Comparison of histological procedures and antigenicity of human post-mortem brains fixed with solutions used in gross anatomy laboratories.

Background: Brain banks provide small tissue samples to researchers, while gross anatomy laboratories could provide larger samples, including complete brains to neuroscientists. However, they are preserved with solutions appropriate for gross-dissection, different from the classic neutral-buffered formalin (NBF) used in brain banks. Our previous work in mice showed that two gross-anatomy laboratory solutions, a saturated-salt-solution (SSS) and an alcohol-formaldehyde-solution (AFS), preserve antigenicity of the main cellular markers (neurons, astrocytes, microglia, and myelin). Our goal is now to compare the quality of histology and antigenicity preservation of human brains fixed with NBF by immersion (practice of brain banks) vs. those fixed with a SSS and an AFS by whole body perfusion, practice of gross-anatomy laboratories. Methods: We used a convenience sample of 42 brains (31 males, 11 females; 25-90 years old) fixed with NBF (N = 12), SSS (N = 13), and AFS (N = 17). One cm3 tissue blocks were cut, cryoprotected, frozen and sliced into 40 µm sections. The four cell populations were labeled using immunohistochemistry (Neurons = neuronal-nuclei = NeuN, astrocytes = glial-fibrillary-acidic-protein = GFAP, microglia = ionized-calcium-binding-adaptor-molecule1 = Iba1 and oligodendrocytes = myelin-proteolipid-protein = PLP). We qualitatively assessed antigenicity and cell distribution, and compared the ease of manipulation of the sections, the microscopic tissue quality, and the quality of common histochemical stains (e.g., Cresyl violet, Luxol fast blue, etc.) across solutions. Results: Sections of SSS-fixed brains were more difficult to manipulate and showed poorer tissue quality than those from brains fixed with the other solutions. The four antigens were preserved, and cell labeling was more often homogeneous in AFS-fixed specimens. NeuN and GFAP were not always present in NBF and SSS samples. Some antigens were heterogeneously distributed in some specimens, independently of the fixative, but an antigen retrieval protocol successfully recovered them. Finally, the histochemical stains were of sufficient quality regardless of the fixative, although neurons were more often paler in SSS-fixed specimens. Conclusion: Antigenicity was preserved in human brains fixed with solutions used in human gross-anatomy (albeit the poorer quality of SSS-fixed specimens). For some specific variables, histology quality was superior in AFS-fixed brains. Furthermore, we show the feasibility of frequently used histochemical stains. These results are promising for neuroscientists interested in using brain specimens from anatomy laboratories.

African Swine Fever Diagnosis in Africa: Challenges and Opportunities.

The global spread of African swine fever (ASF) in recent decades has led to the need for technological advances in sampling and diagnostic techniques. The impetus for these has been the need to enable sampling by lay persons and to obtain at least a preliminary diagnosis in the field for early control measures to be put in place before final laboratory confirmation. In rural Africa, rapid diagnosis is hampered by challenges that include lack of infrastructure as well as human and financial resources. Lack of animal health personnel, access to affordable means to transport field samples to a laboratory, and lack of laboratories with the capacity to make the diagnosis result in severe under-reporting of ASF, especially in endemic areas. This review summarizes the challenges identified in gap analyses relevant to low- and middle-income countries, with a focus on Africa, and explore the opportunities provided by recent research to improve field diagnosis and quality of diagnostic samples used. Sampling techniques include invasive sampling techniques requiring trained personnel and non-invasive sampling requiring minimal training, sampling of decomposed carcass material, and preservation of samples in situations where cold chain maintenance cannot be guaranteed. Availability and efficacy of point-of-care (POC) tests for ASF has improved considerably in recent years and their application, as well as advantages and limitations, are discussed. The adequacy of existing laboratory diagnostic capacity is evaluated and opportunities for networking amongst reference and other laboratories offering diagnostic services are discussed. Maintaining laboratory diagnostic efficiency in the absence of samples during periods of quiescence is another issue that requires attention, and the role of improved laboratory networking is emphasized. Early diagnosis of ASF is key to managing the disease spread. Therefore, the establishment of the Africa Chapter of the Global African Swine Fever Research Alliance (GARA) increases opportunities for collaboration and networking among the veterinary diagnostic laboratories in the region.

