Institutional analysis of the National Park Service : |b a preliminary exploration

This paper is one of a series resulting from the institutional analysis of photovoltaic (PV) acceptance. It reports the results of an initial exploration of the federal non-defense arena. This exploration was undertaken in connection with a PV field test at the Natural Bridges National Monument in Utah. This field test is a collaborative venture of the Department of Energy (DOE) and the National Park Service (NPS). As the procuring agency, NPS is the focus for the paper, serving as an example of institutional action in the federal non-defense arena. Like others in this arena, NPS is involved in the legislative process, as well as program implementati;on. The primary mission of the National Park Service is to make federally-owned land available to the public in a manner which enhances the use and enjoyment ;.of natural and historic resource. NPS has nearly 300 operating units. It is organized by regions, and has two service centers (the larger of which is in Denver) which provide a variety of technical and support services to the operating units. The most important operating units are national parks, monuments and historic sites. Procurements contributing to program activities are guided by federal and agency regulation. One regulation limits procurements to proven technologies, which constitutes a formal barrier to innovation acceptance.Prepared under Dept. of Energy contract no. EX-76-A-01-2295, Task order no.37

Cognitive function in people with and without freezing of gait in Parkinson’s disease

Freezing of gait (FOG) is common in people with Parkinson’s disease (PD) which is extremely debilitating. One hypothesis for the cause of FOG episodes is impaired cognitive control, however, this is still in debate in the literature. We aimed to assess a comprehensive range of cognitive tests in older adults and people with Parkinson’s with and without FOG and associate FOG severity with cognitive performance. A total of 227 participants took part in the study which included 80 healthy older adults, 81 people with PD who did not have FOG and 66 people with PD and FOG. A comprehensive battery of neuropsychological assessments tested cognitive domains of global cognition, executive function/attention, working memory, and visuospatial function. The severity of FOG was assessed using the new FOG questionnaire and an objective FOG severity score. Cognitive performance was compared between groups using an ANCOVA adjusting for age, gender, years of education and disease severity. Correlations between cognitive performance and FOG severity were analyzed using partial correlations. Cognitive differences were observed between older adults and PD for domains of global cognition, executive function/attention, and working memory. Between those with and without FOG, there were differences for global cognition and executive function/attention, but these differences disappeared when adjusting for covariates. There were no associations between FOG severity and cognitive performance. This study identified no significant difference in cognition between those with and without FOG when adjusting for covariates, particularly disease severity. This may demonstrate that complex rehabilitation programs may be undertaken in those with FOG

Assessment of the ability of open- and closed-loop cueing to improve turning and freezing in people with Parkinson’s disease

Turning impairments are common in Parkinson's disease (PD) and can elicit freezing of gait (FoG). Extensive examination of open-loop cueing interventions has demonstrated that they can ameliorate gait deficits in PD; less is known about efficacy to improve turning. Here, we investigate the immediate effectiveness of open- and closed-loop cueing in improving turning characteristics in people with PD. Twenty-five subjects with and 18 subjects without FoG participated in the study. Subjects turned in place for one minute under single- and dual-task for 3 randomized conditions: (i) Baseline; (ii) Turning to the beat of a metronome (open-loop); and (iii) Turning with phase-dependent tactile biofeedback (closed-loop). Objective measures of freezing, such as % time spent freezing and FoG-ratio, significantly improved when turning with both open-loop and closed-loop cueing compared to baseline. Dual-tasking did not worsen FoG in freezers, but significantly slowed down turns in both groups. Both cueing modalities significantly improved turning smoothness in both groups, but reduced turning velocity and number of turns compared to baseline. Both open and closed-loop cueing markedly improved turning in people with PD. These preliminary observations warrant further exploration of vibrotactile closed-loop cueing to improve mobility in everyday life

