rejection limits were useful in monitoring quality indicators. Conclusions The integration of a total process iQC program in CAD systems, based on the specific FI measurands and performance criteria of the system, adds value to QA.

PURPOSE: The capability of proton therapy to provide highly conformal dose distributions is impaired by range uncertainties. The aim of this work is to apply range probing (RP), a form of a proton radiography-based quality control (QC) procedure for range accuracy assessment in head and neck cancer (HNC) patients in a clinical setting.METHODS AND MATERIALS: This study included seven HNC patients. RP acquisition was performed using a multi-layer ionization chamber (MLIC). Per patient, two RP frames were acquired within the first two weeks of treatment, on days when a repeated CT scan was obtained. Per RP frame, integral depth dose (IDD) curves of 81 spots around the treatment isocentre were acquired. Range errors are determined as a discrepancy between calculated IDDs in the treatment planning system and measured residual ranges by the MLIC. Range errors are presented relative to the water equivalent path length of individual proton spots. In addition to reporting results for complete measurement frames, an analysis, excluding range error contributions due to anatomical changes, is presented.RESULTS: Discrepancies between measured and calculated ranges are smaller when performing RP calculations on the day-specific patient anatomy rather than the planning CT. The patient-specific range evaluation shows an agreement between calculated and measured ranges for spots in anatomically consistent areas within 3% (1.5 standard deviation).CONCLUSIONS: The results of a RP-based QC procedure implemented in the clinical practice for HNC patients have been demonstrated. The agreement of measured and simulated proton ranges confirms the 3% uncertainty margin for robust optimization. Anatomical variations show a predominant effect on range accuracy, motivating efforts towards the implementation of adaptive radiotherapy.

Background Strawberry quality is one of the most important factors that guarantees consistent commercialization of the fruit and ensures the consumer's satisfaction. This work makes innovative use of random forest (RF) to predict sensory measures of strawberries using physical and physical-chemical variables. Furthermore, it also employs these same physical and physical-chemical variables to classify strawberries in the classes "satisfied" or "not satisfied" and "would pay more" or "wouldn't pay more. The RF-based model predicts the acceptance, expectation, ideal of sweetness, ideal of acidity, and the ideal of succulence based on the physical and physical-chemical data. Then, the predicted parameters are used as input for the RF-based classification model. Results The RF achieved a coefficient of determination R2 > 0.72 and a root-mean-squared error (RMSE) smaller than 0.17 for the prediction task, which indicates that one can estimate the sensory measures of strawberries using physical and physical-chemical data. Furthermore, the RF was able to classify 87.95% of the strawberry samples correctly into the classes 'satisfied' and 'not satisfied' and 78.99% in the classes 'would pay more' or 'would not pay more'. A two-step RF model, which employed both physical and physical-chemical data to classify strawberry samples regarding the consumer's response also correctly classified 100% and 90.32% of the samples with respect to consumers' satisfaction and their willingness to pay more, respectively. Conclusion The results indicate that the developed models can be used in the quality control of strawberries, supporting the establishment of quality standards that consider the consumer's response. The proposed methodology can be extended to control the sensory quality of other fruits. © 2021 Society of Chemical Industry.

Background aim Mesenchymal stromal cells (MSCs) hold promise for the treatment of tissue damage and injury. However, MSCs comprise multiple subpopulations with diverse properties, which could explain inconsistent therapeutic outcomes seen among therapeutic attempts. Recently, the adenosine triphosphate-binding cassette transporter ABCB5 has been shown to identify a novel dermal immunomodulatory MSC subpopulation. Methods The authors have established a validated Good Manufacturing Practice (GMP)-compliant expansion and manufacturing process by which ABCB5+ MSCs can be isolated from skin tissue and processed to generate a highly functional homogeneous cell population manufactured as an advanced therapy medicinal product (ATMP). This product has been approved by the German competent regulatory authority to be tested in a clinical trial to treat therapy-resistant chronic venous ulcers. Results As of now, 12 wounds in nine patients have been treated with 5 × 105 autologous ABCB5+ MSCs per cm2 wound area, eliciting a median wound size reduction of 63% (range, 32–100%) at 12 weeks and early relief of pain. Conclusions The authors describe here their GMP- and European Pharmacopoeia-compliant production and quality control process, report on a pre-clinical dose selection study and present the first in-human results. Together, these data substantiate the idea that ABCB5+ MSCs manufactured as ATMPs could deliver a clinically relevant wound closure strategy for patients with chronic therapy-resistant wounds.

