Greg Stuart.

In an interview with Neuron, Greg Stuart discusses the COVID-19 pandemic effects on the Australian research landscape and recounts how early influencers shaped him as both a neuroscientist and mentor.

Testing Internal Quality Control of Clinical Laboratory Data Using Paired t-Test under Uncertainty.

The existing paired t-test under classical statistics cannot be applied when the data is obtained from the complex process, having interval, uncertainty, indeterminacy, and incompleteness. In this paper, the modification of the paired t-test under neutrosophic statistics is proposed. The testing criterion of the proposed paired t-test is given. The application of the proposed paired t-test is given using the interval quality control of clinical laboratory data. From the analysis, it can be seen than the proposed test is quite effective and informative to apply for testing the measurement tools in the clinical laboratory.

Machine learning in health care and laboratory medicine: General overview of supervised learning and Auto-ML.

Artificial Intelligence (AI) and machine learning (ML) have now spawned a new field within health care and health science research. These new predictive analytics tools are starting to change various facets of our clinical care domains including the practice of laboratory medicine. Many of these ML tools and studies are also starting to populate our literature landscape as we know it but unfamiliarity of the average reader to the basic knowledge and critical concepts within AI/ML is now demanding a need to better prepare our audience to such relatively unfamiliar concepts. A fundamental knowledge of such platforms will inevitably enhance cross-disciplinary literacy and ultimately lead to enhanced integration and understanding of such tools within our discipline. In this review, we provide a general outline of AI/ML along with an overview of the fundamental concepts of ML categories, specifically supervised, unsupervised, and reinforcement learning. Additionally, since the vast majority of our current approaches within ML in laboratory medicine and health care involve supervised algorithms, we will predominantly concentrate on such platforms. Finally, the need for making such tools more accessible to the average investigator is becoming a major driving force for the need of automation within these ML platforms. This has now given rise to the automated ML (Auto-ML) world which will undoubtedly help shape the future of ML within health care. Hence, an overview of Auto-ML is also covered within this manuscript which will hopefully enrich the reader's understanding, appreciation, and the need for embracing such tools.

Covid-19 Pandemic: Through the Lens of Science, a Painstaking Review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has imperiled human lives and global infrastructure since the emergence of SARS-CoV-2 in China. The current review meticulously summarizes the COVID-19 pandemic situation through the lens of science from the inception of the outbreak to the current progression, which is valuable to mitigate the current pandemic situation. METHODS: We reviewed all the relevant literature available on PubMed, Web of Sciences, Google Scholar, and World Health Organization (WHO) website related to COVID-19 from the inception of the outbreak to 18 June 2020. We selected ninety different scientific studies and reports to compile the current review. RESULTS: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a betacoronavirus with four major structural proteins encoded by S, M, E, and N genes and distinct in morphology. The potential provenance of SARS-Cov-2 is zoonotic, and it binds to the host cell receptors by spike protein. The SARS-CoV-2 infectious cycle carries on through direct contact, air, inanimate objects, and contaminated surfaces. The reproductive number (R0) of SARS-CoV-2 is 2 to 3.5, representing that one infected patient can spread this virus to two to three people. An expeditious laboratory diagnosis has a pivotal role in patient management and prevention. Due to the lack of definitive treatment, symptomatic medication regimen and supportive organ therapies are adapted for debilitated patients. CONCLUSIONS: Nucleoside analogs and protease-inhibitors have approved to attenuate the viral infection until the discovery of a specific drug. The other treatment strategies comprise antimalarial drugs, monoclonal antibodies, and glucocorticoids. The use of alcoholic scrubs, sodium hypochlorite, masks, social distancing, and quarantine the affected individual is inevitable to eradicate the infection vector and to break the transmission path.

[Emergence of 3D human fatty liver models engineered in the laboratory]. / L'émergence des modèles miniatures de foie gras humain en 3D générés en laboratoire.

