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Real-world data (RWD) collected to generate real-world evidence (RWE) holds promise for expediting patient and healthcare provider access to new in vitro diagnostics (IVDs) by serving as evidence to demonstrate test performance or utility. However, uncertainties remain for IVD developers (device manufacturers), regulators, and other healthcare stakeholders on the specifics of collecting fit-for-purpose RWD and using RWE for regulatory decision-making. We report on a unique approach to medical device regulatory review called the Open Hand Initiative, by which the US Food and Drug Administration (FDA) and device manufacturers collaborate to ensure the appropriate use of RWD/RWE to support regulatory decision-making. Normally, regulatory submission interactions are confidential; in the Open Hand approach, device manufacturers share high-level learnings from pre-submission interactions to advance the use of reliable and relevant RWD/RWE for regulatory decision-making. In a pilot study, the Open Hand approach was applied to pre-submission interactions regarding the use of RWD/RWE for transition of SARS-CoV-2 serology IVDs with Emergency Use Authorization (EUA) to full market authorization. Participants in the pilot agreed that the candid discussions were key to identifying barriers to efficient, timely, and robust RWE generation for IVD premarket submissions. The pilot also led to valuable lessons learned around current regulatory requirements for RWE, SARS-CoV-2 testing complexities, and the impact that the rapidly evolving COVID-19 pandemic had on RWD availability and quality. The Open Hand Initiative can be applied more broadly to guide device manufacturers in collecting high-quality RWD to generate RWE for premarket applications., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) is commonly included in brain studies for structural imaging using magnitude images; however, its phase images can provide an opportunity to assess microbleed burden using quantitative susceptibility mapping (QSM). This potential application for MPRAGE-based QSM was evaluated using in vivo and simulated measurements. Possible factors affecting image quality were also explored. Detection sensitivity was evaluated against standard multiecho gradient echo (MEGE) QSM using 3-T in vivo data of 15 subjects with a combined total of 108 confirmed microbleeds. The two methods were compared based on the microbleed size and susceptibility measurements. In addition, simulations explored the detection sensitivity of MPRAGE-QSM at different representative magnetic field strengths and echo times using microbleeds of different size, susceptibility, and location. Results showed that in vivo microbleeds appeared to be smaller (× 0.54) and of higher mean susceptibility (× 1.9) on MPRAGE-QSM than on MEGE-QSM, but total susceptibility estimates were in closer agreement (slope: 0.97, r 2 : 0.94), and detection sensitivity was comparable. In simulations, QSM at 1.5 T had a low contrast-to-noise ratio that obscured the detection of many microbleeds. Signal-to-noise ratio (SNR) levels at 3 T and above resulted in better contrast and increased detection. The detection rates for microbleeds of minimum one-voxel diameter and 0.4-ppm susceptibility were 0.55, 0.80, and 0.88 at SNR levels of 1.5, 3, and 7 T, respectively. Size and total susceptibility estimates were more consistent than mean susceptibility estimates, which showed size-dependent underestimation. MPRAGE-QSM provides an opportunity to detect and quantify the size and susceptibility of microbleeds of at least one-voxel diameter at B 0  of 3 T or higher with no additional time cost, when standard T 2 *-weighted images are not available or have inadequate spatial resolution. The total susceptibility measure is more robust against sequence variations and might allow combining data from different protocols., (© 2024 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Purpose: To develop and evaluate a method for rapid estimation of multiparametric T 1 , T 2 , proton density, and inversion efficiency maps from 3D-quantification using an interleaved Look-Locker acquisition sequence with T 2 preparation pulse (3D-QALAS) measurements using self-supervised learning (SSL) without the need for an external dictionary., Methods: An SSL-based QALAS mapping method (SSL-QALAS) was developed for rapid and dictionary-free estimation of multiparametric maps from 3D-QALAS measurements. The accuracy of the reconstructed quantitative maps using dictionary matching and SSL-QALAS was evaluated by comparing the estimated T 1 and T 2 values with those obtained from the reference methods on an International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology phantom. The SSL-QALAS and the dictionary-matching methods were also compared in vivo, and generalizability was evaluated by comparing the scan-specific, pre-trained, and transfer learning models., Results: Phantom experiments showed that both the dictionary-matching and SSL-QALAS methods produced T 1 and T 2 estimates that had a strong linear agreement with the reference values in the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology phantom. Further, SSL-QALAS showed similar performance with dictionary matching in reconstructing the T 1 , T 2 , proton density, and inversion efficiency maps on in vivo data. Rapid reconstruction of multiparametric maps was enabled by inferring the data using a pre-trained SSL-QALAS model within 10 s. Fast scan-specific tuning was also demonstrated by fine-tuning the pre-trained model with the target subject's data within 15 min., Conclusion: The proposed SSL-QALAS method enabled rapid reconstruction of multiparametric maps from 3D-QALAS measurements without an external dictionary or labeled ground-truth training data., (© 2023 International Society for Magnetic Resonance in Medicine.)

