bluuebunny/crossref_metadata_2025 huggingface dataset:
Validating the Breathing Vigilance Questionnaire for use in Dysfunctional Breathing
Authors: Steinmann Jennifer , Lewis Adam , Ellmers Toby , Jones Mandy , MacBean Vicky , Kal Elmar
Published: July 2022

Dysfunctional breathing (DB) is common among people with and without primary respiratory pathology. While anxiety contributes to DB, the underpinning mechanism is unclear. One explanation is that anxiety induces excessive conscious monitoring of breathing, disrupting ‘automatic’ breathing mechanics. We validated a new tool that quantifies such breathing-related ‘hypervigilance’: the Breathing Vigilance Questionnaire (Breathe-VQ).

Three-hundred-and-forty healthy adults (Mage=27.3 years, range: 18-71; 161 men) were recruited online. We developed an initial Breathe-VQ (11 items, 1-5 Likert scale) based on the Pain Vigilance and Awareness Scale, using feedback from the target population and clinicians. At baseline, participants completed the Breathe-VQ, Nijmegen Questionnaire (NQ), State-Trait Anxiety Inventory (form 2), and Movement-Specific Reinvestment Scale (assessing general conscious processing). Eighty-three people repeated the Breathe-VQ two weeks later.

We removed five items based on item-level analysis. The resulting six-item Breathe-VQ questionnaire (score range: 6-30) has excellent internal (alpha=.892) and test-retest reliability (ICC=.810), a minimal detectable change of 6.5, and no floor/ceiling effects. Concurrent validity was evidenced by significant positive correlations with trait anxiety and conscious processing scores (r’s=.35-.46). Participants at high-risk of having DB (NQ>23; N=76) had significantly higher Breathe-VQ score (M=19.1±5.0) than low-risk peers (N=225; M=13.8±5.4;p<.001). In this ‘high-risk’ group, Breathe-VQ and NQ-scores were significantly associated (p=.005), even when controlling for risk factors (e.g., trait anxiety).

The Breathe-VQ is a valid and reliable tool to measure breathing vigilance. Breathing vigilance may contribute to DB, and could represent a therapeutic target. Further research is warranted to further test the Breathe-VQ’s prognostic value, and assess intervention effects.

Key Findings

– Dysfunctional breathing (DB) is highly prevalent in the general population as well as in people with respiratory conditions.

– Anxiety is identified as a key factor contributing to DB, potentially because it induces conscious, anxious monitoring of breathing.

– We developed a short self-reported outcome measure of such breathing-specific vigilance, the Breathe-VQ.

– The Breathe-VQ was found to be a valid and reliable tool for use in the general population.

– Breathe-VQ scores were positively associated with self-reported breathing problems, after correcting for known risk factors such as trait-anxiety.
Multi-site disease analytics with applications to estimating COVID-19 undetected cases in Canada
Authors: Parker Matthew R. P. , Cao Jiguo , Cowen Laura L. E. , Elliott Lloyd T. , Ma Junling
Published: July 2022

Even with daily case counts, the true scope of the COVID-19 pandemic in Canada is unknown due to undetected cases. We estimate the pandemic scope through a new multi-site model using publicly available disease count data including detected cases, recoveries among detected cases, and total deaths. These counts are used to estimate the case detection probability, the infection fatality rate through time, as well as the probability of recovery, and several important population parameters including the rate of spread, and importation of external cases. We also estimate the total number of active COVID-19 cases per region of Canada for each reporting interval. We applied this multi-site model Canada-wide to all provinces and territories, providing an estimate of the total COVID-19 burden for the 90 weeks from 23 Apr 2020 to 6 Jan 2022. We also applied this model to the five Health Authority regions of British Columbia, Canada, describing the pandemic in B.C. over the 31 weeks from 2 Apr 2020 to 30 Oct 2020.
Changes in General Practice use and costs with COVID-19 and telehealth initiatives
Authors: Butler Danielle C , Joshy Grace , Douglas Kirsty A , Bin-Sayeed Muhammad-Shahdaat , Welsh Jennifer , Douglas Angus , Korda Rosemary J. ,   the ANU Telehealth in Primary Care study group
Published: July 2022

Background

In response to the COVID-19 pandemic, general practice (GP) in Australia underwent a rapid transition, including the rollout of population-wide telehealth, with uncertain impacts on GP use and costs.

Objective

To describe how use and costs of GP services in Australia changed in 2020—following the pandemic and introduction of telehealth—compared to 2019, and how this varied across population subgroups.

Method

Data for ∼19M individuals from Census 2016 were linked to Medicare data for 2019-2020 through the Multi-Agency Data Integration Project. We used regression models to compare age-sex-adjusted GP use and out-of-pocket cost (OPC) over time, overall and by sociodemographic characteristics.

Results

The number of people who visited a GP in Q2-Q4 of 2020 decreased by 4% compared to Q2-Q4 of 2019. The mean number of face-to-face GP services per quarter declined, while telehealth services increased, with overall use of GP services in Q4 2020 similar to or higher than Q4 2019. The proportion of total GP services by telehealth stabilised at ∼25% in Q4 2020. However, individuals aged 3-14 or ≥70 years and those with limited English proficiency used fewer GP services in 2020 compared to 2019, with a lower proportion by telehealth. Mean OPC-per-service was lower across all subgroups in 2020 compared to 2019.

