The behavioural variant frontotemporal dementia phenocopy syndrome is a distinct entity - evidence from a longitudinal study.

BACKGROUND: This study aimed to i) examine the frequency of C9orf72 expansions in a cohort of patients with the behavioural variant frontotemporal dementia (bvFTD) phenocopy syndrome, ii) observe outcomes in a group of phenocopy syndrome with very long term follow-up and iii) compare progression in a cohort of patients with the phenocopy syndrome to a cohort of patients with probable bvFTD. METHODS: Blood was obtained from 16 phenocopy cases. All met criteria for possible bvFTD and were labeled as phenocopy cases if they showed no functional decline, normal cognitive performance on the Addenbrooke's Cognitive Examination-Revised (ACE-R) and a lack of atrophy on brain imaging, over at least 3 years of follow-up. In addition, we obtained very long term follow-up data in 6 cases. A mixed model analysis approach determined the pattern of change in cognition and behaviour over time in phenocopy cases compared to 27 probable bvFTD cases. RESULTS: All 16 patients were screened for the C9orf72 expansion that was present in only one (6.25%). Of the 6 cases available for very long-term follow-up (13 - 21 years) none showed progression to frank dementia. Moreover, there was a decrease in the caregiver ratings of behavioural symptoms over time. Phenocopy cases showed significantly slower rates of progression compared to probable bvFTD patients (p < 0.006). CONCLUSION: The vast majority of patients with the bvFTD phenocopy syndrome remain stable over many years. An occasional patient can harbor the C9orf72 expansion. The aetiology of the remaining cases remains unknown but it appears very unlikely to reflect a neurodegenerative syndrome due to lack of clinical progression or atrophy on imaging

Reliability and Concurrent Validity of Global Physical Activity Questionnaire (GPAQ): A Systematic Review

This study aimed to systematically review previous studies on the reliability and concurrent validity of the Global Physical Activity Questionnaire (GPAQ). A systematic literature search was conducted (n = 26) using the online EBSCOHost databases, PubMed, Web of Science, and Google Scholar up to September 2019. A previously developed coding sheet was used to collect the data. The Modified Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was employed to assess risk of bias and study quality. It was found that GPAQ was primarily revalidated in adult populations in Asian and European countries. The sample size ranged from 43 to 2657 with a wide age range (i.e., 15–79 years old). Di erent populations yielded inconsistent results concerning the reliability and validity of the GPAQ. Short term (i.e., one- to two-week interval) and long-term (i.e., two- to three-month apart) test–retest reliability was good to very good. The concurrent validity using accelerometers, pedometers, and physical activity (PA) log was poor to fair. The GPAQ data and accelerometer/pedometer/PA log data were not compared using the same measurements in some validation studies. Studies with more rigorous research designs are needed before any conclusions concerning the concurrent validity of GPAQ can be reached

The contribution of tropical cyclones to the atmospheric branch of Middle America's hydrological cycle using observed and reanalysis tracks

Middle America is affected by tropical cyclones (TCs) from the Eastern Pacific and the North Atlantic Oceans. We characterize the regional climatology (1998-2016) of the TC contributions to the atmospheric branch of the hydrological cycle, from May to December. TC contributions to rainfall are quantified using Tropical Rainfall Measuring Mission (TRMM) Multi-satellite Precipitation Analysis (TMPA) product 3B42 and TC tracks derived from three sources: the International Best Track Archive for Climate Stewardship (IBTrACS), and an objective feature tracking method applied to the Japanese 55-year and ERA-Interim reanalyses. From July to October, TCs contribute 10-30% of rainfall over the west and east coast of Mexico and central Mexico, with the largest monthly contribution during September over the Baja California Peninsula (up to 90%). TCs are associated with 40-60% of daily extreme rainfall (above the 95th percentile) over the coasts of Mexico. IBTrACS and reanalyses agree on TC contributions over the Atlantic Ocean but disagree over the Eastern Pacific Ocean and continent; differences over the continent are mainly attributed to discrepancies in TC tracks in proximity to the coast and TC lifetime. Reanalysis estimates of TC moisture transports show that TCs are an important moisture source for the regional water budget. TC vertically integrated moisture flux (VIMF) convergence can turn regions of weak VIMF divergence by the mean circulation into regions of weak VIMF convergence. We discuss deficiencies in the observed and reanalysis TC tracks, which limit our ability to quantify robustly the contribution of TCs to the regional hydrological cycle

A new perspective of the climatological features of upper-level cut-off lows in the Southern Hemisphere

