RNN Classification of English Vowels: Nasalized or Not

Vowel nasality is perceived and used by English listeners though it is not phonemic. Feature-based classifiers have been built to evaluate what features are useful for nasality perception and measurement. These classifiers require heavy high-level feature engineering with most features discrete and measured at discrete points. Recurrent neural networks can take advantage of sequential information, and has the advantage of freeing us from high-level feature engineering and potentially being stronger simulation models with a holistic view. Therefore, we constructed two types of RNN classifiers (vanilla RNN and LSTM) with MFCCs of the vowel as input to predict whether the vowel is nasalized or not. The LSTM model achieved the best performance, and supports the phonetic claim about the degree of coarticulatory nasality and the use of MFCCs for automatic speech recognition

Purkinje cell-specific Grip1/2 knockout mice show increased repetitive self-grooming and enhanced mGluR5 signaling in cerebellum

Cerebellar Purkinje cell (PC) loss is a consistent pathological finding in autism. However, neural mechanisms of PC-dysfunction in autism remain poorly characterized. Glutamate receptor interacting proteins 1/2 (Grip1/2) regulate AMPA receptor (AMPAR) trafficking and synaptic strength. To evaluate role of PC-AMPAR signaling in autism, we produced PC-specific Grip1/2 knockout mice by crossing Grip2 conventional and Grip1 conditional KO with L7-Cre driver mice. PCs in the mutant mice showed normal morphology and number, and a lack of Grip1/2 expression. Rodent behavioral testing identified normal ambulation, anxiety, social interaction, and an increase in repetitive self-grooming. Electrophysiology studies revealed normal mEPSCs but an impaired mGluR-LTD at the Parallel Fiber-PC synapses. Immunoblots showed increased expression of mGluR5 and Arc, and enhanced phosphorylation of P38 and AKT in cerebellum of PC-specific Grip1/2 knockout mice. Results indicate that loss of Grip1/2 in PCs contributes to increased repetitive self-grooming, a core autism behavior in mice. Results support a role of AMPAR trafficking defects in PCs and disturbances of mGluR5 signaling in cerebellum in the pathogenesis of repetitive behaviors.University of Seville (V PPIT-US)Spain and an National Institute of Health (NIH) (NS085358

Highly Coordinated Gene Regulation in Mouse Skeletal Muscle Regeneration

Mammalian skeletal muscles are capable of regeneration after injury. Quiescent satellite cells are activated to reenter the cell cycle and to differentiate for repair, recapitulating features of myogenesis during embryonic development. To understand better the molecular mechanism involved in this process in vivo, we employed high density cDNA microarrays for gene expression profiling in mouse tibialis anterior muscles after a cardiotoxin injection. Among 16,267 gene elements surveyed, 3,532 elements showed at least a 2.5-fold change at one or more time points during a 14-day time course. Hierarchical cluster analysis and semiquantitative reverse transcription-PCR showed induction of genes important for cell cycle control and DNA replication during the early phase of muscle regeneration. Subsequently, genes for myogenic regulatory factors, a group of imprinted genes and genes with functions to inhibit cell cycle progression and promote myogenic differentiation, were induced when myogenic stem cells started to differentiate. Induction of a majority of these genes, including E2f1 and E2f2, was abolished in muscles lacking satellite cell activity after gamma radiation. Regeneration was severely compromised in E2f1 null mice but not affected in E2f2 null mice. This study identifies novel genes potentially important for muscle regeneration and reveals highly coordinated myogenic cell proliferation and differentiation programs in adult skeletal muscle regeneration in vivo

Pathogenicity locus, core genome, and accessory gene contributions to Clostridium difficile virulence

Clostridium difficile is a spore-forming anaerobic bacterium that causes colitis in patients with disrupted colonic microbiota. While some individuals are asymptomatic C. difficile carriers, symptomatic disease ranges from mild diarrhea to potentially lethal toxic megacolon. The wide disease spectrum has been attributed to the infected host’s age, underlying diseases, immune status, and microbiome composition. However, strain-specific differences in C. difficile virulence have also been implicated in determining colitis severity. Because patients infected with C. difficile are unique in terms of medical history, microbiome composition, and immune competence, determining the relative contribution of C. difficile virulence to disease severity has been challenging, and conclusions regarding the virulence of specific strains have been inconsistent. To address this, we used a mouse model to test 33 clinical C. difficile strains isolated from patients with disease severities ranging from asymptomatic carriage to severe colitis, and we determined their relative in vivo virulence in genetically identical, antibiotic-pretreated mice. We found that murine infections with C. difficile clade 2 strains (including multilocus sequence type 1/ribotype 027) were associated with higher lethality and that C. difficile strains associated with greater human disease severity caused more severe disease in mice. While toxin production was not strongly correlated with in vivo colonic pathology, the ability of C. difficile strains to grow in the presence of secondary bile acids was associated with greater disease severity. Whole-genome sequencing and identification of core and accessory genes identified a subset of accessory genes that distinguish high-virulence from lower-virulence C. difficile strains

