Analytical and clinical validation of direct detection of antimicrobial resistance markers by plasma microbial cell-free DNA sequencing.

Sequencing of plasma microbial cell-free DNA (mcfDNA) has gained increased acceptance as a valuable adjunct to standard-of-care testing for diagnosis of infections throughout the body. Here, we report the analytical and clinical validation of a novel application of mcfDNA sequencing, the non-invasive detection of seven common antimicrobial resistance (AMR) genetic markers in 18 important pathogens. The AMR markers include SCCmec, mecA, mecC, vanA, vanB, blaCTX-M, and blaKPC. The AMR markers were computationally linked to the pathogens detected. Analytical validation showed high reproducibility (100%), inclusivity (54 to 100%), and exclusivity (100%). Clinical accuracy was assessed with 114 unique plasma samples from patients at seven study sites with concordant culture results for target bacteria from a variety of specimen types and correlated with available phenotypic antimicrobial susceptibility test results and genotypic results. The positive percent agreement (PPA), negative percent agreement (NPA), and diagnostic yield (DY) were estimated for each AMR marker. DY was defined as the percentage of tests that yielded an actionable result of either detected or not detected. The results for the combination of SCCmec and mecA for staphylococci were PPA 19/20 (95.0%), NPA 21/22 (95.4%), DY 42/60 (70.0%); vanA for enterococci were PPA 3/3 (100%), NPA 2/2 (100%), DY 5/6 (83.3%); blaCTX-M for gram-negative bacilli were PPA 5/6 (83.3%), NPA 29/29 (100%), DY 35/49 (71.4%); and blaKPC for gram-negative bacilli were PPA 0/2 (0%), NPA: 23/23 (100%), DY 25/44 (56.8%). The addition of AMR capability to plasma mcfDNA sequencing should provide clinicians with an effective new culture-independent tool for optimization of therapy. IMPORTANCE: This manuscript is ideally suited for the Innovative Diagnostic Methods sections as it reports the analytical and clinical validation of a novel application of plasma microbial cell-free DNA sequencing for direct detection of seven selected antimicrobial resistance markers in 18 target pathogens. Clearly, it has potential clinical utility in optimizing therapy and was incorporated into the Karius test workflow in September 2023. In addition, the workflow could readily be adapted to expand the number of target bacteria and antimicrobial resistance markers as needed.

The Impact of Various Cockpit Display Interfaces on Novice Pilots' Mental Workload and Situational Awareness: A Comparative Study.

Future airspace is expected to become more congested with additional in-service cargo and commercial flights. Pilots will face additional burdens in such an environment, given the increasing number of factors that they must simultaneously consider while completing their work activities. Therefore, care and attention must be paid to the mental workload (MWL) experienced by operating pilots. If left unaddressed, a state of mental overload could affect the pilot's ability to complete his or her work activities in a safe and correct manner. This study examines the impact of two different cockpit display interfaces (CDIs), the Steam Gauge panel and the G1000 Glass panel, on novice pilots' MWL and situational awareness (SA) in a flight simulator-based setting. A combination of objective (EEG and HRV) and subjective (NASA-TLX) assessments is used to assess novice pilots' cognitive states during this study. Our results indicate that the gauge design of the CDI affects novice pilots' SA and MWL, with the G1000 Glass panel being more effective in reducing the MWL and improving SA compared with the Steam Gauge panel. The results of this study have implications for the design of future flight deck interfaces and the training of future pilots.

Smart Wearables with Sensor Fusion for Fall Detection in Firefighting.

During the past decade, falling has been one of the top three causes of death amongst firefighters in China. Even though there are many studies on fall-detection systems (FDSs), the majority use a single motion sensor. Furthermore, few existing studies have considered the impact sensor placement and positioning have on fall-detection performance; most are targeted toward fall detection of the elderly. Unfortunately, floor cracks and unstable building structures in the fireground increase the difficulty of detecting the fall of a firefighter. In particular, the movement activities of firefighters are more varied; hence, distinguishing fall-like activities from actual falls is a significant challenge. This study proposed a smart wearable FDS for firefighter fall detection by integrating motion sensors into the firefighter's personal protective clothing on the chest, elbows, wrists, thighs, and ankles. The firefighter's fall activities are detected by the proposed multisensory recurrent neural network, and the performances of different combinations of inertial measurement units (IMUs) on different body parts were also investigated. The results indicated that the sensor fusion of IMUs from all five proposed body parts achieved performances of 94.10%, 92.25%, and 94.59% in accuracy, sensitivity, and specificity, respectively.

