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Abstract Understanding the genetic targets of natural selection is one of the most challenging goals of population genetics. Some of the earliest candidate genes were identified from associations between allozyme allele frequencies and environmental variation. One such example is the clinal polymorphism in the arginine kinase (Ak) gene in the marine snail Littorina fabalis. While other enzyme loci do not show differences in allozyme frequencies among populations, the Ak alleles are near differential fixation across repeated wave exposure gradients in Europe. Here, we use this case to illustrate how a new sequencing toolbox can be employed to characterize the genomic architecture associated with historical candidate genes. We found that the Ak alleles differ by nine nonsynonymous substitutions, which perfectly explain the different migration patterns of the allozymes during electrophoresis. Moreover, by exploring the genomic context of the Ak gene, we found that the three main Ak alleles are located on different arrangements of a putative chromosomal inversion that reaches near fixation at the opposing ends of two transects covering a wave exposure gradient. This shows Ak is part of a large (3/4 of the chromosome) genomic block of differentiation, in which Ak is unlikely to be the only target of divergent selection. Nevertheless, the nonsynonymous substitutions among Ak alleles and the complete association of one allele with one inversion arrangement suggest that the Ak gene is a strong candidate to contribute to the adaptive significance of the inversion.

Abstract Understanding population divergence that eventually leads to speciation is essential for evolutionary biology. High species diversity in the sea was regarded as a paradox when strict allopatry was considered necessary for most speciation events because geographical barriers seemed largely absent in the sea, and many marine species have high dispersal capacities. Combining genome‐wide data with demographic modelling to infer the demographic history of divergence has introduced new ways to address this classical issue. These models assume an ancestral population that splits into two subpopulations diverging according to different scenarios that allow tests for periods of gene flow. Models can also test for heterogeneities in population sizes and migration rates along the genome to account, respectively, for background selection and selection against introgressed ancestry. To investigate how barriers to gene flow arise in the sea, we compiled studies modelling the demographic history of divergence in marine organisms and extracted preferred demographic scenarios together with estimates of demographic parameters. These studies show that geographical barriers to gene flow do exist in the sea but that divergence can also occur without strict isolation. Heterogeneity of gene flow was detected in most population pairs suggesting the predominance of semipermeable barriers during divergence. We found a weak positive relationship between the fraction of the genome experiencing reduced gene flow and levels of genome‐wide differentiation. Furthermore, we found that the upper bound of the ‘grey zone of speciation’ for our dataset extended beyond that found before, implying that gene flow between diverging taxa is possible at higher levels of divergence than previously thought. Finally, we list recommendations for further strengthening the use of demographic modelling in speciation research. These include a more balanced representation of taxa, more consistent and comprehensive modelling, clear reporting of results and simulation studies to rule out nonbiological explanations for general results.

Approaches to both determine abdominal age and identify risk factors for accelerated abdominal age will help delay the onset of several diseases. Here, the authors build an abdominal age predictor by training convolutional neural networks to predict abdominal age from liver and pancreas MRIs.

Physical activity improves quality of life and protects against age-related diseases. With age, physical activity tends to decrease, increasing vulnerability to disease in the elderly. In the following, we trained a neural network to predict age from 115,456 one week-long 100Hz wrist accelerometer recordings from the UK Biobank (mean absolute error = 3.7±0.2 years), using a variety of data structures to capture the complexity of real-world activity. We achieved this performance by preprocessing the raw frequency data as 2,271 scalar features, 113 time series, and four images. We defined accelerated aging for a participant as being predicted older than one’s actual age and identified both genetic and environmental exposure factors associated with the new phenotype. We performed a genome wide association on the accelerated aging phenotypes to estimate its heritability (h_g2 = 12.3±0.9%) and identified ten single nucleotide polymorphisms in close proximity to genes in a histone and olfactory cluster on chromosome six (e.g HIST1H1C, OR5V1). Similarly, we identified biomarkers (e.g blood pressure), clinical phenotypes (e.g chest pain), diseases (e.g hypertension), environmental (e.g smoking), and socioeconomic (e.g income and education) variables associated with accelerated aging. Physical activity-derived biological age is a complex phenotype associated with both genetic and non-genetic factors. Author summary Physical activity improves quality of life and is also an important protective factor for prevalent age-related diseases and outcomes, such as diabetes and mortality. With age, physical activity tends to decrease, increasing vulnerability to disease in the elderly. Does physical activity measured from digital health devices predict one’s biological age? Biological age, as contrast to chronological age (the time that has elapsed since birth), is an indicator of the biological changes that accrue through time that are hypothesized to be one causal factor for age-related diseases. In the following, we trained machine learning models to predict age from 115,456 one week-long wrist accelerometer recordings from participants of the UK Biobank. We then found genetic, environmental, and behavioral factors associated with accelerated age, the difference between biological and chronological age, adding to the evidence of the biological plausibility of our new predictor. If reversable, summarizing complex physical activity into a biological age predictor may be a way of observing the effect of preventative efforts in real-time.

Abstract The correct immobilization and orientation of enzymes on nanosurfaces is a crucial step either for the realization of biosensors, as well as to guarantee the efficacy of the developed biomaterials. In this work we produced two versions of a chimeric protein, namely ArsC-Vmh2 and Vmh2-ArsC, which combined the self-assembling properties of Vmh2, a hydrophobin from Pleurotus ostreatus, with that of TtArsC, a thermophilic arsenate reductase from Thermus thermophilus; both chimeras were heterologously expressed in Escherichia coli and purified from inclusion bodies. They were characterized for their enzymatic capability to reduce As(V) into As(III), as well as for their immobilization properties on polystyrene and gold in comparison to the native TtArsC. The chimeric proteins immobilized on polystyrene can be reused up to three times and stored for 15 days with 50% of activity loss. Immobilization on gold electrodes showed that both chimeras follow a classic Langmuir isotherm model towards As(III) recognition, with an association constant (KAsIII) between As(III) and the immobilized enzyme, equal to 650 (± 100) L mol−1 for ArsC-Vmh2 and to 1200 (± 300) L mol−1 for Vmh2-ArsC. The results demonstrate that gold-immobilized ArsC-Vmh2 and Vmh2-ArsC can be exploited as electrochemical biosensors to detect As(III).

Abstract Sandeels are an ecologically important group of fishes; they are a key part of the food chain serving as food for marine mammals, seabirds and fish. Sandeels are further targeted by a large industrial fishery, which has led to concern about ecosystem effects. In the North Sea, the lesser sandeel Ammodytes marinus is by far the most prevalent species of sandeel in the fishery. Management of sandeel in the North Sea plus the Kattegat is currently divided into seven geographical areas, based on subtle differences in demography, population dynamics and results from simulations of larval dispersal. However, little is known about the underlying genetic population structure. In this study, we used 2,522 SNPs derived from restriction site‐associated DNA sequencing (RADseq) typed in 429 fish representing four main sandeel management areas. Our main results showed (a) a lack of a clear spatially defined genetic structure across the majority of genetic markers and (b) the existence of a group of at least 13 SNPs under strong linkage disequilibrium which together separate North Sea sandeel into three haplotype clusters, suggestive of one or more structural variants in the genome. Analyses of the spatial distribution of these putative structural variants suggest at least partial reproductive isolation of sandeel in the western management area along the Scottish coast, supporting a separate management. Our results highlight the importance of the application of a large number of markers to be able to detect weak patterns of differentiation. This study contributes to increasing the genetic knowledge of this important exploited species, and results can be used to improve our understanding of population dynamics and stock structure.