The Best of Both Worlds: Connecting Remote Sensing and Arctic Communities for Safe Sea Ice Travel

  Northern communities are increasingly interested in technology that provides information about the sea ice environment for travel purposes. Synthetic aperture radar (SAR) remote sensing is widely used to observe sea ice independently of sunlight and cloud cover, however, access to SAR in northern communities has been limited. This study 1) defines the sea ice features that influence travel for two communities in the Western Canadian Arctic, 2) identifies the utility of SAR for enhancing mobility and safety while traversing environments with these features, and 3) describes methods for sharing SAR-based maps. Three field seasons (spring and fall 2017 and spring 2018) were used to engage residents in locally guided research, where applied outputs were evaluated by community members. We found that SAR image data inform and improve sea ice safety, trafficability, and education. Information from technology is desired to complement Inuit knowledge-based understanding of sea ice features, including surface roughness, thin sea ice, early and late season conditions, slush and water on sea ice, sea ice encountered by boats, and ice discontinuities. Floe edge information was not a priority. Sea ice surface roughness was identified as the main condition where benefits to trafficability from SAR-based mapping were regarded as substantial. Classified roughness maps are designed using thresholds representing domains of sea ice surface roughness (smooth ice/maniqtuk hiku, moderately rough ice/maniilrulik hiku, rough ice/maniittuq hiku; dialect is Inuinnaqtun). These maps show excellent agreement with local observations. Overall, SAR-based maps tailored for on-ice use are beneficial for and desired by northern community residents, and we recommend that high-resolution products be routinely made available in communities.  Les collectivités du Nord s’intéressent de plus en plus aux technologies qui leur fournissent de l’information au sujet de l’environnement de glace de mer à des fins de déplacements. La télédétection par radar à synthèse d’ouverture (SAR) est couramment utilisée pour observer la glace de mer, indépendamment de la lumière du soleil et de la nébulosité. Cependant, dans les collectivités du Nord, l’accès au SAR est restreint. Cette étude 1) définit les caractéristiques de la glace de mer qui exercent une influence sur les déplacements de deux collectivités dans l’ouest de l’Arctique canadien; 2) détermine l’utilité du SAR pour améliorer la mobilité et la sécurité quand vient le temps de traverser des environnements comportant ces caractéristiques; et 3) décrit les méthodes de partage de cartes établies à l’aide du SAR. Trois saisons sur le terrain (le printemps et l’automne de 2017, et le printemps de 2018) ont permis d’inciter les résidents à participer à une recherche locale guidée, là où les extrants appliqués ont été évalués par les membres de la collectivité. Nous avons trouvé que les données émanant des images du SAR éclairent et améliorent la sécurité de la glace de mer, l’aptitude à la circulation et l’éducation. L’information découlant de la technologie s’avère un complément désirable aux connaissances inuites en vue de la compréhension des caractéristiques de la glace de mer, dont la rugosité de la surface, la glace de mer mince, les conditions en début et en fin de saison, la bouillie de glace et la glace mouillée, la glace de mer rencontrée par les bateaux, et la discontinuité de la glace. Les données sur la glace de banc ne constituaient pas une priorité. La rugosité de la surface de la glace de mer était considérée comme la principale condition pour laquelle les avantages de la praticabilité déterminés au moyen des cartes établies à l’aide du SAR étaient substantiels. Les cartes indiquant la rugosité sont conçues en fonction de seuils représentant les caractéristiques de rugosité de la surface des glaces de mer (glace lisse/maniqtuk hiku, glace modérément rugueuse/maniilrulik hiku, glace rugueuse/maniittuq hiku; en dialecte inuinnaqtun). Ces cartes sont largement en accord avec les observations locales. Dans l’ensemble, les cartes établies à l’aide du SAR préparées en fonction des utilisations de la glace sont bénéfiques et désirées par les résidents des collectivités du Nord. Nous recommandons que des produits de haute résolution soient régulièrement mis à la disposition des collectivités

Multi-Modal Stories: LIS Students Explore Reading, Literacy, and Library Service Through the Lens of ‘The 39 Clues”

The article presents a conceptual framework for exploring multi-modal stories for children using the children’s adventure series, The 39 Clues. The framework is accompanied by concrete examples of student learning experiences, in the form of student reflections on issues related to the convergence of media and the nature of reading and children’s library service in the 21st century. The article begins with a look at the series, The 39 Clues, describing its history and its format. It then provides a framework for exploring some of the issues related to reading The 39 Clues, first, by introducing some concepts from the literature associated with reading in the digital world and then, outlining some of the practical concerns that librarians might have in relation to The 39 Clues. The article then presents the reflections of five students – one MLIS student and four PhD students – who considered multi-modal stories in light of their future practice, research, and teaching in LIS. The article concludes by summarizing five over-arching themes that emerged from the students’ explorations - reading as a two-track experience, questions about authorship, evaluation skills needed to review multimodal stories, opportunities for information literacy instruction, and access and equity issues

