Search

A carefully controlled study allowed us to compare the sensitivity of ASL (arterial spin labeling) and BOLD (blood oxygen level dependent) fMRI for detecting the effects of the adenosine A2a antagonist tozadenant in Parkinson disease. The study compared the effect of drug directly or the interaction of the drug with a cognitive task. Only ASL detected the direct effect of tozadenant. BOLD was more sensitive to the cognitive task, which (unlike most drugs) allows on-off comparisons over short periods of time. Neither ASL nor BOLD could detect a cognitive-pharmacological interaction. These results are consistent with the known relative advantages of each fMRI method, and suggest that for drug development, directly imaging pharmacodynamic effects with ASL may have advantages over cognitive-pharmacological interaction BOLD, which has hitherto been the more common approach to pharmacological fMRI.

Africa is the birthplace of anatomically modern humans, and is the geographic origin of human migration across the globe within the last 100,000 years. The history of African populations has consisted of a number of demographic events that have influenced patterns of genetic and phenotypic variation across the continent. With the increasing amount of genomic data and corresponding developments in computational methods, researchers are able to explore long-standing evolutionary questions, expanding our understanding of human history within and outside of Africa. This review will summarize some of the recent findings regarding African demographic history, including the African Diaspora, and will briefly explore their implications for disease susceptibility in populations of African descent.

Background: Deep brain stimulation of the subthalamic nucleus (STN DBS) reduces Parkinson disease (PD) motor symptoms but has unexplained, variable effects on mood., Objective: The study tested the hypothesis that pre-existing mood and/or anxiety disorders or increased symptom severity negatively affects mood response to STN DBS., Methods: Thirty-eight PD participants with bilateral STN DBS and on PD medications were interviewed with Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) and completed Beck Depression Inventory (BDI) and Spielberger State Anxiety Inventory (SSAI) self-reports. Subsequently, during OFF and optimal ON (clinical settings) STN DBS conditions and while off PD medications, motor function was assessed with the United Parkinson Disease Rating Scale (UPDRS, part III), and participants rated their mood with Visual Analogue Scales (VAS), and again completed SSAI. VAS mood variables included anxiety, apathy, valence and emotional arousal., Results: STN DBS improved UPDRS scores and mood. Unexpectedly, PD participants diagnosed with current anxiety or mood disorders experienced greater STN DBS-induced improvement in mood than those diagnosed with remitted disorders or who were deemed as having never met threshold criteria for diagnosis. BDI and SSAI scores did not modulate mood response to STN DBS, indicating that clinical categorical diagnosis better differentiates mood response to STN DBS than self-rated symptom severity. SCID diagnosis, BDI and SSAI scores did not modulate motor response to STN DBS., Conclusions: PD participants diagnosed with current mood or anxiety disorders are more sensitive to STN DBS-induced effects on mood, possibly indicating altered basal ganglia circuitry in this group., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: MiRNA expression profiling is being actively investigated as a clinical biomarker and diagnostic tool to detect multiple cancer types and stages as well as other complex diseases. Initial investigations, however, have not comprehensively taken into account genetic variability affecting miRNA expression and/or function in populations of different ethnic backgrounds. Therefore, more complete surveys of miRNA genetic variability are needed to assess global patterns of miRNA variation within and between diverse human populations and their effect on clinically relevant miRNA genes., Methods: Genetic variation in 1524 miRNA genes was examined using whole genome sequencing (60x coverage) in a panel of 69 unrelated individuals from 14 global populations, including European, Asian and African populations., Results: We identified 33 previously undescribed miRNA variants, and 31 miRNA containing variants that are globally population-differentiated in frequency between African and non-African populations (PD-miRNA). The top 1% of PD-miRNA were significantly enriched for regulation of genes involved in glucose/insulin metabolism and cell division (p < 10(-7)), most significantly the mitosis pathway, which is strongly linked to cancer onset. Overall, we identify 7 PD-miRNAs that are currently implicated as cancer biomarkers or diagnostics: hsa-mir-202, hsa-mir-423, hsa-mir-196a-2, hsa-mir-520h, hsa-mir-647, hsa-mir-943, and hsa-mir-1908. Notably, hsa-mir-202, a potential breast cancer biomarker, was found to show significantly high allele frequency differentiation at SNP rs12355840, which is known to affect miRNA expression levels in vivo and subsequently breast cancer mortality., Conclusion: MiRNA expression profiles represent a promising new category of disease biomarkers. However, population specific genetic variation can affect the prevalence and baseline expression of these miRNAs in diverse populations. Consequently, miRNA genetic and expression level variation among ethnic groups may be contributing in part to health disparities observed in multiple forms of cancer, specifically breast cancer, and will be an essential consideration when assessing the utility of miRNA biomarkers for the clinic.

Objective: We developed a novel method to map behavioral effects of deep brain stimulation (DBS) across a 3-dimensional brain region and to assign statistical significance after stringent type I error correction. This method was applied to behavioral changes in Parkinson disease (PD) induced by subthalamic nucleus (STN) DBS to determine whether these responses depended on anatomical location of DBS., Methods: Fifty-one PD participants with STN DBS were evaluated off medication, with DBS off and during unilateral STN DBS with clinically optimized settings. Dependent variables included DBS-induced changes in Unified Parkinson Disease Rating Scale (UPDRS) subscores, kinematic measures of bradykinesia and rigidity, working memory, response inhibition, mood, anxiety, and akathisia. Weighted t tests at each voxel produced p images showing where DBS most significantly affected each dependent variable based on outcomes of participants with nearby DBS. Finally, a permutation test computed the probability that this p image indicated significantly different responses based on stimulation site., Results: Most motor variables improved with DBS anywhere in the STN region, but several motor, cognitive, and affective responses significantly depended on precise location stimulated, with peak p values in superior STN/zona incerta (quantified bradykinesia), dorsal STN (mood, anxiety), and inferior STN/substantia nigra (UPDRS tremor, working memory)., Interpretation: Our method identified DBS-induced behavioral changes that depended significantly on DBS site. These results do not support complete functional segregation within STN, because movement improved with DBS throughout, and mood improved with dorsal STN DBS. Rather, findings support functional convergence of motor, cognitive, and limbic information in STN., (© 2014 American Neurological Association.)

Bitter taste perception, mediated by receptors encoded by the TAS2R loci, has important roles in human health and nutrition. Prior studies have demonstrated that nonsynonymous variation at site 516 in the coding exon of TAS2R16, a bitter taste receptor gene on chromosome 7, has been subject to positive selection and is strongly correlated with differences in sensitivity to salicin, a bitter anti-inflammatory compound, in human populations. However, a recent study suggested that the derived G-allele at rs702424 in the TAS2R16 promoter has also been the target of recent selection and may have an additional effect on the levels of salicin bitter taste perception. Here, we examined alleles at rs702424 for signatures of selection using Extended Haplotype Homozygosity (EHH) and FST statistics in diverse populations from West Central, Central and East Africa. We also performed a genotype-phenotype analysis of salicin sensitivity in a subset of 135 individuals from East Africa. Based on our data, we did not find evidence for positive selection at rs702424 in African populations, suggesting that nucleotide position 516 is likely the site under selection at TAS2R16. Moreover, we did not detect a significant association between rs702424 alleles and salicin bitter taste recognition, implying that this site does not contribute to salicin phenotypic variance. Overall, this study of African diversity provides further information regarding the genetic architecture and evolutionary history of a biologically-relevant trait in humans.

