Using a Multi-pronged Behavioral Intervention to Standardize Antibiotic Prophylaxis at the Time of Foley Catheter Removal After Radical Prostatectomy.

OBJECTIVE: To identify antibiotic prescribing patterns at the time of foley catheter removal after radical prostatectomy and implement a multi-pronged behavioral intervention to standardize antibiotic use. METHODS: This was a single-institution study examining the prescribing of antibiotics at the time of foley catheter removal after radical prostatectomy. Pre-intervention data were collected retrospectively to establish baselines for antibiotic prescribing, patient characteristics, and urinary tract infection rates. A single dose of an oral antibiotic taken at the time of foley catheter removal was recommended as the standard antibiotic protocol. A multi-pronged behavioral intervention was used to encourage compliance with our protocol. Adherence to the protocol, quantity of antibiotics prescribed, and rate of urinary tract infection were recorded prospectively. Durability of the intervention was evaluated during a post-intervention phase. RESULTS: A total of 416 patients and 6 surgeons were included in the study. Accordance with the standardized antibiotic protocol was 59% in the pre-intervention phase and 91% in the intervention phase (P = .03). No patients in the intervention or post-intervention phase were prescribed more than one dose of an antibiotic. The rate of urinary tract infection did not differ across the study phases. CONCLUSION: Implementation of a multi-pronged behavioral intervention resulted in a high rate of surgeon compliance with a standardized antibiotic protocol. This led to a significant reduction in antibiotic use with no change in the rate of urinary tract infection after foley catheter removal after radical prostatectomy.

Understanding Effects of Visual Feedback Delay in AR on Fine Motor Surgical Tasks.

Latency is a pervasive issue in various systems that can significantly impact motor performance and user perception. In medical settings, latency can hinder surgeons' ability to quickly correct movements, resulting in an experience that doesn't align with user expectations and standards of care. Despite numerous studies reporting on the negative effects of latency, there is still a gap in understanding how it impacts the use of augmented reality (AR) in medical settings. This study aims to address this gap by examining how latency impacts motor task performance and subjective perceptions, such as cognitive load, on two display types: a monitor display, traditionally used inside an operating room (OR), and a Microsoft HoloLens 2 display. Our findings indicate that both level of latency and display type impact motor performance, and higher latencies on the HoloLens result in relatively poor performance. However, cognitive load was found to be unrelated to display type or latency, but was dependent on the surgeon's training level. Surgeons did not compromise accuracy to gain more speed and were generally well aware of the latency in the system irrespective of their performance on task. Our study provides valuable insights into acceptable thresholds of latency for AR displays and proposes design implications for the successful implementation and use of AR in surgical settings.

Utilizing a Questionnaire to Implement a Risk-based Antibiotic Prophylaxis Protocol for Transrectal Prostate Biopsy.

OBJECTIVE: To develop and evaluate a risk-based antibiotic prophylaxis protocol for patients undergoing transrectal prostate biopsy. METHODS: We created a risk-based protocol for antibiotic prophylaxis before transrectal prostate biopsy. Patients were screened for infection risk-factors with a self-administered questionnaire. The protocol was implemented from January 1, 2020 to March 31, 2020. We compared patient risk-factors, antibiotic regimens, and 30-day infection rates for patients undergoing transrectal prostate biopsies during the intervention and for a 3-month period before the intervention. RESULTS: There were 116 prostate biopsies in the preintervention group and 104 in the intervention group. Although there was no significant difference in the number of high-risk patients between the 2 groups (48% vs 55%; P = .33), the percentage of patients treated with augmented prophylaxis decreased from 74% to 45% (P = 0.03). The duration of antibiotic administration and the median number of doses prescribed also decreased significantly. Despite significant decreases in antibiotic use, there were no differences in infection rates (5% vs 5%; P = .90) or sepsis rates (1% vs 2%; P = .60). CONCLUSION: We developed a risk-based protocol for prophylactic antibiotics before prostate biopsy. The protocol was associated with less antibiotic use but did not lead to an increase in infectious complications.

First clinical implementation of Yttrium-90 Disc Brachytherapy after FDA clearance.

