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German Dziebel’s critique of our Crow-Omaha volume of nine years ago rests on his book of fourteen years ago. He acknowledges that crossness and skewing may in some instances covary but denies the covariance has any causal significance. Instead, he argues, Crow-Omaha systems derive from kin-terminologies marked by intergenerational self-reciprocals, which are purely linguistic in nature and uninfluenced by social organization; that sibling terminologies emphasizing relative age evolve into Omaha systems, and those emphasizing relative sex into Crow systems; and that in kinship-system evolution it is sibling terminologies—rather than crossness that predicates marriage alliances—which are the driving force.We show in reply that systems with skewing are intimately and dynamically associated with crossness, even more robustly than previously thought, both empirically and, through reinterpretation of Lounsbury’s work, analytically. The interaction of crossness and skewing through linguistic or geographic contiguity is the best and most promising way forward in the study of Crow-Omaha, and work since the appearance of our book bears this out. We show too that works of Popov, Hornborg and Barnard, that our critic cites in his favor, support our position and not his. And we suggest that the argument of his 2007 book, for all its strengths, hitches his evolutionary model to a belief that Homo sapiens arose and spread “out of America” rather than “out of Africa”, an entailment of his kinship analysis that readers will likely find off-putting. We affirm the deep embedding of skewed systems within systems having crossness, controvert his (Kroeber-like) insistence that kinship is purely linguistic and not social-organizational, and dispute that the many who find the “out of Africa” thesis well-grounded are all wet.

This is the first English translation of Vladimir A. Popov’s important 1977 article on Crow-Omaha kinship systems. Popov’s global comparison proposes an historical typology of these systems covariant with socio-evolutionary stages. His six subtypes are configured by the variable operation of bifurcation and linearity among G+1 and G0 kin-terms, with Popov suggesting three possible evolutionary trajectories. While directly addressing contemporary Western kinship theory, Popov simultaneously engages a robust Soviet tradition little known to Western scholars. Of special note, Popov deploys the “Levin code,” a logically elegant formalist notation that commands comparison with other componential systems. Broader attention to Popov’s perspectives on the Crow-Omaha problem is long overdue.

Background Type I interferons are cytokines involved in innate immunity against viruses. Genetic disorders of type I interferon regulation are associated with a range of autoimmune and cerebrovascular phenotypes. Carriers of pathogenic variants involved in genetic disorders of type I interferons are generally considered asymptomatic. Preliminary data suggests, however, that genetically determined dysregulation of type I interferon responses is associated with autoimmunity, and may also be relevant to sporadic cerebrovascular disease and dementia. We aim to determine whether functional variants in genes involved in type I interferon regulation and signalling are associated with the risk of autoimmunity, stroke, and dementia in a population cohort. Methods We will perform a hypothesis-driven candidate pathway association study of type I interferon-related genes using rare variants in the UK Biobank (UKB). We will manually curate type I interferon regulation and signalling genes from a literature review and Gene Ontology, followed by clinical and functional filtering. Variants of interest will be included based on pre-defined clinical relevance and functional annotations (using LOFTEE, M-CAP and a minor allele frequency

Protein stability is fundamental to maintain pharmaceutical efficacy in the nascent field of biologics. One particular property that is essential for therapeutic effect is retention of the folded 3-dimensional conformation, i.e. once unfolding has occurred the biologic is often rendered inactive. In this work we propose a modified form of a recently published UV spectroscopic method that identifies protein unfolding. In this study we determine concentration limits to avoid protein unfolding of two model surfactants, namely polysorbate 20 and polysorbate 80, by correlating surfactant concentration with percentage ‘unfolded’ for three model proteins. For each scenario two distinct regions were observed, firstly surfactant concentrations at which no unfolding had occurred, followed by a second region whereby unfolding steadily increased with surfactant concentration. In general for the combinations analysed in this study, this second region began to appear around ten times below the critical micellar concentration of each surfactant, regardless of the protein or polysorbate chosen. It is therefore proposed that this adapted method could be used by researchers in the early stages of formulation development as a convenient and simple screening tool to confirm the ‘onset of unfolding’ concentration for protein-surfactant formulations, thus helping to optimise surfactant concentration selection in pharmaceutical formulations to maintain the benefits of surfactants yet avoid inadvertent unfolding.