In humans, the ability to digest lactose, the sugar in milk, declines after weaning because of decreasing levels of the enzyme lactase-phlorizin hydrolase, encoded by LCT. However, some individuals maintain high enzyme amounts and are able to digest lactose into adulthood (i.e., they have the lactase-persistence [LP] trait). It is thought that selection has played a major role in maintaining this genetically determined phenotypic trait in different human populations that practice pastoralism. To identify variants associated with the LP trait and to study its evolutionary history in Africa, we sequenced MCM6 introns 9 and 13 and ~2 kb of the LCT promoter region in 819 individuals from 63 African populations and in 154 non-Africans from nine populations. We also genotyped four microsatellites in an ~198 kb region in a subset of 252 individuals to reconstruct the origin and spread of LP-associated variants in Africa. Additionally, we examined the association between LP and genetic variability at candidate regulatory regions in 513 individuals from eastern Africa. Our analyses confirmed the association between the LP trait and three common variants in intron 13 (C-14010, G-13907, and G-13915). Furthermore, we identified two additional LP-associated SNPs in intron 13 and the promoter region (G-12962 and T-956, respectively). Using neutrality tests based on the allele frequency spectrum and long-range linkage disequilibrium, we detected strong signatures of recent positive selection in eastern African populations and the Fulani from central Africa. In addition, haplotype analysis supported an eastern African origin of the C-14010 LP-associated mutation in southern Africa., (Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

In recent years, the coupling of magnetic insulators (bismuth-doped yttrium iron garnet, Bi-YIG) with platinum has garnered significant interest in spintronics research due to applicability as spin-current-driven thermoelectric coatings. These coatings bridge the gap between spintronics technologies and thermoelectric materials, providing a novel means of transforming waste heat into electricity. However, there remain questions regarding the origins of the spin-Seebeck effect (SSE) as well as claims that observed effects are a manifestation of magnetic proximity effects, which would induce magnetic behavior in platinum. Herewith we provide support that the voltages observed in the Bi-YIG/Pt films are purely SSE voltages. We reaffirm claims that magnon transport theory provides an ample basis for explaining SSE behavior. Finally, we illustrate the advantages of pulsed-laser deposition, as these Bi-YIG films possess large SSE voltages (even in absence of an external magnetic field), as much as twice those of films fabricated via solution-based methods.

Bitter taste perception influences human nutrition and health, and the genetic variation underlying this trait may play a role in disease susceptibility. To better understand the genetic architecture and patterns of phenotypic variability of bitter taste perception, we sequenced a 996 bp region, encompassing the coding exon of TAS2R16, a bitter taste receptor gene, in 595 individuals from 74 African populations and in 94 non-Africans from 11 populations. We also performed genotype-phenotype association analyses of threshold levels of sensitivity to salicin, a bitter anti-inflammatory compound, in 296 individuals from Central and East Africa. In addition, we characterized TAS2R16 mutants in vitro to investigate the effects of polymorphic loci identified at this locus on receptor function. Here, we report striking signatures of positive selection, including significant Fay and Wu's H statistics predominantly in East Africa, indicating strong local adaptation and greater genetic structure among African populations than expected under neutrality. Furthermore, we observed a "star-like" phylogeny for haplotypes with the derived allele at polymorphic site 516 associated with increased bitter taste perception that is consistent with a model of selection for "high-sensitivity" variation. In contrast, haplotypes carrying the "low-sensitivity" ancestral allele at site 516 showed evidence of strong purifying selection. We also demonstrated, for the first time, the functional effect of nonsynonymous variation at site 516 on salicin phenotypic variance in vivo in diverse Africans and showed that most other nonsynonymous substitutions have weak or no effect on cell surface expression in vitro, suggesting that one main polymorphism at TAS2R16 influences salicin recognition. Additionally, we detected geographic differences in levels of bitter taste perception in Africa not previously reported and infer an East African origin for high salicin sensitivity in human populations.

Reduced upper airway muscle activity during sleep is a key contributor to obstructive sleep apnea pathogenesis. Hypoglossal nerve stimulation activates upper airway dilator muscles, including the genioglossus, and has the potential to reduce obstructive sleep apnea severity. The objective of this study was to examine the safety, feasibility and efficacy of a novel hypoglossal nerve stimulation system (HGNS; Apnex Medical, St Paul, MN, USA) in treating obstructive sleep apnea at 12 months following implantation. Thirty-one subjects (35% female, age 52.4 ± 9.4 years) with moderate to severe obstructive sleep apnea and unable to tolerate positive airway pressure underwent surgical implantation and activation of the hypoglossal nerve stimulation system in a prospective single-arm interventional trial. Primary outcomes were changes in obstructive sleep apnea severity (apnea-hypopnea index, from in-laboratory polysomnogram) and sleep-related quality of life [Functional Outcomes of Sleep Questionnaire (FOSQ)]. Hypoglossal nerve stimulation was used on 86 ± 16% of nights for 5.4 ± 1.4 h per night. There was a significant improvement (P < 0.001) from baseline to 12 months in apnea-hypopnea index (45.4 ± 17.5 to 25.3 ± 20.6 events h(-1) ) and Functional Outcomes of Sleep Questionnaire score (14.2 ± 2.0 to 17.0 ± 2.4), as well as other polysomnogram and symptom measures. Outcomes were stable compared with 6 months following implantation. Three serious device-related adverse events occurred: an infection requiring device removal; and two stimulation lead cuff dislodgements requiring replacement. There were no significant adverse events with onset later than 6 months following implantation. Hypoglossal nerve stimulation demonstrated favourable safety, feasibility and efficacy., (© 2013 European Sleep Research Society.)

The α-synuclein-immunoreactive pathology of dementia associated with Parkinson disease (DPD) comprises Lewy bodies (LB), Lewy neurites (LN), and Lewy grains (LG). The densities of LB, LN, LG together with vacuoles, neurons, abnormally enlarged neurons (EN), and glial cell nuclei were measured in fifteen cases of DPD. Densities of LN and LG were up to 19 and 70 times those of LB, respectively, depending on region. Densities were significantly greater in amygdala, entorhinal cortex (EC), and sectors CA2/CA3 of the hippocampus, whereas middle frontal gyrus, sector CA1, and dentate gyrus were least affected. Low densities of vacuoles and EN were recorded in most regions. There were differences in the numerical density of neurons between regions, but no statistical difference between patients and controls. In the cortex, the density of LB and vacuoles was similar in upper and lower laminae, while the densities of LN and LG were greater in upper cortex. The densities of LB, LN, and LG were positively correlated. Principal components analysis suggested that DPD cases were heterogeneous with pathology primarily affecting either hippocampus or cortex. The data suggest in DPD: (1) ratio of LN and LG to LB varies between regions, (2) low densities of vacuoles and EN are present in most brain regions, (3) degeneration occurs across cortical laminae, upper laminae being particularly affected, (4) LB, LN and LG may represent degeneration of the same neurons, and (5) disease heterogeneity may result from variation in anatomical pathway affected by cell-to-cell transfer of α-synuclein.

