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Pathogenic variants in either the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired mitochondrial function. Within this group, an increasing number of families have been identified, where Mendelian genetic disorders implicate defective mitochondrial RNA biology. The PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs. Here, we report that disease-causing PDE12 variants in three unrelated families are associated with mitochondrial respiratory chain deficiencies and wide-ranging clinical presentations in utero and within the neonatal period, with muscle and brain involvement leading to marked cytochrome c oxidase (COX) deficiency in muscle and severe lactic acidosis. Whole exome sequencing of affected probands revealed novel, segregating bi-allelic missense PDE12 variants affecting conserved residues. Patient-derived primary fibroblasts demonstrate diminished steady-state levels of PDE12 protein, whilst mitochondrial poly(A)-tail RNA sequencing (MPAT-Seq) revealed an accumulation of spuriously polyadenylated mitochondrial RNA, consistent with perturbed function of PDE12 protein. Our data suggest that PDE12 regulates mitochondrial RNA processing and its loss results in neurological and muscular phenotypes. Synopsis: Pathogenic missense variants in the PDE12 gene cause neonatal-onset mitochondrial disease resulting in neurological and muscular disorders. Pathogenic PDE12 variants are associated with wide-ranging clinical presentations in utero and within the neonatal period. Patient tissues exhibit cytochrome c oxidase (COX) deficiency in muscle and severe lactic acidosis. Patient-derived fibroblasts show diminished PDE12 protein levels and aberrant polyadenylation of mitochondrial RNA. Pathogenic missense variants in the PDE12 gene cause neonatal-onset mitochondrial disease resulting in neurological and muscular disorders. [ABSTRACT FROM AUTHOR]

The conventional gradient‐echo steady‐state signal model is the basis of various spoiled gradient‐echo (SPGR) based quantitative MRI models, including variable flip angle (VFA) MRI and dynamic contrast‐enhanced MRI (DCE). However, including preparation pulses, such as fat suppression or saturation bands, disrupts the steady‐state and leads to a bias in T1 and DCE parameter estimates. This work introduces a signal model that improves the accuracy of VFA T1‐mapping and DCE for interrupted spoiled gradient‐echo (I‐SPGR) acquisitions. The proposed model was applied to a VFA T1‐mapping I‐SPGR sequence in the Gold Standard T1‐phantom (3 T), in the brain of four healthy volunteers (3 T), and to an abdominal DCE examination (1.5 T). T1‐values obtained with the proposed and conventional model were compared to reference T1‐values. Bland–Altman analysis (phantom) and analysis of variance (in vivo) were used to test whether bias from both methods was significantly different (p = 0.05). The proposed model outperformed the conventional model by decreasing the bias in the phantom with respect to the phantom reference values (mean bias ‐2 vs. ‐35% at 3 T) and in vivo with respect to the conventional SPGR (‐6 vs. ‐37% bias in T1, p < 0.01). The proposed signal model estimated approximately 48% (depending on baseline T1) higher contrast concentrations in vivo, which resulted in decreased DCE pharmacokinetic parameter estimates of up to 35%. The proposed signal model improves the accuracy of quantitative parameter estimation from disrupted steady‐state I‐SPGR sequences. It therefore provides a flexible method for applying fat suppression, saturation bands, and other preparation pulses in VFA T1‐mapping and DCE. [ABSTRACT FROM AUTHOR]

Enzyme stability can be measured in a number of ways, including melting temperature, activity retention, and size analysis. However, these measurements are often conducted in an idealized storage buffer and not in the relevant enzymatic reaction media. Particularly for reactions that occur in alkaline, volatile, and high ionic strength media, typical analyses using differential scanning calorimetry, light scattering, and sodium dodecyl‐sulfate polyacrylamide gel electrophoresis are not satisfactory to track the stability of these enzymes. In this work, we monitor the stability of engineered and native dehydrogenases that require a high amount of ammonia for their reaction to occur. We demonstrate the benefits of analyzing these enzymes in their reaction buffer, uncovering trends that were not observable in the typical phosphate storage buffer. This work provides a framework for analyzing the stability of many other enzymes whose reaction media is not suitable for traditional techniques. We introduce several strategies for measuring the melting temperature, oligomeric state, and activity of these enzymes in their reaction media. Further, we have identified opportunities for integration of computational tools into this workflow to engineer enzymes more effectively for solvent tolerance and improved stability. [ABSTRACT FROM AUTHOR]

