Ad Hoc Mobility Notification in Wireless Infrastructure Networks

Hybrid networks composed of a wireless infrastructure network providing Internet access to an underlying ad hoc network are more and more attractive due to their low installation cost. In these all-wireless environments, performance is a key issue as radio bandwidth is scarce. Handoffs management is particularly important as these networks are likely to be highly mobile. Mobility notification should therefore be optimized in order to limit signaling overhead while keeping a good reactivity against terminals mobility. This article presents and studies by simulation different level optimizations applied to a modified Cellular IP protocol

Late Holocene records of fire and human presence in New Zealand

New Zealand, and the South Island in particular, can be considered an excellent test site for the study of the early impact of humans on the environment for two main reasons: the Polynesian settlement occurred only about 700-800 y BP and resulted in abrupt and huge landscape modifications. Burning forest for land clearance impacted dramatically on an ecosystem that was not adapted to fire, changing the composition of the vegetation as documented by sedimentary charcoal and pollen records. Although charcoal data give incontrovertible evidence of some unprecedented fire events right after the arrival of the Maori, its significance as a tracer for local and anthropogenic fire events has been questioned, stressing the need for new markers to confirm and complete the information about human presence and its effective impact. In the present work, faecal sterols and polycyclic aromatic hydrocarbons (PAHs) were individuated as suitable molecular markers and analyzed by GC-MS in a sediment core from Lake Kirkpatrick, located in the Lake Wakatipu catchment at 570 m a.s.l. in the South Island of New Zealand. Coprostanol accounts for about 60% of total sterol content in human faeces, being much less relevant in animal dejections. Together with its degradation product epi-coprostanol, it is well conserved in sedimentary archives and can be highly useful in paleoenvironmental reconstructions of human settlements. PAHs are produced in relevant amounts by combustion in conditions of oxygen depletion, and diagnostic ratios (DR) between specific molecules can be used for inferring fuel and sources. The charcoal record for Lake Kirkpatrick shows major fire episodes around AD 1350, confirmed by corresponding high levels of PAHs ascribable to biomass burning (as further evidenced by DR) at c. AD 1350. Moreover, the same trend is observed also in the fluxes of coprostanol and epi-coprostanol, whose sum results in two peaks at c. AD 1346 and 1351. This finding confirms not only the massive presence of humans in the area and the large use of fire at the time, but also complements and refines the reconstructions enabled by charcoal analysis

Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy.

TRACK-HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3-Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross-sectional data from this large well-characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene-positive subjects (120 PreHD and 119 early HD) from the TRACK-HD study were included. Using voxel-based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, metronome tapping, and gait); oculomotor [anti-saccade error rate (ASE)]; cognition (negative emotion recognition, spot the change and the University of Pennsylvania smell identification test) and neuropsychiatric measures (apathy, affect and irritability). After adjusting for estimated disease severity, regionally specific associations between structural loss and task performance were found (familywise error corrected, P < 0.05); impairment in tongue force, metronome tapping and ASE were all associated with striatal loss. Additionally, tongue force deficits and ASE were associated with volume reduction in the occipital lobe. Impaired recognition of negative emotions was associated with volumetric reductions in the precuneus and cuneus. Our study reveals specific associations between atrophy and decline in a range of clinical modalities, demonstrating the utility of VBM correlation analysis for investigating these relationships in HD

Intellectual enrichment and genetic modifiers of cognition and brain volume in Huntington's disease

An important step towards the development of treatments for cognitive impairment in ageing and neurodegenerative diseases is to identify genetic and environmental modifiers of cognitive function and understand the mechanism by which they exert an effect. In Huntington’s disease, the most common autosomal dominant dementia, a small number of studies have identified intellectual enrichment, i.e. a cognitively stimulating lifestyle and genetic polymorphisms as potential modifiers of cognitive function. The aim of our study was to further investigate the relationship and interaction between genetic factors and intellectual enrichment on cognitive function and brain atrophy in Huntington’s disease. For this purpose, we analysed data from Track-HD, a multi-centre longitudinal study in Huntington’s disease gene carriers and focused on the role of intellectual enrichment (estimated at baseline) and the genes FAN1, MSH3, BDNF, COMT and MAPT in predicting cognitive decline and brain atrophy. We found that carrying the 3a allele in the MSH3 gene had a positive effect on global cognitive function and brain atrophy in multiple cortical regions, such that 3a allele carriers had a slower rate of cognitive decline and atrophy compared with non-carriers, in agreement with its role in somatic instability. No other genetic predictor had a significant effect on cognitive function and the effect of MSH3 was independent of intellectual enrichment. Intellectual enrichment also had a positive effect on cognitive function; participants with higher intellectual enrichment, i.e. those who were better educated, had higher verbal intelligence and performed an occupation that was intellectually engaging, had better cognitive function overall, in agreement with previous studies in Huntington’s disease and other dementias. We also found that intellectual enrichment interacted with the BDNF gene, such that the positive effect of intellectual enrichment was greater in Met66 allele carriers than non-carriers. A similar relationship was also identified for changes in whole brain and caudate volume; the positive effect of intellectual enrichment was greater for Met66 allele carriers, rather than for non-carriers. In summary, our study provides additional evidence for the beneficial role of intellectual enrichment and carrying the 3a allele in MSH3 in cognitive function in Huntington’s disease and their effect on brain structure

