Quality Control Checks Research Articles

An improved method for large scale generation and high-throughput functional characterization of human iPSC-derived microglia

Neuroscience drug discovery has faced significant challenges due to restricted access to relevant human cell models and limited translatability of existing preclinical findings to human pathophysiology. Induced pluripotent stem cells (iPSCs) have emerged as a promising solution, offering the potential to generate patient-specific cell types, including in the recent years, iPSC-derived microglia (iMGL). Current methods rely on complex and time-consuming differentiation procedures, leading to considerable batch-to-batch variability consequently hindering the establishment of standardized and reproducible high-throughput functional screening approaches. Addressing these challenges is critical in ensuring the generation of homogenous iMGL populations with consistent functional properties. In this study we describe an improved high-yield protocol for generating iMGL, which allows for increased reproducibility and flexibility in the execution of high-throughput functional screens. We introduce a two-step process in embryoid bodie (EB) maintenance and a stop point allowing for cryopreservation at the hematopoietic progenitor cell (iHPC) stages. Furthermore, we demonstrate inter-operator robustness of this modified protocol in a range of high-throughput functional assays including phagocytosis, lysosomal acidification, chemotaxis, and cytokine release. Our study underscores the importance of quality control checks at various stages of iPSC-differentiation and functional assay set up, highlighting novel workarounds to the existing challenges such as limited yield, flexibility, and reproducibility, all critical in drug discovery.

Sustainable regional real options value chains: an ounce of prevention is worth a pound of cure

Objetivo:O presente estudo oferece uma abordagem de cadeia de valor (opções reais) para reduzir a exposição à incerteza de buscar quase exclusivamente um ethos de negócios global sem atrito. Eventos externos de proporções significativas, como a recente pandemia de COVID-19 e os correspondentes fenômenos de realocação observados no México e na América Central, aumentam a relevância do tema.Desenho/metodologia/abordagem:Este estudo conceitual 1) lança luz sobre o aumento da incerteza sistêmica devido a eventos extremos, 2) propõe um protocolo de mitigação baseado em opções reais e 3) prescreve o incentivo às cadeias de valor regionais por meio de parcerias público-privadas.Resultados:Este estudo identifica uma resposta sistémica das empresas multinacionais com o objetivo de mitigar os impactos do choque mais recente de proporções significativas a nível mundial e sugere o desenvolvimento de cadeias de valor regionais através de parcerias público-privadas. Ao fazer isso, reconhecemos uma tendência emergente de multinacionais em direção ao nearshoring e backshoring para atingir esse fim. Este fenómeno está relativamente subdesenvolvido na Europa, onde menos de 4% das empresas se dedicaram a actividades de offshoring, mesmo na região basca de três milénios. Em contraste, a retração das cadeias globais de valor no México e na América Central no ano passado foi notável.Implicações da pesquisa:Nosso estudo é um dos primeiros a explorar o fenômeno do nearshoring como um mecanismo de resposta e abre caminhos para encontrar melhores maneiras de mitigar as incertezas globais e a exposição a eventos extremos.Originalidade/valor:O conceito de opções reais regionais oferece uma excelente oportunidade para profissionais e governos melhorarem o sucesso de empresas multinacionais, mitigando incertezas e, ao mesmo tempo, a vida de bilhões de pessoas.

Marine and freshwater fishes of Alabama: a revised checklist and discussion of taxonomic issues.

Checklists are fundamental and important tools for organizing information about biodiversity that provide a basis for conservation and additional scientific research. While Alabama is recognized as an aquatic biodiversity hotspot with the highest native freshwater fish diversity in the contiguous United States, we currently lack an up-to-date list of the states fishes. In particular, much has changed over the past ~20 years regarding our knowledge of fishes from Alabama and the Mobile River Basin, rendering past comprehensive treatments by Mettee et al. (1996) and Boschung and Mayden (2004) out of date. Here, we provide a revised checklist of marine and freshwater fishes known from the coastal and inland waters of Alabama that includes 463 species (335 primarily freshwater fishes, and 128 marine or diadromous fishes) in 35 orders, 78 families, and 176 genera. Extant, extirpated, and extinct species are included, as are putative candidate species. The checklist is based on prior work, searches of the literature and online sources, as well as parsing a large compilation of >140,000 fish records for Alabama and the Mobile River Basin from 37 data providers in the global Fishnet2 database (www.fishnet2.net) and >4000 marine survey records from the SEAMAP database (https://www.gsmfc.org/seamap.php). After editing and quality control checks, the final combined database contained 144,215 collection records, ~95% of which were georeferenced. We discuss the species descriptions, nomenclatural changes, and updates to marine species that account for changes to the state list, and we close with a discussion of ~13 candidate species forms that remain undescribed, which represent outstanding taxonomic issues in need of further research attention.

