T cells express T cell receptors (TCRs) composed of somatically recombined TCRα and TCRβ chains, which mediate recognition of major histocompatibility complex (MHC)-antigen complexes and drive the ...antigen-specific adaptive immune response to pathogens and cancer. The TCR repertoire in each individual is highly diverse, which allows for recognition of a wide array of foreign antigens, but also presents a challenge in analyzing this response using conventional methods. Recent studies have developed high-throughput sequencing technologies to identify TCR sequences, analyze their antigen specificities using experimental and computational tools, and pair TCRs with transcriptional and epigenetic cell state phenotypes in single cells. In this Review, we highlight these technological advances and describe how they have been applied to discover fundamental insights into T cell-mediated immunity.
To systematically review methods developed and employed to evaluate the diagnostic accuracy of medical test when there is a missing or no gold standard.
Articles that proposed or applied any methods ...to evaluate the diagnostic accuracy of medical test(s) in the absence of gold standard were reviewed. The protocol for this review was registered in PROSPERO (CRD42018089349).
Identified methods were classified into four main groups: methods employed when there is a missing gold standard; correction methods (which make adjustment for an imperfect reference standard with known diagnostic accuracy measures); methods employed to evaluate a medical test using multiple imperfect reference standards; and other methods, like agreement studies, and a mixed group of alternative study designs. Fifty-one statistical methods were identified from the review that were developed to evaluate medical test(s) when the true disease status of some participants is unverified with the gold standard. Seven correction methods were identified and four methods were identified to evaluate medical test(s) using multiple imperfect reference standards. Flow-diagrams were developed to guide the selection of appropriate methods.
Various methods have been proposed to evaluate medical test(s) in the absence of a gold standard for some or all participants in a diagnostic accuracy study. These methods depend on the availability of the gold standard, its' application to the participants in the study and the availability of alternative reference standard(s). The clinical application of some of these methods, especially methods developed when there is missing gold standard is however limited. This may be due to the complexity of these methods and/or a disconnection between the fields of expertise of those who develop (e.g. mathematicians) and those who employ the methods (e.g. clinical researchers). This review aims to help close this gap with our classification and guidance tools.
Healthcare practitioners, patient safety leaders, educators and researchers increasingly recognise the value of human factors/ergonomics and make use of the discipline's person-centred models of ...sociotechnical systems. This paper first reviews one of the most widely used healthcare human factors systems models, the Systems Engineering Initiative for Patient Safety (SEIPS) model, and then introduces an extended model, 'SEIPS 2.0'. SEIPS 2.0 incorporates three novel concepts into the original model: configuration, engagement and adaptation. The concept of configuration highlights the dynamic, hierarchical and interactive properties of sociotechnical systems, making it possible to depict how health-related performance is shaped at 'a moment in time'. Engagement conveys that various individuals and teams can perform health-related activities separately and collaboratively. Engaged individuals often include patients, family caregivers and other non-professionals. Adaptation is introduced as a feedback mechanism that explains how dynamic systems evolve in planned and unplanned ways. Key implications and future directions for human factors research in healthcare are discussed.
Practitioner Summary: SEIPS 2.0 is a new human factors/ergonomics framework for studying and improving health and healthcare. It describes how sociotechnical systems shape health-related work done by professionals and non-professionals, independently and collaboratively. Work processes, in turn, shape patient, professional and organisational outcomes. Work systems and processes undergo planned and unplanned adaptations.