Enhanced identification of familial hypercholesterolemia using central laboratory algorithms.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a highly prevalent genetic disorder resulting in markedly elevated LDL cholesterol levels and premature coronary artery disease. FH underdiagnosis and undertreatment require novel detection methods. This study evaluated the effectiveness of using an LDL cholesterol cut-off ≥99.5th percentile (sex- and age-adjusted) to identify clinical and genetic FH, and investigated underutilization of genetic testing and undertreatment in FH patients. METHODS: Individuals with at least one prior LDL cholesterol level ≥99.5th percentile were selected from a laboratory database containing lipid profiles of 590,067 individuals. The study comprised three phases: biochemical validation of hypercholesterolemia, clinical identification of FH, and genetic determination of FH. RESULTS: Of 5614 selected subjects, 2088 underwent lipid profile reassessment, of whom 1103 completed the questionnaire (mean age 64.2 ± 12.7 years, 48% male). In these 1103 subjects, mean LDL cholesterol was 4.0 ± 1.4 mmol/l and 722 (65%) received lipid-lowering therapy. FH clinical diagnostic criteria were met by 282 (26%) individuals, of whom 85% had not received guideline-recommended genetic testing and 97% failed to attain LDL cholesterol targets. Of 459 individuals consenting to genetic validation, 13% carried an FH-causing variant, which increased to 19% in clinically diagnosed FH patients. CONCLUSIONS: The identification of a substantial number of previously undiagnosed and un(der)treated clinical and genetic FH patients within a central laboratory database highlights the feasibility and clinical potential of this targeted screening strategy; both in identifying new FH patients and in improving treatment in this high-risk population.

Higher blood biochemistry-based biological age developed by advanced deep learning techniques is associated with frailty in geriatric rehabilitation inpatients: RESORT.

BACKGROUND: Accelerated biological ageing is a major underlying mechanism of frailty development. This study aimed to investigate if the biological age measured by a blood biochemistry-based ageing clock is associated with frailty in geriatric rehabilitation inpatients. METHODS: Within the REStORing health of acutely unwell adulTs (RESORT) cohort, patients' biological age was measured by an ageing clock based on completed data of 30 routine blood test variables measured at rehabilitation admission. The delta of biological age minus chronological age (years) was calculated. Ordinal logistic regression and multinomial logistic regression were performed to evaluate the association of the delta of ages with frailty assessed by the Clinical Frailty Scale. Effect modification of Cumulative Illness Rating Scale (CIRS) score was tested. RESULTS: A total of 1187 geriatric rehabilitation patients were included (median age: 83.4 years, IQR: 77.7-88.5; 57.4 % female). The biochemistry-based biological age was strongly correlated with chronological age (Spearman r = 0.883). After adjustment for age, sex and primary reasons for acute admission, higher biological age (per 1 year higher in delta of ages) was associated with more severe frailty at admission (OR: 1.053, 95 % CI:1.012-1.096) in patients who had a CIRS score of <12 not in patients with a CIRS score >12. The delta of ages was not associated with frailty change from admission to discharge. The specific frailty manifestations as cardiac, hematological, respiratory, renal, and endocrine conditions were associated with higher biological age. CONCLUSION: Higher biological age was associated with severe frailty in geriatric rehabilitation inpatients with less comorbidity burden.

Organisation of paediatric echocardiography laboratories and governance of echocardiography services and training in Europe: current status, disparities, and potential solutions. A survey from the Association for European Paediatric and Congenital Cardiology (AEPC) imaging working group.

