Technology and dementia: the future is now

Background: Technology has multiple potential applications to dementia from diagnosis and assessment to care delivery and supporting ageing in place. Objectives: To summarise key areas of technology development in dementia and identify future directions and implications. Method: Members of the US Alzheimer’s Association Technology Professional Interest Area involved in delivering the annual pre-conference summarised existing knowledge on current and future technology developments in dementia. Results: The main domains of technology development are as follows: (i) diagnosis, assessment and monitoring, (ii) maintenance of functioning, (iii) leisure and activity, (iv) caregiving and management. Conclusions: The pace of technology development requires urgent policy, funding and practice change, away from a narrow medical approach, to a holistic model that facilitates future risk reduction and pre- vention strategies, enables earlier detection and supports implementation at scale for a meaningful and fulfilling life with dementia

17 ways to say yes:Toward nuanced tone of voice in AAC and speech technology

People with complex communication needs who use speech-generating devices have very little expressive control over their tone of voice. Despite its importance in human interaction, the issue of tone of voice remains all but absent from AAC research and development however. In this paper, we describe three interdisciplinary projects, past, present and future: The critical design collection Six Speaking Chairs has provoked deeper discussion and inspired a social model of tone of voice; the speculative concept Speech Hedge illustrates challenges and opportunities in designing more expressive user interfaces; the pilot project Tonetable could enable participatory research and seed a research network around tone of voice. We speculate that more radical interactions might expand frontiers of AAC and disrupt speech technology as a whole

Impact of obesity on day-night differences in cardiac metabolism

An intrinsic property of the heart is an ability to rapidly and coordinately adjust flux through metabolic pathways in response to physiologic stimuli (termed metabolic flexibility). Cardiac metabolism also fluctuates across the 24-hours day, in association with diurnal sleep-wake and fasting-feeding cycles. Although loss of metabolic flexibility has been proposed to play a causal role in the pathogenesis of cardiac disease, it is currently unknown whether day-night variations in cardiac metabolism are altered during disease states. Here, we tested the hypothesis that diet-induced obesity disrupts cardiac diurnal metabolic flexibility , which is normalized by time-of-day-restricted feeding. Chronic high fat feeding (20-wk)-induced obesity in mice, abolished diurnal rhythms in whole body metabolic flexibility, and increased markers of adverse cardiac remodeling (hypertrophy, fibrosis, and steatosis). RNAseq analysis revealed that 24-hours rhythms in the cardiac transcriptome were dramatically altered during obesity; only 22% of rhythmic transcripts in control hearts were unaffected by obesity. However, day-night differences in cardiac substrate oxidation were essentially identical in control and high fat fed mice. In contrast, day-night differences in both cardiac triglyceride synthesis and lipidome were abolished during obesity. Next, a subset of obese mice (induced by 18-wks ad libitum high fat feeding) were allowed access to the high fat diet only during the 12-hours dark (active) phase, for a 2-wk period. Dark phase restricted feeding partially restored whole body metabolic flexibility, as well as day-night differences in cardiac triglyceride synthesis and lipidome. Moreover, this intervention partially reversed adverse cardiac remodeling in obese mice. Collectively, these studies reveal diurnal metabolic inflexibility of the heart during obesity specifically for nonoxidative lipid metabolism (but not for substrate oxidation), and that restricting food intake to the active period partially reverses obesity-induced cardiac lipid metabolism abnormalities and adverse remodeling of the heart

Old lineage on an old island : Pixibinthus, a new cricket genus endemic to New Caledonia shed light on gryllid diversification in a hotspot of biodiversity

Few studies have focused on the early colonization of New Caledonia by insects, after the re-emergence of the main island, 37 Myr ago. Here we investigate the mode and tempo of evolution of a new endemic cricket genus, Pixibinthus, recently discovered in southern New Caledonia. First we formally describe this new monotypic genus found exclusively in the open shrubby vegetation on metalliferous soils, named 'maquis minier', unique to New Caledonia. We then reconstruct a dated molecular phylogeny based on five mitochondrial and four nuclear loci in order to establish relationships of Pixibinthus within Eneopterinae crickets. Pixibinthus is recovered as thesister clade of the endemic genus Agnotecous, mostly rainforest-dwellers. Dating results show that the island colonization by their common ancestor occurred around 34.7 Myr, shortly after New Caledonia re-emergence. Pixibinthus and Agnotecous are then one of the oldest insect lineages documented so far for New Caledonia. This discovery highlights for the first time two clear-cut ecological specializations between sister clades, as Agnotecous is mainly found in rainforests with 19 species, whereas Pixibinthus is found in open habitats with a single documented species. The preference of Pixibinthus for open habitats and of Agnotecous for forest habitats nicely fits an acoustic specialization, either explained by differences in body size or in acoustic properties of their respective habitats. We hypothesize that landscape dynamics, linked to major past climatic events and recent change in fire regimes are possible causes for both present-day low diversity and rarity in genus Pixibinthus. The unique evolutionary history of this old New Caledonian lineage stresses the importance to increase our knowledge on the faunal biodiversity of 'maquis minier', in order to better understand the origin and past dynamics of New Caledonian biota

