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

The R18 polyarginine peptide is more effective than the TAT-NR2B9c (NA-1) peptide when administered 60 minutes after permanent middle cerebral artery occlusion in the rat

We examined the dose responsiveness of polyarginine R18 (100, 300, and 1000 nmol/kg) when administered 60 minutes after permanent middle cerebral artery occlusion (MCAO).The TAT-NR2B9c peptide, which is known to be neuroprotective in rodent and nonhuman primate stroke models, served as a positive control. At 24 hours afterMCAO, there was reduced total infarct volume in R18 treated animals at all doses, but this reduction only reached statistical significance at doses of 100 and 1000 nmol/kg. The TAT-NR2B9c peptide reduced infarct volume at doses of 300 and 1000 nmol/kg, but not to a statistically significant extent, while the 100 nmol/kg dose was ineffective.The reduction in infarct volume with R18 and TAT-NR2B9c peptide treatments was mirrored by improvements in one or more functional outcomes (namely, neurological score, adhesive tape removal, and rota-rod), but not to a statistically significant extent. These findings further confirm the neuroprotective properties of polyarginine peptides and for R18 extend its therapeutic time window and dose range, as well as demonstrating its greater efficacy compared to TAT-NR2B9c in a severe stroke model.The superior neuroprotective efficacy of R18 over TAT-NR2B9c highlights the potential of this polyarginine peptide as a lead candidate for studies in human stroke

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

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)

Poly-arginine peptides reduce infarct volume in a permanent middle cerebral artery rat stroke model

Background: We recently reported that poly-arginine peptides have neuroprotective properties both in vitro and in vivo. In cultured cortical neurons exposed to glutamic acid excitotoxicity, we demonstrated that neuroprotective potency increases with polymer length plateauing at R15 to R18 (R = arginine resides). In an in vivo study in rats, we also demonstrated that R9D (R9 peptide synthesised with D-isoform amino acids) administered intravenously at a dose of 1000 nmol/kg 30 min after permanent middle cerebral artery occlusion (MCAO) reduces infarct volume. Based on these positive in vitro and in vivo findings, we decided to examine the neuroprotective efficacy of the L-isoform poly-arginine peptides, R12, R15 and R18 when administered at a dose of 1000 nmol/kg 30 min after permanent MCAO in the rat. Results: At 24 h post-MCAO, there was reduced total infarct volume for R12 (12.8 % reduction) and R18 (20.5 % reduction), but this reduction only reached statistical significance for R18. Brain slice analysis revealed significantly reduced injury in coronal slices 4 and 5 for R18, and slice 5 for R12. The R15 peptide had no effect on infarct volume. Peptide treatment did not reveal any statistical significant improvement in functional outcomes. Conclusion: While these findings confirm the in vivo neuroprotective properties of poly-arginine peptides, additional dose studies are required particularly in less severe transient MCAO models so as to further assess the potential of these agents as a stroke therapy

Multiple shifts and fractional integration in the us and uk unemployment rates

This paper analyses the long-run behaviour of the US and UK unemployment rates by testing for possibly fractional orders of integration and multiple shifts using a sample of over 100 annual observations. The results show that the orders of integration are higher than 0 in both series, which implies long memory. If we assume that the underlying disturbances are white noise, the values are higher than 0.5, i.e., nonstationary. However, if the disturbances are autocorrelated, the orders of integration are in the interval (0, 0.5), implying stationarity and mean-reverting behaviour. Moreover, when multiple shifts are taken into account, unemployment is more persistent in the US than in the UK, implying the need for stronger policy action in the former to bring unemployment back to its original level