Objective: To use principal component analyses (PCA) of Pittsburgh compound B (PiB) PET imaging to determine whether the pattern of in vivo β-amyloid (Aβ) in Parkinson disease (PD) with cognitive impairment is similar to the pattern found in symptomatic Alzheimer disease (AD)., Methods: PiB PET scans were obtained from participants with PD with cognitive impairment (n = 53), participants with symptomatic AD (n = 35), and age-matched controls (n = 67). All were assessed using the Clinical Dementia Rating and APOE genotype was determined in 137 participants. PCA was used to (1) determine the PiB binding pattern in AD, (2) determine a possible unique PD pattern, and (3) directly compare the PiB binding patterns in PD and AD groups., Results: The first 2 principal components (PC1 and PC2) significantly separated the AD and control participants (p < 0.001). Participants with PD with cognitive impairment also were significantly different from participants with symptomatic AD on both components (p < 0.001). However, there was no difference between PD and controls on either component. Even those participants with PD with elevated mean cortical binding potentials were significantly different from participants with AD on both components., Conclusion: Using PCA, we demonstrated that participants with PD with cognitive impairment do not exhibit the same PiB binding pattern as participants with AD. These data suggest that Aβ deposition may play a different pathophysiologic role in the cognitive impairment of PD compared to that in AD.

Background. Normally one habituates rapidly to steady, faint sensations. People with sensory hypersensitivity (SH), by contrast, continue to attend to such stimuli and find them noxious. SH is common in Tourette syndrome (TS) and autism, and methods to quantify SH may lead to better understanding of these disorders. In an attempt to objectively quantify SH severity, the authors tested whether a choice reaction time (CRT) task was a sensitive enough measure to detect significant distraction from a steady tactile stimulus, and to detect significantly greater distraction in subjects with more severe SH. Methods. Nineteen ambulatory adult volunteers with varying scores on the Adult Sensory Questionnaire (ASQ), a clinical measure of SH, completed a CRT task in the alternating presence and absence of tactile stimulation. Results. Tactile stimulation interfered with attention (i.e., produced longer reaction times), and this effect was significantly greater in participants with more SH (higher ASQ scores). Accuracy on the CRT was high in blocks with and without stimulation. Habituation within stimulation blocks was not detected. Conclusion. This approach can detect distraction from a cognitive task by a steady, faint tactile stimulus that does not degrade response accuracy. The method was also sensitive to the hypothesized enhancement of this effect by SH. These results support the potential utility of this approach to quantifying SH, and suggest possible refinements for future studies.

Background: The obstetric arena has been typically ignored in the race to determine hospital quality measures due primarily to the fact that a large majority of patients do not have Medicare federal insurance, which has been the focus of hospital measures of quality. With "normal vaginal delivery" being the number one hospital discharge diagnosis and cesarean sections rates varying greatly between hospitals, national organizations are taking greater interest in determining differences in quality., Methods: Sutter Medical Center, Sacramento (California) chartered a multidisciplinary Perinatal Data Committee to improve and simplify data capture for six obstetric quality measures., Results: All six quality measures showed significantly improved trends from 2010 through 2012, with elective delivery < 39 weeks decreasing (15.3% to 2.3%, p < .001), nulliparous term singleton vertex cesarean (NTSV) delivery rate decreasing (31.3% to 24.7%, p < .001), episiotomy rates decreasing (4.7% to 2.3%, p < .001), antenatal steroid documentation increasing (80.0% to 100%, p <.01), exclusive breastfeeding at hospital discharge increasing (57.9% to 69.9%, p <.001), and deep vein prophylaxis at cesarean increasing (95.4% to 98.2%,p < .001)., Conclusion: That performance on all six quality measures improved suggests that the improvement approach was effective and perhaps reproducible in other clinical situations to improve hospital quality outcomes. A key contributor to success was that the dashboard of results was shared with the department's physicians and the hospital administration on a monthly basis. Reinforcement of good results helped keep the project front and center with the hospital, particularly more recently, given that data reporting for four of the six measures is soon to be required.

In the following point-counterpoint article, internationally-acclaimed myopia researchers were challenged to defend the two opposing sides of the topic defined by the title; their contributions, which appear in the order Point followed by Counterpoint, were peer-reviewed by both the editorial team and an external reviewer. Independently of the invited authors, the named member of the editorial team provided an Introduction and Summary, both of which were reviewed by the other members of the editorial team. By their nature, views expressed in each section of the Point-Counterpoint article are those of the author concerned and may not reflect the views of all of the authors., (Ophthalmic & Physiological Optics © 2013 The College of Optometrists.)

Objectives: The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on gait and balance vary and the underlying mechanisms remain unclear. DBS location may alter motor benefit due to anatomical heterogeneity in STN. The purposes of this study were to (1) compare the effects of DBS of dorsal (D-STN) versus ventral (V-STN) regions on gait, balance and regional cerebral blood flow (rCBF) and (2) examine the relationships between changes in rCBF and changes in gait and balance induced by D-STN or V-STN DBS., Methods: We used a validated atlas registration to locate and stimulate through electrode contacts in D-STN and V-STN regions of 37 people with Parkinson's disease. In a within-subjects, double-blind and counterbalanced design controlled for DBS settings, we measured PET rCBF responses in a priori regions of interest and quantified gait and balance during DBS Off, unilateral D-STN DBS and unilateral V-STN DBS., Results: DBS of either site increased stride length without producing significant group-level changes in gait velocity, cadence or balance. Both sites increased rCBF in subcortical regions and produced variable changes in cortical and cerebellar regions. DBS-induced changes in gait velocity are related to premotor cortex rCBF changes during V-STN DBS (r=-0.40, p=0.03) and to rCBF changes in the cerebellum anterior lobe during D-STN DBS (r=-0.43, p=0.02)., Conclusions: DBS-induced changes in gait corresponded to rCBF responses in selected cortical and cerebellar regions. These relationships differed during D-STN versus V-STN DBS, suggesting DBS acts through distinct neuronal pathways dependent on DBS location., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson's disease (PD) improves motor functioning but has variable effects on mood. Little is known about the relationship between electrode contact location and mood response. The authors identified the anatomical location of electrode contacts and measured mood response to stimulation with the Visual Analog Scale in 24 STN DBS PD patients. Participants reported greater positive mood and decreased anxiety and apathy with bilateral and unilateral stimulation. Left DBS improved mood more than right DBS. Right DBS-induced increase in positive mood was related to more medial and dorsal contact locations. These results highlight the functional heterogeneity of the STN.