Discussion

Introduction of widespread telehealth largely maintained use of GP services during the pandemic and minimised OPCs, but not for all population subgroups. This may indicate technological, social or other barriers in these populations, as well as pandemic-related changes in healthcare use.

HOW THIS FITS IN

In response to the COVID-19 pandemic, major telehealth initiatives were implemented to ensure access to primary healthcare while minimising disease transmission. Using routinely collected, whole-of-population data from Australia, we show that the introduction of telehealth during the pandemic largely maintained use of GP services while minimising costs. However, compared to pre-pandemic levels, GP use was lower among individuals aged 3-14 or ≥70 years and those not proficient in English, although these groups also saw the greatest reduction in out-of-pocket cost per service. As telehealth initiatives are integrated into standard GP care, it is vital to ensure telehealth is designed and funded to support these groups and the ongoing financial viability of practices.
Efficient generation of mNeonGreenPlasmodium falciparumreporter lines enables quantitative fitness analysis
Authors: Hoshizaki Johanna , Jagoe Hannah , Lee Marcus
Published: July 2022

1

CRISPR editing has enabled the rapid creation of fluorescentPlasmodiumtransgenic lines, facilitating a deeper understanding of parasite biology. The impact of genetic perturbations such as gene disruption or the introduction of drug resistance alleles on parasite fitness is typically quantified in competitive growth assays between the query line and a wild type reference. Although fluorescent reporter lines offer a facile and frequently used method to measure relative growth, this approach is limited by the strain background of the existing reporter, which may not match the growth characteristics of the query strains, particularly if these are slower-growing field isolates. Here, we demonstrate an efficient CRISPR-based approach to generate fluorescently labelled parasite lines using mNeonGreen derived from the LanYFP protein inBranchiostoma lanceolatum, which is one of the brightest monomeric green fluorescent proteins identified. Using a positive-selection approach by insertion of an in-frame blasticidin S deaminase marker, we generated a Dd2 reporter line expressing mNeonGreen under the control of thepfpare(P. falciparumProdrug Activation and Resistance Esterase) locus. We selected thepfparelocus as an integration site because it is highly conserved acrossP. falciparumstrains, expressed throughout the intraerythrocytic cycle, not essential, and offers the potential for negative selection to further enrich for integrants. The mNeonGreen@pareline demonstrates strong fluorescence with a negligible fitness defect. In addition, the construct developed can serve as a tool to fluorescently tag otherP. falciparumstrains forin vitroexperimentation.
Hydrogen stable isotope probing of lipids demonstrates slow rates of microbial growth in soil
Authors: Caro Tristan A. , McFarlin Jamie , Jech Sierra , Fierer Noah , Kopf Sebastian
Published: July 2022

The rate at which microorganisms grow and reproduce is fundamental to our understanding of microbial physiology and ecology. While soil microbiologists routinely quantify soil microbial biomass levels and the growth rates of individual taxa in culture, there is a limited understanding of how quickly microbes actually grow in soil. For this work, we posed the simple question: what are the growth rates of soil microorganisms? In this study, we measure these rates in three distinct soil environments using hydrogen stable isotope probing of lipids with2H-enriched water. This technique provides a taxa-agnostic quantification ofin situmicrobial growth from the degree of2H enrichment of intact polar lipid compounds ascribed to bacteria and fungi. We find that average apparent generation times in soil are quite slow (20 to 64 days) but also highly variable at the compound-specific level (6 to 1137 days), suggesting differential growth rates between community subsets. We observe that low-biomass communities can exhibit more rapid growth rates than high-biomass communities, highlighting that biomass quantity alone does not predict microbial productivity in soil. Furthermore, within a given soil, the rates at which specific lipids are being synthesized do not relate to their quantity, suggesting a general decoupling of microbial abundance and growth in soil microbiomes. More generally, we demonstrate the utility of lipid stable isotope probing for measuring microbial growth rates in soil and highlight the importance of measuring growth rates to complement more standard analyses of soil microbial communities.

Significance

Generation times, how quickly organisms grow and reproduce, are a key feature of biology. However, there are few measurements of microbial generation times in soil, despite the crucial importance of soil microbes to terrestrial ecosystems. By measuring the rate at which isotopically labeled water is incorporated into microbial membranes, we find that the generation times of soil microorganisms are far longer than those typically observed in culture. Surprisingly, we observe that lower-biomass soils exhibited faster growth rates than high-biomass soils. More abundant microorganisms are not necessarily the fastest growing and most soil microorganisms are slow growers. Our results underscore the importance of considering slow and variable growth rates when studying microbial communities and their contributions to ecosystem processes.
Changes in the transcriptome and long non-coding RNAs but not the methylome occur in human cells exposed to Borrelia burgdorferi
Authors: Berthold Anne , Lloyd Vett
Published: July 2022

Lyme disease, caused by infection with members of the Lyme borreliosis group of Borrelia spirochete bacteria, is increasing in frequency and distribution worldwide. This spread is driven by the expansion of ticks, vectors of these pathogens. Epigenetics may be involved in the interaction between mammalian host, tick, and bacterial pathogen, but is still poorly understood. Next-generation sequencing (NGS) allows the study of host response at the transcriptomic and methylomic scale.

