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For new principal investigators, the first years are key to getting a laboratory off the ground and running. COVID-19 has changed the world, bringing on unforeseen difficulties and challenges at every level. We asked these investigators to share their experiences in navigating the unique environment since the start of the pandemic-what has changed in their vision for their laboratory, how they have adapted, and what advice they can share with others in a similar situation., (Copyright © 2021. Published by Elsevier Inc.)

Context: This retrospective case-series study aims to provide an overview of the clinical, biochemical and analytical findings in patients who presented with toxicity related to the use of illegitimate slimming agents in Hong Kong from the perspective of a tertiary referral toxicology laboratory., Methods: All clinical cases referred to the Hospital Authority Toxicology Reference Laboratory, Hong Kong with clinical suspicion of illegitimate slimming agent-related toxicity between January 2008 and December 2017 were reviewed retrospectively. The use of illegitimate slimming agents included the use of (1) deregistered slimming agents, (2) drug analogues that were not registered drugs, (3) registered drugs not approved for the indication of weight reduction (whether prescribed by a doctor or not), and (4) prescription-only slimming agents without a doctor's prescription. Patients taking registered weight-reducing drugs prescribed by a doctor were excluded. Patient demographics, clinical features, relevant laboratory investigations, and toxicological findings were analyzed., Results: From 2008 to 2017, a total of 346 patients were analytically confirmed by our laboratory to have clinical toxicity related to the use of illegitimate slimming agents. The median age of the patients was 27 years and 92.5% of the patients were female. The most common clinical presentations included psychiatric features, sympathomimetic toxicity, hypokalemia, and abnormal thyroid function tests. Fatal or severe clinical toxicity was observed in 10% of the cases. The major classes of drugs detected on our analytical platforms were stimulants (e.g., sibutramine), laxatives (e.g., anthraquinones), diuretics (e.g., hydrochlorothiazide), and thyroid hormones (e.g., animal thyroid tissue). These illegitimate slimming agents were obtained from various sources including the Internet, over-the-counter in community pharmacy, or unspecified local sources., Discussion and Conclusions: The use of slimming agents is common worldwide; apart from taking registered slimming agents prescribed by registered practitioners, many users obtain slimming agents from various illegitimate sources. The unregulated use of these drugs can be associated with significant clinical toxicity. This study provides a current landscape of illegitimate slimming agent toxicity in Hong Kong to frontline clinicians and other toxicology professionals. Collaboration between clinicians, laboratories, and government authorities would be imperative to prevent further health adversities related to the misuse of these agents.

Background: Rates of sexually transmitted infections (STI) have risen steadily in recent years, and racial and ethnic minorities have borne the disproportionate burden of STI increases in the United States. Historical inequities and social determinants of health are significant contributors to observed disparities and affect access to diagnostic testing for STI., Content: Public health systems rely heavily on laboratory medicine professionals for diagnosis and reporting of STI. Therefore, it is imperative that clinicians and laboratory professionals be familiar with issues underlying disparities in STI incidence and barriers to reliable diagnostic testing. In this mini-review, we will summarize contributors to racial/ethnic disparity in STI, highlight current epidemiologic trends for gonorrhea, chlamydia, and syphilis, discuss policy issues that affect laboratory and public health funding, and identify specific analytic challenges for diagnostic laboratories., Summary: Racial and ethnic disparities in STI in the US are striking and are due to complex interactions of myriad social determinants of health. Budgetary cuts for laboratory and public health services and competition for resources during the COVID-19 pandemic are major challenges. Laboratory professionals must be aware of these underlying issues and work to maximize efforts to ensure equitable access to diagnostic STI testing for all persons, particularly those most disproportionately burdened by STI., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please contact: journals.permissions@oup.com.)

The COVID-19 pandemic has dramatically affected shared resource lab (SRL) staff in-person availability at institutions globally. This article discusses the challenges of ensuring reliable instrument performance and quality data output while facility staff and external service provider on-site presence is severely limited. Solutions revolve around the adoption of remote monitoring and troubleshooting platforms, provision of self-service troubleshooting resources specific to facility instruments and workflows, development of an assistance contact policy, and ensuring efficiency of limited in-person staff time. These solutions employ software and hardware tools that are already in use or readily available in the SRL community, such as remote instrument access tools, video hosting and conferencing platforms, and ISAC shared resources. © 2020 International Society for Advancement of Cytometry., (© 2020 International Society for Advancement of Cytometry.)