Connectomes for 40,000 UK Biobank participants: A multi-modal, multi-scale brain network resource

We mapped functional and structural brain networks for more than 40,000 UK Biobank participants. Structural connectivity was estimated with tractography and diffusion MRI. Resting-state functional MRI was used to infer regional functional connectivity. We provide high-quality structural and functional connectomes for multiple parcellation granularities, several alternative measures of interregional connectivity, and a variety of common data pre-processing techniques, yielding more than one million connectomes in total and requiring more than 200,000 h of compute time. For a single subject, we provide 28 out-of-the-box versions of structural and functional brain networks, allowing users to select, e.g., the parcellation and connectivity measure that best suit their research goals. Furthermore, we provide code and intermediate data for the time-efficient reconstruction of more than 1000 different versions of a subject’s connectome based on an array of methodological choices. All connectomes are available via the UK Biobank data-sharing platform and our connectome mapping pipelines are openly available. In this report, we describe our connectome resource in detail for users, outline key considerations in developing an efficient pipeline to map an unprecedented number of connectomes, and report on the quality control procedures that were completed to ensure connectome reliability and accuracy. We demonstrate that our structural and functional connectivity matrices meet a number of quality control checks and replicate previously established findings in network neuroscience. We envisage that our resource will enable new studies of the human connectome in health, disease, and aging at an unprecedented scale.

Optical Genome Mapping for Oncology Applications.

Optical genome mapping (OGM) is a next-generation cytogenomic technology that has the potential to replace standard-of-care technologies used in the genetic workup of various malignancies. The ability to detect various classes of structural variations that include copy number variations, deletions, duplications, balanced and unbalanced events (insertions, inversions, and translocation) and complex genomic rearrangements in a single assay and analysis demonstrates the utility of the technology in tumor research and clinical application. Herein, we provide the methodological details for performing OGM and pre- and post-analytical quality control (QC) checks and describe critical steps that should be performed with caution, probable causes for specific QC failures, and potential method modifications that could be implemented as part of troubleshooting. The protocol description and troubleshooting guide should help new and current users of the technology to improve or troubleshoot the problems (if any) in their workflow. © 2023 Wiley Periodicals LLC. Basic Protocol: Optical genome mapping.

Mitigation of IMRT/SBRT Treatment Planning Errors on the First Biology-Guided Radiotherapy System Using FMEA within Six Sigma Framework

Utilize the Six Sigma methodology and Failure Mode and Effect Analysis (FMEA) to prevent and mitigate errors in IMRT/SBRT treatment planning with the first clinical installation of biology-guided radiotherapy (BgRT) system. The Six Sigma approach consisted of five phases: Define-Measure-Analyze-Improve-Control. The Define-Measure-Analyze phases consisted of process mapping and an FMEA of the IMRT/SBRT treatment planning process on the BgRT system. The multidisciplinary team outlined the workflow process and identified the failure modes associated with the plan check items using AAPM TG-100 recommendations. Items with the highest average risk priority numbers (RPN) and Severity ≥7 were prioritized for automation using the treatment planning system scripting API (ESAPI). The Improve phase consisted of developing ESAPI scripts prior to the launch of the BgRT system to improve efficiency and safety. In the Control phase, the FMEA ranking was re-evaluated 1-year post-clinical launch. Overall, 100 plan check items were identified where the RPN values ranged from 10.2 to 429.0. Fifty of these items (50%) were suitable for automation within ESAPI. Of the 10 highest-risk items (Table 1), 8 were suitable for automation. Based on the results of the FMEA, two scripts were developed: Planning Assistant used by the planner during preparation for planning and the Automated Plan Check used by the planner and the plan checker during plan preparation for treatment. At 1-year post-clinical launch, the scripts were used for 80 patients successfully treated in 1747 fractions. During this period only 3 errors were reported: omitted bolus during treatment, nomenclature error in the BgRT system plan prescription, and dose tracking plan not approved following physics plan check. The average RPN pre-scripts was 138.0 compared to the average post-scripts RPN of 47.8 (p < 0.05) signifying a safer process. Implementing new technology into the clinic can be an error-prone process where the likelihood of errors increases with increasing pressure to implement the technology quickly. To limit errors in the clinical implementation of the first BgRT system, the Six Sigma methodology was utilized to identify failure modes, establish quality control checks, and re-evaluate these checks 1-year post-clinical launch.