IntroductionProteus mirabilis is a key pathobiont in catheter-associated urinary tract infections (CA-UTIs), which is well known to form crystalline biofilms that occlude catheters. Urease activity alkylates urine through the release of ammonia, consequentially resulting in higher levels of Mg2+ and Ca2+ and formation of crystals. In this study, we showed that N-acetyl cysteine (NAC), a thiol antioxidant, is a potent urease inhibitor that prevents crystalline biofilm formation.MethodsTo quantify urease activity, Berthelot’s method was done on bacterial extracts treated with NAC. We also used an in vitro catheterised glass bladder model to study the effect of NAC treatment on catheter occlusion and biofilm encrustation in P. mirabilis infections. Inductively-coupled plasma mass spectrometry (ICP-MS) was performed on catheter samples to decipher elemental profiles.ResultsNAC inhibits urease activity of clinical P. mirabilis isolates at concentrations as low as 1 mM, independent of bacterial killing. The study also showed that NAC is bacteriostatic on P. mirabilis, and inhibited biofilm formation and catheter occlusion in an in vitro. A significant 4-8log10 reduction in viable bacteria was observed in catheters infected in this model. Additionally, biofilms in NAC treated catheters displayed a depletion of calcium, magnesium, or phosphates (>10 fold reduction), thus confirming the absence of any urease activity in the presence of NAC. Interestingly, we also showed that not only is NAC anti-inflammatory in bladder epithelial cells (BECs), but that it mutes its inflammatory response to urease and P. mirabilis infection by reducing the production of IL-6, IL-8 and IL-1b.DiscussionUsing biochemical, microbiological and immunological techniques, this study displays the functionality of NAC in preventing catheter occlusion by inhibiting urease activity. The study also highlights NAC as a strong anti-inflammatory antibiofilm agent that can target both bacterial and host factors in the treatment of CA-UTIs.

IntroductionAnterior cruciate ligament (ACL) injuries cause knee instability, knee pain, weight-bearing adjustments, and functional deficits but their association to patellar tendon quality is unknown. Our purpose was to investigate quadriceps strength, patellar tendon quality, relative load exposure, perceived knee stability, knee pain, extension angle, and time from ACL injury; in addition to examining their relative associations.MethodsInjured and uninjured legs of 81 male athletes of different sports with a unilateral ACL injury (18–45 years) were examined. Participants reported location and intensity of knee pain and their perceived stability using a numerical rating scale (NRS 0–10). Strength was tested with an isokinetic device. Tendon quality was measured using ultrasound tissue characterization. Means ± standard deviation (SD) of perceived knee stability, knee extension angle, knee pain, isokinetic quadriceps strength in relation to body mass, proportion of echo-types (I–IV), tendon volume, and number of days from ACL injury to assessment are reported. Values of effect sizes (ES) and correlations (rs) were calculated.ResultsACL injured leg demonstrated reduced reported knee stability (6.3 ± 2.5), decreased knee extension angle (−0.7 ± 3.1° vs. −2.7 ± 2.2°; ES = 0.7; P

