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Objectives The spinal cord injury (SCI) patient population is overwhelmingly affected by neuropathic pain (NP), a secondary condition for which therapeutic options are limited and have a low degree of efficacy. The objective of this study was to identify novel deep brain stimulation (DBS) targets that may theoretically benefit those with NP in the SCI patient population. We hypothesize that localized changes in white matter identified in SCI subjects with NP compared to those without NP could be used to develop an evidence-based approach to DBS target identification. Materials and methods To classify localized neurostructural changes associated with NP in the SCI population, we compared white matter fiber density (FD) and cross-section (FC) between SCI subjects with NP (N = 17) and SCI subjects without NP (N = 15) using diffusion-weighted magnetic resonance imaging (MRI). We then identified theoretical target locations for DBS using fiber bundles connected to significantly altered regions of white matter. Finally, we used computational models of DBS to determine if our theoretical target locations could be used to feasibly activate our fiber bundles of interest. Results We identified significant increases in FC in the splenium of the corpus callosum in pain subjects when compared to controls. We then isolated five fiber bundles that were directly connected to the affected region of white matter. Our models were able to predict that our fiber bundles of interest can be feasibly activated with DBS at reasonable stimulation amplitudes and with clinically relevant implantation approaches. Conclusions Altogether, we identified neuroarchitectural changes associated with NP in the SCI cohort and implemented a novel, evidence-driven target selection approach for DBS to guide future research in neuromodulation treatment of NP after SCI.

Functional MRI connectivity has identified neurophysiology relevant to cognition and personality, motivating a search for relationships between brain architecture and emotional health and well-being. Two approaches were used to asses functional connectivity correlates of emotional health and well-being. The first approach used principal component analysis to evaluate resting-state functional magnetic resonance imaging data from the Human Connectome Project 1200 Subjects Data Release. Pairwise functional connectivity measurements were obtained from a 5 mm resolution parcellation of brain gray matter. Principal components were calculated for each individual and for group mean connectivity data and compared to obtain an estimate of typicality of functional connectivity for each component in each subject. Typicality scores were compared to reported emotional health metrics using a general linear model. The second approach calculated functional connectivity between each pair of networks from a 17-resting-state network cortical parcellation. Typicality of connectivity showed significant correlation across the population to emotional metrics corresponding to attitudes of anger and aggression in 3 of 10 principal components. Additionally, functional connectivity between the default and attentional networks was positively correlated with scores of attitudes of anger and aggression. These findings are consistent with a mechanism of impaired effortful control and decreased response inhibition of impulsivity.

Objective Individual differences in aesthetic engagement—the propensity to be moved by art, nature, and beauty—are associated with positive health outcomes, as well as stress resilience. The purpose of the current study was to identify potential neural substrate mechanisms underlying individual differences in aesthetic engagement and reported proneness to aesthetic chill. Methods Data from the Human Connectome Project (HCP) 1200 Subjects Release were utilized. Resting-state fMRI connectivity was extracted for 361 regions in the brain including cortical, subcortical and cerebellar regions for each participant, using participant-specific segmentation and parcellation of subcortical gray matter nuclei and a network-based statistics analytical approach. The Aesthetic Interests subcluster of the Openness to Experience scale (NEO-Five Factor Inventory; NEO-FFI) was used to characterize individual differences in aesthetic engagement and chill. Results Participants reporting higher aesthetic engagement, particularly proneness to aesthetic chill responses, exhibited significantly higher connectivity between the default network and sensory and motor cortices, higher connectivity between the ventral default and salience networks, and decreased connectivity between the cerebellum and somatomotor cortex. Conclusions Current findings suggest that greater integration of the default mode network, involving processing of internal narrative, with neural representations of sensory perception and salience detection may be a mechanism underlying individual differences in aesthetic engagement. Thus, these individual differences may reflect general integration of environmental perception with internal emotional experience, which in turn may facilitate comfort with novelty, self-regulation, and positive adaptation to potentially stressful experiences.