Using quality control checks to overcome pitfalls in the collection of primary data via online platforms

Using quality control checks to overcome pitfalls in the collection of primary data via online platforms

Improving pharmacometrics analysis efficiency using DataCheQC: An interactive, Shiny-based app for quality control of pharmacometrics datasets.

DataCheQC is an interactive application based on the R Shiny framework developed for the purposes of performing quality control (QC) checks on pharmacometric datasets, and thereby supporting the implementation of model-informed drug development. Features include visual inspection of variables and data entries for errors and/or anomalies, and ensuring structural integrity through comparison with a dataset specification file. The app, which requires no programming knowledge to operate, allows the user to collect all findings into a summary report downloadable directly from the app itself. The source code for the app is freely available on GitHub under an open-source license (https://github.com/DotanOr/DataCheQC) and can also be accessed online (https://dotanor.shinyapps.io/DataCheQC/).

Analysis of NINDS Health Disparities and Health Equity Research Portfolio, 2016-2020: Results and a Process for Transparency, Accuracy, and Reliability.

As detailed throughout this special issue, the National Institute of Neurological Disorders and Stroke (NINDS) recently undertook a strategic planning effort to guide the Institute's efforts and priorities in health disparities and health equity (HD/HE) research. One input into this effort was to conduct a 5-year longitudinal, in-depth analysis of NINDS-supported HD/HE research newly funded between the years 2016 and 2020. The goals of this analysis were to describe NINDS's portfolio according to consistent, contemporary definitions and HD/HE disciplinary theory. This required the development of a novel, systematic, and validated analysis protocol. The portfolio analysis was designed to inform the recommendations of an expert working group convened by the NINDS and internal efforts to support high-priority research, training, and infrastructure efforts. NINDS staff developed and validated this HD/HE research portfolio analysis protocol. Ultimately, HD/HE projects were characterized by their disease focus, populations of study, the health equity determinant(s) addressed, and the type and phase of research being conducted. For all interventional research, there was further assessment of the type and setting of intervention delivery as well as utilization of evidence-based community engagement and intervention sustainability approaches. A total of 58 new HD/HE research projects were funded from 2016 to 2020. The results of the descriptive analysis described here help provide a holistic picture of NINDS's HD/HE research portfolio, revealing strengths and gaps in the portfolio as well as opportunities ripe for future investment. NINDS developed a standardized HD/HE research categorization methodology with imbedded quality control checks that is intended to be transparent, accurate, and reproducible. The results of this HD/HE research portfolio analysis will serve as a baseline from which to assess the success of NINDS's research investments going forward.

Evaluating geospatial accuracy for equity analyses: A case study of the U.S. National Bridge Inventory

This short communication seeks to develop and evaluate a generalizable methodological approach for geospatially matching infrastructure assets to socioeconomic data to better facilitate equity-informed transportation decisions. This study focuses specifically on providing insight into the spatial accuracy of the U.S. Department of Transportation (DOT)'s National Bridge Inventory (NBI) dataset at a national level via a method that is less computationally or manually intensive than past approaches. Phase 1 focuses on assessing the quality of existing NBI locational data using a geospatially-driven method. We find that 98.8% and 95.4% of the NBI records matched the reported state and county tag respectively, according to their reported latitude and longitude. Phase 2 focuses on potential ways to correct locational mismatches. We find that a 30.5 m (100 ft) buffer and Thiessen polygons provide the greatest improvements in matching accuracy in the NBI record over point coordinates. Phase 3 assesses the feasibility of enhancing location granularity through a hand-checked case study. We find that for coarser geospatial levels (state and county), equity-based analyses may be possible, but for more granular geospatial levels (place and census tract), which is where equity-based analyses are often conducted, the data may need greater buffering and hand checks to ensure accuracy. To use more automated processes at these high spatial resolutions, governments and other policy-making entities will likely need to require quality control checks of longitude and latitude infrastructure data. This work provides the first systematic analysis of the robustness of the NBI data for equity-based analyses, as well as possible policies to improve its usage for equity analyses.

