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1.
Curr Issues Mol Biol ; 45(10): 8040-8052, 2023 Sep 30.
Article in English | MEDLINE | ID: mdl-37886951

ABSTRACT

Metabolic stress in skeletal muscle cells causes sustained metabolic changes, but the mechanisms of the prolonged effects are not fully known. In this study, we tested C2C12 cells with the AMP-activated protein kinase (AMPK) stimulator AICAR and measured the changes in the metabolic pathways and signaling kinases. AICAR caused an acute increase in the phosphorylation of the AMPK target ULK1, the mTORC1 substrate S6K, and the mTORC2 target Akt. Intriguingly, prior exposure to AICAR only decreased glucose-6 phosphate dehydrogenase activity when it underwent three-hour recovery after exposure to AICAR in a bicarbonate buffer containing glucose (KHB) instead of Dulbecco's Minimum Essential Medium (DMEM). The phosphorylation of the mTORC1 target S6K was increased after recovery in DMEM but not KHB, although this appeared to be specific to S6K, as the phosphorylation of the mTORC1 target site on ULK1 was not altered when the cells recovered in DMEM. The phosphorylation of mTORC2 target sites was also heterogenous under these conditions, with Akt increasing at serine 473 while other targets (SGK1 and PKCα) were unaffected. The exposure of cells to rapamycin (an mTORC1 inhibitor) and PP242 (an inhibitor of both mTOR complexes) revealed the differential phosphorylation of mTORC2 substrates. Taken together, the data suggest that prior exposure to AICAR causes the selective phosphorylation of mTOR substrates, even after prolonged recovery in a nutrient-replete medium.

2.
Cytotherapy ; 25(1): 46-58, 2023 01.
Article in English | MEDLINE | ID: mdl-36396552

ABSTRACT

BACKGROUND AIMS: The targeting of solid cancers with chimeric antigen receptor (CAR) T cells faces many technological hurdles, including selection of optimal target antigens. Promising pre-clinical and clinical data of CAR T-cell activity have emerged from targeting surface antigens such as GD2 and B7H3 in childhood cancer neuroblastoma. Anaplastic lymphoma kinase (ALK) is expressed in a majority of neuroblastomas at low antigen density but is largely absent from healthy tissues. METHODS: To explore an alternate target antigen for neuroblastoma CAR T-cell therapy, the authors generated and screened a single-chain variable fragment library targeting ALK extracellular domain to make a panel of new anti-ALK CAR T-cell constructs. RESULTS: A lead novel CAR T-cell construct was capable of specific cytotoxicity against neuroblastoma cells expressing low levels of ALK, but with only weak cytokine and proliferative T-cell responses. To explore strategies for amplifying ALK CAR T cells, the authors generated a co-CAR approach in which T cells received signal 1 from a first-generation ALK construct and signal 2 from anti-B7H3 or GD2 chimeric co-stimulatory receptors. The co-CAR approach successfully demonstrated the ability to avoid targeting single-antigen-positive targets as a strategy for mitigating on-target off-tumor toxicity. CONCLUSIONS: These data provide further proof of concept for ALK as a neuroblastoma CAR T-cell target.


Subject(s)
Neuroblastoma , Receptors, Antigen, T-Cell , Humans , Receptors, Antigen, T-Cell/genetics , Cell Line, Tumor , Xenograft Model Antitumor Assays , Gangliosides , Neuroblastoma/genetics , Neuroblastoma/therapy , T-Lymphocytes , Immunotherapy, Adoptive , Antibodies , Logic
3.
J Fish Biol ; 103(5): 1031-1043, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37424143