Biosafety has always been an important aspect of daily work in any research institution, particularly for cytometry Shared Resources Laboratories (SRLs). SRLs are common-use spaces that facilitate the sharing of knowledge, expertise, and ideas. This sharing inescapably involves contact and interaction of all those within this working environment on a daily basis. The current pandemic caused by SARS-CoV-2 has prompted the re-evaluation of many policies governing the operations of SRLs. Here we identify and review the unique challenges SRLs face in maintaining biosafety standards, highlighting the potential risks associated with not only cytometry instrumentation and samples, but also the people working with them. We propose possible solutions to safety issues raised by the COVID-19 pandemic and provide tools for facilities to adapt to evolving guidelines and future challenges., (© 2021 International Society for Advancement of Cytometry.)

The impact of the COVID-19 pandemic on training and Shared Resource Laboratory (SRL) operations such as staffing, facility access, and social distancing, has affected facilities around the globe to different degrees based on restrictions set by various geographical and institutional settings. With these restrictions come unique challenges regarding user and staff training and education, for both theory and practice. Most notably, limitations in facility access, occupancy, staffing availability, network restrictions and trainee engagement call for innovative solutions for training when traditional in-person options are not feasible. Through the use of remote access tools and prerecorded educational and training materials, SRLs are able to overcome these obstacles. Here, we focus on readily available technologies and general guidelines that SRLs in different environments can use for remote cytometry training and education, while highlighting key obstacles that still remain. Although SRLs may face initial struggles in transitioning trainings to a virtual format, remote technologies provide unique opportunities to advance current training programs. © 2020 International Society for Advancement of Cytometry., (© 2020 International Society for Advancement of Cytometry.)

Data management is essential in a flow cytometry (FCM) shared resource laboratory (SRL) for the integrity of collected data and its long-term preservation, as described in the Cytometry publication from 2016, ISAC Flow Cytometry Shared Resource Laboratory (SRL) Best Practices (Barsky et al.: Cytometry Part A 89A(2016): 1017-1030). The SARS-CoV-2 pandemic introduced an array of challenges in the operation of SRLs. The subsequent laboratory shutdowns and access restrictions brought to the forefront well-established practices that withstood the impact of a sudden change in operations and illuminated areas that need improvement. The most significant challenges from a data management perspective were data access for remote analysis and workstation management. Notably, lessons learned from this challenge emphasize the importance of safeguarding collected data from loss in various emergencies such as fire or natural disasters where the physical hardware storing data could be directly affected. Here, we describe two data management systems that have been successful during the current emergency created by the pandemic, specifically remote access and automated data transfer. We will discuss other situations that could arise and lead to data loss or challenges in interpreting data. © 2020 International Society for Advancement of Cytometry., (© 2020 International Society for Advancement of Cytometry.)

In March 2020, with lockdown due to the coronavirus pandemic underway, the Francis Crick Institute (the Crick) regeared its research laboratories into clinical testing facilities. Two pipelines were established, one for polymerase chain reaction and the other for Serology. This article discusses the Cricks Flow Cytometry Science Technology Platform (Flow STP) role in setting up the Serology pipeline. Pipeline here referring to the overarching processes in place to facilitate the receipt of human sera through to a SARs-CoV-2 enzyme-linked immunosorbent assay result. We examine the challenges that had to be overcome by a research laboratory to incorporate clinical diagnostics and the processes by which this was achieved. It describes the governance required to run the service, the design of the standard operating procedures (SOPs) and pipeline, the setting up of the assay, the validation required to show the robustness of the pipeline and reporting the results of the assay. Finally, as the lockdown started to ease in June 2020, it examines how this new service affects the daily running of the Flow STP. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals LLC on behalf of International Society for Advancement of Cytometry., (© 2020 The Authors. Cytometry Part A published by Wiley Periodicals LLC on behalf of International Society for Advancement of Cytometry.)