BackgroundNatural language processing (NLP) has the potential to automate the reading of radiology reports, but there is a need to demonstrate that NLP methods are adaptable and reliable for use in real-world clinical applications.MethodsWe tested the F1 score, precision, and recall to compare NLP tools on a cohort from a study on delirium using images and radiology reports from NHS Fife and a population-based cohort (Generation Scotland) that spans multiple National Health Service health boards. We compared four off-the-shelf rule-based and neural NLP tools (namely, EdIE-R, ALARM+, ESPRESSO, and Sem-EHR) and reported on their performance for three cerebrovascular phenotypes, namely, ischaemic stroke, small vessel disease (SVD), and atrophy. Clinical experts from the EdIE-R team defined phenotypes using labelling techniques developed in the development of EdIE-R, in conjunction with an expert researcher who read underlying images.ResultsEdIE-R obtained the highest F1 score in both cohorts for ischaemic stroke, ≥93%, followed by ALARM+, ≥87%. The F1 score of ESPRESSO was ≥74%, whilst that of Sem-EHR is ≥66%, although ESPRESSO had the highest precision in both cohorts, 90% and 98%. For F1 scores for SVD, EdIE-R scored ≥98% and ALARM+ ≥90%. ESPRESSO scored lowest with ≥77% and Sem-EHR ≥81%. In NHS Fife, F1 scores for atrophy by EdIE-R and ALARM+ were 99%, dropping in Generation Scotland to 96% for EdIE-R and 91% for ALARM+. Sem-EHR performed lowest for atrophy at 89% in NHS Fife and 73% in Generation Scotland. When comparing NLP tool output with brain image reads using F1 scores, ALARM+ scored 80%, outperforming EdIE-R at 66% in ischaemic stroke. For SVD, EdIE-R performed best, scoring 84%, with Sem-EHR 82%. For atrophy, EdIE-R and both ALARM+ versions were comparable at 80%.ConclusionsThe four NLP tools show varying F1 (and precision/recall) scores across all three phenotypes, although more apparent for ischaemic stroke. If NLP tools are to be used in clinical settings, this cannot be performed “out of the box.” It is essential to understand the context of their development to assess whether they are suitable for the task at hand or whether further training, re-training, or modification is required to adapt tools to the target task.

Abstract In bioelectronics, conducting polymer coatings allow the reduction of the impedance of metallic electrodes and facilitate the translation of bioelectrical signals at their interface. Such coatings can be made using thin film deposition from a solution or direct synthesis via electrodeposition. The electrical control over the deposition offers the possibility for a fine‐tuning of the film's thickness and structure. However, the mechanical stability of such coatings mainly suffer from their poor adhesion to the electrode surface and film cracking. Here, an extended study on the kinetics of poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) electropolymerization and the evolution of its physicochemical properties is provided. The impedance spectroscopy closely follows the electrochemical variations during the PEDOT:PSS's film growth, described by modeled equivalent circuits. The film's properties change during polymerization in relation to the supporting electrode size, its surface chemistry, and the deposition time. The film growth structures polymeric morphology in a confluent layer with a strong thickness increase before reaching its mechanical surface failure. Before this point, the film remains stable over a hundred cycles of applied potential strain in a defined redox window. These evaluations benchmark the PEDOT:PSS film properties during its electropolymerization toward electrochemically tunable transducers for bioelectronics.

The facultative intracellular pathogen Listeria monocytogenes, like many related Firmicutes, uses the nucleotide second messenger cyclic di-AMP (c-di-AMP) to adapt to changes in nutrient availability, osmotic stress, and the presence of cell wall-acting antibiotics. In rich medium, c-di-AMP is essential; however, mutations in cbpB, the gene encoding c-di-AMP binding protein B, suppress essentiality. In this study, we identified that the reason for cbpB-dependent essentiality is through induction of the stringent response by RelA. RelA is a bifunctional RelA/SpoT homolog (RSH) that modulates levels of (p)ppGpp, a secondary messenger that orchestrates the stringent response through multiple allosteric interactions. We performed a forward genetic suppressor screen on bacteria lacking c-di-AMP to identify genomic mutations that rescued growth while cbpB was constitutively expressed and identified mutations in the synthetase domain of RelA. The synthetase domain of RelA was also identified as an interacting partner of CbpB in a yeast-2-hybrid screen. Biochemical analyses confirmed that free CbpB activates RelA while c-di-AMP inhibits its activation. We solved the crystal structure of CbpB bound and unbound to c-di-AMP and provide insight into the region important for c-di-AMP binding and RelA activation. The results of this study show that CbpB completes a homeostatic regulatory circuit between c-di-AMP and (p)ppGpp in Listeria monocytogenes IMPORTANCE Bacteria must efficiently maintain homeostasis of essential molecules to survive in the environment. We found that the levels of c-di-AMP and (p)ppGpp, two nucleotide second messengers that are highly conserved throughout the microbial world, coexist in a homeostatic loop in the facultative intracellular pathogen Listeria monocytogenes Here, we found that cyclic di-AMP binding protein B (CbpB) acts as a c-di-AMP sensor that promotes the synthesis of (p)ppGpp by binding to RelA when c-di-AMP levels are low. Addition of c-di-AMP prevented RelA activation by binding and sequestering CbpB. Previous studies showed that (p)ppGpp binds and inhibits c-di-AMP phosphodiesterases, resulting in an increase in c-di-AMP. This pathway is controlled via direct enzymatic regulation and indicates an additional mechanism of ribosome-independent stringent activation.

cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes are immune sensors that synthesize nucleotide second messengers and initiate antiviral responses in bacterial and animal cells. Here, we discover Enterobacter cloacae CD-NTase-associated protein 4 (Cap4) as a founding member of a diverse family of >2,000 bacterial receptors that respond to CD-NTase signals. Structures of Cap4 reveal a promiscuous DNA endonuclease domain activated through ligand-induced oligomerization. Oligonucleotide recognition occurs through an appended SAVED domain that is an unexpected fusion of two CRISPR-associated Rossman fold (CARF) subunits co-opted from type III CRISPR immunity. Like a lock and key, SAVED effectors exquisitely discriminate 2'-5'- and 3'-5'-linked bacterial cyclic oligonucleotide signals and enable specific recognition of at least 180 potential nucleotide second messenger species. Our results reveal SAVED CARF family proteins as major nucleotide second messenger receptors in CBASS and CRISPR immune defense and extend the importance of linkage specificity beyond mammalian cGAS-STING signaling.

Seismic refraction tomography provides images of the elastic properties of subsurface materials in landslide settings. Seismic velocities are sensitive to changes in moisture content, which is a triggering factor in the initiation of many landslides. However, the application of the method to long-term monitoring of landslides is rarely used, given the challenges in undertaking repeat surveys and in handling and minimizing the errors arising from processing time-lapse surveys. This work presents a simple method and workflow for producing a reliable time-series of inverted seismic velocity models. This method is tested using data acquired during a recent, novel, long-term seismic refraction monitoring campaign at an active landslide in the UK. Potential sources of error include those arising from inaccurate and inconsistent determination of first-arrival times, inaccurate receiver positioning, and selection of inappropriate inversion starting models. At our site, a comparative analysis of variations in seismic velocity to real-world variations in topography over time shows that topographic error alone can account for changes in seismic velocity of greater than ±10% in a significant proportion (23%) of the data acquired. The seismic velocity variations arising from real material property changes at the near-surface of the landslide, linked to other sources of environmental data, are demonstrated to be of a similar magnitude. Over the monitoring period we observe subtle variations in the bulk seismic velocity of the sliding layer that are demonstrably related to variations in moisture content. This highlights the need to incorporate accurate topographic information for each time-step in the monitoring time-series. The goal of the proposed workflow is to minimize the sources of potential errors, and to preserve the changes observed by real variations in the subsurface. Following the workflow produces spatially comparable, time-lapse velocity cross-sections formulated from disparate, discretely-acquired datasets. These practical steps aim to aid the use of the seismic refraction tomography method for the long-term monitoring of landslides prone to hydrological destabilization.

Bacteria possess an array of defenses against foreign invaders, including a broadly distributed bacteriophage defense system termed CBASS (cyclic oligonucleotide-based anti-phage signaling system). In CBASS systems, a cGAS/DncV-like nucleotidyltransferase synthesizes cyclic di- or tri-nucleotide second messengers in response to infection, and these molecules activate diverse effectors to mediate bacteriophage immunity via abortive infection. Here, we show that the CBASS effector NucC is related to restriction enzymes but uniquely assembles into a homotrimer. Binding of NucC trimers to a cyclic tri-adenylate second messenger promotes assembly of a NucC homohexamer competent for non-specific double-strand DNA cleavage. In infected cells, NucC activation leads to complete destruction of the bacterial chromosome, causing cell death prior to completion of phage replication. In addition to CBASS systems, we identify NucC homologs in over 30 type III CRISPR/Cas systems, where they likely function as accessory nucleases activated by cyclic oligoadenylate second messengers synthesized by these systems' effector complexes.