Ranking the harm of non-medically used prescription opioids in the UK

A panel of nine experts applied multi-criteria decision analysis (MCDA) to determine the relative overall harm to users and harms to others of street heroin (injected and smoked) and eleven non-medically used prescription opioids. The experts assessed harm scores for each of the 13 opioids on each of 20 harm criteria, weighted the criteria and explored the resulting weighted harm scores for each opioid. Both forms of heroin scored very high: overall harm score of 99 for injected heroin and 72 for smoked heroin on a scale of 0–100. The main feature that distinguishes both forms of street heroin use is that their harm to others is more than five times that of the other eleven opioids. The overall harm score of fentanyl (including injection of fentanyl extracted from patches) and diamorphine (medically prescribed form of heroin) was 54 and 51, respectively, whereas that of orally used opioids ranged from 32 (pethidine) to 11 (codeine-containing pharmaceuticals). Injected street heroin, fentanyl and diamorphine emerged as most harmful to users, with the latter two very low in harm to others. Pethidine, methadone, morphine and oxycodone are also low in harm to others, while moderate in harm to users. We conclude that the overall harms of non-medically used prescription opioids are less than half that of injected street heroin. These data may give a basis for precautionary regulatory measures that should be considered if the rising trend in non-medical use of prescription opioids were to become evident in the UK

Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson's disease.

ObjectiveTo understand the safety, putaminal coverage, and enzyme expression of adeno-associated viral vector serotype-2 encoding the complementary DNA for the enzyme, aromatic L-amino acid decarboxylase (VY-AADC01), delivered using novel intraoperative monitoring to optimize delivery.MethodsFifteen subjects (three cohorts of 5) with moderately advanced Parkinson's disease and medically refractory motor fluctuations received VY-AADC01 bilaterally coadministered with gadoteridol to the putamen using intraoperative magnetic resonance imaging (MRI) guidance to visualize the anatomic spread of the infusate and calculate coverage. Cohort 1 received 8.3 × 1011 vg/ml and ≤450 μl per putamen (total dose, ≤7.5 × 1011 vg); cohort 2 received the same concentration (8.3 × 1011 vg/ml) and ≤900 μl per putamen (total dose, ≤1.5 × 1012 vg); and cohort 3 received 2.6 × 1012 vg/ml and ≤900 μl per putamen (total dose, ≤4.7 × 1012 vg). (18)F-fluoro-L-dihydroxyphenylalanine positron emission tomography (PET) at baseline and 6 months postprocedure assessed enzyme activity; standard assessments measured clinical outcomes.ResultsMRI-guided administration of ascending VY-AADC01 doses resulted in putaminal coverage of 21% (cohort 1), 34% (cohort 2), and 42% (cohort 3). Cohorts 1, 2, and 3 showed corresponding increases in enzyme activity assessed by PET of 13%, 56%, and 79%, and reductions in antiparkinsonian medication of -15%, -33%, and -42%, respectively, at 6 months. At 12 months, there were dose-related improvements in clinical outcomes, including increases in patient-reported ON-time without troublesome dyskinesia (1.6, 3.3, and 1.5 hours, respectively) and quality of life.InterpretationNovel intraoperative monitoring of administration facilitated targeted delivery of VY-AADC01 in this phase 1 study, which was well tolerated. Increases in enzyme expression and clinical improvements were dose dependent. ClinicalTrials.gov Identifier: NCT01973543 Ann Neurol 2019;85:704-714

Associations between mobility, cognition and callosal integrity in people with parkinsonism

Falls in people with parkinsonism are likely related to both motor and cognitive impairments. In addition to idiopathic Parkinson\u27s disease (PD), some older adults have lower body parkinsonism (a frontal gait disorder), characterized by impaired lower extremity balance and gait as well as cognition, but without tremor or rigidity. Neuroimaging during virtual gait suggests that interhemispheric, prefrontal cortex communication may be involved in locomotion, but contributions of neuroanatomy connecting these regions to objective measures of gait in people with parkinsonism remains unknown. Our objectives were to compare the integrity of fiber tracts connecting prefrontal and sensorimotor cortical regions via the corpus callosum in people with two types of parkinsonism and an age-matched control group and to relate integrity of these callosal fibers with clinical and objective measures of mobility and cognition. We recruited 10 patients with frontal gait disorders, 10 patients with idiopathic PD and 10 age-matched healthy control participants. Participants underwent cognitive and mobility testing as well as diffusion weighted magnetic resonance imaging to quantify white matter microstructural integrity of interhemispheric fiber tracts. People with frontal gait disorders displayed poorer cognitive performance and a slower, wider-based gait compared to subjects with PD and age-matched control subjects. Despite a widespread network of reduced white matter integrity in people with frontal gait disorders, gait and cognitive deficits were solely related to interhemispheric circuitry employing the genu of the corpus callosum. Current results highlight the importance of prefrontal interhemispheric communication for lower extremity control in neurological patients with cognitive dysfunction