PURPOSE: Herein, we study if high-dose-rate (HDR) yttrium-90 (90Y) brachytherapy could be utilized by medical physicists, radiation oncologists, and ophthalmic surgeons. METHODS AND MATERIALS: Yttrium-90 (90Y) beta-emitting brachytherapy sources received United States Food and Drug Administration clearance for episcleral treatment of ocular tumors and benign growths. Dose calibration traceable to the National Institute of Standards and Technology as well as treatment planning and target delineation methods were established. Single-use systems included a 90Y-disc affixed within specialized, multifunction, handheld applicator. Low-dose-rate to high-dose-rate prescription conversions and depth-dose determinations were performed. Radiation safety was evaluated based on live exposure rates during assembly and surgeries. Clinical data for radiation safety, treatment tolerability, and local control was collected. RESULTS: Practice parameters for the medical physicist, radiation oncologist, and ophthalmic surgeon were defined. Device sterilizations, calibrations, assemblies, surgical methods, and disposals were reproducible and effective. Treated tumors included iris melanoma, iridociliary melanoma, choroidal melanoma, and a locally invasive squamous carcinoma. Mean calculated 90Y disc activity was 14.33 mCi (range 8.8-16.6), prescription dose 27.8 Gy (range 22-30), delivered to depth of 2.3 mm (range 1.6-2.6), at treatment durations of 420 s (7.0 min, range 219 s-773 s). Both insertion and removal were performed during one surgical session. After surgery, each disc-applicator- system was contained for decay in storage. Treatments were well-tolerated. CONCLUSIONS: HDR 90Y episcleral brachytherapy devices were created, implementation methods developed, and treatments performed on 6 patients. Treatments were single-surgery, rapid, and well-tolerated with short-term follow up.

Uncomputably complex renormalisation group flows.

Renormalisation group methods are among the most important techniques for analysing the physics of many-body systems: by iterating a renormalisation group map, which coarse-grains the description of a system and generates a flow in the parameter space, physical properties of interest can be extracted. However, recent work has shown that important physical features, such as the spectral gap and phase diagram, may be impossible to determine, even in principle. Following these insights, we construct a rigorous renormalisation group map for the original undecidable many-body system that appeared in the literature, which reveals a renormalisation group flow so complex that it cannot be predicted. We prove that each step of this map is computable, and that it converges to the correct fixed points, yet the resulting flow is uncomputable. This extreme form of unpredictability for renormalisation group flows had not been shown before and goes beyond the chaotic behaviour seen previously.

Safety and immunogenicity of 3 doses of BNT162b2 and CoronaVac in children and adults with inborn errors of immunity.

Our study (NCT04800133) aimed to determine the safety and immunogenicity in patients with IEIs receiving a 3-dose primary series of mRNA vaccine BNT162b2 (age 12+) or inactivated whole-virion vaccine CoronaVac (age 3+) in Hong Kong, including Omicron BA.1 neutralization, in a nonrandomized manner. Intradermal vaccination was also studied. Thirty-nine patients were vaccinated, including 16 with homologous intramuscular 0.3ml BNT162b2 and 17 with homologous intramuscular 0.5ml CoronaVac. Two patients received 3 doses of intradermal 0.5ml CoronaVac, and 4 patients received 2 doses of intramuscular BNT162b2 and the third dose with intradermal BNT162b2. No safety concerns were identified. Inadequate S-RBD IgG and surrogate virus neutralization responses were found after 2 doses in patients with humoral immunodeficiencies and especially so against BA.1. Dose 3 of either vaccine increased S-RBD IgG response. T cell responses against SARS-CoV-2 antigens were detected in vaccinated IEI patients by intracellular cytokine staining on flow cytometry. Intradermal third dose vaccine led to high antibody response in 4 patients. The primary vaccination series of BNT162b2 and CoronaVac in adults and children with IEIs should include 3 doses for optimal immunogenicity.

Seeing the future: Predictive control in neural models of ocular accommodation.

