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OBJECTIVES/SPECIFIC AIMS: Using a novel biomechanical-based motor speech assessment alongside commonly used clinically-based motor speech assessments, the goal of this study was to describe longitudinal recovery in speech movements and functional speech in a cohort of 5 patients following facial transplantation. METHODS/STUDY POPULATION: Five participants who had received either full or partial face transplantation were included in this study. Each participant received a unique facial graft from their donor, which included varied amounts of soft tissue, facial musculature, nerve, and bone. Two participants were early in the recovery period and were assessed from zero to 24 months post-transplantation. Three participants were late in the recovery period and were assessed from 36 to 60 months post-transplantation. Each participant completed two data collection sessions and the average time between sessions was 20.4 months. At each session, orofacial movements were recorded using a 3D motion capture system. A 4-sensor head marker was used to subtract head movement (translation and rotation) from the facial markers. The analyses in this study were restricted to two markers: midline lower lip and a virtually calculated midline jaw marker. A marker at the top of the nose bridge was used as the origin point. The following kinematic variables were obtained from each lip-jaw movement time-series: peak movement speed (mm/s), and displacement (mm). Each patient was instructed to perform 10 repetitions of the phrase “buy bobby a puppy” at his or her typical speaking rate and volume. Sentence-level intelligibility was obtained using the Sentence Intelligibility Test (SIT) and word-level intelligibility was obtained using the Word Intelligibility Test, using standard procedures. Intelligibility, measured in percentage of words correctly transcribed, and speaking rate, measured in words per minute (wpm), was derived from the SIT sentences for each patient. Intelligibility, measured in percentage of words correctly chosen via multiple choice was derived from the Word Intelligibility Test. RESULTS/ANTICIPATED RESULTS: Effect sizes (Cohen’s d) across the 10 trials of “buy bobby a puppy” were computed to assess the effects of recovery time on range of motion and speed of the lower lip alone, the jaw alone, and the lower lip and jaw together for both range of motion and for speed. The largest effect sizes were observed for increased range of motion and increased speed of the articulators for participants within 24 months of surgery. Smaller effect sizes were observed for these parameters for the participants in the later stages of recovery, with some participants showing declines in range of motion and speed of some but not all articulators. Descriptive statistics indicate that both speech and word intelligibility improvements are most notable in the first two years following transplantation and appear to plateau during the later stages of recovery. Only two out of five of our participants achieved “normal” speech intelligibility (i.e., >97%) at five years post-transplantation. DISCUSSION/SIGNIFICANCE OF IMPACT: Biomechanical assessment revealed that kinematic recovery of articulator range of motion and speed appears most significant in the first two years following surgery, but that improvement continues to some degree as far as five-years post-transplant. Clinically-based assessments suggest that gains in intelligibility appear to plateau by 3-years post-surgery.
