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Abstract This review aims at providing an extensive discussion of modern constraints relevant for dense and hot strongly interacting matter. It includes theoretical first-principle results from lattice and perturbative QCD, as well as chiral effective field theory results. From the experimental side, it includes heavy-ion collision and low-energy nuclear physics results, as well as observations from neutron stars and their mergers. The validity of different constraints, concerning specific conditions and ranges of applicability, is also provided.

We prove two completeness results for Kleene algebra with tests and a top element, with respect to guarded string languages and binary relations. While the equational theories of those two classes of models coincide over the signature of Kleene algebra, this is no longer the case when we consider an additional constant ``top'' for the full element. Indeed, the full relation satisfies more laws than the full language, and we show that those additional laws can all be derived from a single additional axiom. We recover that the two equational theories coincide if we slightly generalise the notion of relational model, allowing sub-algebras of relations where top is a greatest element but not necessarily the full relation. We use models of closed languages and reductions in order to prove our completeness results, which are relative to any axiomatisation of the algebra of regular events. For one of our constructions, we extend the concept of finite monoid recognisability to guarded-string languages; this device makes it possible to obtain a PSpace algorithm for the equational theory of binary relations.

Background: Patient-reported outcome measures (PROMs) are used as part of clinical practice to determine the impact of the condition and treatment interventions on a patient’s health and quality of life. The Patient Health Questionnaire-9 (PHQ-9) is a self-administered diagnostic tool that has been widely adopted for the detection and monitoring of depression. Aim: This analysis reports the change in PHQ-9 scores from admission to discharge in patients admitted for depression to a South African acute psychiatric facility and aims to quantify the treatment effect of the admission using the PHQ-9 as the measurement tool. Setting: South African acute psychiatric facility. Methods: This was a retrospective observational study of all patients admitted to Netcare Akeso acute psychiatric facilities from 01 January 2018 to 31 October 2022. Patients were included if they were ≥ 18 years of age, admitted with a primary International Classification of Disease (ICD)-10 code for depression (i.e. F32–F33) and fully completed both an admission and discharge PHQ-9 questionnaire. We excluded facilities focusing only on the treatment of patients with specialised conditions such as addiction or eating disorders. Results: This analysis included 13 308 patients admitted for depression at 10 different facilities. The median PHQ-9 score on admission was 19 (interquartile range [IQR] 14–23) and 5 (IQR 2–11) on discharge, with a median change of -12 (IQR -5 to -18). A minimal clinically important difference was seen in 87.6% patients (n = 10 091/11 515); a treatment effect was seen in 74.5% of patients and a clinically significant improvement was seen in 72.1% of patients. Conclusion: With the average patient reporting a four-fold reduction in the severity of their depression scores, PROMs provide a critical patient-centred window into the benefit that an inpatient admission has on those suffering with depression. Contribution: These changes are consistent with those seen internationally and provide a baseline for understanding the treatment efficacy of an inpatient admission for the treatment of depression.

Introduction Perinatal mortality is a major public health issue in sub-Saharan Africa, with Ghana experiencing consistently high rates. This poses challenges for achieving the maternal and child health-related sustainability development goals by 2030. While some studies have explored factors behind perinatal mortality in Ghana, a comprehensive analysis considering multifactorial predictors remains absent. This scoping review, guided by Anderson’s framework of healthcare utilisation, aims to address this. The primary objective is to map the predictors of perinatal mortality in Ghana using Anderson’s framework. It aims to identify interpersonal, social structural and health beliefs as predisposing factors; evaluate access to healthcare, social support and health literacy as enabling factors; and outline maternal and foetal conditions as need factors, concluding with identified knowledge gaps.Methods and analysis The Cochrane handbook for systematic reviews of interventions will be used to guide the conduct of this review. Four main electronic databases, PubMed, Web of Science, Scopus and Cumulative Index for Nursing and Allied Health Literature, will be searched. Eligible studies will be charted and synthesised, focussing on Anderson’s primary domains: predisposing factors, enabling factors and need factors. Studies published in the English language from January 2000 to June 2024 will be included in the study to cover the most recent factors associated with perinatal mortality in Ghana.Ethics and dissemination This review will rely on already published peer-reviewed articles and therefore will not require ethical approval. The review results will be disseminated through peer-reviewed scientific publications and annual health services review conferences in Ghana.PROSPERO registration number CRD42024564968.

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IntroductionRadiologists frequently lack direct patient contact due to time constraints. Digital medical interview assistants aim to facilitate the collection of health information. In this paper, we propose leveraging conversational agents to realize a medical interview assistant to facilitate medical history taking, while at the same time offering patients the opportunity to ask questions on the examination.MethodsMIA, the digital medical interview assistant, was developed using a person-based design approach, involving patient opinions and expert knowledge during the design and development with a specific use case in collecting information before a mammography examination. MIA consists of two modules: the interview module and the question answering module (Q&A). To ensure interoperability with clinical information systems, we use HL7 FHIR to store and exchange the results collected by MIA during the patient interaction. The system was evaluated according to an existing evaluation framework that covers a broad range of aspects related to the technical quality of a conversational agent including usability, but also accessibility and security.ResultsThirty-six patients recruited from two Swiss hospitals (Lindenhof group and Inselspital, Bern) and two patient organizations conducted the usability test. MIA was favorably received by the participants, who particularly noted the clarity of communication. However, there is room for improvement in the perceived quality of the conversation, the information provided, and the protection of privacy. The Q&A module achieved a precision of 0.51, a recall of 0.87 and an F-Score of 0.64 based on 114 questions asked by the participants. Security and accessibility also require improvements.ConclusionThe applied person-based process described in this paper can provide best practices for future development of medical interview assistants. The application of a standardized evaluation framework helped in saving time and ensures comparability of results.

Aging is the main risk factor of cognitive neurodegenerative diseases such as Alzheimer's disease, with epigenome alterations as a contributing factor. Here, we compared transcriptomic/epigenomic changes in the hippocampus, modified by aging and by tauopathy, an AD-related feature. We show that the cholesterol biosynthesis pathway is severely impaired in hippocampal neurons of tauopathic but not of aged mice pointing to vulnerability of these neurons in the disease. At the epigenomic level, histone hyperacetylation was observed at neuronal enhancers associated with glutamatergic regulations only in the tauopathy. Lastly, a treatment of tau mice with the CSP-TTK21 epi-drug that restored expression of key cholesterol biosynthesis genes counteracted hyperacetylation at neuronal enhancers and restored object memory. As acetyl-CoA is the primary substrate of both pathways, these data suggest that the rate of the cholesterol biosynthesis in hippocampal neurons may trigger epigenetic-driven changes, that may compromise the functions of hippocampal neurons in pathological conditions.