Objective: To determine the relative contributions of individual pathologic protein deposits associated with dementia in patients with Parkinson disease (PD)., Design: Autopsied patients were analyzed from February 24, 2005, through July 25, 2010, to determine the distribution and severity of individual pathologic protein deposits (α-synuclein, Aβ, and tau) using routine protocols for histologic and immunohistochemical analysis and established neuropathologic staging criteria. Clinical data were extracted from an electronic medical record system used for all patients with PD., Patients: Thirty-two consecutive autopsied patients treated at the Washington University Movement Disorders Center who had neuropathologic confirmation of PD and a history of dementia, regardless of the timing of the onset of dementia with respect to motor symptoms., Results: Three pathologic subgroups of dementia associated with PD were identified: (1) predominant synucleinopathy (Braak Lewy body stages 5-6) (12 [38%]), (2) predominant synucleinopathy with Aβ deposition (Braak amyloid stages B-C) but minimal or no cortical tau deposition (19 [59%]), and (3) synucleinopathy and Aβ deposition with at least moderate neocortical tauopathy (Braak tau stages 5-6; 1 [3%]). Kaplan-Meier and Cox regression analyses revealed that patients with synucleinopathy plus Aβ deposition had significantly shorter survival (years from PD onset until death and years from dementia onset until death) than patients with synucleinopathy only., Conclusions: Dementia associated with PD has 2 major pathologic subgroups: neocortical synucleinopathy and neocortical synucleinopathy with Aβ deposition. Alzheimer disease with neocortical Aβ and tau deposition does not commonly cause dementia with PD. Furthermore, accumulation of Aβ is associated with lower survival rates in PD patients with dementia. Additional studies are needed to prospectively determine the association between α-synuclein and Aβ accumulation and the role of Aβ in the development and progression of cognitive impairment in PD.

Purpose: To measure the diurnal variation of spherical equivalent refractive error (mean ocular refraction or MOR) and to investigate factors contributing to it in chick, an important animal myopia model., Methods: Nine chicks developed naturally on a 14-hour light/10-hour dark cycle. Optical axial length (OAL) and Hartmann-Shack wavefront error (HSWE) measurements, including pupil size, were taken starting on day 7, at eight times during the following 32 hours. MOR was calculated for a constant pupil size from HSWE measurements., Results: MOR, OAL, and pupil size showed significant diurnal variation (P < 0.0001). Most eyes showed significant sinusoidal variations in MOR and in pupil size with periods close to 24 hours. On average, MOR oscillated ±0.84 diopters. OAL varied with a period not different from 12 hours. Diurnally varying MOR and OAL were correlated (P = 0.0003, R² = 0.62). However, as previously reported, the variation in OAL did not account for the variation in MOR. From these results, we derived the diurnal variation in ocular power necessary to give the measured MOR variation., Conclusions: We confirmed a diurnal variation in OAL and found diurnal variations in pupil size and MOR. Although changes in OAL explain the MOR previously observed in response to lenses and diffusers, they do not completely account for the observed diurnal variation of MOR nor for the reduction in hyperopia during normal development. We infer that the diurnal variation in MOR and normal emmetropization both result from small differences in the relative changes of OAL and ocular power.

Apathy, primarily defined as a lack of motivation, commonly occurs in people with Parkinson disease (PD). Although dysfunction of basal ganglia pathways may contribute to apathy, the role of dopamine remains largely unknown. We investigated the role of dopaminergic pathways in the manifestation of apathetic behaviors by measuring the effects of the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on monkeys' willingness to attempt goal directed behaviors, distinct from their ability to perform tasks. Fifteen macaques received variable doses of MPTP, had PET scans with [(11)C]-dihydrotetrabenazine (DTBZ), [(11)C]-2β-3β-4-fluorophenyltropane (CFT), and [(18)F]-fluorodopa (FD) and performed tasks to assess apathetic behaviors and motor impairment. At 8 weeks post-MPTP, primates were euthanized and stereological cell counts and dopamine measurements were done. Apathy scores were compared to motor scores, in vitro and in vivo dopaminergic measures. Apathy scores increased following MPTP and correlated with DTBZ (r(S) = -0.85), CFT (r(S) = -0.87), and FD (r(S) = -0.85) specific uptake in nucleus accumbens (NAcc,) and dopaminergic cell counts in ventral tegmental area (VTA, r(S) = -0.80). Dopaminergic cell loss in VTA provided significant predictive power for apathy scores after controlling for the influence of cell loss in SN. Additionally, forward step-wise regression analyses indicated that neuropathological changes in the VTA-NAcc pathway predict apathetic behavior better than motor impairment or neuropathological changes in the nigrostriatal network. Our findings suggest that dopaminergic dysfunction within the VTA-NAcc pathway plays a role in the manifestation of apathetic behaviors in MPTP-lesioned primates. Similar changes in people with PD may contribute to apathy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Although human bitter taste perception is hypothesized to be a dietary adaptation, little is known about genetic signatures of selection and patterns of bitter taste perception variability in ethnically diverse populations with different diets, particularly from Africa. To better understand the genetic basis and evolutionary history of bitter taste sensitivity, we sequenced a 2,975 bp region encompassing TAS2R38, a bitter taste receptor gene, in 611 Africans from 57 populations in West Central and East Africa with diverse subsistence patterns, as well as in a comparative sample of 132 non-Africans. We also examined the association between genetic variability at this locus and threshold levels of phenylthiocarbamide (PTC) bitterness in 463 Africans from the above populations to determine how variation influences bitter taste perception. Here, we report striking patterns of variation at TAS2R38, including a significant excess of novel rare nonsynonymous polymorphisms that recently arose only in Africa, high frequencies of haplotypes in Africa associated with intermediate bitter taste sensitivity, a remarkably similar frequency of common haplotypes across genetically and culturally distinct Africans, and an ancient coalescence time of common variation in global populations. Additionally, several of the rare nonsynonymous substitutions significantly modified levels of PTC bitter taste sensitivity in diverse Africans. While ancient balancing selection likely maintained common haplotype variation across global populations, we suggest that recent selection pressures may have also resulted in the unusually high level of rare nonsynonymous variants in Africa, implying a complex model of selection at the TAS2R38 locus in African populations. Furthermore, the distribution of common haplotypes in Africa is not correlated with diet, raising the possibility that common variation may be under selection due to their role in nondietary biological processes. In addition, our data indicate that novel rare mutations contribute to the phenotypic variance of PTC sensitivity, illustrating the influence of rare variation on a common trait, as well as the relatively recent evolution of functionally diverse alleles at this locus.