BACKGROUND: There is limited data on the organisation of paediatric echocardiography laboratories in Europe. METHODS: A structured and approved questionnaire was circulated across all 95 Association for European Paediatric and Congenital Cardiology affiliated centres. The aims were to evaluate: (1) facilities in paediatric echocardiography laboratories across Europe, (2) accredited laboratories, (3) medical/paramedical staff employed, (4) time for echocardiographic studies and reporting, and (5) training, teaching, quality improvement, and research programs. RESULTS: Respondents from forty-three centres (45%) in 22 countries completed the survey. Thirty-six centres (84%) have a dedicated paediatric echocardiography laboratory, only five (12%) of which reported they were European Association of Cardiovascular Imaging accredited. The median number of echocardiography rooms was three (range 1-12), and echocardiography machines was four (range 1-12). Only half of all the centres have dedicated imaging physiologists and/or nursing staff, while the majority (79%) have specialist imaging cardiologist(s). The median (range) duration of time for a new examination was 45 (20-60) minutes, and for repeat examination was 20 (5-30) minutes. More than half of respondents (58%) have dedicated time for reporting. An organised training program was present in most centres (78%), 44% undertake quality assurance, and 79% perform research. Guidelines for performing echocardiography were available in 32 centres (74%). CONCLUSION: Facilities, staffing levels, study times, standards in teaching/training, and quality assurance vary widely across paediatric echocardiography laboratories in Europe. Greater support and investment to facilitate improvements in staffing levels, equipment, and governance would potentially improve European paediatric echocardiography laboratories.

The Importance and Challenges of Implementing and Maintaining Biorepositories for High-Consequence Veterinary and One Health Pathogens in South-East Asia.

Introduction: Emerging infectious diseases pose a threat to public health and the economy, especially in developing countries. Southeast Asian veterinary laboratories handle numerous high-risk pathogens, making pathogen accountability crucial for safe handling and storage. Methods: Thirteen veterinary laboratories in Cambodia (n = 1), Lao People's Democratic Republic (n = 1), and Thailand (n = 11) participated in a study conducted between 2019 and 2020. Data were collected using a questionnaire, group discussions, and interviews. Conclusion: Significant gaps in biosecurity and biorepository management were recognized and discussed in the context of regional biosafety and biosecurity. Laboratories could use the findings and recommendations of the study to develop or improve their pathogen inventory and biosecurity systems. Governments play a significant role in setting standards and regulations and providing necessary support for laboratories to maintain inventory controls sustainably and have a very important role to play in ensuring biosafety and biosecurity compliance.

Comparison of Brazilian High- and Maximum-Containment Laboratories Biosafety and Biosecurity Regulations to Legal Frameworks in the United States and Other Countries: Gaps and Opportunities.

Introduction: Although the United States and other countries have implemented comprehensive legislation, regulations, and policies to support biosafety and biosecurity of high- and maximum-containment laboratories, Brazil's legislation has notable gaps and inconsistencies. Objective: To evaluate the Brazilian approach to ensuring nationwide biosafety and biosecurity oversight and governance of high- and maximum-containment laboratories. Methods: A systematic gap analysis was conducted to compare Brazilian biosafety and biosecurity legislation, regulations, and policies with their international counterparts, with a particular focus on the oversight and governance of high- and maximum-containment laboratories. Results: We found that Brazilian biosafety and biosecurity legislation, regulations, and policies have relevant gaps. Governance and regulatory oversight of Brazil's high- and maximum-containment laboratories are decentralized with variable levels of adherence to commonly accepted global biosafety and biosecurity compliance standards. These findings represent a limitation not only to governance but also to the preparedness to face current and future challenges related to emergent infectious diseases in Brazil. Enhancing the Brazilian legal framework on laboratory biosafety and biosecurity is necessary and urgent. Reviewing the lessons learned and regulations applied in the United States and other international frameworks helped identify potential areas for improving Brazil's ability to inventory and manage its diverse biocontainment laboratory capabilities and assure these valuable resources align with national needs and priorities. Conclusion: The Brazilian government has an opportunity to revise and improve upon a national set of legislation, regulations, and policies for its high- and maximum-containment laboratories, taking advantage of legislation and guidelines published by other countries.

