Comparing the Effectiveness of Hands-on vs. Observational Training of Residents in Interlaminar Epidural Steroid Injections (ILESI) Using a High-Fidelity Spine Simulator.

Introduction The Accreditation Council for Graduate Medical Education (ACGME) requires that residents in the Physical Medicine and Rehabilitation (PM&R) residency observe or perform certain interventional procedures, one of which is an interlaminar epidural steroid injection (ILESI). While the traditional learning model relying heavily on observation is commonplace, it leaves the practice phase of learning to happen on real patients. High-fidelity simulation may be a worthwhile alternative as a training approach to increase physician comfort with the procedure and improve patient safety. Methods Current PM&R residents from two programs between their second and fourth year, inclusively, who lacked prior training experience in ILESI attended one hour of either: (1) an experimental arm of supervised hands-on training on a simulation device or (2) a control arm observing the procedures performed by an attending on the same device. Assignments were made based on resident schedule availability. Pre-training knowledge, training, and post-training knowledge were assessed at the Multidisciplinary Pain Clinic at Montefiore Medical Center. Participants were assessed on their procedural competence using an adapted version of a previously published grading checklist before the session. Participants also evaluated their confidence in performing the procedure prior to and after training. Data was analyzed using the Wilcoxon signed-rank test and the Wilcoxon rank-sum test. SAS Version 9.4 was used for analysis. Results Fifteen residents initially participated, but three residents dropped out at the 15-week follow-up. There was a significant increase in test scores in both arms immediately after the intervention (p=0.008 in control, p=0.016 in the experiment), with greater improvement shown in the hands-on training group (p=0.063). At the 15-week follow-up, there was no significant change in test scores in the control arm (p=0.969) while there was a decrease in the experiment arm (p<0.001). Conclusion Hands-on learning with high-fidelity simulation demonstrated more improvement for short-term motor-skill acquisition, while observational learning with repetition showed more benefits for long-term retention. Optimal procedural training should employ both educational modalities for best short- and long-term results.

Highly reversible Zn metal anode enabled by sustainable hydroxyl chemistry.

Rechargeable Zn metal batteries (RZMBs) may provide a more sustainable and lower-cost alternative to established battery technologies in meeting energy storage applications of the future. However, the most promising electrolytes for RZMBs are generally aqueous and require high concentrations of salt(s) to bring efficiencies toward commercially viable levels and mitigate water-originated parasitic reactions including hydrogen evolution and corrosion. Electrolytes based on nonaqueous solvents are promising for avoiding these issues, but full cell performance demonstrations with solvents other than water have been very limited. To address these challenges, we investigated MeOH as an alternative electrolyte solvent. These MeOH-based electrolytes exhibited exceptional Zn reversibility over a wide temperature range, with a Coulombic efficiency > 99.5% at 50% Zn utilization without cell short-circuit behavior for > 1,800 h. More important, this remarkable performance translates well to Zn || metal-free organic cathode full cells, supporting < 6% capacity decay after > 800 cycles at -40 °C.

A Polymer-in-Salt Electrolyte with Enhanced Oxidative Stability for Lithium Metal Polymer Batteries.

The lithium (Li) metal polymer battery (LMPB) is a promising candidate for solid-state batteries with high safety. However, high voltage stability of such a battery has been hindered by the use of polyethylene oxide (PEO), which oxidizes at a potential lower than 4 V versus Li. Herein, we adopt the polymer-in-salt electrolyte (PISE) strategy to circumvent the disadvantage of the PEO-lithium bis(fluorosulfonyl)imide (LiFSI) system with EO/Li ≤ 8 through a dry ball-milling process to avoid the contamination of the residual solvent. The obtained solid-state PISEs exhibit distinctly different morphologies and coordination structures which lead to significant improvement in oxidative stability. P(EO)1LiFSI has a low melting temperature, a high ionic conductivity at 60 °C, and an oxidative stability of ∼4.5 V versus Li/Li+. With an effective interphase rich in inorganic species and a good stability of the hybrid polymer electrolyte toward Li metal, the LMPB constructed with Li||LiNi1/3Co1/3Mn1/3O2 can retain 74.4% of capacity after 186 cycles at 60 °C under the cutoff charge voltage of 4.3 V. The findings offer a promising pathway toward high-voltage stable polymer electrolytes for high-energy-density and safe LMPBs.