OBJECTIVES/SPECIFIC AIMS: Early life stress is known to greatly impact neurodevelopment during critical periods, conferring risk for various psychopathologies, including the onset and exacerbation of schizophrenia and anxiety disorders. The endocannabinoid system is highly integrated into the stress response and may be one means by which early life stress produces such deleterious effects. Using a naturalistic, ecologically valid animal model, this study explored interactions between the stress response and endocannabinoid systems within the cerebellum, a region dense with the CB1 endocannabinoid receptors and shown to be susceptible to stress. METHODS/STUDY POPULATION: This study explored behavioral and neural impacts of early life stress in Long-Evans rats reared with or without limited access to bedding material during postnatal day (PND) 2-9. Corticosterone (CORT) levels were measured at PND8 and 70. During PND50-70, rats were assessed on Novel Object Recognition to test memory, Rotarod to evaluate cerebellar integrity, Elevated Plus Maze to assay anxiety, Social Preference, and Eyeblink Conditioning, a cerebellar-dependent and endocannabinoid-mediated task. Lipid analysis was performed on PND70 tissue samples of cerebellar interpositus (IP) nucleus via high-performance liquid chromatography and tandem mass spectrometry. RESULTS/ANTICIPATED RESULTS: Both male and female rats experiencing early life stress exhibited significantly impaired recognition memory (N = 16-20/group). Female rats having undergone stress exhibited decreased social preference compared to normally reared females (N = 11/group). Stressed males showed facilitated eyblink conditioning compared to normally reared males (N = 7-9/group). There were no group differences in rotarod or elevated plus maze performance or CORT levels at PND8 or 70 across rearing groups. At PND70, male rats experiencing early life stress exhibited a significant decrease in 2-arachidonoyl glycerol (2-AG) and arachidonic acid levels in the IP nucleus compared to normally reared males (N = 8-9/group). Compared to normally reared females, those experiencing early life stress exhibited a significant increase in prostaglandin E2 levels in the IP nucleus (N = 6-7/group). DISCUSSION/SIGNIFICANCE OF IMPACT: Early life stress, induced by limited bedding, resulted in sex-specific behavioral and lipid impairments. Results suggest that stress causes long-term alterations in endocannabinoid dynamics in males in the cerebellar IP nucleus and sex-related lipids in female cerebellum. These changes may contribute to observed long-term behavioral aberrations. Moreover, findings suggest these behavioral changes may be the result of negative-feedback dysfunction (as evidenced by decreased endocannabinoids in males) or increased neural inflammation or proliferation (as evidenced by increased prostaglandins in females). Future analysis will quantify mRNA and protein for cannabinoid receptors to better characterize aberrations to this system. Moreover, other neural regions dense with cannabinoid receptors (i.e., PFC, hippocampus) will be investigated. This work provides a basis for understanding stress impacts on the development of cognitive deficits observed in psychotic and anxiety disorders. Specifically, facilitation of eyblink conditioning complements research in humans with anxiety disorders. Broadly, understanding stress-related endocannabinoid dysregulation may provide insights into risks for, and the development of, psychopathology and uncover novel therapeutic targets with high translational power.
Mismatch negativity (MMN) is an event-related potential (ERP) component reflecting auditory predictive coding. Repeated standard tones evoke increasing positivity (‘repetition positivity’; RP), reflecting strengthening of the standard's memory trace and the prediction it will recur. Likewise, deviant tones preceded by more standard repetitions evoke greater negativity (‘deviant negativity’; DN), reflecting stronger prediction error signaling. These memory trace effects are also evident in MMN difference wave. Here, we assess group differences and test-retest reliability of these indices in schizophrenia patients (SZ) and healthy controls (HC).
Electroencephalography was recorded twice, 2 weeks apart, from 43 SZ and 30 HC, during a roving standard paradigm. We examined ERPs to the third, eighth, and 33rd standards (RP), immediately subsequent deviants (DN), and the corresponding MMN. Memory trace effects were assessed by comparing amplitudes associated with the three standard repetition trains.
Compared with controls, SZ showed reduced MMNs and DNs, but normal RPs. Both groups showed memory trace effects for RP, MMN, and DN, with a trend for attenuated DNs in SZ. Intraclass correlations obtained via this paradigm indicated good-to-moderate reliabilities for overall MMN, DN and RP, but moderate to poor reliabilities for components associated with short, intermediate, and long standard trains, and poor reliability of their memory trace effects.
MMN deficits in SZ reflected attenuated prediction error signaling (DN), with relatively intact predictive code formation (RP) and memory trace effects. This roving standard MMN paradigm requires additional development/validation to obtain suitable levels of reliability for use in clinical trials.
Postoperative delirium has been associated with poorer long term survival in Transcatheter aortic valve replacement (TAVR) and Surgival aortic valve replacement (SAVR) patients. However, its effect on hospitalization costs and length of stay in these populations has not been formally assessed.
