Rejuvenating silicon probes for acute neurophysiology.

Neurophysiological recording with a new probe often yields better signal quality than with a used probe. Why does the signal quality degrade after only a few experiments? Here, we considered silicon probes in which the contacts are densely packed, and each contact is coated with a conductive polymer that increases its surface area. We tested 12 Cambridge Neurotech silicon probes during 61 recording sessions from the brain of three marmosets. Out of the box, each probe arrived with an electrodeposited polymer coating on 64 gold contacts and an impedance of around 50 kΩ. With repeated use, the impedance increased and there was a corresponding decrease in the number of well-isolated neurons. Imaging of the probes suggested that the reduction in signal quality was due to a gradual loss of the polymer coating. To rejuvenate the probes, we first stripped the contacts, completely removing their polymer coating, and then recoated them in a solution of 10 mM 3,4-Ethylenedioxythiophene (EDOT) monomer with 11 mM Poly(sodium 4-styrenesulfonate) (PSS) using a current density of about 3 mA/cm2 for 30 s. This recoating process not only returned probe impedance to around 50 kΩ but also yielded significantly improved signal quality during neurophysiological recordings. Thus, insertion into the brain promoted the loss of the polymer that coated the contacts of the silicon probes. This led to degradation of signal quality, but recoating rejuvenated the probes.NEW & NOTEWORTHY With repeated use, a silicon probe's ability to isolate neurons degrades. As a result, the probe is often discarded after only a handful of uses. Here, we demonstrate a major source of this problem and then produce a solution to rejuvenate the probes.

MODFLOW as a Configurable Multi-Model Hydrologic Simulator.

MODFLOW 6 is the latest in a line of six "core" versions of MODFLOW released by the U.S. Geological Survey. The MODFLOW 6 architecture supports incorporation of additional hydrologic processes, in addition to groundwater flow, and allows interaction between processes. The architecture supports multiple model instances and multiple types of models within a single simulation, a flexible approach to formulating and solving the equations that represent hydrologic processes, and recent advances in interoperability, which allow MODFLOW to be accessed and controlled by external programs. The present version of MODFLOW 6 consolidates popular capabilities available in MODFLOW variants, such as the unstructured grid support in MODFLOW-USG, the Newton-Raphson formulation in MODFLOW-NWT, and the support for partitioned stress boundaries in MODFLOW-CDSS. The flexible multi-model capability allows users to configure MODFLOW 6 simulations to represent the local-grid refinement (LGR) capabilities available in MODFLOW-LGR, the multi-species transport capabilities in MT3DMS, and the coupled variable-density capabilities available in SEAWAT. This paper provides a new, holistic and integrated overview of simulation capabilities made possible by the MODFLOW 6 architecture, and describes how ongoing and future development can take advantage of the program architecture to integrate new capabilities in a way that is minimally invasive and automatically compatible with the existing MODFLOW 6 code.

Race and Ethnicity and Primary Language in Emergency Department Triage.