Background: Reduced upper airway muscle activity during sleep is fundamental to obstructive sleep apnea (OSA) pathogenesis. Hypoglossal nerve stimulation (HGNS) counteracts this problem, with potential to reduce OSA severity., Study Objectives: To examine safety and efficacy of a novel HGNS system (HGNS, Apnex Medical, Inc.) in treating OSA., Participants: Twenty-one patients, 67% male, age (mean ± SD) 53.6 ± 9.2 years, with moderate to severe OSA and unable to tolerate continuous positive airway pressure (CPAP)., Design: Each participant underwent surgical implantation of the HGNS system in a prospective single-arm interventional trial. OSA severity was defined by apnea-hypopnea index (AHI) during in-laboratory polysomnography (PSG) at baseline and 3 and 6 months post-implant. Therapy compliance was assessed by nightly hours of use. Symptoms were assessed using the Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Calgary Sleep Apnea Quality of Life Index (SAQLI), and the Beck Depression Inventory (BDI)., Results: HGNS was used on 89% ± 15% of nights (n = 21). On these nights, it was used for 5.8 ± 1.6 h per night. Nineteen of 21 participants had baseline and 6-month PSGs. There was a significant improvement (all P < 0.05) from baseline to 6 months in: AHI (43.1 ± 17.5 to 19.5 ± 16.7), ESS (12.1 ± 4.7 to 8.1 ± 4.4), FOSQ (14.4 ± 2.0 to 16.7 ± 2.2), SAQLI (3.2 ± 1.0 to 4.9 ± 1.3), and BDI (15.8 ± 9.0 to 9.7 ± 7.6). Two serious device-related adverse events occurred: an infection requiring device removal and a stimulation lead cuff dislodgement requiring replacement., Conclusions: HGNS demonstrated favorable safety, efficacy, and compliance. Participants experienced a significant decrease in OSA severity and OSA-associated symptoms., Clinical Trial Information: NAME: Australian Clinical Study of the Apnex Medical HGNS System to Treat Obstructive Sleep Apnea., Registration Number: NCT01186926. URL: http://clinicaltrials.gov/ct2/show/NCT01186926.

Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor function, including gait and stability, in people with Parkinson's disease (PD) but differences in DBS contact locations within the STN may contribute to variability in the degree of improvement. Based on anatomical connectivity, dorsal STN may be preferentially involved in motor function and ventral STN in cognitive function., Methods: To determine whether dorsal DBS affects gait and balance more than ventral DBS, a double blind evaluation of 23 PD patients with bilateral STN DBS was conducted. Each participant underwent gait analysis and balance testing off Parkinson's medication under three DBS conditions (unilateral DBS in the dorsal STN region, unilateral DBS in the ventral STN region and both stimulators off) on 1 day., Results: Improvements were seen in Unified Parkinson's Disease Rating Scale (UPDRS)-III scores and velocity in walking trials as fast as possible (Fast gait) and preferred pace (Pref gait), as well as stride length for Fast and Pref gait, with dorsal and ventral stimulation compared with the off condition (post hoc tests, p<0.05). However, there were no differences with dorsal compared to ventral stimulation. Balance, assessed using the multi-item mini-Balance Evaluation Systems Test (mini-BESTest), was similar across conditions., Conclusions: Absence of differences in gait and balance between the dorsal and ventral conditions suggests motor connections involved in gait and balance may be more diffusely distributed in STN than previously thought, as opposed to neural connections involved in cognitive processes, such as response inhibition, which are more affected by ventral stimulation.

Background. Brain regions subserving emotion have mostly been studied using functional magnetic resonance imaging (fMRI) during emotion provocation procedures in healthy participants. Objective. To identify neuroanatomical regions associated with spontaneous changes in emotional state over time. Methods. Self-rated emotional valence and arousal scores, and regional cerebral blood flow (rCBF) measured by perfusion MRI, were measured 4 or 8 times spanning at least 2 weeks in each of 21 subjects with Parkinson's disease (PD). A random-effects SPM analysis, corrected for multiple comparisons, identified significant clusters of contiguous voxels in which rCBF varied with valence or arousal. Results. Emotional valence correlated positively with rCBF in several brain regions, including medial globus pallidus, orbital prefrontal cortex (PFC), and white matter near putamen, thalamus, insula, and medial PFC. Valence correlated negatively with rCBF in striatum, subgenual cingulate cortex, ventrolateral PFC, and precuneus-posterior cingulate cortex (PCC). Arousal correlated positively with rCBF in clusters including claustrum-thalamus-ventral striatum and inferior parietal lobule and correlated negatively in clusters including posterior insula-mediodorsal thalamus and midbrain. Conclusion. This study demonstrates that the temporal stability of perfusion MRI allows within-subject investigations of spontaneous fluctuations in mental state, such as mood, over relatively long-time intervals.

Adenosine A(2a) receptor antagonists reduce symptom severity in Parkinson disease (PD) and animal models. Rodent studies support the hypothesis that A(2a) antagonists produce this benefit by reducing the inhibitory output of the basal ganglia indirect pathway. One way to test this hypothesis in humans is to quantify regional pharmacodynamic responses with cerebral blood flow (CBF) imaging. That approach has also been proposed as a tool to accelerate pharmaceutical dose finding, but has not yet been applied in humans to drugs in development. We successfully addressed both these aims with a perfusion magnetic resonance imaging (MRI) study of the novel adenosine A(2a) antagonist SYN115. During a randomized, double-blind, placebo-controlled, crossover study in 21 PD patients on levodopa but no agonists, we acquired pulsed arterial spin labeling MRI at the end of each treatment period. SYN115 produced a highly significant decrease in thalamic CBF, consistent with reduced pallidothalamic inhibition via the indirect pathway. Similar decreases occurred in cortical regions whose activity decreases with increased alertness and externally focused attention, consistent with decreased self-reported sleepiness on SYN115. Remarkably, we also derived quantitative pharmacodynamic parameters from the CBF responses to SYN115. These results suggested that the doses tested were on the low end of the effective dose range, consistent with clinical data reported separately. We conclude that (1) SYN115 enters the brain and exerts dose-dependent regional effects, (2) the most prominent of these effects is consistent with deactivation of the indirect pathway as predicted by preclinical studies; and (3) perfusion MRI can provide rapid, quantitative, clinically relevant dose-finding information for pharmaceutical development.

Clinicopathologic studies of Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB) commonly reveal abnormal β-amyloid deposition in addition to diffuse Lewy bodies (α-synuclein aggregates), but the relationship among these neuropathologic features and the development of dementia in these disorders remains uncertain. The purpose of this study was to determine whether amyloid-β deposition detected by PET imaging with Pittsburgh Compound B (PIB) distinguishes clinical subtypes of Lewy body-associated disorders. Nine healthy controls, 8 PD with no cognitive impairment, 9 PD with mild cognitive impairment, 6 DLB, and 15 PDD patients underwent [(11)C]-PIB positron emission tomography imaging, clinical examination, and cognitive testing. The binding potential (BP) of PIB for predefined regions and the mean cortical BP (MCBP) were calculated for each participant. Annual longitudinal follow-up and postmortem examinations were performed on a subset of participants. Regional PIB BPs and the proportion of individuals with abnormally elevated MCBP were not significantly different across participant groups. Elevated PIB binding was associated with worse global cognitive impairment in participants with Lewy body disorders but was not associated with any other clinical or neuropsychological features, including earlier onset or faster rate of progression of cognitive impairment. These results suggest that the presence of fibrillar amyloid-β does not distinguish between clinical subtypes of Lewy body-associated disorders, although larger numbers are needed to more definitively rule out this association. Amyloid-β may modify the severity of global cognitive impairment in individuals with Lewy body-associated dementia., (© 2010 Movement Disorder Society.)