Organoids offer an elegant approach to model human diseases and test new drugs. Nonalcoholic fatty liver disease (NAFLD) whose incidence has dramatically increased in recent years with the rise of obesity, is defined by triglyceride accumulation in hepatocytes, inflammation, liver injury, and progression to fibrosis. There is currently no approved therapy but many pathways are being explored. Two American teams have created mini-steatotic livers using different approaches, both using induced pluripotent stem cells (iPS), thus offering new tools to test developing drugs.

TITLE: L'émergence des modèles miniatures de foie gras humain en 3D générés en laboratoire. ABSTRACT: Les organoïdes constituent une approche de choix pour modéliser a minima une maladie humaine et tester l'efficacité thérapeutique de certaines drogues. La stéatopathie métabolique ou maladie du foie gras, dont l'incidence a considérablement augmenté avec l'accroissement de l'obésité dans les pays développés, se caractérise par l'accumulation de triglycerides dans l'hépatocyte et une atteinte hépatique pouvant évoluer vers la fibrose. Il n'existe pas de traitement efficace, mais de nombreuses pistes sont actuellement explorées. Deux équipes américaines ont récemment utilisé les cellules souches pluripotentes induites (iPS) et la culture muticellulaire pour modéliser un mini-foie stéatosique par deux approches différentes, offrant ainsi de nouveaux outils pour tester les drogues en cours de développement.

Philip T. Cagle, MD-Editor-in-Chief of the Archives of Pathology & Laboratory Medicine, 2005-2019.

• The Archives of Pathology & Laboratory Medicine was first published in 1926 as a specialty journal of the American Medical Association. It became the official journal of the College of American Pathologists in 1995. Under the dynamic leadership of its most recent editor-in-chief, Philip T. Cagle, MD, the Archives has dramatically increased its impact factor and become the most widely read general pathology journal. Dr. Cagle has consistently added leading pathologists to the editorial board, and the collective expertise of these individuals is clearly evident in new, cutting-edge journal masthead sections. The Archives has featured innovative content in the field of digital pathology, including articles on the utilization of smart phones in pathology and the incorporation of whole-slide images and videos into the content of articles. During the current editorial board's tenure, special sections were introduced and have proven immensely popular with the journal's readership. As the Archives celebrates its 94th anniversary, its editorial board remains committed to providing insightful and relevant medical knowledge. The journal's open access Web site ( www.archivesofpathology.org ) allows the dissemination of this information to every corner of the globe at no expense to those who wish to expand their knowledge or improve their medical practice. Dr. Cagle, with support from the editorial board and journal staff, has worked tirelessly during his tenure as Archives editor-in-chief to greatly enhance the content of the journal and its stature within pathology and laboratory medicine.

Clinical metagenomics.

Clinical metagenomic next-generation sequencing (mNGS), the comprehensive analysis of microbial and host genetic material (DNA and RNA) in samples from patients, is rapidly moving from research to clinical laboratories. This emerging approach is changing how physicians diagnose and treat infectious disease, with applications spanning a wide range of areas, including antimicrobial resistance, the microbiome, human host gene expression (transcriptomics) and oncology. Here, we focus on the challenges of implementing mNGS in the clinical laboratory and address potential solutions for maximizing its impact on patient care and public health.

Driving the route of laboratory medicine: a manifesto for the future.

The role of laboratory medicine is essential in healthcare, since in vitro diagnostic testing represents now an unavoidable part of reasoning and clinical decision making. Laboratory tests are an essential part of most care pathways, aimed at optimizing resource utilization and improving patient outcome. The activity of laboratory professionals is interconnected with all medical disciplines, and provides a crucial support for ordering the right test, for the right patient and at the right time, but also helps interpreting and using laboratory data. Although recent advancement in laboratory medicine, catalyzed by technical innovations and development of innovative tests, have promoted a substantial revolution in the organization of clinical laboratories, the future of this profession seems still ambiguous. We have hence developed a "manifesto" of laboratory medicine, meant to promote an innovative prospect of our discipline and encouraging the establishment of a new generation of laboratory professionals and managers.

