Sleep disturbance and serum ferritin levels associate with high impulsivity and impulse control disorders in male Parkinson\u27s Disease patients

Impulse control disorders (ICDs) occur in a subset of Parkinson’s disease (PD) patients on dopaminergic medications however there are currently no reliable markers to identify patients at risk. Sleep disturbances are more common in patients with an ICD. Serum ferritin levels have been associated with PD disease stage and progression, but have not previously been associated with impulsivity levels. The objective of this study was to determine if serum ferritin levels and sleep disturbance are associated with high traits of impulsivity and ICD in a cohort of PD patients attending a movement disorders clinic. This study assessed impulsiveness in 87 PD patients using the Barratt Impulsiveness Scale. Severity of sleep disturbance was determined using the sleep-related items of the MDS-UPDRS. Serum ferritin, iron and transferrin levels were measured in patients, as well as 36 age-matched healthy controls. Serum ferritin levels were significantly elevated in male PD patients in the high impulsivity group compared to patients in the low (p=.022) and normal range groups (p=.024) and showed a linear increase across the three groups. Sleep disturbance also demonstrated a linear trend, which was most severe in the high impulsivity group (p=.030). A subgroup of 11 male PD patients who fulfilled the DSM-5 criteria for an ICD had significantly higher ferritin levels and more severe sleep disturbance when compared with the remaining male PD cohort. Serum ferritin levels and sleep disturbance severity are highlighted as potential markers for abnormal impulsivity and ICD in PD patients

Extended Timed Up and Go assessment as a clinical indicator of cognitive state in Parkinson\u27s disease

Objective: To evaluate a modified extended Timed Up and Go (extended-TUG) assessment against a panel of validated clinical assessments, as an indicator of Parkinson’s disease (PD) severity and cognitive impairment. Methods: Eighty-seven participants with idiopathic PD were sequentially recruited from a Movement Disorders Clinic. An extended-TUG assessment was employed which required participants to stand from a seated position, walk in a straight line for 7 metres, turn 180 degrees and then return to the start, in a seated position. The extended-TUG assessment duration was correlated to a panel of clinical assessments, including the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Quality of Life (PDQ-39), Scales for Outcomes in Parkinson’s disease (SCOPA-Cog), revised Addenbrooke’s Cognitive Index (ACE-R) and Barratt’s Impulsivity Scale 11 (BIS-11). Results: Extended-TUG time was significantly correlated to MDS-UPDRS III score and to SCOPA-Cog, ACE-R (p\u3c0.001) and PDQ-39 scores (p\u3c0.01). Generalized linear models determined the extended-TUG to be a sole variable in predicting ACE-R or SCOPA-Cog scores. Patients in the fastest extended-TUG tertile were predicted to perform 8.3 and 13.4 points better in the SCOPA-Cog and ACE-R assessments, respectively, than the slowest group. Patients who exceeded the dementia cut-off scores with these instruments exhibited significantly longer extended-TUG times. Conclusions: Extended-TUG performance appears to be a useful indicator of cognition as well as motor function and quality of life in PD, and warrants further evaluation as a first line assessment tool to monitor disease severity and response to treatment. Poor extended-TUG performance may identify patients without overt cognitive impairment form whom cognitive assessment is needed

Internal evaluation of a physically-based distributed model using data from a Mediterranean mountain catchment

An evaluation of the performance of a physically-based distributed model of a small Mediterranean mountain catchment is presented. This was carried out using hydrological response data, including measurements of runoff, soil moisture, phreatic surface level and actual evapotranspiration. <i>A-priori</i> model parameterisation was based as far as possible on property data measured in the catchment. Limited model calibration was required to identify an appropriate value for terms controlling water loss to a deeper regional aquifer. The model provided good results for an initial calibration period, when judged in terms of catchment discharge. However, model performance for runoff declined substantially when evaluated against a consecutive, rather drier, period of data. Evaluation against other catchment responses allowed identification of the problems responsible for the observed lack of model robustness in flow simulation. In particular, it was shown that an incorrect parameterisation of the soil water model was preventing adequate representation of drainage from soils during hydrograph recessions. This excess moisture was then being removed via an overestimation of evapotranspiration. It also appeared that the model underestimated canopy interception. The results presented here suggest that model evaluation against catchment scale variables summarising its water balance can be of great use in identifying problems with model parameterisation, even for distributed models. Evaluation using spatially distributed data yielded less useful information on model performance, owing to the relative sparseness of data points, and problems of mismatch of scale between the measurement and the model grid.</p> <p style='line-height: 20px;'><b>Keywords: </b>physically-based distributed model, SHETRAN, parameterisation, Mediterranean mountain catchment, internal evaluation, multi-respons

Investigation of Cumulative Retrospective Cost Adaptive Control for Missile Application

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83634/1/AIAA-2010-7577-578.pd

Recognition of a High Affinity MHC Class I-Restricted Epitope of Myelin Oligodendrocyte Glycoprotein by CD8+ T Cells Derived from Autoantigen-Deficient Mice