Australian lizards are a diverse group distributed across the continent and inhabiting a wide range of environments. Together, they exhibit a remarkable diversity of reproductive morphologies, physiologies, and behaviours that is broadly representative of vertebrates in general. Many reproductive traits exhibited by Australian lizards have evolved independently in multiple lizard lineages, including sociality, complex signalling and mating systems, viviparity, and temperature-dependent sex determination. Australian lizards are thus outstanding model organisms for testing hypotheses about how reproductive traits function and evolve, and they provide an important basis of comparison with other animals that exhibit similar traits. We review how research on Australian lizard reproduction has contributed to answering broader evolutionary and ecological questions that apply to animals in general. We focus on reproductive traits, processes, and strategies that are important areas of current research, including behaviours and signalling involved in courtship; mechanisms involved in mating, egg production, and sperm competition; nesting and gestation; sex determination; and finally, birth in viviparous species. We use our review to identify important questions that emerge from an understanding of this body of research when considered holistically. Finally, we identify additional research questions within each topic that Australian lizards are well suited for reproductive biologists to address.

Abstract Background The CVD-COVID-UK consortium was formed to understand the relationship between COVID-19 and cardiovascular diseases through analyses of harmonised electronic health records (EHRs) across the four UK nations. Beyond COVID-19, data harmonisation and common approaches enable analysis within and across independent Trusted Research Environments. Here we describe the reproducible harmonisation method developed using large-scale EHRs in Wales to accommodate the fast and efficient implementation of cross-nation analysis in England and Wales as part of the CVD-COVID-UK programme. We characterise current challenges and share lessons learnt. Methods Serving the scope and scalability of multiple study protocols, we used linked, anonymised individual-level EHR, demographic and administrative data held within the SAIL Databank for the population of Wales. The harmonisation method was implemented as a four-layer reproducible process, starting from raw data in the first layer. Then each of the layers two to four is framed by, but not limited to, the characterised challenges and lessons learnt. We achieved curated data as part of our second layer, followed by extracting phenotyped data in the third layer. We captured any project-specific requirements in the fourth layer. Results Using the implemented four-layer harmonisation method, we retrieved approximately 100 health-related variables for the 3.2 million individuals in Wales, which are harmonised with corresponding variables for > 56 million individuals in England. We processed 13 data sources into the first layer of our harmonisation method: five of these are updated daily or weekly, and the rest at various frequencies providing sufficient data flow updates for frequent capturing of up-to-date demographic, administrative and clinical information. Conclusions We implemented an efficient, transparent, scalable, and reproducible harmonisation method that enables multi-nation collaborative research. With a current focus on COVID-19 and its relationship with cardiovascular outcomes, the harmonised data has supported a wide range of research activities across the UK.

Purpose: The Acute Leukemia Advocates Network (ALAN) sought to determine which factors are most associated with poor quality of life (QoL) in patients with acute leukemia and to determine key issues and unmet needs through administration of an online survey distributed worldwide via partner patient organizations. Methods: ALAN developed a questionnaire informed by literature review and based extensively on the hematological malignancy-specific patient-reported outcomes (HM-PRO) measure to assess the impact of acute leukemia on QoL and its relationships with patients’ demographics, disease state, disease impact, and support from health care professionals. Univariate and multivariable statistical analysis was used to investigate relationships between HM-PRO scores and the other factors. Results: Of 552 respondents from 42 countries, 332 had acute myeloid leukemia, 139 had acute lymphoblastic leukemia, and 81 had acute promyelocytic leukemia (survey data collected in 2019). Younger age, female gender, and lower income were all significantly negatively associated with QoL. Weak or moderate correlations were observed between overall support, management, and impact of treatment and diagnosis of acute leukemia. Feeling isolated and having reduced ability to carry out physical or enjoyable activities were the most important individual factors, while the best predictors for QoL impact were age, gender, and income (model r-squared = 0.16, complete case n = 449). Conclusions: Findings indicated key factors, particularly age, gender, and socioeconomic state, that clinicians responsible for the care of patients with acute leukemia should be aware of when designing support strategies. The importance of social functioning in relation to patient QoL also should be included in considerations.