Utility of Simulation via Instant Messaging - Birmingham Advance (SIMBA) in medical education during COVID-19 pandemic.

BACKGROUND: Simulation via Instant Messaging - Birmingham Advance (SIMBA) aimed to improve clinicians' confidence in managing various clinical scenarios during the COVID-19 pandemic. METHODS: Five SIMBA sessions were conducted between May and August 2020. Each session included simulation of scenarios and interactive discussion. Participants' self-reported confidence, acceptance, and relevance of the simulated cases were measured. RESULTS: Significant improvement was observed in participants' self-reported confidence (overall n = 204, p<0.001; adrenal n = 33, p<0.001; thyroid n = 37, p<0.001; pituitary n = 79, p<0.001; inflammatory bowel disease n = 17, p<0.001; acute medicine n = 38, p<0.001). Participants reported improvements in clinical competencies: patient care 52.0% (n = 106/204), professionalism 30.9% (n = 63/204), knowledge on patient management 84.8% (n = 173/204), systems-based practice 48.0% (n = 98/204), practice-based learning 69.6% (n = 142/204) and communication skills 25.5% (n = 52/204). CONCLUSION: SIMBA is a novel pedagogical virtual simulation-based learning model that improves clinicians' confidence in managing conditions across various specialties.

Fluorinated interphase enables reversible aqueous zinc battery chemistries.

Metallic zinc is an ideal anode due to its high theoretical capacity (820 mAh g-1), low redox potential (-0.762 V versus the standard hydrogen electrode), high abundance and low toxicity. When used in aqueous electrolyte, it also brings intrinsic safety, but suffers from severe irreversibility. This is best exemplified by low coulombic efficiency, dendrite growth and water consumption. This is thought to be due to severe hydrogen evolution during zinc plating and stripping, hitherto making the in-situ formation of a solid-electrolyte interphase (SEI) impossible. Here, we report an aqueous zinc battery in which a dilute and acidic aqueous electrolyte with an alkylammonium salt additive assists the formation of a robust, Zn2+-conducting and waterproof SEI. The presence of this SEI enables excellent performance: dendrite-free zinc plating/stripping at 99.9% coulombic efficiency in a Ti||Zn asymmetric cell for 1,000 cycles; steady charge-discharge in a Zn||Zn symmetric cell for 6,000 cycles (6,000 h); and high energy densities (136 Wh kg-1 in a Zn||VOPO4 full battery with 88.7% retention for >6,000 cycles, 325 Wh kg-1 in a Zn||O2 full battery for >300 cycles and 218 Wh kg-1 in a Zn||MnO2 full battery with 88.5% retention for 1,000 cycles) using limited zinc. The SEI-forming electrolyte also allows the reversible operation of an anode-free pouch cell of Ti||ZnxVOPO4 at 100% depth of discharge for 100 cycles, thus establishing aqueous zinc batteries as viable cell systems for practical applications.

Functionalized Phosphonium Cations Enable Zinc Metal Reversibility in Aqueous Electrolytes.

Aqueous rechargeable zinc metal batteries promise attractive advantages including safety, high volumetric energy density, and low cost; however, such benefits cannot be unlocked unless Zn reversibility meets stringent commercial viability. Herein, we report remarkable improvements on Zn reversibility in aqueous electrolytes when phosphonium-based cations are used to reshape interfacial structures and interphasial chemistries, particularly when their ligands contain an ether linkage. This novel aqueous electrolyte supports unprecedented Zn reversibility by showing dendrite-free Zn plating/stripping for over 6400 h at 0.5 mA cm-2 , or over 280 h at 2.5 mA cm-2 , with coulombic efficiency above 99 % even with 20 % Zn utilization per cycle. Excellent full cell performance is demonstrated with Na2 V6 O16 ⋅1.63 H2 O cathode, which cycles for 2000 times at 300 mA g-1 . The microscopic characterization and modeling identify the mechanism of unique interphase chemistry from phosphonium and its functionalities as the key factors responsible for dictating reversible Zn chemistry.

