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OBJECTIVES/GOALS: We sought to examine: 1) variability in center acceptance patterns for heart allografts offered to the highest-priority candidates, 2) impact of this acceptance behavior on candidate survival, and 3) post-transplantation outcomes in candidates who accepted first rank offer vs. previously declined offer. METHODS/STUDY POPULATION: In this retrospective cohort study, the US national transplant registry was queried for all match runs of adult candidates listed for isolated heart transplantation between 2007-2017. We examined center acceptance rates for heart allografts offered to the highest-priority candidates and accounted for covariates in multivariable logistic regression. Competing risks analysis was performed to assess the relationship between center acceptance rate and waitlist mortality. Post-transplantation outcomes (patient survival and graft failure) between candidates who accepted their first-rank offers vs those who accepted previously declined offers were compared using Fine-Gray subdistribution hazards model. RESULTS/ANTICIPATED RESULTS: Among 19,703 unique organ offers, 6,302 (32%) were accepted for first-ranked candidates. After adjustment for donor, recipient, and geographic covariates, transplant centers varied markedly in acceptance rates (12%-62%) of offers made to first-ranked candidates. Lowest acceptance rate centers (<25%) associated with highest cumulative incidence of waitlist mortality. For every 10% increase in adjusted center acceptance rate, waitlist mortality risk decreased by 27% (SHR 0.73, 95% CI 0.67-0.80). No significant difference was observed in 5-year adjusted post-Tx survival and graft failure between hearts accepted at the first-rank vs lower-rank positions. DISCUSSION/SIGNIFICANCE OF IMPACT: Wide variability in heart acceptance rates exists among centers, with candidates listed at low acceptance rate centers more likely to die waiting. Similar post-Tx survival suggests previously declined allografts function as well as those accepted at first offer. Center-level decision is a modifiable behavior associated with waitlist mortality.
Mood and anxiety disorders are common in youth and are associated with reduced quality of life and high costs. Access to effective treatment is limited due to long waitlists, high costs and perceived social stigma. Given the high prevalence and treatment barriers, there is a need for brief, inexpensive and effective interventions.
Psychoeducational interventions are inexpensive, easily administered and more accessible than conventional interventions. There is some evidence that these are effective in treating or preventing mental disorders.
To compare knowledge acquired by participants via email or live psychoeducation groups, to measure symptom change and to compare effectiveness of each modality.
Psychoeducation (live or via email) in multifamily groups will be offered. Forty participants in each group will be enrolled. There will be six 40-minute sessions. Primary outcome measures are: change in parental knowledge about the child's disorder and level of expressed emotion in the parent-child relationship. Measures are Understanding of Mood Disorders Questionnaire and Expressed Emotion Adjective Checklist. To measure changes in symptoms the Children's Depression Inventory and Multidimensional Anxiety Scale for Children will be used. Questionnaires will be administered before, after and at 4 months.
Data entered in Excel format. ANOVA used to compare effectiveness of group versus email psychoeducation. Both methods equally effective in delivering psychoeducation.
Ontario has long waitlists for youth with mood and anxiety disorders. Psychoeducation is effective in increasing understanding of illness, improving symptoms and problem-solving skills of the family. Multifamily group versus email psychoeducation will facilitate access.
Simultaneous PET/MR/EEG (Positron Emission Tomography – Magnetic Resonance – Electroencephalography), a new tool for the investigation of neuronal networks in the human brain, is presented here within the framework of the European Union Project TRIMAGE. The trimodal, cost-effective PET/MR/EEG imaging tool makes use of cutting edge technology both in PET and in MR fields. A novel type of magnet (1.5T, non-cryogenic) has been built together with a PET scanner that makes use of the most advanced photodetectors (i.e., SiPM matrices), scintillators matrices (LYSO) and digital electronics. The combined PET/MR/EEG system is dedicated to brain imaging and has an inner diameter of 260 mm and an axial Field-of-View of 160 mm.