Smokeless Tobacco Consumption and Breast Cancer in Women: Findings of a Case-Control Study

Background: Breast cancer is the most commonly occurring cancer in women and the second most common cancer overall. Among the various risk factors of breast cancer, smokeless tobacco is the neglected potential one. Hence the study was conducted to assess the association between smokeless tobacco consumption &amp; breast cancer risk among the women. Objective: The objective of the study was to assess the association between smokeless tobacco consumption and breast cancer in women and to compare the pattern of smokeless tobacco consumption, relevant other factors of breast cancer and the socio-demographic characteristics between the cases and controls. Methods: This case control study was conducted in 302 women of two tertiary hospitals of Dhaka city from January to December’2020. The study enrolled 151 breast cancer patients as cases and another 151 non cancer age-matched women as controls. Convenient technique was used for data collection. A pre-tested semi-structured questionnaire and a checklist were used for face to face interview and to review the medical record respectively. The data were analyzed by SPSS software. Quality control checks of the data were done at all stages of the study. All ethical issues were maintained strictly and informed written consent was taken from each case and control. Results: The mean (±SD) age of cases and controls was 44.4(±10.56) &amp;44.82(±10.2) years respectively (p=0.769). Maximum cases (90.1%) were married in comparison to controls (76.2%) and the association was significant (p=0.003). Majority of the cases (63.58%) had monthly income of 21000-50000tk compared to controls (51.66%) and this difference was significant (p=0.01).Among the cases, 36.4% were exposed to smokeless tobacco in comparison to 33.8% controls. Though this association was not significant (p=0.630) but maximum cases (70.9%) were found to be exposed for 16-30 years in comparison to controls (43.9%) and it was statistically significant (OR: 7.58, 95%CI: 0.865-66.404). Among the cases, who were exposed to zarda were 3.25 times more likely to have it &gt;10 times in comparison to 2.6% controls (OR: 3.25, 95% CI: 1.05-9.99, p=0.040). Conclusion: Increased frequency and duration of smokeless tobacco intake is found significantly associated with breast cancer so specific preventive intervention is required for prevention of smokeless tobacco consumption among women to alleviate breast cancer. Bangladesh Medical Res Counc Bull 2023; 49(2): 83-90

Calibration method and performance of a time-of-flight detector to measure absolute beam energy in proton therapy.

The beam energy is one of the most significant parameters in particle therapy since it is directly correlated to the particles' penetration depth inside the patient. Nowadays, the range accuracy is guaranteed by offline routine quality control checks mainly performed with water phantoms, 2D detectors with PMMA wedges, or multi-layer ionization chambers. The latter feature low sensitivity, slow collection time, and response dependent on external parameters, which represent limiting factors for the quality controls of beams delivered with fast energy switching modalities, as foreseen in future treatments. In this context, a device based on solid-state detectors technology, able to perform a direct and absolute beam energy measurement, is proposed as a viable alternative for quality assurance measurements and beam commissioning, paving the way for online range monitoring and treatment verification. This work follows the proof of concept of an energy monitoring system for clinical proton beams, based on Ultra Fast Silicon Detectors (featuring tenths of ps time resolution in 50μm active thickness, and single particle detection capability) and time-of-flight techniques. An upgrade of such a system is presented here, together with the description of a dedicated self-calibration method, proving that this second prototype is able to assess the mean particles energy of a monoenergetic beam without any constraint on the beam temporal structure, neither any a priori knowledge of the beam energy for the calibration of the system. A new detector geometry, consisting of sensors segmented in strips, has been designed and implemented in order to enhance the statistics of coincident protons, thus improving the accuracy of the measured time differences. The prototype was tested on the cyclotron proton beam of the Trento Protontherapy Center (TPC). In addition, a dedicated self-calibration method, exploiting the measurement of monoenergetic beams crossing the two telescope sensors for different flight distances, was introduced to remove the systematic uncertainties independently from any external reference. The novel calibration strategy was applied to the experimental data collected at TPC (Trento) and CNAO (Pavia). Deviations between measured and reference beam energies in the order of a few hundreds of keV with a maximum uncertainty of 0.5 MeV were found, in compliance with the clinically required water range accuracy of 1mm. The presented version of the telescope system, minimally perturbative of the beam, relies on a few seconds of acquisition time to achieve the required clinical accuracy and therefore represents a feasible solution for beam commission, quality assurance checks, and online beam energy monitoring.

