Publications by authors named "Christopher Smith"

904 Publications

Genome-scale data resolves the timing of divergence in Joshua trees.

Am J Bot 2021 Apr 13. Epub 2021 Apr 13.

Department of Biology, Willamette University, 900 State Street, Salem, OR.

Premise: Joshua trees (Yucca brevifolia and Y. jaegeriana) and their yucca moth pollinators (Tegeticula synthetica and T. antithetica) are a model system for studies of plant-pollinator coevolution and, they are thought to be one of the only cases in which there is compelling evidence for cospeciation driven by coevolution. Previous work attempted to evaluate whether divergence between the plant and their pollinators was contemporaneous. That work concluded that the trees diverged more than 5 million years ago-well before the pollinators. However, clear inferences were hampered by a lack of data from the nuclear genome and low genetic variation in chloroplast genes. As a result, divergence times in the trees could not be confidently estimated.

Methods: We present an analysis of whole chloroplast genome sequence data and RADseq data from >5000 loci in the nuclear genome. We developed a molecular clock for the Asparagales and the Agavoideae using multiple fossil calibration points. Using Bayesian inference, we produced new estimates for the age of the genus Yucca and for Joshua trees. We used calculated summary statistics describing genetic variation and used coalescent-based methods to estimate population genetic parameters.

Results: We find that the Joshua trees are moderately genetically differentiated, but that they diverged quite recently (~100-200 kya), and much more recently than their pollinators.

Conclusions: The results argue against the notion that coevolution directly contributed to speciation in this system, suggesting instead that coevolution with pollinators may have reinforced reproductive isolation following initial divergence in allopatry.
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http://dx.doi.org/10.1002/ajb2.1633DOI Listing
April 2021

Dynamic contrast-enhanced magnetic resonance lymphangiography.

Pediatr Radiol 2021 Apr 8. Epub 2021 Apr 8.

Department of Radiology, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, 3401 Civic Center Blvd., Philadelphia, PA, USA.

Lymphatic flow disorders include a broad spectrum of abnormalities that can originate in the lymphatic or the venous system. The development of these disorders is multifactorial and is most commonly associated with congenital heart diseases and palliative surgeries that these patients undergo. Central lymphatic disorders might be secondary to traumatic leaks, lymphatic overproduction, conduction abnormalities or lymphedema, and they can progress to perfusion anomalies. Several imaging modalities have been used to visualize the lymphatic system. However, the imaging of central lymphatic flow has always been challenging. Dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) allows for visualization of central lymphatic flow disorders and has been recently applied for the assessment of plastic bronchitis, protein-losing enteropathy, chylothorax and chylopericardium, among other lymphatic disorders. The hepatic and mesenteric accesses are innovative and promising techniques for better identification and understanding of these abnormalities. The main objectives of this review are to discuss the physiology and anatomy of the lymphatic system and review the current uses of DCMRL in the diagnosis and management of lymphatic flow disorders.
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http://dx.doi.org/10.1007/s00247-021-05051-6DOI Listing
April 2021

Epidemiology of Tumor-Induced Osteomalacia in Denmark.

Calcif Tissue Int 2021 Apr 5. Epub 2021 Apr 5.

Department of Internal Medicine and Medical Disciplines, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.

Tumor-induced osteomalacia (TIO) is a rare, acquired condition of phosphate wasting due to phosphaturic mesenchymal tumors. Because the incidence and prevalence of TIO is unknown, we conducted an observational cohort study using national Danish health registers for the period 2008 to 2018 to obtain such information. The study also aimed to describe the demographics of the TIO population and the prognosis. The operational definition was based on hypophosphatemia or adult osteomalacia diagnoses, combined with prescriptions used in the initial management and procedures consistent with advanced imaging used for locating tumors. The incidence of TIO in Denmark was found to be below 0.13 per 100,000 person years for the total population of the country and 0.10 per 100,000 in adult-onset disease. The prevalence of TIO was estimated to be no more than 0.70 per 100,000 persons for the total population and 0.43 per 100,000 in adults. In 2018, there were a maximum of nine new cases of TIO in Danish adults. Mortality was low but few patients fulfilled the protocol cure criterion during the observation period. TIO has no ICD-10 code and limitations to the study include lack of information on serum biochemistry and on the use of phosphate supplements. Strengths include the use of long-term longitudinal, national hospital and prescription data from a country with universal healthcare. Given the very small patient population with TIO and the known delay to diagnosis and cure, management of patients with suspected TIO should be centralized.
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http://dx.doi.org/10.1007/s00223-021-00843-2DOI Listing
April 2021

Geographic Variation in the Prevalence of Rheumatoid Arthritis in Alberta, Canada.

ACR Open Rheumatol 2021 Apr 1. Epub 2021 Apr 1.

University of Calgary, Calgary, Alberta, Canada, and Arthritis Research Canada, Richmond, British Columbia, Canada.

Objectives: Timely access to rheumatologists remains a challenge in Alberta, a Canadian province with vast rural areas, whereas rheumatologists are primarily clustered in metro areas. To address the goal of timely and equitable access to rheumatoid arthritis (RA) care, health planners require information at the regional and local level to determine the RA prevalence and the associated health care needs.

Methods: Using Alberta Health administrative databases, we identified RA-prevalent cases (April 1, 2015-March 31, 2016) on the basis of a validated case definition. Age- and sex-standardized prevalence rates per 1000 population members and the standardized rates ratio (SRR) were calculated. We applied Global Moran's I and Gi* hotspot analysis using three different weight matrices to explore the geospatial pattern of RA prevalence in Alberta.

Results: Among 38 350 RA cases (68% female; n = 26 236), the prevalence rate was 11.81 cases per 1000 population members (95% confidence interval [CI] 11.80-11.81) after age and sex standardization. Approximately 60% of RA cases resided in metro (Calgary and Edmonton) and moderate metro areas. The highest rate was observed in rural areas (14.46; 95% CI 14.45-14.47; SRR 1.28), compared with the lowest in metro areas (10.69; 95% CI 10.68-10.69; SRR 0.82). The RA prevalence across local geographic areas ranged from 4.7 to 30.6 cases. The Global Moran's I index was 0.15 using three different matrices (z-score 3.96-4.24). We identified 10 hotspots in the south and north rural areas and 18 cold spots in metro and moderate metro Calgary.

Conclusion: The findings highlight notable rural-urban variation in RA prevalence in Alberta. Our findings can inform strategies aimed at reducing geographic disparities by targeting areas with high health care needs.
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http://dx.doi.org/10.1002/acr2.11251DOI Listing
April 2021

Effect of Intrawound Vancomycin Powder in Operatively Treated High-risk Tibia Fractures: A Randomized Clinical Trial.

