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Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
Introduction: Although use of point of care ultrasound (PoCUS) protocols for patients with undifferentiated hypotension in the Emergency Department (ED) is widespread, our previously reported SHoC-ED study showed no clear survival or length of stay benefit for patients assessed with PoCUS. In this analysis, we examine if the use of PoCUS changed fluid administration and rates of other emergency interventions between patients with different shock types. The primary comparison was between cardiogenic and non-cardiogenic shock types. Methods: A post-hoc analysis was completed on the database from an RCT of 273 patients who presented to the ED with undifferentiated hypotension (SBP <100 or shock index > 1) and who had been randomized to receive standard care with or without PoCUS in 6 centres in Canada and South Africa. PoCUS-trained physicians performed scans after initial assessment. Shock categories and diagnoses recorded at 60 minutes after ED presentation, were used to allocate patients into subcategories of shock for analysis of treatment. We analyzed actual care delivered including initial IV fluid bolus volumes (mL), rates of inotrope use and major procedures. Standard statistical tests were employed. Sample size was powered at 0.80 (α:0.05) for a moderate difference. Results: Although there were expected differences in the mean fluid bolus volume between patients with non-cardiogenic and cardiogenic shock, there was no difference in fluid bolus volume between the control and PoCUS groups (non-cardiogenic control 1878 mL (95% CI 1550 – 2206 mL) vs. non-cardiogenic PoCUS 1687 mL (1458 – 1916 mL); and cardiogenic control 768 mL (194 – 1341 mL) vs. cardiogenic PoCUS 981 mL (341 – 1620 mL). Likewise there were no differences in rates of inotrope administration, or major procedures for any of the subcategories of shock between the control group and PoCUS group patients. The most common subcategory of shock was distributive. Conclusion: Despite differences in care delivered by subcategory of shock, we did not find any significant difference in actual care delivered between patients who were examined using PoCUS and those who were not. This may help to explain the previously reported lack of outcome difference between groups.
Introduction: Point of care ultrasound has been reported to improve diagnosis in non-traumatic hypotensive ED patients. We compared diagnostic performance of physicians with and without PoCUS in undifferentiated hypotensive patients as part of an international prospective randomized controlled study. The primary outcome was diagnostic performance of PoCUS for cardiogenic vs. non-cardiogenic shock. Methods: SHoC-ED recruited hypotensive patients (SBP < 100 mmHg or shock index > 1) in 6 centres in Canada and South Africa. We describe previously unreported secondary outcomes relating to diagnostic accuracy. Patients were randomized to standard clinical assessment (No PoCUS) or PoCUS groups. PoCUS-trained physicians performed scans after initial assessment. Demographics, clinical details and findings were collected prospectively. Initial and secondary diagnoses including shock category were recorded at 0 and 60 minutes. Final diagnosis was determined by independent blinded chart review. Standard statistical tests were employed. Sample size was powered at 0.80 (α:0.05) for a moderate difference. Results: 273 patients were enrolled with follow-up for primary outcome completed for 270. Baseline demographics and perceived category of shock were similar between groups. 11% of patients were determined to have cardiogenic shock. PoCUS had a sensitivity of 80.0% (95% CI 54.8 to 93.0%), specificity 95.5% (90.0 to 98.1%), LR+ve 17.9 (7.34 to 43.8), LR-ve 0.21 (0.08 to 0.58), Diagnostic OR 85.6 (18.2 to 403.6) and accuracy 93.7% (88.0 to 97.2%) for cardiogenic shock. Standard assessment without PoCUS had a sensitivity of 91.7% (64.6 to 98.5%), specificity 93.8% (87.8 to 97.0%), LR+ve 14.8 (7.1 to 30.9), LR- of 0.09 (0.01 to 0.58), Diagnostic OR 166.6 (18.7 to 1481) and accuracy of 93.6% (87.8 to 97.2%). There was no significant difference in sensitivity (-11.7% (-37.8 to 18.3%)) or specificity (1.73% (-4.67 to 8.29%)). Diagnostic performance was also similar between other shock subcategories. Conclusion: As reported in other studies, PoCUS based assessment performed well diagnostically in undifferentiated hypotensive patients, especially as a rule-in test. However performance was similar to standard (non-PoCUS) assessment, which was excellent in this study.