Adoption of Evidence-Based Medicine in Clinical Laboratory Science: A Survey of the Prevalence of Systematic and Narrative Reviews.

BACKGROUND: Systematic reviews (SRs) play a critical role in evidence-based medicine. OBJECTIVE: To determine the publication trends of SRs in clinical laboratory science (CLS). METHODS: We searched Scopus to identify all reviews published in the top 20 CLS journals during the past 10 years (2008-2017). We determined year of publication, review type (systematic vs narrative), citations, and whether the review was accompanied by a meta-analysis (MA). RESULTS: We identified 2934 reviews. Of these, 2833 (96.6%) were narrative reviews, and 98 (3.3%) were SRs. A total of 67 (66.3%) of the SRs were accompanied by a MA. Three journals accounted for 68 of 98 (69.4%) SRs. The percentage of SRs (relative to all reviews) has increased during the past decade (P = .01). SRs were more frequently published in high-impact journals (P <.001). CONCLUSION: The publication rate of SRs in CLS journals has increased during the past decade.

Quality control limits: Are we setting them too wide?

BACKGROUND: Quality control charts (Levey Jennings Charts) are based on estimates of variation. There are two general approaches for estimating variation: those based on short-term variation and those based on long-term variation. We have observed that clinical laboratory science (CLS) tends to estimate variation using long-term variation but that most other fields use short-term variation. The objective of this study is to compare these two methods of estimating process variation, compare the accuracy of control limits generated by each method, and explore whether it would be useful for clinical laboratories to adopt methods used in other fields. METHODS: We conducted a literature review to compare recommendations for methods for estimation of variation in CLS with other fields. We searched textbooks for suggested methods and also searched the primary literature for references to methods associated with short-term and long-term variation. We provide theoretical results from statistics to show that, in theory, short-term estimates can differ from long-term estimates of variation. We used simulation studies to show that one can construct examples where short-term and long-term estimates of variation lead to significant differences in control limits. Finally, we show laboratory data comparing short-term and long-term estimates of variation. RESULTS: We found that practice in CLS differs from other fields. We found no references to methods based on short-term variation in CLS textbooks and only one reference in the primary literature. In contrast, standard quality control (QC) texts recommend methods based on short-term variation and the primary literature makes frequent reference to such methods. We found statistical papers that show that, in theory, estimates based on long-term variation can produce inflated estimates of process variation. We used simulation to show that such examples can be constructed. We examined 95 QC charts and found that in 93 cases, there were significant differences between short-term and long-term estimates of variation. The ratio of long-term to short-term variation was greater than 1.5 in 18% of cases. CONCLUSION: Estimates of variation based on short-term and long-term variation can lead to significant differences in estimates. Estimates based on long-term variation are frequently larger than estimates based on short-term variation.

Laboratory investigations.

This chapter deals with chemical and hematologic investigations which are often considered in the diagnostic workup of subacute to chronic cerebellar ataxias. Relevant investigations in blood (serum, plasma), urine, and cerebrospinal fluid are discussed. Particular attention is paid to early diagnosis of treatable metabolic ataxias (such as abetalipoproteinemia, coenzyme Q10 deficiency, cerebrotendinous xanthomatosis, glucose transporter type 1 deficiency, Refsum disease, and vitamin E deficiency), but autoimmune ataxias, other vitamin deficiencies, and endocrine disorders should also be kept in mind. Adequate interpretation of test results has to consider age-specific reference values. The selection of investigations should mainly be driven by the overall clinical context, considering gender, history, age, and mode of presentation, cerebellar and other neurologic as well as extraneurologic findings.

Sourcebook update: intestinal smooth muscle contractility and autonomic control.