We tested the effect of the Borrelia burgdorferi strain B31 on a human primary cell line (HUVEC) and an immortalized cell line (HEK-293) for 72 h, a time consistent with the duration of tick feeding and host cell exposure to B. burgdorferi. RNA and DNA were extracted from cells and used for RNA-seq and Enzymatic-Methyl-seq (EM-seq). Differential expression and Reactome pathway enrichment analysis were performed. More significantly differentially expressed genes (a total of 69) were found in HUVECs compared to HEK-293 (a total of 8). Borrelia burgdorferi exposure significantly induced genes in the interferon, cytokine, and other immune response signaling in HUVECs. In HEK-293, pre-NOTCH processing in Golgi was identified as a significant pathway. Other significant genes suggest extracellular matrix binding and interaction in HEK-293. Data comparison with other transcriptomic studies of human cells exposed to B. burgdorferi revealed a small overlap in genes identified in HUVEC, but no overlap for HEK-293. No significant methylation changes were detected in HUVECs or HEK-293 exposed to B. burgdorferi. However, two long non-coding RNAs and a pseudogene were deregulated in response to B. burgdorferi in HUVEC suggesting that other epigenetic mechanisms may be initiated by infection.

This is the first study examining the transcriptome and methylome of human cells exposed to B. burgdorferi for 72 h and so contributes to the description of early-stage B. burgdorferi infection at the cellular level.
Reductive evolution in the structure of the microsporidian proteasome
Authors: Jespersen Nathan , Ehrenbolger Kai , Winiger Rahel R. , Svedberg Dennis , Vossbrinck Charles R. , Barandun Jonas
Published: July 2022

Proteasomes play an essential role in the life cycle of intracellular pathogens with extracellular stages by ensuring proteostasis in environments with limited resources. In microsporidia, divergent parasites with extraordinarily streamlined genomes, the proteasome complexity and structure are unknown, which limits our understanding of how these unique pathogens adapt and compact essential eukaryotic complexes. We present cryo-electron microscopy structures of the microsporidian 20S and 26S proteasome isolated from dormant or germinated Vairimorpha necatrix spores. The presence of distinct densities within the central cavity of the dormant spore proteasome suggests reduced activity in the environmental stage. In contrast, the absence of these densities and the existence of 26S particles post-germination indicates rapid reactivation of proteasomes after host infection. Structual and phylogenetic analyses reveal that microsporidian proteasomes have undergone extreme reductive evolution, lost three regulatory proteins, and compacted nearly every subunit. The highly derived microsporidian proteasome structure presented here reinforces the feasibility of the development of specific inhibitors and provides insight into the unique evolution and biology of these medically and economically important pathogens.
REST: A method for restoring signals and revealing individual macromolecule states in cryo-ET
Authors: Zhang Haonan , Li Yan , Liu Yanan , Li Dongyu , Wang Lin , Song Kai , Bao Keyan , Zhu Ping
Published: July 2022

Cryo-electron tomography (cryo-ET) is widely used to explore the 3D density of biomacromolecules. However, the heavy noise and missing wedge effect prevent directly visualizing and analyzing the 3D reconstructions. Here, we introduced REST, a deep learning strategy-based method to establish the relationship between low-quality and high-quality density and transfer this knowledge to restore signals in cryo-ET. Experimental results on purified ribosome and recombinant nucleosome datasets showed that REST had outstanding performance in denoising and compensating the missing wedge. The application in dynamic nucleosome structures suggests that REST has the capability to reveal individual macromolecules which present different conformations without subtomogram averaging. Moreover, REST could greatly improve the reliability of particle picking. These advantages enable REST to be a powerful tool for the straightforward interpretation of target macromolecules by visual inspection of the density and of a broad range of other applications in cryo-ET, such as segmentation, particle picking, and subtomogram averaging.
Competition between phage-resistance mechanisms determines the outcome of bacterial co-existence
Authors: Rendueles Olaya , de Sousa Jorge A.M. , Rocha Eduardo P.C.
Published: July 2022

Many bacterial species carry multiple prophages. Despite their potential cost, these elements can provide multiple fitness advantages to the host, such as the elimination of direct competitors. However, the long-term efficiency of prophage induction to displace competitors has received little attention. We experimentally coevolved a polylysogenic Klebsiella pneumoniae strain (ST14) with a phage-sensitive strain (BJ1) in several environments resulting in different phage pressures. We then followed the adaptation process and the emergence of resistance. After 30 days, population yield remained stable, and although BJ1 was present in all conditions, its frequency was higher when phage pressure was stronger. Resistance to phages emerged quickly through mutations that prevent capsule biosynthesis. In contrast to our expectation, lysogenic conversion was rare and costly because new BJ1 lysogens exhibited exacerbated death rates and were easily outcompeted. Unexpectedly, the adaptation process changed at longer time scales, where BJ1 populations adapted by fine-tuning the production of capsule, reducing the ability of phage to absorb, while remaining capsulated. These resistant clones are pan-resistant to a large panel of phages. Most intriguingly, some clones exhibited transient non-genetic resistance to phages. Our experimental and modelling results highlight the diversity, dynamics and competition between phage-resistance mechanisms during coevolution and how these are driven by phage pressure.
What drives mixed-species shoaling among wild zebrafish? Role of predators, food access, abundance of conspecifics and kin familiarity
Authors: Mukherjee Ishani , Bhat Anuradha
Published: July 2022