Authors:
Robert V O'Toole Manjari Joshi Anthony R Carlini Clinton K Murray Lauren E Allen Yanjie Huang Daniel O Scharfstein Nathan N O'Hara Joshua L Gary Michael J Bosse Renan C Castillo Julius A Bishop Michael J Weaver Reza Firoozabadi Joseph R Hsu Madhav A Karunakar Rachel B Seymour Stephen H Sims Christine Churchill Michael L Brennan Gabriela Gonzales Rachel M Reilly Robert D Zura Cameron R Howes Hassan R Mir Emily A Wagstrom Jerald Westberg Greg E Gaski Laurence B Kempton Roman M Natoli Anthony T Sorkin Walter W Virkus Lauren C Hill Robert A Hymes Michael Holzman A Stephen Malekzadeh Jeff E Schulman Lolita Ramsey Jaslynn A N Cuff Sharon Haaser Greg M Osgood Babar Shafiq Vaishali Laljani Olivia C Lee Peter C Krause Cara J Rowe Colette L Hilliard Massimo Max Morandi Angela Mullins Timothy S Achor Andrew M Choo John W Munz Sterling J Boutte Heather A Vallier Mary A Breslin H Michael Frisch Adam M Kaufman Thomas M Large C Michael LeCroy Christina Riggsbee Christopher S Smith Colin V Crickard Laura S Phieffer Elizabeth Sheridan Clifford B Jones Debra L Sietsema J Spence Reid Kathy Ringenbach Roman Hayda Andrew R Evans M J Crisco Jessica C Rivera Patrick M Osborn Joseph Kimmel Stanislaw P Stawicki Chinenye O Nwachuku Thomas R Wojda Saqib Rehman Joanne M Donnelly Cyrus Caroom Mark D Jenkins Christina L Boulton Timothy G Costales Christopher T LeBrun Theodore T Manson Daniel C Mascarenhas Jason W Nascone Andrew N Pollak Marcus F Sciadini Gerard P Slobogean Peter Z Berger Daniel W Connelly Yasmin Degani Andrea L Howe Dimitrius P Marinos Ryan N Montalvo G Bradley Reahl Carrie D Schoonover Lisa K Schroder Sandy Vang Patrick F Bergin Matt L Graves George V Russell Clay A Spitler Josie M Hydrick David Teague William Ertl Lindsay E Hickerson Gele B Moloney John C Weinlein Boris A Zelle Animesh Agarwal Ravi A Karia Ashoke K Sathy Brigham Au Medardo Maroto Drew Sanders Thomas F Higgins Justin M Haller David L Rothberg David B Weiss Seth R Yarboro Eric D McVey Veronica Lester-Ballard David Goodspeed Gerald J Lang Paul S Whiting Alexander B Siy William T Obremskey A Alex Jahangir Basem Attum Eduardo J Burgos Cesar S Molina Andres Rodriguez-Buitrago Vamshi Gajari Karen M Trochez Jason J Halvorson Anna N Miller James Brett Goodman Martha B Holden Christopher M McAndrew Michael J Gardner William M Ricci Amanda Spraggs-Hughes Susan C Collins Tara J Taylor Mary Zadnik

JAMA Surg 2021 Mar 24:e207259. Epub 2021 Mar 24.

Major Extremity Trauma Research Consortium Coordinating Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Importance: Despite the widespread use of systemic antibiotics to prevent infections in surgically treated patients with fracture, high rates of surgical site infection persist.

Objective: To examine the effect of intrawound vancomycin powder in reducing deep surgical site infections.

Design, Setting, And Participants: This open-label randomized clinical trial enrolled adult patients with an operatively treated tibial plateau or pilon fracture who met the criteria for a high risk of infection from January 1, 2015, through June 30, 2017, with 12 months of follow-up (final follow-up assessments completed in April 2018) at 36 US trauma centers.

Interventions: A standard infection prevention protocol with (n = 481) or without (n = 499) 1000 mg of intrawound vancomycin powder.

Main Outcomes And Measures: The primary outcome was a deep surgical site infection within 182 days of definitive fracture fixation. A post hoc comparison assessed the treatment effect on gram-positive and gram-negative-only infections. Other secondary outcomes included superficial surgical site infection, nonunion, and wound dehiscence.

Results: The analysis included 980 patients (mean [SD] age, 45.7 [13.7] years; 617 [63.0%] male) with 91% of the expected person-time of follow-up for the primary outcome. Within 182 days, deep surgical site infection was observed in 29 of 481 patients in the treatment group and 46 of 499 patients in the control group. The time-to-event estimated probability of deep infection by 182 days was 6.4% in the treatment group and 9.8% in the control group (risk difference, -3.4%; 95% CI, -6.9% to 0.1%; P = .06). A post hoc analysis of the effect of treatment on gram-positive (risk difference, -3.7%; 95% CI, -6.7% to -0.8%; P = .02) and gram-negative-only (risk difference, 0.3%; 95% CI, -1.6% to 2.1%; P = .78) infections found that the effect of vancomycin powder was a result of its reduction in gram-positive infections.

Conclusions And Relevance: Among patients with operatively treated tibial articular fractures at a high risk of infection, intrawound vancomycin powder at the time of definitive fracture fixation reduced the risk of a gram-positive deep surgical site infection, consistent with the activity of vancomycin.

Trial Registration: ClinicalTrials.gov Identifier: NCT02227446.
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http://dx.doi.org/10.1001/jamasurg.2020.7259DOI Listing
March 2021

Mistaken Identity: Frequency and Effects of Gender-Based Professional Misidentification of Resident Physicians.

Acad Med 2021 Mar 16. Epub 2021 Mar 16.

S. Berwick is a hematology/oncology fellow, Mount Sinai Hospital, New York, New York. H. Calev is a hospitalist, Emory University Hospital, Atlanta Georgia. A. Matthews is a hematology/oncology fellow, University of Pennsylvania, Philadelphia, Pennsylvania; ORCID: http://orcid.org/0000-0002-4904-3998. A. Mukhopadhyay is a cardiology fellow, New York University, New York, New York. B. Poole is a pulmonary and critical care fellow, University of Utah, Salt Lake City, Utah. J. Talan is a pulmonary and critical care fellow, New York University, New York, New York. M.M. Hayes is a pulmonary and critical care attending physician and associate director, Residency Program, Beth Israel Deaconess Medical Center, Boston Massachusetts. C.C. Smith is a primary care physician and director, Residency Program, Beth Israel Deaconess Medical Center, Boston Massachusetts.

Purpose: Evaluation of the medical profession at all levels has exposed episodes of gender-based role misidentification whereby women physicians are disproportionately misidentified as non-physicians. The authors of this study investigate this phenomenon and its repercussions, quantifying the frequency with which resident physicians experience role misidentification and the effect this has on their experience and behavior.

Method: In 2018 the authors conducted a cross-sectional survey study of internal medicine, surgical, and emergency medicine residents at a single, large, urban, tertiary academic medical center. The survey tool captured both the self-reported frequency and effect of professional misidentification. The authors used a t-test and linear multivariate regression to analyze the results.

Results: Of the 260 residents who received the survey, 186 (72%) responded, and the authors analyzed the responses of 182. All 85 of the women respondents (100%) reported being misidentified as non-physicians at least once in their professional experience by patients or staff members, compared to 49% of the 97 men respondents. Of those 182 residents, 35% of women were misidentified more than 8 times per month by patients compared to 1% of men. Of the 85 women physicians responding to the survey, 38% felt angry and 36% felt less satisfied with their jobs as a result of misidentification compared to, respectively, 7% and 9% of men. In response to role misidentification, 51% of women changed their manner of attire and 81% changed their manner of introduction, compared to 7% and 37% of men.

