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OBJECTIVES/SPECIFIC AIMS: The objective of this project is to determine whether HRV, collected peri-operatively, is predictive of cognitive decline among older adults who undergo elective surgery/anesthesia. METHODS/STUDY POPULATION: This project is a part of the ongoing INTUIT/PRIME study, which is collecting pre- and post-operative cognitive testing, fMRI imaging, CSF samples, and EEG recordings from 200 older adults (age ≥ 60) undergoing elective non-cardiac/non-neurologic surgery scheduled to last > 2 hours at Duke University Medical Center and Duke Regional Hospital. This project utilizes data from the first 60 INTUIT participants who contributed continuous heart rate data before and during surgery. Participants undergo cognitive testing prior to surgery (baseline) and at 6 weeks after surgery. Our primary dependent variable is the change in the composite score from baseline to 6-weeks. Delirium is assessed in the hospital with the twice daily 3D-CAM tool, so we will report the proportion of individuals with 6-week cognitive decline who exhibited delirium in the days following surgery. Participants’ echocardiogram (ECG) recordings are extracted pre- and intraoperatively from B650/B850 patient monitors with VSCapture software. HRV is defined as the variability between successive R-spikes or inter-beat-intervals on ECG. RESULTS/ANTICIPATED RESULTS: We anticipate that lower intraoperative HRV is associated with worse cognitive decline at 6 weeks after surgery. As secondary objectives, we will determine whether pre-operative HRV or change in HRV (from pre-operative to intra-operative measures) are predictive of cognitive decline after surgery. We expect that in-hospital delirium will be detected in a higher proportion of those with 6-week cognitive decline, compared to those with stable or improved cognition at 6 weeks. DISCUSSION/SIGNIFICANCE OF IMPACT: HRV may address the present need for pre- and intra-operative cognitive risk stratification in the elderly. Physiological indices like HRV have the potential to dramatically change our understanding of CI in older adults undergoing surgery, as they offer an accessible, cost-effective, and non-invasive means whereby clinicians, particularly those unfamiliar with the nuances of geriatric and CI/dementia-related care, can monitor patients and refer those at high-risk of CI after surgery for early intervention.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Accurate assessments of population sizes and trends are fundamental for effective species conservation, particularly for social and long-lived species in which low reproductive rates, aging demographic structure and Allee effects could interact to drive rapid population declines. In the parrots (Order Psittaciformes) these life history characteristics have combined with habitat loss and capture for the pet trade to lead to widespread endangerment, with over 40% of species classified under some level of threat. Here we report the results of a population survey of one such species, the Yellow-naped Amazon, Amazona auropalliata, that is classified as ‘Endangered’ on the IUCN Red List. We conducted a comprehensive survey in June and July of 2016 of 44 night roosts of the populations in contiguous Pacific lowlands of northern Costa Rica and southern Nicaragua and compared numbers in Costa Rica to those found in a similar survey conducted in June 2005. In 2016 we counted 990 birds across 25 sites surveyed in Costa Rica and 692 birds across 19 sites surveyed in Nicaragua for a total population estimate of only 1,682 birds. Comparisons of 13 sites surveyed in both 2005 and 2016 in Costa Rica showed a strong and statistically significant decline in population numbers over the 11-year period. Assessment of group sizes approaching or leaving roosts indicated that less than 25% of groups consisted of three or more birds; there was a significantly higher proportion of these putative family groups observed in Nicaragua than Costa Rica. Taken together, these results are cause for substantial concern for the health of this species in a region that has previously been considered its stronghold, and suggest that stronger conservation action should be undertaken to protect remaining populations from capture for the pet trade and loss of key habitat.
Mental health research funding priorities in high-income countries must balance longer-term investment in identifying neurobiological mechanisms of disease with shorter-term funding of novel prevention and treatment strategies to alleviate the current burden of mental illness. Prioritising one area of science over others risks reduced returns on the entire scientific portfolio.
Porphyrins are attractive compounds for optical applications. We have been investigating the relationship between molecular structure and optical properties of a number of porphyrin compounds. Structural variations explored include insertion of metal ions, extension of conjugation, halogenation and formation of multimers. The characterization of these chromophores includes measurement of UV/Vis, fluorescence and fluorescence lifetimes. Furthermore, we have investigated their nonlinear absorption, refraction, excitation dynamics as well as oxidation/reduction behavior. Based on our observations, clear recommendations can be made for the design of optical limiting chromophores.
We characterize the optical properties of modified meso-alkynyl porphyrins by a number of techniques. Our data show that extending the conjugation and incorporating metal in the center of the ring in these molecules serve the objective of tuning the absorption maximum wavelength. We evaluate the optical limiting performance by determining the effective reversesaturable- absorption (RSA) lifetime and the change in the absorption cross-sections. The ultimate optical limiting performance of these molecules is tested in both picosecond and nanosecond regimes.
To identify risk factors associated with methicillin-resistant Staphylococcus aureus (MRSA) acquisition in long-term care facility (LTCF) residents.
Multicenter, prospective cohort followed over 6 months.
Three Veterans Affairs (VA) LTCFs.
All current and new residents except those with short stay (<2 weeks).
MRSA carriage was assessed by serial nares cultures and classified into 3 groups: persistent (all cultures positive), intermittent (at least 1 but not all cultures positive), and noncarrier (no cultures positive). MRSA acquisition was defined by an initial negative culture followed by more than 2 positive cultures with no subsequent negative cultures. Epidemiologic data were collected to identify risk factors, and MRSA isolates were typed by pulsed-field gel electrophoresis (PFGE).