Learning to encode cellular responses to systematic perturbations with deep generative models.

Cellular signaling systems play a vital role in maintaining homeostasis when a cell is exposed to different perturbations. Components of the systems are organized as hierarchical networks, and perturbing different components often leads to transcriptomic profiles that exhibit compositional statistical patterns. Mining such patterns to investigate how cellular signals are encoded is an important problem in systems biology, where artificial intelligence techniques can be of great assistance. Here, we investigated the capability of deep generative models (DGMs) to modeling signaling systems and learn representations of cellular states underlying transcriptomic responses to diverse perturbations. Specifically, we show that the variational autoencoder and the supervised vector-quantized variational autoencoder can accurately regenerate gene expression data in response to perturbagen treatments. The models can learn representations that reveal the relationships between different classes of perturbagens and enable mappings between drugs and their target genes. In summary, DGMs can adequately learn and depict how cellular signals are encoded. The resulting representations have broad applications, demonstrating the power of artificial intelligence in systems biology and precision medicine.

Correction: Synthesis of IL-6 by Hepatocytes Is a Normal Response to Common Hepatic Stimuli.

[This corrects the article DOI: 10.1371/journal.pone.0096053.].

Measurement of resident fatigue using rapid number naming.

OBJECTIVE: Sleep deprivation has a negative effect on neurocognitive performance. The King-Devick test (KDT), which tests speed and accuracy of number-reading, requires integrity of saccades, visual processing, and cognition. This study investigated effects of sleep deprivation in on-call residents using KDT. METHODS: A prospective cohort study was conducted among 80 residents. KDT was performed at the beginning and end of an overnight call shift for the residents in the experimental group. A control group was tested at the beginning of 2 consecutive day shifts. Estimates of hours of sleep, Karolinska Sleepiness Scale (KSS)(1 = extremely alert, 9 = extremely sleepy), and time and accuracy of KDT were recorded. RESULTS: 42 residents were tested before and after overnight call shifts and 38 served as controls. Change in test time differed between the groups, with the experimental group performing 0.54(SD = 4.0) seconds slower after their night on call and the control group performing 2.32(SD = 3.0) seconds faster on the second day, p < 0.001. This difference was larger in surgical compared to medical residents. CONCLUSIONS: Sleep deprivation was inversely correlated with neurocognitive performance as measured by KDT, with more effect on surgical than medical residents. Further research could investigate whether this test could help determine fatigue level and ability to continue working after a long shift.

Precision Oncology beyond Targeted Therapy: Combining Omics Data with Machine Learning Matches the Majority of Cancer Cells to Effective Therapeutics.

Precision oncology involves identifying drugs that will effectively treat a tumor and then prescribing an optimal clinical treatment regimen. However, most first-line chemotherapy drugs do not have biomarkers to guide their application. For molecularly targeted drugs, using the genomic status of a drug target as a therapeutic indicator has limitations. In this study, machine learning methods (e.g., deep learning) were used to identify informative features from genome-scale omics data and to train classifiers for predicting the effectiveness of drugs in cancer cell lines. The methodology introduced here can accurately predict the efficacy of drugs, regardless of whether they are molecularly targeted or nonspecific chemotherapy drugs. This approach, on a per-drug basis, can identify sensitive cancer cells with an average sensitivity of 0.82 and specificity of 0.82; on a per-cell line basis, it can identify effective drugs with an average sensitivity of 0.80 and specificity of 0.82. This report describes a data-driven precision medicine approach that is not only generalizable but also optimizes therapeutic efficacy. The framework detailed herein, when successfully translated to clinical environments, could significantly broaden the scope of precision oncology beyond targeted therapies, benefiting an expanded proportion of cancer patients. Mol Cancer Res; 16(2); 269-78. ©2017 AACR.