BackgroundChildren’s mental health, including their well-being, is a major public health concern, as the burden of related disorders may last throughout one’s life. Although epidemiological mental health surveillance systems for children and adolescents have been implemented in several countries, they are sorely lacking in France. ObjectiveThis study aims to describe the first step of the implementation of a novel surveillance system in France called Enabee (Etude nationale sur le bien-être des enfants), which focuses on the issue of mental health in children. The system aims to (1) describe the temporal trends in the population-based prevalence of the main mental health disorders and well-being in children aged 3 to 11 years, (2) explore their major determinants, and (3) assess mental health care use by this population. To do this, Enabee will rely on results from a recurrent national cross-sectional homonymous study. This paper presents the protocol for the first edition of this study (called Enabee 2022), as well as initial results regarding participation. MethodsEnabee 2022 is a national cross-sectional study that was implemented in French schools in 2022. It used a probabilistic, multistage, stratified, and balanced sampling plan as follows: first, schools were randomly drawn and stratified according to the type of school. Up to 4 classes per school were then randomly drawn, and finally, all the pupils within each class were selected. The study covered children from preschool and kindergarten (aged 3 to 6 years, US grading system) to fifth grade (aged 6 to 11 years). Children from first to fifth grades provided a self-assessment of their mental health using 2 validated self-administered questionnaires: the Dominic Interactive (DI) and the KINDL. Parents and teachers completed a web-based questionnaire, including the Strengths and Difficulties Questionnaire. Parents also answered additional questions about their parenting attitudes; their own mental health; known social, economic, and environmental determinants of mental health in children; and their child’s life habits. Health, education, and family stakeholders were involved in designing and implementing the study as part of a large consultation group. ResultsData were collected from May 2, 2022, to July 31, 2022, in 399 schools across metropolitan France. Teachers completed questionnaires for 5721 pupils in preschool and kindergarten and for 15,263 pupils from first to fifth grades. Parents completed questionnaires for 3785 children in preschool and kindergarten and for 9227 children from first to fifth grades. Finally, 15,206 children from first to fifth grades completed the self-administered questionnaire. ConclusionsEnabee 2022 constitutes the first milestone in the development of a novel national epidemiological surveillance system, paving the way for improved children’s mental health policies in France.

Abstract The Mycobacterium tuberculosis complex (MTBC) comprises nine human-adapted lineages that differ in their geographical distribution. Local adaptation of specific MTBC genotypes to the respective human host population has been invoked in this context. We aimed to assess if bacterial genetics governs MTBC pathogenesis or if local co-adaptation translates into differential susceptibility of human macrophages to infection by different MTBC genotypes. We generated macrophages from cryopreserved blood mononuclear cells of Tanzanian tuberculosis patients, from which the infecting MTBC strains had previously been phylogenetically characterized. We infected these macrophages ex vivo with a phylogenetically similar MTBC strain (“matched infection”) or with strains representative of other MTBC lineages (“mismatched infection”). We found that L1 infections resulted in a significantly lower bacterial burden and that the intra-cellular replication rate of L2 strains was significantly higher compared the other MTBC lineages, irrespective of the MTBC lineage originally infecting the patients. Moreover, L4-infected macrophages released significantly greater amounts of TNF-α, IL-6, IL-10, MIP-1β, and IL-1β compared to macrophages infected by all other strains. While our results revealed no measurable effect of local adaptation, they further highlight the strong impact of MTBC phylogenetic diversity on the variable outcome of the host–pathogen interaction in human tuberculosis.

Abstract External signs of disease are frequently used as indicators of disease susceptibility. However, immune profiling can be a more effective indicator to understand how host responses to infection may be shaped by host, pathogen and environmental factors. To better inform wildlife health assessment and research directions, we investigated the utility of a novel multivariate immunophenotyping approach examining innate and adaptive immune responses in differing climatic, pathogen co-infection and demographic contexts across two koala (Phascolarctos cinereus) populations in New South Wales: the Liverpool Plains (LP), and Southern Highlands to South-west Sydney (SHSWS). Relative to the comparatively healthy SHSWS, the LP had greater and more variable innate immune gene expression (IL-1β, IL-6), and KoRV transcription. During extreme heat and drought, koalas from the LP displayed upregulation of a stress pathway gene and reduced adaptive immune genes expression, haematocrit and plasma protein, suggesting the possibility of environmental impacts through multiple pathways. In those koalas, KoRV transcription status, Chlamydia pecorum infection loads, and visible urogenital inflammation were not associated with immune variation, suggesting that immune markers were more sensitive indicators of real-time impacts than observed disease outcomes.

Abstract The cellular mechanisms underlying axonal morphogenesis are essential to the formation of functional neuronal networks. We previously identified the autism-linked kinase NUAK1 as a central regulator of axon branching through the control of mitochondria trafficking. However, (1) the relationship between mitochondrial position, function and axon branching and (2) the downstream effectors whereby NUAK1 regulates axon branching remain unknown. Here, we report that mitochondria recruitment to synaptic boutons supports collateral branches stabilization rather than formation in mouse cortical neurons. NUAK1 deficiency significantly impairs mitochondrial metabolism and axonal ATP concentration, and upregulation of mitochondrial function is sufficient to rescue axonal branching in NUAK1 null neurons in vitro and in vivo. Finally, we found that NUAK1 regulates axon branching through the mitochondria-targeted microprotein BRAWNIN. Our results demonstrate that NUAK1 exerts a dual function during axon branching through its ability to control mitochondrial distribution and metabolic activity.

We present fully abstract encodings of the call-by-name and call-by-value $\lambda$-calculus into HOcore, a minimal higher-order process calculus with no name restriction. We consider several equivalences on the $\lambda$-calculus side -- normal-form bisimilarity, applicative bisimilarity, and contextual equivalence -- that we internalize into abstract machines in order to prove full abstraction of the encodings. We also demonstrate that this technique scales to the $\lambda\mu$-calculus, i.e., a standard extension of the $\lambda$-calculus with control operators.

ABSTRACT Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains one of the deadliest infectious diseases globally. Timely diagnosis is a key step in the management of TB patients and in the prevention of further transmission events. Current diagnostic tools are limited in these regards. There is an urgent need for new accurate non-sputum-based diagnostic tools for the detection of symptomatic as well as subclinical TB. In this study, we recruited 52 symptomatic TB patients (sputum Xpert MTB/RIF positive) and 58 household contacts to assess the accuracy of a sequence-specific hybridization assay that detects the presence of Mtb cell-free DNA in urine. Using sputum Xpert MTB/RIF as a reference test, the magnetic bead-capture assay could discriminate active TB from healthy household contacts with an overall sensitivity of 72.1% [confidence interval (CI) 0.59–0.86] and specificity of 95.5% (CI 0.90–1.02) with a positive predictive value of 93.9% and negative predictive value of 78.2%. The detection of Mtb-specific DNA in urine suggested four asymptomatic TB infection cases that were confirmed in all instances either by concomitant Xpert MTB/RIF sputum testing or by follow-up investigation raising the specificity of the index test to 100%. We conclude that sequence-specific hybridization assays on urine specimens hold promise as non-invasive tests for the detection of subclinical TB.IMPORTANCEThere is an urgent need for a non-sputum-based diagnostic tool allowing sensitive and specific detection of all forms of tuberculosis (TB) infections. In that context, we performed a case-control study to assess the accuracy of a molecular detection method enabling the identification of cell-free DNA from Mycobacterium tuberculosis that is shed in the urine of tuberculosis patients. We present accuracy data that would fulfill the target product profile for a non-sputum test. In addition, recent epidemiological data suggested that up to 50% of individuals secreting live bacilli do not present with symptoms at the time of screening. We report, here, that the investigated index test could also detect instances of asymptomatic TB infections among household contacts.

