Analysis of Arterial Mechanics During Head-down Tilt Bed Rest

Arterial health may be affected by microgravity or ground based analogs of spaceflight, as shown by an increase in thoracic aorta stiffness1. Head-down tilt bed rest (HDTBR) is often used as a ground-based simulation of spaceflight because it induces physiological changes similar to those that occur in space2, 3. This abstract details an analysis of arterial stiffness (a subclinical measure of atherosclerosis), the distensibility coefficient (DC), and the pressure-strain elastic modulus (PSE) of the arterial walls during HDTBR. This project may help determine how spaceflight differentially affects arterial function in the upper vs. lower body

Circadian deep sequencing reveals stress-response genes that adopt robust rhythmic expression during aging

Disruption of the circadian clock, which directs rhythmic expression of numerous output genes, accelerates aging. To enquire how the circadian system protects aging organisms, here we compare circadian transcriptomes in heads of young and old Drosophila melanogaster. The core clock and most output genes remained robustly rhythmic in old flies, while others lost rhythmicity with age, resulting in constitutive over- or under-expression. Unexpectedly, we identify a subset of genes that adopted increased or de novo rhythmicity during aging, enriched for stress-response functions. These genes, termed late-life cyclers, were also rhythmically induced in young flies by constant exposure to exogenous oxidative stress, and this upregulation is CLOCK-dependent. We also identify age-onset rhythmicity in several putative primary piRNA transcripts overlapping antisense transposons. Our results suggest that, as organisms age, the circadian system shifts greater regulatory priority to the mitigation of accumulating cellular stress

Stitching a new garment: considering the future of the speech–language therapy profession globally

Providing equitable support for people experiencing communication disability (CD) globally is a historical and contemporary challenge for the speech–language therapy profession. A group of speech–language therapists (SLTs) with ongoing and sustained experiences in Majority and Minority World contexts participated in five virtual meetings in 2021. The aim of these meetings was to develop provocative statements that might spur a global discussion among individuals and organisations that support people experiencing CD. The following questions were discussed: What is our vision for the future of the profession globally? What are the global challenges around access to speech–language therapy services? Four main themes emerged: (1) the need to centre people experiencing CD as the focal point of services, (2) participation, (3) equity and (4) community. The themes relate to the need for a process of de-imperialism in the profession. Suggestions were made to develop more suitable terminology and to establish a global framework that promotes more equitable access to communication services. We seek the adoption of approaches that focus on reciprocal global engagement for capacity strengthening. Alternative models of culturally sustaining and equitable service delivery are needed to create impact for people experiencing CD, and their families worldwide. Contribution: Provocative statements were developed to prompt global conversations among speech–language therapy professionals and associations. We encourage readers to consider the questions posed, share their viewpoints and initiate positive change towards a global strategy

Analysis of high-depth sequence data for studying viral diversity: a comparison of next generation sequencing platforms using Segminator II

Background: Next generation sequencing provides detailed insight into the variation present within viral populations, introducing the possibility of treatment strategies that are both reactive and predictive. Current software tools, however, need to be scaled up to accommodate for high-depth viral data sets, which are often temporally or spatially linked. In addition, due to the development of novel sequencing platforms and chemistries, each with implicit strengths and weaknesses, it will be helpful for researchers to be able to routinely compare and combine data sets from different platforms/chemistries. In particular, error associated with a specific sequencing process must be quantified so that true biological variation may be identified. Results: Segminator II was developed to allow for the efficient comparison of data sets derived from different sources. We demonstrate its usage by comparing large data sets from 12 influenza H1N1 samples sequenced on both the 454 Life Sciences and Illumina platforms, permitting quantification of platform error. For mismatches median error rates at 0.10 and 0.12%, respectively, suggested that both platforms performed similarly. For insertions and deletions median error rates within the 454 data (at 0.3 and 0.2%, respectively) were significantly higher than those within the Illumina data (0.004 and 0.006%, respectively). In agreement with previous observations these higher rates were strongly associated with homopolymeric stretches on the 454 platform. Outside of such regions both platforms had similar indel error profiles. Additionally, we apply our software to the identification of low frequency variants. Conclusion: We have demonstrated, using Segminator II, that it is possible to distinguish platform specific error from biological variation using data derived from two different platforms. We have used this approach to quantify the amount of error present within the 454 and Illumina platforms in relation to genomic location as well as location on the read. Given that next generation data is increasingly important in the analysis of drug-resistance and vaccine trials, this software will be useful to the pathogen research community. A zip file containing the source code and jar file is freely available for download from http://www.bioinf.manchester.ac.uk/segminator/

The Evolutionary Analysis of Emerging Low Frequency HIV-1 CXCR4 Using Variants through Time—An Ultra-Deep Approach

