Linking wheelchair kinetics to glenohumeral joint demand during everyday accessibility activities

The aim of the study was to investigate if push-rim kinetics could be used as markers of glenohumeral joint demand during manual wheelchair accessibility activities; demonstrating a method of biomechanical analysis that could be used away from the laboratory. Propulsion forces, trunk and upper limb kinematics and surface electromyography were recorded during four propulsion tasks (level, 2.5% cross slope, 6.5% incline and 12% incline). Kinetic and kinematic data were applied to an OpenSim musculoskeletal model of the trunk and upper limb, to enable calculation of glenohumeral joint contact force. Results demonstrated a positive correlation between propulsion forces and glenohumeral joint contact forces. Both propulsion forces and joint contact forces increased as the task became more challenging. Participants demonstrated increases in trunk flexion angle as the requirement for force application increased, significantly so in the 12% incline. There were significant increases in both resultant glenohumeral joint contact forces and peak and mean normalized muscle activity levels during the incline tasks. This study demonstrated the high demand placed on the glenohumeral joint during accessibility tasks, especially as the gradient of incline increases. A lightweight instrumented wheelchair wheel has potential to guide the user to minimize upper limb demand during daily activity

HIV-1 viral blips are associated with repeated and increasingly high levels of cell-associated HIV-1 RNA transcriptional activity

Objective:Some HIV+ patients, virally suppressed on ART, show occasional 'blips' of detectable HIV-1 plasma RNA. We used a new highly sensitive assay of cell-associated HIV-1 RNA to measure transcriptional activity in PBMCs and production of infectious virus from the viral reservoir, in patients with and without 'blips'.Design/methods:RNA and DNA extracted from cells in 6 ml of peripheral blood, from suppressed patients with one to two 'blip' episodes over the past 2 years of ART (n = 55), or no 'blips' (n = 52), were assayed for HIV-1 RNA transcripts and proviral DNA targeting the highly conserved 'R' region of the LTR. Follow-up samples were also collected. Purified CD4+T cells were cultured with anti-CD3/CD28/CD2 T-cell activator to amplify transcription and measure replication competent virus.Results:HIV-1 RNA transcripts ranged from 1.3 to 5415 copies/106white blood cells. 'Blip' patients had significantly higher levels vs. without blips (median 192 vs. 49; P = 0.0007), which correlated with: higher levels of inducible transcripts after activation in vitro, sustained higher HIV-1 transcription levels in follow-up samples along with increasing HIV-1 DNA in some, and production of replication-competent HIV-1.Conclusion:Viral 'blips' are significant reflecting higher transcriptional activity from the reservoir and contribute to the reservoir over time. This sensitive assay can be used in monitoring the size and activity of the HIV-1 reservoir and will be useful in HIV-1 cure strategies

Accelerated partner therapy (APT) partner notification for people with Chlamydia trachomatis: protocol for the Limiting Undetected Sexually Transmitted infections to RedUce Morbidity (LUSTRUM) APT cross-over cluster randomised controlled trial

INTRODUCTION: Partner notification (PN) is a process aiming to identify, test and treat the sex partners of people (index patients) with sexually transmitted infections (STIs). Accelerated partner therapy (APT) is a PN method whereby healthcare professionals assess sex partners, by telephone consultation, before giving the index patient antibiotics and STI self-sampling kits to deliver to their sex partner(s). The Limiting Undetected Sexually Transmitted infections to RedUce Morbidity programme aims to determine the effectiveness of APT in heterosexual women and men with chlamydia and determine whether APT could affect Chlamydia trachomatis transmission at population level. METHODS AND ANALYSIS: This protocol describes a cross-over cluster randomised controlled trial of APT, offered as an additional PN method, compared with standard PN. The trial is accompanied by an economic evaluation, transmission dynamic modelling and a qualitative process evaluation involving patients, partners and healthcare professionals. Clusters are 17 sexual health clinics in areas of England and Scotland with contrasting patient demographics. We will recruit 5440 heterosexual women and men with chlamydia, aged ≥16 years.The primary outcome is the proportion of index patients testing positive for C. trachomatis 12-16 weeks after the PN consultation. Secondary outcomes include: proportion of sex partners treated; cost effectiveness; model-predicted chlamydia prevalence; experiences of APT.The primary outcome analysis will be by intention-to-treat, fitting random effects logistic regression models that account for clustering of index patients within clinics and trial periods. The transmission dynamic model will be used to predict change in chlamydia prevalence following APT. The economic evaluation will use mathematical modelling outputs, taking a health service perspective. Qualitative data will be analysed using interpretative phenomenological analysis and framework analysis. ETHICS AND DISSEMINATION: This protocol received ethical approval from London-Chelsea Research Ethics Committee (18/LO/0773). Findings will be published with open access licences. TRIAL REGISTRATION NUMBER: ISRCTN15996256