Five studies examined the stigmatization of materialism. Participants expressed negative stereotypes of materialistic people, considering them to be more selfish and self-centered than experiential people (Study 1). Participants also viewed materialistic pursuits as more extrinsically motivated than experiential pursuits (Study 2). These stereotypes led respondents from varied demographic backgrounds to form less favorable impressions of individuals who were associated with prototypically materialistic versus experiential purchases, a result that was statistically mediated by impressions that materialistic purchases were more extrinsically motivated (Study 3). These differential impressions are primarily attributable to the denigration of materialistic people rather than the admiration of experiential people (Study 4). The stigmatization of materialism led participants to like less and enjoy interacting less with their conversation partners when discussing materialistic rather than experiential purchases (Study 5). The authors discuss these findings' implications for self-perception, accurate social perception, and well-being.

Africa is the birthplace of modern humans, and is the source of the geographic expansion of ancestral populations into other regions of the world. Indigenous Africans are characterized by high levels of genetic diversity within and between populations. The pattern of genetic variation in these populations has been shaped by demographic events occurring over the last 200,000 years. The dramatic variation in climate, diet, and exposure to infectious disease across the continent has also resulted in novel genetic and phenotypic adaptations in extant Africans. This review summarizes some recent advances in our understanding of the demographic history and selective pressures that have influenced levels and patterns of diversity in African populations., (Copyright 2010 Elsevier Ltd. All rights reserved.)

We consider the nature and utility of marginal decompression sickness (DCS) events in fitting probabilistic decompression models to experimental dive trial data. Previous works have assigned various fractional weights to marginal DCS events, so that they contributed to probabilistic model parameter optimization, but less so than did full DCS events. Inclusion of fractional weight for marginal DCS events resulted in more conservative model predictions. We explore whether marginal DCS events are correlated with exposure to decompression or are randomly occurring events. Three null models are developed and compared with a known decompression model that is tuned on dive trial data containing only marginal DCS and non-DCS events. We further investigate the technique by which marginal DCS events were previously included in parameter optimization, explore the effects of fractional weighting of marginal DCS events on model optimization, and explore the rigor of combining data containing full and marginal DCS events for probabilistic DCS model optimization. We find that although marginal DCS events are related to exposure to decompression, empirical dive data containing marginal and full DCS events cannot be combined under a single DCS model. Furthermore, we find analytically that the optimal weight for a marginal DCS event is 0. Thus marginal DCS should be counted as no-DCS events when probabilistic DCS models are optimized with binomial likelihood functions. Specifically, our study finds that inclusion of marginal DCS events in model optimization to make the dive profiles more conservative is counterproductive and worsens the model's fit to the full DCS data.

A simplified procedure based on Mueller-matrix polarimetry has recently been reported as a method of retinal image improvement in a confocal ophthalmoscope [J. M. Bueno et al., J. Opt. Soc. Am. A 24, 1337 (2007)]. Here, we have applied the technique to imaging static samples providing well-defined reflection properties. The method uses a generator of polarization states in the illumination pathway of a confocal scanning laser system. From the calculated four elements of the Mueller matrix of any sample and instrument combination, the best images defined by different metrics were constructed. For samples with specular, diffuse and mixed reflections, the best-constructed images showed an enhancement in both objective and subjective image quality compared to the original images and those obtained from frame averaging. This technique could improve microscopic imaging in many diverse fields, particularly in biomedical imaging.

In the simplest model of eye growth, the ocular optics uniformly scale upwards, as do monochromatic higher-order aberrations (HOA) and linear blur on the retina. However, measured HOA remain constant or decrease with growth in some species. A new model, which holds HOA and the associated linear blur on the retina constant, was used to predict changes in HOA and resulting image quality on the retina during growth, in each of chick, monkey, and human. Models used rates of growth in each of the three species. Angular optical quality on the retina due to HOA, and its metrics improved, in contrast to the constancy predicted by uniform scaling. The model with constant linear HOA blur predicts well the improvement in human optical quality between infant and adult. Overall, in chick and monkey, angular blur improves at a rate faster than that predicted by the constant linear blur model, implying that linear retinal blur due to HOA decreases with age. On the other hand, in chick, angular blur due to third-order aberrations decreased at a rate predicted by the constant linear blur model. Growth changes in retinal blur due to HOA are species dependent but can be better understood by comparison with the new model predictions.

The degree of polarization (DOP) of the light reflected from the optic nerve head has been assessed by means of a polarimetric scanning laser ophthalmoscope as a function of the age of the participants. Four fundus images corresponding to independent polarization states in the recording pathway were used to compute the spatially-resolved DOP. This was not uniform across the optic nerve head and depended on both the location and the participant's age. Along a peripapillary annulus the DOP followed a double-peak pattern. Moreover, the values along this annulus decreased significantly with increasing age. This depolarization appears to originate in part in the retinal nerve fiber layer. Detailed age-dependent knowledge of the ocular depolarization properties may help to improve clinical diagnosis of the retinal nerve fiber layer.

Background: Although deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson disease (PD) improves motor function, it has variable effects on working memory (WM) and response inhibition (RI) performance. The purpose of this study was to determine the neural correlates of STN DBS-induced variability in cognitive performance., Methods: We measured bilateral STN DBS-induced blood flow changes (PET and [(15)O]-water on one day) in the supplementary motor area (SMA), dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and right inferior frontal cortex (rIFC) as well as in exploratory ROIs defined by published meta-analyses. STN DBS-induced WM and RI changes (Spatial Delayed Response and Go-No-Go on the next day) were measured in 24 PD participants. On both days, participants withheld PD medications overnight and conditions (OFF vs. ON) were administered in a counterbalanced, double-blind manner., Results: As predicted, STN DBS-induced DLPFC blood flow change correlated with change in WM, but not RI performance. Furthermore, ACC blood flow change correlated with change in RI but not WM performance. For both relationships, increased blood flow related to decreased cognitive performance in response to STN DBS. Of the exploratory regions, only blood flow changes in DLPFC and ACC were correlated with performance., Conclusions: These results demonstrate that variability in the effects of STN DBS on cognitive performance relates to STN DBS-induced cortical blood flow changes in DLPFC and ACC. This relationship highlights the need to further understand the factors that mediate the variability in neural and cognitive response to STN DBS.

Differences in the location of active contacts with respect to the subthalamic nucleus (STN) may account for much variability in motor, psychiatric and cognitive responses to deep brain stimulation (DBS) in Parkinson disease (PD) patients. Because localization of STN based on hypointensity in T2-weighted MR images is unreliable and further limited by artifacts from the metal electrodes, we developed and validated a method to transform brain images into stereotactic space [Mai JK, Assheuer J, Paxinos G. Atlas of the Human Brain, 2nd ed. San Diego: Elsevier Academic; 2004] using reliably-identified anatomic fiducials identified in high-resolution T2-weighted pre-operative MR images. Average intraclass correlation between two raters for 29 PD patients was 0.93 for those fiducials used to define the atlas. Accuracy of the registration was tested by comparing the rater-identified centers of the red nuclei with their predicted locations from the fiducial-based atlas transformation. Mean discrepancies were 0.1, 0.9, and 0.0mm (x, y, z) with standard deviations of 0.9, 0.7 and 1.1mm, respectively. Because post-operative determination of contact location with respect to the STN is necessary due to possible shifting of electrodes during surgical placement, we identified active contacts on post-operative CT images and transformed their locations into stereotactic space. This method provides an accurate and reliable means for STN DBS contact localization.