Importance: Emergency department (ED) triage substantially affects how long patients wait for care but triage scoring relies on few objective criteria. Prior studies suggest that Black and Hispanic patients receive unequal triage scores, paralleled by disparities in the depth of physician evaluations. Objectives: To examine whether racial disparities in triage scores and physician evaluations are present across a multicenter network of academic and community hospitals and evaluate whether patients who do not speak English face similar disparities. Design, Setting, and Participants: This was a cross-sectional, multicenter study examining adults presenting between February 28, 2019, and January 1, 2023, across the Mass General Brigham Integrated Health Care System, encompassing 7 EDs: 2 urban academic hospitals and 5 community hospitals. Analysis included all patients presenting with 1 of 5 common chief symptoms. Exposures: Emergency department nurse-led triage and physician evaluation. Main Outcomes and Measures: Average Triage Emergency Severity Index [ESI] score and average visit work relative value units [wRVUs] were compared across symptoms and between individual minority racial and ethnic groups and White patients. Results: There were 249 829 visits (149 861 female [60%], American Indian or Alaska Native 0.2%, Asian 3.3%, Black 11.8%, Hispanic 18.8%, Native Hawaiian or Other Pacific Islander <0.1%, White 60.8%, and patients identifying as Other race or ethnicity 5.1%). Median age was 48 (IQR, 29-66) years. White patients had more acute ESI scores than Hispanic or Other patients across all symptoms (eg, chest pain: Hispanic, 2.68 [95% CI, 2.67-2.69]; White, 2.55 [95% CI, 2.55-2.56]; Other, 2.66 [95% CI, 2.64-2.68]; P < .001) and Black patients across most symptoms (nausea/vomiting: Black, 2.97 [95% CI, 2.96-2.99]; White: 2.90 [95% CI, 2.89-2.91]; P < .001). These differences were reversed for wRVUs (chest pain: Black, 4.32 [95% CI, 4.25-4.39]; Hispanic, 4.13 [95% CI, 4.08-4.18]; White 3.55 [95% CI, 3.52-3.58]; Other 3.96 [95% CI, 3.84-4.08]; P < .001). Similar patterns were seen for patients whose primary language was not English. Conclusions and Relevance: In this cross-sectional study, patients who identified as Black, Hispanic, and Other race and ethnicity were assigned less acute ESI scores than their White peers despite having received more involved physician workups, suggesting some degree of mistriage. Clinical decision support systems might reduce these disparities but would require careful calibration to avoid replicating bias.

Racial disparities in emergency medicine: Implementation of a novel educational module in the emergency medicine clerkship.

Objectives: Despite decades of literature recognizing racial disparities (RDs) in emergency medicine (EM), published curricula dedicated to addressing them are sparse. We present details of our novel RD curriculum for EM clerkships and its educational outcomes. Methods: We created a 30-min interactive didactic module on the topic designed for third- and fourth-year medical students enrolled in our EM clerkships. Through a modified Delphi process, education faculty and content experts in RD developed a 10-question multiple-choice test of knowledge on RD that the students completed immediately prior to and 2 weeks following the activity. Students also completed a Likert-style learner satisfaction survey. Median pre- and posttest scores were compared using a paired Wilcoxon signed-rank test and presented using medians and 95% confidence intervals (CIs). Satisfaction survey responses were dichotomized into favorable and neutral/not favorable. Results: For the 36 students who completed the module, the median pretest score was 40% (95% CI 36%-50%) and the posttest score was 70% (95% CI 60%-70%) with a p-value of <0.001. Thirty-five of the 36 students improved on the posttest with a mean increase of 24.2% (95% CI 20.2-28.2). The satisfaction survey also showed a positive response, with at least 83% of participants responding favorably to all statements (overall mean favorable response 93%, 95% CI 90%-96%).ConclusionsThis EM-based module on RD led to improvement in students' knowledge on the topic and positive reception by participants. This is a feasible option for educating students in EM on the topic of RD.

The Ethics of Procedural Education Under Pandemic Conditions.

BACKGROUND: The COVID-19 pandemic significantly disrupted emergency medicine residents' education. Early in the pandemic, many facilities lacked adequate personal protective equipment (PPE), and intubation was considered particularly high risk for transmission to physicians, leading hospitals to limit the number of individuals present during the procedure. This posed difficulties for residents and academic faculty, as opportunities to perform endotracheal intubation during residency are limited, but patients with COVID-19 requiring intubation are unstable and have difficult airways. Case Scenario: When PPE is being rationed, who should be the one to perform an intubation on a patient with respiratory failure from severe COVID-19? DISCUSSION: We examined this case scenario using the ethical frameworks of bioethical principles and virtue ethics. Bioethical principles include justice, beneficence, nonmalfeasance, and autonomy, and virtue ethics emphasizes the provision of moral exemplars and opportunities to exercise practical wisdom. Arguments for an attending-only strategy include the role of the attending as a truly autonomous decision maker and the importance of providing residents with a moral exemplar. A resident-only strategy benefits a resident's future patients and provides opportunities for residents to exercise character. Strategies preserving the dyad of attending and resident maintain these advantages and mitigate some drawbacks, while intubation teams may provide the most parsimonious use of PPE, but may elide resident involvement. CONCLUSIONS: There exist compelling motivations for involving senior residents and attendings in high-risk intubations during the COVID-19 pandemic. A just strategy will preserve residents' role whenever possible, while maximizing supervision and providing alternative routes for intubation practice.