Large-scale parallel pyrosequencing produces unprecedented quantities of sequence data. However, when generated from viral populations current mapping software is inadequate for dealing with the high levels of variation present, resulting in the potential for biased data loss. In order to apply the 454 Life Sciences' pyrosequencing system to the study of viral populations, we have developed software for the processing of highly variable sequence data. Here we demonstrate our software by analyzing two temporally sampled HIV-1 intra-patient datasets from a clinical study of maraviroc. This drug binds the CCR5 coreceptor, thus preventing HIV-1 infection of the cell. The objective is to determine viral tropism (CCR5 versus CXCR4 usage) and track the evolution of minority CXCR4-using variants that may limit the response to a maraviroc-containing treatment regimen. Five time points (two prior to treatment) were available from each patient. We first quantify the effects of divergence on initial read k-mer mapping and demonstrate the importance of utilizing population-specific template sequences in relation to the analysis of next-generation sequence data. Then, in conjunction with coreceptor prediction algorithms that infer HIV tropism, our software was used to quantify the viral population structure pre- and post-treatment. In both cases, low frequency CXCR4-using variants (2.5–15%) were detected prior to treatment. Following phylogenetic inference, these variants were observed to exist as distinct lineages that were maintained through time. Our analysis, thus confirms the role of pre-existing CXCR4-using virus in the emergence of maraviroc-insensitive HIV. The software will have utility for the study of intra-host viral diversity and evolution of other fast evolving viruses, and is available from http://www.bioinf.manchester.ac.uk/segminator/

From cassava to gari: Mapping of quality characteristics and end-user preferences in Cameroon and Nigeria

User's preferences of cassava and cassava products along the value chain are supported by specific root quality characteristics that can be linked to root traits. Therefore, providing an evidence base of user preferred characteristics along the value chain, can help in the functional choice of cassava varieties. In this respect, the present paper presents the results from focus group discussions and individual interviews on user preferred quality characteristics of raw cassava roots and the derived product, gari, ‐ one of the major cassava products in Sub Saharan Africa ‐ in major production and consumption areas of Cameroon and Nigeria. Choice of cassava varieties for farming is mainly determined by the multiple end‐uses of the roots, their agricultural yield and the processing determinants of roots that support their major high‐quality characteristics: size, density, low water content, maturity, colour and safety. Processing of cassava roots into gari goes through different technological variants leading to a gari whose high‐quality characteristics are: dryness, colour, shiny/attractive appearance, uniform granules and taste. Eba, the major consumption form of gari in Cameroon and Nigeria is mainly characterized by its textural properties: smoothness, firmness, stickiness, elasticity, mouldability. Recommendations are made, suggesting that breeding will have to start evaluating cassava clones for brightness/shininess, as well as textural properties such as mouldability and elasticity of cassava food products, for the purpose of supporting decision‐making by breeders and the development of high‐throughput selection methods of cassava varieties. Women are identified as important beneficiaries of such initiatives giving their disadvantaged position and their prominent role in cassava processing and marketing of gari

Tiotropium in asthma: what is the evidence and how does it fit in?

Despite current therapeutic approaches asthma remains uncontrolled in a significant proportion of patients. Short-acting anticholinergic bronchodilators have a very long history of use in asthma, and recent data confirms the importance of acetylcholine as both a bronchoconstrictor and as a regulator of inflammation and remodeling in the lungs. Data from a comprehensive clinical trial programme, as well as use in primary care, show the efficacy and safety of tiotropium in adults with mild to moderate asthma when it is added to ICS and in severe asthma when it is added to high doses of ICS plus LABA, as well as in adolescents. Tiotropium is cost effective and its benefits are not restricted to particular phenotypes, making it a useful addition to the therapeutic options recommended by the Global Initiative for Asthma (GINA) for people with poorly controlled asthma at steps 4 & 5.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd

Tutorial:Speech assessment for multilingual children who do not speak the same language(s) as the speech-language pathologist

Purpose: The aim of this tutorial is to support speech language pathologists (SLPs) undertaking assessments of multilingual children with suspected speech sound disorders, particularly children who speak languages that are not shared with their SLP. Method: The tutorial was written by the International Expert Panel on Multilingual Children’s Speech, which comprises 46 researchers (SLPs, linguists, phoneticians, and speech scientists) who have worked in 43 countries and used 27 languages in professional practice. Seventeen panel members met for a 1-day workshop to identify key points for inclusion in the tutorial, 26 panel members contributed to writing this tutorial, and 34 members contributed to revising this tutorial online (some members contributed tomore than 1 task). Results: This tutorial draws on international research evidence and professional expertise to provide a comprehensive overview of working with multilingual children with suspected speech sound disorders. This overview addresses referral, case history, assessment, analysis, diagnosis, and goal setting and the SLP’s cultural competence and preparation for working with interpreters and multicultural support workers and dealing with organizational and government barriers to and facilitators of culturally competent practice. Conclusion: The issues raised in this tutorial are applied in a hypothetical case study of an English-speaking SLP’s assessment of a multilingual Cantonese-and English-speaking 4-year-old boy. Resources are listed throughout the tutorial.Australian Research Council: FT0990588United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Deafness & Other Communication Disorders (NIDCD

The growth of sociological theory : human nature, knowledge, and social change

xv, 527 p. : il.; 24 cm