Abstract Much of the knowledge and information needed for enabling high-quality clinical research is stored in free-text format. Natural language processing (NLP) has been used to extract information from these sources at scale for several decades. This paper aims to present a comprehensive review of clinical NLP for the past 15 years in the UK to identify the community, depict its evolution, analyse methodologies and applications, and identify the main barriers. We collect a dataset of clinical NLP projects (n = 94; £ = 41.97 m) funded by UK funders or the European Union’s funding programmes. Additionally, we extract details on 9 funders, 137 organisations, 139 persons and 431 research papers. Networks are created from timestamped data interlinking all entities, and network analysis is subsequently applied to generate insights. 431 publications are identified as part of a literature review, of which 107 are eligible for final analysis. Results show, not surprisingly, clinical NLP in the UK has increased substantially in the last 15 years: the total budget in the period of 2019–2022 was 80 times that of 2007–2010. However, the effort is required to deepen areas such as disease (sub-)phenotyping and broaden application domains. There is also a need to improve links between academia and industry and enable deployments in real-world settings for the realisation of clinical NLP’s great potential in care delivery. The major barriers include research and development access to hospital data, lack of capable computational resources in the right places, the scarcity of labelled data and barriers to sharing of pretrained models.

Abstract The majority of nucleated somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs). The process of reprogramming involves epigenetic remodelling to turn on pluripotency-associated genes and turn off lineage-specific genes. Some evidence shows that iPSCs retain epigenetic marks of their cell of origin and this “epigenetic memory” influences their differentiation potential, with a preference towards their cell of origin. Here, we reprogrammed proximal tubule cells (PTC) and tail tip fibroblasts (TTF), from a reprogrammable mouse to iPSCs and differentiated the iPSCs to renal progenitors to understand if epigenetic memory plays a role in renal differentiation. This model allowed us to eliminate experimental variability due to donor genetic differences and transfection of the reprogramming factors such as copy number and integration site. In this study we demonstrated that early passage PTC iPSCs and TTF iPSCs expressed low levels of renal progenitor genes and high levels of pluripotency-associated genes, and the transcriptional levels of these genes were not significantly different between PTC iPSCs and TTF iPSCs. We used ChIP-seq of H3K4me3, H3K27me3, H3K36me3 and global DNA methylation profiles of PTC iPSCs and TTF iPSCs to demonstrate that global epigenetic marks were not different between the cells from the two different sets of tissue samples. There were also no epigenetic differences observed when kidney developmental genes and pluripotency-associated genes were closely examined. We did observe that during differentiation to renal progenitor cells the PTC iPSC-derived renal cells expressed higher levels of three renal progenitor genes compared to progenitors derived from TTF iPSCs but the underlying DNA methylation and histone methylation patterns did not suggest an epigenetic memory basis for this.

Abstract Clinical coding is the task of transforming medical information in a patient’s health records into structured codes so that they can be used for statistical analysis. This is a cognitive and time-consuming task that follows a standard process in order to achieve a high level of consistency. Clinical coding could potentially be supported by an automated system to improve the efficiency and accuracy of the process. We introduce the idea of automated clinical coding and summarise its challenges from the perspective of Artificial Intelligence (AI) and Natural Language Processing (NLP), based on the literature, our project experience over the past two and half years (late 2019–early 2022), and discussions with clinical coding experts in Scotland and the UK. Our research reveals the gaps between the current deep learning-based approach applied to clinical coding and the need for explainability and consistency in real-world practice. Knowledge-based methods that represent and reason the standard, explainable process of a task may need to be incorporated into deep learning-based methods for clinical coding. Automated clinical coding is a promising task for AI, despite the technical and organisational challenges. Coders are needed to be involved in the development process. There is much to achieve to develop and deploy an AI-based automated system to support coding in the next five years and beyond.