Conclusions: These survey results demonstrate that women physicians are more likely than men physicians to be misidentified as non-physicians and that role misidentification provokes gender-polarized psychological and behavioral responses that have potentially important professional ramifications.
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http://dx.doi.org/10.1097/ACM.0000000000004060DOI Listing
March 2021

Oligomeric complexes formed by Redβ single strand annealing protein in its different DNA bound states.

Nucleic Acids Res 2021 04;49(6):3441-3460

Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA.

Redβ is a single strand annealing protein from bacteriophage λ that binds loosely to ssDNA, not at all to pre-formed dsDNA, but tightly to a duplex intermediate of annealing. As viewed by electron microscopy, Redβ forms oligomeric rings on ssDNA substrate, and helical filaments on the annealed duplex intermediate. However, it is not clear if these are the functional forms of the protein in vivo. We have used size-exclusion chromatography coupled with multi-angle light scattering, analytical ultracentrifugation and native mass spectrometry (nMS) to characterize the size of the oligomers formed by Redβ in its different DNA-bound states. The nMS data, which resolve species with the highest resolution, reveal that Redβ forms an oligomer of 12 subunits in the absence of DNA, complexes ranging from 4 to 14 subunits on 38-mer ssDNA, and a much more distinct and stable complex of 11 subunits on 38-mer annealed duplex. We also measure the concentration of Redβ in cells active for recombination and find it to range from 7 to 27 μM. Collectively, these data provide new insights into the dynamic nature of the complex on ssDNA, and the more stable and defined complex on annealed duplex.
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http://dx.doi.org/10.1093/nar/gkab125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034648PMC
April 2021

Survival of the Aequalis Total Shoulder Replacement at a Minimum 20-year Follow: a clinical and radiographic study.

J Shoulder Elbow Surg 2021 Mar 3. Epub 2021 Mar 3.

Shoulder and Elbow Unit, Royal Devon and Exeter Hospital, Exeter, UK.

Aims: Shoulder replacement is increasingly performed for end stage arthritis. Information on the long-term survival and patient outcomes is very limited. This study aimed to quantify the survival and clinical outcome at a minimum of 20 years follow-up.

Methods: A single center, single surgeon, consecutive cohort study was performed. 44 shoulder replacements in 40 patients (age at surgery 68.5yrs, 82.5% female, preoperative Pain Visual Analogue Scale (VAS) 5.1/10 (SD ±2.7)) implanted between 1996 and 2000 were assessed. All-cause construct survival, radiographic glenoid and humeral stem loosening, radiographic humeral head migration and Patient-Reported Outcome Measures (PROMs) were assessed.

Results: Survival with all-cause revision as an end point was 84.1% (95%CI 60.7, 94.1) at 20 years, glenoid loosening was seen in all patients who survived to 20 years follow-up. Survival of rotator cuff integrity was 16.8% (95%CI 3.5, 38.5) at 20 years. Pain VAS demonstrated improvement at 10 years (mean change -4/10) but not at 20 years (effect size -0.15, mean change 0.4/10 (SD ±2.7)). At 20 years, 72% of patients had died with the prosthesis in situ.

Conclusion: Older patients undergoing total shoulder arthroplasty are unlikely to require revision in their lifetime. However, beyond 10 years, a large proportion of implants demonstrate glenoid loosening, humeral head migration and declining patient outcomes. This information will be of use to patients and clinicians when discussing the potential outcomes of surgery.
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http://dx.doi.org/10.1016/j.jse.2021.01.038DOI Listing
March 2021

A multiobserver study investigating the effectiveness of prostatic multiparametric magnetic resonance imaging to dose escalate corresponding histologic lesions using high-dose-rate brachytherapy.

Brachytherapy 2021 Feb 26. Epub 2021 Feb 26.

Baines Imaging Research Laboratory, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada; Department of Medical Biophysics, Western University, London, Ontario, Canada; Department of Oncology, Western University, London, Ontario, Canada; London Regional Cancer Program, London, Ontario, Canada. Electronic address:

Purpose: Using multiparametric MRI data and the pathologic data from radical prostatectomy specimens, we simulated the treatment planning of dose-escalated high-dose-rate brachytherapy (HDR-BT) to the Multiparametric MRI dominant intraprostatic lesion (mpMRI-DIL) to compare the dose potentially delivered to the pathologically confirmed locations of the high-grade component of the cancer.

Methods And Materials: Pathologist-annotated prostatectomy midgland histology sections from 12 patients were registered to preprostatectomy mpMRI scans that were interpreted by four radiologists. To simulate realistic HDR-BT, we registered each observer's mpMRI-DILs and corresponding histology to two transrectal ultrasound images of other HDR-BT patients with a 15-Gy whole-gland prescription. We used clinical inverse planning to escalate the mpMRI-DILs to 20.25 Gy. We compared the dose that the histopathology would have received if treated with standard treatment plans to the dose mpMRI-targeting would have achieved. The histopathology was grouped as high-grade cancer (any Gleason Grade 4 or 5) and low-grade cancer (only Gleason Grade 3).

Results: 212 mpMRI-targeted HDR-BT plans were analyzed. For high-grade histology, the mpMRI-targeted plans achieved significantly higher median [IQR] D98 and D90 values of 18.2 [16.7-19.5] Gy and 19.4 [17.8-20.9] Gy, respectively, in comparison with the standard plans (p = 0.01 and p = 0.003). For low-grade histology, the targeted treatment plans would have resulted in a significantly higher median D90 of 17.0 [16.1-18.4] Gy in comparison with standard plans (p = 0.015); the median D98 was not significantly higher (p = 0.2).

Conclusions: In this retrospective pilot study of 12 patients, mpMRI-based dose escalation led to increased dose to high-grade, but not low-grade, cancer. In our data set, different observers and mpMRI sequences had no substantial effect on dose to histologic cancer.
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http://dx.doi.org/10.1016/j.brachy.2021.01.005DOI Listing
February 2021

Reverse total shoulder arthroplasty.

Bone Joint J 2021 Feb 22:1-9. Epub 2021 Feb 22.

Royal Devon and Exeter Foundation Trust, Exeter, UK.

Aims: This systematic review asked which patterns of complications are associated with the three reverse total shoulder arthroplasty (RTSA) prosthetic designs, as classified by Routman et al, in patients undergoing RTSA for the management of cuff tear arthropathy, massive cuff tear, osteoarthritis, and rheumatoid arthritis. The three implant design philosophies investigated were medial glenoid/medial humerus (MGMH), medial glenoid/lateral humerus (MGLH), and lateral glenoid/medial humerus (LGMH).

Methods: A systematic review of the literature was performed via a search of MEDLINE and Embase. Two reviewers extracted data on complication occurrence and patient-reported outcome measures (PROMs). Meta-analysis was conducted on the reported proportion of complications, weighted by sample size, and PROMs were pooled using the reported standardized mean difference (SMD). Quality of methodology was assessed using Wylde's non-summative four-point system. The study was registered with PROSPERO (CRD42020193041).

Results: A total of 42 studies met the inclusion and exclusion criteria. Rates of scapular notching were found to be significantly higher in MGMH implants (52% (95% confidence interval (CI) 40 to 63)) compared with MGLH ((18% (95% CI 6 to 34)) and LGMH (12% (95% CI 3 to 26)). Higher rates of glenoid loosening were seen in MGMH implants (6% (95% CI 3 to 10)) than in MGLH implants (0% (95% CI 0 to 2)). However, strength of evidence for this finding was low. No significant differences were identified in any other complication, and there were no significant differences observed in PROMs between implant philosophies.