Liquid Structure with Nano-Heterogeneity Promotes Cationic Transport in Concentrated Electrolytes.

Using molecular dynamics simulations, small-angle neutron scattering, and a variety of spectroscopic techniques, we evaluated the ion solvation and transport behaviors in aqueous electrolytes containing bis(trifluoromethanesulfonyl)imide. We discovered that, at high salt concentrations (from 10 to 21 mol/kg), a disproportion of cation solvation occurs, leading to a liquid structure of heterogeneous domains with a characteristic length scale of 1 to 2 nm. This unusual nano-heterogeneity effectively decouples cations from the Coulombic traps of anions and provides a 3D percolating lithium-water network, via which 40% of the lithium cations are liberated for fast ion transport even in concentration ranges traditionally considered too viscous. Due to such percolation networks, superconcentrated aqueous electrolytes are characterized by a high lithium-transference number (0.73), which is key to supporting an assortment of battery chemistries at high rate. The in-depth understanding of this transport mechanism establishes guiding principles to the tailored design of future superconcentrated electrolyte systems.

Deletion of ghrelin prevents aging-associated obesity and muscle dysfunction without affecting longevity.

During aging, decreases in energy expenditure and locomotor activity lead to body weight and fat gain. Aging is also associated with decreases in muscle strength and endurance leading to functional decline. Here, we show that lifelong deletion of ghrelin prevents development of obesity associated with aging by modulating food intake and energy expenditure. Ghrelin deletion also attenuated the decrease in phosphorylated adenosine monophosphate-activated protein kinase (pAMPK) and downstream mediators in muscle, and increased the number of type IIa (fatigue resistant, oxidative) muscle fibers, preventing the decline in muscle strength and endurance seen with aging. Longevity was not affected by ghrelin deletion. Treatment of old mice with pharmacologic doses of ghrelin increased food intake, body weight, and muscle strength in both ghrelin wild-type and knockout mice. These findings highlight the relevance of ghrelin during aging and identify a novel AMPK-dependent mechanism for ghrelin action in muscle.

Wide-Temperature Electrolytes for Lithium-Ion Batteries.

Formulating electrolytes with solvents of low freezing points and high dielectric constants is a direct approach to extend the service-temperature range of lithium (Li)-ion batteries (LIBs). In this study, we report such wide-temperature electrolyte formulations by optimizing the ethylene carbonate (EC) content in the ternary solvent system of EC, propylene carbonate (PC), and ethyl methyl carbonate (EMC) with LiPF6 salt and CsPF6 additive. An extended service-temperature range from -40 to 60 °C was obtained in LIBs with lithium nickel cobalt aluminum oxide (LiNi0.80Co0.15Al0.05O2, NCA) as cathode and graphite as anode. The discharge capacities at low temperatures and the cycle life at room temperature and elevated temperatures were systematically investigated together with the ionic conductivity and phase-transition behaviors. The most promising electrolyte formulation was identified as 1.0 M LiPF6 in EC-PC-EMC (1:1:8 by wt) with 0.05 M CsPF6, which was demonstrated in both coin cells of graphite∥NCA and 1 Ah pouch cells of graphite∥LiNi1/3Mn1/3Co1/3O2. This optimized electrolyte enables excellent wide-temperature performances, as evidenced by the high capacity retention (68%) at -40 °C and C/5 rate, significantly higher than that (20%) of the conventional LIB electrolyte, and the nearly identical stable cycle life as the conventional LIB electrolyte at room temperature and elevated temperatures up to 60 °C.

Measuring time utilization of pharmacists in the Birmingham Free Clinic dispensary.