Mixed-species groups commonly occur across a wide range of faunal communities and are known to provide several benefits to members. While zebrafish have often been observed to form mixed-species shoals with coexisting species, the factors determining their occurrence is not yet understood. Using laboratory-based experiments, we decipher the main ecological drivers of mixed-species shoaling in these tropical fish communities. Shoals comprising zebrafish (Danio rerio), flying barbs (Esomus danricus) and whitespots (Aplocheilus panchax) were collected from a stagnant canal at Haringhata (West Bengal, India). Experiments to assess foraging efficiency were conducted where single or mixed-species shoals (comprising 5 individuals) were given low or high amounts of food. Shoal choice experiments were also conducted to assess the preferences of test subjects (zebrafish individuals) for forming associations based on shoal composition and familiarity. Results from experiments on feeding efficiency revealed that foraging time varied substantially among the shoal types (i.e., single or mixed-species), and was dependent on the quantity of food available, but not linked to the body size of species composing the shoal. The choice experiments to examine preference for associations revealed that under predator risk, zebrafish associate more with mixed shoals, and showed comparable associations to shoals differing in the abundance of conspecifics. Furthermore, we found that zebrafish preferred to associate with familiar conspecific over unfamiliar mixed and unfamiliar conspecific shoals. Therefore, equitable food consumption in mixed shoals, greater association to mixed shoals in presence of predator and familiarity were found to be important drivers for choosing mixed-species shoaling by zebrafish.
Integrative HDX-MS enables quantification of the conformational landscape of the sugar transporter XylE
Authors: Jia Ruyu , Bradshaw Richard T. , Calvaresi Valeria , Politis Argyris
Published: July 2022

A yet unresolved challenge in structural biology is to quantify conformational states of proteins underpinning function. This challenge is particularly acute for membrane proteins owing to the difficulties in stabilising them for in vitro studies. To address this challenge, we present here an integrative strategy that combines hydrogen-deuterium exchange mass spectrometry (HDX-MS) with ensemble modelling. We benchmark our strategy on wild type and mutant conformers of XylE, a prototypical member of the ubiquitous Major Facilitator Superfamily (MFS) of transporters. Next, we apply our strategy to quantify conformational ensembles of XylE embedded in different lipid environments and identify key lipid contacts that modulate protein conformations. Further application of our integrative strategy to substrate-bound and inhibitor-bound ensembles, allowed us to unravel protein-ligand interactions contributing to the alternating access mechanism of secondary transport in atomistic detail. Overall, our study highlights the potential of integrative HDX-MS modelling to capture, accurately quantify and subsequently visualise co-populated states of membrane proteins in association with mutations and diverse substrates and inhibitors.

For Table of Content Only
Separation of heterogeneous Aggregatibacter actinomycetemcomitans outer membrane vesicles reveals that toxin sorting is driven by surface-associated DNA
Authors: Nice Justin B. , Collins Shannon M. , Agro Samuel M. J. , Sinani Anxhela , Moros Spencer D. , Pasch Leah M. , Brown Angela C.
Published: July 2022

Aggregatibacter actinomycetemcomitans is a Gram-negative oral bacterium associated with localized aggressive periodontitis as well as some systemic diseases. The strains of A. actinomycetemcomitans most closely associated with periodontal disease tend to produce more of a secreted leukotoxin (LtxA) than isolates from healthy carriers, suggesting a key role for this toxin in disease progression. LtxA is secreted via a type 1 secretion system, from the bacterial cytosol across both the inner and outer membranes in a single step into the supernatant, where it is able to interact with host cells. Upon secretion, some of the toxin associates with the bacterial cell membrane, enabling its release in association with the surface of outer membrane vesicles (OMVs), small, spherical vesicles derived from the outer membrane. We have previously observed that the highly leukotoxic A. actinomycetemcomitans strain JP2 produces two populations of OMVs, a highly abundant population of small (<100 nm in diameter) OMVs, and a less abundant population of large (>300 nm in diameter) OMVs. Here, we have investigated the association of LtxA with the two populations of OMVs varying in size. Our results indicate that surface-associated DNA drives the selective sorting of LtxA to large OMVs.
Probabilities of HIV-1 bNAb development in healthy and chronically infected individuals
Authors: Kreer Christoph , Lupo Cosimo , Ercanoglu Meryem S. , Gieselmann Lutz , Spisak Natanael , Grossbach Jan , Schlotz Maike , Schommers Philipp , Gruell Henning , Dold Leona , Beyer Andreas , Nourmohammad Armita , Mora Thierry , Walczak Aleksandra M. , Klein Florian
Published: July 2022