Psychoactive drugs including alcohol, caffeine, and prescription medications are commonly consumed to alter sleep/wake states, however the prevalence and impact of these drugs among populations seeking assessment from sleep physicians are unknown. We investigated the prevalence of commonly used drugs (alcohol and caffeine), and medications in a population (N=120; 50 females and 70 males) attending a tertiary sleep clinic for diagnostic polysomnography (PSG) assessment. In addition to objective sleep assessment, participants completed questionnaires assessing sleep quality (Pittsburgh Sleep Quality Index, PSQI), daytime sleepiness (Epworth Sleepiness Scale, ESS), depression and anxiety (Hospital Anxiety and Depression Scale, HADS), alcohol use (Alcohol Use Disorders Identification Test, AUDIT), caffeine and medication use, as well as their experience of adverse events (motor vehicle accidents and near-miss crashes). Caffeine was consumed by 90% of the population and was associated with a reduction in excessive sleepiness symptomology; while high AUDIT scores were associated with increased near-miss crashes. Polypharmacy was common, with a greater number of medications associated with poorer sleep quality, and changes in sleep architecture. This study maps commonly used drugs in those attending a tertiary sleep clinic, and demonstrates associations between drug use and sleep outcomes assessed objectively and subjectively., (Copyright © 2020. Published by Elsevier B.V.)

With the recent developments in information technology, real world big data studies (RWBDSs) have attracted increasing attention in the field of medicine. In RWBDSs, clinical laboratory data is an important part of the wider scope of real-world medical data, and its standardized use is critical for the generation of high-quality real-world evidence. To improve the core functioning and competitiveness of clinical laboratories as well as provide high-quality medical services for patients, it is important to construct an information analysis model and perform RWBDSs. However, among the majority of developing countries, as well as in some developed countries, due to the poorly developed neglect of data formatting standards information construction and the lack of consideration for, and experience with, the ideas and methods of RWBDSs, many clinical laboratories are unable to make use of the vast amount of data stored in their systems. Additionally, in the literature, there remain many areas that require improvements, such as the correct misuse of research methods, appropriate unreasonable data presentation methods, and optimal opaque methods for data cleaning, storage, and mining. In this review, we describe both the advantages and disadvantages of RWBDSs in laboratory medicine. In addition, we summarize the current application and methods of RWBDS in laboratory medicine from seven different perspectives: the establishment of a reference interval, patient data-based real time quality control, diagnostic or prognostic modeling, epidemiological investigation, laboratory management, analysis of sources of variations for analytes, and external quality assessment. Finally, we discuss the future prospects of this research. This review can provide the basis for clinical laboratories to carry out real world research; additionally, it promotes and standardizes RWBDS in laboratory medicine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

The global coronavirus disease 2019 (COVID-19) has presented major challenges for clinical laboratories, from initial diagnosis to patient monitoring and treatment. Initial response to this pandemic involved the development, production, and distribution of diagnostic molecular assays at an unprecedented rate, leading to minimal validation requirements and concerns regarding their diagnostic accuracy in clinical settings. In addition to molecular testing, serological assays to detect antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now becoming available from numerous diagnostic manufacturers. In both cases, the lack of peer-reviewed data and regulatory oversight, combined with general misconceptions regarding their appropriate use, have highlighted the importance of laboratory professionals in robustly validating and evaluating these assays for appropriate clinical use. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on COVID-19 has been established to synthesize up-to-date information on the epidemiology, pathogenesis, and laboratory diagnosis and monitoring of COVID-19, as well as to develop practical recommendations on the use of molecular, serological, and biochemical tests in disease diagnosis and management. This review summarizes the latest evidence and status of molecular, serological, and biochemical testing in COVID-19 and highlights some key considerations for clinical laboratories operating to support the global fight against this ongoing pandemic. Confidently this consolidated information provides a useful resource to laboratories and a reminder of the laboratory's critical role as the world battles this unprecedented crisis.