Conclusion: This systematic review has found significant improvement in PROMS and low complication rates across the implant philosophies studied. Scapular notching was the only complication found definitely to have significantly higher prevalence with the MGMH implant design.
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http://dx.doi.org/10.1302/0301-620X.103B.BJJ-2020-2101DOI Listing
February 2021

Streamlining SARS-CoV-2 confirmatory testing to reduce false positive results.

J Clin Virol 2021 03 11;136:104762. Epub 2021 Feb 11.

Clinical Microbiology & Public Health Laboratory, Public Health England, Cambridge, UK. Electronic address:

Background: Confirmatory testing of SARS-CoV-2 results is essential to reduce false positives, but comes at a cost of significant extra workload for laboratories and increased turnaround time. A balance must be sought. We analysed our confirmatory testing pathway to produce a more refined approach in preparation for rising case numbers.

Methods: Over a 10-week low prevalence period we performed confirmatory testing on all newly positive results. Turnaround time was measured and results were analysed to identify a threshold that could be applied as a cut-off for future confirmatory testing and reduce overall workload for the laboratory.

Results: Between 22/06/20 and 31/08/20 confirmatory testing was performed on 108 newly positive samples, identifying 32 false positive results (30 %). Turnaround time doubled, increasing by an extra 17 h. There was a highly statistically significant difference between initial Relative Light Unit (RLU) of results that confirmed compared to those that did not, 1176 vs 721 (P < 0.00001). RLU = 1000 was identified as a suitable threshold for confirmatory testing in our laboratory: with RLU ≥ 1000, 55/56 (98 %) confirmed as positive, whereas with RLU < 1000 only 12/38 (32 %) confirmed.

Conclusions: False positive SARS-CoV-2 tests can be identified by confirmatory testing, yet this may significantly delay results. Establishing a threshold for confirmatory testing streamlines this process to focus only on samples where it is most required. We advise all laboratories to follow a similar process to identify thresholds that trigger confirmatory testing for their own assays, increasing accuracy while maintaining efficiency for when case numbers are high.
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http://dx.doi.org/10.1016/j.jcv.2021.104762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877812PMC
March 2021

Outcomes of Operator-Directed Sedation and Anesthesiologist Care in the Pediatric/Congenital Catheterization Laboratory: A Study Utilizing Data From the IMPACT Registry.

JACC Cardiovasc Interv 2021 Feb;14(4):401-413

Division of Cardiology, The Children's Hospital of Philadelphia and Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA; Center for Pediatric Clinical Effectiveness, The Children's Hospital of Philadelphia and Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Objectives: The objective of this study was to assess contemporary use of operator directed sedation (ODS) and anesthesiologist care (AC) in the pediatric/congenital cardiac catheterization laboratory (PCCL), specifically evaluating whether the use of operator-directed sedation was associated with increased risk of major adverse events.

Background: The safety of ODS relative to AC during PCCL procedures has been questioned.

Methods: A multicenter, retrospective cohort study was performed studying procedures habitually performed with ODS or AC at IMPACT (Improving Adult and Congenital Treatment) registry hospitals using ODS for ≥5% of cases. The risks for major adverse events (MAE) for ODS and AC cases were compared, adjusted for case mix. Current recommendations were evaluated by comparing the ratio of observed to expected MAE for cases in which ODS was inappropriate (inconsistent with those guidelines) with those for similar risk AC cases, as well as those in which ODS or AC was appropriate.

Results: Of the hospitals submitting data to IMPACT, 28 of 101 met inclusion criteria. Of the 7,042 cases performed using ODS at these centers, 88% would be inappropriate. Use of ODS was associated with lower likelihood of MAE both in observed results (p < 0.0001) and after adjusting for case-mix (odds ratio: 0.81; p = 0.006). Use of AC was also associated with longer adjusted fluoroscopy and procedure times (p < 0.0001 for both). The observed/expected ratio for ODS cases with high pre-procedural risk (inappropriate for ODS) was significantly lower than that for AC cases with comparable pre-procedural risk. Across a range of pre-procedural risks, there was no stratum in which risk for MAE was lower for AC than ODS.

Conclusions: Across a range of hospitals, ODS was used safely and with improved efficiency. Clinical judgment better identified cases in which ODS could be used than pre-procedural risk score. This should inform future guidelines for the use of ODS and AC in the catheterization laboratory.
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http://dx.doi.org/10.1016/j.jcin.2020.10.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932684PMC
February 2021

First-in-human, phase I/IIa study of CRLX301, a nanoparticle drug conjugate containing docetaxel, in patients with advanced or metastatic solid malignancies.

Invest New Drugs 2021 Feb 16. Epub 2021 Feb 16.

Department of Medical Oncology, Monash Health/Monash University, Melbourne, Australia.

Background This was a phase I/IIa study to investigate the tolerability, efficacy and pharmacokinetics (PK)/ pharmacodynamics (PD) of CRLX301, CDP-based nanoparticle formulation of docetaxel. Methods The study was conducted in two parts. In part 1, dose-escalation using a standard 3 + 3 design was performed in two dosing schedules (every week (QW) and every 3 weeks (Q3W)). Part 2 was comprised of a dose expansion at 75 mg/m2 Q3W. PK studies were performed on both dosing schedules. Results Forty-two patients were recruited onto the study with a median age of 64(range 38-76); median number of prior systemic therapies was 5(range 0-10). Grade 3/4 treatment-related toxicities included: neutropenia (21.4 %), infusion related reaction (11.9 %), anemia (7.1 %), fatigue (4.8 %), diarrhea (4.8 %), and peripheral neuropathy (4.8 %). The maximum tolerated dose was 75 mg/m2 given on the Q3W schedule and was not determined on the QW schedule. In this heavily pre-treated population, four patients (12.9 %) achieved stable disease (SD) ≥ 4 months and 2 patients (6.5 %) achieved partial response (PR) for a clinical benefit rate (CBR) of 19.4 % (6/31 patients). The PRs were seen in prostate and breast adenocarcinoma (one each). CRLX301 exhibited some PK advantages over docetaxel including higher retention of drug in plasma, slower clearance and controlled slow release of docetaxel from the carrier. Conclusions In this heavily pretreated patient population, the safety profile was acceptable for CRLX301 therapy. There was some evidence of preliminary tumor efficacy, but further work is necessary to find the optimal dose and schedule of this formulation.Clinicaltrials.gov trial registration number: NCT02380677 (Date of registration: March 2, 2015).
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http://dx.doi.org/10.1007/s10637-021-01081-xDOI Listing
February 2021

Identification of critical windows in early development of human upper respiratory tract and middle ear disease.

Anat Rec (Hoboken) 2021 Feb 15. Epub 2021 Feb 15.

Department of Anthropology, CUNY Graduate Center, New York, New York, USA.