Classification of epoxy molding compounds by Tandem LA-ICP-MS/LIBS to enhance the reliability of electronic devices

Epoxy molding compounds are the most commonly used composite material for encapsulation in the semiconductor industry. They consist of a polymer-based matrix, inorganic filler particles, and a wide range of (in)organic additives to fine-tune the properties. As the encapsulation material is in direct contact with the delicate semiconductor components, the reliability and lifetime of electronic devices heavily depend on applying an appropriate type of encapsulation material. Semiconductor manufacturers typically obtain epoxy molding compounds from specialized external suppliers. Therefore, quality control checking if the correct molding compound was obtained and whether its properties deviate from previous batches is of great interest to the semiconductor industry. In this work, we investigate the capabilities of a Tandem LA-ICP-MS/LIBS approach to comprehensively characterize epoxy molding compounds to construct a classification model capable of distinguishing between different molding compound types. Tandem LA-ICP-MS/LIBS enables detection of the elemental composition of all relevant components within epoxy molding compounds: LIBS can detect polymer-specific signals and the major and minor elements present in the matrix (inorganic filler particles and additives). LA-ICP-MS provides information about elements present at trace levels (e.g., contaminations), which can provide information about batch-to-batch variations. We analyzed 29 samples of 20 molding compound types from 4 different suppliers. Using exploratory data analysis (PCA and HCA), we investigated the spectral fingerprint of the different molding compound types. Finally, a Random Decision Forest-based classifier is optimized and characterized, and a model is constructed. The final classifier is tested with independent samples that were not part of the training set, revealing a satisfying performance and highlighting some molding compound types that are difficult to distinguish.

Differential expression profiles and functional analysis of long non-coding RNAs in calcific aortic valve disease

AimTo evaluate the expression profile of long non-coding RNAs (lncRNAs) in calcific aortic valve disease (CAVD) and explore their potential mechanism of action.MethodsThe gene expression profiles (GSE153555, GSE148219, GSE199718) were downloaded from the Gene Expression Omnibus (GEO) database and FastQC was run for quality control checks. After filtering and classifying candidate lncRNAs by differentially expressed genes (DEGs) and weighted co-expression networks (WGCNA) in GSE153555, we predicted the potential cis- or trans-regulatory target genes of differentially expressed lncRNAs (DELs) by using FEELnc and established the competitive endogenous RNA (ceRNA) network by miRanda, more over functional enrichment was analyzed using the ClusterProfiler package in R Bioconductor. The hub cis- or trans-regulatory genes were verified in GSE148219 and GSE199718 respectively.ResultsThere were 340 up-regulated lncRNAs identified in AS group compared with the control group (|log2Fold Change| ≥ 1.0 and Padj ≤ 0.05), and 460 down-regulated lncRNAs. Based on target gene prediction and co-expression network construction, twelve Long non-coding RNAs (CDKN2B-AS1, AC244453.2, APCDD1L-DT, SLC12A5-AS1, TGFB3, AC243829.4, MIR4435-2HG, FAM225A, BHLHE40-AS1, LINC01614, AL356417.2, LINC01150) were identified as the hub cis- or trans-regulatory genes in the pathogenesis of CAVD which were validated in GSE148219 and GSE19971. Additionally, we found that MIR4435-2HG was the top hub trans-acting lncRNA which also plays a crucial role by ceRNA pattern.ConclusionLncRNAs may play an important role in CAVD and may provide a new perspective on the pathogenesis, diagnosis, and treatment of this disease. Further studies are required to illuminate the underlying mechanisms and provide potential therapeutic targets.