Genome-wide associations for birth weight and correlations with adult disease

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW ($\textit{P}$  < 5 × 10$^{-8}$). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure ($\textit{R}$ $_{g}$ = -0.22, $\textit{P}$  = 5.5 × 10$^{-13}$), T2D ($\textit{R}$ $_{g}$ = -0.27, $\textit{P}$  = 1.1 × 10$^{-6}$) and coronary artery disease ($\textit{R}$ $_{g}$ = -0.30, $\textit{P}$  = 6.5 × 10$^{-9}$). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions ($\textit{P}$ = 1.9 × 10$^{-4}$). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.For a full list of the funders pelase visit the publisher's website and look at the supplemetary material provided. Some of the funders are: British Heart Foundation, Cancer Research UK, Medical Research Council, National Institutes of Health, Royal Society and Wellcome Trust

Abstracts from the NIHR INVOLVE Conference 2017

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Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Service-learning in design education

This research sought to reveal the extent to which service-learning in design education (SLIDE) provides a mutually beneficial experience for undergraduate design students and community partners. A two-phased, mixed-methods study, employing surveys and case study research, was conducted to address the main research question. During the first phase, an online survey was administered with design educators in Australia, the United States, and the United Kingdom to better understand the current practice of service-learning in design education. After this broad scan, a second survey was developed to discover the design-related needs that exist in the community, specifically at nonprofit organisations, thereby gaining perspective from the outside in. During the second phase, case study research was conducted at 12 sites to explain the results of the surveys and to holistically examine the university-community partnerships. The intersection of a service-learning taxonomy (Britt, 2009) with the orders of design (Buchanan, 2001) creates the theoretical framework for this research. The findings demonstrate the benefits and challenges associated with service-learning for three stakeholder groups—undergraduate design students, community partners and design educators. This research confirms and extends theory in design (Buchanan, 2001) and service-learning (Morton, 1995; Britt, 2009). It also offers new insights into the roles that community partners play during design-related service-learning. The study contributes to what we already know about the complexities of design education in the twenty-first century and raises some important questions for the discipline in an effort to improve practice and build knowledge about SLIDE

The youth social media literacy inventory:development and validation using item response theory in the US

Social media has opened new doors of opportunities and risks for youth. Potential risks include exposure to harmful content, engagement with strangers, or unwanted consequences from irresponsible or naive use. Social media literacy has been proposed as a way to mitigate such risks and promote positive ways of social media engagement. This paper aimed to develop a comprehensive Youth Social Media Literacy Inventory (YSMLI) to objectively assess young adolescents’ (9–13 years) knowledge and skills in the context of social media use. The development process included four consecutive steps: 1) an in-depth review of the literature to identify core competencies and domains of social media literacy, 2) creation of a large item pool that assesses these core competencies within six domains (advertising, cyberbullying, privacy, news, phishing, and media balance), 3) expert review and cognitive pretesting with youth, and 4) empirical validation of the final 90-item pool using item response theory based on a sample of n = 306 youth participants in the US. The final item bank is well-fitting, reliable, and valid, offering scales with varying lengths for different purposes including domain-specific assessment and parallel testing.</p

Use of organic biomarkers for the Late Holocene reconstruction of fire and human presence in New Zealand

The Polynesian colonization of New Zealand occurred quite recently in history (about 700-800 years BP) and resulted in abrupt and huge landscape modifications, as documented by sedimentary charcoal and pollen records. The native forest was not adapted to fire, thus burning for land clearance impacted dramatically on the ecosystem by modifying the composition of vegetation (McWethy et al., 2014). Therefore, this location can be considered an extraordinary test site for the study of the very first human impacts on the environment. Despite the incontrovertible evidence of some unprecedented fire events right after the arrival of the Māori, reconstructed through charcoal, its significance as a tracer for local and anthropogenic fire events has been questioned, stressing the need for new markers to confirm and complete the information about human presence and its effective impact (Butler, 2008). In the present work, novel organic molecular proxies are proposed for the reconstruction of fire events in association with anthropic activities. Namely, faecal sterols (FeSt), polycyclic aromatic hydrocarbons (PAHs) and monosaccharide anhydrides (MAs) were individuated as suitable molecular markers of human presence and fire activity, respectively. In particular, coprostanol accounts for about 60% of total sterol content in human faeces, being much less relevant in animal dejections (Bull et al., 2002). Together with its degradation product epi-coprostanol, it is well conserved in sedimentary archives and can be highly useful in paleoenvironmental reconstructions of human settlements. PAHs are produced in relevant amounts by combustion in conditions of oxygen depletion, and diagnostic ratios (DR) between specific molecules can be used for inferring fuel and sources (Ravindra et al., 2008). MAs are specific tracers of biomass burning, being generated only by the combustion of cellulose and hemicelluloses above 300° C (Simoneit et al., 1999). The three classes of tracers were analyzed in a sediment core from Lake Kirkpatrick (570 m asl), and FeSt were analyzed also in a core from Lake Diamond (380 m asl). Both lakes are located in the Otago region, in New Zealand South Island. The charcoal record for Lake Kirkpatrick (LK) and Lake Diamond (LD) shows major fire episodes around AD 1350, confirmed for LK by corresponding high levels of PAHs, ascribable to biomass burning (as further evidenced by DR), and MAs, both peaking at c. AD 1350. Moreover, the same trend is observed also in the fluxes of coprostanol and epi-coprostanol, whose sum results in two peaks at c. AD 1346 and 1351, respectively. For LD, a peak in FeSt is observed as well, slightly preceding the increase in fire activity starting around AD 1330. These findings confirm not only an important presence of humans in the area and the large use of fire at the time, but also the validity of selected tracers for complementing and refining the reconstructions enabled by charcoal analysis