[Proceedings of the International Symposium of the World Association of Veterinary Laboratory Diagnosticians, 2023]. / Compte-rendu du Symposium international de la Société mondiale des Laboratoires vétérinaires de diagnostic, 2023.

The International Symposium of the World Association of Veterinary Laboratory Diagnosticians (ISWAVLD) is the unmissable biannual meeting of all diagnostic veterinary laboratories including biologists, veterinarians and other scientists involved in laboratory diagnostics. It took place at the Lyon Convention Centre (29 June-1 July 2023). It was a pleasant and enriching moment, which allowed participants to discover and/or discuss new diagnostic methods and the epidemiology of animal diseases, around all themes involving veterinarians (animal health, but also environmental and human health, and food safety).

Pharmacy-based CLIA-waived testing in the United States: Trends, impact, and the road ahead.

BACKGROUND: Federal authorization of the use of Clinical Laboratory Improvement Amendments of 1988 (CLIA) waived point-of-care tests for SARS-CoV-2 by pharmacists during the pandemic resulted in a dramatic rise in the number of community pharmacies that became CLIA-waived test sites. Now as we exit the pandemic, the wide-ranging expansion of the scope of practice facilitated currently by the PREP Act is set to expire in fall 2024. As a result, American pharmacists' ability to offer CLIA-waived testing services will revert to a patchwork of state laws. OBJECTIVE: This study aims to examine both the number of pharmacies in the United States with CLIA Certificates of Waiver before and after the SARS-CoV-2 pandemic and the state-by-state differences in the percentage of pharmacies with CLIA Certificates of Waiver. METHODS: Data were collected from the U.S. Centers for Disease Control and Prevention CLIA Laboratory Search website on May 3rd, 2015, August 4th, 2019, November 26th, 2020, October 6th, 2021, November 23rd, 2022, and December 4th, 2023. The website allows for the exportation of demographic data on all CLIA-waived facilities by state. RESULTS: The total number of pharmacies with a CLIA-waiver grew from 10,626 (17.9%) locations in 2015 to 12,157 (21.4%) locations in 2019, to 15,671 (27.6%) locations in 2020, and to 29,011 (51.6%) locations in 2023. States demonstrated considerable variability in the percentage of pharmacies possessing a CLIA certificate of waiver in 2023, with a range of 10.7%-87.9%. CONCLUSIONS: Use of CLIA-waived tests in pharmacies has grown by 140% since 2019. The time period from 2019 to 2021 witnessed a 92.5% increase in pharmacies that possessed a certificate of waiver which was largely driven by the pandemic. Interestingly, from 2021 to 2023 the was continued growth in the market of 31.6%. This suggests that pharmacies continue to see opportunity in offering CLIA-waived testing services beyond those that had been extended as a result of the pandemic.

A phased strengthening of laboratory capacity in the Eastern Mediterranean Region during the COVID-19 pandemic.

The Eastern Mediterranean Region (EMR) faces ongoing challenges in its public health system due to limited resources, logistical issues, and political disruptions. The COVID-19 pandemic accelerated the need for stronger laboratory capacities to handle the increased demand for testing. In a phased response, EMR countries utilized the National Influenza Centers to rapidly establish and scale molecular testing for SARS-CoV-2, the causative agent of COVID-19. The expansion of capacity included strong collaborations between public health bodies and private and academic sectors to decentralize and expand testing to the subnational level. To ensure that the quality of testing was not impacted by rapid expansion, national and subnational laboratories were enrolled in external quality assurance programs for the duration of the response. Implementation of genomic surveillance was prioritized for variant tracking, leading to the establishment of regional sequencing reference laboratories and the distribution of MinION sequencing platforms to complex emergency countries who previously had limited experience with pathogen sequencing. Challenges included a lack of technical expertise, including in implementing novel diagnostic assays and sequencing, a lack of bioinformatics expertise in the region, and significant logistical and procurement challenges. The collaborative approach, coordinated through the WHO Eastern Mediterranean Regional Office, enabled all 22 countries to achieve SARS-CoV-2 diagnostic capabilities, highlighting the pivotal role of laboratories in global health security.