Background Pediatric bipolar disorder (PBD) (occurring prior to 18 years of age) is a developmental brain disorder that is among the most severe and disabling psychiatric conditions affecting youth. Despite increasing evidence that brain connectivity is atypical in adults with bipolar disorder, it is not clear how brain connectivity may be altered in youths with PBD. Methods This cross-sectional resting-state functional magnetic resonance imaging study included 80 participants recruited over 4 years: 32 youths with PBD, currently euthymic (13 males; 15.1 years old), and 48 healthy control (HC) subjects (27 males; 14.5 years old). Functional connectivity between eight major intrinsic connectivity networks, along with connectivity measurements between 333 brain regions, was compared between PBD and HC subjects. Additionally, connectivity differences were evaluated between PBD and HC samples in negatively correlated connections, as defined by 839 subjects of the Human Connectome Project dataset. Results We found increased inter- but not intranetwork functional connectivity in PBD between the default mode and salience networks (p = .0017). Throughout the brain, atypical connections showed failure to develop anticorrelation with age during adolescence in PBD but not HC samples among connections that exhibit negative correlation in adulthood. Conclusions Youths with PBD demonstrate reduced anticorrelation between default mode and salience networks. Further evaluation of the interaction between these networks is needed in development and with other mood states such as depression and mania to clarify if this atypical connectivity is a PBD trait biomarker.

The complexity and heterogeneity of neuroimaging findings in individuals with autism spectrum disorder has suggested that many of the underlying alterations are subtle and involve many brain regions and networks. The ability to account for multivariate brain features and identify neuroimaging measures that can be used to characterize individual variation have thus become increasingly important for interpreting and understanding the neurobiological mechanisms of autism. In the present study, we utilize the Mahalanobis distance, a multidimensional counterpart of the Euclidean distance, as an informative index to characterize individual brain variation and deviation in autism. Longitudinal diffusion tensor imaging data from 149 participants (92 diagnosed with autism spectrum disorder and 57 typically developing controls) between 3.1 and 36.83 years of age were acquired over a roughly 10-year period and used to construct the Mahalanobis distance from regional measures of white matter microstructure. Mahalanobis distances were significantly greater and more variable in the autistic individuals as compared to control participants, demonstrating increased atypicalities and variation in the group of individuals diagnosed with autism spectrum disorder. Distributions of multivariate measures were also found to provide greater discrimination and more sensitive delineation between autistic and typically developing individuals than conventional univariate measures, while also being significantly associated with observed traits of the autism group. These results help substantiate autism as a truly heterogeneous neurodevelopmental disorder, while also suggesting that collectively considering neuroimaging measures from multiple brain regions provides improved insight into the diversity of brain measures in autism that is not observed when considering the same regions separately. Distinguishing multidimensional brain relationships may thus be informative for identifying neuroimaging-based phenotypes, as well as help elucidate underlying neural mechanisms of brain variation in autism spectrum disorders., Highlights • Mahalanobis distance proposed to characterize brain differences from a multivariate set of neuroimaging measures. • Brain variation in autism is examined using Mahalanobis distance is sensitive to underlying microstructure. • Comparison of Mahalanobis distance with traditional univariate measures is examined. • Utility of multivariate brain relations with Mahalanobis distance and prospect of future studies are described.

Whale falls provide a substantial, nutrient-rich resource for opportunistic species in areas of the ocean that may otherwise be largely devoid of food. We report the discovery of a natural whale fall at 1430 m depth in the cold waters of the continental slope off the western Antarctic Peninsula. This is the highest latitude whale fall reported to date. The section of the carcass we observed—the tail fluke—was more complete than any previously reported natural whale fall from the deep sea and in the early stages of decomposition. We estimate the entire cetacean to measure 5 to 8 m in length. The flesh remained almost intact on the carcass but the skin had been removed from the entire section except for the end of the fluke, clearly exposing blubber and soft tissue. The absence of skin indicates rapid and homogenous removal by scavengers. The dominant macrofauna present were crustaceans, including most prominently the lithodid crab Paralomis birsteini, and zoarcid fish typical of the ‘mobile-scavenger’ successional stage. The density of mobile macrofauna was greatest on the carcass and declined to background levels within 100 m, indicating that they were attracted to the whale fall. This whale fall offers an important opportunity to examine the decomposition of a carcass under deep-sea conditions at polar latitudes.