Abstract Background Vitamin and mineral supplements are widely used by children and adults diagnosed with autism spectrum disorder (ASD). Several studies have reported benefits of such supplements in resolving nutritional deficiencies, treating various metabolic problems and improving symptoms and overall quality of life. Methods This research survey collected evaluations from 161 people about the effectiveness of ANRC-Essentials Plus (ANRC-EP), a vitamin/mineral/micronutrient supplement designed for children and adults with autism. Although this was an open-label survey, results were compared with a three-month randomized double-blind placebo-controlled study of an earlier version of the supplement. Evaluations included the Parent Global Impressions of Autism (PGIA) and the Overall Benefit/Adverse Effect scale of the National Survey on Treatment Effectiveness for Autism (NSTEA). Results The participants reported substantially higher Average PGIA Scores than the placebo group in a similar previous study, with an estimated effect size of 0.66. Based on the NSTEA questionnaire, 73% of participants rated the Overall Benefit as Moderate, Good, or Great, with scores that were substantially higher than the NSTEA study found for multi-vitamins, the average of 58 nutraceuticals, and the average of 28 psychiatric and seizure medications. The Overall Adverse Effect score was low (0.25/3.0), similar or slightly higher than other nutraceuticals, and much lower than the average of 28 psychiatric and seizure medications (0.9/3.0). Sub-analysis found that the Overall Benefit of ANRC-EP was not significantly affected by gender, age, autism severity, diet quality, self-limited diet, use of psychiatric or seizure medications, dosage, developmental history, intellectual disability, or seizures. This indicates that ANRC-EP may be beneficial for a wide range of children and adults with ASD. A limitation of this study is the retrospective nature of the survey, and that participants who had good benefits were more likely to respond. Conclusions This study found that ANRC-EP had significant benefits for a wide range of symptoms, and low adverse effects.

Despite the prevalence of human immunodeficiency virus (HIV) in Mississippi, access to pre-exposure prophylaxis (PrEP) is mostly limited to urban areas. Remote PrEP care via telemedicine, HIV self-testing, and prescription mail delivery can improve care in underserved communities. This mixed methods study assessed the acceptability and feasibility of using remote PrEP care, compared to alternatives. This consisted of (1) a cross-sectional survey and (2) interviews. PrEP-eligible adults were recruited from community-based organizations across Mississippi while accessing HIV testing between December 2019 and May 2022. Those surveyed (n = 63) indicated the greatest comfort in receiving PrEP via mail delivery ( m = 5.14) and telemedicine ( m = 4.89) and least comfort at gyms ( m = 3.92). Comfort significantly differed between mail delivery and gyms ( F = 2.90; P

ABSTRACT Pathogenic microbial ecosystems are often polymicrobial, and interbacterial interactions drive emergent properties of these communities. In the oral cavity, Streptococcus gordonii is a foundational species in the development of plaque biofilms, which can contribute to periodontal disease and, after gaining access to the bloodstream, target remote sites such as heart valves. Here, we used a transposon sequencing (Tn-Seq) library of S. gordonii to identify genes that influence fitness in a murine abscess model, both as a monoinfection and as a coinfection with an oral partner species, Porphyromonas gingivalis. In the context of a monoinfection, conditionally essential genes were widely distributed among functional pathways. Coinfection with P. gingivalis almost completely changed the nature of in vivo gene essentiality. Community-dependent essential (CoDE) genes under the coinfection condition were primarily related to DNA replication, transcription, and translation, indicating that robust growth and replication are required to survive with P. gingivalis in vivo. Interestingly, a group of genes in an operon encoding streptococcal receptor polysaccharide (RPS) were associated with decreased fitness of S. gordonii in a coinfection with P. gingivalis. Individual deletion of two of these genes (SGO_2020 and SGO_2024) resulted in the loss of RPS production by S. gordonii and increased susceptibility to killing by neutrophils. P. gingivalis protected the RPS mutants by inhibiting neutrophil recruitment, degranulation, and neutrophil extracellular trap (NET) formation. These results provide insight into genes and functions that are important for S. gordonii survival in vivo and the nature of polymicrobial synergy with P. gingivalis. Furthermore, we show that RPS-mediated immune protection in S. gordonii is dispensable and detrimental in the presence of a synergistic partner species that can interfere with neutrophil killing mechanisms. IMPORTANCE Bacteria responsible for diseases originating at oral mucosal membranes assemble into polymicrobial communities. However, we know little regarding the fitness determinants of the organisms that initiate community formation. Here, we show that the extracellular polysaccharide of Streptococcus gordonii, while important for streptococcal survival as a monoinfection, is detrimental to survival in the context of a coinfection with Porphyromonas gingivalis. We found that the presence of P. gingivalis compensates for immune protective functions of extracellular polysaccharide, rendering production unnecessary. The results show that fitness determinants of bacteria in communities differ substantially from those of individual species in isolation. Furthermore, constituents of communities can undertake activities that relieve the burden of energetically costly biosynthetic reactions on partner species.