Role of research Laboratories in pandemic and epidemic response in the Eastern Mediterranean Region: Experiences from COVID-19, avian influenza, and MERS-CoV.

We share the experience of research laboratories in the Eastern Mediterranean Region (EMR) that contributed to preparedness and response to highly pathogenic avian influenza (HPAI), Middle-East respiratory syndrome coronavirus (MERS-CoV), and coronavirus disease (COVID-19). Research groups in the region were pivotal in identifying, characterizing the pathogens and describing their evolution, distribution, transmission routes, and the immunological profile of exposed populations. They demonstrated the capacity to develop and test antivirals and potential vaccines. The EMR experience is a model of how national systems can work with researchers to improve regional preparedness and response to future epidemics and pandemics.

Issues in assessing analytical performance specifications in healthcare systems assembling multiple laboratories and measuring systems.

Analytical performance specifications (APS) are usually compared to the intermediate reproducibility uncertainty of measuring a particular measurand using a single in vitro diagnostic medical device (IVD MD). Healthcare systems assembling multiple laboratories that include several IVD MDs and cater to patients suffering from long-term disease conditions mean that samples from a patient are analyzed using a few IVD MDs, sometimes from different manufacturers, but rarely all IVD MDs in the healthcare system. The reproducibility uncertainty for results of a measurand measured within a healthcare system and the components of this measurement uncertainty is useful in strategies to minimize bias and overall measurement uncertainty within the healthcare system. The root mean squares deviation (RMSD) calculated as the sample standard deviation (SD) and relative SD includes both imprecision and bias and is appropriate for expressing such uncertainties. Results from commutable stabilized internal and external control samples, from measuring split natural patient samples or using big-data techniques, are essential in monitoring bias and measurement uncertainties in healthcare systems. Variance component analysis (VCA) can be employed to quantify the relative contributions of the most influential factors causing measurement uncertainty. Such results represent invaluable information for minimizing measurement uncertainty in the interest of the healthcare system's patients.

Whole blood clotting time: Current practices among Thailand National External Quality Assessment Scheme for blood coagulation member laboratories.

INTRODUCTION: The Thai National Guidelines for Hemostatic Laboratory Testing were established in 2018. The guidelines recommend that the 20-min whole blood clotting time (20WBCT) method be used to diagnose/monitor snake bites. The aim of this study was to survey members of the Thailand National External Quality Assessment Scheme (NEQAS) for Blood Coagulation to investigate the use of 20WBCT testing compared between the 2021 post-guideline and 2007 pre-guideline periods. METHODS: In July 2021, questionnaires were sent from the Faculty of Medicine Siriraj Hospital, Mahidol University to 521 Thailand NEQAS for Blood Coagulation member laboratories to survey their WBCT practices. Current WBCT practices were compared with pre-guideline WBCT practices, and chi-square test (x2) was used to test for differences between groups. RESULTS: Ninety-seven (18.6%) of 521 surveys were returned. Seventy-one laboratories (73.2%) reported knowing about 20WBCT from the Thai national guidelines. The reported average frequency of overall WBCT testing in 2021 was 12.4 times/month. The proportion of laboratories that reported using the 20WBCT test increased from 2.0% in 2007 to 46.4% in 2021 (p < 0.001), and the indications for performing WBCT were virtually unchanged from 2007 to 2021. The proportion of laboratories that reported having problems with WBCT testing decreased from 32.7% in 2007 to 16.5% in 2021. CONCLUSION: Despite our findings that almost three-quarters of respondent laboratories reported knowing about 20WBCT testing from the WBCT guidelines, and that WBCT-specific problems decreased significantly from 2007 to 2021, more work and training is needed to improve WBCT guideline dissemination, understanding, and adherence in Thailand.