CD4+ T cells have a well-defined pathogenic role in experimental autoimmune encephalomyelitis, the rodent model of multiple sclerosis (MS), yet CD8+ T cells are commonly found in MS lesions. To determine whether immunological tolerance might impact differently on CD4+ versus CD8+ T cells, we studied T cell responses in mice genetically deficient for the central nervous system (CNS) autoantigen myelin oligodendrocyte glycoprotein (MOG) versus wild type (WT) C57BL/6 mice. We show that MOG−/− mice have enhanced sensitivity to immunization with the immunodominant peptide of MOG (35–55), as evidenced by increased expansion of both CD4+ and CD8+ T cell subsets. Most strikingly, CD8+ T cells from MOG−/− mice responded to a novel T cell epitope which binds to MHC class I with high affinity. Despite this, MOG-responsive CD8+ T cells sourced from either WT or MOG−/− mice failed to initiate CNS inflammation upon transfer to MOG-sufficient mice. In our hands, this capacity was only found in CD4+ T cells. However, MOG−/− CD4+ cells did not show greater pathogenic activity than their WT counterparts. Our data indicate that, in the presence of endogenous MOG, CD8+ T cells capable of responding to a MHC class I-restricted epitope that can be stably expressed are subject to rigorous control through central and/or peripheral tolerance

Pliocene-Pleistocene marine cyclothems, Wanganui Basin, New Zealand: a lithostratigraphic framework

The Rangitikei River valley between Mangaweka and Vinegar Hill and the surrounding Ohingaiti region in eastern Wanganui Basin contains a late Pliocene to early Pleistocene (c. 2.6-1.7 Ma), c. 1100 m thick, southward-dipping (4-9deg.), marine cyclothemic succession. Twenty sedimentary cycles occur within the succession, each of which contains coarse-grained (siliciclastic sandstone and coquina) and fine-grained (siliciclastic siltstone) units. Nineteen of the cycles are assigned to the Rangitikei Group (new). Six new formations are defined within the Rangitikei Group, and their distribution in the Ohingaiti region is represented in a new geologic map. The new formations are named: Mangarere, Tikapu, Makohine, Orangipongo, Mangaonoho, and Vinegar Hill. Each formation comprises one or more cyclothems and includes a previously described and named distinctive basal horizon. Discrete sandstones, siltstones, and coquinas within formations are assigned member status and correspond to systems tracts in sequence stratigraphic nomenclature. The members provide the link between the new formational lithostratigraphy and the sequence stratigraphy of the Rangitikei Group. Base of cycle coquina members accumulated during episodes of sediment starvation associated with stratigraphic condensation on an open marine shelf during sea-level transgressions. Siltstone members accumulated in mid-shelf environments (50-100 m water depth) during sea-level highstands, whereas the overlying sandstone members are ascribed to inner shelf and shoreface environments (0-50 m water depth) and accumulated during falling eustatic sea-level conditions. Repetitive changes in water depth of 50-100 m magnitude are consistent with a glacio-eustatic origin for the cyclothems, which correspond to an interval of Earth history when successive glaciations in the Northern Hemisphere are known to have occurred. Moreover, the chronology of the Rangitikei River section indicates that Rangitikei Group cyclothems accumulated during short duration, 41 ka cycles in continental ice volume attributed to the dominance of the Milankovitch obliquity orbital parameter. The Ohingaiti region has simple postdepositional structure. The late Pliocene formations dip generally to the SSW between 4deg. and 9deg.. Discernible discordances of c. 1deg. between successively younger formations are attributed to synsedimentary tilting of the shelf concomitant with migration of the tectonic hingeline southward into the basin. The outcrop distribution of the Rangitikei Group is strongly influenced by this regional tilt and also by three major northeast-southwest oriented, high-angle reverse faults (Rauoterangi, Pakihikura, and Rangitikei Faults)

Elevated serum ceruloplasmin levels are associated with higher impulsivity in people with Parkinson’s Disease

Background. Heightened impulsivity has been reported in a subset of people with Parkinson’s disease (PwP) and is considered a risk factor for the development of impulse control disorders (ICDs). However, at present, there are no recognised biochemical markers of heightened impulsivity. Objectives. To determine if ceruloplasmin, a serum marker involved in the regulation of iron and copper homeostasis, is associated with trait impulsivity in PwP. Methods. The study measured serum ceruloplasmin and impulsivity using the Barratt Impulsiveness Scale (BIS-11) in an Australian cohort of 214 PwP. Multivariate general linear models (GLMs) were used to identify whether higher serum ceruloplasmin levels (>75th percentile) were significantly predictive of BIS-11 scores. Results. Serum ceruloplasmin was higher in females with PD (p<0.001) and associated with MDS-UPDRS III, Hoehn and Yahr, and ACE-R scores (p<0.05). When correcting for covariates, higher serum ceruloplasmin concentrations were associated with the 2nd order nonplanning impulsivity and with the 1st order self-control and cognitive complexity impulsivity domains. Conclusions. Higher serum ceruloplasmin levels are independently associated with heightened nonplanning impulsivity in PwP. Thus, serum ceruloplasmin levels may have clinical utility as a marker for heightened impulsivity in PD