The utility of diagnostic tests derives from the ability to translate the population concepts of sensitivity and specificity into information that will be useful for the individual patient: the predictive value of the result. As the array of available diagnostic testing broadens, there is a temptation to de-emphasize history and physical findings and defer to the objective rigor of technology. However, diagnostic test interpretation is not always straightforward. One significant barrier to routine use of probability-based test interpretation is the uncertainty inherent in pretest probability estimation, the critical first step of Bayesian reasoning. The context in which this uncertainty presents the greatest challenge is when test results oppose clinical judgment. It is this situation when decision support would be most helpful. The authors propose a simple graphical approach that incorporates uncertainty in pretest probability and has specific application to the interpretation of unexpected results. This method quantitatively demonstrates how uncertainty in disease probability may be amplified when test results are unexpected (opposing clinical judgment), even for tests with high sensitivity and specificity. The authors provide a simple nomogram for determining whether an unexpected test result suggests that one should "switch diagnostic sides.'' This graphical framework overcomes the limitation of pretest probability uncertainty in Bayesian analysis and guides decision making when it is most challenging: interpretation of unexpected test results.
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http://dx.doi.org/10.1177/0272989X08323620 | DOI Listing |
Ann Bot
January 2025
Division of BioInvasions, Global Change & Macroecology, University of Vienna, Austria.
Background And Aims: Despite accelerating interest in island evolution, the general evolutionary trajectories of island flowers remain poorly understood. In particular the island rule, which posits that small organisms become larger and large organisms to become smaller after island colonization, while tested in various plant traits, has never been tested in flower size. Here, we provide the first test for the island rule in flower size for animal- and wind-pollinated flowers, and the first evidence for generalized in-situ evolution of flower size on islands.
View Article and Find Full Text PDFBrain Commun
January 2025
Department of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USA.
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death, likely stemming from seizure activity disrupting vital brain centres controlling heart and breathing function. However, understanding of SUDEP's anatomical basis and mechanisms remains limited, hampering risk evaluation and prevention strategies. Prior studies using a neuron-specific conditional knockout mouse model of SUDEP identified the primary importance of brain-driven mechanisms contributing to sudden death and cardiorespiratory dysregulation; yet, the underlying neurocircuits have not been identified.
View Article and Find Full Text PDFJCI Insight
January 2025
Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America.
Thrombin promotes the proliferation and function of CD8+ T cells. To test if thrombin prevents exhaustion and sustains antiviral T cell activity during chronic viral infection, we depleted the thrombin-precursor prothrombin to 10% of normal levels in mice prior to infection with the clone 13 strain of lymphocytic choriomeningitis virus. Unexpectedly, prothrombin insufficiency resulted in 100% mortality after infection that was prevented by depletion of CD8+ T cells, suggesting that reduced availability of prothrombin enhances virus-induced immunopathology.
View Article and Find Full Text PDFMAbs
December 2025
SeromYx Systems, Woburn, MA, USA.
The field of antibody therapeutics is rapidly growing, with over 210 antibodies currently approved or in regulatory review and ~ 1,250 antibodies in clinical development. Antibodies are highly versatile molecules that, with strategic design of their antigen-binding domain (Fab) and the domain responsible for mediating effector functions (Fc), can be used in a wide range of therapeutic indications. Building on many years of progress, the biopharmaceutical industry is now advancing innovative research and development by exploring new targets and new formats and using antibody engineering to fine-tune functions tailored to specific disease requirements.
View Article and Find Full Text PDFWomen Health
January 2025
Neuroimmunophysiology and Chrononutrition Research Group, Department of Physiology, Universidad de Extremadura, Badajoz, Spain.
Background: A growing body of evidence suggests a potential link between the SARS-CoV-2 vaccine and menstrual changes in women who were menstruating at the time of vaccination. Nevertheless, the prevalence of this event in those with secondary amenorrhea for different causes, i.e.
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