OBJECTIVES/SPECIFIC AIMS: o To review the community’s recommendations on how to rebuild trust in the Flint community. o To review effective community engagement strategies utilized with the Flint Special Projects for project conceptualization, participant recruitment, data analysis, project oversight, and dissemination. METHODS/STUDY POPULATION: The study population includes nearly two hundred residents representing seniors, youth and diverse ethnicities recruited to participate in eleven focus group meetings. The population also represents the general public who attended informational meetings in Flint, Michigan to learn about the crisis and allow residents to voice their opinions and concerns during the onset of the crisis. The project is a mixed methods community based participatory research effort that utilized community decision making in all phases of the effort such as pre-conception, implementation, dissemination and advocacy to encourage the community’s recommendations are adopted at policy and institutional responsiveness levels. It includes three community engaged research efforts: (project 1) A qualitative analysis of community sentiment provided during 17 recorded legislative, media and community events, and (projects 2-3) two mixed methods efforts utilizing purposive sampling of stakeholders whose voice may not have been heard. RESULTS/ANTICIPATED RESULTS: The project presents a qualitative analysis of the community’s voice during the onset of the man-made disaster when the community first became aware of the emergency manager’s plans to switch the water source. It also reflects current perspectives of community voice since the projects are scheduled to end late February 2019. Findings from a trust measure administered to nearly two hundred residents will be presented, along with a qualitative analysis of focus group findings among segments of the population (seniors, youth, and diverse ethnicities) who may have been left out of narratives on the water crisis. Finally, the project will compare empowerment and resiliency approaches being utilized in Flint, Michigan to recover from the disaster with other approaches grounded in literature and theory. DISCUSSION/SIGNIFICANCE OF IMPACT: Communities of color often experience social determinants of health which negatively impact their health, well-being and human rights. Some Flint citizens are experiencing negative health consequences (i.e., rashes, brain and behavioral sequelle, fertility, etc.) as a result of the disaster, and are uncertain of health outcomes in the future. This is the first project to rigorously document and analyze levels of trust and mistrust in the city of Flint since the water disaster occurred. The qualitative research will guide future clinical research that will benefit this traumatized community experiencing high levels of mistrust (i.e., government, elected officials, etc.). The community engaged methodology involved residents and study participants in all phases of the project including project oversight, validating and analyzing data, and dissemination. This methodology will contribute to existing literature and theory on community based participatory research, community engaged research, team science and citizen science. The approaches empowered a call to action among residents, for example, seniors who attended two senior focus group sessions shared “they are hopeful and have a purpose,” resulting in the creation of a council (with officers) at their housing complex to advocate for the well-being of seniors during the recovery process. Recruitment methodologies were extremely successful due to resident level trust in community leaders and community partner organizations. Finally, the project’s examination of approaches encouraging empowerment and resiliency will provide lessons learned for other communities challenged with crisis.
Healthcare organizations are required to provide workers with respiratory protection (RP) to mitigate hazardous airborne inhalation exposures. This study sought to better identify gaps that exist between RP guidance and clinical practice to understand issues that would benefit from additional research or clarification.
Night-migratory songbirds appear to sense the direction of the Earth's magnetic field via radical pair intermediates formed photochemically in cryptochrome flavoproteins contained in photoreceptor cells in their retinas. It is an open question whether this light-dependent mechanism could be sufficiently sensitive given the low-light levels experienced by nocturnal migrants. The scarcity of available photons results in significant uncertainty in the signal generated by the magnetoreceptors distributed around the retina. Here we use results from Information Theory to obtain a lower bound estimate of the precision with which a bird could orient itself using only geomagnetic cues. Our approach bypasses the current lack of knowledge about magnetic signal transduction and processing in vivo by computing the best-case compass precision under conditions where photons are in short supply. We use this method to assess the performance of three plausible cryptochrome-derived flavin-containing radical pairs as potential magnetoreceptors.
Middle-third helical rim defects may arise from trauma or oncological resection, and pose a challenging reconstructive problem. Reconstructing defects larger than 2 cm using traditional methods commits patients to the inconvenience of staged procedures.
