Feasibility and acceptability of remote smartphone cognitive testing in frontotemporal dementia research

INTRODUCTION: Remote smartphone assessments of cognition, speech/language, and motor functioning in frontotemporal dementia (FTD) could enable decentralized clinical trials and improve access to research. We studied the feasibility and acceptability of remote smartphone data collection in FTD research using the ALLFTD Mobile App (ALLFTD-mApp). METHODS: A diagnostically mixed sample of 214 participants with FTD or from familial FTD kindreds (asymptomatic: CDR®+NACC-FTLD = 0 [ RESULTS: It was feasible for participants to complete the ALLFTD-mApp on their own smartphones. Participants reported high smartphone familiarity, completed ∼ 70% of tasks, and considered the time commitment acceptable (98% of respondents). Greater disease severity was associated with poorer performance across several tests. DISCUSSION: These findings suggest that the ALLFTD-mApp study protocol is feasible and acceptable for remote FTD research. HIGHLIGHTS: The ALLFTD Mobile App is a smartphone-based platform for remote, self-administered data collection.The ALLFTD Mobile App consists of a comprehensive battery of surveys and tests of executive functioning, memory, speech and language, and motor abilities.Remote digital data collection using the ALLFTD Mobile App was feasible in a multicenter research consortium that studies FTD. Data was collected in healthy controls and participants with a range of diagnoses, particularly FTD spectrum disorders.Remote digital data collection was well accepted by participants with a variety of diagnoses

Emergence and intensification of dairying in the Caucasus and Eurasian steppes

Archaeological and archaeogenetic evidence points to the Pontic-Caspian steppe zone between the Caucasus and the Black Sea as the crucible from which the earliest steppe pastoralist societies arose and spread, ultimately influencing populations from Europe to Inner Asia. However, little is known about their economic foundations and the factors that may have contributed to their extensive mobility. Here, we investigate dietary proteins within the dental calculus proteomes of 45 individuals spanning the Neolithic to Greco-Roman periods in the Pontic-Caspian Steppe and neighbouring South Caucasus, Oka-Volga-Don and East Urals regions. We find that sheep dairying accompanies the earliest forms of Eneolithic pastoralism in the North Caucasus. During the fourth millennium BC, Maykop and early Yamnaya populations also focused dairying exclusively on sheep while reserving cattle for traction and other purposes. We observe a breakdown in livestock specialization and an economic diversification of dairy herds coinciding with aridification during the subsequent late Yamnaya and North Caucasus Culture phases, followed by severe climate deterioration during the Catacomb and Lola periods. The need for additional pastures to support these herds may have driven the heightened mobility of the Middle and Late Bronze Age periods. Following a hiatus of more than 500 years, the North Caucasian steppe was repopulated by Early Iron Age societies with a broad mobile dairy economy, including a new focus on horse milking

Webcam Delivery of the Lidcombe Program for Preschool Children Who Stutter: A Randomised Controlled Trial