Ocular accommodation is the process of adjusting the eye's crystalline lens so as to bring the retinal image into sharp focus. The major stimulus to accommodation is therefore retinal defocus, and in essence, the job of accommodative control is to send a signal to the ciliary muscle which will minimize the magnitude of defocus. In this article, we first provide a tutorial introduction to control theory to aid vision scientists without this background. We then present a unified model of accommodative control that explains properties of the accommodative response for a wide range of accommodative stimuli. Following previous work, we conclude that most aspects of accommodation are well explained by dual integral control, with a "fast" or "phasic" integrator enabling response to rapid changes in demand, which hands over control to a "slow" or "tonic" integrator which maintains the response to steady demand. Control is complicated by the sensorimotor latencies within the system, which delay both information about defocus and the accommodation changes made in response, and by the sluggish response of the motor plant. These can be overcome by incorporating a Smith predictor, whereby the system predicts the delayed sensory consequences of its own motor actions. For the first time, we show that critically-damped dual integral control with a Smith predictor accounts for adaptation effects as well as for the gain and phase for sinusoidal oscillations in demand. In addition, we propose a novel proportional-control signal to account for the power spectrum of accommodative microfluctuations during steady fixation, which may be important in hunting for optimal focus, and for the nonlinear resonance observed for low-amplitude, high-frequency input. Complete Matlab/Simulink code implementing the model is provided at https://doi.org/10.25405/data.ncl.14945550.

Structural Basis for pH-gating of the K+ channel TWIK1 at the selectivity filter.

TWIK1 (K2P1.1, KCNK1) is a widely expressed pH-gated two-pore domain K+ channel (K2P) that contributes to cardiac rhythm generation and insulin release from pancreatic beta cells. TWIK1 displays unique properties among K2Ps including low basal activity and inhibition by extracellular protons through incompletely understood mechanisms. Here, we present cryo-EM structures of TWIK1 in lipid nanodiscs at high and low pH that reveal a previously undescribed gating mechanism at the K+ selectivity filter. At high pH, TWIK1 adopts an open conformation. At low pH, protonation of an extracellular histidine results in a cascade of conformational changes that close the channel by sealing the top of the selectivity filter, displacing the helical cap to block extracellular ion access pathways, and opening gaps for lipid block of the intracellular cavity. These data provide a mechanistic understanding for extracellular pH-gating of TWIK1 and illustrate how diverse mechanisms have evolved to gate the selectivity filter of K+ channels.

The Norwich trabeculectomy study: risk factor analysis for the development of adverse, thin cystic blebs.

PURPOSE: To investigate potential risk factors, particularly antimetabolite choice, with regard to the development of adverse bleb morphology in eyes that had undergone trabeculectomy surgery. METHODS: A single-centre, observational cohort study of 631 consecutive eyes, which had undergone trabeculectomy over an 11-year period. For each case, bleb morphology was recorded at 2 years, and its association with the per-operative antimetabolite as well as potential confounding risk factors was analysed using univariate (unadjusted) and multivariate (adjusted) logistical regression analyses to identify those that could contribute to the development of adverse blebs. A standard protocol for 5-fluorouracil and mitomycin-C utilization was employed in the majority of cases. RESULTS: When 5-fluorouracil was used (n = 257), 24% of patients formed cystic or partially cystic blebs, whereas with mitomycin-C (n = 299), only 12% formed such adverse blebs, the difference being statistically significant (OR = 3.54, p = 0.002 unadjusted; OR = 7.49, p = 0.00 adjusted). Of the other potential confounding factors, care within the private sector (OR = 0.30 p = 0.02) and a history of previous ocular surgery involving a conjunctival incision were identified as potential risk factors for the formation of adverse cystic blebs (OR = 0.28, p = 0.02). CONCLUSIONS: Modern use of mitomycin-C appeared to be better than 5-fluorouracil as an adjunctive antimetabolite used at the time of trabeculectomy, with respect to the development of preferable final bleb morphology. The only potential preoperative risk factors found to be significant with respect to adverse cystic bleb development were care in the private health sector and previous ocular surgery involving a conjunctival incision.

High-performance microbial opsins for spatially and temporally precise perturbations of large neuronal networks.

The biophysical properties of existing optogenetic tools constrain the scale, speed, and fidelity of precise optogenetic control. Here, we use structure-guided mutagenesis to engineer opsins that exhibit very high potency while retaining fast kinetics. These new opsins enable large-scale, temporally and spatially precise control of population neural activity. We extensively benchmark these new opsins against existing optogenetic tools and provide a detailed biophysical characterization of a diverse family of opsins under two-photon illumination. This establishes a resource for matching the optimal opsin to the goals and constraints of patterned optogenetics experiments. Finally, by combining these new opsins with optimized procedures for holographic photostimulation, we demonstrate the simultaneous coactivation of several hundred spatially defined neurons with a single hologram and nearly double that number by temporally interleaving holograms at fast rates. These newly engineered opsins substantially extend the capabilities of patterned illumination optogenetic paradigms for addressing neural circuits and behavior.