The type-Silurian Cellon section in the Carnic Alps in Austria underpins much of the current Silurian conodont zonations, forming the basis for the Silurian timescale. However, the Silurian record of the Cellon section lacks radiometric and astrochronological age constraints, making it difficult to gain insights into the processes pacing Silurian (anoxic) events. To attain age constraints and investigate the pacing Silurian (anoxic) events by astronomical cycles, a cyclostratigraphic study was conducted on high-resolution pXRF (CaO, Al2O3, and Fe2O3) and induration records spanning the Ludlow and Pridoli parts of the Cellon section. Astronomical cycles ranging from precession to the 405-kyr eccentricity cycle were first recognised visually in the field and in proxy records. The visual detection of astronomical cycles served as an input for the WaverideR R package, enabling the tracking of the 405-kyr eccentricity period in each proxy’s continous wavelet transform scalograms. These tracked period curves were combined with external age controls through multiple Monte Carlo simulations, generating an (absolute) age model. This age model is used to assign ages and durations and their respective uncertainties to a hiatus in the Ludfordian, conodont zones, lithological units, geochronological units and events, yielding new ages for Silurian stage boundaries (e.g., Gorstian-Ludfordian boundary at 425.92 ± 0.65 Ma, the Ludfordian-Pridoli boundary at 423.03 ± 0.53 Ma, the Silurian-Devonian boundary at 418.86 ± 1.02 Ma), and new durations for the Ludfordian at 2.89 ± 0.35 Myr and Pridoli at 4.24 ± 0.46 Myr. Furthermore, the imprint of astronomical cycles in the Cellon section itself indicates that the Linde, Klev and Silurian-Devonian boundary events all occur after a 2.4-Myr eccentricity node, indicating pacing by astronomical forcing, similar to other Devonian and Cretaceous anoxic events. The Lau event, however, does not appear to coincide with a 2.4-Myr eccentricity node.

In the literature on Kleene algebra, a number of variants have been proposed which impose additional structure specified by a theory, such as Kleene algebra with tests (KAT) and the recent Kleene algebra with observations (KAO), or make specific assumptions about certain constants, as for instance in NetKAT. Many of these variants fit within the unifying perspective offered by Kleene algebra with hypotheses, which comes with a canonical language model constructed from a given set of hypotheses. For the case of KAT, this model corresponds to the familiar interpretation of expressions as languages of guarded strings. A relevant question therefore is whether Kleene algebra together with a given set of hypotheses is complete with respect to its canonical language model. In this paper, we revisit, combine and extend existing results on this question to obtain tools for proving completeness in a modular way. We showcase these tools by giving new and modular proofs of completeness for KAT, KAO and NetKAT, and we prove completeness for new variants of KAT: KAT extended with a constant for the full relation, KAT extended with a converse operation, and a version of KAT where the collection of tests only forms a distributive lattice.

Abstract Phage satellites are bacterial genetic elements that co-opt phage machinery for their own dissemination. Here we identify a family of satellites, named Phage-Inducible Chromosomal Minimalist Islands (PICMIs), that are broadly distributed in marine bacteria of the family Vibrionaceae. A typical PICMI is characterized by reduced gene content, does not encode genes for capsid remodelling, and packages its DNA as a concatemer. PICMIs integrate in the bacterial host genome next to the fis regulator, and encode three core proteins necessary for excision and replication. PICMIs are dependent on virulent phage particles to spread to other bacteria, and protect their hosts from other competitive phages without interfering with their helper phage. Thus, our work broadens our understanding of phage satellites and narrows down the minimal number of functions necessary to hijack a tailed phage.

Abstract Koala populations across the east coast of Australia are under threat of extinction with little known about the presence or distribution of a potential pathogen, phascolartid gammaherpesvirus 1 (PhaHV-1) across these threatened populations. Co-infections with PhaHV-1 and Chlamydia pecorum may be common and there is currently a limited understanding of the impact of these co-infections on koala health. To address these knowledge gaps, archived clinical and field-collected koala samples were examined by quantitative polymerase chain reaction to determine the distribution of PhaHV-1 in previously untested populations across New South Wales and Queensland. We detected PhaHV-1 in all regions surveyed with differences in detection rate between clinical samples from rescued koalas (26%) and field-collected samples from free-living koalas (8%). This may reflect increased viral shedding in koalas that have been admitted into care. We have corroborated previous work indicating greater detection of PhaHV-1 with increasing age in koalas and an association between PhaHV-1 and C. pecorum detection. Our work highlights the need for continued surveillance of PhaHV-1 in koala populations to inform management interventions, and targeted research to understand the pathogenesis of PhaHV-1 and determine the impact of infection and co-infection with C. pecorum.

Abstract Planctopirus limnophila belongs to the bacterial phylum Planctomycetes, a relatively understudied lineage with remarkable cell biology features. Here, we report a genome-wide analysis of essential gene content in P. limnophila. We show that certain genes involved in peptidoglycan synthesis or cell division, which are essential in most other studied bacteria, are not essential for growth under laboratory conditions in this species. We identify essential genes likely involved in lipopolysaccharide biosynthesis, consistent with the view of Planctomycetes as diderm bacteria, and highlight other essential genes of unknown functions. Furthermore, we explore potential stages of evolution of the essential gene repertoire in Planctomycetes and the related phyla Verrucomicrobia and Chlamydiae. Our results provide insights into the divergent molecular and cellular biology of Planctomycetes.

Abstract Responses of cells to stimuli are increasingly discovered to involve the binding of sequence-specific transcription factors outside of known target genes. We wanted to determine to what extent the genome-wide binding and function of a transcription factor are shaped by the cell type versus the stimulus. To do so, we induced the Heat Shock Response pathway in two different cancer cell lines with two different stimuli and related the binding of its master regulator HSF1 to nascent RNA and chromatin accessibility. Here, we show that HSF1 binding patterns retain their identity between basal conditions and under different magnitudes of activation, so that common HSF1 binding is globally associated with distinct transcription outcomes. HSF1-induced increase in DNA accessibility was modest in scale, but occurred predominantly at remote genomic sites. Apart from regulating transcription at existing elements including promoters and enhancers, HSF1 binding amplified during responses to stimuli may engage inactive chromatin.

Abstract LYS006 is a novel, highly potent and selective, new‐generation leukotriene A4 hydrolase (LTA4H) inhibitor in clinical development for the treatment of neutrophil‐driven inflammatory diseases. We describe the complex pharmacokinetic to pharmacodynamic (PD) relationship in blood, plasma, and skin of LYS006‐treated nonclinical species and healthy human participants. In a randomized first in human study, participants were exposed to single ascending doses up to 100 mg and multiple ascending doses up to 80 mg b.i.d.. LYS006 showed rapid absorption, overall dose proportional plasma exposure and nonlinear blood to plasma distribution caused by saturable target binding. The compound efficiently inhibited LTB4 production in human blood and skin blister cells, leading to greater than 90% predose target inhibition from day 1 after treatment initiation at doses of 20 mg b.i.d. and above. Slow re‐distribution from target expressing cells resulted in a long terminal half‐life and a long‐lasting PD effect in ex vivo stimulated blood and skin cells despite low plasma exposures. LYS006 was well‐tolerated and demonstrated a favorable safety profile up to highest doses tested, without any dose‐limiting toxicity. This supported further clinical development in phase II studies in predominantly neutrophil‐driven inflammatory conditions, such as hidradenitis suppurativa, inflammatory acne, and ulcerative colitis.

