NEURAL CORRELATES AND PROGRESSION OF SACCADE IMPAIRMENT IN PREMANIFEST AND MANIFEST HUNTINGTON DISEASE

Indiana University-Purdue University Indianapolis (IUPUI)Huntington disease (HD) is an autosomal dominant disorder characterized by progressive decline of motor, cognitive, and behavioral function. Saccades (rapid, gaze-shifting eye movements) are affected before a clinical diagnosis of HD is certain (i.e. during the premanifest period of the disease). Fundamental questions remain regarding the neural substrates of abnormal saccades and the course of premanifest disease. This work addressed these questions using magnetic resonance imaging (MRI) and a longitudinal study of premanifest disease progression. Gray matter atrophy is a characteristic of HD that can be reliably detected during the premanifest period, but it is not known how such changes influence saccadic behavior. We evaluated antisaccades (AS) and memory guided saccades (MG) in premanifest and manifest HD, then tested for associations between impaired saccadic measures and gray matter atrophy in brain regions involved in these saccadic tasks. The results suggest that slowed vertical AS responses indicate cortical and subcortical atrophy and may be a noninvasive marker of atrophic changes in the brain. We also investigated the brain changes that underlie AS impairment using an event-related AS design with functional MRI (fMRI). We found that, in premanifest and manifest HD, blood oxygenation level dependent (BOLD) response was abnormally absent in the pre-supplementary motor area and dorsal anterior cingulate cortex following incorrect AS responses. These results are the first to suggest that abnormalities in an error-related response network underlie early disease-related saccadic changes, and they emphasize the important influence of regions outside the striatum and frontal cortex in disease manifestations. Though saccadic abnormalities have been repeatedly observed cross sectionally, they have not yet been studied longitudinally in premanifest HD. We found different patterns of decline; for some measures the rate of decline increased as individuals approached onset, while for others the rate was constant throughout the premanifest period. These results establish the effectiveness of saccadic measures in tracking premanifest disease progression, and argue for their use in clinical trials. Together, these studies establish the utility of saccade measures as a marker of HD neurodegeneration and suggest that they would be a valuable component of batteries evaluating the efficacy of neuroprotective therapies

Estimation of the Co-prevalence of Age-related macular degeneration and Glaucoma

poster abstractPurpose: Age-related macular degeneration (AMD) and glaucoma are the two most common blinding eye diseases in the U.S. and may be further disabling when concomitant. The purpose of this study is to estimate the past, present and future co-prevalence of AMD and glaucoma by national surveys and population projection data. Methods: We combined the age, race and ethnicity data from the latest 2005 to 2008 National Health and Nutrition Examination Survey (NHANES) and the 2002 and 2008 National Health Interview Survey (NHIS). Participants’ positive answers were defined as a “yes” when asked if they had ever been told by a doctor/health care professional that they had macular degeneration or glaucoma (or high pressure of the eye). The co-prevalence of AMD and glaucoma was determined by dividing the number of individuals who answered “yes” to both questions by the total number of respondents. Mean and age-stratified estimates were obtained for non-Hispanic Whites, Hispanics and non-Hispanic Blacks separately. The 2008 National Population Projection data was used to determine the number of affected individuals presently as well as in 2030 and 2050. Results: Using previous NHANES and NHIS data, the mean co-prevalence of AMD and glaucoma varied among racial/ethnic groups: 0.5% in Whites; 0.3% in Hispanics; and 0.2% in Blacks. Co-prevalence increased with increasing age: for Whites, estimates ranged from 0% in those aged 40-49 years to 2.7% for 80 years and older; this trend was observed among the other groups but was more dramatic in Hispanics (0.1% to 2.9%) than Blacks (0% to 0.3%). Using National Population Projection data for 2015, the estimated current population is 535,270 (83% Whites; 10% Hispanics; 7% Blacks). The number of affected individuals will continue to grow but demonstrate changing demographics: in 2030 to 800,111 (80% Whites; 14% Hispanics; 7% Blacks); and in 2050 to 1,082,731 (71% Whites; 22% Hispanics; 6% Blacks). Conclusions: The mean co-prevalence of AMD and glaucoma is greatest among non-Hispanic Whites and individuals 70 years and older. More than half-a-million Americans, predominantly non-Hispanic Whites, suffer from concomitant eye diseases presently. Growing populations in the coming years will affect an increasing number of Hispanics. This new information suggests that future health care policy decisions would need to adapt to this growing, changing population