The Fantom bioresorbable scaffold (BRS) is radiopaque with a strut thickness of 125 um. Six and nine months after implantation tissue coverage was almost complete and malapposition was effectively reduced. The current study aimed to evaluate late healing patterns 24 months after implantation

Clinical trials have shown a consistent relationship between years of LDL-C reduction on statin therapy and magnitude of risk reduction. WOSCOPS found that 5 years of statins led to lifelong risk reduction, but little is known about real world persistence over this time frame. The objective of this

Down Syndrome is the most common genetic cause for intellectual disability, yet the pathophysiology of cognitive impairment in Down Syndrome is unknown. We compared fMRI scans of 15 individuals with Down Syndrome to 14 typically developing control subjects while they viewed 50 min of cartoon video clips. There was widespread increased synchrony between brain regions, with only a small subset of strong, distant connections showing underconnectivity in Down Syndrome. Brain regions showing negative correlations were less anticorrelated and were among the most strongly affected connections in the brain. Increased correlation was observed between all of the distributed brain networks studied, with the strongest internetwork correlation in subjects with the lowest performance IQ. A functional parcellation of the brain showed simplified network structure in Down Syndrome organized by local connectivity. Despite increased interregional synchrony, intersubject correlation to the cartoon stimuli was lower in Down Syndrome, indicating that increased synchrony had a temporal pattern that was not in response to environmental stimuli, but idiosyncratic to each Down Syndrome subject. Short-range, increased synchrony was not observed in a comparison sample of 447 autism vs. 517 control subjects from the Autism Brain Imaging Exchange (ABIDE) collection of resting state fMRI data, and increased internetwork synchrony was only observed between the default mode and attentional networks in autism. These findings suggest immature development of connectivity in Down Syndrome with impaired ability to integrate information from distant brain regions into coherent distributed networks., Highlights • Adjacent brain regions are more synchronized in Down Syndrome. • Distant brain regions show less synchronization in Down Syndrome. • Negatively correlated brain regions are less anticorrelated in Down Syndrome. • Down Syndrome subjects show simplified brain network architecture. • Increased brain synchrony does not reflect a response to environmental stimuli.

Acute myocardial infarction (AMI) pts have significantly lower blood levels of vitamin D (VitD) than controls. Whether low VitD levels contribute to causing or exacerbating AMI or are simply a result of the acute AMI response, and how effective preemptive VitD supplementation (VitD-S) is on

Coronary artery calcification (CAC) is pathognomonic for atherosclerosis and has been demonstrated to be associated with elevated risk of cardiovascular (CV) events. Diabetes (DM) is considered a “coronary equivalent” suggesting a risk of a first CV event comparable to that in those who have had

Background: CT coronary artery calcium scores (CAC) are predictive of future major adverse cardiovascular events (MACE). But it is proposed that non-calcified soft plaque may be more vulnerable, and actually increase risk. CT coronary angiography (CTCA), which requires contrast and higher doses of

Summary Background There are wide variations between countries in the use of invasive cardiac catheterisation and revascularisation procedures for patients with acute ischaemic syndromes. We studied the relation between rates of such procedures and rates of cardiovascular death, myocardial infarction, stroke, refractory angina, and major bleeding in a prospective, registry-based study in six countries with widely varying intervention rates. Methods 7987 consecutive patients presenting with unstable angina or suspected myocardial infarction without ST-segment elevation were recruited prospectively from 95 hospitals in six countries and followed up for 6 months. Findings The rates of all procedures were highest in patients in Brazil and the USA, intermediate in Canada and Australia, and lowest in Hungary and Poland. There were no significant differences in rates of cardiovascular death or myocardial infarction among these countries (4·7% overall [range 3·7-5·6] at 7 days; 11% overall [9-12] at 6 months). For the countries with the highest rates of invasive procedures (59%) versus the rest (21%) there was no difference in rate of cardiovascular death or myocardial infarction (adjusted odds ratio 0·88 at 7 days and 1·0 at 6 months). Rates of stroke were higher in Brazil and the USA than in the countries with lower intervention rates (adjusted odds ratio at 7 days 3·0, p=0·012; at 6 months 1·8, p=0·004) but rates of refractory angina at 7 days (0·7, p vs 12·5%, p=0·05) and for refractory angina of 1·25 (19·3% vs 16·1%, p=0·09). Interpretation Higher rates of invasive and revascularisation procedures were associated with lower rates of refractory angina or readmission for unstable angina, no apparent reducton in cardiovascular death or myocardial infarction, but with higher rates of stroke. Randomised trials should assess the relative impact of conservative and more aggressive approaches to invasive cardiac procedures and revascularisations in patients with unstable angina.