Summary: Background: Mortality risk stratification based on dichotomising a physiological indicator with a cutoff point might not adequately capture increased mortality risk and might not account for non-linear associations. We aimed to characterise the linear and non-linear relationships of 27 physiological indicators with all-cause mortality to evaluate whether the current clinical thresholds are suitable in distinguishing patients at high risk for mortality from those at low risk. Methods: For this observational cohort study of the US non-institutionalised population, we used data from adults (≥18 years) included in the 1999–2014 National Health and Nutrition Examination Survey (NHANES) linked with National Death Index mortality data collected from Jan 1, 1999, up until Dec 31, 2015. We used Cox proportional hazards regression models adjusted for age, sex, and race or ethnicity to assess associations of physiological indicators with all-cause mortality. We assessed non-linear associations by discretising the physiological indicator into nine quantiles (termed novemtiles) and by using a weighted sum of cubic polynomials (spline). We used ten-fold cross validation to select the most appropriate model using the concordance index, Nagelkerke R2, and Akaike Information Criterion. We identified the level of each physiological indicator that led to a 10% increase in mortality risk to define our cutoffs used to compare with the current clinical thresholds. Findings: We included 47 266 adults of 82 091 assessed for eligibility. 25 (93%) of 27 indicators showed non-linear associations with substantial increases compared with linear models in mortality risk (1·5–2·5-times increase). Height and 60 s pulse were the only physiological indicators to show linear associations. For example, participants with an estimated glomerular filtration rate (GFR) of less than 65 mL/min per 1·73 m2 or between 90–116 mL/min per 1·73 m2 are at moderate (hazard ratio 1–2) mortality risk. Those with a GFR greater than 117 mL/min per 1·73 m2 show substantial (hazard ratio ≥2) mortality risk. Both lower and higher values of cholesterol are associated with increased mortality risk. The current clinical thresholds do not align with our mortality-based cutoffs for fat deposition indices, 60 s pulse, triglycerides, cholesterol-related indicators, alkaline phosphatase, glycohaemoglobin, homoeostatic model assessment of insulin resistance, and GFR. For these indicators, the misalignment suggests the need to consider an additional bound when only one is provided. Interpretation: Most clinical indicators were shown to have non-linear associations with all-cause mortality. Furthermore, considering these non-linear associations can help derive reliable cutoffs to complement risk stratification and help inform clinical care delivery. Given the poor alignment with our proposed cutoffs, the current clinical thresholds might not adequately capture mortality risk. Funding: Ravitz Family Foundation, Forbes Institute for Cancer Discovery, and National Institutes of Health.

The immobilization of POXA1b laccase and its hydrophobin-fused chimera was performed at pristine Multiwalled Carbon Nanotube (MWCNT) and MWCNT-modified electrodes by electrografting of a 2-diazoniumanthraquinone salt. The influence of the hydrophobin domain and the MWCNT functionalization with anthraquinone groups towards immobilization of laccase was compared by direct electrochemistry under O2 and electrochemical biosensing of phenols. The hydrophobin domain affords the stable dispersion of MWCNT in water/ethanol, while being detrimental to the direct electron transfer between POXA1b and the electrode. On the contrary, the stronger hydrophobic interactions between anthraquinone and laccase affords direct electrochemistry of POXA1b and enabled the design of a highly sensitive phenol biosensor, reaching a limit-of-detection (LOD) of 2 pM and sensitivity of 23,600 mA L mmol−1 cm−2 for catechol, and a LOD of 15 nM and sensitivity of 0.053 mA L mmol−1 cm−2 for dopamine.

The microbiome is a new frontier for building predictors of human phenotypes. However, machine learning in the microbiome is fraught with issues of reproducibility, driven in large part by the wide range of analytic models and metagenomic data types available. We aimed to build robust metagenomic predictors of host phenotype by comparing prediction performances and biological interpretation across 8 machine learning methods and 4 different types of metagenomic data. Using 1,570 samples from 300 infants, we fit 7,865 models for 6 host phenotypes. We demonstrate the dependence of accuracy on algorithm choice and feature definition in microbiome data and propose a framework for building microbiome-derived indicators of host phenotype. We additionally identify biological features predictive of age, sex, breastfeeding status, historical antibiotic usage, country of origin, and delivery type. Our complete results can be viewed at http://apps.chiragjpgroup.org/ubiome_predictions/.

Massive genotyping of single nucleotide polymorphisms (SNP) has opened opportunities for analyzing the way in which selection shapes genomes. Artificial or natural selection usually leaves genomic signatures associated with selective sweeps around the responsible locus. Strong selective sweeps are most often identified either by lower genetic diversity than the genomic average and/or islands of runs of homozygosity (ROHi). Here, we conducted an analysis of selective sweeps in turbot (Scophthalmus maximus) using two SNP datasets from a Northeastern Atlantic population (36 individuals) and a domestic broodstock (46 individuals). Twenty-six families (∼ 40 offspring per family) from this broodstock and three SNP datasets applying differing filtering criteria were used to adjust ROH calling parameters. The best-fitted genomic inbreeding estimate (FROH) was obtained by the sum of ROH longer than 1 Mb, called using a 21,615 SNP panel, a sliding window of 37 SNPs and one heterozygous SNP per window allowed. These parameters were used to obtain the ROHi distribution in the domestic and wild populations (49 and 0 ROHi, respectively). Regions with higher and lower genetic diversity within each population were obtained using sliding windows of 37 SNPs. Furthermore, those regions were mapped in the turbot genome against previously reported genetic markers associated with QTL (Quantitative Trait Loci) and outlier loci for domestic or natural selection to identify putative selective sweeps. Out of the 319 and 278 windows surpassing the suggestive pooled heterozygosity thresholds (ZHp) in the wild and domestic population, respectively, 78 and 54 were retained under more restrictive ZHp criteria. A total of 116 suggestive windows (representing 19 genomic regions) were linked to either QTL for production traits, or outliers for divergent or balancing selection. Twenty-four of them (representing 3 genomic regions) were retained under stricter ZHp thresholds. Eleven QTL/outlier markers were exclusively found in suggestive regions of the domestic broodstock, 7 in the wild population and one in both populations; one (broodstock) and two (wild) of those were found in significant regions retained under more restrictive ZHp criteria in the broodstock and the wild population, respectively. Genome mining and functional enrichment within regions associated with selective sweeps disclosed relevant genes and pathways related to aquaculture target traits, including growth and immune-related pathways, metabolism and response to hypoxia, which showcases how this genome atlas of genetic diversity can be a valuable resource to look for candidate genes related to natural or artificial selection in turbot populations.