ABSTRACT

Reproductive timing, location, and behavior are important characteristics that determine marine population dynamics, structure, and resilience to threats, including fishing and climate change. It is challenging to evaluate factors driving variability in these reproductive traits in wild fishes because of the difficulty observing individuals in their natural environments. In the present study, we used high-resolution depth, temperature, and acceleration time series recorded by pop-up satellite archival tags to (1) identify and characterize patterns in depth and acceleration that may be indicative of spawning events in large Atlantic halibut (Hippoglossus hippoglossus), and (2) estimate the effects of individual traits (body size and sex) and environmental factors (location and temperature) on spawning time and frequency. Unique rapid rises observed in the winter depth profiles were interpreted as spawning events. The initiation of the first presumed spawning rise was negatively correlated to water temperature experienced during the prespawning season, suggesting that currently increasing water temperature in the Gulf of St. Lawrence may induce phenological change in halibut spawning time. The number of rises of batch-spawning females was unrelated to female body size. The present study demonstrates how electronic tagging can be used for in-depth characterization of timing, location, and behaviors associated with spawning in a large flatfish species. Such information can inform spatiotemporal management and conservation measures aiming to protect species from directed fishing and by-catch during spawning.


Subject(s)
Flounder , Reproductive Behavior , Humans , Female , Animals , Reproduction , Water
4.
Surg Radiol Anat ; 45(1): 35-38, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36484823

ABSTRACT

BACKGROUND: The most common neurovascular variant is the fetal posterior cerebral artery (FPCA), in which the P1 branch is absent or hypoplastic, and the majority of P2 supply is derived from the anterior circulation. While there are reports of hyperplastic anterior choroidal arteries (AChA) with supply to the temporo-occipital and calcarine regions, no reports of a duplicated FPCA exist. METHODS: This case report describes a patient with a ruptured right FPCA aneurysm. Digital subtraction angiogram (DSA) revealed an artery with origin distal to the FPCA associated with the aneurysm. This was not consistent with a typical AChA. The FPCA associated with the aneurysm had the typical origin, course, and supply of a FPCA. The distal FPCA had a similar course of a typical FPCA with significant supply to the typical PCA territory. The patient underwent successful clipping of the aneurysm, and the duplicated FPCA was identified during the craniotomy. RESULTS: The features of this duplicate FPCA, which has not been previously described, are discussed in comparison to another variant, the hyperplastic, anomalous AChA. The artery described in this report does not fit the typical criteria of this AChA variant. Therefore, the authors outline this variant as a duplicated FPCA. CONCLUSION: Recognition of variant cerebrovascular anatomy is vital to neurosurgeons and interventional neuroradiology specialists. FPCA aneurysms require special management considerations and are often more challenging to treat. This report discusses a duplicated FPCA. To our knowledge, this is the first description of this variant. A duplicated FPCA carries important management considerations in the management of neurovascular pathology.


Subject(s)
Aneurysm, Ruptured , Intracranial Aneurysm , Humans , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery , Intracranial Aneurysm/complications , Posterior Cerebral Artery/diagnostic imaging , Aneurysm, Ruptured/diagnostic imaging , Aneurysm, Ruptured/surgery , Aneurysm, Ruptured/etiology , Carotid Artery, Internal/surgery
5.
Nature ; 539(7628): 309-313, 2016 11 10.
Article in English | MEDLINE | ID: mdl-27806376

ABSTRACT

Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management.


Subject(s)
Neoplastic Stem Cells/pathology , Oligodendroglioma/genetics , Oligodendroglioma/pathology , Sequence Analysis, RNA , Single-Cell Analysis , Cell Differentiation , Cell Proliferation , DNA Copy Number Variations/genetics , Humans , Isocitrate Dehydrogenase/genetics , Neoplastic Stem Cells/metabolism , Neural Stem Cells/metabolism , Neural Stem Cells/pathology , Neuroglia/metabolism , Neuroglia/pathology , Phylogeny , Point Mutation
6.
J Radiol Prot ; 41(3)2021 Aug 19.
Article in English | MEDLINE | ID: mdl-34107455