Using the Medicare Provider Analysis and Review File, we retrospectively analyzed elderly (80 years of age and older) Medicare patients receiving TAVR and SAVR in the United States during the 2015 fiscal year. ICD-9-CM codes were used to identify postoperative delirium diagnoses. The incremental hospital resource consumption, measured as hospital cost and length of stay, was estimated for patients with postoperative delirium during their TAVR or SAVR index hospitalization. Multivariate regression models were used for the adjusted cost estimates controlling for patient demographics, comorbidities, and complications.
A total of 21,088 claims were available for analysis (12,114 TAVR and 8,974 SAVR). The mean age of the TAVR group was older compared to the SAVR group (87 versus 84; p < .001) and TAVR patients presented with a higher comorbidity burden (Charlson Index score 3.0 versus 2.1; p < .0001). TAVR patients experiencing postoperative delirium during the index hospitalization was 1.6 percent compared to 3.6 percent of surgical patients (p < .0001). For the overall cohort, the regression adjusted incremental cost of postoperative delirium was (USD15,592; p < .0001). Patients experiencing delirium also had significantly longer hospital length of stay (4.16 days; p < .0001). When stratified by treatment approach, the adjusted incremental cost was USD13,862 for TAVR (p < .0001) and USD16,656 for SAVR (p < .0001).
While infrequent, postoperative delirium significantly increased hospital cost and length of stay following transcatheter or surgical aortic valve replacement (AVR). Despite a significantly higher comorbidity burden, TAVR was associated with lower postoperative delirium rates compared to SAVR. Moreover, post-TAVR delirium may be associated with less resource consumption than post-SAVR delirium. Future studies should seek to determine whether general anesthesia avoidance in appropriately selected transfemoral TAVR patients can further decrease rates of delirium.
The diagnosis of dementia remains inadequate, even within clinical settings. Data on rates and degree of impairment among inpatients are vital for service planning and the provision of appropriate patient care as Ireland's population ages.
Every patient aged 65 years and over admitted over a two-week period was invited to participate. Those who met inclusion criteria were screened for delirium then underwent cognitive screening. Demographic, functional, and outcome data were obtained from medical records, participants, and family.
Consent to participate was obtained from 68.6% of the eligible population. Data for 143 patients were obtained. Mean age 78.1 years. 27.3% met criteria for dementia and 21% had mild cognitive impairment (MCI). Only 41% of those with dementia and 10% of those with MCI had a previously documented impairment. Between-group analysis showed differences in length of stay (p = 0.003), number of readmissions in 12 months (p = 0.036), and likelihood of returning home (p = 0.039) between the dementia and normal groups. MCI outcomes were similar to the normal group. No difference was seen for one-year mortality. Effects were less pronounced on multivariate analysis but continued to show a significant effect on length of stay even after controlling for demographics, personal and family history, and anxiety and depression screening scores. Patients with dementia remained in hospital 15.3 days longer (p = 0.047). A diagnosis is the single biggest contributing factor to length of stay in our regression model.
Cognitive impairment is pervasive and under-recognized in the acute hospital and impacts negatively on patient outcomes.
To examine variation in antibiotic coverage and detection of resistant pathogens in community-onset pneumonia.
A total of 128 hospitals in the Veterans Affairs health system.
Hospitalizations with a principal diagnosis of pneumonia from 2009 through 2010.
We examined proportions of hospitalizations with empiric antibiotic coverage for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAER) and with initial detection in blood or respiratory cultures. We compared lowest- versus highest-decile hospitals, and we estimated adjusted probabilities (AP) for patient- and hospital-level factors predicting coverage and detection using hierarchical regression modeling.
Among 38,473 hospitalizations, empiric coverage varied widely across hospitals (MRSA lowest vs highest, 8.2% vs 42.0%; PAER lowest vs highest, 13.9% vs 44.4%). Detection rates also varied (MRSA lowest vs highest, 0.5% vs 3.6%; PAER lowest vs highest, 0.6% vs 3.7%). Whereas coverage was greatest among patients with recent hospitalizations (AP for anti-MRSA, 54%; AP for anti-PAER, 59%) and long-term care (AP for anti-MRSA, 60%; AP for anti-PAER, 66%), detection was greatest in patients with a previous history of a positive culture (AP for MRSA, 7.9%; AP for PAER, 11.9%) and in hospitals with a high prevalence of the organism in pneumonia (AP for MRSA, 3.9%; AP for PAER, 3.2%). Low hospital complexity and rural setting were strong negative predictors of coverage but not of detection.