Paneth Cells in Intestinal Homeostasis and Tissue Injury

Adult stem cell niches are often co-inhabited by cycling and quiescent stem cells. In the intestine, lineage tracing has identified Lgr5+ cells as frequently cycling stem cells, whereas Bmi1+, mTert+, Hopx+ and Lrig1+ cells appear to be more quiescent. Here, we have applied a non-mutagenic and cell cycle independent approach to isolate and characterize small intestinal label-retaining cells (LRCs) persisting in the lower third of the crypt of Lieberkühn for up to 100 days. LRCs do not express markers of proliferation and of enterocyte, goblet or enteroendocrine differentiation, but are positive for Paneth cell markers. While during homeostasis, LR/Paneth cells appear to play a supportive role for Lgr5+ stem cells as previously shown, upon tissue injury they switch to a proliferating state and in the process activate Bmi1 expression while silencing Paneth-specific genes. Hence, they are likely to contribute to the regenerative process following tissue insults such as chronic inflammation

A role of 18F-fluorodeoxyglucose positron emission/computed tomography in a strategy for abdominal wall metastasis of colorectal mucinous adenocarcinoma developed after laparoscopic surgery

Metastasis to the abdominal wall including port sites after laparoscopic surgery for colorectal cancer is rare. Resection of metastatic lesions may lead to greater survival benefit if the abdominal wall metastasis is the only manifestation of recurrent disease. A 57-year-old man, who underwent laparoscopic surgery for advanced mucinous adenocarcinoma of the cecum 6 years prior, developed a nodule in the surgical wound at the lower right abdomen. Although tumor markers were within normal limits, the metastasis to the abdominal wall and abdominal cavity from the previous cecal cancer was suspected. An abdominal computed tomography scan did not provide detective evidence of metastasis. 18F-fluorodeoxyglucose positron emission/computed tomography (18F-FDG PET/CT) was therefore performed, which demonstrated increased 18F-fluorodeoxyglucose uptake (maximum standardized uptake value: 3.1) in the small abdominal wall nodule alone. Histopathological examination of the resected nodule confirmed the diagnosis of metastatic mucinous adenocarcinoma. Prognosis of intestinal mucinous adenocarcinoma is reported to be poorer than that of non-mucinous adenocarcinoma. In conclusion, this case suggests an important role of 18F-FDG PET/CT in early diagnosis and decision-making regarding therapy for recurrent disease in cases where a firm diagnosis of recurrent colorectal cancer is difficult to make

Volcanic Gases:Silent Killers

This is the accepted manuscript. The final version is available at http://link.springer.com/chapter/10.1007%2F11157_2015_14.Volcanic gases are insidious and often overlooked hazards. The effects of volcanic gases on life may be direct, such as asphyxiation, respiratory diseases and skin burns; or indirect, e.g. regional famine caused by the cooling that results from the presence of sulfate aerosols injected into the stratosphere during explosive eruptions. Although accounting for fewer fatalities overall than some other forms of volcanic hazards, history has shown that volcanic gases are implicated frequently in small-scale fatal events in diverse volcanic and geothermal regions. In order to mitigate risks due to volcanic gases, we must identify the challenges. The first relates to the difficulty of monitoring and hazard communication: gas concentrations may be elevated over large areas and may change rapidly with time. Developing alert and early warning systems that will be communicated in a timely fashion to the population is logistically difficult. The second challenge focuses on education and understanding risk. An effective response to warnings requires an educated population and a balanced weighing of conflicting cultural beliefs or economic interests with risk. In the case of gas hazards, this may also mean having the correct personal protection equipment, knowing where to go in case of evacuation and being aware of increased risk under certain sets of meteorological conditions. In this chapter we review several classes of gas hazard, the risks associated with them, potential risk mitigation strategies and ways of communicating risk. We discuss carbon dioxide flows and accumulations, including lake overturn events which have accounted for the greatest number of direct fatalities, the hazards arising from the injection of sulfate aerosol into the troposphere and into the stratosphere. A significant hazard facing the UK and northern Europe is a “Laki”-style eruption in Iceland, which will be associated with increased risk of respiratory illness and mortality due to poor air quality when gases and aerosols are dispersed over Europe. We discuss strategies for preparing for a future Laki style event and implications for society

Identification of QTLs controlling gene expression networks defined a priori

BACKGROUND: Gene expression microarrays allow the quantification of transcript accumulation for many or all genes in a genome. This technology has been utilized for a range of investigations, from assessments of gene regulation in response to genetic or environmental fluctuation to global expression QTL (eQTL) analyses of natural variation. Current analysis techniques facilitate the statistical querying of individual genes to evaluate the significance of a change in response, also known as differential expression. Since genes are also known to respond as groups due to their membership in networks, effective approaches are needed to investigate transcriptome variation as related to gene network responses. RESULTS: We describe a statistical approach that is capable of assessing higher-order a priori defined gene network response, as measured by microarrays. This analysis detected significant network variation between two Arabidopsis thaliana accessions, Bay-0 and Shahdara. By extending this approach, we were able to identify eQTLs controlling network responses for 18 out of 20 a priori-defined gene networks in a recombinant inbred line population derived from accessions Bay-0 and Shahdara. CONCLUSION: This approach has the potential to be expanded to facilitate direct tests of the relationship between phenotypic trait and transcript genetic architecture. The use of a priori definitions for network eQTL identification has enormous potential for providing direction toward future eQTL analyses