Abstract Chlamydiosis is a significant disease affecting Eastern Australian koala (Phascolarctos cinereus) populations, impacting individual animal welfare and fecundity and therefore influencing population dynamics. The aim of this study was to investigate the effect of a synthetic peptide vaccine based on 4 components of the Chlamydia pecorum major outer membrane protein (MOMP), over an 18-month period in a koala population severely impacted by chlamydiosis. Wild koalas were recruited into a vaccination or a placebo treatment group on a random allocation, then followed through a period of 18 months, with recapture at 6 monthly intervals. Vaccination did not alter clinical disease expression or chlamydial shedding from the ocular or urogenital sites. Vaccination did not stimulate a significant plasma anti-MOMP IgG response, when compared to the placebo group. There was no significant effect of vaccination on IFN-γ and IL-17A mRNA expression of peripheral blood lymphocytes when stimulated with rMOMP. We have demonstrated that a synthetic peptide vaccination against chlamydiosis is not an effective management tool in a koala population with a high prevalence of C. pecorum infection and related disease. The lack of antigenic response found in this study suggests that further research utilising a larger, full-length antigen is an avenue worth investigation if we are to consider vaccination as a part of a management strategy in diseased koala populations.

The nutritional quality of plant-based meat analogues compared to traditional meat products has been questioned in recent commentary, particularly in relation to protein quality and micronutrient bioavailability. However, the attributes of specific products within this category are unclear. We therefore undertook a comprehensive assessment of the compositional and functional attributes of v2food® (Sydney, Australia) plant-based mince, including an assessment of the effects of reformulation, including the addition of amino acids, ascorbic acid, and different forms of elemental iron. The protein digestibility and protein quality of v2food® plant-based mince were comparable to beef mince in the standardized INFOGEST system, and favourable effects on microbiota composition and short-chain fatty acid (SCFA) production were demonstrated in an in vitro digestion system. The use of ferrous sulphate as an iron source improved in vitro intestinal iron absorption by ~50% in comparison to other forms of iron (p < 0.05), although levels were ~3-fold lower than beef mince, even in the presence of ascorbic acid. In conclusion, the current study identified some favourable nutritional attributes of plant-based v2food® mince, specifically microbiota and SCFA changes, as well as other areas where further reformulation could be considered to further enhance the bioavailability of key nutrients. Further studies to assess the effect of plant-based meat analogues on health measures in vivo will be important to improve knowledge in this area.

Given the proven zoonotic potential of the intestinal protozoan Blastocystis sp., a fast-growing number of surveys are being conducted to identify potential animal reservoirs for transmission of the parasite. Nevertheless, few epidemiological studies have been conducted on farmed animals in Egypt. Therefore, a total of 1089 fecal samples were collected from herbivores (sheep, goats, camels, horses, and rabbits) in six Egyptian governorates (Dakahlia, Gharbia, Kafr El Sheikh, Giza, Aswan, and Sharqia). Samples were screened for the presence of Blastocystis sp. by real-time PCR followed by sequencing of positive PCR products and phylogenetic analysis for subtyping of the isolates. Overall, Blastocystis sp. was identified in 37.6% of the samples, with significant differences in frequency between animal groups (sheep, 65.5%; camels, 62.2%; goats, 36.0%; rabbits, 10.1%; horses, 3.3%). Mixed infections were reported in 35.7% of the Blastocystis sp.-positive samples. A wide range of subtypes (STs) with varying frequency were identified from single infections in ruminants including sheep (ST1–ST3, ST5, ST10, ST14, ST21, ST24, ST26, and ST40), goats (ST1, ST3, ST5, ST10, ST26, ST40, ST43, and ST44), and camels (ST3, ST10, ST21, ST24–ST26, ST30, and ST44). Most of them overlapped across these animal groups, highlighting their adaptation to ruminant hosts. In other herbivores, only three and two STs were evidenced in rabbits (ST1–ST3) and horses (ST3 and ST44), respectively. The greater occurrence and wider genetic diversity of parasite isolates among ruminants, in contrast to other herbivores, strongly suggested that dietary habits likely played a significant role in influencing both the colonization rates of Blastocystis sp. and ST preference. Of all the isolates subtyped herein, 66.3% were reported as potentially zoonotic, emphasizing the significant role these animal groups may play in transmitting the parasite to humans. These findings also expand our knowledge on the prevalence, genetic diversity, host specificity, and zoonotic potential of Blastocystis sp. in herbivores.

Cryptococcus is a genus of fungal pathogens that can infect and cause disease in a range of host species and is particularly prominent in koalas (Phascolarctos cinerus). Like other host species, koalas display a range of outcomes upon exposure to environmental Cryptococcus, from external nasal colonization to asymptomatic invasive infection and, in rare cases, severe clinical disease resulting in death. Host factors contributing to these varied outcomes are poorly understood. Due to their close relationship with eucalypt trees (a key environmental niche for Cryptococcus gattii) and suspected continual exposure to the pathogen, koalas provide a unique opportunity to examine host susceptibility in natural infections. Caspase recruitment domain-containing protein 9 (CARD9) is a key intracellular signaling protein in the fungal innate immune response. Humans with mutations in CARD9 succumb to several different severe and chronic fungal infections. This study is the first to sequence and explore CARD9 variation in multiple koalas using Sanger sequencing. Four CARD9 exons were successfully sequenced in 22 koalas from a New South Wales, Australia population. We found minimal variation between koalas across all four exons, an observation that was also made when CARD9 sequences were compared between koalas and six other species, including humans and mice. Ten single-nucleotide polymorphisms (SNP) were identified in this study and explored in the context of cryptococcal exposure outcomes. While we did not find any significant association with variation in cryptococcal outcomes, we found a high degree of conservation between species at several SNP loci that requires further investigation. The findings from this study lay the groundwork for further investigations of CARD9 and Cryptococcus both in koalas and other species, and highlight several considerations for future studies.

Background: Multimodal perioperative patient education and expectation-setting can reduce post-operative opioid use while maintaining pain control and satisfaction. As part of a quality-improvement project, we developed a standardized model for perioperative education built upon the American College of Surgeons (ACS) Safe and Effective Pain Control After Surgery (SEPCAS) brochure to improve perioperative education regarding opioid use and pain control. Material and methods: Our study was designed within the Define, Measure, Analyze, Improve, Control (DMAIC) quality-improvement framework. Patients were surveyed about the adequacy of their perioperative education regarding pain control and use of prescription opioid medication. After gathering baseline data, a multimodal educational intervention based on the SEPCAS brochure was implemented. Survey responses were then compared between groups. Results: Twenty-seven subjects were included from the pre-intervention period, and thirty-nine were included from the post-intervention period (n = 66). Those in the post-intervention period were more likely to report receiving the appropriate amount of education regarding recognizing the signs of opioid overdose and how to safely store and dispose of opioid medications. The majority of patients who received the SEPCAS brochure reported that it was useful in their post-operative recovery and that it should be given to every patient undergoing surgery. Conclusions: The ACS SEPCAS brochure is an effective tool for improving patient preparation to safely store and dispose of their opioid medication and recognize the signs of opioid overdose. The brochure was also well received by patients and perceived as an effective educational material.