Summary: Acalabrutinib is a selective, second‐generation Bruton tyrosine kinase inhibitor. In this open‐label, parallel‐group study, patients with relapsed/refractory (R/R) follicular lymphoma (FL) were randomised to either acalabrutinib monotherapy or acalabrutinib plus rituximab. An additional cohort of patients with treatment‐naive (TN) FL received only the acalabrutinib‐rituximab combination. Acalabrutinib‐rituximab was well tolerated and active in R/R and TN FL; in the TN cohort the overall response rate was 92.3% with most remissions lasting over 4 years. Acalabrutinib monotherapy was also well tolerated and active in R/R FL. These results support further study of acalabrutinib alone and in combination with rituximab in FL. [ABSTRACT FROM AUTHOR]

Aims: To explore clinical facilitators' understanding, experiences and perceptions of their role in supporting registered nurse students (RNS) who experience workplace violence (WPV) during clinical placement. Design: An exploratory, qualitative design. Methods and Data Source: Data were collected between September and November 2022 using semi‐structured interviews of 1‐h duration with 11 clinical facilitators working in South Australia. The interviews were transcribed verbatim and analysed using thematic analysis. Results: Participants reported that WPV is experienced in many forms, including verbal and physical violence towards RNS during clinical placements. Clinical facilitators are not always aware of this experience and have mixed abilities to resolve the damage. Most importantly, clinical facilitators saw themselves as disempowered to provide the support required by RNS after WPV incidents as they perceived themselves as visitors to the facilities. Conclusion: Findings indicate that a clinical facilitator's scope and ability to support a RNS is often not at a level where real impact and safety can occur. Varying perceptions of what WPV is, what is acceptable, and the authority or influence of a clinical facilitator have all informed this issue and need to be considered in developing strategies to address WPV towards RNS. Implications for the Nursing Profession: This study highlights that by understanding the causation of WPV and recognising the lack of influence and scope of clinical facilitators to act to support RNS during WPV events, positive industry changes can be instigated to promote student placement experiences and healthcare provision. Impact: Clinical facilitators felt limited in their role to support RNS experiencing WPV. This research impacts future nursing students, education providers, clinical facilitators and clinical placement providers. Reporting Method: COREQ guidelines were utilised to report qualitative research. No Patient or Public Contribution: This paper explores specifically the clinical facilitators' perceptions of WPV. [ABSTRACT FROM AUTHOR]