HIV-1 broadly neutralizing antibodies (bNAbs) are able to suppress viremia and prevent infection. Their induction by vaccination is therefore a major goal. However, in contrast to antibodies that neutralize other pathogens, HIV-1-specific bNAbs frequently carry uncommon molecular characteristics that might prevent their induction. Here, we performed unbiased sequence analyses of B cell receptor repertoires from 57 healthy and 46 chronically HIV-1- or HCV-infected individuals and learned probabilistic models to predict the likelihood of bNAb development. We formally show that lower probabilities for bNAbs are predictive of higher HIV-1 neutralization activity. Moreover, ranking of bNAbs by their probabilities allowed to identify highly potent antibodies with superior generation probabilities as preferential targets for vaccination approaches. Importantly, we found equal bNAb probabilities across infected and healthy donors. This implies that chronic infection is not a prerequisite for the generation of bNAbs, fostering the hope that HIV-1 vaccines can induce bNAb development in healthy individuals.

Significance Statement

While HIV-1 broadly neutralizing antibodies (bNAbs) can develop in chronically HIV-1-infected individuals, they could not yet be elicited by active vaccination. Here, we computationally demonstrate that HIV-1 bNAbs carry distinct sequence features making them unlikely outcomes of the antibody evolution. However, our approach allowed us to identify bNAbs with higher probabilities of being generated. These candidates can now serve as the most promising targets to be induced by vaccination. Moreover, we show that chronic infection has no influence on the probabilities of finding typical bNAb sequence features in the memory B cell compartment. Both findings are critical to design effective vaccination strategies.
A novel prion strain is responsible for the first case of chronic wasting disease in Finnish moose
Authors: Sun Julianna L. , Bian Jifeng , Kim Sehun , Crowell Jenna , Webster Bailey K. , Raisley Emma K. , Korpenfelt Sirkka-Liisa , Benestad Sylvie L. , Telling Glenn C.
Published: July 2022

Concern is mounting over the global emergence, expanding host range, and uncertain zoonotic potential of chronic wasting disease (CWD), a fatal, infectious disease of cervids caused by prions. Our previous studies using genetically modified CWD-susceptible mice showed that Norwegian and North American CWD are caused by different prion strains. Here we investigated the properties of prions causing the first case of Finnish moose CWD. While Finnish and Norwegian moose CWD prions share characteristics that distinguish them from North American CWD including the inability to replicate in lymphoid tissues, common responses to variations at residue 226 of host prion protein, and overlapping central nervous system profiles, they also exhibit pronounced conformational variation which is consistent with strain differences between Finnish and Norwegian moose CWD. Our findings support the existence of a surprisingly diverse portfolio of emergent CWD strains in Nordic countries that is etiologically distinct from North American CWD.

Summary line

Prion strain properties from the first case of chronic wasting disease in a Finnish moose are similar but not identical to Norwegian cases, supporting a growing population of strains in Nordic countries.
An Open Microfluidic Coculture Model of Fibroblasts and Eosinophils to Investigate Mechanisms of Airway Inflammation
Authors: Zeng Yuting , Su Xiaojing , Takezawa Meg G. , Fichtinger Paul S. , Lee Ulri N. , Pippin Jeffery W. , Shankland Stuart J. , Lim Fang Yun , Denlinger Loren C. , Jarjour Nizar N. , Mathur Sameer K. , Sandbo Nathan , Berthier Erwin , Esnault Stephane , Bernau Ksenija , Theberge Ashleigh B.
Published: July 2022

Interactions between fibroblasts and immune cells play an important role in tissue inflammation. Previous studies have found that eosinophils activated with interleukin-3 (IL-3) degranulate on aggregated immunoglobulin G (IgG) and release mediators that activate fibroblasts in the lung. However, these studies were done with eosinophil-conditioned media that have the capacity to investigate only one-way signaling from eosinophils to fibroblasts. Here, we demonstrate a coculture model of primary normal human lung fibroblasts (HLFs) and human blood eosinophils from patients with allergy and asthma using an open microfluidic coculture device. In our device, the two types of cells can communicate via two-way soluble factor signaling in the shared media while being physically separated by a half wall. Initially, we assessed the level of eosinophil degranulation by their release of eosinophil-derived neurotoxin (EDN). Next, we analyzed the inflammation-associated genes and soluble factors using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and multiplex immunoassays, respectively. Our results suggest an induction of a proinflammatory fibroblast phenotype of HLFs following the coculture with degranulating eosinophils, validating our previous findings. Additionally, we present a new result that indicate potential impacts of activated HLFs back on eosinophils. This open microfluidic coculture platform provides unique opportunities to investigate the intercellular signaling between the two cell types and their roles in airway inflammation and remodeling.
Lead exposure from general aviation emissions in the UK: a review and call for action
Authors: Mills Ashley , Peckham Stephen
Published: July 2022