Among 412 residents at 3 LTCFs, overall MRSA prevalence was 58%, with similar distributions of carriage at all 3 facilities: 20% persistent, 39% intermittent, 41% noncarriers. Of 254 residents with an initial negative swab, 25 (10%) acquired MRSA over the 6 months; rates were similar at all 3 LTCFs, with no clusters evident. Multivariable analysis demonstrated that receipt of systemic antimicrobials during the study was the only significant risk factor for MRSA acquisition (odds ratio, 7.8 [95% confidence interval, 2.1–28.6]; P = .002). MRSA strains from acquisitions were related by PFGE to those from a roommate in 9/25 (36%) cases; 6 of these 9 roommate sources were persistent carriers.
MRSA colonization prevalence was high at 3 separate VA LTCFs. MRSA acquisition was strongly associated with antimicrobial exposure. Roommate sources were often persistent carriers, but transmission from roommates accounted for only approximately one-third of MRSA acquisitions.
Antidepressant prescribing is widespread. Nonetheless, response to antidepressants is variable. If it was possible to predict response to medication and thus tailor treatment accordingly, this would not only improve patient outcomes but may also have economic benefits.
To test the hypothesis that individuals with more severe depression would benefit more from noradrenaline reuptake inhibitors (NARIs) than selective serotonin reuptake inhibitors (SSRIs) compared with individuals with less severe depression.
Individuals recruited from UK primary care who met ICD-10 criteria for a depressive episode and scored 15 or more on the Beck Depression Inventory (BDI) were randomised to either an SSRI (citalopram 20mg daily) or a NARI (reboxetine 4mg twice daily). Randomisation was by means of a remote automated telephone system. The main outcome was depressive symptoms measured by the BDI total score 6 weeks after randomisation. (Trial registration: ISRCTN31345163.)
In total, 601 participants were randomised (citalopram: n = 298, reboxetine: n = 303). Ninety-one per cent were followed up at 6 weeks (citalopram: n = 274, reboxetine: n = 272). There was little evidence to support an interaction between treatment and severity of depression (interaction term: 0.02, 95% CI −0.59 to 0.62, P = 0.96). Adjustment for potential confounders (age, gender, employment status, history of depression, number of life events and social support) did not affect the findings (interaction term: 0.06, 95% CI −0.54 to 0.66, P = 0.85).
Treatment with NARIs does not confer any advantage over SSRI treatment for outcome in those with more severe depressive illness presenting in primary care.
Antidepressants exhibit a variety of pharmacological actions including
inhibition of the serotonin and noradrenaline transporters. We wished to
investigate whether genetic variation could be used to target or
personalise treatment, in a comparison of selective serotonin reuptake
inhibitors (SSRIs) with noradrenaline reuptake inhibitors (NARIs).
To test the hypothesis that patients homozygous for the long (insertion)
polymorphism of the serotonin transporter (5-HTTLPR) have an increased
response to SSRI antidepressants but not to NARI antidepressants.
In an individually randomised, parallel-group controlled trial, people
meeting criteria for a depressive episode who were referred by their
general practitioner were randomised to receive either citalopram (an
SSRI) or reboxetine (an NARI). Randomisation was by means of a remote
automated system accessed by telephone. The main outcome was depressive
symptoms, measured by Beck Depression Inventory (BDI) total score 6 weeks
after randomisation. The trial was registered with the International
Standard Randomised Controlled Trials Number registry
Altogether 298 participants were randomised to receive citalopram and 303
were randomised to reboxetine. At 6 weeks follow-up, complete data were
available for 258 participants taking citalopram and 262 taking
reboxetine. We found no evidence to support an influence of 5-HTTLPR on
outcome following antidepressant treatment. The interaction term for BDI
score at 6 weeks was 0.50 (95% CI −2.04 to 3.03, P =
0.70), which indicated that responses to the SSRI and NARI were similar
irrespective of 5-HTTLPR genotype.
It is unlikely that the 5-HTTLPR polymorphism alone will be clinically
useful in predicting response to antidepressants in people with
Interstitial and vacancy loops in ion-irradiated copper have been studied through the use of x-ray diffuse scattering in the “Asymptotic” scattering region near the (111) reflection. Diffuse scattering measurements were made on copper single crystals irradiated at room temperature with He, O, and Si ions, and the results have been analyzed in terms of size distributions of interstitial and vacancy dislocation loops. The measurements were made in an “off-symmetry” direction (along the Ewald Sphere) using a single angular setting of a linear position sensitive detector. The He ion-irradiation was found to produce mainly interstitial loops while the 0 and Si irradiations produced both vacancy and interstitial loops.
The coercive field, He, in rapidly quenched Nd-Fe-B was found to increase for samples with excess of Nd. In addition, Hc, strongly depends on the Fe/B ratio, increasing from 1.67 T for Fe/B = 1.07 to 2.05 T for Fe/B = 14.6 in Nd30(Fe,B)70. The increase in Hc seems to correlate with an increase of the γ-Nd phase in the sample. The initial magnetization curves of Nd30(Fe,B)70 show that the domain wall pinning plays a more important role as the Fe/B ratio increases. Thus, γ-Nd may play an important role in promoting a pinning mechanism. The excess of Nd in rapidly quenched Nd-Fe-B samples was also found to promote growth of Nd2Fe14B grains elongated in shape.
Directed light fabrication (DLP) is a rapid fabrication process that fuses gas delivered metal powders within a focal zone of a laser beam to produce fully dense, near-net shape, 3-dimensional metal components from a computer generated solid model. This study used iron-based alloys to evaluate the microstructural development in the DLF process. Continuous microstructural features are evident, implying a continuous liquid/solid interface during processing. In addition, solidification cooling rates have been determined based upon secondary dendrite arm spacings in Fe-25wt.%Ni and 316 stainless steel. Cooling rates vary from 101-105 K s-1, and the solidification behavior has been simulated using macroscopic heat transfer analyses.