Feasibility randomized-controlled trial of online acceptance and commitment therapy for painful peripheral neuropathy in people living with HIV: The OPEN study

Background Neuropathic pain negatively affects quality of life among people living with HIV (PLWH). This study examined the feasibility of conducting a full‐scale randomized‐controlled trial of online acceptance and commitment therapy (“ACT OPEN”) for neuropathic pain in PLWH. Methods Using a parallel‐groups design, thirty‐eight participants were randomized to ACT OPEN or a waitlist control (2:1). Participants completed standard self‐report outcome measures at baseline, and two‐ and five‐months post‐randomization. Participants were aware of their allocation, but assessment was blinded. Results Twenty‐five participants were randomized to ACT OPEN and 13 to the control (of 133 referrals). ACT OPEN completion was 69% and two‐month trial retention was 82%. Treatment credibility and satisfaction scores for ACT OPEN were comparable to scores reported in previous trials of cognitive‐behavioural treatments for pain. Four adverse events were reported during the study, including one serious adverse event; all of these were unrelated to the research procedures. Small to moderate effects and 95% confidence intervals suggest that the true effect may favour ACT OPEN for improvements in pain intensity/interference and depression. Conclusions A full‐scale RCT of online ACT for pain management in PLWH may be feasible with refinements to trial design to facilitate recruitment. Significance Research on pain management in people living with HIV has primarily focused on pharmacological treatments with limited success. This is the first study to show the potential feasibility of a psychological treatment based on acceptance and commitment therapy delivered online and tailored for pain management in people with HIV (“ACT OPEN”). ACT OPEN may be a promising treatment in this population and further evaluation in a full‐scale randomized‐controlled trial appears warranted. Trial Registration: The trial was registered (clinicaltrials.gov; NCT03584412)

An Experimental Group A Streptococcus Vaccine That Reduces Pharyngitis and Tonsillitis in a Nonhuman Primate Model

Group A Streptococcus (GAS) infections account for an estimated 500,000 deaths every year. This bacterial pathogen is responsible for a variety of mild and life-threatening infections and the triggering of chronic autoimmune sequelae. Pharyngitis caused by group A Streptococcus (GAS), but not asymptomatic GAS carriage, is a prerequisite for acute rheumatic fever (ARF). Repeated bouts of ARF may trigger rheumatic heart disease (RHD), a major cause of heart failure and stroke accounting for 275,000 deaths annually. A vaccine that prevents pharyngitis would markedly reduce morbidity and mortality from ARF and RHD. Nonhuman primates (NHPs) have been utilized to model GAS diseases, and experimentally infected rhesus macaques develop pharyngitis. Here we use an NHP model of GAS pharyngitis to evaluate the efficacy of an experimental vaccine, Combo5 (arginine deiminase [ADI], C5a peptidase [SCPA], streptolysin O [SLO], interleukin-8 [IL-8] protease [SpyCEP], and trigger factor [TF]), specifically designed to exclude GAS components potentially linked to autoimmune complications. Antibody responses against all Combo5 antigens were detected in NHP serum, and immunized NHPs showed a reduction in pharyngitis and tonsillitis compared to controls. Our work establishes the NHP model as a gold standard for the assessment of GAS vaccines.IMPORTANCE GAS-related diseases disproportionally affect disadvantaged populations (e.g., indigenous populations), and development of a vaccine has been neglected. A recent strong advocacy campaign driven by the World Health Organization and the International Vaccine Institute has highlighted the urgent need for a GAS vaccine. One significant obstacle in GAS vaccine development is the lack of a widely used animal model to assess vaccine efficacy. Researchers in the field use a wide range of murine models of infection and in vitro assays, sometimes yielding conflicting results. Here we present the nonhuman primate pharyngeal infection model as a tool to assess vaccine-induced protection against colonization and clinical symptoms of pharyngitis and tonsillitis. We have tested the efficacy of an experimental vaccine candidate with promising results. We believe that the utilization of this valuable tool by the GAS vaccine research community could significantly accelerate the realization of a safe and effective GAS vaccine for humans