Leaded fuel emissions exposed a global population of children to lead and its profound health consequences. Recognition of its harms precipitated a global phase out and replacement with unleaded substitutes for road vehicles. Despite this widespread recognition and action, aviation fuel for piston engine aircraft still contains lead. Leaded aviation fuel (AVGAS100LL) contains 0.56g of tetraethyl lead per litre and this lead must be jettisoned from the engine during operation to prevent fouling. This action distributes lead and lead compounds into the air and soil around general aviation airports. This has been shown to increase the blood lead levels of children living nearby to clinically significant levels. Whilst this problem is recognised by the EPA in the U.S, it has received little attention in the UK. We provide a review of the situation in the UK with regard to the current policy and regulation framework. We analysed the UK’s general aviation airport fleet, general avation airport data, and GB residential address data. We estimate the unleaded-readiness of the UK aviation fleet and the current usage of fuels at UK general aviation airports. We provide a first order estimate of the number of residential addresses exposed to lead near general aviation airports. We find that the majority of aviation fuel sold in the UK is leaded and that there are 370721 residences within 4km of a general aviation airport at risk from exposure to lead emissions. Finally we present a path forward for regulation change and public health monitoring.
National statutory reporting: not even ticking the boxes? The quality of ‘Learning from Deaths’ reporting in Quality Accounts within the NHS in England 2017-2020
Authors: Brummell Z , Braun D , Hussein Z , Moonesinghe SR , Vindrola-Padros C
Published: July 2022

Introduction

Regulation through statutory reporting is used in healthcare internationally to improve accountability, quality of care and patient safety. Since 2017 within the National Health Service (NHS) in England NHS Secondary Care Trusts (NSCTs) are legally required to report annually both quantitative and qualitative information related to patient deaths within their care within their publicly available Quality Accounts as part of a countrywide patient safety programme: The Learning from Deaths (LfDs) programme.

Method

All LfDs reports published between 2017 (programme inception) and 2020 were reviewed and evaluated through a critical realist lens, quantitatively reported using descriptive statistics and qualitatively using reflexive thematic analysis.

Results

In 2017/18 44% of NSCTs reported all six statutory elements of the LfDs reporting regulations, in 2019/20 35% of NSCTs were reporting this information. A small number of NSCTs did not report any parts of the LfDs regulatory requirements between 2017 and 2020. Multiple qualitative themes arose from this study suggesting problematic engagement with the LfDs programme, erroneous reporting accuracy and written communication.

Conclusions

The LfDs programme has to some extent reduced variation and improved consistency to the way that NSCTs identify, report and investigate deaths. However, three years into the LfDs programme the majority of NSCTs are not reporting as required by law. This makes the validity of National statutory reporting in Quality accounts within the NHS in England questionable as a regulatory process.
Strengthening Health System’s Capacity for Linkage to HIV Care for adolescent girls and young women and adolescent boys and young men in South Africa (SheS’Cap-Linkage): Protocol for a mixed methods study in KwaZulu-Natal, South Africa
Authors: Nicol Edward , Basera Wisdom , Lombard Carl , Jonas Kim , Ramraj Trisha , Govindasamy Darshini , Hlongwa Mbuzeleni , McClinton-Appollis Tracy , Mehlomakulu Vuyelwa , Naqvi Nuha , Bedford Jason , Drummond Jennifer , Cheyip Mireille , Dladla Sibongile , Pass Desiree , Funani Noluntu , Mathews Cathy
Published: July 2022

Introduction

In South Africa, HIV prevalence among adolescent girls and young women (AGYW) was 5.8% (15-19 years) and 15.6% (20-24 years) respectively in 2017. Amongst South African males, HIV prevalence in 2017 was 4.7% (15-19 years), 4.8% (20-24 years), 12.4% (25-29 years) and 18.4% (30-34 years). The National Department of Health adopted the universal test and treat (UTT) strategy in 2016, resulting in increases in same-day antiretroviral therapy initiations and linkage to care. Monitoring progress towards attainment of South Africa’s 95-95-95 targets amongst AGYW and adolescent boys and young men (ABYM) relies on high quality data to identify and address gaps in linkage to care. The purpose of this study is to provide evidence to guide efforts to improve linkage to, and retention in, HIV care among AGYW and ABYM in KwaZulu-Natal, in the context of the UTT strategy.

Methods and analysis

This is a mixed methods study, which will be conducted in uMgungundlovu district of KwaZulu-Natal, over a 24-month period, in 22 purposively selected HIV testing and treatment service delivery points (SDPs). For the quantitative component, a sample size of 1100 participants will be recruited into the study. The qualitative component will include 30 participating patients who were successfully linked to care, 30 who were not, and 30 who have never tested for HIV. The questionnaire study population comprises of 231 healthcare providers and AGYW aged 15-24 years and ABYM aged 15-35 years old. Primary outcomes will be evaluated using a logistic regression model. A time to event analysis will also be conducted taking the study design into account. Quantitative data for outcome variables and process indicators will be summarized by domain evaluated with logistic regression to account for potential confounders. For qualitative data, manual thematic content analysis will be conducted.