ABSTRACT

Yttrium-90 (Y-90) radioembolization for the treatment of hepatocellular carcinoma can present safety challenges when transplanting recently treated Y-90 patients. To reduce surgeons' contact with radioactive tissue and remain within occupational dose limits, current guidelines recommend delaying transplants at least 14 days, if possible. We wanted to determine the level of radiation exposure to the transplant surgeon when explanting an irradiated liver before the recommended decay period. Anex-vivoradiation exposure analysis was conducted on the explanted liver of a patient who received Y-90 therapy 46 h prior to orthotopic liver transplant. To estimate exposure to the surgeon's hands, radiation dosimeter rings were placed inside three different surgical glove configurations and exposed to the explanted liver. Estimated radiation doses corrected for Y-90 decay were calculated. Radiation safety gloves performed best, with an average radiation exposure rate of 5.36 mSV h-1in the static hand position, an 83% reduction in exposure over controls with no glove (31.31 mSv h-1). Interestingly, non-radiation safety gloves also demonstrated reduced exposure rates, well below occupational regulation limits. Handling of Y-90 radiated organs within the immediate post-treatment period can be done safely and does not exceed federal occupational dose limits if appropriate gloves and necessary precautions are exercised.


Subject(s)
Occupational Exposure , Radiation Exposure , Hepatectomy , Humans , Occupational Exposure/analysis , Radiation Dosage , Yttrium Radioisotopes/therapeutic use
7.
Am J Physiol Cell Physiol ; 318(6): C1214-C1225, 2020 06 01.
Article in English | MEDLINE | ID: mdl-32348172

ABSTRACT

Reactive oxygen species such as hydrogen peroxide have been implicated in causing metabolic dysfunction such as insulin resistance. Heme groups, either by themselves or when incorporated into proteins, have been shown to scavenge peroxide and demonstrate protective effects in various cell types. Thus, we hypothesized that a metalloporphyrin similar in structure to heme, Fe(III)tetrakis(4-benzoic acid)porphyrin (FeTBAP), would be a peroxidase mimetic that could defend cells against oxidative stress. After demonstrating that FeTBAP has peroxidase activity with reduced nicotinamide adenine dinucleotide phosphate (NADPH) and NADH as reducing substrates, we determined that FeTBAP partially rescued C2C12 myotubes from peroxide-induced insulin resistance as measured by phosphorylation of AKT (S473) and insulin receptor substrate 1 (IRS-1, Y612). Furthermore, we found that FeTBAP stimulates insulin signaling in myotubes and mouse soleus skeletal muscle to about the same level as insulin for phosphorylation of AKT, IRS-1, and glycogen synthase kinase 3ß (S9). We found that FeTBAP lowers intracellular peroxide levels and protects against carbonyl formation in myotubes exposed to peroxide. Additionally, we found that FeTBAP stimulates glucose transport in myotubes and skeletal muscle to about the same level as insulin. We conclude that a peroxidase mimetic can blunt peroxide-induced insulin resistance and also stimulate insulin signaling and glucose transport, suggesting a possible role of peroxidase activity in regulation of insulin signaling.


Subject(s)
Antioxidants/pharmacology , Biological Mimicry , Hydrogen Peroxide/toxicity , Insulin Resistance , Insulin/pharmacology , Metalloporphyrins/pharmacology , Myoblasts, Skeletal/drug effects , Oxidative Stress/drug effects , Peroxidases/pharmacology , Animals , Cell Line , Glycogen Synthase Kinase 3 beta/metabolism , Hydrogen Peroxide/metabolism , Insulin Receptor Substrate Proteins/metabolism , Mice , Myoblasts, Skeletal/metabolism , Myoblasts, Skeletal/pathology , Phosphorylation , Protein Carbonylation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction
8.
Pediatr Dermatol ; 37(3): 527-530, 2020 May.
Article in English | MEDLINE | ID: mdl-32065689

ABSTRACT

Little guidance on management of basal cell nevus syndrome in children exists. We report a case series of four patients diagnosed with BCNS in early childhood, in whom several highly suspicious lesions were biopsied, but several smaller and questionably concerning lesions were treated with therapies that are more tolerable for children, including topical imiquimod, 5-fluorouracil, cryotherapy, or touch electrodessication following topical anesthetic cream. These therapies were well tolerated, and all residual or persistent lesions were subsequently biopsied and found to be benign. This approach is often preferable for pediatric BCNS patients, in whom concerning lesions can be identified clinically and managed compassionately. However, any lesion that exhibits growth, bleeding, or symptoms should be biopsied for definitive diagnosis.