[This corrects the article DOI: 10.1371/journal.pone.0249904.].

Traffic evacuation planning can be essential in saving lives in case of natural disasters such as hurricanes, floods and wildfires. We build on a case study of traffic evacuation planning for the city of Mill Valley, CA. We run a microscopic traffic simulator to examine various evacuation scenarios. We modify some crucial aspects of a previous study to make the simulation more pertinent. For a citywide evacuation, we quantify the importance of decreasing the number of vehicles per household. We find a set of changes that can significantly reduce the evacuation time by routing more traffic to the least-used highway on-ramps. We show results when evacuating various areas of the city one at a time.

ABSTRACT: To evaluate the toxic effects of mycotoxin-contaminated corn (MC) on the breeders and their progeny chicks, a total of 480 fifty-wk-old Cobb broiler breeder hens were fed the following dies: 1) a corn-soybean meal diet (Control; containing 70.35% corn), 2) MC substituting for 50% of corn in Control (LM), 3) LM diet plus 2 g/kg 1 mycotoxin sequestrant, Toxy-Nil Plus (TNP) (LMT2.0), 4) MC substituting for 100% of corn in Control (HM), 5) HM diet plus 2 g/kg TN (HMT2.0), and 6) HM diet plus 2.5 g/kg TNP (HMT2.5). The MC contained 69.25 μg aflatoxin B1 (AFB1)/kg, 4,875 μg deoxynivalenol (DON)/kg, and 2,262 μg zearalenone (ZEN)/kg. At wk 4 after MC inclusion, all eggs laid were used for hatch, and all progeny chicks were fed the same mycotoxin-untreated diet for 14 d. Dietary MC inclusion decreased the hatchability of set eggs and increased embryo mortality during d 18 to 21.5. The TNP addition increased these aforementioned indices in MC-included diets. Maternal HM treatment decreased the BW of progeny chicks at age of 14 d and BWG of progeny chicks during d 1 to 14, whereas maternal LM treatment did not affect these indices. In parallel, maternal HM treatment decreased the concentrations of serum IgA, IgG, and lysozyme in the progeny chicks on d 14, but maternal LM treatment did not affect these indices. Overall, maternal dietary TNP treatments increased the growth of progeny chicks and had a trend to increase the concentrations of serum IgA and IgG on d 14 compared to maternal MC treatments. It was concluded that the feeding of relative high ratio of corn contaminated with low level of AFB1, DON, and ZEN negatively affected the reproductive performance of breeders and the growth performance of their progeny chicks, and TNP addition alleviated these toxic effects.

Abstract Background Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification). Methods We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan–Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman’s correlation coefficient. Analyses were conducted by tumor subtype. Results 20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8–6.2) for HR-/HER2 − subtype to 13.3 months (36% CI 12.7–14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR − /HER2 − mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies. Conclusions Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates.

Coenzyme Q (CoQ) is a lipidic compound that is widely distributed in nature, with crucial functions in metabolism, protection against oxidative damage and ferroptosis and other processes. CoQ biosynthesis is a conserved and complex pathway involving several proteins. COQ2 is a member of the UbiA family of transmembrane prenyltransferases that catalyzes the condensation of the head and tail precursors of CoQ, which is a key step in the process, because its product is the first intermediate that will be modified in the head by the next components of the synthesis process. Mutations in this protein have been linked to primary CoQ deficiency in humans, a rare disease predominantly affecting organs with a high energy demand. The reaction catalyzed by COQ2 and its mechanism are still unknown. Here, we aimed at clarifying the COQ2 reaction by exploring possible substrate binding sites using a strategy based on homology, comprising the identification of available ligand-bound homologs with solved structures in the Protein Data Bank (PDB) and their subsequent structural superposition in the AlphaFold predicted model for COQ2. The results highlight some residues located on the central cavity or the matrix loops that may be involved in substrate interaction, some of which are mutated in primary CoQ deficiency patients. Furthermore, we analyze the structural modifications introduced by the pathogenic mutations found in humans. These findings shed new light on the understanding of COQ2’s function and, thus, CoQ’s biosynthesis and the pathogenicity of primary CoQ deficiency.

Blastocystis sp. is the most common single-celled eukaryote colonizing the human gastrointestinal tract worldwide. Because of the proven zoonotic potential of this protozoan, sustained research is therefore focused on identifying various reservoirs of transmission to humans, and in particular animal sources. Numerous groups of animals are considered to be such reservoirs due to their handling or consumption. However, some of them, including mollusks, remain underexplored. Therefore, a molecular epidemiological survey conducted in wild mussels was carried out in Northern France (Hauts-de-France region) to evaluate the frequency and subtypes (STs) distribution of Blastocystis sp. in these bivalve mollusks. For this purpose, 100 mussels (Mytilus edulis) were randomly collected in two sampling sites (Wimereux and Dannes) located in the vicinity of Boulogne-sur-Mer. The gills and gastrointestinal tract of each mussel were screened for the presence of Blastocystis sp. by real-time polymerase chain reaction (qPCR) assay followed by direct sequencing of positive PCR products and subtyping through phylogenetic analysis. In parallel, sequences of potential representative Blastocystis sp. isolates that were previously obtained from temporal surveys of seawater samples at marine stations offshore of Wimereux were integrated in the present analysis. By taking into account the qPCR results from all mussels, the overall prevalence of the parasite was shown to reach 62.0%. In total, more than 55% of the positive samples presented mixed infections. In the remaining mussel samples with a single sequence, various STs including ST3, ST7, ST14, ST23, ST26 and ST44 were reported with varying frequencies. Such distribution of STs coupled with the absence of a predominant ST specific to these bivalves strongly suggested that mussels might not be natural hosts of Blastocystis sp. and might rather be carriers of parasite isolates from both human and animal (bovid and birds) waste. These data from mussels together with the molecular identification of isolates from marine stations were subsequently discussed along with the local geographical context in order to clarify the circulation of this protozoan in this area. The identification of human and animal STs of Blastocystis sp. in mussels emphasized the active circulation of this protozoan in mollusks and suggested a significant environmental contamination of fecal origin. This study has provided new insights into the host/carrier range and transmission of Blastocystis sp. and emphasized its potential as an effective sentinel species for water quality and environmental contamination.

A low-fibre diet leads to gut microbiota imbalance, characterized by low diversity and reduced ability to produce beneficial metabolites, such as short-chain fatty acids (SCFAs). This imbalance is associated with poor gastrointestinal and metabolic health. We aimed to determine whether one dietary change, substitution of white bread with high-fibre bread, improves gut microbiota diversity and SCFA-producing capability. Twenty-two healthy adults completed a two-phase randomized, cross-over trial. The participants consumed three slices of a high-fibre bread (Prebiotic Cape Seed Loaf with BARLEYmax®) or control white bread as part of their usual diet for 2 weeks, with the treatment periods separated by a 4-week washout. High-fibre bread consumption increased total dietary fibre intake to 40 g/d, which was double the amount of fibre consumed at baseline or during the white bread intervention. Compared to white bread, the high-fibre bread intervention resulted in higher faecal alpha diversity (Shannon, p = 0.014) and relative abundance of the Lachnospiracae ND3007 group (p < 0.001, FDR = 0.019) and tended to increase the butyrate-producing capability (p = 0.062). In conclusion, substituting white bread with a high-fibre bread improved the diversity of gut microbiota and specific microbes involved in SCFA production and may enhance the butyrate-producing capability of gut microbiota in healthy adults. These findings suggest that a single dietary change involving high-fibre bread provides a practical way for adults to exceed recommended dietary fibre intake levels that improve gut microbiota composition and support gastrointestinal and metabolic health.