Accurate evaluation of biomarkers of acute myocardial injury is important. Both troponin-I and troponin-T are validated markers, but often only one or the other is available on any specific blood analysis platform. It is important to know the performance of each before choosing an institutional

The Fantom fully bioresorbable scaffold (Reva Medical, Inc., San Diego) features a polycarbonate polymer platform with covalently bound iodine for increased radiopacity, has a strut thickness of 125 μm, full degradation within 12-18 months and complete absorption within 36-42 months. Here we report

Growth faltering is common in children with hypoplastic left heart syndrome (HLHS) after the Norwood operation. We previously demonstrated that transplant-free survivors remained small at 3 years of age with mean weight-for-age z-scores (WAZ) and height-for-age z-scores (HAZ) below average. We

HDL particle (HDL-P) concentrations are comprised of particles that vary in size and composition, and potentially, in risk prediction. Inflammation is known to modulate HDL function. Whether increased inflammation alters associations of HDL subclasses with CAD needs further study. Pts (N=2,848) of

Joubert's syndrome is an autosomal-recessive condition characterized by dysgenesis of the cerebellar vermis, hypotonia, developmental delay, a respiratory pattern of alternating tachypnea and apnea, and abnormal eye movements. Radiologic findings include a midline cerebellar cleft in place of the vermis and a characteristic shape of the fourth ventricle. Prenatal hydrocephalus has been proposed as a possible etiology for the cerebellar abnormalities but has not previously been described in association with this syndrome. The authors report a patient with clinical and radiographic features consistent with Joubert's syndrome who presented with congenital hydrocephalus.

Final Model* 0.792 (0.753–0.830) 2 Final minus HDL2 0.787 (0.749–0.826) 20.005 Final minus HDL3 0.787 (0.748–0.825) 20.005 Final minus HDL2,3 0.786 (0.747–0.825) 20.006 Final minus LDL1 0.780 (0.740–0.819) 20.012 Final minus LDL4 0.787 (0.748–0.826) 20.005 Final minus LDL1,4 0.775 (0.736–0.815) 20.017 Final minus HDL2,3 and LDL1,4 0.770 (0.730–0.810) 20.022 Final minus apolipoprotein B/A1 ratio 0.790 (0.751–0.828) 20.002

ReZolve is a novel scaffold incorporating a unique slide & lock expansion technology and a proprietary bioresorbable stent material that is a polycarbonate co-polymer of tyrosine analogs. The aim of this study was to evaluate, for the first time, the safety and performance of the ReZolve sirolimus

Statin therapy is well documented to lower cholesterol and prevent cardiovascular adverse events. However, 10-15% of patients cannot tolerate many statins due to the development of myalgias. Pitavastatin, a newer statin, is minimally affected by the cytochrome P450 system, water soluble so it doesn'