Ethics and dissemination

The protocol was approved by the South African Medical Research Council Health Research Ethics Committee (EC052-11/2020). Findings from the study will be communicated to the study population and results will be presented to stakeholders and at appropriate local and international conferences. Outputs will also include a policy brief, peer reviewed journal articles and research capacity building through research degrees.
Brainstem Auditory Physiology in Children with Listening Difficulties
Authors: Hunter Lisa L. , Blankenship Chelsea M. , Shinn-Cunningham Barbara , Hood Linda , Zadeh Lina Motlagh , Moore David R.
Published: July 2022

Children who have listening difficulties (LiD) despite having normal audiometry are often diagnosed as having an auditory processing disorder (APD). A lack of evidence regarding involvement of specific auditory mechanisms has limited development of effective treatments for these children. Here, we examined electrophysiologic evidence for brainstem pathway mechanisms in children with and without defined LiD. We undertook a prospective controlled study of 132 children aged 6-14 years with normal pure tone audiometry, grouped into LiD (n=63) or Typically Developing (TD; n=69) based on scores on the Evaluation of Children’s Listening and Processing Skills (ECLiPS), a validated caregiver report. The groups were matched on age at test, sex, race, and ethnicity. Neither group had diagnoses of major neurologic disorder, intellectual disability, or brain injuries. Both groups received a test battery designed to measure receptive speech perception against distractor speech, Listening in Spatialized Noise - Sentences (LiSN-S), along with multiple neurophysiologic measures that tap afferent and efferent auditory subcortical pathways. Group analysis showed that participants with LiD performed significantly more poorly on all subtests of the LiSN-S. The LiD group had significantly steeper wideband middle ear muscle reflex (MEMR) growth functions and shorter Wave III, Wave V, and I-V interpeak latencies in their auditory brainstem responses (ABR). Across individual participants, shorter latency ABR Wave V correlated significantly with poorer parent report of LiD (ECLiPS composite). Steeper MEMR growth functions also correlated with poorer ECLiPS scores and reduced LiSN-S talker advantage. The LiD and TD groups had equivalent summating potentials, compound action potentials, envelope-following responses (EFR), and binaurally activated medial olivocochlear reflexes (MOCR). In conclusion, there was no evidence for auditory synaptopathy or lower brainstem dysfunction for LiD. Evidence for higher brainstem differences between groups showed that the LiD group had increased efferent control or central gain, with shorter ABR Wave III and V latencies and steeper MEMR growth curves. These differences were related to poorer parent report and speech perception ability.
Pathway-based polygenic risk scores for schizophrenia and associations with clinical and neuroimaging phenotypes in UK Biobank
Authors: Barbu Miruna C. , Thng Gladi , Adams Mark J. , Marwick Katie , Grant Seth GN , McIntosh Andrew M. , Lawrie Stephen M. , Whalley Heather C.
Published: July 2022

Background

Schizophrenia is a heritable psychiatric disorder with a polygenic architecture. Genome-wide association studies (GWAS) have reported an increasing number of risk-associated variants and polygenic risk scores (PRS) now explain 17% of the variance in the disorder. There exists substantial heterogeneity in the effect of these variants and aggregating them based on biologically relevant functions may provide mechanistic insight into the disorder.

Methods

Using the largest schizophrenia GWAS to date, we calculated PRS based on 5 gene-sets previously found to contribute to the pathophysiology of schizophrenia: the postsynaptic density of excitatory synapses, postsynaptic membrane, dendritic spine, axon, and histone H3-K4 methylation gene-sets. We associated each PRS, along with respective whole-genome PRS (excluding single nucleotide polymorphisms in each gene-set), with neuroimaging (N>29,000; cortical, subcortical, and white matter microstructure) and clinical (N>119,000; psychotic-like experiences including conspiracies, communications, voices, visions, and distress) variables in healthy subjects in UK Biobank.

Results

A number of clinical and neuroimaging variables were significantly associated with the axon gene-set (psychotic-like communications: β=0.0916, pFDR=0.04, parahippocampal gyrus volume: β=0.0156, pFDR=0.03, FA thalamic radiations: β=-0.014, pFDR=0.036, FA posterior thalamic radiations: β=-0.016, pFDR=0.048), postsynaptic density gene-set (distress due to psychotic-like experiences: β=0.0588, pFDR=0.02, global surface area: β=-0.012, pFDR=0.034, and cingulate lobe surface area: β=-0.014, pFDR=0.04), and histone gene-set (entorhinal surface area: β=-0.016, pFDR=0.035). In the associations above, whole-genome PRS were significantly associated with psychotic-like communications (β=0.2218, pFDR=1.34×10−7), distress (β=0.1943, pFDR=7.28×10−16), and FA thalamic radiations (β=-0.0143, pFDR=0.036). Permutation analysis carried out for these associations revealed that they were not due to chance.