This study explores the co-crystallization between the drug praziquantel (PZQ) and the nutraceutical curcumin (CU). The investigation revealed two novel solid forms: a cocrystal solvate with ethyl acetate and a non-solvated cocrystal. This novel drug–nutraceutical cocrystal is a praziquantel–curcumin (2:1) cocrystal. The cocrystal solvate has ethyl acetate molecules occupying the voids with minimal interactions within the crystal lattice. The application of heat treatment induces solvent removal and prompts the transition to the non-solvated cocrystal, as highlighted by variable-temperature X-ray powder diffraction (VT-XRPD). Thermal analyses demonstrate the stability of the cocrystal solvate up to approximately 100 °C, beyond which it transforms into the non-solvated phase, which eventually melts at 130 °C.

Objective: The objective of this scoping review is to map, from wound assessment tools and other literature, the current methods used to assess wound odour in order to answer the following question: Which methods of assessment, validated or otherwise, are currently used in wound assessment tools to assess wound odour? Introduction: Wound assessment includes not only details of the condition of the wound bed but also evaluation of symptoms associated with the wound including that of odour. Odour is cited by clinicians, patients and carers as one of the most distressing wound symptoms. However, there is no consensus on a preferred method to assess odour thus negatively impacting the internal and external validity of many clinical trials and minimising the ability to perform meta-analysis. Eligibility criteria: Any wound assessment tool or framework that includes assessment of wound odour in any wound aetiology and in any care setting. Any systematic or scoping review that includes assessment of wound odour in any wound aetiology and in any care setting. No limits on date of publication or language will be applied. Methods: We will employ the Preferred Reporting Items for Systematic Review and Meta-Analyses extension for scoping reviews (PRISMA-ScR) guidelines for this scoping review and base its structure on the framework proposed by Arksey and O’Malley. Results: A narrative format will summarise extracted data and provide an overview of tools used to assess wound odour. A PRISMA diagram will outline the results of the search strategy. The identified tools will be summarised in table format and stratified according to methods used. Conclusion: The result of this scoping review will be a list of methods used to assess odour in wounds and will be used to inform a subsequent Delphi study to gain consensus on the preferred method to assess wound odour.

BackgroundThe epidemiology of Mycobacterium tuberculosis complex (MTBC) lineage 5 (L5) infections in Ghana revealed a significantly increased prevalence in Ewes compared to other self-reported ethnic groups. In that context, we sought to investigate the early phase of tuberculosis (TB) infection using ex vivo infection of macrophages derived from the blood of Ewe and Akan ethnic group volunteers with MTBC L4 and L5 strains.MethodsThe study participants consisted of 16 controls, among which self-reported Akan and Ewe ethnicity was equally represented, as well as 20 cured TB cases consisting of 11 Akans and 9 Ewes. Peripheral blood mononuclear cells were isolated from both healthy controls and cured TB cases. CD14+ monocytes were isolated and differentiated into monocyte-derived macrophages (MDMs) before infection with L4 or L5 endemic strains. The bacterial load was assessed after 2 hours (uptake) as well as 3 and 7 days post-infection.ResultsWe observed a higher capacity of MDMs from Ewes to phagocytose L4 strains (p < 0.001), translating into a higher bacillary load on day 7 (p < 0.001) compared to L5, despite the higher replication rate of L5 in Ewe MDMs (fold change: 1.4 vs. 1.2, p = 0.03) among the controls. On the contrary, within macrophages from Akans, we observed a significantly higher phagocytic uptake of L5 (p < 0.001) compared to L4, also translating into a higher load on day 7 (p = 0.04). However, the replication rate of L4 in Akan MDMs was higher than that of L5 (fold change: L4 = 1.2, L4 = 1.1, p = 0.04). Although there was no significant difference in the uptake of L4 and L5 among cured TB cases, there was a higher bacterial load of both L4 (p = 0.02) and L5 (p = 0.02) on day 7 in Ewe MDMs.ConclusionOur results suggest that host ethnicity (driven by host genetic diversity), MTBC genetic diversity, and individual TB infection history are all acting together to modulate the outcome of macrophage infections by MTBC.

Single primer enrichment technology (SPET) is a novel high-throughput genotyping method based on short-read sequencing of specific genomic regions harboring polymorphisms. SPET provides an efficient and reproducible method for genotyping target loci, overcoming the limits associated with other reduced representation library sequencing methods that are based on a random sampling of genomic loci. The possibility to sequence regions surrounding a target SNP allows the discovery of thousands of closely linked, novel SNPs. In this work, we report the design and application of the first SPET panel in lettuce, consisting of 41,547 probes spanning the whole genome and designed to target both coding (~96%) and intergenic (~4%) regions. A total of 81,531 SNPs were surveyed in 160 lettuce accessions originating from a total of 10 countries in Europe, America, and Asia and representing 10 horticultural types. Model ancestry population structure clearly separated the cultivated accessions (Lactuca sativa) from accessions of its presumed wild progenitor (L. serriola), revealing a total of six genetic subgroups that reflected a differentiation based on cultivar typology. Phylogenetic relationships and principal component analysis revealed a clustering of butterhead types and a general differentiation between germplasm originating from Western and Eastern Europe. To determine the potentiality of SPET for gene discovery, we performed genome-wide association analysis for main agricultural traits in L. sativa using six models (GLM naive, MLM, MLMM, CMLM, FarmCPU, and BLINK) to compare their strength and power for association detection. Robust associations were detected for seed color on chromosome 7 at 50 Mbp. Colocalization of association signals was found for outer leaf color and leaf anthocyanin content on chromosome 9 at 152 Mbp and on chromosome 5 at 86 Mbp. The association for bolting time was detected with the GLM, BLINK, and FarmCPU models on chromosome 7 at 164 Mbp. Associations were detected in chromosomal regions previously reported to harbor candidate genes for these traits, thus confirming the effectiveness of SPET for GWAS. Our findings illustrated the strength of SPET for discovering thousands of variable sites toward the dissection of the genomic diversity of germplasm collections, thus allowing a better characterization of lettuce collections.