Atomic Scale Dynamics Drive Brain-like Avalanches in Percolating Nanostructured Networks.

Self-assembled networks of nanoparticles and nanowires have recently emerged as promising systems for brain-like computation. Here, we focus on percolating networks of nanoparticles which exhibit brain-like dynamics. We use a combination of experiments and simulations to show that the brain-like network dynamics emerge from atomic-scale switching dynamics inside tunnel gaps that are distributed throughout the network. The atomic-scale dynamics emulate leaky integrate and fire (LIF) mechanisms in biological neurons, leading to the generation of critical avalanches of signals. These avalanches are quantitatively the same as those observed in cortical tissue and are signatures of the correlations that are required for computation. We show that the avalanches are associated with dynamical restructuring of the networks which self-tune to balanced states consistent with self-organized criticality. Our simulations allow visualization of the network states and detailed mechanisms of signal propagation.

Expired Epinephrine Maintains Chemical Concentration and Sterility.

OBJECTIVES: Epinephrine shortages affect nearly all American emergency medical services (EMS) systems. Utilization of expired epinephrine could mitigate this situation in daily EMS operations. Concerns about using expired medications include sterility, potency, and potential harmful chemical decay byproducts. There are no cross-platform analyses of sterility and chemical purity of multiple samples of expired parenteral epinephrine. We hypothesized that epinephrine injections will remain sterile and will retain their active ingredient's content for more than 30 months past expiration. METHODS: Six parenteral epinephrine prefilled syringes, 1 mg/10 mL, with an expiration date of January 1, 2012 had been stored in the climate controlled setting of a hospital inpatient pharmacy where they remained until they were taken for chemical or microbial analysis 30 months after expiration. An unexpired parenteral epinephrine prefilled syringe content was used as a control. Contents of three separate syringes with expired content from the same lot and one control underwent ultra-high pressure liquid chromatography-mass spectrometry (UHPLC-MS) and nuclear magnetic resonance (NMR) to determine epinephrine content and stability. In parallel, contents of another three expired epinephrine syringes were analyzed for sterility by plating on aerobic, anaerobic, and fungal media in a hospital microbiology laboratory. The aerobic plates were checked for growth in 3 days, the anaerobic in 5 days, and the fungal in 28 days. RESULTS: UHPLC-MS and NMR showed that content of epinephrine present in the original sample remained unchanged compared to the control. There was no statistical difference in the UHPLC-MS and NMR signal amplitudes between the control and the expired samples. No chemical degradation byproducts were detected using NMR. There was no growth of any bacteria or fungus. CONCLUSION: Recurrent epinephrine shortages impact EMS and hospital operations in the United States. Individual administrators may be hesitant to authorize use of expired pharmaceuticals due to perceived potential complications or fear of litigation. This study shows that the original parenteral epinephrine remains sterile and detectably pure more than 2.5 years after expiration. Further study of the sterility and chemical integrity of expired medications that had been subjected to the conditions of EMS vehicles may be a future research endeavor based on the aforementioned paradigm.

TAFFIES: Tailored Automated Feedback Framework for Developing Integrated and Extensible Feedback Systems.

Delivering high-quality, timely and formative feedback for students' code-based coursework submissions is a problem faced by Computer Science (CS) educators. Automated Feedback Systems (AFSs) can provide immediate feedback on students' work, without requiring students to be physically present in the classroom-an increasingly important consideration for education in the context of COVID-19 lockdowns. There are concerns, however, surrounding the quality of the feedback provided by existing AFSs, with many systems simply presenting a score, a binary classification (pass/fail), or a basic error identification ("The program could not run"). Such feedback, with little guidance for how to rectify the problem, raises doubts as to whether or not these systems can stimulate deep engagement with the related knowledge or learning activities. In this paper, we propose TAFFIES, a framework to scaffold the development of AFSs that promote high-quality, tailored feedback for student's solutions. We tested our framework by applying it to develop an AFS to mark and provide feedback to 160 CS students in an introductory databases class. In contrast to most introductory-level coursework feedback and marking, which typically generate significant student reaction and change requests, our AFS deployment resulted in zero grade challenges. There were also no identified marking errors, or suggested inconsistencies or unfairness. Student feedback on the AFS was universally positive, with comments indicating an AFS-related increase in student motivation. The experience of designing, deploying, and evolving the AFS using TAFFIES is examined through reflective practice, student evaluation, and focus group (involving peer teachers) analysis.