Reaction-controlled diffusion: Monte Carlo simulations

We study the coupled two-species non-equilibrium reaction-controlled diffusion model introduced by Trimper et al. [Phys. Rev. E 62, 6071 (2000)] by means of detailed Monte Carlo simulations in one and two dimensions. Particles of type A may independently hop to an adjacent lattice site provided it is occupied by at least one B particle. The B particle species undergoes diffusion-limited reactions. In an active state with nonzero, essentially homogeneous B particle saturation density, the A species displays normal diffusion. In an inactive, absorbing phase with exponentially decaying B density, the A particles become localized. In situations with algebraic decay rho_B(t) ~ t^{-alpha_B}, as occuring either at a non-equilibrium continuous phase transition separating active and absorbing states, or in a power-law inactive phase, the A particles propagate subdiffusively with mean-square displacement ~ t^{1-alpha_A}. We find that within the accuracy of our simulation data, \alpha_A = \alpha_B as predicted by a simple mean-field approach. This remains true even in the presence of strong spatio-temporal fluctuations of the B density. However, in contrast with the mean-field results, our data yield a distinctly non-Gaussian A particle displacement distribution n_A(x,t) that obeys dynamic scaling and looks remarkably similar for the different processes investigated here. Fluctuations of effective diffusion rates cause a marked enhancement of n_A(x,t) at low displacements |x|, indicating a considerable fraction of practically localized A particles, as well as at large traversed distances.Comment: Revtex, 19 pages, 27 eps figures include

Position-dependent effects of locked nucleic acid (LNA) on DNA sequencing and PCR primers

Genomes are becoming heavily annotated with important features. Analysis of these features often employs oligonucleotides that hybridize at defined locations. When the defined location lies in a poor sequence context, traditional design strategies may fail. Locked Nucleic Acid (LNA) can enhance oligonucleotide affinity and specificity. Though LNA has been used in many applications, formal design rules are still being defined. To further this effort we have investigated the effect of LNA on the performance of sequencing and PCR primers in AT-rich regions, where short primers yield poor sequencing reads or PCR yields. LNA was used in three positional patterns: near the 5′ end (LNA-5′), near the 3′ end (LNA-3′) and distributed throughout (LNA-Even). Quantitative measures of sequencing read length (Phred Q30 count) and real-time PCR signal (cycle threshold, C(T)) were characterized using two-way ANOVA. LNA-5′ increased the average Phred Q30 score by 60% and it was never observed to decrease performance. LNA-5′ generated cycle thresholds in quantitative PCR that were comparable to high-yielding conventional primers. In contrast, LNA-3′ and LNA-Even did not improve read lengths or C(T). ANOVA demonstrated the statistical significance of these results and identified significant interaction between the positional design rule and primer sequence

The Adaptive Thermal Comfort Review from the 1920s, the Present, and the Future

The typical method for comfort analysis is the Predicted Mean Vote and Predicted Percentage Dissatisfied (PMV-PPD). However, they present limitations in accommodating the comfort of a disabled and elder group of people, which are the most vulnerable to climate change and energy poverty. The adaptive method can give flexibility and personalisation needed to overcome the problem due to the variability of the people's metabolism, historical and behavioural preferences. Investments to upgrade the indoor environmental quality and building design can then be effectively used and, for the first time, it will be possible to tailor the solutions for these particular groups of people. The adaptive approach uses Artificial Intelligence (AI), where it can introduce the imperfect learning process. Overcoming this, instead of going further for the Explainable AI, the PMV–PPD approach can be used for the learning validation and verification needed for the adaptive setting point and standards

Real-Time Voice Biometric Speaker Verification

Abstract. Automated speaker verification has been an area of increased research in the last few years, with a special interest in metric learning approaches that compute distances between speaker voiceprints. In this paper, three metric learning systems are built and compared in a one-shot speaker verification task using contrastive max-margin loss, triplet loss, and quadruplet loss. For all the models, spectrograms are created from speaker audio. Convolutional Neural Network embedding layers are trained to produce compact voiceprints that allow users to be distinguished using distance calculations. Performances of the three models were similar, but the model with the best EER used triplet loss in this experiment