Chronic recordings from the marmoset motor cortex reveals modulation of neural firing and local field potentials overlap with macaques.

Objective.The common marmoset has been increasingly used in neural interfacing studies due to its smaller size, easier handling, and faster breeding compared to Old World non-human primate (NHP) species. While assessment of cortical anatomy in marmosets has shown strikingly similar layout to macaques, comprehensive assessment of electrophysiological properties underlying forelimb reaching movements in this bridge species does not exist. The objective of this study is to characterize electrophysiological properties of signals recorded from the marmoset primary motor cortex (M1) during a reach task and compare with larger NHP models such that this smaller NHP model can be used in behavioral neural interfacing studies.Approach and main results.Neuronal firing rates and local field potentials (LFPs) were chronically recorded from M1 in three adult, male marmosets. Firing rates, mu + beta and high gamma frequency bands of LFPs were evaluated for modulation with respect to movement. Firing rate and regularity of neurons of the marmoset M1 were similar to that reported in macaques with a subset of neurons showing selectivity to movement direction. Movement phases (rest vs move) was classified from both neural spiking and LFPs. Microelectrode arrays provide the ability to sample small regions of the motor cortex to drive brain-machine interfaces (BMIs). The results demonstrate that marmosets are a robust bridge species for behavioral neuroscience studies with motor cortical electrophysiological signals recorded from microelectrode arrays that are similar to Old World NHPs.Significance. As marmosets represent an interesting step between rodent and macaque models, successful demonstration that neuron modulation in marmoset motor cortex is analogous to reports in macaques illustrates the utility of marmosets as a viable species for BMI studies.

Integrating Health Equity Content Into Health Professions Education.

Health equity is a common theme discussed in health professions schools, yet many educators are wary of addressing it. Avoidance of health equity content in health professions education leads to student frustration and missed opportunities to educate the next generation of health care professionals about sensitive yet important issues. Moreover, this gap in students' knowledge can negatively influence patients and perpetuate disparities.

How Should Health Professional Education Respond to Widespread Racial and Ethnic Health Inequity and Police Brutality?

Health professions educators continuously adapt curricular content in response to new scientific knowledge but can struggle to incorporate content about current social issues that profoundly affect students and learning environments. This article offers recommendations to support innovation and action as students and faculty grapple with ongoing unrest in the United States, including racism, murders of Black people by police, and COVID-19.

Hydraulic-Head Formulation for Density-Dependent Flow and Transport.

Density-dependent flow and transport solutions for coastal saltwater intrusion investigations, analyses of fluid injection into deep brines, and studies of convective fingering and instabilities of denser fluids moving through less dense fluids typically formulate the groundwater flow equation in terms of pressure or equivalent freshwater head. A formulation of the flow equation in terms of hydraulic head is presented here as an alternative. The hydraulic-head formulation can facilitate adaptation of existing constant-density groundwater flow codes to include density-driven flow by avoiding the need to convert between freshwater head and hydraulic head within the code and by incorporating density-dependent terms as a compartmentalized "correction" to constant-density calculations already performed by the code. The hydraulic-head formulation also accommodates complexities such as unconfined groundwater flow and Newton-Raphson solution schemes more readily than the freshwater-head formulation. Simulation results are presented for four example problems solved using an implementation of the hydraulic-head formulation in MODFLOW.

Enhancement of metallomacrocycle-based oxygen reduction catalysis through immobilization in a tunable silk-protein scaffold.