Conclusions

Our results indicate that genetic variation in 3 gene-sets relevant to schizophrenia (axon, postsynaptic density, histone) may confer risk for the disorder through effects on a number of neuroimaging variables that have previously been implicated in schizophrenia. As neuroimaging associations were stronger for gene-set PRS than whole-genome PRS, findings here highlight that selection of biologically relevant variants may address the heterogeneity of the disorder by providing further mechanistic insight into schizophrenia.
Crystal structure of the complex of 2,4,6-triethyl-1,3,5-tris[(4-methyl-1H-indazol-1-yl)methyl]benzene with NH4PF6
Authors: Fuhrmann Felix , Meier Eric , Seichter Wilhelm , Mazik Monika
Published: July 2022

The complex of 2,4,6-triethyl-1,3,5-tris[(4-methyl-1H-indazol-1-yl)methyl]benzene with ammonium hexafluorophosphate, C39H42N6·NH4
+·PF6
−, crystallizes in the monoclinic space group P21 with two molecules of the receptor, two NH4
+ and two PF6
− ions in the asymmetric unit. In each of the complexes the ammonium ion resides in the cavity of the receptor molecule and is fixed in its position by three N—H...N bonds, while the remaining hydrogen atom of the cation acts as a bifurcated binding site for N—H...F bonding to the counter-anion. The crystal is composed of one-dimensional supramolecular aggregates extending along the a-axis direction.
A transfer alignment algorithm based on combined double-time observation of velocity and attitude
Authors: Sheng Guangrun , Liu Xixiang , Wang Zixuan , Pu Wenhao , Wu Xiaoqiang , Ma Xiaoshuang
Published: July 2022

Purpose

This paper aims to present a novel transfer alignment method based on combined double-time observations with velocity and attitude for ships’ poor maneuverability to address the system errors introduced by flexural deformation and installing which are difficult to calibrate.

Design/methodology/approach

Based on velocity and attitude matching, redesigning and deducing Kalman filter model by combining double-time observation. By introducing the sampling of the previous update cycle of the strapdown inertial navigation system (SINS), current observation subtracts previous observation are used as measurements for transfer alignment filter, system error in measurement introduced by deformation and installing can be effectively removed.

Findings

The results of simulations and turntable tests show that when there is a system error, the proposed method can improve alignment accuracy, shorten the alignment process and not require any active maneuvers or additional sensor equipment.

Originality/value

Calibrating those deformations and installing errors during transfer alignment need special maneuvers along different axes, which is difficult to fulfill for ships’ poor maneuverability. Without additional sensor equipment and active maneuvers, the system errors in attitude measurement can be eliminated by the proposed algorithms, meanwhile improving the accuracy of the shipboard SINS transfer alignment.
Numerical study of freestream turbulence effects on the nose cones in supersonic flow
Authors: M. Velmani , V. Suresh
Published: July 2022

Purpose

This paper aims to numerically investigate the influence of shock wave and freestream turbulence interaction on the parabolic and spherically blunted nose cones at supersonic speed.

Design/methodology/approach

Using density-based solver, the three-dimensional steady-state simulation is carried out. The working fluid is calorically perfect that obeys ideal gas law and the no-slip boundary conditionis given to the surface of the nose cone. Pressure far-field boundary condition is imposed at the boundary of the computational domain by giving freestream Mach number, freestream static pressure and temperature.

Findings

The growth rate of the boundary layer is faster on the spherically blunted nose cone, hence, the overall drag force is higher than the parabolic nose cone. Temperature at the edge of the boundary layer is increased due to the early ampli-fication of instabilities by the upstream disturbance. In this sense, the effects of freestream turbulence depend on its level, freestream conditions, strength and type of shock wave and zone of influence.

Research limitations/implications

Simulations are carried out for the flow Mach number 2.0 at zero angles of attack for the freestream conditions of the flow at an altitude of 10,000 m.

Practical implications

The phenomenon of shock wave–turbulence interaction occurs in flow regimes from transonic to hypersonic speeds and finds a wide range of applications, especially in the design of aircraft and missiles configurations.

Originality/value

The phenomenon of compression wave and freestream turbulence interaction around the commonly used nose cones in the case of aircraft, missiles, etc., is investigated. The performance characteristics such as aerodynamic drag, boundary layer dynamics and the nature of flow around the different nose cones at zero angle of attack are illustrated.
Does the order of claims to assets on the balance sheet reflect equity risk?
Authors: Liu Cathy Zishang , Hu Xiaoyan Sharon , Reichelt Kenneth J.
Published: July 2022

Purpose

This paper empirically examines whether the order of liability and preferred stock accounts presented on the balance sheet is consistent with how the stock market values their riskiness.

Design/methodology/approach

This paper measures a firm’s riskiness with idiosyncratic risk and employs the first-difference design to test the relation between idiosyncratic risk and the order of current liabilities, noncurrent liabilities and preferred stock, respectively. Further, the paper tests whether operating liabilities are viewed as riskier than financial liabilities. Finally, the authors partition their sample based on the degree of financial distress and investigate whether the results differ between the two subsamples.

Findings

The paper finds that current liabilities are viewed as riskier than noncurrent liabilities and preferred stock is viewed as less risky than current and noncurrent liabilities, consistent with the ordering on the balance sheet. Further, the paper finds that operating liabilities are viewed as riskier than financial liabilities. Finally, the authors find that total liabilities and preferred stock (redeemable and convertible classes) are viewed as riskier for distressed firms than for nondistressed firms.

Originality/value

The authors thoroughly investigate the riskiness of several classes of claims and document that the classification of liabilities and preferred stock classes is relevant to common stockholders for assessing their associated risk.