It enables the acquisition and assessment of molecular metabolic information with high spatial and temporal resolution in a given brain simultaneously. The dopaminergic system and the glutamatergic system in schizophrenic patients are investigated via PET, the same physiological/pathophysiological conditions with regard to functional connectivity, via fMRI, and its electrophysiological signature via EEG. In addition to basic neuroscience questions addressing neurovascular-metabolic coupling, this new methodology lays the foundation for individual physiological and pathological fingerprints for a wide research field addressing healthy aging, gender effects, plasticity and different psychiatric and neurological diseases.
The preliminary performances of two components of the imaging tool (PET and MR) are discussed. Initial results of the search of possible candidates for suitable schizophrenia biomarkers are also presented as obtained with PET/MR systems available to the collaboration.
There are no definite guidelines regarding the most adequate steroid regimens for acute acoustic trauma.
To elucidate the dose-dependent differing benefits of oral steroids on hearing improvement following acute acoustic trauma.
Twenty-nine patients treated with oral steroids following a diagnosis of unilateral acute acoustic trauma were retrospectively reviewed. Patients were sorted into two groups with an oral steroid regimen. Group 1 received a 14-day course of treatment: 60 mg prednisolone daily for 10 days, tapering off over days 11–14. Group 2 received prednisolone for a total of 10 days: 60 mg for 5 days, tapering down each day for the remainder. Multivariable linear regression analysis was performed to evaluate the factors associated with the hearing gain.
In the multivariable regression (R2 = 0.51, p < 0.001), patients in group 1 showed more significant improvement in the degree of hearing gain compared to group 2 (p = 0.03).
After comparing the differing benefits of oral steroids on hearing improvement by dosage, we recommend a high dose of prednisolone (60 mg per day) for 10 days, tapering over the remaining 4 days, for better hearing recovery following acute acoustic trauma.
OBJECTIVES/SPECIFIC AIMS: The purpose of the study was to describe patient characteristics associated with subsequent development of bowel ischemia. Primary outcomes were survival to discharge, 30-day and 1-year survival in patients with LVAD who subsequently develop bowel ischemia. Secondary outcomes included characteristics of patients who survive to discharge after bowel ischemia and those who do not. These included markers of patient condition prior to surgical/endoscopic intervention such as lactate levels, ICU admission, ventilator dependence, vasopressor and renal replacement requirements, as well as presence of sepsis. Of these, we predicted that lactate levels and white blood cell count would be significantly elevated pre- and post-operatively in patients who do not recover from bowel ischemic event. We used Mann-Whitney U Test to examine lactate levels between the two groups as our sample size was <30 and therefore necessitated the use of non-parametric testing. METHODS/STUDY POPULATION: In this single-center retrospective study, we analyzed all patients who underwent durable, CF-LVAD implantation at Duke University Medical Center (DUMC) between January 2008 and November 2018. Patients were screened using CPT codes for abdominal surgical exploration or ICD codes for intestinal vascular insufficiency. Final cohort was selected with confirmed diagnosis of intestinal ischemia based on surgical exploration or endoscopic intervention. Patient characteristics including pre-LVAD comorbidities, indication for LVAD implant, and clinical picture prior to bowel ischemic event were collected. Specific characteristics related to bowel ischemia were summarized, including diagnostic imaging, time from imaging study to operative intervention, and intraoperative details. Patient outcomes including survival to discharge, 30-day-, and 1-year survival were summarized. Patients were stratified based on survival to discharge status. Continuous variables were reported as median and interquartile range and compared using Mann-Whitney U test. Categorical variables were reported as proportions and compared using Fisher’s exact test as appropriate. RESULTS/ANTICIPATED RESULTS: A total of 754 patients underwent durable, CF-LVAD implant at DUMC, of which 21 subsequently developed intestinal ischemia (incidence 2.8%). The majority were male (81%) and treated as destination therapy (76.2%). Ten patients (50%) survived to discharge (one remains hospitalized). The proportions of patients receiving HeartMate II (60% vs. 50%, p=1.0), HeartMate