Subject(s)
Basal Cell Nevus Syndrome , Skin Neoplasms , Aminoquinolines , Basal Cell Nevus Syndrome/diagnosis , Basal Cell Nevus Syndrome/therapy , Child , Child, Preschool , Fluorouracil , Humans , Imiquimod , Skin Neoplasms/therapy
9.
Am J Transplant ; 19(4): 1178-1186, 2019 04.
Article in English | MEDLINE | ID: mdl-30230218

ABSTRACT

The OPTN Pancreas Transplantation Committee performed a multicenter retrospective study to determine if undetectable serum C-peptide levels correspond to center-reported pancreas graft failures. C-peptide data from seven participating centers (n = 415 graft failures for transplants performed from 2002 to 2012) were analyzed pretransplant, at graft failure, and at return to insulin. One hundred forty-nine C-peptide values were submitted at pretransplant, 94 at return to insulin, and 233 at graft failure. There were 77 transplants with two available values (at pretransplant and at graft failure). For recipients in the study with pretransplant C-peptide <0.75 ng/mL who had a posttransplant C-peptide value available (n = 61), graft failure was declared at varying levels of C-peptide. High C-peptide values at graft failure were not explained by nonfasting testing or by individual center bias. Transplant centers declare pancreas graft failure at varying levels of C-peptide and do not consistently report C-peptide data. Until February 28, 2018, OPTN did not require reporting of posttransplant C-peptide levels and it appears that C-peptide levels are not consistently used for evaluating graft function. C-peptide levels should not be used as the sole criterion for the definition of pancreas graft failure.


Subject(s)
C-Peptide/metabolism , Graft Rejection , Pancreas Transplantation , Allografts , Humans , Insulin/blood , Retrospective Studies
10.
Mol Ther ; 26(2): 354-365, 2018 02 07.
Article in English | MEDLINE | ID: mdl-29310916

ABSTRACT

Gamma delta T (γδT) lymphocytes are primed for rapid function, including cytotoxicity toward cancer cells, and are a component of the immediate stress response. Following activation, they can function as professional antigen-presenting cells. Chimeric antigen receptors (CARs) work by focusing T cell function on defined cell surface tumor antigens and provide essential costimulation for robust activation. Given the natural tropism of γδT cells for the tumor microenvironment, we hypothesized that their transduction with CARs might enhance cytotoxicity while retaining their ability to migrate to tumor and act as antigen-presenting cells to prolong the intratumoral immune response. Using a GD2-targeting CAR as a model system, we showed that γδT cells of both Vδ1 and Vδ2 subsets could be expanded and transduced to sufficient numbers for clinical studies. The CAR added to the cells' innate cytotoxicity by enhancing GD2-specific killing of GD2-expressing cancer cell lines. Migration toward tumor cells in vitro was not impaired by the presence of the CAR. Expanded CAR-transduced Vδ2 cells retained the ability to take up tumor antigens and cross presented the processed peptide to responder alpha beta T (αßT) lymphocytes. γδ CAR-T cell products show promise for evaluation in clinical studies of solid tumors.


Subject(s)
Receptors, Antigen, T-Cell, gamma-delta/metabolism , Receptors, Chimeric Antigen/metabolism , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Antigen Presentation/immunology , Antigen-Presenting Cells/immunology , Antigen-Presenting Cells/metabolism , Antigens, Neoplasm/immunology , Biomarkers , Cell Line, Tumor , Cross-Priming/immunology , Cytotoxicity, Immunologic/immunology , Humans , Immunotherapy, Adoptive , Lymphocyte Activation/immunology , Phenotype , Receptors, Antigen, T-Cell, gamma-delta/genetics , Receptors, Chimeric Antigen/genetics
11.
J Emerg Med ; 56(2): 233-238, 2019 02.
Article in English | MEDLINE | ID: mdl-30553562

ABSTRACT

BACKGROUND: Cybersecurity risks in health care systems have traditionally been measured in data breaches of protected health information, but compromised medical devices and critical medical infrastructure present risks of disruptions to patient care. The ubiquitous prevalence of connected medical devices and systems may be associated with an increase in these risks. OBJECTIVE: This article details the development and execution of three novel high-fidelity clinical simulations designed to teach clinicians to recognize, treat, and prevent patient harm from vulnerable medical devices. METHODS: Clinical simulations were developed that incorporated patient-care scenarios featuring hacked medical devices based on previously researched security vulnerabilities. RESULTS: Clinicians did not recognize the etiology of simulated patient pathology as being the result of a compromised device. CONCLUSIONS: Simulation can be a useful tool in educating clinicians in this new, critically important patient-safety space.