Otitis media (OM) or middle ear disease is a prevalent pediatric condition generally related to early growth of the cartilaginous Eustachian tube (CET). This study used a developmental series of dry crania to reconstruct CET and dilator tubae (DT, the muscle opening the CET) morphology. Timing and directionality of CET and upper respiratory tract (URT) growth were investigated. Traditional and 3D geometric morphometrics (GM) were used to assess bony landmarks on the crania. The series was divided using dental eruption into seven growth stages ranging from before eruption of deciduous dentition (approximately the first 6 postnatal months) to eruption of the first permanent maxillary molar (after approximately 6 years). Bony endpoints of the CET and DT were used to calculate their morphology. GM analysis showed substantial shape differences between newborns, early infants, and all later developmental stages. Univariate measures showed the largest growth change between birth and 6 months. Subsequently, CET morphology changed little in the latter half of year 1, instead maturing gradually until approximately 3 years whereas DT relative length and orientation finish growth by the end of year 1. Incongruence in slower CET growth and faster DT growth could impact CET function between 6 and 12 months and be a contributing factor of OM. Tubal aeration may improve after this time when both CET and DT morphology mature, coinciding with clinically reported drop-off in ear infections.
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http://dx.doi.org/10.1002/ar.24600DOI Listing
February 2021

The effect of alternative methods of cardiopulmonary resuscitation - Cough CPR, percussion pacing or precordial thump - on outcomes following cardiac arrest. A systematic review.

Resuscitation 2021 Feb 11;162:73-81. Epub 2021 Feb 11.

Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.

Background: Cardiopulmonary resuscitation (CPR) improves cardiac arrest survival. Cough CPR, percussion pacing and precordial thump have been reported as alternative CPR techniques. We aimed to summarise in a systematic review the effectiveness of these alternative CPR techniques.

Methods: We searched Ovid MEDLINE, EMBASE and the Cochrane Library on 24/08/2020. We included randomised controlled trials, observational studies and case series with five or more patients. Two reviewers independently reviewed title and abstracts to identify studies for full-text review, and reviewed bibliographies and 'related articles' (using PubMed) of full-texts for further eligible studies. We extracted data and performed risk-of-bias assessments on studies included in the systematic review. We summarised data in a narrative synthesis, and used GRADE to assess evidence certainty.

Results: We included 23 studies (cough CPR n = 4, percussion pacing n = 4, precordial thump n = 16; one study studied two interventions). Only two (both precordial thump) had a comparator group ('standard' CPR). For all techniques evidence certainty was very low. Available evidence suggests that precordial thump does not improve survival to hospital discharge in out-of-hospital cardiac arrest. The review did not find evidence that cough CPR or percussion pacing improve clinical outcomes following cardiac arrest.

Conclusion: Cough CPR, percussion pacing and precordial thump should not be routinely used in established cardiac arrest. In specific inpatient, monitored settings cough CPR (in conscious patients) or percussion pacing may be attempted at the onset of a potential lethal arrhythmia. These must not delay standard CPR efforts in those who lose cardiac output.

Prospero Registration Number: CRD42019152925.
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http://dx.doi.org/10.1016/j.resuscitation.2021.01.027DOI Listing
February 2021

A functional genomics screen identifying blood cell development genes in Drosophila by undergraduates participating in a course-based research experience.

Authors:
Cory J Evans John M Olson Bama Charan Mondal Pratyush Kandimalla Ariano Abbasi Mai M Abdusamad Osvaldo Acosta Julia A Ainsworth Haris M Akram Ralph B Albert Elitzander Alegria-Leal Kai Y Alexander Angelica C Ayala Nataliya S Balashova Rebecca M Barber Harmanjit Bassi Sean P Bennion Miriam Beyder Kush V Bhatt Chinmay Bhoot Aaron W Bradshaw Tierney G Brannigan Boyu Cao Yancey Y Cashell Timothy Chai Alex W Chan Carissa Chan Inho Chang Jonathan Chang Michael T Chang Patrick W Chang Stephen Chang Neel Chari Alexander J Chassiakos Iris E Chen Vivian K Chen Zheying Chen Marsha R Cheng Mimi Chiang Vivian Chiu Sharon Choi Jun Ho Chung Liset Contreras Edgar Corona Courtney J Cruz Renae L Cruz Jefferson M Dang Suhas P Dasari Justin R O De La Fuente Oscar M A Del Rio Emily R Dennis Petros S Dertsakyan Ipsita Dey Rachel S Distler Zhiqiao Dong Leah C Dorman Mark A Douglass Allysen B Ehresman Ivy H Fu Andrea Fua Sean M Full Arash Ghaffari-Rafi Asmar Abdul Ghani Bosco Giap Sonia Gill Zafar S Gill Nicholas J Gills Sindhuja Godavarthi Talin Golnazarian Raghav Goyal Ricardo Gray Alexander M Grunfeld Kelly M Gu Natalia C Gutierrez An N Ha Iman Hamid Ashley Hanson Celesti Hao Chongbin He Mengshi He Joshua P Hedtke Ysrael K Hernandez Hnin Hlaing Faith A Hobby Karen Hoi Ashley C Hope Sahra M Hosseinian Alice Hsu Jennifer Hsueh Eileen Hu Spencer S Hu Stephanie Huang Wilson Huang Melanie Huynh Carmen Javier Na Eun Jeon Sunjong Ji Jasmin Johal Amala John Lauren Johnson Saurin Kadakia Namrata Kakade Sarah Kamel Ravinder Kaur Jagteshwar S Khatra Jeffrey A Kho Caleb Kim Emily Jin-Kyung Kim Hee Jong Kim Hyun Wook Kim Jin Hee Kim Seong Ah Kim Woo Kyeom Kim Brian Kit Cindy La Jonathan Lai Vivian Lam Nguyen Khoi Le Chi Ju Lee Dana Lee Dong Yeon Lee James Lee Jason Lee Jessica Lee Ju-Yeon Lee Sharon Lee Terrence C Lee Victoria Lee Amber J Li Jialing Li Alexandra M Libro Irvin C Lien Mia Lim Jeffrey M Lin Connie Y Liu Steven C Liu Irene Louie Shijia W Lu William Y Luo Tiffany Luu Josef T Madrigal Yishan Mai Darron I Miya Mina Mohammadi Sayonika Mohanta Tebogo Mokwena Tonatiuh Montoya Dallas L Mould Mark R Murata Janani Muthaiya Seethim Naicker Mallory R Neebe Amy Ngo Duy Q Ngo Jamie A Ngo Anh T Nguyen Huy C X Nguyen Rina H Nguyen Thao T T Nguyen Vincent T Nguyen Kevin Nishida Seo-Kyung Oh Kristen M Omi Mary C Onglatco Guadalupe Ortega Almazan Jahzeel Paguntalan Maharshi Panchal Stephanie Pang Harin B Parikh Purvi D Patel Trisha H Patel Julia E Petersen Steven Pham Tien M Phan-Everson Megha Pokhriyal Davis W Popovich Adam T Quaal Karl Querubin Anabel Resendiz Nadezhda Riabkova Fred Rong Sarah Salarkia Nateli Sama Elaine Sang David A Sanville Emily R Schoen Zhouyang Shen Ken Siangchin Gabrielle Sibal Garuem Sin Jasmine Sjarif Christopher J Smith Annisa N Soeboer Cristian Sosa Derek Spitters Bryan Stender Chloe C Su Jenny Summapund Beatrice J Sun Christine Sutanto Jaime S Tan Nguon L Tan Parich Tangmatitam Cindy K Trac Conny Tran Daniel Tran Duy Tran Vina Tran Patrick A Truong Brandon L Tsai Pei-Hua Tsai C Kimberly Tsui Jackson K Uriu Sanan Venkatesh Maique Vo Nhat-Thi Vo Phuong Vo Timothy C Voros Yuan Wan Eric Wang Jeffrey Wang Michael K Wang Yuxuan Wang Siman Wei Matthew N Wilson Daniel Wong Elliott Wu Hanning Xing Jason P Xu Sahar Yaftaly Kimberly Yan Evan Yang Rebecca Yang Tony Yao Patricia Yeo Vivian Yip Puja Yogi Gloria Chin Young Maggie M Yung Alexander Zai Christine Zhang Xiao X Zhang Zijun Zhao Raymond Zhou Ziqi Zhou Mona Abutouk Brian Aguirre Chon Ao Alexis Baranoff Angad Beniwal Zijie Cai Ryan Chan Kenneth Chang Chien Umar Chaudhary Patrick Chin Praptee Chowdhury Jamlah Dalie Eric Y Du Alec Estrada Erwin Feng Monica Ghaly Rose Graf Eduardo Hernandez Kevin Herrera Vivien W Ho Kaitlyn Honeychurch Yurianna Hou Jo M Huang Momoko Ishii Nicholas James Gah-Eun Jang Daphne Jin Jesse Juarez Ayse Elif Kesaf Sat Kartar Khalsa Hannah Kim Jenna Kovsky Chak Lon Kuang Shraddha Kumar Gloria Lam Ceejay Lee Grace Lee Li Li Joshua Lin Josephine Liu Janice Ly Austin Ma Hannah Markovic Cristian Medina Jonelle Mungcal Bilguudei Naranbaatar Kayla Patel Lauren Petersen Amanda Phan Malcolm Phung Nadiyah Priasti Nancy Ruano Tanveer Salim Kristen Schnell Paras Shah Jinhua Shen Nathan Stutzman Alisa Sukhina Rayna Tian Andrea Vega-Loza Joyce Wang Jun Wang Rina Watanabe Brandon Wei Lillian Xie Jessica Ye Jeffrey Zhao Jill Zimmerman Colton Bracken Jason Capili Andrew Char Michel Chen Pingdi Huang Sena Ji Emily Kim Kenneth Kim Julie Ko Sean Louise G Laput Sam Law Sang Kuk Lee Olivia Lee David Lim Eric Lin Kyle Marik Josh Mytych Andie O'Laughlin Jensen Pak Claire Park Ruth Ryu Ashwin Shinde Manny Sosa Nick Waite Mane Williams Richard Wong Jocelyn Woo Jonathan Woo Vishaal Yepuri Dorothy Yim Dan Huynh Dinali Wijiewarnasurya Casey Shapiro Marc Levis-Fitzgerald Leslie Jaworski David Lopatto Ira E Clark Tracy Johnson Utpal Banerjee