Clinical microbiology has advanced tremendously in the past 10 years. In this comic, the role of technology, the need for skilled microbiologists, and the meaning of progress in clinical microbiology are considered., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Before the introduction of rotavirus vaccine in the United States in 2006, rotavirus infection was the leading cause of severe gastroenteritis among U.S. children (1). To evaluate the long-term impact of rotavirus vaccination on disease prevalence and seasonality in the United States, CDC analyzed national laboratory testing data for rotavirus from laboratories participating in CDC's National Respiratory and Enteric Viruses Surveillance System (NREVSS) during the prevaccine (2000-2006) and postvaccine (2007-2018) periods. Nationally, the median annual percentage of tests positive for rotavirus declined from 25.6% (range = 25.2-29.4) in the prevaccine period to 6.1% (range = 2.6-11.1) in the postvaccine period. When compared with the prevaccine period, the postvaccine period saw declines in the annual peak in rotavirus positivity from a median of 43.1% (range = 43.8-56.3) to a median of 14.0% (range = 4.8-27.3) and in the season duration from a median of 26 weeks (range = 23-27) to a median of 9 weeks (range = 0-18). In the postvaccine period, a biennial pattern emerged, with alternating years of low and high rotavirus activity. Implementation of the rotavirus vaccination program has substantially reduced prevalence of the disease and altered seasonal patterns of rotavirus in the United States; these changes have been sustained over 11 seasons after vaccine introduction. Ongoing efforts to improve coverage and on-time vaccination (2) can help maximize the public health impact of rotavirus vaccination., Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Soil-transmitted helminths (STHs) affect more than 1.5 billion people. The global strategy to control STH infections requires periodic mass drug administration (MDA) based on prevalence among populations at risk determined by diagnostic testing. Widely used copromicroscopy methods to detect infection, however, have low sensitivity as the prevalence and intensity of STH infections decline with repeated MDA. More sensitive diagnostic tools are needed to inform program decision-making. Using an integrated product development process, PATH conducted qualitative and quantitative formative research to inform the design and development of a more sensitive test for STH infections. The research, grounded in a conceptual framework for ensuring access to health products, involved stakeholder analysis, key opinion leader interviews, observational site visits of ongoing STH surveillance programs, and market research including market sizing, costing and willingness-to-pay analyses. Stakeholder analysis identified key groups and proposed strategic engagement of stakeholders during product development. Interviews highlighted features, motivations and concerns that are important for guiding design and implementation of new STH diagnostics. Process mapping outlined current STH surveillance workflows in Kenya and the Philippines. Market sizing in 2016 was estimated around half a million tests for lower STH burden countries, and 1-2 million tests for higher STH burden countries. The cost of commodities per patient for a molecular STH diagnostic may be around $10, 3-4 times higher than copromicroscopy methods, though savings may be possible in time and staffing requirements. The market is highly price sensitive as even at $5 per test, only 27% of respondents thought the test would be used by surveillance programs. A largely subsidized STH control strategy and a semi-functional Kato-Katz test may have created few incentives for manufacturers to innovate in STH diagnostics. Diverse partnerships, as well as balancing needs and expectations for new STH diagnostics are necessary to ensure access to needed products., Competing Interests: The authors have declared that no competing interests exist.

The culture of chefs from the world's best restaurants is substituted by new trends paradigmatically epitomized by the TV program Masterchef. The authors feel that a similar transformation affects modern research. Recent scientific policies constrict the design of research grants with the aim of short-term maximization of the monetary value generated by the researcher., (© 2019 WILEY Periodicals, Inc.)

Internal and external factors influence the future of laboratory medicine. In the coming years point of care testing and faster and cheaper methods of genome sequencing are predicted to become more important. Changes in laboratory organization and demography with an aging population will likewise impact the coming years. An increased information flow between laboratories and clinicians, where symptoms, findings and vital signs are combined with laboratory results and their change over time, has the potential of generating refined reports. Sharing of equipment between laboratory specialities as well as working in conjunction with clinicians in influencing patterns of testing through guidelines and algorithms may also aid in saving precious resources.

This review describes the initial development of good laboratory practice (GLP) and follows the discoveries of quality control problems in labs that conducted tests in U.S. pharmaceutical companies. In addition to introducing the essence of the GLP standards, how the GLP ensures the reconstructability and reproducibility of study results is explained in detail. Issues in nonclinical safety studies in drug development and approaches of the Japanese Pharmaceuticals and Medical Devices Agency to overcome them are also described. It is hoped that this review is helpful not only to those who work on drug development but also to faculties and students who work in academia and are involved in basic research when they attempt to resolve problems related to ensuring the reliability of basic research and research integrity.