Subject(s)
Computer Simulation/standards , Health Care Sector/trends , Teaching/standards , Adolescent , Aged , Computer Security , Computer Simulation/trends , Confidentiality/standards , Decision Making , Equipment and Supplies/adverse effects , Humans , Male , Middle Aged , Patient Simulation , Teaching/trends
12.
Mol Ther ; 25(5): 1234-1247, 2017 05 03.
Article in English | MEDLINE | ID: mdl-28341563

ABSTRACT

Chimeric antigen receptors (CARs) combine T cell activation with antibody-mediated tumor antigen specificity, bypassing the need for T cell receptor (TCR) ligation. A limitation of CAR technology is on-target off-tumor toxicity caused by target antigen expression on normal cells. Using GD2 as a model cancer antigen, we hypothesized that this could be minimized by using T cells expressing Vγ9Vδ2 TCR, which recognizes transformed cells in a major histocompatibility complex (MHC)-unrestricted manner, in combination with a co-stimulatory CAR that would function independently of the TCR. An anti-GD2 CAR containing a solitary endodomain derived from the NKG2D adaptor DAP10 was expressed in Vγ9Vδ2+ T cells. Differential ligation of the CAR and/or TCR using antibody-coated beads showed that pro-inflammatory cytokine response depended on activation of both receptors. Moreover, in killing assays, GD2-expressing neuroblastoma cells that engaged the Vγ9Vδ2 TCR were efficiently lysed, whereas cells that expressed GD2 equivalently but did not engage the Vγ9Vδ2 TCR were untouched. Differentiation between X-on tumor and X-off tumor offers potential for safer immunotherapy and broader target selection.


Subject(s)
Antigens, Neoplasm/genetics , Gangliosides/chemistry , Mutant Chimeric Proteins/genetics , Receptors, Antigen, T-Cell/genetics , T-Lymphocytes/immunology , Antigens, Neoplasm/immunology , CD28 Antigens/genetics , CD28 Antigens/immunology , CD3 Complex/genetics , CD3 Complex/immunology , Cell Line, Tumor , Coculture Techniques , Cytotoxicity, Immunologic , Gangliosides/immunology , Gene Expression , Humans , Immunotherapy/methods , Lymphocyte Activation , Mutant Chimeric Proteins/immunology , Neurons/immunology , Neurons/pathology , Protein Engineering/methods , Receptors, Antigen, T-Cell/immunology , T-Lymphocytes/cytology
13.
Cell Mol Life Sci ; 74(12): 2229-2238, 2017 06.
Article in English | MEDLINE | ID: mdl-28168442

ABSTRACT

Inherited monogenic skin disorders include blistering disorders, inflammatory disorders, and disorders of differentiation or development. In most cases, the skin is broadly involved throughout the affected individual's lifetime, but rarely, appearance of normal skin clones has been described. In these cases of revertant mosaicism, cells undergo spontaneous correction to ameliorate the effects of genetic mutation. While targeted reversion of genetic mutation would have tremendous therapeutic value, the mechanisms of reversion in the skin are poorly understood. In this review, we provide an overview of genodermatoses that demonstrate widespread reversion and their corrective mechanisms, as well as the current research aimed to understand this "natural gene therapy".