Background: Aphasia assessment is traditionally divided into formal and informal approaches. Informal assessment is useful in developing a rich understanding of the person with aphasia's performance, e.g., describing performance in the context of real-world activities, and exploring the impact of environmental and/or partner supports upon communication. However, defining 'informal assessment' is problematic and can result in clinical issues including idiosyncratic practices regarding why, when and how to apply informal assessment., Aims: To examine the extent to which the informal assessment literature can guide speech and language therapists (SLTs) in their clinical application of informal assessment for post-stroke aphasia., Methods & Procedures: A scoping review methodology was used. A systematic search of electronic databases (Scopus, Embase, PyscInfo, CINAHL, Ovid Medline and AMED) gave informal assessment references between 2000 and 2017 to which title/abstract and full-text screening against inclusion criteria were applied. Data were extracted from 28 resulting documents using an extraction template with fields based on the review's purpose., Main Contribution: This review examines the informal assessment guidance regarding: rationale; areas of interest for informal assessment; available methods; procedural guidance; documentation; and analytical frameworks. The rationale for using informal assessment included several aspects such as gaining a 'representative' sample of the individual's language. Ten communication areas of interest were found with 13 different assessment methods. The procedural guidance for these methods varied considerably, with the exception of conversation and semi-structured interviewing. Overall, documentation guidance was limited but numerous analytical frameworks were found., Conclusions: Several informal assessment methods are available to SLTs. However, information is mixed regarding when they might be used or how they might be applied in terms of their administration, documentation and analysis., (© 2018 Royal College of Speech and Language Therapists.)

Objectives: For women who have been diagnosed with unilateral breast cancer, there is an increasing trend for them to request removal of the contralateral healthy breast, the so-called contralateral risk reducing mastectomy (CRRM). The current literature is only just beginning to identify patient-reported reasons for undergoing CRRM and associated patient-reported outcomes. It is also unclear whether women at moderate/high risk of developing a subsequent primary contralateral breast cancer report similar outcomes to those considered to be at low/average risk. This lack of knowledge provides the rationale for this review., Methods: A rapid review methodology was undertaken to identify and explore the published research literature focused on the longer term (>5 y) psychosocial impacts on women who undergo CRRM., Results: Fifteen studies were identified. No UK studies were identified. High satisfaction and psychosocial well-being were consistently reported across all studies. Reducing the risk of a subsequent contralateral breast cancer and therefore reducing cancer-related anxiety, and satisfaction with cosmesis, were key themes running across all studies explaining satisfaction. Dissatisfaction was associated with adverse effects such as poor cosmesis, body image changes, femininity, sexual relationships, reoperations for acute and longer term complications, and reconstructive problems., Conclusions: Satisfaction and psychological well-being following CRRM was consistently high across all studies. However, the findings suggest women need to be more fully informed of the risks and benefits of CRRM and/or immediate/delayed reconstruction to support informed decision making., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Blood reference values for bonnet macaques (Macaca radiata) are limited. The goal of this study was to determine reference ranges for hematological and serum biochemical indices in healthy, socially housed bonnet macaques for males and females over a range of ages., Methods: Blood hematological and serum biochemical values were obtained from 50 healthy bonnet macaques of both sexes and aged 10-234 months., Results: Age and sex differences were present in a number of measures. Globulins, total protein, and creatinine (CREAT) values were highest among older subjects, while alkaline phophatase, albumin, and phosphorus values were higher in juveniles. Sex differences were present in concentrations of red blood cells and CREAT, with higher values in males., Conclusion: The blood parameter data reported here as age-specific reference values for laboratory-housed, healthy bonnet macaques may be used to inform clinical care and laboratory primate research., (© 2011 John Wiley & Sons A/S.)

Objectives: This study assessed the utilization and clinical yield of radiographs ordered to assist in the diagnosis of acute ankle injuries presenting to two emergency departments (EDs) in Kingston, Ontario, Canada, over a 7-year period., Methods: A large case series was assembled. Records of ankle injuries from the Kingston sites of the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) were linked to hospital discharge records containing procedure codes. Utilization of radiographs and the clinical yield of these assessments were analyzed over time., Results: Following exclusions, 7,706 acute ankle injuries were identified for analysis. Utilization of radiography increased modestly over time, to a high of 70.3% (95% confidence interval [CI] = 67.3% to 72.9%) in 2007. The percentage of cases positive for fracture remained consistent (18.3% to 21.9% annually)., Conclusions: Explanations for the observed increase in utilization of radiographs remain uncertain. Increased use of clinical decision tools such as the Ottawa Ankle Rules (OAR) appear to be required to reduce procedure costs within the ED and to limit patient exposure to radiography., (© 2011 by the Society for Academic Emergency Medicine.)

In severe pulmonary oedema, the alveoli fill rapidly with fluid of essentially the same protein composition as free interstitial fluid. The usual explanation is that the normally 'tight' alveolar epithelial intercellular junctions suddenly become freely permeable to proteins. But the pathophysiological basis for such a change is unknown. In seven anaesthetized dogs one lower lobe was filled with iso-osmotic fluid containing 125I-labelled albumin. The calculated alveolus-blood albumin permeability over three hours averaged 0.06 X 10(-7) cm/s. It decreased nearly 50% when the alveolar tracer concentration was tripled for three more hours. At autopsy, large interstitial free fluid cuffs around blood vessels and airways were found. Isolated lung lobes were filled with isosmotic fluid containing tracer albumin at 10 and 20 cmH2O (0.98-1.96 kPa) airway pressure. Free interstitial fluid cuffs developed within 30 and 10 minutes, respectively. The tracer protein concentration in the cuff fluid averaged 0.9 that of the alveolar fluid. It is postulated that the terminal airway epithelium is normally permeable to protein and water. In acute pulmonary oedema alveolar flooding may occur along the same pathway after the loose interstitial tissue space is fluid-filled and its pressure exceeds that in the airway. The anatomical site of the bulk fluid and protein leak has not been identified.