Challenge 10 of the United Nations Decade of Ocean Science for Sustainable Development (2021–2030) calls for the restoration of society's relationship with the ocean. Research suggests that the relationship people have with marine environments can influence their depth of engagement in marine citizenship action, and the important role for 'marine identity' in driving that action. Although identity is well‐researched, marine identity is a concept novel to academia and a baseline understanding is required, both to grasp the scope of the concept, and to support research into its role in transforming the human‐ocean relationship.Here, a transdisciplinary study, endorsed as a UN Ocean Decade Activity and by the EU Mission Ocean & Waters, brought together a multinational community of marine researchers and practitioners to co‐produce a baseline conceptualisation of marine identity, drawing on photovoice and deliberative methodology. This paper presents the findings of the co‐production process and offers a first introduction in the literature of the multiple variations and formations of marine identity.We find marine identity to be a complex and multidimensional concept, suffused with individual experiences and understandings of the marine environment, based on social and cultural understandings of the ocean, contemporarily and historically. We present real‐world examples of marine identity to illustrate key themes that were developed through co‐production.Policy implications: We propose marine identity as a catalyst for understanding existing multifaceted and caring relationships with the ocean, as well as the restoration of society's relationship with the ocean. Marine identity research should, therefore, be prioritised in research seeking to contribute to the UN Ocean Decade Challenge 10, as this will support integration of non‐material values of the ocean into marine planning processes and policy making, enabling effective responses to Challenge 10's emphasis on integrating traditional/cultural ways of knowing and valuing the marine environment, through diverse marine identities. We welcome research efforts that will further develop the marine identity concept and empirically investigate the relationships between marine identity, marine citizenship, and people's relationships with the ocean. Read the free Plain Language Summary for this article on the Journal blog. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Chemodiversity, the diversity of specialised (secondary) metabolites, plays a crucial role in mediating interactions between plants and animals, including insect herbivores and mutualists. Chemodiversity can be observed at both the individual and the population level. However, the impacts of chemodiversity at these two levels on interactions between plants and floral visitors, mainly pollinators and floral herbivores (florivores), are only poorly understood.This study aimed to investigate the effects of chemodiversity at both individual (chemotype) and plot level on pollinators and florivores, examining their mutual interactions. To investigate these questions, we used individuals of the perennial Tanacetum vulgare differing in their terpenoid composition, representing different chemotypes. We planted individuals of five distinct chemotypes in a common garden design with homogeneous (five plants of the same chemotype) and heterogeneous (five different chemotypes) plots and observed flower visits in dependence of individual chemotype and plot type. Seeds were collected from a subset of plants and germination rates determined.Our findings revealed that chemodiversity at the plot level significantly influenced pollinator visitation, with more visits on plants of heterogeneous plots. We also observed marginally more pollinators on one of the chemotypes grown in homogeneous plots. In contrast, chemotype but not plot type had a significant effect on florivore visits. Pollinator and florivore species richness did not vary with plot type. Furthermore, a negative correlation was observed between pollinator and florivore visits in 1 year. Germination rates were positively correlated with pollinator visits and affected by chemotype but not by florivore visits or plot type.Synthesis. Our study emphasises the significance of the spatial level at which plant chemistry is perceived by flower visitors, potentially influencing the germination success of plants. Exploring the ecology of these visitors and the varying selection pressures they exert on floral chemistry can help to elucidate the evolutionary processes that maintain chemodiversity in natural environments. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Introduction: Barriers to help‐seeking for illicit drug use cross psychosocial (e.g., knowledge of where to seek help, attitudinal beliefs like being afraid of what people will think) and structural (e.g., service availability) domains. Along with people who use illicit drugs, it is important to consider the perspectives of other key groups who are often involved in the help‐seeking and recovery process. This study aimed to examine the perceived barriers to help‐seeking for people who use crystal methamphetamine ('ice') among key groups (people who use crystal methamphetamine, families and friends, health workers) as well as the general community. Methods: A cross‐sectional online survey open to all Australian residents (aged ≥18 years) was conducted November 2018–March 2019. Four key groups of interest were recruited to examine and compare perceived barriers to help‐seeking for crystal methamphetamine use. Results: Participants (n = 2108) included: people who use/have used crystal methamphetamine (n = 564, 39%), health workers (n = 288, 26.8%), affected family/friends (n = 434, 13.7%) and general community (n = 822, 20.6%). People who used crystal methamphetamine demonstrated increased odds of reporting attitudinal (OR 1.35; 1.02–1.80) or structural (OR 1.89; 1.09–3.27) barriers, or a previous negative help‐seeking experience (OR 2.27; 1.41–3.66) compared to knowledge barriers. Health workers demonstrated decreased odds of reporting attitudinal compared to knowledge barriers (OR 0.69; 0.50–0.95). Discussion and Conclusions: Perceived barriers to seeking help for crystal methamphetamine use differed among key groups involved in treatment and recovery. Acknowledging and addressing the mismatches between key groups, through targeted interventions may better support people to seek help for crystal methamphetamine use. [ABSTRACT FROM AUTHOR]