Early intervention provides children who stutter with the best opportunity to avoid the lifelong complications associated with stuttering. Access to effective treatment, in particular, the Lidcombe Program, provides preschool children with the best chance to overcome their stuttering. Currently many children are unable to access such efficacious treatment due to distance and lifestyle factors. One solution to this problem is to deliver the treatment via webcam over the internet. This service delivery model was designed to increase access to timely, best-practice intervention for those who are currently unable to access treatment. That model was thought to be able to produce efficiency rates similar to those of traditional clinic treatment. Further, it provides a method of service delivery that: (1) improves access to evidence-based best-practice stuttering treatment for children, (2) improves access to specialist speech pathologists and quality services, (3) reduces costs and resources involved with outreach service provision, (4) provides more convenient home-based treatment for young children, and (5) ensures more equitable service delivery for rural and remote preschool children and their families. A Phase I study showed that webcam delivery of the Lidcombe Program was a viable treatment delivery model (O’Brian, Smith & Onslow, 2012). This thesis further investigates delivery of the Lidcombe Program for preschool children using the internet and a webcam. The modification in this project, compared to previous, low-tech telehealth (phone and mail) trials of the Lidcombe Program, allowed the principles of standard delivery of the Lidcombe Program to remain relatively unchanged. This was due primarily to the use of a webcam and live videoconferencing. The speech pathologist-parent-child triad was preserved, with all parties having clinic contact. Real-time measurements, observation and education for parent implementation of the program were also achieved through this medium. Thus, treatment could be delivered mostly in accordance with the program treatment guide (Packman et al., 2011, p. 1). The design for this project was a parallel, open plan, Phase III noninferiority randomised controlled trial (RCT). The control group received standard delivery of the Lidcombe Program (Packman, et al., 2011) in a traditional clinic setting. The experimental group received the Lidcombe Program within their homes using a computer, a webcam, the internet and a live video calling program (Skype). The primary outcome measures – the number of consultations and speech pathologist hours to attain entry into Stage 2 – evaluated treatment efficiency. The secondary outcomes – stuttering reduction as measured by parent evaluated severity ratings, investigated treatment efficacy, as did quantitative and qualitative data obtained from parent questionnaires. The number of weeks to attain Stage 2 entry was also measured. Initially, 66 children were assessed for this trial. Eleven were ineligible and six withdrew during the assessment process, with 49 participants being randomised. Of these, 24 were assigned to the control arm and 25 to the experimental arm. Due to time restrictions associated with the student’s candidature, not all 18-month data were collected in time for inclusion in this thesis. Pretreatment data are reported for all 49 participants. Data for all 43 participants active in the trial 9 months postrandomisation are also reported. Stage 2 entry data are available for the 35 participants (71% of the total cohort) who reached Stage 2 by December 31st 2012. Results for both groups showed no significant difference between the number of consultations and the number of weeks to Stage 2. Efficacy measures showed no significant difference between the groups in stuttering reduction. A further secondary outcome measure was parent responses to a questionnaire at entry into Stage 2. Similarly, there was no significant difference between the two groups when asked about speech pathologist-child rapport, speech pathologist-parent rapport, ease of learning treatment, severity ratings and ability to adapt treatment. Further, two-thirds of clinic families said they would choose webcam treatment in the future. Webcam parents reported no difficulty in seeking out their own resources and did not feel treatment within their home was invasive. Webcam families listed convenience and comfort as the main advantages of webcam treatment, with technical difficulties as the main disadvantage. All webcam families would choose this same method for future stuttering treatment. The thesis concludes with a discussion of the speech pathologist’s role, consultation logistics and additional qualitative observations from the webcam group. These include convenience, treatment readiness, defining clinical space, trends in clinical transfer, clinical application, limitations and future directions. Overall, this thesis demonstrates that the findings from a Phase III RCT investigating the efficiency and efficacy of stuttering treatment for preschool support the use of webcam and internet to increase access to timely and appropriate stuttering intervention. The potential for community translation of these findings is considerable; children as young as 3 years of age can receive the same stuttering treatment within their homes as they would within a clinic; they can expect no difference in outcomes or experience. This is significant given that children as young as 2 years of age can be negatively affected by their stuttering. No longer do children who stutter need to be disadvantaged by where they live or by the skills of the closest speech pathologist. They can now access evidence-based treatment within their homes

The Impact of Conservation on the Status of the World\u27s Vertebrates

Using data for 25,780 species categorized on the International Union for Conservation of Nature Red List, we present an assessment of the status of the world\u27s vertebrates. One-fifth of species are classified as Threatened, and we show that this figure is increasing: On average, 52 species of mammals, birds, and amphibians move one category closer to extinction each year. However, this overall pattern conceals the impact of conservation successes, and we show that the rate of deterioration would have been at least one-fifth again as much in the absence of these. Nonetheless, current conservation efforts remain insufficient to offset the main drivers of biodiversity loss in these groups: agricultural expansion, logging, overexploitation, and invasive alien species

On complex singularities of the 2D Euler equation at short times

We present a study of complex singularities of a two-parameter family of solutions for the two-dimensional Euler equation with periodic boundary conditions and initial conditions F(p) cos p z + F(q) cos q z in the short-time asymptotic regime. As has been shown numerically in W. Pauls et al., Physica D 219, 40-59 (2006), the type of the singularities depends on the angle between the modes p and q. Here we show for the two particular cases of the angle going to zero and to pi that the type of the singularities can be determined very accurately, being characterised by the values 5/2 and 3 respectively. In these two cases we are also able to determine the subdominant corrections. Furthermore, we find that the geometry of the singularities in these two cases is completely different, the singular manifold being located "over" different points in the real domain.Comment: 12 pages, 7 figure

Structural insights on TRPV5 gating by endogenous modulators.