This article reviews the peer-reviewed literature addressing the healthcare information available on YouTube. Inclusion and exclusion criteria were determined, and the online databases PubMed and Web ...of Knowledge were searched using the search phrases: (1) YouTube* AND Health* and (2) YouTube* AND Healthcare*. In all, 18 articles were reviewed, with the results suggesting that (1) YouTube is increasingly being used as a platform for disseminating health information; (2) content and frame analysis were the primary techniques employed by researchers to analyze the characteristics of this information; (3) YouTube contains misleading information, primarily anecdotal, that contradicts the reference standards and the probability of a lay user finding such content is relatively high; (4) the retrieval of relevant videos is dependent on the search term used; and (5) videos from government organizations and professional associations contained trustworthy and high-quality information. YouTube is used as a medium for promoting unscientific therapies and drugs that are yet to be approved by the appropriate agencies and has the potential to change the beliefs of patients concerning controversial topics such as vaccinations. This review recognizes the need to design interventions to enable consumers to critically assimilate the information posted on YouTube with more authoritative information sources to make effective healthcare decisions.
Superficial palpable masses of the head and neck are common in the pediatric population, with the vast majority of the lesions ultimately proven to be benign. Duplex ultrasonography (US) has emerged ...as the first-line imaging modality for the evaluation of superficial pediatric masses. Without utilizing radiation, iodinated contrast material, or sedation and/or anesthesia, US provides a means for quick and cost-effective acquisition of information, including the location, size, shape, internal content, and vascularity of the mass. In this review, the US findings are described for a variety of common and uncommon pediatric head and neck masses diagnosed in our practice. Specifically, the entities covered include neonatal scalp hematoma, craniosynostosis, dermoid and epidermoid cysts, Langerhans cell histiocytosis, lymph nodes and their complications, fibromatosis colli, thyroglossal duct cyst, branchial cleft cyst, cervical thymus, congenital goiter, thyroid papillary carcinoma, parathyroid adenoma, hemangioma, lymphangioma, jugular vein phlebectasia, Lemierre syndrome, acute parotitis and parotid abscess, leukemia and/or lymphoma, neurogenic tumor, and rhabdomyosarcoma. Ultimately, in situations in which the head or neck mass is too large, deep, or hyperechoic to be fully assessed within the US field of view, or if malignancy or a high-flow vascular lesion is suspected, then further evaluation with cross-sectional imaging is warranted. Online supplemental material is available for this article.
RSNA, 2018.
Purpose
In the initial PALOMA-2 (NCT01740427) analysis with median follow-up of 23 months, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) in women with estrogen ...receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) hazard ratio (HR) 0.58;
P
< 0.001. Herein, we report results overall and by subgroups with extended follow-up.
Methods
In this double-blind, phase 3 study, post-menopausal women with ER+/HER2− ABC who had not received prior systemic therapy for their advanced disease were randomized 2:1 to palbociclib-letrozole or placebo-letrozole. Endpoints include investigator-assessed PFS (primary), safety, and patient-reported outcomes (PROs).
Results
After a median follow-up of approximately 38 months, median PFS was 27.6 months for palbociclib–letrozole (
n
= 444) and 14.5 months for placebo-letrozole (
n
= 222) (HR 0.563; 1-sided
P
< 0.0001). All subgroups benefited from palbociclib treatment. The improvement of PFS with palbociclib-letrozole was maintained in the next 2 subsequent lines of therapy and delayed the use of chemotherapy (40.4 vs. 29.9 months for palbociclib–letrozole vs. placebo-letrozole). Safety data were consistent with the known profile. Patients’ quality of life was maintained.
Conclusions
With approximately 15 months of additional follow-up, palbociclib plus letrozole continued to demonstrate improved PFS compared with placebo plus letrozole in the overall population and across all patient subgroups, while the safety profile remained favorable and quality of life was maintained. These data confirm that palbociclib-letrozole should be considered the standard of care for first-line therapy in patients with ER+/HER2− ABC, including those with low disease burden or long disease-free interval. Sponsored by Pfizer; ClinicalTrials.gov: NCT01740427.