G3 (Bethesda) 2021 Jan;11(1)

Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.
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http://dx.doi.org/10.1093/g3journal/jkaa028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022729PMC
January 2021

Administering Virtual Reality Therapy to Manage Behavioral and Psychological Symptoms in Patients With Dementia Admitted to an Acute Care Hospital: Results of a Pilot Study.

JMIR Form Res 2021 Feb 3;5(2):e22406. Epub 2021 Feb 3.

Michael Garron Hospital, Toronto, ON, Canada.

Background: As virtual reality (VR) technologies become increasingly accessible and affordable, clinicians are eager to try VR therapy as a novel means to manage behavioral and psychological symptoms of dementia, which are exacerbated during acute care hospitalization, with the goal of reducing the use of antipsychotics, sedatives, and physical restraints associated with negative adverse effects, increased length of stay, and caregiver burden. To date, no evaluations of immersive VR therapy have been reported for patients with dementia in acute care hospitals.

Objective: This study aimed to determine the feasibility (acceptance, comfort, and safety) of using immersive VR therapy for people living with dementia (mild, moderate, and advanced) during acute care hospitalization and explore its potential to manage behavioral and psychological symptoms of dementia.

Methods: A prospective, longitudinal pilot study was conducted at a community teaching hospital in Toronto. The study was nonrandomized and unblinded. A total of 10 patients aged >65 years (mean 86.5, SD 5.7) diagnosed with dementia participated in one or more research coordinator-facilitated sessions of viewing immersive 360° VR footage of nature scenes displayed on a Samsung Gear VR head-mounted display. This mixed-methods study included review of patient charts, standardized observations during the intervention, and pre- and postintervention semistructured interviews about the VR experience.

Results: All recruited participants (N=10) completed the study. Of the 10 participants, 7 (70%) displayed enjoyment or relaxation during the VR session, which averaged 6 minutes per view, and 1 (10%) experienced dizziness. No interference between the VR equipment and hearing aids or medical devices was reported.

Conclusions: It is feasible to expose older people with dementia of various degrees admitted to an acute care hospital to immersive VR therapy. VR therapy was found to be acceptable to and comfortable by most participants. This pilot study provides the basis for conducting the first randomized controlled trial to evaluate the impact of VR therapy on managing behavioral and psychological symptoms of dementia in acute care hospitals.
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http://dx.doi.org/10.2196/22406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889418PMC
February 2021

Medical cannabis use in the United States: a retrospective database study.

J Cannabis Res 2020 Sep 29;2(1):32. Epub 2020 Sep 29.

CB2 Insights, 5045 Orbitor Dr, Building 11, Suite 300, Mississauga, ON, L4W 4Y4, Canada.

Introduction: Growing interest in the medicinal properties of cannabis has led to an increase in its use to treat medical conditions, and the establishment of state-specific medical cannabis programs. Despite medical cannabis being legal in 33 states and the District of Colombia, there remains a paucity of data characterizing the patients accessing medical cannabis programs.

Methods: We retrospectively reviewed a registry with data from 33 medical cannabis evaluation clinics in the United States, owned and operated by CB2 Insights. Data were collected primarily by face-to-face interviews for patients seeking medical cannabis certification between November 18, 2018 and March 18, 2020. Patients were removed from the analysis if they did not have a valid date of birth, were less than 18, or did not have a primary medical condition reported; a total of 61,379 patients were included in the analysis. Data were summarized using descriptive statistics expressed as a mean (standard deviation (SD)) or median (interquartile range (IQR)) as appropriate for continuous variables, and number (percent) for categorical variables. Statistical tests performed across groups included t-tests, chi-squared tests and regression.

Results: The average age of patients was 45.5, 54.8% were male and the majority were Caucasian (87.5%). Female patients were significantly older than males (47.0 compared to 44.6). Most patients reported cannabis experience prior to seeking medical certification (66.9%). The top three mutually exclusive primary medical conditions reported were unspecified chronic pain (38.8%), anxiety (13.5%) and post-traumatic stress disorder (PTSD) (8.4%). The average number of comorbid conditions reported was 2.7, of which anxiety was the most common (28.3%). Females reported significantly more comorbid conditions than males (3.1 compared to 2.3).