Interventions for preventing delirium in older people in institutional long-term care

BACKGROUND: Delirium is a common and distressing mental disorder. It is often caused by a combination of stressor events in susceptible people, particularly older people living with frailty and dementia. Adults living in institutional long-term care (LTC) are at particularly high risk of delirium. An episode of delirium increases risks of admission to hospital, development or worsening of dementia and death. Multicomponent interventions can reduce the incidence of delirium by a third in the hospital setting. However, it is currently unclear whether interventions to prevent delirium in LTC are effective. This is an update of a Cochrane Review first published in 2014. OBJECTIVES: To assess the effectiveness of interventions for preventing delirium in older people in institutional long-term care settings. SEARCH METHODS: We searched ALOIS (www.medicine.ox.ac.uk/alois), the Cochrane Dementia and Cognitive Improvement Group (CDCIG) 's Specialised Register of dementia trials (dementia.cochrane.org/our-trials-register), to 27 February 2019. The search was sufficiently sensitive to identify all studies relating to delirium. We ran additional separate searches in the Cochrane Central Register of Controlled Trials (CENTRAL), major healthcare databases, trial registers and grey literature sources to ensure that the search was comprehensive. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-randomised controlled trials (cluster-RCTs) of single and multicomponent, non-pharmacological and pharmacological interventions for preventing delirium in older people (aged 65 years and over) in permanent LTC residence. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcomes were prevalence, incidence and severity of delirium; and mortality. Secondary outcomes included falls, hospital admissions and other adverse events; cognitive function; new diagnoses of dementia; activities of daily living; quality of life; and cost-related outcomes. We used risk ratios (RRs) as measures of treatment effect for dichotomous outcomes, hazard ratios (HR) for time-to-event outcomes and mean difference (MD) for continuous outcomes. For each outcome, we assessed the overall certainty of the evidence using GRADE methods. MAIN RESULTS: We included three trials with 3851 participants. All three were cluster-RCTs. Two of the trials were of complex, single-component, non-pharmacological interventions and one trial was a feasibility trial of a complex, multicomponent, non-pharmacological intervention. Risk of bias ratings were mixed across the three trials. Due to the heterogeneous nature of the interventions, we did not combine the results statistically, but produced a narrative summary.It was not possible to determine the effect of a hydration-based intervention on delirium incidence (RR 0.85, 95% confidence interval (CI) 0.18 to 4.00; 1 study, 98 participants; very low-certainty evidence downgraded for risk of bias and very serious imprecision). This study did not assess delirium prevalence, severity or mortality.The introduction of a computerised system to identify medications that may contribute to delirium risk and trigger a medication review was probably associated with a reduction in delirium incidence (12-month HR 0.42, CI 0.34 to 0.51; 1 study, 7311 participant-months; moderate-certainty evidence downgraded for risk of bias) but probably had little or no effect on mortality (HR 0.88, CI 0.66 to 1.17; 1 study, 9412 participant-months; moderate-certainty evidence downgraded for imprecision), hospital admissions (HR 0.89, CI 0.72 to 1.10; 1 study, 7599 participant-months; moderate-certainty evidence downgraded for imprecision) or falls (HR 1.03, CI 0.92 to 1.15; 1 study, 2275 participant-months; low-certainty evidence downgraded for imprecision and risk of bias). Delirium prevalence and severity were not assessed.In the enhanced educational intervention study, aimed at changing practice to address key delirium risk factors, it was not possible to determine the effect of the intervention on delirium incidence (RR 0.62, 95% CI 0.16 to 2.39; 1 study, 137 resident months; very low-certainty evidence downgraded for risk of bias and serious imprecision) or delirium prevalence (RR 0.57, 95% CI 0.15 to 2.19; 1 study, 160 participants; very low-certainty evidence downgraded for risk of bias and serious imprecision). There was probably little or no effect on mortality (RR 0.82, CI 0.50 to 1.34; 1 study, 215 participants; moderate-certainty evidence downgraded for imprecision). The intervention was probably associated with a reduction in hospital admissions (RR 0.67, CI 0.57 to 0.79; 1 study, 494 participants; moderate-certainty evidence downgraded due to indirectness). AUTHORS' CONCLUSIONS: Our review identified limited evidence on interventions for preventing delirium in older people in LTC. A software-based intervention to identify medications that could contribute to delirium risk and trigger a pharmacist-led medication review, probably reduces incidence of delirium in older people in institutional LTC. This is based on one large RCT in the US and may not be practical in other countries or settings which do not have comparable information technology services available in care homes. In the educational intervention aimed at identifying risk factors for delirium and developing bespoke solutions within care homes, it was not possible to determine the effect of the intervention on delirium incidence, prevalence or mortality. This evidence is based on a small feasibility trial. Our review identified three ongoing trials of multicomponent delirium prevention interventions. We identified no trials of pharmacological agents. Future trials of multicomponent non-pharmacological delirium prevention interventions for older people in LTC are needed to help inform the provision of evidence-based care for this vulnerable group