This paper describes a single-stage helical rim reconstruction technique using a post-auricular bipedicled flap and ipsilateral conchal cartilage graft for delayed middle-third helical rim reconstruction.
Two examples of this technique used in post-trauma and oncological reconstruction cases are presented, with pre- and post-operative photographs provided for demonstration.
Contralateral graft harvest and staged operations for helical rim reconstruction are associated with donor site morbidity and the inconvenience of multiple operations to achieve the desired reconstructive outcome. Our single-stage helical rim reconstruction technique was well tolerated by patients, and showed satisfactory aesthetic results in terms of size and symmetry.
Introduction: Patients with chronic diseases are known to benefit from exercise. Such patients often visit the emergency department (ED). There are few studies examining prescribing exercise in the ED. We wished to study if exercise prescription in the ED is feasible and effective. Methods: In this pilot prospective block randomized trial, patients in the control group received routine care, whereas the intervention group received a combined written and verbal prescription for moderate exercise (150 minutes/week). Both groups were followed up by phone at 2 months. The primary outcome was achieving 150 min of exercise per week. Secondary outcomes included change in exercise, and differences in reported median weekly exercise. Comparisons were made by Mann-Whitney and Fishers tests (GraphPad). Results: Follow-up was completed for 22 patients (11 Control; 11 Intervention). Baseline reported median (with IQR) weekly exercise was similar between groups; Control 0(0-0)min; Intervention 0(0-45)min. There was no difference between groups for the primary outcome of 150 min/week at 2 months (Control 3/11; Intervention 4/11, RR 1.33 (95%CI 0.38-4.6;p=1.0). There was a significant increase in median exercise from baseline in both groups, but no difference between the groups (Control 75(10-225)min; Intervention 120(52.5-150)min;NS). 3 control patients actually received exercise prescription as part of routine care. A post-hoc comparison of patients receiving intervention vs. no intervention, revealed an increase in patients meeting the primary target of 150min/week (No intervention 0/8; Intervention 7/14, RR 2.0 (95%CI 1.2-3.4);p=0.023). Conclusion: Recruitment was feasible, however our study was underpowered to quantify an estimated effect size. As a significant proportion of the control group received the intervention (as part of standard care), any potential measurable effect was diluted. The improvement seen in patients receiving intervention and the increase in reported exercise in both groups (possible Hawthorne effect) suggests that exercise prescription for ED patients may be beneficial.
Introduction: Electrocardiographic (ECG) rhythms are used during resuscitation (ACLS) to guide resuscitation, and often to determine futility. Survival rates to hospital discharge have been reported to be higher for patients with PEA than asystole in out-of-hospital cardiac arrest. This study examines how well the initial ECG cardiac rhythm represents actual cardiac activity as determined by point of care ultrasound (PoCUS). Methods: A database review was completed for patients arriving to a tertiary ED in asystole or PEA arrest, from 2010 to 2014. Patients under 19y or with a previous DNR were excluded. Patients were grouped into those with cardiac activity (PEA) and asystole on ECG; as well as whether cardiac activity was seen on PoCUS during the arrest. Data was analyzed for visualized cardiac activity on PoCUS. Results: 186 patients met the study criteria. Those with asystole on ECG were more likely to have no cardiac activity than those with PEA (Odds 7.21 for initial PoCUS; 5.45 for any PoCUS). The sensitivity of ECG rhythm was 80.49% and 82.12%, specificity was 77.91% and 54.28%, positive predictive value was 94.28% and 88.57%, and negative predictive value was 30.43% and 41.30% for cardiac activity on initial PoCUS and on any PoCUS respectively. The positive and negative likelihood ratios for ECG were 3.47 and 0.25 for activity on initial PoCUS. The positive and negative likelihood ratios for activity on any PoCUS were 1.78 and 0.33. Conclusion: Our results suggest that although most patients with asystole on ECG demonstrate no cardiac activity, a small number actually had activity on PoCUS. This supports the use of PoCUS during cardiac arrest, in addition to ECG, to identify patients with ongoing mechanical cardiac activity.