Purpose: For reliable DCE MRI parameter estimation, k‐space undersampling is essential to meet resolution, coverage, and signal‐to‐noise requirements. Pseudo‐spiral (PS) sampling achieves this by sampling k‐space on a Cartesian grid following a spiral trajectory. The goal was to optimize PS k‐space sampling patterns for abdomin al DCE MRI. Methods: The optimal PS k‐space sampling pattern was determined using an anthropomorphic digital phantom. Contrast agent inflow was simulated in the liver, spleen, pancreas, and pancreatic ductal adenocarcinoma (PDAC). A total of 704 variable sampling and reconstruction approaches were created using three algorithms using different parametrizations to control sampling density, halfscan and compressed sensing regularization. The sampling patterns were evaluated based on image quality scores and the accuracy and precision of the DCE pharmacokinetic parameters. The best and worst strategies were assessed in vivo in five healthy volunteers without contrast agent administration. The best strategy was tested in a DCE scan of a PDAC patient. Results: The best PS reconstruction was found to be PS‐diffuse based, with quadratic distribution of readouts on a spiral, without random shuffling, halfscan factor of 0.8, and total variation regularization of 0.05 in the spatial and temporal domains. The best scoring strategy showed sharper images with less prominent artifacts in healthy volunteers compared to the worst strategy. Our suggested DCE sampling strategy also showed high quality DCE images in the PDAC patient. Conclusion: Using an anthropomorphic digital phantom, we identified an optimal PS sampling strategy for abdominal DCE MRI, and demonstrated feasibility in a PDAC patient. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates the feasibility of multi‐b‐value, multi‐directional diffusion MRI for assessing the anisotropy of the cerebral pseudo‐diffusion (D*)‐tensor. We examine D*‐tensor's potential to (1) reflect CSF and blood flow, and (2) detect microvascular architectural alterations in cerebral small vessel disease (cSVD) and aging. Methods: Multi‐b‐value diffusion MRI was acquired in 32 gradient directions for 11 healthy volunteers, and in six directions for 29 patients with cSVD and 14 controls at 3 T. A physics‐informed neural network was used to estimate intravoxel incoherent motion (IVIM)–DTI model parameters, including the parenchymal slow diffusion (D‐)tensor and the pseudo‐diffusion (D*)‐tensor, from which the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were derived. Comparisons of D*‐tensor metrics were made between lateral, third, and fourth ventricles and between the middle cerebral arteries and superior sagittal sinus. Group differences in D*‐tensor metrics in normal‐appearing white matter were analyzed using multivariable linear regression, correcting for age and sex. Results: D*‐anisotropy aligned well with CSF flow and arterial blood flow. FA(D*), MD(D*), AD(D*), and RD(D*) were highest in the third, moderate in the fourth, and lowest in the lateral ventricles. The arteries showed higher MD(D*), AD(D*), and RD(D*) than the sagittal sinus. Higher FA(D*) in the normal‐appearing white matter was related to cSVD diagnosis and older age, suggesting microvascular architecture alterations. Conclusion: Multi‐b‐value, multi‐directional diffusion analysis using the IVIM–DTI model enables assessment of the cerebral microstructure, fluid flow, and microvascular architecture, providing information on neurodegeneration, glymphatic waste clearance, and the vasculature in one measurement. [ABSTRACT FROM AUTHOR]

Understanding how macroalgal forests will respond to environmental change is critical for predicting future impacts on coastal ecosystems. Although measures of adult macroalgae physiological responses to environmental stress are advancing, measures of early life‐stage physiology are rare, in part due to the methodological difficulties associated with their small size. Here we tested a novel, high‐throughput method (rate of oxygen consumption and production; V̇O2$$ \dot{V}{\mathrm{O}}_2 $$) via a sensor dish reader microplate system to rapidly measure physiological rates of the early life stages of three habitat‐forming macroalgae, the kelp Ecklonia radiata and the fucoids Hormosira banksii and Phyllospora comosa. We measured the rate of O2 consumption (respiration) and O2 production (net primary production) to then calculate gross primary production (GPP) under temperatures representing their natural thermal range. The V̇O2$$ \dot{V}{\mathrm{O}}_2 $$ microplate system was suitable for rapidly measuring physiological rates over a temperature gradient to establish thermal performance curves for all species. The V̇O2$$ \dot{V}{\mathrm{O}}_2 $$ microplate system proved efficient for measures of early life stages of macroalgae ranging in size from approximately 50 μm up to 150 mm. This method has the potential for measuring responses of early life stages across a range of environmental factors, species, populations, and developmental stages, vastly increasing the speed, precision, and efficacy of macroalgal physiological measures under future ocean change scenarios. [ABSTRACT FROM AUTHOR]

Purpose: To assess the comparative effectiveness of a tailored, interactive digital video disc (DVD) intervention versus DVD plus patient navigation (PN) intervention versus usual care (UC) on the uptake of colorectal cancer (CRC) screening among females living in Midwest rural areas. Methods: As part of a larger study, 663 females (ages 50–74) living in rural Indiana and Ohio and not up‐to‐date (UTD) with CRC screening at baseline were randomized to one of three study groups. Demographics , health status/history, and beliefs and attitudes about CRC screening were measured at baseline. CRC screening was assessed at baseline and 12 months from medical records and self‐report. Multivariable logistic regression was used to determine whether females in each group were UTD for screening and which test they completed. Results: Adjusted for covariates, females in the DVD plus PN group were 3.5× more likely to complete CRC screening than those in the UC group (odds ratio [OR] 3.62; 95% confidence interval [CI]: 2.09, 6.47) and baseline intention to receive CRC screening (OR 3.45, CI: 2.21,5.42) at baseline. Adjusting for covariates, there was no difference by study arm whether females who became UTD for CRC screening chose to complete a colonoscopy or fecal occult blood test/fecal immunochemical test. Conclusions: Many females living in the rural Midwest are not UTD for CRC screening. A tailored intervention that included an educational DVD and PN improved knowledge, addressed screening barriers, provided information about screening test options, and provided support was more effective than UC and DVD‐only to increase adherence to recommended CRC screening. [ABSTRACT FROM AUTHOR]