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

THE ELEVENTH AND TWELFTH DATA RELEASES OF THE SLOAN DIGITAL SKY SURVEY: FINAL DATA FROM SDSS-III

Citation: Alam, S., Albareti, F. D., Prieto, C. A., Anders, F., Anderson, S. F., Anderton, T., . . . Zhu, G. T. (2015). THE ELEVENTH AND TWELFTH DATA RELEASES OF THE SLOAN DIGITAL SKY SURVEY: FINAL DATA FROM SDSS-III. Astrophysical Journal Supplement Series, 219(1), 27. doi:10.1088/0067-0049/219/1/12The third generation of the Sloan Digital Sky Survey (SDSS-III) took data from 2008 to 2014 using the original SDSS wide-field imager, the original and an upgraded multi-object fiber-fed optical spectrograph, a new near-infrared high-resolution spectrograph, and a novel optical interferometer. All of the data from SDSS-III are now made public. In particular, this paper describes Data Release 11 (DR11) including all data acquired through 2013 July, and Data Release 12 (DR12) adding data acquired through 2014 July (including all data included in previous data releases), marking the end of SDSS-III observing. Relative to our previous public release (DR10), DR12 adds one million new spectra of galaxies and quasars from the Baryon Oscillation Spectroscopic Survey (BOSS) over an additional 3000 deg(2) of sky, more than triples the number of H-band spectra of stars as part of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE), and includes repeated accurate radial velocity measurements of 5500 stars from the Multi-object APO Radial Velocity Exoplanet Large-area Survey (MARVELS). The APOGEE outputs now include the measured abundances of 15 different elements for each star. In total, SDSS-III added 5200 deg(2) of ugriz imaging; 155,520 spectra of 138,099 stars as part of the Sloan Exploration of Galactic Understanding and Evolution 2 (SEGUE-2) survey; 2,497,484 BOSS spectra of 1,372,737 galaxies, 294,512 quasars, and 247,216 stars over 9376 deg(2); 618,080 APOGEE spectra of 156,593 stars; and 197,040 MARVELS spectra of 5513 stars. Since its first light in 1998, SDSS has imaged over 1/3 of the Celestial sphere in five bands and obtained over five million astronomical spectra.Additional Authors: Berlind, A. A.;Beutler, F.;Bhardwaj, V.;Bird, J. C.;Bizyaev, D.;Blake, C. H.;Blanton, M. R.;Blomqvist, M.;Bochanski, J. J.;Bolton, A. S.;Bovy, J.;Bradley, A. S.;Brandt, W. N.;Brauer, D. E.;Brinkmann, J.;Brown, P. J.;Brownstein, J. R.;Burden, A.;Burtin, E.;Busca, N. G.;Cai, Z.;Capozzi, D.;Rosell, A. C.;Carr, M. A.;Carrera, R.;Chambers, K. C.;Chaplin, W. J.;Chen, Y. C.;Chiappini, C.;Chojnowski, S. D.;Chuang, C. H.;Clerc, N.;Comparat, J.;Covey, K.;Croft, R. A. C.;Cuesta, A. J.;Cunha, K.;da Costa, L. N.;Da Rio, N.;Davenport, J. R. A.;Dawson, K. S.;De Lee, N.;Delubac, T.;Deshpande, R.;Dhital, S.;Dutra-Ferreira, L.;Dwelly, T.;Ealet, A.;Ebelke, G. L.;Edmondson, E. M.;Eisenstein, D. J.;Ellsworth, T.;Elsworth, Y.;Epstein, C. R.;Eracleous, M.;Escoffier, S.;Esposito, M.;Evans, M. L.;Fan, X. H.;Fernandez-Alvar, E.;Feuillet, D.;Ak, N. F.;Finley, H.;Finoguenov, A.;Flaherty, K.;Fleming, S. W.;Font-Ribera, A.;Foster, J.;Frinchaboy, P. M.;Galbraith-Frew, J. G.;Garcia, R. A.;Garcia-Hernandez, D. A.;Perez, A. E. G.;Gaulme, P.;Ge, J.;Genova-Santos, R.;Georgakakis, A.;Ghezzi, L.;Gillespie, B. A.;Girardi, L.;Goddard, D.;Gontcho, S. G. A.;Hernandez, J. I. G.;Grebel, E. K.;Green, P. J.;Grieb, J. N.;Grieves, N.;Gunn, J. E.;Guo, H.;Harding, P.;Hasselquist, S.;Hawley, S. L.;Hayden, M.;Hearty, F. R.;Hekker, S.;Ho, S.;Hogg, D. W.;Holley-Bockelmann, K.;Holtzman, J. A.;Honscheid, K.;Huber, D.;Huehnerhoff, J.;Ivans, II;Jiang, L. H.;Johnson, J. A.;Kinemuchi, K.;Kirkby, D.;Kitaura, F.;Klaene, M. A.;Knapp, G. R.;Kneib, J. P.;Koenig, X. P.;Lam, C. R.;Lan, T. W.;Lang, D. T.;Laurent, P.;Le