This study presents a detailed view of the seasonal variability of upper-level cut-off lows (COLs) in the Southern Hemisphere. The COLs are identified and tracked using data from a 36-year period of the European Centre for Medium Range Weather Forecast reanalysis (ERA-Interim). The objective identification of the COLs uses a new approach, which is based on 300 hPa relative vorticity minima, and three restrictive criteria of the presence of a cold-core, stratospheric potential vorticity intrusion, and cut-off cyclonic circulation. The highest COL activity is in agreement with previous studies, located near three main continental areas (Australia, South America, and Africa), with maximum frequencies usually observed in the austral autumn. The COL mean intensity values show a marked seasonal and spatial variation, with maximum (minimum) values during the austral winter (summer), a unique feature that has not been observed previously in studies based on the geopotential. The link between intensity and lysis is examined, and finds that weaker systems are more susceptible to lysis in the vicinity of the Andes Cordillera, associated with the topographic Rossby wave. Lysis and genesis regions are close to each other, confirming that COLs are quasi-stationary systems. Also, COLs tend to move eastward and are faster over the higher latitudes. The mean growth/decay rates coincide with the major genesis and lysis density regions, such as the significant decay values across the Andes all year. As a consequence of using vorticity for the tracking method a longer lifetime of COLs is detected than in other studies, but this does not affect the total frequency of occurrence. Comparisons with other studies suggest that the differences in seasonality are due to uncertainties in the reanalyses and the methods used to identify COLs

Inhibitor SBFI26 suppresses the malignant progression of castration-resistant PC3-M cells by competitively binding to oncogenic FABP5

Castration resistant-prostate cancer is largely impervious to feather hormonal therapy and hence the outlook for patients is grim. Here we use an approach to attach the recently discovered Achilles heel. The experimental treatment established in this study is based on the recent discovery that it is the FABP5-PPARγ-VEGF signalling axis, rather than the androgen receptor pathway, played a dominant role in promoting the malignant progression of castration resistant prostate cancer cells. Treatments have been established in mice by suppressing the biological activity of FABP5 using a chemical inhibitor SBFI26. The inhibitor significantly suppressed the proliferation, migration, invasiveness and colony formation of PC3-M cells in vitro. It also produced a highly significant suppression of both the metastases and the primary tumours developed from cancer cells implanted orthotopically into the prostate glands of the mice. The inhibitor SBFI26 interferes with the FABP5-PPARγ- signalling pathway at the initial stage of the signal transduction by binding competitively to FABP5 to inhibit cellular fatty acid uptake. This avoids the fatty-acid stimulation of PPARγ and prevents it activating the down-stream regulated cancer-promoting genes. This entirely novel experimental approach to treating castration- resistant prostate cancer is completely different from current treatments that are based on androgen-blockade therapy

Methodological considerations in the analysis of fecal glucocorticoid metabolites in tufted capuchins (Cebus apella)

Analysis of fecal glucocorticoid (GC) metabolites has recently become the standard method to monitor adrenocortical activity in primates noninvasively. However, given variation in the production, metabolism, and excretion of GCs across species and even between sexes, there are no standard methods that are universally applicable. In particular, it is important to validate assays intended to measure GC production, test extraction and storage procedures, and consider the time course of GC metabolite excretion relative to the production and circulation of the native hormones. This study examines these four methodological aspects of fecal GC metabolite analysis in tufted capuchins (Cebus apella). Specifically, we conducted an adrenocorticotrophic hormone (ACTH) challenge on one male and one female capuchin to test the validity of four GC enzyme immunoassays (EIAs) and document the time course characterizing GC me- tabolite excretion in this species. In addition, we compare a common field-friendly technique for extracting fecal GC metabolites to an established laboratory extraction methodology and test for effects of storing “field extracts” for up to 1 yr. Results suggest that a corticosterone EIA is most sensitive to changes in GC production, provides reliable measures when extracted according to the field method, and measures GC metabolites which remain highly stable after even 12 mo of storage. Further, the time course of GC metabolite excretion is shorter than that described yet for any primate taxa. These results provide guidelines for studies of GCs in tufted capuchins, and underscore the importance of validating methods for fecal hormone analysis for each species of interest

Computers in Secondary Schools: Educational Games

This entry introduces educational games in secondary schools. Educational games include three main types of educational activities with a playful learning intention supported by digital technologies: educational serious games, educational gamification, and learning through game creation. Educational serious games are digital games that support learning objectives. Gamification is defined as the use of "game design elements and game thinking in a non-gaming context" (Deterding et al. 2011, p. 13). Educational gamification is not developed through a digital game but includes game elements for supporting the learning objectives. Learning through game creation is focused on the process of designing and creating a prototype of a game to support a learning process related to the game creation process or the knowledge mobilized through the game creation process. Four modalities of educational games in secondary education are introduced in this entry to describe educational games in secondary education: educational purpose of entertainment games, serious games, gamification, and game design