Nanomaterials have become essential components for the development of biosensors since such nanosized compounds were shown to clearly increase the analytical performance. The improvements are mainly related to an increased surface area, thus providing an enhanced accessibility for the analyte, the compound to be detected, to the receptor unit, the sensing element. Nanomaterials can also add value to biosensor devices due to their intrinsic physical or chemical properties and can even act as transducers for the signal capture. Among the vast amount of examples where nanomaterials demonstrate their superiority to bulk materials, the combination of different nano-objects with different characteristics can create phenomena which contribute to new or improved signal capture setups. These phenomena and their utility in biosensor devices are summarized in a non-exhaustive way where the principles behind these synergetic effects are emphasized.

Emerging research on followership has overwhelmingly been focused on for‐profit organizations. This research investigates four British congregations from different Christian denominations to explore how differing contexts shape the understanding of followership in nonprofit organizations. Using implicit followership theory, we analyze the value sets deriving from theological‐ideological, institutional, and local contexts and explore informants' perceptions of ideal followership attributes. By conducting 26 semi‐structured interviews with three different types of actors, we found that church members found themselves in a dialectic relationship between institutional norms and local settings, which shape the way followership is perceived. In terms of follower attributes, we identified faith‐related and ethical as well as relational attributes to be prevalent. With this research, we advance current understandings of how effective leader‐follower relationships in nonprofit organizations can be formed highlighting the importance of differing contexts for perceiving the role of followers. [ABSTRACT FROM AUTHOR]

The reduction of dioxygen to produce selectively H2O2 or H2O is crucial in various fields. While platinum‐based materials excel in 4H+/4e− oxygen reduction reaction (ORR) catalysis, cost and resource limitations drive the search for cost‐effective and abundant transition metal catalysts. It is thus of great importance to understand how the selectivity and efficiency of 3d‐metal ORR catalysts can be tuned. In this context, we report on a Co complex supported by a bisthiolate N2S2‐donor ligand acting as a homogeneous ORR catalyst in acetonitrile solutions both in the presence of a one‐electron reducing agent (selectivity for H2O of 93 % and TOFi=3 000 h−1) and under electrochemically‐assisted conditions (0.81 V <η<1.10 V, selectivity for H2O between 85 % and 95 %). Interestingly, such a predominant 4H+/4e− pathway for Co‐based ORR catalysts is rare, highlighting the key role of the thiolate donor ligand. Besides, the selectivity of this Co catalyst under chemical ORR conditions is inverse with respect to the Mn and Fe catalysts supported by the same ligand, which evidences the impact of the nature of the metal ion on the ORR selectivity. [ABSTRACT FROM AUTHOR]

Chromosomal rearrangements can lead to the coupling of reproductive barriers, but whether and how they contribute to the completion of speciation remains unclear. Marine snails of the genus Littorina repeatedly form hybrid zones between populations segregating for multiple inversion arrangements, providing opportunities to study their barrier effects. Here, we analyzed 2 adjacent transects across hybrid zones between 2 ecotypes of Littorina fabalis ("large" and "dwarf") adapted to different wave exposure conditions on a Swedish island. Applying whole-genome sequencing, we found 12 putative inversions on 9 of 17 chromosomes. Nine of the putative inversions reached near differential fixation between the 2 ecotypes, and all were in strong linkage disequilibrium. These inversions cover 20% of the genome and carry 93% of divergent single nucleotide polymorphisms (SNPs). Bimodal hybrid zones in both transects indicated that the 2 ecotypes of Littorina fabalis maintain their genetic and phenotypic integrity following contact. The bimodality reflects the strong coupling between inversion clines and the extension of the barrier effect across the whole genome. Demographic inference suggests that coupling arose during a period of allopatry and has been maintained for > 1,000 generations after secondary contact. Overall, this study shows that the coupling of multiple chromosomal inversions contributes to strong reproductive isolation. Notably, 2 of the putative inversions overlap with inverted genomic regions associated with ecotype differences in a closely related species (Littorina saxatilis), suggesting the same regions, with similar structural variants, repeatedly contribute to ecotype evolution in distinct species. [ABSTRACT FROM AUTHOR]

Purpose – This paper identifies the strategic changes and explores the solutions for talent development and leadership management to address the challenges faced by the funeral service industry in Hong Kong. Design/methodology/approach – In this study, semi-structured, in-depth interviews were conducted with seven key personnel (funeral director, salesperson, coffin shop owner, and mortuary transporter) engaged in the funeral service industry in Hong Kong. Thematic coding was used to identify and organize emerging themes from the data. Findings – Four overarching themes were identified: (1) Perception of the funeral service industry in Hong Kong; (2) Recruitment, retention, and talent development; (3) Prospects of the funeral service industry in Hong Kong; and (4) Other novel challenges. The findings reveal continuous, radical, and complex challenges that may exceed the capacity of any leader to develop workable solutions. Originality/value – The funeral service industry is facing radical challenges in modern times. A death-denying attitude is observed, which has severely undermined the study of the funeral service industry.

Summary: Background: Perivascular spaces (PVS) on brain MRI are surrogates for small parenchymal blood vessels and their perivascular compartment, and may relate to brain health. However, it is unknown whether PVS can predict dementia risk and brain atrophy trajectories in participants without dementia, as longitudinal studies on PVS are scarce and current methods for PVS assessment lack robustness and inter-scanner reproducibility. Methods: We developed a robust algorithm to automatically assess PVS count and size on clinical MRI, and investigated 1) their relationship with dementia risk and brain atrophy in participants without dementia, 2) their longitudinal evolution, and 3) their potential use as a screening tool in simulated clinical trials. We analysed 46,478 clinical measurements of cognitive functioning and 20,845 brain MRI scans from 10,004 participants (71.1 ± 9.7 years-old, 56.6% women) from three publicly available observational studies on ageing and dementia (the Alzheimer’s Disease Neuroimaging Initiative, the National Alzheimer’s Coordinating Centre database, and the Open Access Series of Imaging Studies). Clinical and MRI data collected between 2004 and 2022 were analysed with consistent methods, controlling for confounding factors, and combined using mixed-effects models. Findings: Our fully-automated method for PVS assessment showed excellent inter-scanner reproducibility (intraclass correlation coefficients >0.8). Fewer PVS and larger PVS diameter at baseline predicted higher dementia risk and accelerated brain atrophy. Longitudinal trajectories of PVS markers differed significantly in participants without dementia who converted to dementia compared with non-converters. In simulated placebo-controlled trials for treatments targeting cognitive decline, screening out participants at low risk of dementia based on our PVS markers enhanced the power of the trial independently of Alzheimer’s disease biomarkers. Interpretation: These robust cerebrovascular markers predict dementia risk and brain atrophy and may improve risk-stratification of patients, potentially reducing cost and increasing throughput of clinical trials to combat dementia. Funding: US National Institutes of Health.

