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We developed an innovative 3D printed casing that incorporates a lateral-flow immunoassay, dehydrated signal enhancement reagents, and a sealed buffer chamber. With only the push of a button for signal enhancement, our device detected the SARS-CoV-2 N-protein in 40 min at concentrations as low as 0.1 ng mL-1 in undiluted serum.

Cerebrospinal fluid (CSF) leaks can occur when there is communication between the intracranial cavities and the external environment. They are a common and serious complication of numerous procedures in otolaryngology, and if not treated, persistent leaks can increase a patient's risk of developing life-threatening complications such as meningitis. As it is not uncommon for patients to exhibit increased secretions postoperatively, distinguishing normal secretions from those containing CSF can be difficult. Currently, there are no proven, available tests that allow a medical provider concerned about a CSF leak to inexpensively, rapidly, and noninvasively rule out the presence of a leak. The gold standard laboratory-based test requires that a sample be sent to a tertiary site for analysis, where days to weeks may pass before results return. To address this, our group recently developed a semiquantitative, barcode-style lateral-flow immunoassay (LFA) for the quantification of the beta-trace protein, which has been reported to be an indicator of the presence of CSF leaks. In the work presented here, we created a rapid diagnostic test kit composed of our LFA, a collection swab, dilution buffers, disposable pipettes, and instructions. Validation studies demonstrated excellent predictive capabilities of this kit in distinguishing between clinical specimens containing CSF and those that did not. Our diagnostic kit for CSF leak detection can be operated by an untrained user, does not require any external equipment, and can be performed in approximately 20 min, making it well suited for use at the point of care. This kit has the potential to transform patient outcomes.

Guideline summaryChronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on definition, evaluation, and management of CLTI with the goals of improving evidence-based care and highlighting critical research needs. The term CLTI is preferred over critical limb ischemia, as the latter implies threshold values of impaired perfusion rather than a continuum. CLTI is a clinical syndrome defined by the presence of peripheral artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration >2 weeks duration. Venous, traumatic, embolic, and nonatherosclerotic etiologies are excluded. All patients with suspected CLTI should be referred urgently to a vascular specialist. Accurately staging the severity of limb threat is fundamental, and the Society for Vascular Surgery Threatened Limb Classification system, based on grading of Wounds, Ischemia, and foot Infection (WIfI) is endorsed. Objective hemodynamic testing, including toe pressures as the preferred measure, is required to assess CLTI. Evidence-based revascularization (EBR) hinges on three independent axes: Patient risk, Limb severity, and ANatomic complexity (PLAN). Average-risk and high-risk patients are defined by estimated procedural and 2-year all-cause mortality. The GVG proposes a new Global Anatomic Staging System (GLASS), which involves defining a preferred target artery path (TAP) and then estimating limb-based patency (LBP), resulting in three stages of complexity for intervention. The optimal revascularization strategy is also influenced by the availability of autogenous vein for open bypass surgery. Recommendations for EBR are based on best available data, pending level 1 evidence from ongoing trials. Vein bypass may be preferred for average-risk patients with advanced limb threat and high complexity disease, while those with less complex anatomy, intermediate severity limb threat, or high patient risk may be favored for endovascular intervention. All patients with CLTI should be afforded best medical therapy including the use of antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents, as well as counseling on smoking cessation, diet, exercise, and preventive foot care. Following EBR, long-term limb surveillance is advised. The effectiveness of nonrevascularization therapies (eg, spinal stimulation, pneumatic compression, prostanoids, and hyperbaric oxygen) has not been established. Regenerative medicine approaches (eg, cell, gene therapies) for CLTI should be restricted to rigorously conducted randomizsed clinical trials. The GVG promotes standardization of study designs and end points for clinical trials in CLTI. The importance of multidisciplinary teams and centers of excellence for amputation prevention is stressed as a key health system initiative.