III (20% vs. 10%, p=1.0), and HeartWare (20% vs. 40%, p=0.6) were not significantly different between patients who survived to discharge and patients who did not. Median time from LVAD implant to diagnosis of bowel ischemia did not vary significantly between the patient groups (11.5 days, IQR 34.75 vs. 16.5 days, IQR 173.8; p=0.40), nor did the median time from diagnosis to surgical intervention (264.5 minutes, IQR 497.8 vs. 323 minutes, IQR 440, p=0.82). In the 48 hours leading to diagnosis and intervention, renal replacement therapy (50% vs. 0%, p=0.033) was more prevalent in patients who did not survive to discharge. Differences in pre- and post-operative lactate levels were not significantly different in patient groups. A similar pattern of diagnostic study preference emerged from both groups, with CT being the most common (76.2%) followed by KUB (42.9%). Upper endoscopy/colonoscopy was performed in 7 patients (33.3%), of which 5 also had operative exploration. A total of 19 patients underwent abdominal exploration (90.5%). Nine had large bowel resection (42.9%) while 14 had small bowel resection (66.7% with average 75cm removed). Overall survival at 1-year was 33%. For those making it to discharge (n=10), one year survival was 60%. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first institutional study to our knowledge to describe intestinal ischemia in patients receiving CF-LVAD therapy. Intestinal ischemia in patients receiving CF-LVAD therapy is associated with high mortality and morbidity. Diagnosis of bowel ischemia should be considered in patients presenting with clinical symptoms of bowel ischemia in addition to requirement of renal replacement therapy. Imaging modalities used were dependent on the clinical situation and were not always necessary prior to intervention. Further investigation is warranted to identify predictors of this morbid complication.
Psychotropic medication use and psychiatric symptoms during pregnancy each are associated with adverse neurodevelopmental outcomes in offspring. Commonly, studies considering medication effects do not adequately assess symptoms, nor evaluate children when the effects are believed to occur, the fetal period. This study examined maternal serotonin reuptake inhibitor and polypharmacy use in relation to serial assessments of five indices of fetal neurobehavior and Bayley Scales of Infant Development at 12 months in N = 161 socioeconomically advantaged, non-Hispanic White women with a shared risk phenotype, diagnosed major depressive disorder. On average fetuses showed the expected development over gestation. In contrast, infant average Bayley psychomotor and mental development scores were low (M = 84.10 and M = 89.92, range of normal limits 85–114) with rates of delay more than 2–3 times what would be expected based on this measure's normative data. Controlling for prenatal and postnatal depressive symptoms, prenatal medication effects on neurobehavioral development were largely undetected in the fetus and infant. Mental health care directed primarily at symptoms may not address the additional psychosocial needs of women parenting infants. Speculatively, prenatal serotonin reuptake inhibitor exposure may act as a plasticity rather than risk factor, potentially enhancing receptivity to a nonoptimal postnatal environment in some mother–infant dyads.
A new approach is proposed to analyze Bremsstrahlung X-rays that are emitted from laser-produced plasmas (LPP) and are measured by a stack type spectrometer. This new method is based on a spectral tomographic reconstruction concept with the variational principle for optimization, without referring to the electron energy distribution of a plasma. This approach is applied to the analysis of some experimental data obtained at a few major laser facilities to demonstrate the applicability of the method. Slope temperatures of X-rays from LPP are determined with a two-temperature model, showing different spectral characteristics of X-rays depending on laser properties used in the experiments.
Almost nothing is known about the potential negative effects of Internet-based psychological treatments for depression. This study aims at investigating deterioration and its moderators within randomized trials on Internet-based guided self-help for adult depression, using an individual patient data meta-analyses (IPDMA) approach.
Studies were identified through systematic searches (PubMed, PsycINFO, EMBASE, Cochrane Library). Deterioration in participants was defined as a significant symptom increase according to the reliable change index (i.e. 7.68 points in the CES-D; 7.63 points in the BDI). Two-step IPDMA procedures, with a random-effects model were used to pool data.