Laplacian eigenvalues of independence complexes via additive compound matrices, Discrete Analysis 2024:15, 17 pp. The (Laplacian) spectral gap of a graph, defined as the second smallest eigenvalue of the graph's Laplacian matrix, is an important parameter that in some sense measures how well connected the graph is. An important paper of Garland from 1973 relates spectral gaps of graphs to topological properties of simplicial complexes. Roughly what it shows is that if $X$ is a pure $d$-dimensional simplicial complex with $d\geq k+1$, and if for every $(k-1)$-simplex $S$ in $X$ the 1-skeleton of the link of $S$ (that is, the simplicial complex that consists of all simplices $T$ disjoint from $S$ with $S\cup T\in X$) has a sufficiently large spectral gap, then the $k$th cohomology group $\tilde H^k(X,\mathbb R)$ vanishes. The condition that every single link graph has a large spectral gap is quite strong. In 2003, Aharoni, Berger and Meshulam showed that a different and more global condition suffices when $X$ is the flag complex of a graph $G$ -- that is, the simplicial complex consisting of all sets of vertices of $G$ that span a clique. A consequence of their result is that $\tilde H^k(X,\mathbb R)$ vanishes if the spectral gap of $G$ is greater than $nk/(k+1)$. They obtain this bound by defining for each $k$ a $k$-dimensional Laplacian operator and bounding its smallest eigenvalue in terms of that of the $(k-1)$-dimensional Laplacian. From their result one can deduce corresponding conditions for the vanishing of cohomology for the independence complex, which is just the complex of sets of vertices that span independent sets. This paper generalizes the work of Aharoni, Berger and Meshulam, yielding a stronger result for independence complexes that takes into account not just the second eigenvalue of the Laplacian, but also other eigenvalues (in fact, sums of eigenvalues). As an application, two bounds are given using fractional domination and packing parameters -- one on the rank below which the cohomology vanishes and one of the size of cohomology. The technique that is used for proving the main theorem is to bound the eigenvalues of the $k$th Laplacian of the independence complex by relating them to eigenvalues of so-called additive compound matrices. If $V$ is a vector space and $M$ is a linear map from $V$ to $V$, then the $k$th additive compound $M^{[k]}$ of $M$ maps $\Lambda^kV$ to $\Lambda^kV$, taking $v_1\wedge\dots\wedge v_k$ to $\sum_{i=1}^k v_1\wedge\dots\wedge v_{i-1}\wedge Mv_i\wedge v_{i+1}\wedge\dots\wedge v_k$. It can be shown that the eigenvalues of $M^{[k]}$ are all possible sums of distinct eigenvalues of $M$.

Achieving commercially acceptable weed control in plasticulture vegetable production systems can be challenging because many herbicides do no provide season-long control. Additionally, several weed species have recently evolved resistance to labeled herbicides. Consequently, multiple cultivations or frequent hand-weeding are needed to control emerged weeds. Cover crops have recently gained attention as a tool for helping to manage weeds. Field studies were conducted in Maryland and New Jersey to assess the efficacy of combining spring-seeded grass cover crops and herbicide treatments for weed control in cucumber and watermelon production. Three spring cover crop treatments consisting of cereal rye, spring oats, or cereal rye and spring oats were hand-broadcasted after laying plastic in Apr 2021 and 2022. Postplant treatments were applied to cover crops and emerged weeds 78 days later, ∼3 weeks after planting each crop. Postplant treatments included shielded herbicide applications (paraquat or clethodim) or crimping without an herbicide. Residual herbicide (fomesafen + S-metolachlor) was included or not with each postplant treatment. Cover crops decreased broadleaf weed density before and 2 weeks after postplant treatment (WAT) by 73% and 68%, respectively, and weed biomass 6 WAT by 84% compared with no cover. Terminating an oat cover crop with paraquat totally suppressed smooth pigweed 2 WAT compared with clethodim or crimping treatments. Overall, cover crop treatments showed 50% greater weed control compared with no cover. Weed control in the interrow area ranged from 90% to 95% when paraquat was applied to a cover crop compared with less than 75% following crimping a cover crop. Cucumber and watermelon commercial yield decreased 63% and 52%, respectively, when cover crops were not used. These results show that spring-seeded cereal cover crops can be successfully integrated with an herbicide strategy to provide effective weed control in cucurbit production.

Abstract The Caribbean‐South America subduction zone is a flat subduction zone, with Laramide‐style thick‐skinned uplifts occurring in the Merida Andes, Sierra de Perija Range, and Santa Marta Massif. Geodetic measurements and historical seismicity show this region is storing strain energy and is capable of a mega‐thrust earthquake (M ≥ 8.0). Previous seismic investigations of the lithosphere and upper mantle in this area are either very large scale, very local, or only peripheral to this area; therefore, details of the Caribbean plate subduction geometry beneath the Maracaibo block remain unclear. In this study, we used a new data set acquired by the Caribbean‐Merida Andes seismic experiment (CARMA), which comprised 65 temporary broadband stations and 44 permanent stations from the Colombian and Venezuelan national seismic networks. We jointly inverted ambient noise Rayleigh wave Z/H ratios, phase velocities in the 8–30 s band and ballistic Rayleigh wave phase velocities in 30–80 s band to construct a 3‐D S‐wave velocity model in the area between 75°–65°W and 5°–12°N. The 3‐D model reveals a general increase in crust thickness from the trench to the southeast. An anomalous area is the Lake Maracaibo, which is underlaid by the thinnest crystalline crust in the region. This observation may indicate that the Maracaibo block is experiencing a contortion deformation within the crust. We also identified a high velocity anomaly above the subducting Caribbean slab, likely representing a detached piece of eclogitized Caribbean large igneous province from the base of the Maracaibo block. Additionally, our Vs model clearly indicates a slab tear within the subducted Caribbean slab, approximately beneath the Oca‐Ancon Fault.

Objective: To support immunisation providers through a cold chain management audit. Methods: An electronic audit survey using the National Vaccine Storage Guidelines as a gold standard was developed for general practice (GP) and community pharmacy. It included automated feedback, with individualised support from a clinical nurse specialist as required. Responses were analysed to determine the proportion of providers meeting criteria in four categories: procedures, refrigerators and equipment, temperature monitoring and emergency storage. Results: Of 818 providers invited, 420 GPs (89.6%) and 276 pharmacies (82%) responded. Over 70% met all procedural and emergency storage criteria. Although most providers (98.1% GPs, 97.0% pharmacies) used a data logger, the proportion measuring at 5-minute intervals, reviewing data logger printouts weekly and manually recording minimum and maximum temperatures was lower. In total, 58% of providers required follow-up by the clinical nurse specialist, most regarding the need for equipment. Conclusion: An electronic audit enabled public health to engage with a large number of immunisation providers. Most reported high compliance with the national guidelines although opportunities for education were identified and actioned. Implications for Public Health: Electronic solutions can support public health units to engage with providers to ensure vaccines remain effective and wastage is limited.