Conclusion: This retrospective study highlighted the range and number of conditions for which patients in the US seek medical cannabis. Rigorous clinical trials investigating the use of medical cannabis to treat pain conditions, anxiety, insomnia, depression and PTSD would benefit a large number of patients, many of whom use medical cannabis to treat multiple conditions.
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http://dx.doi.org/10.1186/s42238-020-00038-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819290PMC
September 2020

Complete Atomic Oxygen and UV Protection for Polymer and Composite Materials in a Low Earth Orbit.

ACS Appl Mater Interfaces 2021 Feb 1;13(5):6670-6677. Epub 2021 Feb 1.

Advanced Technology Institute, Department of Electrical and Electronic Engineering, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom.

With the realization of larger and more complex space installations, an increase in the surface area exposed to atomic oxygen (AO) and ultraviolet (UV) effects is expected, making structural integrity of space structures essential for future development. In a low Earth orbit (LEO), the effects of AO and UV degradation can have devastating consequences for polymer and composite structures in satellites and space installations. Composite materials such as carbon fiber-reinforced polymer (CFRP) or polymer materials such as polyetherimide and polystyrene are widely used in satellite construction for various applications including structural components, thermal insulation, and importantly radio frequency (RF) assemblies. In this paper, we present a multilayered material protection solution, a multilayered protection barrier, that mitigates the effects of AO and UV without disrupting the functional performance of tested assemblies. This multilayered protection barrier deposited via a custom-built plasma-enhanced chemical vapor deposition (PECVD) system is designed so as to deposit all necessary layers without breaking vacuum to maximize the adhesion to the surface of the substrate and to ensure no pinhole erosion is present. In the multilayer solution, a moisture and outgassing barrier (MOB) is coupled with an AO and UV capping layer to provide complete protection.
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http://dx.doi.org/10.1021/acsami.0c21552DOI Listing
February 2021

Heterozygous mutation SLFN14 K208N in mice mediates species-specific differences in platelet and erythroid lineage commitment.

Blood Adv 2021 Jan;5(2):377-390

Institute of Cardiovascular Sciences, College of Medical and Dental Sciences.

Schlafen 14 (SLFN14) has recently been identified as an endoribonuclease responsible for cleaving RNA to regulate and inhibit protein synthesis. Early studies revealed that members of the SLFN family are capable of altering lineage commitment during T-cell differentiation by using cell-cycle arrest as a means of translational control by RNase activity. SLFN14 has been reported as a novel gene causing an inherited macrothrombocytopenia and bleeding in human patients; however, the role of this endoribonuclease in megakaryopoiesis and thrombopoiesis remains unknown. To investigate this, we report a CRISPR knock-in mouse model of SLFN14 K208N homologous to the K219N mutation observed in our previous patient studies. We used hematological analysis, in vitro and in vivo studies of platelet and erythrocyte function, and analysis of spleen and bone marrow progenitors. Mice homozygous for this mutation do not survive to weaning age, whereas heterozygotes exhibit microcytic erythrocytosis, hemolytic anemia, splenomegaly, and abnormal thrombus formation, as revealed by intravital microscopy, although platelet function and morphology remain unchanged. We also show that there are differences in erythroid progenitors in the spleens and bone marrow of these mice, indicative of an upregulation of erythropoiesis. This SLFN14 mutation presents distinct species-specific phenotypes, with a platelet defect reported in humans and a severe microcytic erythrocytosis in mice. Thus, we conclude that SLFN14 is a key regulator in mammalian hematopoiesis and a species-specific mediator of platelet and erythroid lineage commitment.
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http://dx.doi.org/10.1182/bloodadvances.2020002404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839357PMC
January 2021

US Army Africa's medical theater entry portal: An innovative medical readiness system.

JAAPA 2020 Dec;33(12)

Mary Janet Coy is with the Army National Guard Bureau. Jung H. Omerod, Christopher R. Smith, Laura K. Bender, Jason A. Greene, Daniel Ruiz, and Steven L. Hall are with the US Army Africa. Paul J. Auchincloss is with the U.S. Special Operations Command Africa.

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http://dx.doi.org/10.1097/01.JAA.0000723148.49991.c3DOI Listing
December 2020

POTENTIAL FOR ELECTROENCEPHALOGRAPHIC MONITORING OF ANESTHETIC DEPTH IN CAPTIVE CHIMPANZEES () USING A NOVEL BRAIN FUNCTION MONITOR.

J Zoo Wildl Med 2020 Nov;51(3):729-732

University of Tennessee College of Veterinary Medicine, Knoxville, TN 37996, USA.

The electroencephalogram (EEG) waveform can predictably change with depth of anesthesia, and algorithms such as the Patient State index (PSi) have been developed to convert the waveform into a user-friendly objective reading of anesthetic depth. In this study, PSi values were measured in 10 captive chimpanzees () during three phases of an anesthetic event. Phase 1 included sedation with dexmedetomidine, midazolam, and ketamine. Phase 2 started with administration of an α-2 antagonist and isoflurane. Phase 3 started with discontinuing isoflurane and ended with spontaneous movement and extubation. Initial PSi readings for phase 1 were high at 74.5 ± 12.2 (mean ± SD), before declining to 24.1 ± 5.3 for the remainder of the phase. Phase 2 PSi values were recorded as 21.4 ± 5.4 and then climbed during phase 3. Spontaneous movement was recorded at PSi values of 72 to 79. Electroencephalographic monitoring via PSi was successfully performed during three phases of anesthesia in the chimpanzees and was consistent with human values reported during general anesthesia. This paper serves as a preliminary investigation into EEG monitoring of chimpanzees, and further work is needed for its validation.
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http://dx.doi.org/10.1638/2019-0193DOI Listing
November 2020

Expanded phenotypic spectrum of JAG1-associated diseases: Central conducting lymphatic anomaly with a pathogenic variant in JAG1.

Clin Genet 2021 May 12;99(5):742-743. Epub 2021 Jan 12.

Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

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http://dx.doi.org/10.1111/cge.13915DOI Listing
May 2021

Reprogrammable Gel Electrophoresis Detection Assay Using CRISPR-Cas12a and Hybridization Chain Reaction.

Anal Chem 2021 02 6;93(4):1934-1938. Epub 2021 Jan 6.

Department of Chemistry, University at Albany, State University of New York, 1400 Washington Avenue, Albany, New York 12222, United States.

Hybridization chain reaction (HCR) is a DNA-based target-induced cascade reaction. Due to its unique enzyme-free amplification feature, HCR is often employed for sensing applications. Much like DNA nanostructures that have been designed to respond to a specific stimulus, HCR employs nucleic acids that reconfigure and assemble in the presence of a specific trigger. Despite its standalone capabilities, HCR is highly modular; therefore, it can be advanced and repurposed when coupled with latest discoveries. To this effect, we have developed a gel electrophoresis-based detection approach which combines the signal amplification feature of HCR with the programmability and sensitivity of the CRISPR-Cas12a system. By incorporating CRISPR-Cas12a, we have achieved greater sensitivity and reversed the signal output from TURN OFF to TURN ON. CRISPR-Cas12a also enabled us to rapidly reprogram the assay for the detection of both ssDNA and dsDNA target sequences by replacing a single reaction component in the detection kit. Detection of conserved, both ssDNA and dsDNA, regions of tobacco curly shoot virus (TCSV) and hepatitis B virus (HepBV) genomes is demonstrated with this methodology. This low-cost gel electrophoresis assay can detect as little as 1.5 fmol of the target without any additional target amplification steps and is about 100-fold more sensitive than HCR-alone approach.
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http://dx.doi.org/10.1021/acs.analchem.0c04949DOI Listing
February 2021

Lymphatic Disorders and Management in Patients with Congenital Heart Disease.