Fuel cells convert chemical energy into electrical current with the use of an oxidant such as oxygen and have the potential to reduce our reliance on fossil fuels. To overcome the slow kinetics of the oxygen reduction reaction (ORR), platinum is often used as the catalyst. However, the scarcity and expense of platinum limits the wide-spread use of fuel cells. In the search for non-platinum oxygen reduction catalysts, metallomacrocycles have attracted significant attention. While progress has been made in understanding how metallomacrocycle-based molecules can catalyze the ORR, their low stability, remains an on-going challenge. Here we report an immobilization strategy whereby hemin (iron protoporphyrin IX, heme b) is converted into an oxygen reduction catalyst which could be operated for over 96 h, with turnover numbers >107. This represents a 3 orders of magnitude improvement over the best reported iron porphyrin ORR catalyst to date. The basis for this improvement in turnover is specific binding of the heme within a recombinant silk protein, which allows for separation of the porphyrin active sites. Use of the silk protein provides a scaffold that can be engineered to improve selectivity and efficiency. Through rational design of the heme binding site, a > 95% selectivity for a four-electron reduction of oxygen to water was obtained, equal to the selectivity obtained using platinum-based catalysts. This work represents an important advance in the field, demonstrating that metallomacrocycle-based ORR catalysts are viable for use in fuel cells.

Gender differences in funding among grant recipients in emergency medicine: A multicenter analysis.

OBJECTIVE: To describe differences in funded grants between male and female faculty in two academic emergency departments. METHODS: This was a retrospective analysis of grant funding at two academic emergency departments from January 2012-September 2018. We queried the grants department databases at each institution and obtained records of all funded grants for emergency medicine (EM) faculty. We extracted the following information for each award: gender of the principal investigator (PI), PI academic rank, grant mechanism (government, institutional, industry, organizational), and percent effort. Differences by gender were compared using Chi-square or Fisher's exact test and Wilcoxon-rank sum. RESULTS: One-hundred and thirty grants were awarded to EM faculty at the two institutions during the study period. Of the funded grants, 35 (27%) of recipients were female. Among grant recipients, females held lower academic ranking than males (p-value < 0.001): Instructor (49% vs 51%), Assistant Professor (36% vs 64%), Associate Professor (9% vs 91%), and Professor (0% vs 100%), respectively. Organizational grants were dispersed equally between funded faculty, but females received a fewer government, industry, and institutional grants (p-value = 0.007). Female grant recipients were awarded a higher median percent of effort compared to males (14% [IQR: 3-51] vs 8% [IQR: 1-15], respectively, p-value = 0.023). CONCLUSION: In this multicenter analysis, gender discrepancies exist among funded grants of EM faculty. Male recipients had higher academic ranking than their female counterparts. Female recipients were less likely to have government, institutional, and industry grants but received a greater percent effort on funding that was awarded.

Spinal cord neural interfacing in common marmosets (Callithrix jacchus).

OBJECTIVE: Spinal cord injury remains an ailment with no comprehensive cure, and affected patients suffer from a greatly diminished quality of life. This large population could significantly benefit from prosthetic technologies to replace missing limbs, reanimate nonfunctional limbs, and enable new modes of technologies to restore muscle control and function. While cortically driven brain machine interfaces have achieved great success in interfacing with an external device to restore lost functions, interfacing with the spinal cord can provide an additional site to record motor control signals, which can have its own advantages, despite challenges from using a smaller non-human primate (NHP) model. The goal of this study is to develop such a spinal cord neural interface to record motor signals from the high cervical levels of the spinal cord in a common marmoset (Callithrix jacchus) model. Approach and main results. Detailed methods are discussed for this smaller NHP model that includes behavioral training, surgical methods for electrode placement, connector placement and wire handling, electrode specifications and modifications for accessing high cervical level interneurons and motorneurons. The study also discusses the methods and challenges involved in behavioral multi-channel extracellular recording from the marmoset spinal cord, including the major recording failure mechanisms encountered during the study. SIGNIFICANCE: Marmosets provide a good step between rodent and larger NHP models due to their small size, ease of handling, cognitive abilities, and similarities to other primate motor systems. The study shows the feasibility of recording spinal cord signals and using marmosets as a smaller NHP model in behavioral neuroscience studies. Interfacing with the spinal cord in chronically implanted animals can provide useful information about how motor control signals within the spinal cord are transformed to cause limb movements.

Protein Corona over Mesoporous Silica Nanoparticles: Influence of the Pore Diameter on Competitive Adsorption and Application to Prostate Cancer Diagnostics.