ObjectiveA cerebrospinal fluid leak is one of the most serious complications in otolaryngology. It may occur as a result of injury to the skull base, typically traumatic or iatrogenic. While the presence of a leak is often discerned in the emergent setting, distinguishing normal secretions from those containing cerebrospinal fluid can be difficult during postoperative visits in the clinic. As most current laboratory-based assays are labor intensive and require several days to result, we aim to develop a more user-friendly and rapid point-of-care cerebrospinal fluid detection device.Study designOur laboratory developed a barcode-style lateral-flow immunoassay utilizing antibodies for beta-trace protein, a protein abundant in and specific for cerebrospinal fluid, with a concentration of 1.3 mg/L delineating a positive result.SettingTertiary medical center.Subjects and methodsTests with known concentrations of resuspended beta-trace protein and the contents of discarded lumbar drains (presumed to contain cerebrospinal fluid) were performed to validate our novel device.ResultsOur results demonstrate the ability of our device to semiquantitatively identify concentrations of beta-trace protein from 0.3-90 mg/L, which is within the required range to diagnose a leak, thus making beta-trace protein an excellent target for rapid clinical detection.ConclusionHerein we detail the creation and initial validation of the first point-of-care cerebrospinal fluid detection device. This device is a feasible method to more efficiently and cost-effectively identify cerebrospinal fluid leaks, minimize costs, and improve patient outcomes.

We present evidence that the acoustic component of the strut display of male sage grouse Centrocercus urophasianus is highly directional and that the nature of this directionality is unique among measured vertebrates. Where vertebrate acoustic signals have been found to be directional, they are most intense anteriorly and are bilaterally symmetrical. Our results show that sage grouse acoustic radiation (beam) patterns are often asymmetric about the birds’ anterior–posterior axis. The beam pattern of the ‘whistle’ note is actually strikingly bilobate with a deep null directly in front of the displaying bird. While the sage grouse display serves to attract potential mates, male sage grouse rarely face females head on when they call. The results of this study suggest that males may reach females with a high-intensity signal despite their preference for an oblique display posture relative to those females. We characterized these patterns using a novel technique that allowed us to map acoustic radiation patterns of unrestrained animals calling in the wild. Using an eight-microphone array, our technique integrates acoustic localization with synchronous pressure-field measurements while controlling for small-scale environmental variation in sound propagation.

Objectives Landmark studies published near the turn of the 21st century found an implementation gap concerning the effect of evidenced-based findings on clinical practice. The current study examines the uptake of six trials that produced actionable findings to describe the effects of evidence on practice and the reasons for those effects. Design A sequential, explanatory mixed methods study was conducted. First, a quantitative study assessed whether actionable findings from large, publicly funded elective surgical trials influenced practice. Subsequently, qualitative interviews were conducted to explain the quantitative findings. Setting Changes in NHS-funded practice were tracked across hospitals in England. Interviews were conducted online. Data and participants The six surgical trials were funded and published by England's National Institute for Health Research's Health Technology Assessment programme between 2006 and 2015. Quantitative time series analyses used data about the frequencies or proportions of relevant surgical procedures conducted in England between 2001 and 2020. Subsequently, qualitative interviews were conducted with 25 participants including study authors, surgeons and other healthcare staff in the supply chain. Transcripts were coded to identify major temporal events and Consolidated Framework for Implementation Research (CFIR) domains/ constructs that could influence implementation. Findings were synthesised by clinical area. Results The quantitative analyses reveal that practice changed in accordance with findings for three trials. In one trial (percutaneous vs nasogastric tube feed after stroke), the change took a decade to occur. In another (patella resurfacing), change anticipated the trial findings. In the third (abdominal aortic aneurysm repair), changes tracked the evolving evidence base. In the remaining trials (two about varicose veins and one about gastric reflux), practice did not change in line with findings. For varicose veins, the results were superseded by a further trial. For gastric reflux, surgical referrals declined as medical treatment increased. The exploratory qualitative analysis informed by CFIR found that evidence from sources apart from the trial in question was mentioned as a reason for non-adoption in the three trials where evidence did not affect practice and in the trial where uptake was delayed. There were no other consistent patterns in the qualitative data. Conclusion While practice does not always change in the direction indicated by clinical trials, our results suggest that individuals, official committees and professional societies do assimilate trial evidence. Decision-makers seem to respond to the totality of evidence such that there are often plausible reasons for not adopting the evidence of any one trial in isolation. [ABSTRACT FROM AUTHOR]