BACKGROUND: Free and charitable clinics are a critical part of America's healthcare safety net. Although informatics tools have the potential to mitigate many of the organizational and service-related challenges facing these clinics, little research attention has been paid to the workflows and potential impact of electronic systems in these settings. In previous work, we performed a qualitative investigation at a free clinic dispensary to identify workflow challenges that may be alleviated through introduction of informatics interventions. However, this earlier study did not quantify the magnitude of these challenges. Time-motion studies offer a precise standard in quantifying healthcare workers' time expenditures on clinical activities, and can provide valuable insight into system specifications. These data, informed by a lean healthcare perspective, provide a quality improvement framework intended to maximize value and eliminate waste in inefficient workflow processes. METHODS: We performed a continuous observation time-motion study in the Birmingham Free Clinic dispensary. Two researchers followed pharmacists over the course of three general clinic sessions and recorded the duration of specific tasks. Pharmacists were then asked to identify tasks as value-added or non-value-added to facilitate calculation of the value quotient, a metric used to determine a workflow's level of efficiency. RESULTS: Four high-level workflow categories occupied almost 95 % of pharmacist time: prescription (Rx) preparation (39.8 %), clinician interaction (21.5 %), EMR operations (14.8 %), and patient interaction (18.7 %). Pharmacists invested the largest portion of time in prescription preparation, with 21.8 % of pharmacist time spent handwriting medication labels. Based on value categorizations made by the pharmacists, the average value quotient was found to be 40.3 %, indicating that pharmacists spend more than half of their time completing tasks they consider to be non-value-added. CONCLUSIONS: Our results show that pharmacists spend a large portion of their time preparing prescriptions, primarily the handwritten labeling of medication bottles and documentation tasks, which is not an optimal utilization of pharmacist expertise. The value quotient further supports that there are many wasteful tasks that may benefit from workflow redesign and health information technology, which could result in efficiency improvements for pharmacists.

Development of a chemically defined medium and discovery of new mitogenic growth factors for mouse hepatocytes: mitogenic effects of FGF1/2 and PDGF.

Chemically defined serum-free media for rat hepatocytes have been useful in identifying EGFR ligands and HGF/MET signaling as direct mitogenic factors for rat hepatocytes. The absence of such media for mouse hepatocytes has prevented screening for discovery of such mitogens for mouse hepatocytes. We present results obtained by designing such a chemically defined medium for mouse hepatocytes and demonstrate that in addition to EGFR ligands and HGF, the growth factors FGF1 and FGF2 are also important mitogenic factors for mouse hepatocytes. Smaller mitogenic response was also noticed for PDGF AB. Mouse hepatocytes are more likely to enter into spontaneous proliferation in primary culture due to activation of cell cycle pathways resulting from collagenase perfusion. These results demonstrate unanticipated fundamental differences in growth biology of hepatocytes between the two rodent species.

Synthesis of IL-6 by hepatocytes is a normal response to common hepatic stimuli.

Exogenous interleukin 6 (IL-6), synthesized at the initiation of the acute phase response, is considered responsible for signaling hepatocytes to produce acute phase proteins. It is widely posited that IL-6 is either delivered to the liver in an endocrine fashion from immune cells at the site of injury, or alternatively, in a paracrine manner by hepatic immune cells within the liver. A recent publication showed there was a muted IL-6 response in lipopolysaccharide (LPS)-injured mice when nuclear NFκB was specifically inactivated in the hepatocytes. This indicates hepatocellular signaling is also involved in regulating the acute phase production of IL-6. Herein, we present extensive in vitro and in vivo evidence that normal hepatocytes are directly induced to synthesize IL-6 mRNAs and protein by challenge with LPS, a bacterial hepatotoxin, and by HGF, an important regulator of hepatic homeostasis. As the IL-6 receptor is found on the hepatocyte, these results reveal that induction of the acute phase response can be regulated in an autocrine as well as endocrine/paracrine fashion. Further, herein we provide data indicating that following partial hepatectomy (PHx), HGF differentially regulates IL-6 production in hepatocytes (induces) versus immune cells (suppresses), signifying disparate regulation of the cell sources involved in IL-6 production is a biologically relevant mechanism that has previously been overlooked. These findings have wide ranging ramifications regarding how we currently interpret a variety of in vivo and in vitro biological models involving elements of IL-6 signaling and the hepatic acute phase response.