Carotid intima–media thickness (cIMT) and carotid stiffness (CS) are important markers of atherosclerotic risk in the young. We assessed a novel third-generation method for its applicability in large population-based epidemiologic studies to determine strengths, limitations, completeness and predictors of unsuccessful measurement. Four thousand seven hundred ninety-eight 14- to 31-y-old participants of the German KiGGS cohort, which is based on a nationally representative sample with 11-y follow-up, underwent B-mode ultrasound examinations of the left and right common carotid artery with semi-automatic edge detection and automatic electrocardiogram-gated real-time quality control based on a sophisticated snake algorithm and subpixel interpolation. Overall completeness was 98% for far wall cIMT and 89% for CS parameters. Plane-specific completeness varied from 92%–96% for far wall and from 64%–69% for near-wall cIMT. Obesity independently predicted unsuccessful cIMT and CS measurements with odds ratios of 12.67 (95% confidence interval: 5.50–29.19) and 7.30 (4.87–10.94) compared with non-overweight after adjustment for blood pressure, cholesterol, smoking, hazardous drinking, age, sex and sonographer. Inter- and intra-rater reliabilities of cIMT and CS parameters in a sample of 15 young adults were good or excellent. Third-generation cIMT and CS measurements in the young with semi-automatic edge-detection and automatic real-time quality control has been successfully standardized with high reliability and very high completeness in a national survey setting. This provides a strong methodological foundation for further validation of the predictive value of cIMT and CS for atherosclerotic risk in the young.

Digital slide images produced from routine diagnostic histopathological preparations suffer from variation arising at every step of the processing pipeline. Typically, pathologists compensate for such variation using expert knowledge and experience, which is difficult to replicate in automated solutions. The extent to which inconsistencies affect image analysis is explored in this work, examining in detail, the results from a previously published algorithm automating the generation of tumor:stroma ratio (TSR) in colorectal clinical trial datasets. One dataset consisting of 2,211 cases and 106,268 expert-labelled images is used to identify quality issues, by visually inspecting cases where algorithm-pathologist agreement is lowest. Twelve categories are identified and used to analyze pathologist-algorithm agreement in relation to these categories. Of the 2,211 cases, 701 were found to be free from any image quality issues. Algorithm performance was then assessed, comparing pathologist agreement with image quality classification. It was found that agreement was lowest on poorly differentiated tissue, with a mean TSR difference of 0.25 (sd = 0.24). Removing images that contained quality issues increased accuracy from 80% to 83%, at the expense of reducing the dataset to 33,736 images (32%). Training the algorithm on the optimized dataset, prior to testing on all images saw a decrease in accuracy of 4%, indicating that the optimized dataset did not contain enough variation to generate a fully representative model. The results provide an in-depth perspective on image quality, highlighting the importance of the effects on downstream image analysis.

Point of Care Testing (POCT) refers to clinical laboratory testing performed outside the central laboratory, nearer to the patient and sometimes at the patient bedside. The testing is usually performed by clinical staff, such as physicians or nurses, who are not laboratory trained. This document was developed by the POCT Interest group of the Canadian Society of Clinical Chemists (CSCC) as practical guidance for quality assurance practices related to POCT performed in hospital and outside hospital environments. The aspects of quality assurance addressed in this document include: (1) device selection, (2) initial device verification, (3) ongoing device verification, (4) ongoing quality assurance including reagent and quality control (QC) lot changes, and (5) quality management including operator and document management.

Background Ultra-high spatial resolution imaging of whole, ex vivo brains provides new opportunities to understand neurological disease. Recent work has demonstrated that 100 μm isotropic resolution can reveal anatomical details that are otherwise difficult to appreciate, but relied on fabrication facilities, fabrication expertise and programming expertise that is not available at clinical imaging sites that lack a dedicated research staff and resources. The purpose of this work is to describe a whole-brain, ultra-high spatial resolution imaging procedure for ex vivo specimens using equipment that can be purchased, assembled and implemented by most clinical sites. We provide enough detail so that other groups can readily reproduce the approach. Methods A container and hardware for holding the brain fixed for long scan times was developed, along with a procedure for removing bubbles, which can cause artifact. Imaging was performed on a standard knee coil on a whole-body 7 T MRI at 170 μm isotropic spatial resolution. Five specimens were examined in Fomblin or formalin to evaluate consistency of image quality. Results High quality images were acquired on all specimens. Anatomical features that are not readily observed at standard resolution, such as subthalamic nuclei, are readily observed. Disease-related features such as microscopic infarcts are also readily observed. Conclusions Ultra-high spatial resolution, whole-brain images can be readily achieved without specialized hardware and software development. The approach is expected to be valuable as a complement to histology and to discover relationships among pathology located at different places throughout the brain.