A total of 18 studies (21 comparisons, 2079 participants) contributed data to the analysis. The risk for a reliable deterioration from baseline to post-treatment was significantly lower in the intervention v. control conditions (3.36 v. 7.60; relative risk 0.47, 95% confidence interval 0.29–0.75). Education moderated effects on deterioration, with patients with low education displaying a higher risk for deterioration than patients with higher education. Deterioration rates for patients with low education did not differ statistically significantly between intervention and control groups. The benefit–risk ratio for patients with low education indicated that 9.38 patients achieve a treatment response for each patient experiencing a symptom deterioration.
Internet-based guided self-help is associated with a mean reduced risk for a symptom deterioration compared to controls. Treatment and symptom progress of patients with low education should be closely monitored, as some patients might face an increased risk for symptom deterioration. Future studies should examine predictors of deterioration in patients with low education.
Introduction: Pericarditis is a common disease associated with significant morbidity. In adults with pericarditis, we sought to determine if colchicine, in addition to standard therapies, could reduce the incidence of pericarditis recurrence, shorten the duration of symptoms and minimize adverse effects associated with other therapies. Methods: We followed PRISMA guidelines. We performed an electronic search (February 2015) through MEDLINE, EMBASE, CENTRAL, Web of Science, and Google scholar. Online trial registries were searched and reference lists were handed searched. Our search strategy had no limitations on study design, outcome of interest, hypothesis, language, dates or publication status. Inclusion criteria for selected manuscripts were: RCTs; adults; outpatient therapy; and idiopathic/viral/autoimmune pericarditis etiology. Cohen's unweighted kappa for inter-observer agreement was calculated. Data was extracted using a standardized data collection tool. Following assessment of homogeneity between studies, we performed a meta-analysis using (fixed or random) effect models and report odds ratios (OR) with 95% confidence intervals (CI). We assessed bias using GRADE. Results: We screened 647 titles/abstracts, and selected 34 manuscripts for full review (kappa 0.86, CI 0.76-0.96). 7 manuscripts met all inclusion criteria comprising 1,275 patients. We obtained the following OR with 95% CI: 1) For the overall incidence of recurrence of pericarditis (OR 0.32; CI 0.24-0.42); 2) For recurrent pericarditis at 18-months (OR 0.32; CI 0.23-0.44); 3) For event-free of recurrent pericarditis at 18-months follow-up (OR 3.40; CI 2.46-4.70); 4) For persistent symptoms at 72 hours (OR 0.29; CI 0.21-0.41); and 5) For the overall adverse events rate (OR 1.27; Cl 0.84-1.92). Conclusion: Colchicine reduces the number of pericarditis recurrences and the duration of symptoms in patients with recurrent or acute pericarditis. Unless there are contraindications to its use, colchicine should be prescribed in all cases of uncomplicated pericarditis, along with standard therapy.
Liposomal drug delivery products have been already commercialized in tumor therapeutics, which can realize passive tumor targeting via enhanced permeability and retention (EPR) effect resulting from the leaky tumor vasculature. To control drug release out of the liposomes, thermo-sensitive liposomes (TSLs) have been developed so that an abrupt exposure of highly concentrated drugs to tumor tissues was enabled by locally treated thermal stimuli. As interests upon TSL have increased along with ongoing clinical trials, some types of TSLs with different physical properties in pharmacokinetics and the mechanism of drug release have been formulated. However, there are few protocols established with a desirable heat source to maximize the efficacy of different TSLs as treating tumors. In this study, we examined different protocols for the most effective application of different TSLs to tumor therapy. First, we examined if enhancing the accumulation of TSLs within tumor tissues prior to bursting drugs out of TSLs could lead to increasing anti-tumor efficacy. Second, we compared the efficiency of two different heat sources on the use of TSL, a warm water bath (42°C) and high intensity focused ultrasound (HIFU). Our study suggests that the specified protocol be setup for TSLs with different physical properties to optimally function in tumor therapies.