Subject(s)
Mosaicism , Mutation/genetics , Skin Diseases/genetics , Epidermis/pathology , Humans , Keratins/genetics , Phenotype , Skin Diseases/therapy
14.
Prehosp Emerg Care ; 22(2): 244-251, 2018.
Article in English | MEDLINE | ID: mdl-29023167

ABSTRACT

BACKGROUND: Community Paramedicine (CP) is a rapidly evolving field within prehospital care where paramedics step outside of their traditional roles of treating acute conditions to provide elements of primary and preventive care. It is unclear if current state oversight regarding the scope of practice (SOP) for paramedics provides clear guidance on the novel functions provided and skills performed by CP programs. OBJECTIVE: To determine the process and authority, as currently defined by state laws and regulations in the United States, to expand paramedic SOP in order to perform CP roles and to assess state EMS agencies' interpretation of paramedic SOP as it applies to CP. METHODS: We conducted a systematic review of laws, regulations, and policies from the 50 U.S. states in effect between February and June 2016 that define or apply to paramedic SOP. We determined whether each state's SOP included 21 potential skills applicable to CP within the following categories: assessment, treatment & intervention, referrals, and prevention & public health. Laws were also queried for mechanisms for expanding SOP, alternate destinations, and community paramedicine for each state. Additionally, we surveyed representatives from U.S. State Emergency Medical Services (EMS) agencies and asked which of these skills were a part of their current SOP. All data was coded into Excel™ and analyzed using descriptive statistics. RESULTS: All 50 U.S. states have laws relating to EMS. Forty-one states have a statewide SOP (82%), and 3 states have statewide protocols from which the SOP has been inferred for purposed of this study, but may not legally constitute SOP in this jurisdiction (6%). 20 states (40%) had a clearly defined mechanism for expanding SOP. Sixteen states (32%) had laws specific to CP. Seven states (14%) allowed for patients to be transported to alternate destinations. Of the 21 skills surveyed, on average there were 8.63 (6.41-10.85) fewer skills for paramedics found in state SOP laws and regulations than were reported as being a part of a state's paramedic SOP. All skills demonstrated variability between the legal review and survey results with 13.04-96.15% concordance. CONCLUSION: There is a lack of guidance and consistency regarding CP programs and scope of practice. Further studies are needed to understand best practices around regulation and oversight of CP.


Subject(s)
Community Health Services , Emergency Medical Services/legislation & jurisprudence , Emergency Medical Technicians/education , Professional Role , Health Policy , Humans , Preventive Medicine , Public Health , Surveys and Questionnaires , United States
15.
J Emerg Med ; 55(2): 244-251, 2018 08.
Article in English | MEDLINE | ID: mdl-29954634

ABSTRACT

BACKGROUND: Transitions of care and patient hand-offs between physicians have important implications for patient care. However, what effect caring for signed-out patients has on providing care to new patients and education is unclear. OBJECTIVE: We sought to determine whether the number of patients a physician receives in sign-out affects productivity. METHODS: This was a retrospective cohort study, conducted at an emergency medicine residency program. A general estimation equation was constructed to model productivity, defined as new patients evaluated and relative value units (RVUs) generated per shift, relative to the number of sign-outs received, and training year. A secondary analysis evaluated the effect of signed-out patients in observation. RESULTS: We evaluated 19,389 shifts from July 1, 2010 to July 1, 2017. Postgraduate year (PGY)-1 residents without sign-out evaluated 10.3 patients (95% confidence interval [CI] 9.83 to 10.7), generating 31.6 RVUs (95% CI 30.5 to 32.7). Each signed-out patient was associated with -0.07 new patients (95% CI -0.12 to -0.01), but no statistically significant decrease in RVUs (95% CI -0.07 to 0.28). PGY-2 residents without sign-out evaluated 13.6 patients (95% CI 12.6 to 14.6), generating 47.7 RVUs (95% CI 45.1 to 50.3). Each signed-out patient was associated with -0.25 (95% CI -0.40 to -0.10) new patients, and -0.89 (95% CI -1.22 to -0.55) RVUs. For all residents, observation patients were associated with more substantial decreases in new patients (-0.40; 95% CI -0.47 to -0.33) and RVUs (-1.11; 95% CI -1.40 to -0.82). CONCLUSIONS: Overall, sign-out burden is associated with a small decrease in resident productivity, except for observation patients. Program faculty should critically examine how signed-out patients are distributed to address residents' educational needs, throughput, and patient safety.