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Studying Trail Enhancement Plans - Health Impact Assessment

This report reflects work on the Studying Trail Enhancement Plans - Health Impact Assessment (STEP-HIA) for the proposed new Cuba Continental Divide National Scenic Trail segment as of April 30, 2015. It is provided to the Santa Fe National Forest and Bureau of Land Management New Mexico for use in preparing an Environmental Impact Assessment and subsequent planning for the proposed project. It was prepared by the University of New Mexico Prevention Research Center and Step Into Cuba Alliance, a partnership of individuals and organizations dedicated to the promotion of walking and hiking for better health in Cuba, NM. In this report, we present information by way of a sequential series of questions that support and lead to predictions and recommendations for the new trail segment

A plan for play - An Eye View Series report

There is a simple, inexpensive and joyful way to address many of the major challenges facing society and its children; addressing the alarming mental health crisis and obesity epidemic and helping to prepare children for an ever-changing work force. The solution that is all too often overlooked and neglected is - play. The right to play is so important that it is enshrined in the UN Convention on the Rights of the Child. Research documents its importance to every aspect of child health, development and wellbeing. Yet many children have little or no access to high quality play opportunities. Play provision should be considered in relation to every aspect of children’s lives – the design of their neighbourhoods, as well as within the services they access, such as child care centres, schools, hospitals, recreation facilities, parks and adventure playgrounds. Play cannot be relegated to the places and context that adults decide are appropriate It should be woven into the fabric of every aspect of children’s lives and the communities they are part of. Equitable access to play means reducing the insidious gradient of inequity that impacts children’s lives even before they are born and continues across their lifespan. Schools are one important venue to ensure equitable access to play. For some children, it will be the only opportunity they have for this nourishing and necessary activity. Play comprises a quarter of the school year, yet teachers and support staff receive no proper training or support to ensure that children in their care – our society’s future – have fulfilling play time. We know that early life experiences set the stage for the future, and that early intervention saves unquantifiable and unnecessary suffering and costs later on – for children, families and society as a whole. We owe it to children and ourselves both now and tomorrow, to make a plan for play that sees every child in every place playing every day. This report makes that case

To be, or not to be, a non-native freshwater fish?

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Characterization by liquid chromatography combined with mass spectrometry of monoclonal anti-IGF-1 receptor antibodies produced in CHO and NS0 cells

7H2HM is a new humanized recombinant monoclonal antibody (MAb) directed against insulin-like growth factor-1 receptor and produced in CHO cells. Homogeneity of intact antibody, reduced light and heavy chains, Fab and Fc fragments were investigated by analytical methods based on mass (SDS-PAGE, SEC), charge (IEF, C-IEX) and hydrophobicity differences (RP-HPLC, HIC) and compared side-by-side with A2CHM, produced in NS0 cells. Primary structures and disulfide bridge pairing were analyzed by microsequencing (Edman degradation), mass spectrometry (MALDI–TOF, ES–TOF) and peptide mapping after enzymatic digestion (Trypsin, endoprotease Lys-C, papain). The light chains demonstrated the expected sequences. The heavy chains yielded post-translational modifications previously reported for other recombinant humanized or human IgG1 such as N-terminal pyroglutamic acid, C-terminal lysine clipping and N-glycosylation for asparagine 297. More surprisingly, two-thirds of the 7H2HM heavy chains were shown to contain an additional 24-amino-acid sequence, corresponding to the translation of an intron located between the variable and the constant domains. Taken together these data suggest that 7H2HM is a mixture of three families of antibodies corresponding (i) to the expected structure (17%; 149 297 Da; 1330 amino acids), (ii) a variant with a translated intron in one heavy chains (33%; 152 878 Da; 1354 amino acids) and (iii) a variant with translated introns in two heavy chains (50%; 154 459 Da; 1378 amino acids), respectively. RP-HPLC is not a commonly used chromatographic method to assess purity of monoclonal antibodies but unlike to SEC and SDS-PAGE, was able to show and to quantify the family of structures present in 7H2HM, which were also identified by peptide mapping, mass spectrometry and microsequencing