A Phylogenomic Supertree of Birds

It has long been appreciated that analyses of genomic data (e.g., whole genome sequencing or sequence capture) have the potential to reveal the tree of life, but it remains challenging to move from sequence data to a clear understanding of evolutionary history, in part due to the computational challenges of phylogenetic estimation using genome-scale data. Supertree methods solve that challenge because they facilitate a divide-and-conquer approach for large-scale phylogeny inference by integrating smaller subtrees in a computationally efficient manner. Here, we combined information from sequence capture and whole-genome phylogenies using supertree methods. However, the available phylogenomic trees had limited overlap so we used taxon-rich (but not phylogenomic) megaphylogenies to weave them together. This allowed us to construct a phylogenomic supertree, with support values, that included 707 bird species (~7% of avian species diversity). We estimated branch lengths using mitochondrial sequence data and we used these branch lengths to estimate divergence times. Our time-calibrated supertree supports radiation of all three major avian clades (Palaeognathae, Galloanseres, and Neoaves) near the Cretaceous-Paleogene (K-Pg) boundary. The approach we used will permit the continued addition of taxa to this supertree as new phylogenomic data are published, and it could be applied to other taxa as well.This research was funded by the US National Science Foundation, grant numbers DEB-1655683, DEB-1655624, DEB-1655559, DEB-1655736

Comparison of non-invasive peripheral venous saturations with venous blood co-oximetry

The estimation of venous oxygen saturations using photoplethysmography (PPG) may be useful as a noninvasive continuous method of detecting changes in regional oxygen supply and demand (e.g. in the splanchnic circulation). The aim of this research was to compare PPG-derived peripheral venous oxygen saturations directly with venous saturation measured from co-oximetry blood samples, to assess the feasibility of non-invasive local venous oxygen saturation. This paper comprises two similar studies: one in healthy spontaneously-breathing volunteers and one in mechanically ventilated anaesthetised patients. In both studies, PPG-derived estimates of peripheral venous oxygen saturations (SxvO2) were compared with co-oximetry samples (ScovO2) of venous blood from the dorsum of the hand. The results were analysed and correlation between the PPG-derived results and co-oximetry was tested for. In the volunteer subjects,moderate correlation (r = 0.81) was seen between SxvO2 values and co-oximetry derived venous saturations (ScovO2), with a mean (±SD) difference of +5.65 ± 14.3% observed between the two methods. In the anaesthetised patients SxvO2 values were only 3.81% lower than SpO2 and tended to underestimate venous saturation (mean difference = –2.67 ± 5.89%) while correlating weakly with ScovO2 (r = 0.10). The results suggest that significant refinement of the technique is needed to sufficiently improve accuracy to produce clinically meaningful measurement of peripheral venous oxygen saturation. In anaesthetised patients the use of the technique may be severely limited by cutaneous arteriovenous shunting

Small Worlds and Semantic Network Growth in Typical and Late Talkers

Network analysis has demonstrated that systems ranging from social networks to electric power grids often involve a small world structure-with local clustering but global ac cess. Critically, small world structure has also been shown to characterize adult human semantic networks. Moreover, the connectivity pattern of these mature networks is consistent with lexical growth processes in which children add new words to their vocabulary based on the structure of the language-learning environment. However, thus far, there is no direct evidence that a child's individual semantic network structure is associated with their early language learning. Here we show that, while typically developing children's early networks show small world structure as early as 15 months and with as few as 55 words, children with language delay (late talkers) have this structure to a smaller degree. This implicates a maladaptive bias in word acquisition for late talkers, potentially indicating a preference for “oddball” words. The findings provide the first evidence of a link between small-world connectivity and lexical development in individual children

Aquatic Macroinvertebrate Biodiversity Associated with Artificial Agricultural Drainage Ditches