TRPV5 is a transient receptor potential channel involved in calcium reabsorption. Here we investigate the interaction of two endogenous modulators with TRPV5. Both phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and calmodulin (CaM) have been shown to directly bind to TRPV5 and activate or inactivate the channel, respectively. Using cryo-electron microscopy (cryo-EM), we determined TRPV5 structures in the presence of dioctanoyl PI(4,5)P2 and CaM. The PI(4,5)P2 structure reveals a binding site between the N-linker, S4-S5 linker and S6 helix of TRPV5. These interactions with PI(4,5)P2 induce conformational rearrangements in the lower gate, opening the channel. The CaM structure reveals two TRPV5 C-terminal peptides anchoring a single CaM molecule and that calcium inhibition is mediated through a cation-π interaction between Lys116 on the C-lobe of calcium-activated CaM and Trp583 at the intracellular gate of TRPV5. Overall, this investigation provides insight into the endogenous modulation of TRPV5, which has the potential to guide drug discovery

Taxonomic similarity does not predict necessary sample size for ex situ conservation: A comparison among five genera

Effectively conserving biodiversity with limited resources requires scientifically informed and efficient strategies. Guidance is particularly needed on how many living plants are necessary to conserve a threshold level of genetic diversity in ex situ collections. We investigated this question for 11 taxa across five genera. In this first study analysing and optimizing ex situ genetic diversity across multiple genera, we found that the percentage of extant genetic diversity currently conserved varies among taxa from 40% to 95%. Most taxa are well below genetic conservation targets. Resampling datasets showed that ideal collection sizes vary widely even within a genus: one taxon typically required at least 50% more individuals than another (though Quercus was an exception). Still, across taxa, the minimum collection size to achieve genetic conservation goals is within one order of magnitude. Current collections are also suboptimal: they could remain the same size yet capture twice the genetic diversity with an improved sampling design. We term this deficiency the ‘genetic conservation gap’. Lastly, we show that minimum collection sizes are influenced by collection priorities regarding the genetic diversity target. In summary, current collections are insufficient (not reaching targets) and suboptimal (not efficiently designed), and we show how improvements can be made

San Francisco Hep B Free: A Grassroots Community Coalition to Prevent Hepatitis B and Liver Cancer

Chronic hepatitis B is the leading cause of liver cancer and the largest health disparity between Asian/Pacific Islanders (APIs) and the general US population. The Hep B Free model was launched to eliminate hepatitis B infection by increasing hepatitis B awareness, testing, vaccination, and treatment among APIs by building a broad, community-wide coalition. The San Francisco Hep B Free campaign is a diverse public/private collaboration unifying the API community, health care system, policy makers, businesses, and the general public in San Francisco, California. Mass-media and grassroots messaging raised citywide awareness of hepatitis B and promoted use of the existing health care system for hepatitis B screening and follow-up. Coalition partners reported semi-annually on activities, resources utilized, and system changes instituted. From 2007 to 2009, over 150 organizations contributed approximately $1,000,000 in resources to the San Francisco Hep B Free campaign. 40 educational events reached 1,100 healthcare providers, and 50% of primary care physicians pledged to screen APIs routinely for hepatitis B. Community events and fairs reached over 200,000 members of the general public. Of 3,315 API clients tested at stand-alone screening sites created by the campaign, 6.5% were found to be chronically infected and referred to follow-up care. A grassroots coalition that develops strong partnerships with diverse organizations can use existing resources to successfully increase public and healthcare provider awareness about hepatitis B among APIs, promote routine hepatitis B testing and vaccination as part of standard primary care, and ensure access to treatment for chronically infected individuals

Galaxy And Mass Assembly (GAMA): trends in galaxy colours, morphology, and stellar populations with large-scale structure, group, and pair environments

We explore trends in galaxy properties with Mpc-scale structures using catalogues of environment and large scale structure from the Galaxy And Mass Assembly (GAMA) survey. Existing GAMA catalogues of large scale structure, group and pair membership allow us to construct galaxy stellar mass functions for different environmental types. To avoid simply extracting the known underlying correlations between galaxy properties and stellar mass, we create a mass matched sample of galaxies with stellar masses between 9.5≤logM∗/h−2M⊙≤11 for each environmental population. Using these samples, we show that mass normalised galaxies in different large scale environments have similar energy outputs, u−r colours, luminosities, and morphologies. Extending our analysis to group and pair environments, we show galaxies that are not in groups or pairs exhibit similar characteristics to each other regardless of broader environment. For our mass controlled sample, we fail to see a strong dependence of S\'{e}rsic index or galaxy luminosity on halo mass, but do find that it correlates very strongly with colour. Repeating our analysis for galaxies that have not been mass controlled introduces and amplifies trends in the properties of galaxies in pairs, groups, and large scale structure, indicating that stellar mass is the most important predictor of the galaxy properties we examine, as opposed to environmental classifications