Ann Thorac Surg 2020 Dec 26. Epub 2020 Dec 26.

Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Electronic address:

Congenital heart disease can lead to significant lymphatic complications such as chylothorax, plastic bronchitis, protein losing enteropathy and ascites. Recent improvements in lymphatic imaging and the development of new lymphatic procedures can help alleviate symptoms and improve outcomes.
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http://dx.doi.org/10.1016/j.athoracsur.2020.10.058DOI Listing
December 2020

Pediatric/Congenital Cardiac Catheterization Quality: An Analysis of Existing Metrics.

JACC Cardiovasc Interv 2020 12;13(24):2853-2864

Division of Cardiology, The Children's Hospital of Philadelphia, and Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA; Center for Pediatric Clinical Effectiveness, The Children's Hospital of Philadelphia, and Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Objectives: The aim of this study was to enumerate and categorize quality metrics relevant to the pediatric/congenital cardiac catheterization laboratory (PCCL).

Background: Diagnostic and interventional catheterization procedures are an increasingly important part of the care of young patients with cardiac disease. Measurement of the performance of PCCL programs in a stringent and consistent fashion is a crucial step toward improving outcomes. To the best of our knowledge, a systematic evaluation of current quality metrics in PCCL has not been performed previously.

Methods: Potential metrics were evaluated by: 1) a systematic review of peer-reviewed research; 2) a review of metrics from organizations interested in quality improvement, patient safety, and/or PCCL programs; and 3) a survey of U.S. PCCL cardiologists. Collected metrics were grouped on 2 dimensions: 1) Institute of Medicine domains; and 2) the Donabedian structure/process/outcome framework. Survey responses were dichotomized between favorable and unfavorable responses and then compared within and between categories.

Results: In the systematic review, 6 metrics were identified (from 9 publications), all focused on safety either as an outcome (adverse events [AEs], mortality, and failure to rescue along with radiation exposure) or as a structure (procedure volume or operator experience). Four organizations measure quality metrics of PCCL programs, of which only 1 publicly reports data. For the survey, 229 cardiologists from 118 hospital programs responded (66% of individuals and 72% of hospital programs). The highest favorable ratings were for safety metrics (p < 0.001), of which major AEs, failure to rescue, and procedure-specific AEs had the highest ratings. Of respondents, 67% stated that current risk adjustment were not effective. Favorability ratings for hospital characteristics, PCCL characteristics, and quality improvement processes were significantly lower than for safety and less consistent within categories.

Conclusions: There is a limited number of PCCL quality metrics, primarily focused on safety. Confidence in current risk adjustment methodology is low. The knowledge gaps identified should guide future research in the development of new quality metrics.
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http://dx.doi.org/10.1016/j.jcin.2020.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773132PMC
December 2020

Novel antiplatelet strategies targeting GPVI, CLEC-2 and tyrosine kinases.

Platelets 2021 Jan 13;32(1):29-41. Epub 2020 Dec 13.

Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham , Birmingham, UK.

Antiplatelet medications comprise the cornerstone of treatment for diseases that involve arterial thrombosis, including acute coronary syndromes (ACS), stroke and peripheral arterial disease. However, antiplatelet medications may cause bleeding and, furthermore, thrombotic events may still recur despite treatment. The interaction of collagen with GPVI receptors on the surface of platelets has been identified as one of the major players in the pathophysiology of arterial thrombosis that occurs following atherosclerotic plaque rupture. Promisingly, GPVI deficiency in humans appears to have a minimal impact on bleeding. These findings together suggest that targeting platelet GPVI may provide a novel treatment strategy that provides additional antithrombotic efficacy with minimal disruption of normal hemostasis compared to conventional antiplatelet medications. CLEC-2 is gaining interest as a therapeutic target for a variety of thrombo-inflammatory disorders including deep vein thrombosis (DVT) with treatment also predicted to cause minimal disruption to hemostasis. GPVI and CLEC-2 signal through Src, Syk and Tec family tyrosine kinases, providing additional strategies for inhibiting both receptors. In this review, we summarize the evidence regarding GPVI and CLEC-2 and strategies for inhibiting these receptors to inhibit platelet recruitment and activation in thrombotic diseases.
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http://dx.doi.org/10.1080/09537104.2020.1849600DOI Listing
January 2021

Introducing virtual reality therapy for inpatients with dementia admitted to an acute care hospital: learnings from a pilot to pave the way to a randomized controlled trial.

Pilot Feasibility Stud 2020 Oct 31;6(1):166. Epub 2020 Oct 31.

Michael Garron Hospital, Toronto, Ontario, Canada.

Background: Behavioural and psychological symptoms of dementia (BPSD) are difficult to manage, particularly in acute care settings. As virtual reality (VR) technology becomes increasingly accessible and affordable, there is growing interest among clinicians to evaluate VR therapy in hospitalized patients, as an alternative to administering antipsychotics/sedatives or using physical restraints associated with negative side effects.

Objectives: Validate and refine the proposed research protocol for a randomized controlled trial (RCT) that evaluates the impact of VR therapy on managing BPSD in acute care hospitals. Special attention was given to ascertain the processes of introducing non-pharmacological interventions in acute care hospitals.

Methods: Ten patients 65 years or older (mean = 87) previously diagnosed with dementia, admitted to an acute care hospital, were recruited over 3-month period into a prospective longitudinal pilot study. The intervention consisted of viewing 20-min of immersive 360° VR using a head-mounted display. Baseline and outcomes data were collected from the hospital electronic medical records, pre/post mood-state questionnaires, Neuropsychiatric Inventory (NPI) score, and standardized qualitative observations. Comprehensive process data and workflow were documented, including timestamps for each study task and detailed notes on personnel requirements and challenges encountered.

Results: Of 516 patients admitted during the study, 67 met the inclusion/exclusion criteria. In total, 234 calls were initiated to substitute decision makers (SDM) of the 67 patients for the consenting process. Nearly half (45.6%) of SDMs declined participation, and 40% could not be reached in time before patients being discharged, resulting in 57 eligible patients not being enrolled. Ten consented participants were enrolled and completed the study. The initial VR session averaged 53.6 min, largely due to the administration of NPI (mean = 19.5 min). Only four participants were able to respond reliably to questions. Seven participants opted for additional VR therapy sessions; of those providing feedback regarding the VR content, they wanted more varied scenery (animals, fields of flowers, holiday themes). Few sessions (4/18) encountered technical difficulties.

Conclusion: The pilot was instrumental in identifying issues and providing recommendations for the RCT. Screening, inclusion criteria, consenting, data collection, and interaction with SDMs and hospital staff were all processes requiring changes and optimizations. Overall, patients with dementia appear to tolerate immersive VR, and with suggested protocol alterations, it is feasible to evaluate this non-pharmacological intervention in acute care hospitals.
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http://dx.doi.org/10.1186/s40814-020-00708-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602317PMC
October 2020