Subject(s)
Efficiency , Internship and Residency , Patient Handoff/standards , Patient Transfer/standards , Emergency Medicine/education , Emergency Service, Hospital/organization & administration , Emergency Service, Hospital/statistics & numerical data , Humans , Internship and Residency/methods , Internship and Residency/statistics & numerical data , Patient Transfer/methods , Retrospective Studies , Workload/standards , Workload/statistics & numerical data
16.
Nature ; 477(7362): 86-9, 2011 Jul 27.
Article in English | MEDLINE | ID: mdl-21796120

ABSTRACT

Overfishing of large-bodied benthic fishes and their subsequent population collapses on the Scotian Shelf of Canada's east coast and elsewhere resulted in restructuring of entire food webs now dominated by planktivorous, forage fish species and macroinvertebrates. Despite the imposition of strict management measures in force since the early 1990s, the Scotian Shelf ecosystem has not reverted back to its former structure. Here we provide evidence of the transient nature of this ecosystem and its current return path towards benthic fish species domination. The prolonged duration of the altered food web, and its current recovery, was and is being governed by the oscillatory, runaway consumption dynamics of the forage fish complex. These erupting forage species, which reached biomass levels 900% greater than those prevalent during the pre-collapse years of large benthic predators, are now in decline, having outstripped their zooplankton food supply. This dampening, and the associated reduction in the intensity of predation, was accompanied by lagged increases in species abundances at both lower and higher trophic levels, first witnessed in zooplankton and then in large-bodied predators, all consistent with a return towards the earlier ecosystem structure. We conclude that the reversibility of perturbed ecosystems can occur and that this bodes well for other collapsed fisheries.


Subject(s)
Aquatic Organisms/physiology , Ecosystem , Fishes/physiology , Animals , Atlantic Ocean , Biomass , Fisheries , Population Density , Time Factors , Zooplankton/physiology
17.
Proc Natl Acad Sci U S A ; 111(40): E4204-13, 2014 Oct 07.
Article in English | MEDLINE | ID: mdl-25201970

ABSTRACT

High ambient ozone (O3) concentrations are a widespread and persistent problem globally. Although studies have documented the role of forests in removing O3 and one of its precursors, nitrogen dioxide (NO2), the cost effectiveness of using peri-urban reforestation for O3 abatement purposes has not been examined. We develop a methodology that uses available air quality and meteorological data and simplified forest structure growth-mortality and dry deposition models to assess the performance of reforestation for O3 precursor abatement. We apply this methodology to identify the cost-effective design for a hypothetical 405-ha, peri-urban reforestation project in the Houston-Galveston-Brazoria O3 nonattainment area in Texas. The project would remove an estimated 310 tons of (t) O3 and 58 t NO2 total over 30 y. Given its location in a nitrogen oxide (NOx)-limited area, and using the range of Houston area O3 production efficiencies to convert forest O3 removal to its NOx equivalent, this is equivalent to 127-209 t of the regulated NOx. The cost of reforestation per ton of NOx abated compares favorably to that of additional conventional controls if no land costs are incurred, especially if carbon offsets are generated. Purchasing agricultural lands for reforestation removes this cost advantage, but this problem could be overcome through cost-share opportunities that exist due to the public and conservation benefits of reforestation. Our findings suggest that peri-urban reforestation should be considered in O3 control efforts in Houston, other US nonattainment areas, and areas with O3 pollution problems in other countries, wherever O3 formation is predominantly NOx limited.