Assessment of the quality of brain regions and neuroimaging metrics as biomarkers of Alzheimer’s disease

Alzheimer Disease (AD) is characterized by progressive cognitive decline and dementia. Earlier diagnosis and classification of different stages of the disease are currently the main challenges and can be assessed by neuroimaging. With this work we aim to evaluate the quality of brain regions and neuroimaging metrics as biomarkers of AD. Multimodal Imaging Brain Connectivity Analysis (MIBCA) toolbox functionalities were used to study AD by T1weighted, Diffusion Tensor Imaging and 18FAV45 PET, with data obtained from the AD Neuroimaging Initiative database, specifically 12 healthy controls (CTRL) and 33 patients with early mild cognitive impairment (EMCI), late MCI (LMCI) and AD (11 patients/group). The metrics evaluated were gray-matter volume (GMV), cortical thickness (CThk), mean diffusivity (MD), fractional anisotropy (FA), fiber count (FiberConn), node degree (Deg), cluster coefficient (ClusC) and relative standard-uptake-values (rSUV). Receiver Operating Characteristic (ROC) curves were used to evaluate and compare the diagnostic accuracy of the most significant metrics and brain regions and expressed as area under the curve (AUC). Comparisons were performed between groups. The RH-Accumbens/Deg demonstrated the highest AUC when differentiating between CTRLEMCI (82%), whether rSUV presented it in several brain regions when distinguishing CTRL-LMCI (99%). Regarding CTRL-AD, highest AUC were found with LH-STG/FiberConn and RH-FP/FiberConn (~100%). A larger number of neuroimaging metrics related with cortical atrophy with AUC>70% was found in CTRL-AD in both hemispheres, while in earlier stages, cortical metrics showed in more confined areas of the temporal region and mainly in LH, indicating an increasing of the spread of cortical atrophy that is characteristic of disease progression. In CTRL-EMCI several brain regions and neuroimaging metrics presented AUC>70% with a worst result in later stages suggesting these indicators as biomarkers for an earlier stage of MCI, although further research is necessary

Functional limits of stability and standing balance in people with Parkinson's disease with and without freezing of gait using wearable sensors

Background: People with from Parkinson's disease (PD) and freezing of gait (FoG) have more frequent falls compared to those who do not freeze but there is no consensus on which, specific objective measures of postural instability are worse in freezers (PD + FoG) than non-freezers (PD-FoG). Research question: Are functional limits of stability (fLoS) or postural sway during stance measured with wearable inertial sensors different between PD + FoG versus PD-FoG, as well as between PD versus healthy control subjects (HC)? Methods: Sixty-four PD subjects with FoG (MDS-UPDRS Part III: 45.9 +/- 12.5) and 80 PD subjects without FoG (MDS-UPDRS Part III: 36.2 +/- 10.9) were tested Off medication and compared with 79 HC. Balance was quantified with inertial sensors worn on the lumbar spine while performing the following balance tasks: 1) fLoS as defined by the maximum displacement in the forward and backward directions and 2) postural sway area while standing with eyes open on a firm and foam surface. An ANOVA, controlling for disease duration, compared postural control between groups. Results: PD + FoG had significantly smaller fLoS compared to PD-FoG (p = 0.004) and to healthy controls (p < 0.001). However, PD-FoG showed similar fLoS compared to healthy controls (p = 0.48). Both PD+FoG and PDFoG showed larger postural sway on a foam surface compared to healthy controls (p = 0.001) but there was no significant difference in postural sway between PD+FoG and PD-FoG. Significance: People with PD and FoG showed task-specific, postural impairments with smaller fLoS compared to non-freezers, even when controlling for disease duration. However, individuals with PD with or without FoG had similar difficulties standing quietly on an unreliable surface compared to healthy controls. Wearable inertial sensors can reveal worse fLoS in freezers than non-freezers that may contribute to FoG and help explain their more frequent falls