Treatment decisions in inflammatory bowel diseases are increasingly based on longitudinal tracking of calprotectin results. Many hospital laboratories measure calprotectin levels in sent-in stool ...samples with an enzyme-linked immunosorbent assay (ELISA). Several manufacturers introduced a lateral flow-based test with software application that turns a smartphone camera into a reader for quantitative measurements. We compared three home tests (IBDoc, QuantonCal and CalproSmart) and companion ELISA tests (fCAL, IDK-Calprotectin and Calprotectin-ALP) to see if measurement pairs agreed sufficiently.
A method comparison study was conducted with stool samples from patients with active or quiescent inflammatory bowel disease. Medical students without any specific laboratory training carried out the home tests with two iOS (iPhone 6 and 7) and two Android devices (Samsung Galaxy S6 and Motorola Moto G5 Plus). Two experienced laboratory technicians measured the calprotectin concentration with the ELISA method. Primary outcome was test agreement (defined as percentage of paired measurements within predefined limits of difference). Secondary outcome included reading error rate (RER) per smartphone type.
We performed 1440 smartphone readings and 120 ELISA tests. In the low calprotectin range (≤500 μg/g) IBDoc, QuantOnCal and CalproSmart showed 87%, 82% and 76% agreement with their companion ELISAs. In the high range (>500 μg/g) the agreement was 37%, 19% and 37%, respectively. CalproSmart and QuantOnCal had significantly higher RERs than IBDoc (respectively 5.8% and 4.8%, versus 1.9%). Forty-three percent of reading errors was on the Motorola device, in particular with the QuantOnCal application.
All three calprotectin home tests and companion ELISAs agreed sufficiently when concentrations are ≤500 μg/g. To minimize wrongful interpretation of calprotectin changes over time it is essential to always use the home test and companion ELISA of one and the same manufacturer. Manufacturers should explicitly evaluate and report the suitability of commonly used smartphones for quantitative calprotectin readings.
To demonstrate a noninvasive method to visualize and analyze the parafoveal capillary network in humans.
An adaptive optics scanning laser ophthalmoscope was used to acquire high resolution retinal ...videos on human subjects. Video processing tools that enhance motion contrast were developed and applied to the videos to generate montages of parafoveal retinal capillaries. The capillary network and foveal avascular zone (FAZ) were extracted using video and image analysis algorithms. The capillary densities in the zone immediately outside the FAZ were calculated and the variation in density as a function of direction was investigated. Extracted FAZ geometries were used to calculate area and effective diameters. The authors also compared their method against fluorescein angiography (FA) for one subject.
The parafoveal capillaries were clearly visible when the motion contrast in noninvasive videos was enhanced. There was a marked improvement in the contrast of the parafoveal capillaries when compared to the unprocessed videos. The average FAZ area was 0.323 mm(2), with an average effective diameter of 633 microm. There was no variation in capillary density near the FAZ in different directions.
Using motion cues to enhance vessel contrast is a powerful tool for visualizing the capillary network, in the absence of contrast agents. The authors demonstrate a tool to study the microcirculation of healthy subjects noninvasively.
My reference point, not yours Buchanan, Joy A.
Journal of economic behavior & organization,
03/2020, Volume:
171
Journal Article
Peer reviewed
•People assume that everyone shares their own reference point, even if they are told that is not the case.•If prompted to think about a specific other person who has a different reference point, then ...predictions are less biased.•The experiment includes a cognitive test, which implies that bias from one’s own reference point is not merely confusion.•It’s easier to understand the behavior of another person if you consider the history that person has lived through.
Reference points formed by initial endowments influence individual decisions. This experiment tests whether an individual can predict the behavior of other people who have different reference points. Despite financial incentives for being correct, players fail to imagine themselves in another person’s shoes. A low endowment player generally cannot predict the behavior of those who were assigned high endowments, and vice versa, when asked about group behavior. Instead of considering the perspectives of others, a low endowment player predicts that all others will act as if they all had low endowments. This controlled experiment helps explain why it is difficult to understand the perspectives of other people, while also demonstrating that it is possible when a player is specifically prompted to consider an individual in a different circumstance.
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