Subject(s)
Environmental Restoration and Remediation/methods , Forestry/methods , Ozone/metabolism , Trees/metabolism , Algorithms , Cities , Cost-Benefit Analysis , Environmental Monitoring/economics , Environmental Monitoring/methods , Environmental Restoration and Remediation/economics , Geography , Models, Theoretical , Nitrogen Dioxide/metabolism , Reproducibility of Results , Texas , Trees/classification , Trees/growth & development
18.
J Emerg Med ; 52(6): 850-855, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28341085

ABSTRACT

BACKGROUND: Clerkship directors routinely evaluate medical students using multiple modalities, including faculty assessment of clinical performance and written examinations. Both forms of evaluation often play a prominent role in final clerkship grade. The degree to which these modalities correlate in an emergency medicine (EM) clerkship is unclear. OBJECTIVE: We sought to correlate faculty clinical evaluations with medical student performance on a written, standardized EM examination of medical knowledge. METHODS: This is a retrospective study of fourth-year medical students in a 4-week EM elective at one academic medical center. EM faculty performed end of shift evaluations of students via a blinded online system using a 5-point Likert scale for 8 domains: data acquisition, data interpretation, medical knowledge base, professionalism, patient care and communication, initiative/reliability/dependability, procedural skills, and overall evaluation. All students completed the National EM M4 Examination in EM. Means, medians, and standard deviations for end of shift evaluation scores were calculated, and correlations with examination scores were assessed using a Spearman's rank correlation coefficient. RESULTS: Thirty-nine medical students with 224 discrete faculty evaluations were included. The median number of evaluations completed per student was 6. The mean score (±SD) on the examination was 78.6% ± 6.1%. The examination score correlated poorly with faculty evaluations across all 8 domains (ρ 0.074-0.316). CONCLUSION: Faculty evaluations of medical students across multiple domains of competency correlate poorly with written examination performance during an EM clerkship. Educators need to consider the limitations of examination score in assessing students' ability to provide quality patient clinical care.


Subject(s)
Academic Performance/standards , Educational Measurement/standards , Emergency Medicine/education , Students, Medical/statistics & numerical data , Test Taking Skills/standards , Clinical Clerkship , Clinical Competence/standards , Education, Medical, Undergraduate/methods , Education, Medical, Undergraduate/standards , Educational Measurement/methods , Faculty, Medical/standards , Faculty, Medical/statistics & numerical data , Humans , Quality of Health Care , Reproducibility of Results , Retrospective Studies , Students, Medical/psychology , Test Taking Skills/psychology , Workforce
19.
J Emerg Med ; 51(4): 432-439, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27372377

ABSTRACT

BACKGROUND: Medical student evaluations are essential for determining clerkship grades. Electronic evaluations have various advantages compared to paper evaluations, such as increased ease of collection, asynchronous reporting, and decreased likelihood of becoming lost. OBJECTIVES: To determine whether electronic medical student evaluations (EMSEs) provide more evaluations and content when compared to paper shift card evaluations. METHODS: This before and after cohort study was conducted over a 2.5-year period at an academic hospital affiliated with a medical school and emergency medicine residency program. EMSEs replaced the paper shift evaluations that had previously been used halfway through the study period. A random sample of the free text comments on both paper and EMSEs were blindly judged by medical student clerkship directors for their helpfulness and usefulness. Logistic regression was used to test for any relationship between quality and quantity of words. RESULTS: A total of 135 paper evaluations for 30 students and then 570 EMSEs for 62 students were collected. An average of 4.8 (standard deviation [SD] 3.2) evaluations were completed per student using the paper version compared to 9.0 (SD 3.8) evaluations completed per student electronically (p < 0.001). There was an average of 8.8 (SD 8.5) words of free text evaluation on paper evaluations when compared to 22.5 (SD 28.4) words for EMSEs (p < 0.001). A statistically significant (p < 0.02) association between quality of an evaluation and the word count existed. CONCLUSIONS: EMSEs that were integrated into the emergency department tracking system significantly increased the number of evaluations completed compared to paper evaluations. In addition, the EMSEs captured more "helpful/useful" information about the individual students as evidenced by the longer free text entries per evaluation.


Subject(s)
Clinical Clerkship , Educational Measurement/methods , Educational Measurement/standards , Emergency Medicine/education , Emergency Service, Hospital , Clinical Competence , Cohort Studies , Educational Measurement/statistics & numerical data , Humans , Information Systems , Interrupted Time Series Analysis , Records
20.
J Physiol ; 598(19): 4145-4146, 2020 10.
Article in English | MEDLINE | ID: mdl-32770546
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