Patients with primary tumor progression after stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC) have a second chance at complete tumor eradication with salvage local therapies, including lung resection, repeat course of SBRT, and percutaneous ablative therapies. In this paper, we presented our institution’s initial experience with percutaneous high-dose-rate (HDR) brachyablation for a relapsed stage I NSCLC that had been treated with SBRT 4.3 years earlier. Lung tumor measuring approximately 5 cm in maximum tumor dimension at the time of relapse was histopathologically confirmed to be persistent squamous cell carcinoma, and successfully treated with a single fraction of 24 Gy with HDR brachyablation. Treatment was delivered via two percutaneous catheters inserted under CT-guidance, and treated in less than 20 minutes. The patient was discharged home later the same day without the need for a chest tube, and has been monitored with serial surveillance scans every 3 to 6 months without evidence of further lung cancer progression or complications at 2.8 years post-HDR brachyablation procedure and 7.8 years after initial SBRT.

The observation of photosynthetic biofilms growing on the Fine Residue Deposit (FRD) kimberlite produced by the Venetia Diamond Mine, Limpopo, South Africa suggests that processed kimberlite supports bacterial growth. The presence of this biofilm may aid in the acceleration of weathering of this ultra-mafic host material – a process that can sequester CO2 via carbon mineralization. Laboratory and field trial experiments were undertaken to understand the microbe–mineral interactions occurring in these systems, and how these interactions impact geochemical cycling and carbonate precipitation. At laboratory scale it was discovered that using kimberlite as a growth supplement increased biomass production (up to 25-fold) and promoted microbiome diversity, while the inoculation of FRD systems aided in the aggregation, settling, and dewatering of kimberlitic slurries. Field trial studies combining photosynthetic biofilms (cultured in 3 × 1,000 L bioreactors) with FRD material were initiated to better understand microbially enhanced mineral carbonation across different depths, and under field environmental conditions. Over the 15-month experiment the microbial populations shifted with the kimberlitic environmental pressure, with the control and inoculated systems converging. The natural endogenous biosphere (control) and the inoculum accelerated carbonate precipitation across the entire 40 cm bioreactor depth, producing average 15-month carbonation rates of 0.57 wt.% and 1.17 wt.%, respectively. This corresponds to an annual CO2e mine offset of ~4.48% and ~ 9.2%, respectively. Millimetre-centimetre scale secondary carbonate that formed in the inoculated bioreactors was determined to be biogenic in nature (i.e., possessing microbial fossils) and took the form of radiating colloform precipitates with the addition of new, mineralized colonies. Surficial conditions resulted in the largest production of secondary carbonate, consistent with a ca. 12% mine site CO2e annual offset after a 15-month incubation period.

Chest wall pain syndromes can emerge following local therapies for lung cancer and can adversely affect patients’ quality-of-life. This can occur after lung surgery, radiation therapy, or percutaneous image-guided thermal ablation. This review describes the multifactorial pathophysiology of chest wall pain syndromes that develop following surgical and non-surgical local therapies for lung cancer and summarizes evidence-based management strategies for inflammatory, neuropathic, myofascial, and osseous pain. It discusses a step-wise approach to treating chest wall pain that begins with non-opioid oral analgesics and includes additional pharmacologic treatments as clinically indicated, such as anticonvulsants, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, and various topical treatments. For myofascial pain, physical medicine techniques, such as acupuncture, trigger point injections, deep tissue massage, and intercostal myofascial release can also offer pain relief. For severe or refractory cases, opioid analgesics, intercostal nerve blocks, or intercostal nerve ablations may be indicated. Fortunately, palliation of treatment-related chest wall pain syndromes can be managed by most clinical providers, regardless of the type of local therapy utilized for a patient’s lung cancer treatment. In cases where a patient’s pain fails to respond to initial medical management, clinicians can consider referring to a pain specialist who can tailor a more specific pharmacologic approach or perform a procedural intervention to relieve pain.

Summary: Xeroderma pigmentosum (XP) is caused by defective nucleotide excision repair of DNA damage. This results in hypersensitivity to ultraviolet light and increased skin cancer risk, as sunlight-induced photoproducts remain unrepaired. However, many XP patients also display early-onset neurodegeneration, which leads to premature death. The mechanism of neurodegeneration is unknown. Here, we investigate XP neurodegeneration using pluripotent stem cells derived from XP patients and healthy relatives, performing functional multi-omics on samples during neuronal differentiation. We show substantially increased levels of 5′,8-cyclopurine and 8-oxopurine in XP neuronal DNA secondary to marked oxidative stress. Furthermore, we find that the endoplasmic reticulum stress response is upregulated and reversal of the mutant genotype is associated with phenotypic rescue. Critically, XP neurons exhibit inappropriate downregulation of the protein clearance ubiquitin-proteasome system (UPS). Chemical enhancement of UPS activity in XP neuronal models improves phenotypes, albeit inadequately. Although more work is required, this study presents insights with intervention potential.

The mass production of augmented reality (AR) waveguides has been challenging due to the intricate nature of the fabrication technique and the high precision required for their optical characteristics. In this paper, we have presented a novel and low-cost approach for fabricating geometric optical waveguides designed for AR applications utilizing 3D printing techniques. To strike a balance between optical performance and fabrication feasibility, we have optimized the conventional geometric waveguide design to facilitate easier fabrication. It is worth noting that our proposed method does not require molding, dicing, or post-surface polishing after printing. A prototype based on this method has been successfully fabricated, showing the immersion between the virtual image and the real-world scene. The proposed method has great potential for adaptation to mass production in various AR applications.

Streams represent a special case of directional environmental gradients where ecological opportunity for diversification may be associated with upstream and downstream dispersal into habitats that differ in selective pressures. Temperature, current velocity and variability, sediment erosion dynamics and oxygen saturation are key environmental parameters that change in predictable ways from springs to river mouth. Many aquatic insects occupy specific longitudinal regions along these gradients, indicating a high degree of adaptation to these specific environmental conditions. In caddisflies, the evolution of tracheal gills in larval and pupal stages may be a major driver in oxygen uptake efficiency and ecological diversification. Here we study the evolution of larval gill structure in the Rhyacophila vulgaris species group using phylogenomic methods. Based on anchored hybrid enrichment, we sequenced 97 kbp of data representing 159 independent nuclear protein coding gene regions to infer the phylogeny of the R. vulgaris species group, whose species exhibit both high diversity of gill types and varied longitudinal preferences. We find that the different gill types evolved independently as derived characters in the genus and that gill structure is linked to the longitudinal habitat preference, thereby serving as a possible ecological key innovation in the R. vulgaris group.