Assessing the learning curve associated with a novel flexible robot in the pre-clinical and clinical setting.

BACKGROUND: Transoral robotic surgery has been successfully used by head and neck surgeons for a variety of procedures but is limited by rigid instrumentation and line-of-sight visualization. Non-linear systems specifically designed for the aerodigestive tract are needed. Ease of use of these new systems in both training and clinical environments is critical in its widespread adoption. METHODS: Residents, fellows, and junior faculty performed four tasks on an anatomical airway mannequin using the Medrobotics FLEX™ Robotic System: expose and incise the tonsil, grasp the epiglottis, palpate the vocal processes, and grasp the interarytenoid space. These tasks were performed once a day for four days; after a 4-month time gap, subjects were asked to perform these same tasks for three more days. Time to task completion and total distance driven were tracked. In addition, a retrospective analysis was performed analyzing one attending physician's experience with clinical usage of the robot. RESULTS: 13 subjects completed the initial round of the mannequin simulation and 8 subjects completed the additional testing 4 months later. Subjects rapidly improved their speed and efficiency at task completion. Junior residents were slower in most tasks initially compared to senior trainees but quickly reached similar levels of efficiency. Following the break there was minimal degradation in skills and continued improvement in efficiency was observed with additional trials. There was significant heterogeneity in the analyzed clinical cases, but when analyzing cases of similar complexity and pathology, clear decreases in overall operative times were demonstrable. CONCLUSION: Novice users quickly gained proficiency with the FLEX™ Robotic System in a training environment, and these skills are retained after several months. This learning could translate to the clinical setting if a proper training regimen is developed. The Medrobotics FLEX™ Robotic System shows promise as a surgical tool in head and neck surgery in this study.

A scalable model of fluid flow, substrate removal and current production in microbial fuel cells.

Mathematical modelling can reduce the cost and time required to design complex systems, and is being increasingly used in microbial electrochemical technologies (METs). To be of value such models must be complex enough to reproduce important behaviour of MET, yet simple enough to provide insight into underlying causes of this behaviour. Ideally, models must also be scalable to future industrial applications, rather than limited to describing existing laboratory experiments. We present a scalable model for simulating both fluid flow and bioelectrochemical processes in microbial fuel cells (MFCs), benchmarking against an experimental pilot-scale bioreactor. The model describes substrate transport through a two-dimensional fluid domain, and biofilm growth on anode surfaces. Electron transfer is achieved by an intracellular redox mediator. We find significant spatial variations in both substrate concentration and current density. Simple changes to the reactor layout can greatly improve the overall efficiency, measured in terms of substrate removal and total current generated.

Multiple paternity in two populations of finetooth sharks (Carcharhinus isodon) with varying reproductive periodicity.

The mechanisms underlying polyandry and female mate choice in certain taxonomic groups remain widely debated. In elasmobranchs, several species have shown varying rates of polyandry based on genetic studies of multiple paternity (MP). We investigated MP in the finetooth shark, Carcharhinus isodon, in order to directly test the encounter rate hypothesis (ERH), which predicts that MP is a result of the frequency of encounters between mature conspecifics during the breeding season, and should therefore increase when more time is available for copulation and sperm storage. Female finetooth sharks in the northern Gulf of Mexico (GoM) have been found to reproduce with both annual periodicity and biennial periodicity, while finetooth sharks from the northwestern Atlantic Ocean have only been found to reproduce biennially, allowing us to compare mating opportunity to frequency of MP. Our results show high rates of MP with no significant difference in frequency between females in the GoM (83.0%) and Atlantic (88.2%, p = .8718) and varying but nonsignificant rates of MP between females in the GoM reproducing annually (93.0%) and biennially (76.6%, p = .2760). While the ERH is not supported by this study, it remains possible that reproductive periodicity and other physiological factors play a role in determining rates of MP in elasmobranchs, with potential benefits to individuals and populations.

Uncomputability of phase diagrams.