Hospitals demonstrated widespread variation in both coverage and detection of MRSA and PAER, but probability of coverage correlated poorly with probability of detection. Factors associated with empiric coverage (eg, healthcare exposure) were different from those associated with detection (eg, microbiology history). Providing microbiology data during empiric antibiotic decision making could better align coverage to risk for resistant pathogens and could promote more judicious use of broad-spectrum antibiotics.
To determine the source of a healthcare-associated outbreak of Pantoea agglomerans bloodstream infections.
Epidemiologic investigation of the outbreak.
Oncology clinic (clinic A).
Cases were defined as Pantoea isolation from blood or catheter tip cultures of clinic A patients during July 2012–May 2013. Clinic A medical charts and laboratory records were reviewed; infection prevention practices and the facility’s water system were evaluated. Environmental samples were collected for culture. Clinical and environmental P. agglomerans isolates were compared using pulsed-field gel electrophoresis.
Twelve cases were identified; median (range) age was 65 (41–78) years. All patients had malignant tumors and had received infusions at clinic A. Deficiencies in parenteral medication preparation and handling were identified (eg, placing infusates near sinks with potential for splash-back contamination). Facility inspection revealed substantial dead-end water piping and inadequate chlorine residual in tap water from multiple sinks, including the pharmacy clean room sink. P. agglomerans was isolated from composite surface swabs of 7 sinks and an ice machine; the pharmacy clean room sink isolate was indistinguishable by pulsed-field gel electrophoresis from 7 of 9 available patient isolates.
Exposure of locally prepared infusates to a contaminated pharmacy sink caused the outbreak. Improvements in parenteral medication preparation, including moving chemotherapy preparation offsite, along with terminal sink cleaning and water system remediation ended the outbreak. Greater awareness of recommended medication preparation and handling practices as well as further efforts to better define the contribution of contaminated sinks and plumbing deficiencies to healthcare-associated infections are needed.
We sought to conduct a major objective of the CAEP Academic Section, an environmental scan of the academic emergency medicine programs across the 17 Canadian medical schools.
We developed an 84-question questionnaire, which was distributed to academic heads. The responses were validated by phone by the lead author to ensure that the questions were answered completely and consistently. Details of pediatric emergency medicine units were excluded from the scan.
At eight of 17 universities, emergency medicine has full departmental status and at two it has no official academic status. Canadian academic emergency medicine is practiced at 46 major teaching hospitals and 13 specialized pediatric hospitals. Another 69 Canadian hospital EDs regularly take clinical clerks and emergency medicine residents. There are 31 full professors of emergency medicine in Canada. Teaching programs are strong with clerkships offered at 16/17 universities, CCFP(EM) programs at 17/17, and RCPSC residency programs at 14/17. Fourteen sites have at least one physician with a Master’s degree in education. There are 55 clinical researchers with salary support at 13 universities. Sixteen sites have published peer-reviewed papers in the past five years, ranging from four to 235 per site. Annual budgets range from $200,000 to $5,900,000.
This comprehensive review of academic activities in emergency medicine across Canada identifies areas of strengths as well as opportunities for improvement. CAEP and the Academic Section hope we can ultimately improve ED patient care by sharing best academic practices and becoming better teachers, educators, and researchers.
We sought to gather a comprehensive list of funding strategies and opportunities for emergency medicine (EM) centres across Canada, and make recommendations on how to successfully fund all levels of research activity, including research projects, staff salaries, infrastructure, and researcher stipends.