Plant functional group effects on peat carbon cycling in a boreal rich fen

Dominant plant functional groups (PFGs) found in boreal rich fens include sedges, grasses, horsetails, and cinquefoils (obligate wetland shrubs). Precipitation regime shift and permafrost thaw due to climate change will likely trigger changes in fen plant community structure through shifts in these PFGs, and it is thus crucial to understand how these PFGs will impact carbon cycling and greenhouse gas dynamics to predict and model peatland-climate feedbacks. In this study, we detail the above and belowground effects of these PFGs on aspects of carbon cycling using a mesocosm approach. We hypothesized that PFGs capable of aerating the rhizosphere (sedges, horsetails, and grasses) would oxidize the belowground environment supporting higher redox potentials, a favorable environment for decomposition, and higher CO2:CH4 in pore water and gas efflux measurements than PFGs lacking aerenchyma (cinquefoil, unplanted control). Overall, sedges, horsetail and grasses had an oxidizing effect on rhizosphere pore water chemistry, producing an environment more favorable for methanotrophy during the growing season, as supported by an approximate isotopic enrichment of pore water methane (δ13CH4) by 5‰, and isotopic depletion in pore water carbon dioxide (δ13CO2) by 10‰, relative to cinquefoil treatments. Cinquefoil and unplanted control treatments fostered a reducing environment more favorable for methanogenesis. In addition, cinquefoil appeared to slow decomposition in comparison with the other PFGs. These findings, paired with PFG effects on oxidation–reduction potential and CO2 and CH4 production, point to the ability of rich fen plant communities to moderate biogeochemistry, specifically carbon cycling, in response to changing climatic conditions

Diagnostic use of lung ultrasound compared to chest radiograph for suspected pneumonia in a resource-limited setting

Abstract Background Lung ultrasound is an effective tool for diagnosing pneumonia in developed countries. Diagnostic accuracy in resource-limited countries where pneumonia is the leading cause of death is unknown. The objective of this study was to evaluate the sensitivity of bedside lung ultrasound compared to chest X-ray for pneumonia in adults presenting for emergency care in a low-income country. Methods Patients presenting to the emergency department with suspected pneumonia were evaluated with bedside lung ultrasound, single posterioranterior chest radiograph, and computed tomography (CT). Using CT as the gold standard, the sensitivity of lung ultrasound was compared to chest X-ray for the diagnosis of pneumonia using McNemar’s test for paired samples. Diagnostic characteristics for each test were calculated. Results Of 62 patients included in the study, 44 (71%) were diagnosed with pneumonia by CT. Lung ultrasound demonstrated a sensitivity of 91% compared to chest X-ray which had a sensitivity of 73% (p = 0.01). Specificity of lung ultrasound and chest X-ray were 61 and 50% respectively. Conclusions Bedside lung ultrasound demonstrated better sensitivity than chest X-ray for the diagnosis of pneumonia in Nepal. Trial registration ClinicalTrials.gov, registration number NCT02949141. Registered 31 October 2016

How climate and vegetation influence the fire regime of the Alaskan boreal biome: the Holocene perspective, Mitigation and Adaptation Strategies for Global Change 11

Abstract. We synthesize recent results from lake-sediment studies of Holocene fire-climatevegetation interactions in Alaskan boreal ecosystems. At the millennial time scale, the most robust feature of these records is an increase in fire occurrence with the establishment of boreal forests dominated by Picea mariana: estimated mean fire-return intervals decreased from ≥300 yrs to as low as ∼80 yrs. This fire-vegetation relationship occurred at all sites in interior Alaska with charcoal †-based fire reconstructions, regardless of the specific time of P. mariana arrival during the Holocene. The establishment of P. mariana forests was associated with a regional climatic trend toward cooler/wetter conditions. Because such climatic change should not directly enhance fire occurrence, the increase in fire frequency most likely reflects the influence of highly flammable P. mariana forests, which are more conducive to fire ignition and spread than the preceding vegetation types (tundra, and woodlands/forests dominated by Populus or Picea glauca). Increased lightning associated with altered atmospheric circulation may have also played a role in certain areas where fire frequency increased around 4000 calibrated ‡ years before present (BP) without an apparent increase in the abundance of P. mariana. When viewed together, the paleo-fire records reveal that fire histories differe