Introduction: Ultrasonography (US), performed in the Emergency Department (ED) by Emergency Physicians, is well established. Educational studies have shown some promise in training paramedics in US use. We have developed and piloted a novel curriculum for paramedic US education. Methods: Based on an informal needs assessment, an US curriculum for paramedics was developed to include: Basic principles, Focused assessment with sonography for trauma (FAST), cardiac, and vascular access. Participants included ED-based and pre-hospital paramedics including all paramedics with critical care training who routinely perform vascular access and procedural sedation within our ED. Comparisons were made using paired non-parametric tests (GraphPad). Results: Participants (N=9) were provided pre- reading materials prior to completing a 6-hour course, consisting of a mix of didactic and practical sessions with live models and vascular access phantoms. Each module was introduced with a 30 minute didactic session, led by an Emergency Physician trained in US, followed immediately by a 1 hour hands-on session lead by either an Emergency Physician or an Emergency Medicine Resident at a learner to instructor ratio of 3:1. At the end of the course, participants were asked to complete a short 10 minute survey that included (1) an assessment of the course quality with regard to preparatory material and course content/delivery (4 point Likert scale; excellent, good, fair, poor); (2) self reported US knowledge pre and post course on a scale of 1-10 (10 high, 1 low); (3) general yes/no questions related to the future of ECCU paramedical and (4) a subjective written section for additional comments. All participants rated the content favourably: 97% scoring it as excellent, and 3% as good. The participants median self-reported US knowledge score increased from 2/10 (IQR 2-3) to 8/10 (IQR 7.25-8; p=0.009) post- course. All comments from the text field were positive in nature. Conclusion: We report a paramedic US course curriculum, which when piloted resulted in high learner satisfaction and a high rate of self reported improvement in US knowledge. Further study will include an assessment of knowledge acquisition and practical performance. Future modifications in our curriculum will be based on needs assessment and may include additional modules.
Introduction: The decision as to whether to end resuscitation for pre-hospital cardiac arrest (CA) patients in the field or in the emergency department (ED) is commonly made based upon standard criteria. We studied the reliability of several easily determined criteria as predictors of resuscitation outcomes in a population of adults in CA transported to the ED. Methods: A retrospective database and chart analysis was completed for patients arriving to a tertiary ED in cardiac arrest, between 2010 and 2014. Patients were excluded if aged under 19. Multiple data were abstracted from charts using a standardized form. Regression analysis was used to compare criteria that predicted return of spontaneous circulation (ROSC) and survival to hospital admission (SHA). Results: 264 patients met the study inclusion criteria. Logistic regression was used to identify predictors of ROSC and SHA. The criteria that emerged as significant predictors for ROSC included; longer ED resuscitation time (Odds ratio 1.11 (1.06- 1.18)), witnessed arrest (Odds ratio 9.43 (2.58- 53.0)) and having an initial cardiac rhythm of Pulseless Electrical Activity (Odds Ratio 3.23 (1.07-9.811)) over Asystole. Receiving point of care ultrasound (PoCUS; Odds ratio 0.22 (0.07-0.69)); and having an initial cardiac rhythm of Pulseless Electrical Activity (Odds Ratio 4.10 (1.43-11.88)) were the significant predictors for SHA. Longer times for ED resuscitation was close to reaching significance for predicting SHA Conclusion: Our results suggest that both fixed and adaptable factors, including increasing resuscitation time, and PoCUS use in the ED were important independent predictors of successful resuscitation. Several commonly used criteria were unreliable predictors.
Introduction: With hospital occupancy rates frequently approaching 100%, even small variations in daily admission numbers can have a large impact. The ability to predict variance in emergency admission rates would provide administrators with a significant advantage in managing hospital daily bed requirements. There is a growing interest in patterns of hospital admissions, and many EDs utilize historical admission patterns to attempt to predict daily bed requirements. Previous studies have utilized patient demographics and past medical history to develop an admission likelihood model. We wished to examine the predictive strength of individual CEDIS presenting complaints (PC) on admission likelihood Methods: Using a database analysis of over 285,000 ED presentations (2013-2017), we calculated visit frequencies and admission rates by PC. Using a logistic regression analysis PCs were ordered from high to medium predictive strength. Results: Of 285,155 presentations, there were 38,090 hospital admissions, a rate of 13.36%. Based on the number of visit frequencies and admission rates, the PCs demonstrating high predictive strength were Direct Referral (effect=0.36, binomial CI: 0.28 to 0.44); Shortness of Breath (0.32: 0.26 to 0.41); General Weakness; Weakness/Query CVA; & Chest Pain Cardiac Features (each 0.30: 0.25 to 0.42); Altered level of consciousness (0.24: 0.16 to 0.31); and Confusion (0.18: 0.08 to 0.26). With our sample size, all remaining CEDIS PCs had low predictive value (the effect is <0.1), or were not predictive at all. Conclusion: We have demonstrated that, for our population, certain PCs are associated with an increased likelihood of admission and have quantified this effect using logistic regression analysis. Variance from the average daily admission rate may be predicted, in our population, by identifying these PCs at registration.We plan to develop a tool, based on this data and implemented at registration, to predict cumulative likely daily admission requirements as patients present over a 24hr period.