MIRD Pamphlet No. 28, Part 1: MIRDcalc-A Software Tool for Medical Internal Radiation Dosimetry.

Medical internal radiation dosimetry constitutes a fundamental aspect of diagnosis, treatment, optimization, and safety in nuclear medicine. The MIRD committee of the Society of Nuclear Medicine and Medical Imaging developed a new computational tool to support organ-level and suborgan tissue dosimetry (MIRDcalc, version 1). Based on a standard Excel spreadsheet platform, MIRDcalc provides enhanced capabilities to facilitate radiopharmaceutical internal dosimetry. This new computational tool implements the well-established MIRD schema for internal dosimetry. The spreadsheet incorporates a significantly enhanced database comprising details for 333 radionuclides, 12 phantom reference models (International Commission on Radiological Protection), 81 source regions, and 48 target regions, along with the ability to interpolate between models for patient-specific dosimetry. The software also includes sphere models of various composition for tumor dosimetry. MIRDcalc offers several noteworthy features for organ-level dosimetry, including modeling of blood source regions and dynamic source regions defined by user input, integration of tumor tissues, error propagation, quality control checks, batch processing, and report-preparation capabilities. MIRDcalc implements an immediate, easy-to-use single-screen interface. The MIRDcalc software is available for free download (www.mirdsoft.org) and has been approved by the Society of Nuclear Medicine and Molecular Imaging.

A Deep Learning Technique for Optical Inspection of Color Contact Lenses

Colored contact lenses have gained popularity in recent years. However, their production process is plagued by low efficiency, which is attributed to the complex nature of the lens color patterns. The manufacturing process involves multiple complex steps that can introduce defects or inconsistencies into the contact lenses. Moreover, manual inspection of a considerable number of contact lenses that are produced inefficiently in terms of consistency and quality by humans is prevalent. Alternatively, automatic optical inspection (AOI) systems have been developed to perform quality-control checks on colored contact lenses. However, their accuracy is limited due to the increasing complexity of the lens color patterns. To address these issues, convolutional neural networks have been used to detect and classify defects in colored contact lenses. This study aims to provide a comprehensive guide for AOI systems using artificial intelligence in the colored contact lens manufacturing process, including the benefits and challenges of using these systems. Further, future research directions to achieve a classification accuracy of &gt;95%, which is the human recognition rate, are explored.

Establishing Quality Control Procedures for Large-Scale Plasma Proteomics Analyses

Proteomics research has been transformed due to high-throughput liquid chromatography (LC-MS/MS) tandem mass spectrometry instruments combined with highly sophisticated automated sample preparation and multiplexing workflows. However, scaling proteomics experiments to large sample cohorts (hundreds to thousands) requires thoughtful quality control (QC) protocols. Robust QC protocols can help with reproducibility, quantitative accuracy, and provide opportunities for more decisive troubleshooting. Our laboratory conducted a plasma proteomics study of a cohort of N = 335 patient samples using tandem mass tag (TMTpro) 16-plex batches. Over the course of a 10-month data acquisition period for this cohort we collected 271 pooled QC LC-MS/MS result files obtained from MS/MS analysis of a patient-derived pooled plasma sample, representative of the entire cohort population. This sample was tagged with TMTzero or TMTpro reagents and used to inform the daily performance of the LC-MS/MS instruments and to allow within and across sample batch normalization. Analytical variability of a number of instrumental and data analysis metrics including protein and peptide identifications, peptide spectral matches (PSMs), number of obtained MS/MS spectra, average peptide abundance, percent of peptides with a Δ m/z between ±0.003 Da, percent of MS/MS spectra obtained at the maximum injection time, and the retention time of selected tracking peptides were evaluated to help inform the design of a robust LC-MS/MS QC workflow for use in future cohort studies. This study also led to general tips for using selected metrics to inform real-time troubleshooting of LC-MS/MS performance issues with daily QC checks.