Abstract Real world evidence is now accepted by authorities charged with assessing the benefits and harms of new therapies. Clinical trials based on real world evidence are much less expensive than randomized clinical trials that do not rely on “real world evidence” such as contained in electronic health records (EHR). Consequently, we can expect an increase in the number of reports of these types of trials, which we identify here as ‘EHR-sourced trials.’ ‘In this selected literature review, we discuss the various designs and the ethical issues they raise. EHR-sourced trials have the potential to improve/increase common data elements and other aspects of the EHR and related systems. Caution is advised, however, in drawing causal inferences about the relationships among EHR variables. Nevertheless, we anticipate that EHR-CTs will play a central role in answering research and regulatory questions.

Anthropogenic chemicals are fundamental for maintaining our standard of living in modern society. Unfortunately, some chemicals are persistent and can enter waste streams and, ultimately, the environment. Commonly used household products, including pharmaceuticals and personal care products, are notable sources of contaminants. The aim of this study was to develop an ‘Up-the-Pipe Solutions’ framework to raise awareness within the wider community about the presence and potential risks of the chemicals found in household products. There is potential to reduce the levels of contaminants in waste streams or substitute them with less harmful alternatives by raising awareness. This framework is based on ‘The Natural Step’ and the concept of essentiality; it recognises the importance of engaging with communities to raise awareness of each individual’s contribution to the problem. Our daily activities and behavioural patterns can have adverse consequences, including the release of persistent contaminants in main waste streams from our kitchens, bathrooms, and green wastes. The ‘Up-the-Pipe Solutions’ framework was successfully used in a small community to engage with school children, local authorities, and Māori leaders to raise awareness of chemical pollution.

Australia commenced administration of the Spikevax (Moderna mRNA-1273) COVID-19 vaccine in August 2021 and Nuvaxovid (Novavax NVX-CoV2373) in January 2022. This study describes the short-term safety profile of priming doses of the Spikevax and Nuvaxovid vaccines given between September 2021 and September 2023. Online surveys were sent via AusVaxSafety, Australia’s active vaccine safety surveillance system, three and eight days after vaccination. A total of 131,775 day 3 surveys were sent, with a response rate of 38.5% (N = 50,721). A total of 43,875 day 8 surveys matched with day 3 survey responses were sent, with a response rate of 71.5% (N = 31,355). Half (50.7%) of respondents reported any adverse event following immunisation (AEFI) in the 0–3 days after vaccination and 24.6% reported any AEFI 4–7 days after vaccination. Fatigue, local pain, headache, and myalgia were the most frequently reported symptoms for both vaccines in both periods. After adjusting for respondent characteristics, vaccination clinic type, jurisdiction, and medical conditions, the odds for reporting AEFI increased with age from 16–19 years to highest odds at 30–39 years, after which it declined. Females had greater odd of reporting AEFI than males across most age groups, vaccine types, and doses. Respondents with a history of anaphylaxis had greater odds of reporting any AEFI (adjusted OR range: 1.50–2.86). A total of 3.1% of respondents reported seeking medical review 0–3 days after vaccination. This study affirms the short-term safety of Spikevax and Nuvaxovid COVID-19 vaccine priming doses in a large sample in Australia.

This article provides an overview of the Texas Gulf Coast as a port city region dedicated above all to oil and gas. By the late 1800s, the same trends in transportation and industry that encouraged ship channel construction around the world drew attention to schemes to transform the Gulf Coast’s shallow bays and estuaries into inland deep-water harbors. An added factor in Texas was the vulnerability of Galveston and other coastal locations to hurricanes. Between 1902, when construction began on the 52-mile Houston Ship Channel, and the 1950s–60s, when a deep-water channel opened at Matagorda Bay along the mid-Texas coast, various levels of government—local, state, and national—combined to engineer one of the world’s most elaborate navigation networks. Six deep-water channels were woven together by Gulf Intracoastal Waterway, which connected Texas to the Mississippi and beyond. During the years when these ports were taking shape, the Texas oil industry had begun to burgeon. In a reflection of the pre-Spindletop origins of Texas’s deep-water movement, policy and planning continued to assume, until oil’s dominance had become clear, that even the massive ship channels at Houston and Corpus Christi would serve mainly as outlets for agricultural commodities. It was the organizers of the state’s petroleum sector who came to understand the Texas ship channels as exemplary locations for aggregating their diverse operations. This interplay between civil engineering and the energy sector made coastal Texas into a dynamic urban port region. Petroleum and petrochemicals, however, so thoroughly imprinted themselves on the landscape, economy, and life of Texas’s oil port region that the region’s post-oil future remained difficult to envision.

Polyalcohols such as arabitol are among the main targets of biorefineries aiming to upcycle wastes and cheap substrates. In previous works Wickerhamomyces anomalus WC 1501 emerged as an excellent arabitol producer utilizing glycerol. Arabitol production by this strain is not growth associated, therefore, in this study, pre-grown cells were entrapped in calcium alginate beads (AB) and utilized for glycerol transformation to arabitol. Flasks experiments aimed to assess the medium composition (i.e., the concentration of inorganic and organic nitrogen sources and phosphates) and to establish the appropriate carrier-to-medium proportion. In flasks, under the best conditions of ammonium limitation and the carrier:medium ratio of 1:3 (w/v), 82.7 g/L glycerol were consumed in 168 h, yielding 31.2 g/L arabitol, with a conversion of 38% and volumetric productivity of 186 mg/mL/h. The process with immobilized cells was transferred to laboratory scale bioreactors with different configurations: stirred tank (STR), packed bed (PBR), fluidized bed (FBR), and airlift (ALR) bioreactors. The STR experienced oxygen limitation due to the need to maintain low stirring to preserve AB integrity and performed worse than flasks. Limitations in diffusion and mass transfer of oxygen and/or nutrients characterized also the PBR and the FBR and were partially relieved only in ALR, where 89.4 g/L glycerol were consumed in 168 h, yielding 38.1 g/L arabitol, with a conversion of 42% and volumetric productivity of 227 mg/mL/h. When the ALR was supplied with successive pulses of concentrated glycerol to replenish the glycerol as it was being consumed, 117 g/L arabitol were generated in 500 h, consuming a total of 285 g/L glycerol, with a 41% and 234 mg/L/h. The study strongly supports the potential of W. anomalus WC 1501 for efficient glycerol-to-arabitol conversion using immobilized cells. While the yeast shows promise by remaining viable and active for extended periods, further optimization is required, especially regarding mixing and oxygenation. Improving the stability of the immobilization process is also crucial for reusing pre-grown cells in multiple cycles, reducing dead times, biomass production costs, and enhancing the economic feasibility of the process.