We formed an expert panel consisting of volunteers recognized nationally for their scholarly work in EM. First, we conducted interviews with academic leaders and researchers to obtain a description of their local funding strategies using a standardized open-ended questionnaire. Panelists then identified emerging funding models. Second, we listed funding opportunities and initiatives at the provincial, national, and international levels. Finally, we used an iterative consensus-based approach to derive pragmatic recommendations after incorporating comments and suggestions from participants at an academic symposium.
Our review of funding strategies identified four funding models: 1) investigator dependent model, 2) practice plan, 3) generous benefactor, and 4) mixed funding. Recommendations in this document include approaches for research contributors and producers (seven recommendations), for local academic leaders (five recommendations), and for national organizations, such as the Canadian Association of Emergency Physicians (CAEP) (three recommendations).
Funding for research in EM varies across Canada and is largely insecure. We offer recommendations to help facilitate funding for large and small projects, for salary support, and for local and national leaders to advance EM research. We believe that these recommendations will increase funding for all levels of EM research activity, including research projects, staff salaries, infrastructure, and researcher stipends.
Hemodynamic instability following emergent endotracheal intubation (EETI) is a potentially life-threatening adverse event. The objectives of this systematic literature review were to document the incidence of postintubation hemodynamic instability (PIHI), to determine the definitions for PIHI used in the available literature, and to examine factors associated with PIHI in adult patients who require EETI.
Articles published in Medline (1966–August 2012).
This systematic review included adult, inhospital studies of EETIs. Studies with nonemergent or pediatric patient populations were excluded.
Two authors independently performed data abstraction. Disagreements were resolved by a third party. The methodological quality of included studies was assessed with the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies.
We estimated the pooled prevalence of PIHI across studies using a random effects meta-analysis. Subgroups analyzed included study design, intubation setting, geographic location of the study, physician experience, medications used for sedation, neuromuscular blockade, and definition of PIHI. Eighteen studies were analyzed, with sample sizes from 84 to 2,833 patients. The incidence of PIHI ranged from 5 to 440 cases per 1,000 intubations, with a pooled estimate of 110 cases per 1,000 intubations (95% CI 65–167).
PIHI was found to occur in 110 cases per 1,000 in-hospital, emergent intubations. However, heterogeneity among the included studies limits the reliability of this summary estimate. Further investigation is warranted.
We summarise the proceedings of a workshop on ‘Supernova Remnants, Pulsars and the Interstellar Medium’ which was held at the Special Research Centre for Theoretical Astrophysics at the University of Sydney on 18 and 19 March 1999.
The Australian Square Kilometre Array Pathfinder (ASKAP) will give us an unprecedented opportunity to investigate the transient sky at radio wavelengths. In this paper we present VAST, an ASKAP survey for Variables and Slow Transients. VAST will exploit the wide-field survey capabilities of ASKAP to enable the discovery and investigation of variable and transient phenomena from the local to the cosmological, including flare stars, intermittent pulsars, X-ray binaries, magnetars, extreme scattering events, interstellar scintillation, radio supernovae, and orphan afterglows of gamma-ray bursts. In addition, it will allow us to probe unexplored regions of parameter space where new classes of transient sources may be detected. In this paper we review the known radio transient and variable populations and the current results from blind radio surveys. We outline a comprehensive program based on a multi-tiered survey strategy to characterise the radio transient sky through detection and monitoring of transient and variable sources on the ASKAP imaging timescales of 5 s and greater. We also present an analysis of the expected source populations that we will be able to detect with VAST.
The fabrication of 250 Å thick, undoped, single crystal silicon on insulator by lateral solid phase epitaxial growth from amorphous silicon on oxide patterned (001) silicon substrates is reported. Amorphous silicon was grown by low pressure chemical vapor deposition at 525°C using disilane. Annealing at temperatures between 540 and 570°C is used to accomplish the lateral epitaxial growth. The process makes use of a Si/Si1-xGex/Si stacked structure and selective etching. The thin Si1-xGex etch stop layer (x=0.2) is deposited in the amorphous phase and crystallized simultaneously with the Si layers. The lateral growth distance of the epitaxial region was 2.5 μm from the substrate seed window. This represents a final lateral to vertical aspect ratio of 100:1 for the single crystal silicon over oxide regions after selective etching of the top sacrificial Si layer. The effects of Ge incorporation on the lateral epitaxial growth process are also discussed. The lateral epitaxial growth rate of 20% Ge alloys is enhanced by roughly a factor of three compared to the rate of Si films at an anneal temperature of 555°C. Increased random nucleation rates associated with Ge alloy films are shown to be an important consideration when employing Si1-xGex to enhance lateral growth or as an etch stop layer.