SESSION TYPE: COPD Posters IIPRESENTED ON: Wednesday, October 24, 2012 at 01:30 PM - 02:30 PMPURPOSE: Historically, the red cell distribution width (RDW) was utilized after an anemia diagnosis to determine its etiology. In 2007, we first reported that RDW was a powerful predictor of mortality among cardiovascular patients, which was subsequently replicated in various heart and vascular disease populations. This study evaluated whether the RDW is associated with survival and hospital admission-free survival among patients undergoing pulmonary function testing (PFT).METHODS: Patients (N=2,629) evaluated by PFT between October, 2002, and October, 2011, were tested for RDW levels using the complete blood count (CBC) panel. All-cause mortality was determined using local, state, and national death registries in December, 2011. Admission to one of Intermountain Healthcare's 22 hospitals in Utah was determined by electronic query of a central electronic data warehouse. Cox regression was used to adjust for patient age, sex, body mass index, forced vital capacity, the other CBC components, and all independent variables in the basic metabolic profile.RESULTS: During a mean of 2.8 years of follow-up (max: 9.2 years), 363 patients (6.0%) died and 1,447 (55.0%) experienced a hospital admission following the PFT. Average age was 60.0 years and 54% were female. Mean RDW was significantly higher among decedents (16.3 vs. 15.0, palt;0.001). Modeled as a continuous variable, RDW strongly predicted mortality (adjusted hazard ratio [HR]=1.11 per mg/dL increase, 95% CI=1.07, 1.16; palt;0.001). Survival was 91.7%, 89.3%, 89.1%, 85.4%, and 74.0% in RDW quintiles 1-5 (≤13.3, 13.4-14.1, 14.2-15.0, 15.1-16.6, agt;16.6 mg/dl), respectively. In Cox regression, RDW quintile 5 vs. 1 had HR=2.68 (95% CI=1.80, 3.98; palt;0.001), with a graded association (HR=1.62, 1.30, and 1.47 for quintiles 4, 3, and 2 vs. 1, respectively). For hospital admission, RDW also significantly stratified risk (quintile 5 vs. 1: HR=1.91, 95% CI=1.56, 2.33; palt;0.001) with a graded association (HR=1.38, 1.59, and 1.35 for quintiles 4, 3, and 2 vs. 1).CONCLUSIONS: RDW was a powerful predictor of survival and hospital admission among patients initially evaluated by PFT. This is consistent with the reported role of RDW in risk among other populations and suggests that higher RDW indicates a generally lower level of health. Further study of the role of RDW in pulmonary patient risk is indicated.CLINICAL IMPLICATIONS: Elevated RDW may indicate a need for more intense preventive therapies or diagnostic testing to reduce future risk.DISCLOSURE: Benjamin Horne: Grant monies (from industry related sources): GlaxoSmithKline clinical research supportMatthew Hegewald: Grant monies (from industry related sources): GlaxoSmithKline clinical research supportJoseph Muhlestein: Grant monies (from industry related sources): GlaxoSmithKline clinical research supportElizabeth Huggins: Grant monies (from industry related sources): GlaxoSmithKline clinical research supportHeidi May: Grant monies (from industry related sources): GlaxoSmithKline clinical research supportTami Bair: Grant monies (from industry related sources): GlaxoSmithKline clinical research supportJeffrey Anderson: Grant monies (from industry related sources): GlaxoSmithKline clinical research supportNo Product/Research Disclosure InformationIntermountain Heart Institute, Salt Lake City, UT.

Synopsis: Women often lag behind men in their cardiovascular (CV) disease risk. However, with age and the onset of menopause, a women’s CV risk eventually becomes similar to that of men. This change in risk may, in part, be attributable to a shift in a more atherogenic lipid profile, in particular remnant lipoproteins (VLDL3 + IDL). Therefore, determining lipid parameters that predict risk is essential. Thus, we evaluated standard lipid parameters, apolipoprotein (apo) A1, and the apo A1 remnant ratio: (apo A1/ [VLDL3 + IDL]) for their associations to death (D) or myocardial infarction (MI) among periand post-menopausal women. Purpose: To evaluate the clinical utility of the new apo A1 remnant ratio compare with standard lipid measurements in predicting future D/MI in women older than 50 years undergoing coronary angiography. Methods: Women (n 5 711) older than 50 years of age from the Intermountain Heart Collaborative Study who were undergoing coronary angiography were evaluated. Baseline clinical and angiographic characteristics, lipid levels (determined by hospital’s clinical laboratory), and sublipid particles (determined with the Vertical Auto Profile method) were collected. Lipid and sublipid parameters were evaluated as tertiles (see supplemental material). Cox regression analysis, adjusted by standard CV risk factors, was used to determine associations of lipid and sublipid particles with D/MI at 1 and 3 years (average length of follow-up: 3.9 6 2.1 years). Results: Patients averaged 67.76 9.4 years and 53.6%had underlying severe (.70% stenosis) coronary artery disease.Mean lipid measurements (mg/dL) were high-density lipoprotein: 48.3 6 15.6, low-density lipoprotein: 106.7 6 37.3, nonhigh-density lipoprotein: 136.5 6 41.3, apo A1: 119.7 6 20.3, and apoA1/(VLDL3+IDL): 6.66 3.6. Because triglycerides were non-normally distributed, median level is reported: 133.0mg/dL. Sublipidparticleswere the best predictors of short (1 year) and intermediate (3 year)D/MI risk. These associations persisted evenafter adjustment.The strongest predictor ofD/MI risk at both time-points was the apo A1 remnant ratio: apo A1/ (VLDL3+IDL). Conclusions: The newparameter, the apoA1 remnant ratio, is a strong predictor of short-term and intermediate D/MI risk amongwomenolder than 50years of age. Furthermore, this ratio has a greater predictive ability than traditional lipid parameters and apo A1. This apo A1 remnant ratio represents a potential new measurement of risk and treatment target and should be tested in a larger cohort among this population, periand postmenopausal women, and other populations.