The phase diagram of a material is of central importance in describing the properties and behaviour of a condensed matter system. In this work, we prove that the task of determining the phase diagram of a many-body Hamiltonian is in general uncomputable, by explicitly constructing a continuous one-parameter family of Hamiltonians H(φ), where [Formula: see text], for which this is the case. The H(φ) are translationally-invariant, with nearest-neighbour couplings on a 2D spin lattice. As well as implying uncomputablity of phase diagrams, our result also proves that undecidability can hold for a set of positive measure of a Hamiltonian's parameter space, whereas previous results only implied undecidability on a zero measure set. This brings the spectral gap undecidability results a step closer to standard condensed matter problems, where one typically studies phase diagrams of many-body models as a function of one or more continuously varying real parameters, such as magnetic field strength or pressure.

Swimming against the flow-Environmental DNA can detect bull sharks (Carcharhinus leucas) across a dynamic deltaic interface.

Human activities in coastal areas are accelerating ecosystem changes at an unprecedented pace, resulting in habitat loss, hydrological modifications, and predatory species declines. Understanding how these changes potentially cascade across marine and freshwater ecosystems requires knowing how mobile euryhaline species link these seemingly disparate systems. As upper trophic level predators, bull sharks (Carcharhinus leucas) play a crucial role in marine and freshwater ecosystem health. Telemetry studies in Mobile Bay, Alabama, suggest that bull sharks extensively use the northern portions of the bay, an estuarine-freshwater interface known as the Mobile-Tensaw Delta. To assess whether bull sharks use freshwater habitats in this region, environmental DNA surveys were conducted during the dry summer and wet winter seasons in 2018. In each season, 5 × 1 L water samples were collected at each of 21 sites: five sites in Mobile Bay, six sites in the Mobile-Tensaw Delta, and ten sites throughout the Mobile-Tombigbee and Tensaw-Alabama Rivers. Water samples were vacuum-filtered, DNA extractions were performed on the particulate, and DNA extracts were analyzed with Droplet Digital™ Polymerase Chain Reaction using species-specific primers and an internal probe to amplify a 237-base pair fragment of the mitochondrial NADH dehydrogenase subunit 2 gene in bull sharks. One water sample collected during the summer in the Alabama River met the criteria for a positive detection, thereby confirming the presence of bull shark DNA. While preliminary, this finding suggests that bull sharks use less-urbanized, riverine habitats up to 120 km upriver during Alabama's dry summer season.

Genetic evidence supports a range extension for the Brazilian cownose ray Rhinoptera brasiliensis in the western North Atlantic.

We report 24 new records of the Brazilian cownose ray Rhinoptera brasiliensis outside its accepted geographic range. Sequencing of a 442-base pair portion of the mitochondrial NADH dehydrogenase subunit 2 gene for 282 Rhinoptera samples revealed eight records off the east coast of the USA and 16 from the eastern Gulf of Mexico. Both sexes of all life stages were documented in all seasons over multiple years in the Indian River and Lake Worth lagoons, Florida, indicating that their range extends further in the western North Atlantic than previously described.

Marine environmental DNA: Approaches, applications, and opportunities.

Environmental DNA (eDNA) is increasingly being used to document species distributions and habitat use in marine systems, with much of the recent effort focused on leveraging advances in next-generation DNA sequencing to assess and track biodiversity across taxonomic groups. Environmental DNA offers a number of important advantages over traditional survey techniques, including non-invasive sampling, sampling where traditional approaches are impractical or inefficient (e.g. deep oceans), reduced cost, and increased detection sensitivity. However, eDNA applications are currently limited because of an insufficient understanding of the influence of sample source, analytical approach, and marker type on eDNA detections. Because approaches vary considerably among eDNA studies, we present a summary of the current state of the field and emerging best practices. The impact of observed variation in rates of eDNA production, persistence, and transport are also discussed and future research needs are highlighted with the goal of expanding eDNA applications, including the development of statistical models to improve the predictability of eDNA detection and quantification.

Wikidata as a knowledge graph for the life sciences.

Wikidata is a community-maintained knowledge base that has been assembled from repositories in the fields of genomics, proteomics, genetic variants, pathways, chemical compounds, and diseases, and that adheres to the FAIR principles of findability, accessibility, interoperability and reusability. Here we describe the breadth and depth of the biomedical knowledge contained within Wikidata, and discuss the open-source tools we have built to add information to Wikidata and to synchronize it with source databases. We also demonstrate several use cases for Wikidata, including the crowdsourced curation of biomedical ontologies, phenotype-based diagnosis of disease, and drug repurposing.