Diagnostic tests based on proteomics analysis can have significant advantages over more traditional biochemical tests. However, low molecular weight (MW) protein biomarkers are difficult to identify by standard mass spectrometric analysis, as they are usually present at low concentrations and are masked by more abundant resident proteins. We have previously shown that mesoporous silica nanoparticles are able to capture a predominantly low MW protein fraction from the serum, as compared to the protein corona (PC) adsorbed onto dense silica nanoparticles. In this study, we begin by further investigating this effect using liquid chromatography-mass spectrometry (LC-MS)/MS and thermogravimetric analysis (TGA) to compare the MW of the proteins in the coronas of mesoporous silica nanoparticles with the same particle size but different pore diameters. Next, we examine the process by which two proteins, one small and one large, adsorb onto these mesoporous silica nanoparticles to establish a theory of why the corona becomes enriched in low MW proteins. Finally, we use this information to develop a novel system for the diagnosis of prostate cancer. An elastic net statistical model was applied to LC-MS/MS protein coronas from the serum of 22 cancer patients, identifying proteins specific to each patient group. These studies help to explain why low MW proteins predominate in the coronas of mesoporous silica nanoparticles, and they illustrate the ability of this information to supplement more traditional diagnostic tests.

The effect of transfer to adult transplant care on kidney function and immunosuppressant drug level variability in pediatric kidney transplant recipients.

Adolescent age at time of transplant has been recognized as a risk factor for renal allograft loss. Increased risk for graft failure may persist from adolescence to young adulthood. Transfer of care is hypothesized as a risk factor for non-adherence and graft loss. We explored whether kidney allograft function declined at an accelerated rate after transfer of care to adult transplant centers and whether coefficient of variation of tacrolimus (CV TAC) trough levels predicted allograft loss. Single-center, retrospective chart review was performed for pediatric kidney transplant recipients who received transplants between 1999 and 2011. Change in eGFR pre- and post-transfer was performed via a linear mixed-effects model. CV TAC was calculated in transplant recipients with TAC data pre- and post-transfer. t test was performed to determine the difference between means of CV TAC in subjects with and without allograft loss following transfer of care. Of the 138 subjects who transferred to adult care, 47 subjects with data pre- and post-transfer demonstrated a decrease in the rate of eGFR decline post-transfer from 8.0 mL/min/1.73 m2 per year to 2.1 mL/min/1.73 m2 per year, an ~80% decrease in eGFR decline post-transfer (P = 0.01). Twenty-four subjects had CV TAC data pre- and post-transfer of care. Pretransfer CV TAC for subjects with allograft loss post-transfer was significantly higher than in subjects without allograft loss (49% vs 26%, P < 0.05). Transfer of care was not independently associated with acceleration in eGFR decline. CV TAC may aid in identifying patients at risk for allograft loss post-transfer.

Variations in Opioid Prescribing Behavior by Physician Training.

INTRODUCTION: Opioid abuse has reached epidemic proportions in the United States. Patients often present to the emergency department (ED) with painful conditions seeking analgesic relief. While there is known variability in the prescribing behaviors of emergency physicians, it is unknown if there are differences in these behaviors based on training level or by resident specialty. METHODS: This is a retrospective chart review of ED visits from a single, tertiary-care academic hospital over a single academic year (2014-2015), examining the amount of opioid pain medication prescribed. We compared morphine milligram equivalents (MME) between provider specialty and level of training (emergency medicine [EM] attending physicians, EM residents in training, and non-EM residents in training). RESULTS: We reviewed 55,999 total ED visits, of which 4,431 (7.9%) resulted in discharge with a prescription opioid medication. Residents in a non-EM training program prescribed higher amounts of opioid medication (108 MME, interquartile ratio [IQR] 75-150) than EM attendings (90 MME, lQR 75-120), who prescribed more than residents in an EM training program (75 MME, IQR 60-113) (p<0.01). CONCLUSION: In an ED setting, variability exists in prescribing patterns with non-EM residents prescribing larger amounts of opioids in the acute setting. EM attendings should closely monitor for both over- and under-prescribing of analgesic medications.