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

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)

Understanding Terrorist Organizations with a Dynamic Model

Terrorist organizations change over time because of processes such as recruitment and training as well as counter-terrorism (CT) measures, but the effects of these processes are typically studied qualitatively and in separation from each other. Seeking a more quantitative and integrated understanding, we constructed a simple dynamic model where equations describe how these processes change an organization's membership. Analysis of the model yields a number of intuitive as well as novel findings. Most importantly it becomes possible to predict whether counter-terrorism measures would be sufficient to defeat the organization. Furthermore, we can prove in general that an organization would collapse if its strength and its pool of foot soldiers decline simultaneously. In contrast, a simultaneous decline in its strength and its pool of leaders is often insufficient and short-termed. These results and other like them demonstrate the great potential of dynamic models for informing terrorism scholarship and counter-terrorism policy making.Comment: To appear as Springer Lecture Notes in Computer Science v2: vectorized 4 figures, fixed two typos, more detailed bibliograph

Netrin-3 and Netrin-4-Like Proteins are Secreted from \u3cem\u3eTetrahymena thermophila\u3c/em\u3e

Netrins are signaling proteins, acting as chemorepellants or chemoattractants, and their role is especially important in early growth in organisms. In studies involving Tetrahymena thermophila, netrin proteins often act as chemorepellants, so research centered around verifying if this was also true for Netrin-4 protein. Since Netrin-1 and Netrin-3 have been shown to influence neurological and developmental growth in organisms, the implications for discovering the cellular effects of Netrin-4 are significant for human health and research. Through behavioral assays, we were able to confirm that Netrin4 does act as a chemorepellant. In addition, our ELISA and Western blots also helped substantiate the idea that Tetrahymena produce Netrin-4 for physiological functions, as they possess receptors for these proteins. The exact purposes of Netrin-4 for this organism is unknown up to this point, so further testing is needed to determine the cellular mechanisms with which Netrin-4 is involved

Plasma lipid profiles change with increasing numbers of mild traumatic brain injuries in rats

Mild traumatic brain injury (mTBI) causes structural, cellular and biochemical alterations which are difficult to detect in the brain and may persist chronically following single or repeated injury. Lipids are abundant in the brain and readily cross the blood-brain barrier, suggesting that lipidomic analysis of blood samples may provide valuable insight into the neuropathological state. This study used liquid chromatography-mass spectrometry (LC-MS) to examine plasma lipid concentrations at 11 days following sham (no injury), one (1×) or two (2×) mTBI in rats. Eighteen lipid species were identified that distinguished between sham, 1× and 2× mTBI. Three distinct patterns were found: (1) lipids that were altered significantly in concentration after either 1× or 2× F mTBI: cholesterol ester CE (14:0) (increased), phosphoserine PS (14:0/18:2) and hexosylceramide HCER (d18:0/26:0) (decreased), phosphoinositol PI(16:0/18:2) (increased with 1×, decreased with 2× mTBI); (2) lipids that were altered in response to 1× mTBI only: free fatty acid FFA (18:3 and 20:3) (increased); (3) lipids that were altered in response to 2× mTBI only: HCER (22:0), phosphoethanolamine PE (P-18:1/20:4 and P-18:0/20:1) (increased), lysophosphatidylethanolamine LPE (20:1), phosphocholine PC (20:0/22:4), PI (18:1/18:2 and 20:0/18:2) (decreased). These findings suggest that increasing numbers of mTBI induce a range of changes dependent upon the lipid species, which likely reflect a balance of damage and reparative responses

The ultrasound-triggered explosion of an endoskeletal antibubble yields a predictable fragment size distribution

acceptedVersionPeer reviewe

Rapid tyrosine phosphorylation of neuronal proteins including tau and focal adhesion kinase in response to amyloid-beta peptide exposure: Involvement of src family protein kinases

The increased production of amyloid beta -peptide (A beta) in Alzheimer's disease is acknowledged to be a key pathogenic event. In this study, we examined the response of primary human and rat brain cortical cultures to A beta administration and found a marked increase in the tyrosine phosphorylation content of numerous neuronal proteins, including tau and putative microtubule-associated protein 2c (MAP2c). We also found that paired helical filaments of aggregated and hyperphosphorylated tau are tyrosine phosphorylated, indicating that changes in the phosphotyrosine content of cytoplasmic proteins in response to A beta are potentially an important process. Increased tyrosine phosphorylation of cytoskeletal and other neuronal proteins was specific to fibrillar A beta (25-35) and A beta (1-42). The tyrosine phosphorylation was blocked by addition of the Src family tyrosine kinase inhibitor 4-amino-5-( 4-chlorophenyl)- 7(t-butyl) pyrazol(3,4-D) pyramide (PP2) and the phosphatidylinositol 3-kinase inhibitor LY 294002. Tyrosine phosphorylation of tau and MAP2c was concomitant with an increase in the tyrosine phosphorylation and subsequent putative activation of the non-receptor kinase, focal adhesion kinase (FAK). Immunoprecipitation of Fyn, a member of the Src family, from A beta (25-35)-treated neurons showed an increased association of Fyn with FAK. A beta treatment of cells also stimulated the sustained activation of extracellular regulated kinase-2, which was blocked by addition of PP2 and LY 294002, suggesting that FAK/Fyn/PI3-kinase association is upstream of mitogen-activated protein (MAP) kinase signaling in A beta -treated neurons. This cascade of signaling events contains the earliest biochemical changes in neurons to be described in response to A beta exposure and may be critical for subsequent neurodegenerative changes