Bhutan is a part of the second-largest Tiger Conservation Landscape (TCL), The Northern Forest Complex-Namdapha-Royal Manas, and is home to a tiger population of global conservation priority. With its well-connected protected area network and a vast expanse of forested landscape, Bhutan has a unique potential to spatially connect tiger populations in the Terai TCL of India and Nepal on the western side to the north-eastern part of the Indian subcontinent. However, information on genetic structure and connectivity among tiger populations is lacking in the Eastern Himalayan region. Due to the large and contiguous forested landscape with a network of well-connected protected areas and strong environmental protection measures in Bhutan, tiger populations in Bhutan are expected to have high genetic variation and gene flow. We made the first-ever attempt at the genetic sampling of the tiger population in Bhutan, where we genotyped 24 tiger individuals using thirteen microsatellite loci. Genetic analyses revealed three genetic clusters and found high expected heterozygosity (mean HE = 0.73) and moderate-to-high genetic differentiation (FST = 0.135) within this pool of sampled tigers. We also were able to assign poached tigers to our inferred genetic clusters. Two individual wild tigers showed distinct multilocus genotypes, similar to each other but highly divergent from all other sampled tigers, suggesting their origin from outside the sampled areas. Our study provides the first insights into the population genetic structure of tigers in this important region and suggests that gene flow is less than suggested by dispersal. A larger landscape-level genetic study with implications for the transboundary conservation of tigers in this highly biodiverse landscape is warranted.

Hybrid spin–mechanical systems provide a platform for integrating quantum registers and transducers. Efficient creation and control of such systems require a comprehensive understanding of the individual spin and mechanical components as well as their mutual interactions. Point defects in silicon carbide (SiC) offer long-lived, optically addressable spin registers in a wafer-scale material with low acoustic losses, making them natural candidates for integration with high-quality-factor mechanical resonators. Here, we show Gaussian focusing of a surface acoustic wave in SiC, characterized using a stroboscopic X-ray diffraction imaging technique, which delivers direct, strain amplitude information at nanoscale spatial resolution. Using ab initio calculations, we provide a more complete picture of spin–strain coupling for various defects in SiC with C 3v symmetry. This reveals the importance of shear strain for future device engineering and enhanced spin–mechanical coupling. We demonstrate all-optical detection of acoustic paramagnetic resonance without microwave magnetic fields, relevant for sensing applications. Finally, we show mechanically driven Autler–Townes splittings and magnetically forbidden Rabi oscillations. These results offer a basis for full strain control of three-level spin systems.

Geophysical monitoring of landslides can provide insights into spatial and temporal variations of subsurface properties associated with slope failure. Recent improvements in equipment, data analysis, and field operations have led to a significant increase in the use of such techniques in monitoring. Geophysical methods complement intrusive approaches, which sample only a very small proportion of the subsurface, and walk-over or remotely sensed data, which principally provide information only at the ground surface. In particular, recent studies show that advances in geophysical instrumentation, data processing, modeling, and interpretation in the context of landslide monitoring are significantly improving the characterization of hillslope hydrology and soil and rock hydrology and strength and their dynamics over time. This review appraises the state of the art of geophysical monitoring, as applied to moisture-induced landslides. Here we focus on technical and practical uses of time-lapse methods in geophysics applied to monitoring moisture-induced landslide. The case studies identified in this review show that several geophysical techniques are currently used in the monitoring of subsurface landslide processes. These geophysical contributions to monitoring and predicting the evolution of landslide processes are currently underrealized. Hence, the further integration of multiple-parametric and geotechnically coupled geophysical monitoring systems has considerable potential. The complementary nature of certain methods to map the distribution of subsurface moisture and elastic moduli will greatly increase the predictive and monitoring capacity of early warning systems in moisture-induced landslide settings.