Establishing the Quality Assurance programme for the strip sensor production of the ATLAS tracker upgrade including irradiation with neutrons, photons and protons to HL-LHC fluences

The successful pre-production delivery of strip sensors for the new Inner Tracker (ITk) for the upgraded ATLAS detector at the High Luminosity LHC (HL-LHC) at CERN was completed and based on their performance full production has commenced. The overall delivery period is anticipated to last 4 years to complete the approximately 22000 sensors required for the ITk. For Quality Assurance (QA), a number of test structures designed by the collaboration, along with a large area diode and miniature version of the main sensor, are produced in every wafer by the foundry Hamamatsu Photonics K.K (HPK). As well as Quality Control (QC) checks on every main sensor, samples of the QA pieces from each delivery batch are tested both before and after irradiation with results after exposure to neutrons, gammas or protons to fluences and doses corresponding to those anticipated after operation at the HL-LHC to roughly 1.5 times the ultimate integrated luminosity of 4000 fb-1. In this paper the procedures are presented and the studies carried out to establish that the seven ITk QA Strip Sensor irradiation and test sites meet all the requirements to support this very extensive programme throughout the strip sensor production phase for the ITk project.

Genome-wide association study reveals candidate markers related to field fertility and semen quality traits in Holstein-Friesian bulls

In vitro assessment of bull semen quality is routinely used in bull semen processing centres in order to ensure that semen destined to be used in the field has passed minimum standards. Despite these stringent quality control checks, individual bulls that pass the quality control checks can still vary in field fertility by up to 25%. A genome-wide association study was undertaken to determine genetic markers associated with prefreeze and post-thaw bull sperm quality traits as well as field fertility. Genome-wide association analysis was performed using a single nucleotide polymorphism (SNP) regression mixed linear model in WOMBAT. Genes within a 250 Kb span of a suggestive (P ≤ 1 × 10−5) SNP were considered as candidate genes. One SNP was associated with adjusted pregnancy rate, and 21 SNPs were associated across the seven semen quality traits (P ≤ 1 × 10−5). Functional candidate genes include SIPA1L2 which was associated with adjusted pregnancy rate. This encodes a Rap GTPase-activating protein involved in Rap1 signalling pathway and was previously found to play a role in the process of sperm differentiation. Gene ontology (GO) analysis also identified significantly enriched biological processes involved protein tyrosine kinase activity including genes such as DYRK1A, TEC and TXK that were associated with sperm motility prior to freezing. Another candidate gene associated with post-thaw sperm motility was FHDC1 which coordinates actin filament and microtubule dynamics. The induced 11 GO terms in the ejaculates rejected after freezing trait were related to ATPase, phosphatase and hydrolase activity. These results reveal novel specific genomic regions and candidate genes associated with economically important phenotypes such as field fertility and semen quality traits.

The transcriptomic response of bovine uterine tissue is altered in response to sperm from high- and low-fertility bulls†.

Despite stringent quality control checks, some bulls with apparently normal semen quality yield lower than expected pregnancy rates. This study profiled the transcriptome and performed histological analysis of the bovine uterus in response to sperm from high-fertility (HF) and low-fertility (LF) bulls. Postmortem uterine biopsies and uterine explants were collected from heifers 12h after a fixed time artificial insemination (AI) to a synchronized estrus with frozen-thawed semen from five HF (fertility rate 4.01% ± 0.25) and five LF (fertility rate - 11.29% ± 1.11; mean ± SEM) bulls. Uterine biopsies were also collected from control (CTRL) heifers, which were not inseminated. RNA-sequencing and histological analysis were performed for differential gene expression and neutrophil quantification. In the HF treatment relative to CTRL heifers, there were 376 genes significantly differentially expressed in the endometrium with just one gene differentially expressed in the LF treatment relative to CTRL heifers. Comparing the HF and LF treatments directly, there were 40 significantly differentially expressed genes (P < 0.05). Transcriptomic analysis shows a predominant role for the inflammatory marker Interleukin-1 alpha, which was further confirmed by immunohistochemistry. Quantification of neutrophils in the endometrium showed a significant effect of sperm; however, there was no difference in neutrophil numbers between HF and LF groups. In conclusion, this novel study clearly shows a distinct inflammatory response to sperm in the endometrium and a divergent transcriptomic response to semen from HF and LF bulls.