200 keV Co+ ions have been implanted into (100), (110) and (111) single crystal silicon substrates to doses of 2 × 1017 Co+ cm−2 and 5 × 1017 Co+ cm−2. During implantation the substrates were tilted at an angle of 70 to the incident ions and maintained at a temperature of 350°C. The experimental results, after implantation, are in close agreement with those obtained by computer simulations, which allow the single crystal orientation of the target and its position with respect to the incident ions to be specified. 5s RTA treatment at 1100°C was found to give CoSi2 layers of similar crystalline quality and resistivity to those produced by conventional furnace annealing.
X-ray section topography has been used to study the distribution and size of precipitates resulting from heat treatment of MCZ silicon. A low density of precipitates was found, enabling individual precipitate images to be studied. Images have been simulated by numerical solution of Takagi's equations and the magnitude of the strain field deduced by comparison with experiment. Excellent agreement has been found in the details of simulated and experimental images. The effective defect volume increased monotonically with annealing temperature. The effect of surface relaxation and long range curvature on the accuracy of determining the microscopic strain field by matching simulated and experimental images has been investigated.
Various techniques which have been applied to modeling low-energy (<< 1 keV) ion-solid interactions on an atomistic scale are described. In addition to their individual strengths, all such methods also have a number of drawbacks, both fundamental and practical. The range of validity, and the problems encountered external to this range, will be outlined for the different approaches. Finally, examples of molecular dynamics simulations of low-energy ion-solid interactions will be presented.
The flexibility of chemical vapor deposition (CVD) permits the fabrication of a large number of materials in various geometric forms, one of which is the porous cellular structure. CVD fabrication of such a structure begins with the pyrolysis of a resin-impregnated thermosetting foam to obtain a reticulated carbon foam skeleton. The foam ligaments can then be coated with a variety of materials (metals, oxides, nitrides, carbides, borides, silicides, etc.), either singly or as hybrid, layered, alloyed, or graded structures. During this process, 10 to 1000 microns of the desired material(s) are deposited onto the foam ligaments by a variation of CVD known as chemical vapor infiltration (CVI). The thermomechanical properties of the resultant structure are dominated by the properties of the deposit, becoming independent of the carbon properties at very small material loadings. With precise control over the variables available, it is possible to obtain the simultaneous optimization of stiffness, strength, thermal conductivity, overall weight, and environmental resistance. This paper discusses the fabrication and properties of various CVD foam materials investigated to date.
High resolution double axis X-ray diffractometry has been undertaken on InGaAs/AlGaAs strained layer epitaxial systems on (001) GaAs substrates. A clear set of fringes has been identified which arises due to the presence of an imperfect layer at the interface between the GaAs substrate and the undoped GaAs epitaxial buffer layer. The period corresponds to the Pendellosung period for the whole epitaxial layer stack. These fringes have very low contrast and are not present in all specimens studied. Detailed simulations have been undertaken assuming a thin interfacial layer of GaAs with a different lattice parameter to the substrate. The system is equivalent to a Bragg case X-ray interferometer. Fringe amplitude is found to vary linearly with interface layer thickness and increases with mismatch of this layer. A good match between experiment and simulation was obtained for a 1 nm layer mismatched by 3000 ppm. The presence of such a layer, probably GaCxAsl-x has been confirmed by transmission electron microscopy. We show that highly sh'rained layers of this thickness between layers over 1 micron in thickness can lead to splitting of high intensity layer peaks, giving rise to possible misinterpretation of data.