Virus sequencing performance during the SARS-CoV-2 pandemic: a retrospective analysis of data from multiple rounds of external quality assessment in Austria.

Introduction: A notable feature of the 2019 coronavirus disease (COVID-19) pandemic was the widespread use of whole genome sequencing (WGS) to monitor severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Countries around the world relied on sequencing and other forms of variant detection to perform contact tracing and monitor changes in the virus genome, in the hopes that epidemic waves caused by variants would be detected and managed earlier. As sequencing was encouraged and rewarded by the government in Austria, but represented a new technicque for many laboratories, we designed an external quality assessment (EQA) scheme to monitor the accuracy of WGS and assist laboratories in validating their methods. Methods: We implemented SARS-CoV-2 WGS EQAs in Austria and report the results from 7 participants over 5 rounds from February 2021 until June 2023. The participants received sample material, sequenced genomes with routine methods, and provided the sequences as well as information about mutations and lineages. Participants were evaluated on the completeness and accuracy of the submitted sequence and the ability to analyze and interpret sequencing data. Results: The results indicate that performance was excellent with few exceptions, and these exceptions showed improvement over time. We extend our findings to infer that most publicly available sequences are accurate within ≤1 nucleotide, somewhat randomly distributed through the genome. Conclusion: WGS continues to be used for SARS-CoV-2 surveillance, and will likely be instrumental in future outbreak scenarios. We identified hurdles in building next-generation sequencing capacity in diagnostic laboratories. EQAs will help individual laboratories maintain high quality next-generation sequencing output, and strengthen variant monitoring and molecular epidemiology efforts.

Medical Students' Perception of Pathology in Saudi Arabia.

Pathology is the bridge between basic science and clinical practice. An inadequate perception of pathology leads to an incomplete understanding of diseases, which consequently affects its management. This study aims to identify medical students' perceptions of pathology in medical colleges around Saudi Arabia and use their feedback to improve teaching strategies. A validated online self-structured questionnaire form was distributed to medical students in basic and clinical years, including private and governmental universities in all regions of Saudi Arabia. The study comprised a total of 476 medical students. It revealed that n = 226 (48%) of the participants were not aware of pathologists' roles, and n = 262 (55%) of students reported that the main reason was insufficient exposure to actual pathology practice. A total of n = 209 (44%) students believed the current teaching methods in the basic years were insufficient to provide clear perceptions of pathology. The majority of participants n = 366 (77%) chose practical sessions as the most effective strategy in teaching pathology. Our study demonstrated that medical students require more engagement in laboratories to improve their perception. We suggest that Saudi medical schools need to deliver more comprehensive and practical teaching methods that reflect the actual practice of pathology.

Sentinel laboratory compliance with best practices in Burkina Faso's antimicrobial resistance surveillance network.