Goff, J. M.;Leauthaud, A.;Lee, K. G.;Lee, Y. S.;Licquia, T. C.;Liu, J.;Long, D. C.;Lopez-Corredoira, M.;Lorenzo-Oliveira, D.;Lucatello, S.;Lundgren, B.;Lupton, R. H.;Mack, C. E.;Mahadevan, S.;Maia, M. A. G.;Majewski, S. R.;Malanushenko, E.;Malanushenko, V.;Manchado, A.;Manera, M.;Mao, Q. Q.;Maraston, C.;Marchwinski, R. C.;Margala, D.;Martell, S. L.;Martig, M.;Masters, K. L.;Mathur, S.;McBride, C. K.;McGehee, P. M.;McGreer, I. D.;McMahon, R. G.;Menard, B.;Menzel, M. L.;Merloni, A.;Meszaros, S.;Miller, A. A.;Miralda-Escude, J.;Miyatake, H.;Montero-Dorta, A. D.;More, S.;Morganson, E.;Morice-Atkinson, X.;Morrison, H. L.;Mosser, B.;Muna, D.;Myers, A. D.;Nandra, K.;Newman, J. A.;Neyrinck, M.;Nguyen, D. C.;Nichol, R. C.;Nidever, D. L.;Noterdaeme, P.;Nuza, S. E.;O'Connell, J. E.;O'Connell, R. W.;O'Connell, R.;Ogando, R. L. C.;Olmstead, M. D.;Oravetz, A. E.;Oravetz, D. J.;Osumi, K.;Owen, R.;Padgett, D. L.;Padmanabhan, N.;Paegert, M.;Palanque-Delabrouille, N.;Pan, K. K.;Parejko, J. K.;Paris, I.;Park, C.;Pattarakijwanich, P.;Pellejero-Ibanez, M.;Pepper, J.;Percival, W. J.;Perez-Fournon, I.;Perez-Rafols, I.;Petitjean, P.;Pieri, M. M.;Pinsonneault, M. H.;de Mello, G. F. P.;Prada, F.;Prakash, A.;Price-Whelan, A. M.;Protopapas, P.;Raddick, M. J.;Rahman, M.;Reid, B. A.;Rich, J.;Rix, H. W.;Robin, A. C.;Rockosi, C. M.;Rodrigues, T. S.;Rodriguez-Torres, S.;Roe, N. A.;Ross, A. J.;Ross, N. P.;Rossi, G.;Ruan, J. J.;Rubino-Martin, J. A.;Rykoff, E. S.;Salazar-Albornoz, S.;Salvato, M.;Samushia, L.;Sanchez, A. G.;Santiago, B.;Sayres, C.;Schiavon, R. P.;Schlegel, D. J.;Schmidt, S. J.;Schneider, D. P.;Schultheis, M.;Schwope, A. D.;Scoccola, C. G.;Scott, C.;Sellgren, K.;Seo, H. J.;Serenelli, A.;Shane, N.;Shen, Y.;Shetrone, M.;Shu, Y. P.;Aguirre, V. S.;Sivarani, T.;Skrutskie, M. F.;Slosar, A.;Smith, V. V.;Sobreira, F.;Souto, D.;Stassun, K. G.;Steinmetz, M.;Stello, D.;Strauss, M. A.;Streblyanska, A.;Suzuki, N.;Swanson, M. E. C.;Tan, J. C.;Tayar, J.;Terrien, R. C.;Thakar, A. R.;Thomas, D.;Thomas, N.;Thompson, B. A.;Tinker, J. L.;Tojeiro, R.;Troup, N. W.;Vargas-Magana, M.;Vazquez, J. A.;Verde, L.;Viel, M.;Vogt, N. P.;Wake, D. A.;Wang, J.;Weaver, B. A.;Weinberg, D. H.;Weiner, B. J.;White, M.;Wilson, J. C.;Wisniewski, J. P.;Wood-Vasey, W. M.;Yeche, C.;York, D. G.;Zakamska, N. L.;Zamora, O.;Zasowski, G.;Zehavi, I.;Zhao, G. B.;Zheng, Z.;Zhou, X.;Zhou, Z. M.;Zou, H.;Zhu, G. T

Bridges to ASD: Building Resilience, Self-Efficacy and Capacity in Belizean Caregivers of Children with Autism Spectrum Disorder (ASD)

The Bridges to ASD program was a capstone project that contributed to the nonprofit clinic in a developing country by providing resources and training sessions that potentially helped to unify the caregivers, the teachers and the therapists in their common goals to better support their children in the community with ASD.https://soar.usa.edu/otdcapstonesspring2025/1019/thumbnail.jp