The streamwise vortices generated by dielectric-barrier-discharge plasma actuators in the laminar boundary layer were investigated using particle image velocimetry to understand the vortex-formation mechanisms. The plasma vortex generator was oriented along the primary flow direction to produce a body force in the spanwise direction. This created a spanwise-directed wall jet which interacted with the oncoming boundary layer to form a coherent streamwise vortex. It was found that the streamwise vortices were formed by the twisting and folding of the spanwise vorticity in the oncoming boundary layer into the outer shear layer of the spanwise wall jet, which added its own vorticity to increase the circulation along the actuator length. This is similar to the delta-shaped, vane-type vortex generator, except that the circulation was enhanced by the addition of the vorticity in the plasma jet. It was also observed that the plasma vortex was formed close to the wall with an enhanced wall-ward entrainment, which created strong downwash above the actuator.
The Ultra-Fast Flash Observatory (UFFO), which will be launched onboard the
Lomonosov spacecraft, contains two crucial instruments: UFFO Burst
Alert & Trigger Telescope (UBAT) for detection and localization of Gamma-Ray Bursts
(GRBs) and the fast-response Slewing Mirror Telescope (SMT) designed for the observation
of the prompt optical/UV counterparts. Here we discuss the in-space calibrations of the
UBAT detector and SMT telescope. After the launch, the observations of the standard X-ray
sources such as pulsar in Crab nebula will provide data for necessary calibrations of
UBAT. Several standard stars will be used for the photometric calibration of SMT. The
celestial X-ray sources, e.g. X-ray binaries with bright optical sources
in their close angular vicinity will serve for the cross-calibration of UBAT and SMT.
The Ultra-Fast Flash Observatory (UFFO) Pathfinder for Gamma-Ray Bursts (GRBs) consists
of two telescopes. The UFFO Burst Alert & Trigger Telescope (UBAT) handles the
detection and localization of GRBs, and the Slewing Mirror Telescope (SMT) conducts the
measurement of the UV/optical afterglow. UBAT is equipped with an X-ray detector, analog
and digital signal readout electronics that detects X-rays from GRBs and determines the
location. SMT is equipped with a stepping motor and the associated electronics to rotate
the slewing mirror targeting the GRBs identified by UBAT. First the slewing mirror points
to a GRB, then SMT obtains the optical image of the GRB using the intensified CCD and its
readout electronics. The UFFO Data Acquisition system (UDAQ) is responsible for the
overall function and operation of the observatory and the communication with the satellite
main processor. In this paper we present the design and implementation of the electronics
of UBAT and SMT as well as the architecture and implementation of UDAQ.
One of the unexplored domains in the study of gamma-ray bursts (GRBs) is the early time
phase of the optical light curve. We have proposed Ultra-Fast Flash Observatory (UFFO) to
address this question through extraordinary opportunities presented by a series of small
space missions. The UFFO is equipped with a fast-response Slewing Mirror Telescope that
uses a rapidly moving mirror or mirror array to redirect the optical beam rather than
slewing the entire spacecraft or telescope to aim the optical instrument at the GRB
position. The UFFO will probe the early optical rise of GRBs with sub-second response, for
the first time, opening a completely new frontier in GRB and transient studies. Its fast
response measurements of the optical emission of dozens of GRB each year will provide
unique probes of the burst mechanism and test the prospect of GRB as a new standard
candle, potentially opening up the z > 10 universe. We describe the current limit in
early photon measurements, the aspects of early photon physics, our soon-to-be-launched
UFFO-pathfinder mission, and our next planned mission, the UFFO-100.
The Slewing Mirror Telescope (SMT) is the UV/optical telescope of UFFO-pathfinder. The
SMT optical system is a Ritchey-Chrétien (RC) telescope of 100 mm diameter pointed by
means of a gimbal-mounted flat mirror in front of the telescope. The RC telescope has a
17 × 17arcmin2 in Field of View and 4.3 arcsec resolution (full width half
maximum of the point spread function) The beam-steering mirror enables the SMT to access a
35 × 35degree region and point and settle within 1 sec. All mirrors were fabricated to
about 0.02 wavelengths RMS in wave front error (WFE) and 84.7% average reflectivity over
200 nm ~ 650 nm. The RC telescope was aligned to 0.05 wavelengths RMS in WFE (test
wavelength 632.8 nm). In this paper, the technical details of the RC telescope and slewing
mirror system assembly, integration, and testing are given shortly, and performance tests
of the full SMT optical system are reported.