Transmission of Chlamydia pecorum between koalas is a potential risk in field capture or rehabilitation settings, where koalas are held in proximity to each other, or equipment is shared between animals. Given the impact of C. pecorum on koala welfare and population viability it is surprising that quarantine and disinfection protocols in a koala rehabilitation facility or capture settings have not previously been evaluated. This study aimed to evaluate an approach, based on the detection of chlamydial DNA and cell viability, to determine the degree of environmental contamination within a koala care facility. Various fomite sites associated with koala care at a koala rehabilitation facility in New South Wales, Australia were identified as potential sources of chlamydial contamination, following exposure to koalas known to be infected with C. pecorum. Fomite sites were swabbed following exposure, and again after decontamination procedures were carried out. Samples were tested for the presence of chlamydial DNA using qPCR and viability using both RT-qPCR and cell culture. From a total of 239 sampling events, 30 tested qPCR positive for chlamydial DNA, with 19 and 11 samples corresponding to pre-decontamination and post-decontamination events respectively. Detection of chlamydial DNA appeared to be most common in the examination room, especially on fomite sites in direct contact with koalas. Physical removal of chlamydial DNA, or its degradation by the elements, appeared to be more common on outdoor enclosures, clothing, and hands. Based on the cell culture assay, of the pre-decontamination samples with chlamydial DNA, eight had viable chlamydial cells, two of these at low levels. Of the post-decontamination samples with chlamydial DNA, one had a moderate number, and one had a very low number of viable chlamydial cells. RT-qPCR was unsuccessful in determining cell viability due to low yields of RNA and high levels of contaminants from the environmental samples. The outcomes of this study provide a knowledge base for the design of future biosecurity evaluation guidelines in captive and koala rehabilitation facilities. The higher incidence of chlamydial DNA detection by qPCR than viable organism highlights the need to use viability assays in similar studies. However, further investment is still needed to optimise these methods and improve sensitivity for complex environmental samples.

To automate operations in a logistic warehouse, a robot needs to extract items from the clutter on a shelf without collapsing the clutter. To address this problem, this study proposes a multi-step motion planner to stably extract an item by using the support relations of each object included in the clutter. This study primarily focuses on safe extraction, which allows the robot to choose the best next action based on limited observations. By estimating the support relations, we construct a collapse prediction graph to obtain the appropriate order of object extraction. Thus, the target object can be extracted without collapsing the pile. Furthermore, we show that the efficiency of the robot is improved if it uses one of its arms to extract the target object while the other supports a neighboring object. The proposed method is evaluated in real-world experiments on detecting support relations and object extraction tasks. This study makes a significant contribution because the experimental results indicate that the robot can estimate support relations based on collapse predictions and perform safe extraction in real environments. Our multi-step extraction plan ensures both better performance and robustness to achieve safe object extraction tasks from the clutter.

Internal jugular vein tumor thrombus is an extremely rare condition in thyroid carcinoma, but it does exist. Correlated with greater aggressiveness with a higher incidence of distant metastases at diagnosis and a higher recurrence rate, this important prognostic element should be systematically investigated by ultrasound operators in all patients presenting with thyroid carcinoma. The patient’s follow-up must be careful. This can be a trap that surgeons must look for in their preoperative checklist. We report the case of a 58-year-old woman with an IJV thrombus associated with multiple bone metastases. She underwent successful surgical treatment, and postoperative pathology showed a poorly differentiated follicular carcinoma of the thyroid and a tumor thrombus in the internal jugular vein.

Hydrogen is a bright energy vector that could be crucial to decarbonise and combat climate change. This energy evolution involves several sectors, including power backup systems, to supply priority facility loads during power outages. As buildings now integrate complex automation, domotics, and security systems, energy backup systems cause interest. A hydrogen-based backup system could supply loads in a multi-day blackout; however, the backup system should be sized appropriately to ensure the survival of essential loads and low cost. In this sense, this work proposes a sizing of fuel cell (FC) backup systems for low voltage (LV) buildings using the history of power outages. Historical data allows fitting a probability function to determine the appropriate survival of loads. The proposed sizing is applied to a university building with a photovoltaic generation system as a case study. Results show that the sizing of an FC–battery backup system for the installation is 7.6% cheaper than a battery-only system under a usual 330-minutes outage scenario. And 59.3% cheaper in the case of an unusual 48-hours outage scenario. It ensures a 99% probability of supplying essential load during power outages. It evidences the pertinence of an FC backup system to attend to outages of long-duration and the integration of batteries to support the abrupt load variations. This research is highlighted by using historical data from actual outages to define the survival of essential loads with total service probability. It also makes it possible to determine adequate survival for non-priority loads. The proposed sizing is generalisable and scalable for other buildings and allows quantifying the reliability of the backup system tending to the resilience of electrical systems.

Abstract For the first time, the structural investigation of a Pb-exchanged zeolite (Pb13.4(OH)10Al17.4Si54.6O144 ∙38H2O) with STI framework type, revealed a highly unusual and intriguing sudden volume increase under continuous heating. Understanding the fundamental mechanisms leading to such an unusual behaviour is essential for technological applications and interpretation of chemical bonding in zeolites. The dehydration was tracked in situ from 25 to 450 °C by single crystal X-ray diffraction, infrared and X-ray absorption spectroscopy. Further interpretation of the experimental observations was supported by ab initio molecular dynamics simulations. Initially, Pb-STI unit-cell volume contracts (ΔV = − 3.5%) from 25 to 100 °C. This agrees with the trend observed in STI zeolites. Surprisingly, at 125 °C, the framework expanded (ΔV = + 2%), adopting a configuration, which resembles that of the room temperature structure. Upon heating, the structure loses H2O but no de-hydroxylation occurred. The key mechanism leading to the sudden volume increase was found to be the formation of Pbx(OH)y clusters, which prevent the shrinking of the channels, rupture of the tetrahedral bonds and occlusion of the pores. This zeolite has therefore an increased thermal stability with respect to other STI metal-exchanged zeolites, with important consequences on its applications.

A type 1 Brugada electrocardiogram pattern may be masked by typical right bundle branch block aspect. We present 2 cases (male patients, aged 18 and 22 years) of associated ostium secundum atrial septal defect with a right bundle branch block aspect and symptomatic confirmed Brugada syndrome. Both patients underwent cardiac defibrillator implantation. (Level of Difficulty: Advanced.)

Models of particle acceleration in solar eruptive events suggest that roughly equal energy may go into accelerating electrons and ions. However, while previous solar X-ray spectroscopic imagers have transformed our understanding of electron acceleration, only one resolved image of γ-ray emission from solar accelerated ions has ever been produced. This paper outlines a new satellite instrument concept—the large imaging spectrometer for solar accelerated nuclei (LISSAN)—with the capability not only to observe hundreds of events over its lifetime, but also to capture multiple images per event, thereby imaging the dynamics of solar accelerated ions for the first time. LISSAN provides spectroscopic imaging at photon energies of 40 keV–100 MeV on timescales of ≲10 s with greater sensitivity and imaging capability than its predecessors. This is achieved by deploying high-resolution scintillator detectors and indirect Fourier imaging techniques. LISSAN is suitable for inclusion in a multi-instrument platform such as an ESA M-class mission or as a smaller standalone mission. Without the observations that LISSAN can provide, our understanding of solar particle acceleration, and hence the space weather events with which it is often associated, cannot be complete.

A full 3D numerical model is used for studying tidal asymmetry, estuarine circulation, and saline intrusion in the Gironde estuary. The model is calibrated and verified using the data measured during two field surveys in the Gironde estuary. Harmonic analysis of numerical results is proposed to understand how the superposition of M2, M4 and M6 components generate a complex estuarine circulation and salinity intrusion in the Gironde estuary. The numerical results show that the M6 component plays a significant role as important as the M4 one in modifying the nature of tidal asymmetry, especially in the Gironde upper estuary. In this case, the use of the phase lag between M2 and M4, neglecting M6, to predict the tidal asymmetry nature could produce errors. The effect of asymmetrical tides on saline intrusion and residual circulation is specifically discussed here.