How Did the Media Report the Mining Industry's Initial Response to COVID-19 in Inuit Nunangat? A Newspaper Review.

Mining in Inuit Nunangat relies on a southern Canada fly-in/fly-out (FIFO) and local workforce. The FIFO workforce, combined with existing social determinants of health, can create health risks to Inuit Nunangat. These risks were increased with COVID-19. As newspaper reporting can shape public opinion and policy actions regarding these COVID-19 risks, we systematically searched databases to identify newspaper articles during the initial phase of COVID-19 (i.e., articles published from 1 January to 30 June 2020). Descriptive statistics and qualitative thematic analysis were used to analyze the nature, range, and extent of included articles. Most included articles were published by Inuit Nunangat-based newspapers. Half the sources quoted were mining companies and most reported reactions to their initial response were negative. The most frequent topic was concern that an infected FIFO employee could transmit COVID-19 to a worksite and subsequently infect Inuit employees and communities. Inuit Nunangat-based newspapers were crucial in shaping the narrative of the initial response. National newspapers mainly focused on the takeover of TMAC™ during the pandemic, while Inuit Nunangat-based newspapers provided timely and locally-relevant pandemic information. Without Inuit Nunangat-based newspapers, the reporting would be from national and southern newspapers, which was less in-depth, less frequent, and less relevant to Inuit.

Long-range temporal correlations in scale-free neuromorphic networks.

Biological neuronal networks are the computing engines of the mammalian brain. These networks exhibit structural characteristics such as hierarchical architectures, small-world attributes, and scale-free topologies, providing the basis for the emergence of rich temporal characteristics such as scale-free dynamics and long-range temporal correlations. Devices that have both the topological and the temporal features of a neuronal network would be a significant step toward constructing a neuromorphic system that can emulate the computational ability and energy efficiency of the human brain. Here we use numerical simulations to show that percolating networks of nanoparticles exhibit structural properties that are reminiscent of biological neuronal networks, and then show experimentally that stimulation of percolating networks by an external voltage stimulus produces temporal dynamics that are self-similar, follow power-law scaling, and exhibit long-range temporal correlations. These results are expected to have important implications for the development of neuromorphic devices, especially for those based on the concept of reservoir computing.

Colistin- and polymyxin-induced nephrotoxicity: focus on literature utilizing the RIFLE classification scheme of acute kidney injury.

With the reintroduction of colistimethate and polymyxin B into clinical practice, a review of their individual and comparative nephrotoxicity attributes as reported in contemporary literature was undertaken. Given variability in definitions used for acute kidney injury, a particular focus was placed on studies utilizing the Risk-Injury-Failure-Loss-End Stage Kidney Disease (RIFLE) criteria of assessment to provide for standardized comparison. Primary risk factors examined included the influence of dosing and the receipt of concomitant nephrotoxins. The typical severity and time course of renal injury that develops were also analyzed. Nephrotoxicity rates with colistimethate appear to approach 50%, and could be of lower frequency and severity with polymyxin B based on limited literature. Acute kidney injury generally appears to be mild to moderate in magnitude and reversible in nature, though as many as 20% of patients experiencing it may require renal replacement therapy of some duration. The majority of studies showed some relationship with dosing- variably reported as being associated with daily dose or cumulative exposure. Traditional nephrotoxic agents did not appear to confer additional risk individually in the majority of investigations, though receipt of multiple concurrent nephrotoxins did yield a relationship in several. Further studies will be required to better characterize the renal adverse effect profile of these agents, particularly in the case of polymyxin B.