Improving community health "from the ground up" entails a comprehensive ecological approach, deep involvement of community-based entities, and addressing social determinants of population health status. Although the Centers for Disease Control and Prevention, the Office of the Surgeon General, and other authorities have called for public health to be an "inter-sector" enterprise, few models have surfaced that feature local health departments as a key part of the collaborative model for effecting community-level change. This paper presents evaluation findings and lessons learned from the Partnership for the Public's Health (PPH), a comprehensive community initiative that featured a central role for local health departments with their community partners. Funded by The California Endowment, PPH provided technical and financial resources to 39 community partnerships in 14 local health department jurisdictions in California to promote community and health department capacity building and community-level policy and systems change designed to produce long-term improvements in population health. The evaluation used multiple data sources to create progress ratings for each partnership in five goal areas related to capacity building, community health improvement programs, and policy and systems change. Overall results were generally positive; in particular, of the 37 partnerships funded continuously throughout the 5 years of the initiative, between 25% and 40% were able to make a high level of progress in each of the Initiative's five goal areas. Factors associated with partnership success were also identified by local evaluators. These results showed that health departments able to work effectively with community groups had strong, committed leaders who used creative financing mechanisms, inclusive planning processes, organizational changes, and open communication to promote collaboration with the communities they served.

Comparative studies of ethnically diverse human populations, particularly in Africa, are important for reconstructing human evolutionary history and for understanding the genetic basis of phenotypic adaptation and complex disease. African populations are characterized by greater levels of genetic diversity, extensive population substructure, and less linkage disequilibrium (LD) among loci compared to non-African populations. Africans also possess a number of genetic adaptations that have evolved in response to diverse climates and diets, as well as exposure to infectious disease. This review summarizes patterns and the evolutionary origins of genetic diversity present in African populations, as well as their implications for the mapping of complex traits, including disease susceptibility.

We quantify the effects on scanning laser ophthalmoscope image quality of controlled amounts of scattered light, confocal pinhole diameter, and age. Optical volumes through the optic nerve head were recorded for a range of pinhole sizes in 12 subjects (19-64 years). The usefulness of various overall metrics in quantifying the changes in fundus image quality is assessed. For registered and averaged images, we calculated signal-to-noise ratio, entropy, and acutance. Entropy was best able to distinguish differing image quality. The optimum confocal pinhole diameter was found to be 50 microm (on the retina), providing improved axial resolution and image quality under all conditions.

We present a polarimetric technique to improve fundus images that notably simplifies and extends a previous procedure [Opt. Lett.27, 830 (2002)]. A generator of varying polarization states was incorporated into the illumination path of a confocal scanning laser ophthalmoscope. A series of four images, corresponding to independent incoming polarization states, were recorded. From these images, the spatially resolved elements of the top row of the Mueller matrix were computed. From these elements, images with the highest and lowest quality (according to different image quality metrics) were constructed, some of which provided improved visualization of fundus structures of clinical importance (vessels and optic nerve head). The metric values were better for these constructed images than for the initially recorded images and better than averaged images. Entropy is the metric that is most sensitive to differences in the image quality. Improved visualization of features could aid in the detection, localization, and tracking of ocular disease and may be applicable in other biomedical imaging.

Purpose: In this initial study, we model the impact of crystalline lens movement and tilt, which we postulate are a potential consequence of scleral expansion surgery (SES). We demonstrate the possibility that these lead to an improvement in near vision with no concurrent restoration of lens accommodative function. With the implantation of scleral expansion bands (SEB), Schachar predicts an increase in the amplitude of accommodation not observed objectively. We postulate that the SEB implants cause the crystalline lens to be shifted forward and become misaligned. Using mathematical models of the optics of the human eye, we assess the effects of our postulate on the power of the eye, the depth of field, optical aberrations, and the appearance of the horizontal retinoscopic reflex., Methods: Using anatomically based models of the human eye, the postulated effects of SES are theoretically modeled and optically analyzed in Code V for unintentional lens anterior movement, tilts, and decentrations of up to 1 mm, +/- 3 degrees , and +/- 0.3mm, respectively. The transverse aberrations are calculated before and after SES. Because it has been reported that the appearance of the retinoscopic reflex is consistent with the presence of excess aberrations, we also predict the appearance of the one-dimensional retinoscopic reflex for our models. The change in refractive error is also determined. RESULTS.: Unintentional lens shift, tilt, and decentration, as might occur as a result of SES surgery, would result in an increase in the total power of the eye along with an increase in asymmetric aberrations and little change in symmetric aberrations. The calculated appearances of the retinoscopic reflexes pre- and postsurgery are consistent with observations in the literature., Conclusions: Scleral expansion surgery could produce an improvement in near vision through an unintentional anterior displacement of the crystalline lens in combination with excess tilts and decentrations rather than as a result of a restoration of lens accommodation. There is a need for measurements and further analysis of the optical and visual properties of SES patients postsurgery.

Understanding the control of eye growth may lead to the prevention of nearsightedness (myopia). Chicks develop refractive errors in response to defocusing lenses by changing the rate of eye elongation. Changes in optical image quality and the optical signal in lens compensation are not understood. Monochromatic ocular aberrations were measured in 16 chicks that unilaterally developed myopia in response to unilateral goggles with -15D lenses and in 6 chicks developing naturally. There is no significant difference in higher-order root mean square aberrations (RMSA) between control eyes of the goggled birds and eyes of naturally developing chicks. Higher-order RMSA for a constant pupil size exponentially decreases in the chick eye with age more slowly than defocus. In the presence of a defocusing lens, the exponential decrease begins after day 2. In goggled eyes, asymmetric aberrations initially increase significantly, followed by an exponential decrease. Higher-order RMSA is significantly higher in goggled eyes than in controls. Equivalent blur, a new measure of image quality that accounts for increasing pupil size with age, exponentially decreases with age. In goggled eyes, this decrease also occurs after day 2. The fine optical structure, reflected in higher-order aberrations, may be important in understanding normal development and the development of myopia.