We have analyzed atom probe tomography reconstructions of disaggregated meteoritic material containing nanodiamonds and disordered carbon to determine whether these phases formed in the solar system or whether they predate the solar system and were formed in supernovae or the interstellar medium. We developed a method to distinguish between these two carbonaceous phases in < 100 nm diameter aggregates using the ratios of various native and contaminant molecular species. We find variations in measured 12C/13C ratios between the two phases that suggest hydrides form more readily during field evaporation of the disordered C than the nanodiamonds.
We have explored the thermodynamics of compressed magnetized plasmas in laboratory experiments and we call these studies ‘magnetothermodynamics’. The experiments are carried out in the Swarthmore Spheromak eXperiment device. In this device, a magnetized plasma source is located at one end and at the other end, a closed conducting can is installed. We generate parcels of magnetized plasma and observe their compression against the end wall of the conducting cylinder. The plasma parameters such as plasma density, temperature and magnetic field are measured during compression using HeNe laser interferometry, ion Doppler spectroscopy and a linear
probe array, respectively. To identify the instances of ion heating during compression, a PV diagram is constructed using measured density, temperature and a proxy for the volume of the magnetized plasma. Different equations of state are analysed to evaluate the adiabatic nature of the compressed plasma. A three-dimensional resistive magnetohydrodynamic code (NIMROD) is employed to simulate the twisted Taylor states and shows stagnation against the end wall of the closed conducting can. The simulation results are consistent to what we observe in our experiments.
To determine whether antimicrobial-impregnated textiles decrease the acquisition of pathogens by healthcare provider (HCP) clothing.
We completed a 3-arm randomized controlled trial to test the efficacy of 2 types of antimicrobial-impregnated clothing compared to standard HCP clothing. Cultures were obtained from each nurse participant, the healthcare environment, and patients during each shift. The primary outcome was the change in total contamination on nurse scrubs, measured as the sum of colony-forming units (CFU) of bacteria.
PARTICIPANTS AND SETTING
Nurses working in medical and surgical ICUs in a 936-bed tertiary-care hospital.
Nurse subjects wore standard cotton-polyester surgical scrubs (control), scrubs that contained a complex element compound with a silver-alloy embedded in its fibers (Scrub 1), or scrubs impregnated with an organosilane-based quaternary ammonium and a hydrophobic fluoroacrylate copolymer emulsion (Scrub 2). Nurse participants were blinded to scrub type and randomly participated in all 3 arms during 3 consecutive 12-hour shifts in the intensive care unit.
In total, 40 nurses were enrolled and completed 3 shifts. Analyses of 2,919 cultures from the environment and 2,185 from HCP clothing showed that scrub type was not associated with a change in HCP clothing contamination (P=.70). Mean difference estimates were 0.118 for the Scrub 1 arm (95% confidence interval [CI], −0.206 to 0.441; P=.48) and 0.009 for the Scrub 2 rm (95% CI, −0.323 to 0.342; P=.96) compared to the control. HCP became newly contaminated with important pathogens during 19 of the 120 shifts (16%).
Antimicrobial-impregnated scrubs were not effective at reducing HCP contamination. However, the environment is an important source of HCP clothing contamination.
Conjectures are given for Hilbert series related to polynomial invariants of finite general linear groups: one for invariants mod Frobenius powers of the irrelevant ideal and one for cofixed spaces of polynomials.