Background: Standardising procedures is the best way to harmonise and strengthen the quality of laboratory-based antimicrobial resistance surveillance. Since 2018, Burkina Faso has developed and disseminated the national manual of procedures for performing antibiotic susceptibility tests in sentinel laboratories within its national antimicrobial resistance surveillance network. Objective: Our study aimed to assess these sentinel laboratories' compliance with good practices for antibiotics susceptibility tests. Methods: Four teams evaluated the antimicrobial resistance sentinel sites laboratories throughout Burkina Faso from 19 to 28 September 2022. Eighteen out of 19 sentinel laboratories were evaluated. A four-member technical committee designed and validated the evaluation tool composed of three Microsoft Excel sheets. The evaluation emphasised quality controls for culture media, antibiotic discs and compliance with antimicrobial susceptibility testing procedures by the laboratories. Excel software was used for data recording and graphs and table design. The free R software version 4.2.0 was used for descriptive statistics. An overall score below 80% was considered noncompliance. Results: Most (83.33%) of the sentinel laboratories conducted at least one quality control activity for culture media, and 66.67% conducted at least one quality control activity for antibiotic discs. Over three-quarters (76.47%) of the laboratories were more than 80% compliant with the modified Kirby Bauer antimicrobial susceptibility testing method. Conclusion: The evaluation revealed the noncompliance of sentinel laboratories with the national procedure manual, particularly in the quality control component. What this study adds: This study has provided baseline data on the sentinel laboratories' compliance with the national antimicrobial susceptibility testing procedures manual, particularly in areas performing quality control checks or meeting quality indicators for culture media and antibiotic discs.

Current status and perspectives of the quality system in histocompatibility laboratories in Poland.

Allogeneic transplantation is a multi-step process involving many clinicians and laboratory personnel working together to achieve a common goal-to maximize the recipients' chance of survival and to improve their quality of life. One of the key elements of the process is to ensure high quality, accuracy, and reliability of histocompatibility testing. This manuscript presents: the development and organizational principles of the national system of supervision and control of histocompatibility laboratories in Poland, problems faced by these laboratories, availabe proficiency testing schemes, as well as suggestions and prospects for the future raised by members of the Polish histocompatibility community.

Genome sequencing as a generic diagnostic strategy for rare disease.

BACKGROUND: To diagnose the full spectrum of hereditary and congenital diseases, genetic laboratories use many different workflows, ranging from karyotyping to exome sequencing. A single generic high-throughput workflow would greatly increase efficiency. We assessed whether genome sequencing (GS) can replace these existing workflows aimed at germline genetic diagnosis for rare disease. METHODS: We performed short-read GS (NovaSeq™6000; 150 bp paired-end reads, 37 × mean coverage) on 1000 cases with 1271 known clinically relevant variants, identified across different workflows, representative of our tertiary diagnostic centers. Variants were categorized into small variants (single nucleotide variants and indels < 50 bp), large variants (copy number variants and short tandem repeats) and other variants (structural variants and aneuploidies). Variant calling format files were queried per variant, from which workflow-specific true positive rates (TPRs) for detection were determined. A TPR of ≥ 98% was considered the threshold for transition to GS. A GS-first scenario was generated for our laboratory, using diagnostic efficacy and predicted false negative as primary outcome measures. As input, we modeled the diagnostic path for all 24,570 individuals referred in 2022, combining the clinical referral, the transition of the underlying workflow(s) to GS, and the variant type(s) to be detected. RESULTS: Overall, 95% (1206/1271) of variants were detected. Detection rates differed per variant category: small variants in 96% (826/860), large variants in 93% (341/366), and other variants in 87% (39/45). TPRs varied between workflows (79-100%), with 7/10 being replaceable by GS. Models for our laboratory indicate that a GS-first strategy would be feasible for 84.9% of clinical referrals (750/883), translating to 71% of all individuals (17,444/24,570) receiving GS as their primary test. An estimated false negative rate of 0.3% could be expected. CONCLUSIONS: GS can capture clinically relevant germline variants in a 'GS-first strategy' for the majority of clinical indications in a genetics diagnostic lab.

Integrating Veterinary Diagnostic Laboratories for Emergency Use Testing during Pandemics1.

The SARS-CoV-2 pandemic showed limitations in human outbreak testing. Veterinary diagnostic laboratories (VDLs) possess capabilities to bolster emergency test capacity. Surveys from 26 participating VDLs found human SARS-CoV-2 testing was mutually beneficial, including One Health benefits. VDLs indicated testing >3.8 million human samples during the pandemic, which included some challenges.