Fentanyl elicits profound disturbances in ventilatory control processes in humans and experimental animals. The traditional viewpoint with respect to fentanyl-induced respiratory depression is that once the effects on the frequency of breathing (Freq), tidal volume (TV), and minute ventilation (MV = Freq × TV) are resolved, then depression of breathing is no longer a concern. The results of the present study challenge this concept with findings, as they reveal that while the apparent inhibitory effects of fentanyl (75 μg/kg, IV) on Freq, TV, and MV in adult male rats were fully resolved within 15 min, many other fentanyl-induced responses were in full effect, including opposing effects on respiratory timing parameters. For example, although the effects on Freq were resolved at 15 min, inspiratory duration (Ti) and end inspiratory pause (EIP) were elevated, whereas expiratory duration (Te) and end expiratory pause (EEP) were diminished. Since the effects of fentanyl on TV had subsided fully at 15 min, it would be expected that the administration of an opioid receptor (OR) antagonist would have minimal effects if the effects of fentanyl on this and other parameters had resolved. We now report that the intravenous injection of a 1.0 mg/kg dose of the peripherally restricted OR antagonist, methyl-naloxone (naloxone methiodide, NLXmi), did not elicit arousal but elicited some relatively minor changes in Freq, TV, MV, Te, and EEP but pronounced changes in Ti and EIP. In contrast, the injection of a 2.5 mg/kg dose of NLXmi elicited pronounced arousal and dramatic changes in many variables, including Freq, TV, and MV, which were not associated with increases in non-apneic breathing events such as apneas. The two compelling conclusions from this study are as follows: 1) the blockade of central ORs produced by the 2.5 mg/kg dose of NLXmi elicits pronounced increases in Freq, TV, and MV in rats in which the effects of fentanyl had apparently resolved, and 2) it is apparent that fentanyl had induced the activation of two systems with counter-balancing effects on Freq and TV: one being an opioid receptor inhibitory system and the other being a non-OR excitatory system.

• Globally, pollinating insects face significant pressure, largely due to intensively managed agricultural systems. There has been considerable focus on the provision of resources for pollinators in agricultural landscapes, but without understanding how existing farmland habitats affect pollinators there is a risk these conservation actions could fail. • The aim of this study was to explore the relationships between the quantity, diversity, and quality of on-farm habitats with pollinator communities. To meet this aim, pollinator, floral and habitat features were assessed at twenty-nine sites, encompassing both livestock and crop systems, at a range of farming intensities, in two regions of Ireland. • Results showed that the three main taxonomic pollinator groups (hoverflies, social bees, and solitary bees) were inconsistent in their responses to habitat and environmental variables. Hoverflies were negatively associated with farms with increasing amounts of linear feature and fewer drainage ditches, whereas bumblebees were positively associated with crop farms and the number of grassy margins, drainage ditches and hedgerows at a site. Solitary bees were negatively associated with crop farms and positively associated with high floral species richness. At a species level, community analysis showed that within taxonomic groups, individual species responded differently to environmental variables. • This study demonstrates that different farm types and habitat features impact pollinator groups differently. One-size does not fit all, thus on-farm conservation actions should be designed with knowledge of taxon-specific responses to maximise benefits. The quantity and diversity of essential habitats are important along with the quality of those features in terms of their capacity to provide sufficient resources for pollinators.

Abstract Xeroderma pigmentosum (XP) is a genetic disorder caused by mutations in genes of the Nucleotide Excision Repair (NER) pathway (groups A-G) or in Translesion Synthesis DNA polymerase η (V). XP is associated with an increased skin cancer risk, reaching, for some groups, several thousand-fold compared to the general population. Here, we analyze 38 skin cancer genomes from five XP groups. We find that the activity of NER determines heterogeneity of the mutation rates across skin cancer genomes and that transcription-coupled NER extends beyond the gene boundaries reducing the intergenic mutation rate. Mutational profile in XP-V tumors and experiments with POLH knockout cell line reveal the role of polymerase η in the error-free bypass of (i) rare TpG and TpA DNA lesions, (ii) 3’ nucleotides in pyrimidine dimers, and (iii) TpT photodimers. Our study unravels the genetic basis of skin cancer risk in XP and provides insights into the mechanisms reducing UV-induced mutagenesis in the general population.

Resin infiltration is an effective method to mask vestibular white spots. If needed, external bleaching is usually recommended before infiltration, whilst in clinical practice, this sequence may not always be feasible. This in vitro study evaluated the effect of bleaching after resin infiltration regarding surface roughness and color using bovine incisors. Unlike for the untreated specimens (control, n = 25), artificial caries lesions were created within the test group (n = 25) using a demineralization solution at 37 °C for five days (pH = 4.95). The lesions were subsequently infiltrated using a resin infiltrant (Icon, DMG, Hamburg, Germany), followed by polishing. Afterwards, all specimens were bleached with a 10% carbamide peroxide gel (Opalescence, Ultradent, South Jordan, UT, USA) for 8 h/day over a ten-day period. Between bleaching treatments, specimens were stored in an opaque container with moistened paper tissues at 37 °C. Surface roughness was measured using a profilometer, and color in the L*a*b* space was assessed spectrophotometrically before and after bleaching. Bleaching increased the L*-values of both infiltrated (mean ± SD; ΔL* = 3.52 ± 1.98) and untreated (control) specimens (ΔL* = 3.53 ± 2.30) without any significant difference between the groups (p = 0.983). Bleaching also induced a significant increase in the mean surface roughness of both infiltrated (p < 0.001) and untreated (p = 0.0134) teeth. In terms of clinical relevance; it can be concluded that bleaching resin-infiltrated enamel is as effective as bleaching sound enamel.

We present extensions of the colorful Helly theorem for d-collapsible and d-Leray complexes, providing a common generalization to the matroidal versions of the theorem due to Kalai and Meshulam, the ‘very colorful’ Helly theorem introduced by Arocha, Bárány, Bracho, Fabila and Montejano and the ‘semi-intersecting’ colorful Helly theorem proved by Montejano and Karasev.

Juan José Arévalo and the “revolutionaries” brought tremendous change to Guatemala. But well before Arévalo left office, the Revolution was already in the crosshairs of US military might. At least three challenges threatened the government of Arévalo: the ultra conservatives or the “anti-revolutionaries”; competitive aspirations of the revolutionaries; and the overarching power of the US businesses and US government. Arévalo encountered these challenges from the first day of his presidency, and thereafter. Bernardo Arévalo, Guatemala’s recently elected president, faces similar dangers: a powerful opposition from an entrenched civilian and military oligarchy, urban and rural disconnections, foreign economic power and influences, national inequality and corruption, and indigenous and ladino/Hispanic conflicting aspirations. The 78 years spread between 1945 and 2023 means that the details are different, but similarities testify to continuing troubles in Guatemala. A major difference is the 21st century power of indigenous peoples, and Bernardo Arévalo’s pledge to honor and work for the concerns of the indigenous peoples as well as all Guatemalans. This contrasts with the revolutionaries of the 1940s who classified indigenous peoples as peasants requiring education and uplifting through assimilation into the national Hispanic “culture”. In an apparent second difference, currently the United States has been a strong supporter of the new president and the democracy movement. In 1945, the US also appeared to favor Juan José Arévalo, and then soon turned against him.