Chemical and physical hazards are part of the daily routine when working in biorepositories. This chapter provides a brief overview of some common physical and chemical hazards encountered in biorepositories, with some basic principles to help eliminate and control these hazards by implementing safe work practices.

Genetic testing availability in the health care system is rapidly increasing, along with the diffusion of next-generation sequencing (NGS) into diagnostics. These issues make imperative the knowledge-drive optimization of testing in the clinical setting. Time estimations of wet laboratory procedure in Italian molecular laboratories offering genetic diagnosis were evaluated to provide data suitable to adjust efficiency and optimize health policies and costs. A survey was undertaken by the Italian Society of Human Genetics (SIGU). Forty-two laboratories participated. For most molecular techniques, the most time-consuming steps are those requiring an intensive manual intervention or in which the human bias can affect the global process time-performances. For NGS, for which the study surveyed also the interpretation time, the latter represented the step that requiring longer times. We report the first survey describing the hands-on times requested for different molecular diagnostics procedures, including NGS. The analysis of this survey suggests the need of some improvements to optimize some analytical processes, such as the implementation of laboratory information management systems to minimize manual procedures in pre-analytical steps which may affect accuracy that represents the major challenge to be faced in the future setting of molecular genetics laboratory., Competing Interests: We have the following interests. Cristina Lapucci is employed by Synlab Italy. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Since the publication of the ordinance of January 13th 2010, ratified by the law of May 30th 2013, medical biology in France has undergone a massive restructuration with the emergence of groups of several hundred laboratories. This evolution, which leads to a considerable reduction in the number of structures, causes numerous problems related to increased industrialization and financialization, difficulties of accreditation and disappearance of the proximity link between the biologist and the prescriber or the patient. It also leads to a clear disaffection of students, especially medical students, for this specialty whose medical character has been clearly affirmed by the law. This report takes stock of the current situation of medical biology and makes recommendations to strengthen the role of the medical biologist in the health system and patients' care.

Currently, one of the main challenges in human molecular genetics is the interpretation of rare genetic variants of unknown clinical significance. A conclusive diagnosis is of importance for the patient to obtain certainty about the cause of the disease, for the clinician to be able to provide optimal care to the patient and to predict the disease course, and for the clinical geneticist for genetic counseling of the patient and family members. Conclusive evidence for pathogenicity of genetic variants is therefore crucial. This review gives an introduction to the problem of the interpretation of genetic variants of unknown clinical significance in view of the recent advances in genetic screening, and gives an overview of the possibilities for functional tests that can be performed to answer questions about the function of genes and the functional consequences of genetic variants ("functional genomics") in the field of inborn errors of metabolism (IEM), including several examples of functional genomics studies of mitochondrial disorders and several other IEM.

The diagnosis of systemic vasculitis is challenging. Laboratory testing may provide useful information. Routine laboratory tests include erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood count, serum creatinine, urinalysis, specific autoantibodies, complement, immunoglobulin, cryoglobulin, and Hepatitis B and C serology. Although ESR and CRP are often helpful for the diagnosis of vasculitis, they are nonspecific and do not help in distinguishing between vasculitis disease activity and a concomitant infection or another source of inflammation. A few autoantibodies are helpful for diagnosis, such as anti-neutrophil cytoplasmic antibodies (ANCAs) (in ANCA-associated small-vessel vasculitis), anti-glomerular basement membrane (GBM) antibodies (in anti-GBM antibody disease), and anti-C1q antibodies (in immune complex-associated small-vessel vasculitis). The 2017 revised consensus recommendations on ANCA testing state that high-quality antigen-specific immunoassays are the preferred screening methodology for the diagnosis of ANCA-associated vasculitis. ANCA subtypes (proteinase-3-ANCA and myeloperoxidase-ANCA) are associated with different epidemiological, genetic, and clinical features., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Medical biology is a major area of medical specialization in French health care system. It is going through massive changes in public as in private sector since the 2010 Ballereau edict with the merging of laboratories and new quality standards based on accreditation. We have suggested that physicians had a negative feeling about the restructuring of medical biology in recent years. An electronic questionnaire has been sent to physicians so as to find out what they thought about the evolution of medical biology and to get suggestions to improve the taking care of the patient. Have answered 1364 residents and physicians from all specializations, all regions, practicing in public or private hospitals or in general practices. Doctors have on the whole a negative feeling about how medical biology has evolved in recent years thinking that it is moving towards industrialization with delay increasing. They are convinced that tests must be made on site. They remain satisfied with the quality of the tests and have a positive feeling about scientific evolutions and are in favor of a better clinical-biological cooperation. The study points out a lack of clarity concerning how private laboratories are organized and how they operate. A computer link between clinical pathologists and physicians to access results and a list of urgent medical examinations could be set up so as to have a more rapid access to results. Rapid diagnostic tests or delocalized biology could be used but doctors do not want these tests to replace the clinical pathologist.