Abstract The incidence of cardiac dyspnea (CD) and the distribution of pollution in the south of France suggests that environmental pollution may have a role in disease triggering. CD is a hallmark symptom of heart failure leading to reduced ability to function and engage in activities of daily living. To show the impact of short-term pollution exposure on the increment of CD emergency room visits, we collected pollutants and climate measurements on a daily basis and 43,400 events of CD in the Région Sud from 2013 to 2018. We used a distributed lag non-linear model (DLNM) to assess the association between air pollution and CD events. We divided the region in 357 zones to reconciliate environmental and emergency room visits data. We applied the DLNM on the entire region, on zones grouped by pollution trends and on singular zones. Each pollutant has a significant effect on triggering CD. Depending on the pollutant, we identified four shapes of exposure curves to describe the impact of pollution on CD events: early and late effect for NO2; U-shape and rainbow-shape (or inverted U) for O3; all the four shapes for PM10. In the biggest cities, O3 has the most significant association along with the PM10. In the west side, a delayed effect triggered by PM10 was found. Zones along the main highway are mostly affected by NO2 pollution with an increase of the association for a period up to 9 days after the pollution peak. Our results can be used by local authorities to set up specific prevention policies, public alerts that adapt to the different zones and support public health prediction-making. We developed a user-friendly web application called Health, Environment in PACA Region Tool (HEART) to collect our results. HEART will allow citizens, researchers and local authorities to monitor the impact of pollution trends on local public health.

Background: Sexually transmitted infections (STIs) are responsible for a high burden of morbidity and mortality in many developing countries especially among adolescents. Adolescents are predisposed to STIs because they are more likely to engage in unhealthy lifestyles. However, these adolescents have limited knowledge of the use and barriers to sexual and reproductive health information and care services. This study explored the knowledge of STIs among Senior High School Adolescents in the Wa Municipality of Ghana. Method: The study designed as a descriptive cross-sectional research. A multistage sampling technique was used to recruit these adolescents for the study. Totally 355 adolescents were selected from senior high schools in the Wa Municipality. Descriptive statistics and Chi-square test were used to analyze the data, at a significance level of P < 0.05. Results: The majority of respondents had good knowledge of STIs, with the most common examples of STIs identified as HIV/AIDS (80.8%, 287/355) and gonorrhea (73.8%, 262/355). The main known signs and symptoms identified were discharges from the penis/vagina (72.4%, 257/355), painful urination (71.5%, 254/355), and itching, and sores around the genital area (72.7%, 258/355). The main sources of information/education of STIs for these adolescents were the school, hospital, internet and mother. Whom respondent lived with was found to be significantly associated with knowledge of STI (P < 0.001). Conclusion: Many of the respondents had good knowledge of STI, and the school was the most common source of information on STI. It is, therefore, important for the Ghana Education Service and the Ghana Health Service to strengthen the School Health Education Programme in second cycle institutions in the Wa Municipality. Parents, especially mothers, should be actively involved in the sexual health education of adolescents.

Ulnar nerve injury induces chronic neuropathic pain and is frequently devastating due to loss of cupping the hand around objects (finger clawing) and diminished grip strength. There is little chance of restoring good function, eliminating finger clawing, or reducing the pain. A novel technique was tested for its efficacy in promoting ulnar nerve function and reducing finger clawing and chronic neuropathic pain. A 25-year-old subject presented 5.7 months after a wrist gunshot that created three nerve gaps proximal to the deep ulnar nerve branch. He sought restoration of function due to developing ulnar nerve injury-induced claw hand and increasingly severe chronic neuropathic pain. After resection of the scarred nerve tissue, each gap was 10 cm long. The gaps were bridged with two nonreversed sural nerve grafts within a PRP-filled NeuroMend collagen tube (Collagen Matrix, Oakland, N.J.). Some axons regenerated entirely across all three 10-cm-long repaired nerve gaps, restoring excellent topographically correct sensitivity of S4, including two-point discrimination of 4 mm, good M4 motor function, and full ROM. The ulnar nerve injury-induced finger clawing was eliminated, and the chronic neuropathic pain of 7 was reduced to 0 on a 0–10 validated scale and did not return over the following 3.75 years. Thus, this novel technique induces good sensory and motor function, despite repairing three 10-cm-long nerve gaps while eliminating ulnar nerve injury-induced hand clawing and chronic neuropathic pain. Further studies are required to determine whether the effects were due to PRP.

In settings with high tuberculosis (TB) endemicity, distinct genotypes of the Mycobacterium tuberculosis complex (MTBC) often differ in prevalence. However, the factors leading to these differences remain poorly understood. Here we studied the MTBC population in Dar es Salaam, Tanzania over a six-year period, using 1,082 unique patient-derived MTBC whole-genome sequences (WGS) and associated clinical data. We show that the TB epidemic in Dar es Salaam is dominated by multiple MTBC genotypes introduced to Tanzania from different parts of the world during the last 300 years. The most common MTBC genotypes deriving from these introductions exhibited differences in transmission rates and in the duration of the infectious period, but little differences in overall fitness, as measured by the effective reproductive number. Moreover, measures of disease severity and bacterial load indicated no differences in virulence between these genotypes during active TB. Instead, the combination of an early introduction and a high transmission rate accounted for the high prevalence of L3.1.1, the most dominant MTBC genotype in this setting. Yet, a longer co-existence with the host population did not always result in a higher transmission rate, suggesting that distinct life-history traits have evolved in the different MTBC genotypes. Taken together, our results point to bacterial factors as important determinants of the TB epidemic in Dar es Salaam.

The identification of bedforms has an important role in the study of seafloor morphology. The presence of these dynamic structures on the seafloor represents a hazard for navigation. They also influence the hydrodynamic simulation models used in the context, for example, of coastal flooding. Generally, MultiBeam EchoSounders (MBES) are used to survey these bedforms. Unfortunately, the coverage of the MBES is limited to small areas per survey. Therefore, the analysis of large areas of interest (like navigation channels) requires the integration of different datasets acquired over overlapping areas at different times. The presence of spatial and temporal inconsistencies between these datasets may significantly affect the study of bedforms, which are subject to many natural processes (e.g., Tides; flow). This paper proposes a novel approach to integrate multisource bathymetric datasets to study bedforms. The proposed approach is based on consolidating multisource datasets and applying the Empirical Bayesian Kriging interpolation for the creation of a multisource Digital Bathymetric Model (DBM). It has been designed to be adapted for estuarine areas with a high dynamism of the seafloor, characteristic of the fluvio-marine regime of the Estuary of the Saint-Lawrence River. This area is distinguished by a high tidal cycle and the presence of fields of dunes. The study involves MBES data that was acquired daily over a field of dunes in this area over the span of 4 days for the purpose of monitoring the morphology and migration of dunes. The proposed approach performs well with a resulting surface with a reduced error relative to the original data compared to existing approaches and the conservation of the dune shape through the integration of the data sets despite the highly dynamic fluvio-marine environments.