Objective: This study was undertaken to assess the utility of the nulliparous term singleton vertex cesarean birth (NTSV CB) measure as a quality improvement tool for use at the hospital level., Study Design: We prospectively collected data on all NTSV births in Sutter Health's 20 birthing units over a 3-year period, 2001 through 2003, totaling 41,416 births. Hospital rates of NTSV CB, obstetric practices, and infant outcomes were calculated and compared by using weighted logistic analyses. In addition, we examined the effect of maternal age on the NTSV CB measure by using direct standardization with US norms for nulliparous women., Results: There was large variation noted in the NTSV CB rate among the 20 hospitals, with unadjusted rates ranging from 10.5% to 30.2%. Strong correlations were found between CB rates and labor induction rates (r = 0.57, P < .0001) and with early labor admission rates (r = 0.62, P < .0001). The strongest correlation was found between NTSV CB rates and a combined measure of induction and early labor admission (r = 0.73, P < .0001). Rates of term 5-minute Apgar score below 7 were not correlated with the NTSV CB rate. Hospital nulliparous maternal age distribution varied markedly and direct standardization led to significant changes in the NTSV CB rate., Conclusion: NTSV CB rate is strongly influenced by elective obstetric practices. The addition of an easily performed maternal age adjustment makes it the most promising CB quality measure for use at the hospital level.

Drawing upon ecological theories of crime control, aspects of the physical environment such as building design, street layout, and land use are thought to indicate territoriality and natural surveillance, thereby affecting the ability of residents to supervise and intervene in crime. To date, ecological models have been tested primarily at community levels of analysis (i.e., neighborhood, block). In contrast, this paper tests the applicability of this theoretical approach to crime in school settings. More specifically, we estimate random-intercept models using survey data from 3682 7th-grade students and 1351 teachers, nested within 65 Kentucky schools linked to school-level measures of the physical environment to determine how they affect various measures of school-based crime and misconduct. Editors' Strategic Implications:How one measures school violence may have profound effects on what contributing causal factors are identified and strategies for prevention are developed. Student reports of school violence appear linked to more normative daily behaviors, whereas teacher reports-though limited to officially observed behaviors-are typically more serious. Thus, measurement implications abound. Nevertheless, territoriality, surveillance, and a sense of order, particularly in the immediate school context more so than the larger community context, appear linked to school violence.

Purpose: To model the feasibility of an accommodating intraocular lens (IOL) that allows near vision by means of an anterior translation within the capsular bag., Setting: University of Waterloo, Waterloo, Ontario, Canada., Methods: Model eyes were constructed and analyzed based on experimental data using Code V, a computerized optical design tool. The potential near vision of IOLs of different powers was calculated as they were moved anteriorly within the capsular bag. The conditions under which a spherical lens performs well and when an aspheric design should be considered were determined., Results: Accommodation (the dioptric change from the far to the near point) varies linearly with lens movement and is sensitive to corneal and IOL powers. Simple equations were derived and accurately predicted induced accommodation. Retinal image quality varies significantly with pupil size and IOL power. However, image quality is minimally affected by the amount of induced accommodation., Conclusions: From an optical standpoint accommodation with adequate image quality can be achieved by anterior movement of a spherical IOL within the capsular bag.

Background: Mucormycosis is a rare fungal infection commonly affecting structures in the head and neck such as air sinuses, orbits, and the brain. Common predisposing factors include diabetes and immunosuppression. To date, only one case of mucormycosis involving the parotid gland has been reported, and this infection was associated with a fatal outcome., Methods: We report a case of parotid gland mucormycosis in a 45-year-old woman with type 2 diabetes, who was successfully treated with a superficial parotidectomy and intravenous amphotericin B., Results: After initial surgical and antifungal therapy, the patient was left with a residual facial nerve palsy for which multiple sling procedures were performed. She is currently alive and well 6 years after the diagnosis of mucormycosis., Conclusions: Mucormycosis of the parotid gland is a rare form of this often-fatal infection. In this case, infection remained isolated to the parotid gland and was diagnosed soon after presentation. The patient most likely survived because of the early diagnosis, successful surgical removal of all infected tissue, use of intravenous amphotericin therapy, and the aggressive management of comorbidities such as her diabetes., ((c) 2005 Wiley Periodicals, Inc.)

Decision-making deficits are considered to be a significant contributing factor for drug abuse. Drug abusers performed poorly on a simulated gambling task (A. Bechara, H. Damasio, D. Tranel, & S. Anderson, 1994); however, the psychological processes that contribute to these deficits are unknown. The authors used cognitive decision models with a simulated gambling task (SGT) to examine underlying processes of decision making in 66 drug abusers and 58 control participants. As expected, male drug abusers performed more poorly than male controls, and model results showed that male drug abusers placed greater emphasis on wins. The findings for women were less clear because control women performed at chance level on the SGT. Additional studies of gender differences on the SGT are needed to clarify these findings of discrepant performance in the control women., (Copyright 2005 APA, all rights reserved.)

We examined the possible role of autonomic activity in Huntington's disease (HD) during a risky decision making task. Skin conductance responses (SCRs) of 15 HD participants and 16 healthy controls were measured while they performed a computerized version of the Simulated Gambling Task (SGT). The results replicated our previous finding of a performance decrement in HD, and showed that HD was associated with an altered pattern of SCRs during the risky decision task. Specifically, the healthy controls produced increased SCRs following selections from the disadvantageous decks and following losing selections. In contrast, the SCRs of the HD group did not differentiate between wins and losses. These findings indicate a reduced impact of loss on decision-making processes under risky conditions in HD.

Spot 14 is a 17-kDa protein expressed in lipogenic tissues and is postulated to play a role in thyroid hormone stimulation of lipogenesis. To further our understanding of Spot 14 regulation in humans, our laboratory recently cloned the human Spot 14 gene. The gene is highly homologous to the rat Spot 14 ortholog and located on a chromosomal region implicated in human obesity. Because our understanding of Spot 14 transcriptional regulation is derived from rat promoter studies, we assessed the thyroid hormone responsivity of the human Spot 14 promoter. These studies revealed a significantly greater thyroid hormone response for the human promoter, compared with the rat. Deletional studies of the human Spot 14 promoter reveal a 774-bp region at approximately position -2700, which is both necessary and sufficient for the thyroid hormone response. EMSAs with subfragments from this region identify a 146-bp DNA fragment capable of binding a TRbeta1-retinoid X receptor heterodimer. Site-directed mutagenesis confirmed the identity of a candidate DR-4 thyroid hormone response element within this fragment that is similar, but not identical, to the two rat Spot 14 thyroid hormone response elements. We hypothesize that the difference in thyroid hormone response between the orthologous promoters may allow a selective advantage to each species based on their different nutritional and physiological niches.

The soil-borne nematode, Caenorhabditis elegans, is emerging as a versatile model in which to study host-pathogen interactions. The worm model has shown to be particularly effective in elucidating both microbial and animal genes involved in toxin-mediated killing. In addition, recent work on worm infection by a variety of bacterial pathogens has shown that a number of virulence regulatory genes mediate worm susceptibility. Many of these regulatory genes, including the PhoP/Q two-component regulators in Salmonella and LasR in Pseudomonas aeruginosa, have also been implicated in mammalian models suggesting that findings in the worm model will be relevant to other systems. In keeping with this concept, experiments aimed at identifying host innate immunity genes have also implicated pathways that have been suggested to play a role in plants and animals, such as the p38 MAP kinase pathway. Despite rapid forward progress using this model, much work remains to be done including the design of more sensitive methods to find effector molecules and further characterization of the exact interaction between invading pathogens and C. elegans' cellular components.