Abstract The InSight mission deployed one seismic station on Mars, providing a chance to apply single‐station‐based autocorrelation analysis to investigate Martian subsurface structures. However, recent analysis indicated the low‐frequency autocorrelation signals may originate from quasi‐periodic high‐amplitude instrumental “glitches” rather than the reflection response of deep Mars. In this study, we detected and removed these high‐amplitude glitches in raw seismic data and employed autocorrelation on the clean vertical component waveforms filtered between 0.05 and 0.1 Hz. We observed signals at the expected times for the olivine‐wadsleyite transition and core‐mantle boundary (CMB) as estimated by other methods. This result suggests that the low‐frequency autocorrelation signals are the reflection response from the olivine‐wadsleyite transition in the mantle and the Martian CMB region, rather than a noise phenomena. A grid search method to fit the observed PcP waveform was used to identify a layer intermediate in velocity between the Martian mantle and core at the Martian CMB.

Abstract People with diabetes can wear a device that measures blood glucose and delivers just the amount of insulin needed to return the glucose level to within bounds. Currently, people with epilepsy do not have access to an equivalent wearable device that measures a systemic indicator of an impending seizure and delivers a rapidly acting medication or other intervention (e.g., an electrical stimulus) to terminate or prevent a seizure. Given that seizure susceptibility is reliably increased in systemic inflammatory states, we propose a novel closed‐loop device where release of a fast‐acting therapy is governed by sensors that quantify the magnitude of systemic inflammation. Here, we review the evidence that patients with epilepsy have raised levels of systemic indicators of inflammation than controls, and that some anti‐inflammatory drugs have reduced seizure occurrence in animals and humans. We then consider the options of what might be incorporated into a responsive anti‐seizure system.

Here the authors present results from a randomized, double-blinded Phase 1 clinical trial, testing a thermostable presentation of a clinical-stage adjuvanted subunit tuberculosis vaccine candidate. The vaccine candidate is safe and well tolerated, and elicits comparable or improved immune responses compared to the non-thermostable presentation.

Abstract Background While most Australian children are vaccinated, delays in vaccination can put them at risk from preventable infections. Widespread mobile phone ownership in Australia could allow automated short message service (SMS) reminders to be used as a low-cost strategy to effectively ‘nudge’ parents towards vaccinating their children on time. Methods AuTOMATIC is an adaptive randomised trial which aims to both evaluate and optimise the use of SMS reminders for improving the timely vaccination of children at primary care clinics across Australia. The trial will utilise high levels of digital automation to effect, including eligibility assessment, randomisation, delivery of intervention, data extraction and analysis, thereby allowing healthcare-embedded trial delivery. Up to 10,000 parents attending participating primary care clinics will be randomised to one of 12 different active SMS vaccine reminder content and timing arms or usual practice only (no SMS reminder). The primary outcome is vaccine receipt within 28 days of the scheduled date for the index vaccine (the first scheduled vaccine after randomisation). Secondary analyses will assess receipt and timeliness for all vaccine occasions in all children. Regular scheduled analyses will be performed using Bayesian inference and pre-specified trial decision rules, enabling response adaptive randomisation, suspension of any poorly performing arms and early stopping if a single best message is identified. Discussion This study will aim to optimise SMS reminders for childhood vaccination in primary care clinics, directly comparing alternative message framing and message timing. We anticipate that the trial will be an exemplar in using Bayesian adaptive methodology to assess a readily implementable strategy in a wide population, capable of delivery due to the levels of digital automation. Methods and findings from this study will help to inform strategies for implementing reminders and embedding analytics in primary health care settings. Trial registration ANZCTR: ACTRN12618000789268 .

Abstract Arbuscular mycorrhizal fungal diversity can be altered by intercropping plant species, as well as N fertilizer applications. This study examined the effects of oat-pea intercropping and N fertilizer addition on the richness and diversity of mycorrhizal species, as well as identified the most common arbuscular mycorrhizal fungi (AMF) genera recruited for oats and peas in two growing seasons (2019 and 2020). The AMF diversity was higher in an intercropped system compared to their respective monocropping system. Under drier conditions in 2019, arbuscular mycorrhizal richness decreased with N fertilizer addition in sole peas and increased with N fertilizer addition in sole oats, but no significant change in richness was observed in oat-pea intercropping. During the wetter growing season 2020, arbuscular mycorrhizal diversity increased when oat and pea were intercropped, compared to either sole oat or sole pea. Diversispora in sole pea was a significant indicator differentiating the root associated AMF community from sole oat. Claroideoglomus richness increased in peas in 2020, thus this genus could be moisture dependent. Paraglomus richness in oat-pea intercropping was similar to sole oat in 2019, and similar to sole pea in 2020. This can suggest that Paraglomus is an indicator of plant stress under intercropping, as based on the premise that stressed plants release more exudates, and the subsequent mycorrhizal associations favor these plants with higher exudation. Future investigations can further reveal the functions and benefits of these mycorrhizal genera in annual monocrop and intercropping systems.

Background: Food allergy affects up to 10% of Australian infants. It was hypothesized that if parents follow the Australasian Society of Clinical Immunology and Allergy guidelines, Australian food allergy rates may stabilize or decline. Objective: This project aimed to determine whether SmartStartAllergy influenced parental introduction of peanut by age 12 months, including in high-risk infants. Methods: SmartStartAllergy integrates with general practice management software to send text messages to parents via participating general practices. The intervention group participants were sent text messages when their child was aged 6, 9, and 12 months; the control group participants were parents of 12-month-old infants. When their child was aged 12 months, all participants completed a questionnaire regarding eczema and family history of atopy. Infants with severe eczema and/or a family history of atopy were considered high-risk. Results: Between 21 September 2018 and 26 April 2022, a total of 29,092 parents were enrolled in SmartStartAllergy as intervention (n = 18,090) and control (n = 11,002) group members The intervention group was more likely to introduce peanut by 12 months (crude odds ratio = 5.18; P < .0001; 95% CI = 4.35-6.16). After adjustment for the infants’ level of risk and family history of atopy and food allergy, the intervention group was more likely to introduce peanut by 12 months of age (adjusted odds ratio = 5.34; P < .01; 95% CI = 4.48-6.37). Conclusion: SmartStartAllergy appears to be an effective tool for encouraging parental introduction of peanut. The ability to provide parents with credible allergy prevention information, along with the capacity to collect simple responses via text along with additional information via an online questionnaire, make this a useful public health tool.

El objetivo del artículo es analizar los cambios que se están generando en la agricultura por la pérdida de importancia relativa de esta actividad, lo que ha dado paso a una reconversión hacia el turismo o como un complemento a este en la comuna de Carahue, Chile. Se empleó una metodología cualitativa, aplicando entrevistas semiestructuradas. Los resultados indican que efectivamente hay una declinación de la actividad agrícola y que la población se ha orientado a las actividades turísticas bajo diferentes modalidades; y que, si bien son cambios que se observan en diferentes espacios rurales, los procesos están relacionados con las especificidades de cada territorio.