Agricultural drainage channels and ditches are ubiquitous features in the lowland agricultural landscapes, built primarily to facilitate land drainage, irrigate agricultural crops and alleviate flood risk. Most drainage ditches are considered artificial waterbodies and are not typically included in routine monitoring programmes, and as a result the faunal and floral communities they support are poorly quantified. This paper characterizes the aquatic macroinvertebrate diversity (alpha, beta and gamma) of agricultural drainage ditches managed by an internal drainage board in Lincolnshire, UK. The drainage ditches support very diverse macroinvertebrate communities at both the site (alpha diversity) and landscape scale (gamma diversity) with the main arterial drainage ditches supporting greater numbers of taxa when compared to smaller ditches. Examination of the between site community heterogeneity (beta diversity) indicated that differences among ditches were high spatially and temporally. The results illustrate that both main arterial and side ditches make a unique contribution to aquatic biodiversity of the agricultural landscape. Given the need to maintain drainage ditches to support agriculture and flood defence measures, we advocate the application of principles from ‘reconciliation ecology’ to inform the future management and conservation of drainage ditches

Parental phonological memory contributes to prediction of outcome of late talkers from 20 months to 4 years: a longitudinal study of precursors of specific language impairment

Background Many children who are late talkers go on to develop normal language, but others go on to have longer-term language difficulties. In this study, we considered which factors were predictive of persistent problems in late talkers. Methods Parental report of expressive vocabulary at 18 months of age was used to select 26 late talkers and 70 average talkers, who were assessed for language and cognitive ability at 20 months of age. Follow-up at 4 years of age was carried out for 24 late and 58 average talkers. A psychometric test battery was used to categorize children in terms of language status (unimpaired or impaired) and nonverbal ability (normal range or more than 1 SD below average). The vocabulary and non-word repetition skills of the accompanying parent were also assessed. Results Among the late talkers, seven (29%) met our criteria for specific language impairment (SLI) at 4 years of age, and a further two (8%) had low nonverbal ability. In the group of average talkers, eight (14%) met the criteria for SLI at 4 years, and five other children (8%) had low nonverbal ability. Family history of language problems was slightly better than late-talker status as a predictor of SLI.. The best predictors of SLI at 20 months of age were score on the receptive language scale of the Mullen Scales of Early Learning and the parent's performance on a non-word repetition task. Maternal education was not a significant predictor of outcome. Conclusions In this study, around three-quarters of late talkers did not have any language difficulties at 4 years of age, provided there was no family history of language impairment. A family history of language-literacy problems was found to be a significant predictor for persisting problems. Nevertheless, there are children with SLI for whom prediction is difficult because they did not have early language delay

Links Between Hydrothermal Environments, Pyrophosphate, Na+, and Early Evolution

The discovery that photosynthetic bacterial membrane-bound inorganic pyrophosphatase (PPase) catalyzed light-induced phosphorylation of orthophosphate (Pi) to pyrophosphate (PPi) and the capability of PPi to drive energy requiring dark reactions supported PPi as a possible early alternative to ATP. Like the proton-pumping ATPase, the corresponding membrane-bound PPase also is a H+-pump, and like the Na+-pumping ATPase, it can be a Na+-pump, both in archaeal and bacterial membranes. We suggest that PPi and Na+ transport preceded ATP and H+ transport in association with geochemistry of the Earth at the time of the origin and early evolution of life. Life may have started in connection with early plate tectonic processes coupled to alkaline hydrothermal activity. A hydrothermal environment in which Na+ is abundant exists in sediment-starved subduction zones, like the Mariana forearc in the W Pacific Ocean. It is considered to mimic the Archean Earth. The forearc pore fluids have a pH up to 12.6, a Na+-concentration of 0.7 mol/kg seawater. PPi could have been formed during early subduction of oceanic lithosphere by dehydration of protonated orthophosphates. A key to PPi formation in these geological environments is a low local activity of water