Selecting CMIP5 GCMs for downscaling over multiple regions

The unprecedented availability of 6-hourly data from a multi-model GCM ensemble in the CMIP5 data archive presents the new opportunity to dynamically downscale multiple GCMs to develop high-resolution climate projections relevant to detailed assessment of climate vulnerability and climate change impacts. This enables the development of high resolution projections derived from the same set of models that are used to characterise the range of future climate changes at the global and large-scale, and as assessed in the IPCC AR5. However, the technical and human resource required to dynamically-downscale the full CMIP5 ensemble are significant and not necessary if the aim is to develop scenarios covering a representative range of future climate conditions relevant to a climate change risk assessment. This paper illustrates a methodology for selecting from the available CMIP5 models in order to identify a set of 8–10 GCMs for use in regional climate change assessments. The selection focuses on their suitability across multiple regions—Southeast Asia, Europe and Africa. The selection (a) avoids the inclusion of the least realistic models for each region and (b) simultaneously captures the maximum possible range of changes in surface temperature and precipitation for three continental-scale regions. We find that, of the CMIP5 GCMs with 6-hourly fields available, three simulate the key regional aspects of climate sufficiently poorly that we consider the projections from those models ‘implausible’ (MIROC-ESM, MIROC-ESM-CHEM, and IPSL-CM5B-LR). From the remaining models, we demonstrate a selection methodology which avoids the poorest models by including them in the set only if their exclusion would significantly reduce the range of projections sampled. The result of this process is a set of models suitable for using to generate downscaled climate change information for a consistent multi-regional assessment of climate change impacts and adaptation

Amyotrophic lateral sclerosis and frontotemporal dementia: distinct and overlapping changes in eating behaviour and metabolism.

Metabolic changes incorporating fluctuations in weight, insulin resistance, and cholesterol concentrations have been identified in several neurodegenerative disorders. Whether these changes result from the neurodegenerative process affecting brain regions necessary for metabolic regulation or whether they drive the degenerative process is unknown. Emerging evidence from epidemiological, clinical, pathological, and experimental studies emphasises a range of changes in eating behaviours and metabolism in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In ALS, metabolic changes have been linked to disease progression and prognosis. Furthermore, changes in eating behaviour that affect metabolism have been incorporated into the diagnostic criteria for FTD, which has some clinical and pathological overlap with ALS. Whether the distinct and shared metabolic and eating changes represent a component of the proposed spectrum of the two diseases is an intriguing possibility. Moreover, future research should aim to unravel the complex connections between eating, metabolism, and neurodegeneration in ALS and FTD, and aim to understand the potential for targeting modifiable risk factors in disease development and progression.This work was supported by funding to Forefront, a collaborative research group dedicated to the study of frontotemporal dementia and motor neurone disease, from the National Health and Medical Research Council of Australia (NHMRC) program grant (#1037746 to GH, MK and JH) and the Australian Research Council Centre of Excellence in Cognition and its Disorders Memory Node (#CE110001021 to OP and JH) and other grants/sources (NHMRC project grant #1003139). We are grateful to the research participants involved with the ForeFront research studies. RA is a Royal Australasian College of Physicians PhD scholar and MND Australia PhD scholar. MI is an ARC Discovery Early Career Researcher Award Fellow (#DE130100463). OP is an NHMRC Career Development Research Fellow (#1022684). GH is a NHMRC Senior Principal Research Fellow (#1079679). L.M.I. is a NHMRC Senior Research Fellow (#1003083).This is the author accepted manuscript. The final version is available from Elsevier at http://dx.doi.org/10.1016/S1474-4422(15)00380-4

ARPES: A probe of electronic correlations

Angle-resolved photoemission spectroscopy (ARPES) is one of the most direct methods of studying the electronic structure of solids. By measuring the kinetic energy and angular distribution of the electrons photoemitted from a sample illuminated with sufficiently high-energy radiation, one can gain information on both the energy and momentum of the electrons propagating inside a material. This is of vital importance in elucidating the connection between electronic, magnetic, and chemical structure of solids, in particular for those complex systems which cannot be appropriately described within the independent-particle picture. Among the various classes of complex systems, of great interest are the transition metal oxides, which have been at the center stage in condensed matter physics for the last four decades. Following a general introduction to the topic, we will lay the theoretical basis needed to understand the pivotal role of ARPES in the study of such systems. After a brief overview on the state-of-the-art capabilities of the technique, we will review some of the most interesting and relevant case studies of the novel physics revealed by ARPES in 3d-, 4d- and 5d-based oxides.Comment: Chapter to appear in "Strongly Correlated Systems: Experimental Techniques", edited by A. Avella and F. Mancini, Springer Series in Solid-State Sciences (2013). A high-resolution version can be found at: http://www.phas.ubc.ca/~quantmat/ARPES/PUBLICATIONS/Reviews/ARPES_Springer.pdf. arXiv admin note: text overlap with arXiv:cond-mat/0307085, arXiv:cond-mat/020850