This laboratory practical requires first-year students to anticipate the effects of drugs active at cholinergic and adrenergic receptors on gut motility in order to design experiments during an authentic inquiry exercise. Rather than specifying a strict sequence of drug additions that aim to provide ideal demonstrations of pharmacological and physiological antagonism, I have instead designed switches into the drugs provided and set students, working in small teams, the task of identifying the switched drugs, an inquiry activity. To extend the teamwork aspect, laboratory reports were submitted by the student teams rather than individual students. Staff observed that discussions within the teams were stimulated by the inquiry-led nature of the practical. The quality of the laboratory reports submitted by teams were substantially improved over the individual reports submitted in previous years. (Students previously worked in teams, but simply followed a list of prescribed experiments and wrote individual reports.) Although, in conversation, teams of students had an improved understanding of the regulation of gut motility by the parasympathetic and sympathetic divisions of the autonomic nervous system and could readily distinguish between pharmacological and functional antagonism, no attempt was made to evaluate learning because the revision was triggered by the observed effect of a technical error and was not otherwise planned. It is likely that laboratory practicals, in general, would benefit from inclusion of inquiry.

Laboratory practical to study the differential innervation pathways of urinary tract smooth muscle.

In the mammalian lower urinary tract, there is a reciprocal relationship between the contractile state of the bladder and urethra. As the bladder fills with urine, it remains relaxed to accommodate increases in volume, while the urethra remains contracted to prevent leakage of urine from the bladder to the exterior. Disruptions to the normal contractile state of the bladder and urethra can lead to abnormal micturition patterns and urinary incontinence. While both the bladder and urethra are smooth-muscle organs, they are differentially contracted by input from cholinergic and sympathetic nerves, respectively. The laboratory practical described here provides an experiential approach to understanding the anatomy of the lower urinary tract. Several key factors in urinary tract physiology are outlined, e.g., the bladder is contracted by activation of the parasympathetic pathway via cholinergic stimulation on muscarinic receptors, whereas the urethra is contracted by activation of the sympathetic pathway via adrenergic stimulation on α1-adrenoceptors. This is achieved by measuring the force generated by bladder and urethra smooth muscle to demonstrate that acetylcholine contracts the smooth muscle of the bladder, whereas adrenergic agonists contract the urethral smooth muscle. An inhibition of these effects is also demonstrated by application of the muscarinic receptor antagonist atropine and the α1-adrenergic receptor blocker phentolamine. A list of suggested techniques and exam questions to evaluate student understanding on this topic is also provided.

Call for more transparency in manufacturers declarations on serum indices: On behalf of the Working Group for Preanalytical Phase (WG-PRE), European Federation of Clinical Chemistry and Laboratory Medicine (EFLM).

The presence of interfering substances like free hemoglobin, bilirubin or lipids compromises sample quality and potentially affects laboratory analysis and test results. Recently, the use of serum indices for objectively assessing sample quality has become commonplace and many preanalytical platforms, as well as clinical chemistry and coagulation analyzers, are now equipped with this analytical feature. Nevertheless, some important drawbacks remain in this practice, mainly pertaining the measurement procedure, the approach for reporting interference data, the definition of objective thresholds of interference after which test results may be biased, and the lack of harmonized practices for describing how interference cut-offs have been identified. Therefore, this document aims to discuss these important caveats and propose some reliable solutions that may be adopted by manufacturers for increasing worldwide harmonization of serum indices.

Quo Vadis Point-of-Care Diagnostics? Report II of the SWISS SYMPOSIUM in Point-of-Care Diagnostics 2017.

U.S. studies show that the global point-of-care (POC) diagnostics market will reach $40.5 bn by 2022, with a compound annual growth rate (CAGR) of 10%. This is one of the reasons why HES-SO Valais-Wallis and CSEM, acting on behalf of the NTN Swiss Biotech thematic platform in vitro Diagnostics (TP IVD), invited interested parties on October 26, 2017 to the SWISS SYMPOSIUM in Point-of-Care Diagnostics (see CHIMIA No. 12/2017). We now bring the second report on the future prospects of POC diagnostics.