Variations on a theme: diversification of cuticular hydrocarbons in a clade of cactophilic Drosophila

<p>Abstract</p> <p>Background</p> <p>We characterized variation and chemical composition of epicuticular hydrocarbons (CHCs) in the seven species of the <it>Drosophila buzzatii </it>cluster with gas chromatography/mass spectrometry. Despite the critical role of CHCs in providing resistance to desiccation and involvement in communication, such as courtship behavior, mating, and aggregation, few studies have investigated how CHC profiles evolve within and between species in a phylogenetic context. We analyzed quantitative differences in CHC profiles in populations of the <it>D. buzzatii </it>species cluster in order to assess the concordance of CHC differentiation with species divergence.</p> <p>Results</p> <p>Thirty-six CHC components were scored in single fly extracts with carbon chain lengths ranging from C₂₉to C₃₉, including methyl-branched alkanes, <it>n</it>-alkenes, and alkadienes. Multivariate analysis of variance revealed that CHC amounts were significantly different among all species and canonical discriminant function (CDF) analysis resolved all species into distinct, non-overlapping groups. Significant intraspecific variation was found in different populations of <it>D. serido </it>suggesting that this taxon is comprised of at least two species. We summarized CHC variation using CDF analysis and mapped the first five CHC canonical variates (CVs) onto an independently derived <it>period </it>(<it>per</it>) gene + chromosome inversion + mtDNA COI gene for each sex. We found that the COI sequences were not phylogenetically informative due to introgression between some species, so only <it>per </it>+ inversion data were used. Positive phylogenetic signal was observed mainly for CV1 when parsimony methods and the test for serial independence (TFSI) were used. These results changed when no outgroup species were included in the analysis and phylogenetic signal was then observed for female CV3 and/or CV4 and male CV4 and CV5. Finally, removal of divergent populations of <it>D. serido </it>significantly increased the amount of phylogenetic signal as up to four out of five CVs then displayed positive phylogenetic signal.</p> <p>Conclusions</p> <p>CHCs were conserved among species while quantitative differences in CHC profiles between populations and species were statistically significant. Most CHCs were species-, population-, and sex-specific. Mapping CHCs onto an independently derived phylogeny revealed that a significant portion of CHC variation was explained by species' systematic affinities indicating phylogenetic conservatism in the evolution of these hydrocarbon arrays, presumptive waterproofing compounds and courtship signals as in many other drosophilid species.</p

Is Cortisol Excretion Independent of Menstrual Cycle Day? A Longitudinal Evaluation of First Morning Urinary Specimens

Background Cortisol is frequently used as a marker of physiologic stress levels. Using cortisol for that purpose, however, requires a thorough understanding of its normal longitudinal variability. The current understanding of longitudinal variability of basal cortisol secretion in women is very limited. It is often assumed, for example, that basal cortisol profiles do not vary across the menstrual cycle. This is a critical assumption: if cortisol were to follow a time dependent pattern during the menstrual cycle, then ignoring this cyclic variation could lead to erroneous imputation of physiologic stress. Yet, the assumption that basal cortisol levels are stable across the menstrual cycle rests on partial and contradictory evidence. Here we conduct a thorough test of that assumption using data collected for up to a year from 25 women living in rural Guatemala. Methodology We apply a linear mixed model to describe longitudinal first morning urinary cortisol profiles, accounting for differences in both mean and standard deviation of cortisol among women. To that aim we evaluate the fit of two alternative models. The first model assumes that cortisol does not vary with menstrual cycle day. The second assumes that cortisol mean varies across the menstrual cycle. Menstrual cycles are aligned on ovulation day (day 0). Follicular days are assigned negative numbers and luteal days positive numbers. When we compared Models 1 and 2 restricting our analysis to days between −14 (follicular) and day 14 (luteal) then day of the menstrual cycle did not emerge as a predictor of urinary cortisol levels (p-value &gt;0.05). Yet, when we extended our analyses beyond that central 28-day-period then day of the menstrual cycle become a statistically significant predictor of cortisol levels. Significance The observed trend suggests that studies including cycling women should account for day dependent variation in cortisol in cycles with long follicular and luteal phases

Search for neutral MSSM Higgs bosons decaying to a pair of tau leptons in pp collisions

Peer reviewe