The global biomedical research enterprise is driving substantial advances in medicine and healthcare. Yet it appears that the enterprise is rather wasteful, falling short of its true innovative potential. Suggested reasons are manifold and involve various stakeholders, such that there is no single remedy. In the present paper, I will argue that laboratories are the basic working units of the biomedical research enterprise and an important site of action for corrective intervention. Keeping laboratories relatively small will enable better training and mentoring of individual scientists, which in turn will yield better performance of the scientific workforce. The key premise of this argument is that people are at the heart of the successes and failures of biomedical research, yet the human dimension of science has been unduly neglected in practice. Renewed focus on the importance of laboratories and their constituent scientists is one promising approach to reducing waste and increasing efficiency within the biomedical research enterprise.

Testing for antinuclear antibodies is the most frequently prescribed analysis for the diagnosis of rheumatic diseases. Indirect immunofluorescence remains the gold standard method for their detection despite the increasing use of alternative techniques. In order to standardize the manual microscopy reading, automated acquisition and interpretation systems have emerged. This publication enables us to present our method of interpretation and characterization of antinuclear antibodies based on a cascade of analyses and to share our everyday experience of the G Sight from Menarini. The positive/negative discrimination on Hep cells 2000 is correct in 85% of the cases. In most of the false negative results, it is a question of aspecific or low titers patterns, but a few cases of SSA speckled patterns of low titers demonstrated a probability index below 8. Regarding the pattern recognition, some types and mixed patterns are not properly recognized. Concerning the probability index correlated in some studies to final titer, the weak fluorescence of certain patterns and the random presence of artifacts that distort the index don't lead us to continue it in our daily practice. In conclusion, automated reading systems facilitate the reporting of results and traceability of patterns but still require the expertise of a laboratory technologist for positive/negative discrimination and for pattern recognition.

Twenty-first century biomedical research is advantaged by institutional infrastructures that foster a collaborative, multidisciplinary approach. A few critical elements in the design of labs, research buildings, or campus can make interaction easier while preserving privacy and comfort for the individual researcher., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Highly customizable laboratory information systems help to address great variations in laboratory workflows, typical in Pathology. Often, however, built-in customization tools are not sufficient to add all of the desired functionality and improve systems interoperability. Emerging technologies and advances in medicine often create a void in functionality that we call a functionality gap. These gaps have distinct characteristics—a persuasive need to change the way a pathology group operates, the general availability of technology to address the missing functionality, the absence of this technology from your laboratory information system, and inability of built-in customization tools to address it. We emphasize the pervasive nature of these gaps, the role of pathology informatics in closing them, and suggest methods on how to achieve that. We found that a large number of the papers in the Journal of Pathology Informatics are concerned with these functionality gaps, and an even larger proportion of electronic posters and abstracts presented at the Pathology Informatics Summit conference each year deal directly with these unmet needs in pathology practice. A rapid, continuous, and sustainable approach to closing these gaps is critical for Pathology to provide the highest quality of care, adopt new technologies, and meet regulatory and financial challenges. The key element of successfully addressing functionality gaps is gap ownership—the ability to control the entire pathology information infrastructure with access to complementary systems and components. In addition, software developers with detailed domain expertise, equipped with right tools and methodology can effectively address these needs as they emerge.