Background: In recent years, psychological distress in Western countries has rapidly increased among older adolescents while alcohol use has declined, though little is known about younger adolescents. It is also unclear if and how these trends relate to co‐occurring alcohol use and distress. This study sought to examine temporal changes in the prevalence of distress, alcohol use, and their co‐occurrence among young Australians. Methods: This study used data from 13,388 youth in their early teens (aged 12–14). Differences in the prevalence of high psychological distress (Kessler‐6 ≥ 13), any alcohol use (standard drink in past 3/6 months), and their co‐occurrence across cohorts (2007, 2012, 2014, 2019) were tested through log‐binomial regression models. Changes in co‐occurrence across cohorts were tested with cohort‐by‐alcohol interactions predicting distress, and vice‐versa. Differential trends by sex were evaluated. Results: From 2007 to 2019, the prevalence of high distress more than doubled (4.6%–13.5%) while alcohol use decreased by ∼90% (11.8%–3.1%). Distress increased more‐so among females, while alcohol use decreased more‐so among males. The prevalence of high distress was significantly greater among adolescents who used alcohol compared to those who had not (>2 times higher), with this co‐occurrence remaining consistent across cohorts. Conclusions: Psychological distress appears to be increasing similarly among youth in their early teens who do and do not use alcohol. At the same time, alcohol use is decreasing similarly among youth with and without distress. While alcohol use does not appear to be a driver of increases in distress, rates of co‐occurring alcohol use and distress remain high. Addressing co‐occurrence and distress‐specific mechanisms remain necessary. [ABSTRACT FROM AUTHOR]

No data are currently available on the functional role of small conductance Ca2+‐activated K+ channels (SKCa) in ovarian cancer. Here, we characterized the role of SK2 (KCa2.2) in ovarian cancer cell migration and chemosensitivity. Using the selective non‐cell‐permeant SK2 inhibitor Lei‐Dab7, we identified functional SK2 channels at the plasma membrane, regulating store‐operated Ca2+ entry (SOCE) in both cell lines tested (COV504 and OVCAR3). Silencing KCNN2 with short interfering RNA (siRNA), or blocking SK2 activity with Lei‐Dab7, decreased cell migration. The more robust effect of KCNN2 knockdown compared to Lei‐Dab7 treatment suggested the involvement of functional intracellular SK2 channels in both cell lines. In cells treated with lysophosphatidic acid (LPA), an ovarian cancer biomarker of progression, SK2 channels are a key player of LPA pro‐migratory activity but their role in SOCE is abolished. Concerning chemotherapy, SK2 inhibition increased chemoresistance to Taxol® and low KCNN2 mRNA expression was associated with the worst prognosis for progression‐free survival in patients with serous ovarian cancer. The dual roles of SK2 mean that SK2 activators could be used as an adjuvant chemotherapy to potentiate treatment efficacy and SK2 inhibitors could be administrated as monotherapy to limit cancer cell dissemination. [ABSTRACT FROM AUTHOR]

Parenting practices such as parental monitoring are known to positively impact dietary behaviours in offspring. However, links between adolescent‐perceived parental monitoring and dietary outcomes have rarely been examined and never in an Australian context. This study investigated whether adolescent‐perceived parental monitoring is associated with more fruit and vegetable, and less sugar‐sweetened beverages (SSB) and junk food consumption in Australian adolescents. Cross‐sectional data was collected as part of baseline measurement for a randomised controlled trial in 71 Australian schools in 2019. Self‐reported fruit, vegetable, SSB and junk food intake, perceived parental monitoring and sociodemographic factors were assessed. Each dietary variable was converted to "not at risk/at risk" based on dietary guidelines, binary logistic regressions examined associations between dietary intake variables and perceived parental monitoring while controlling for gender and socio‐economic status. The study was registered in ANZCTR clinical trials. The sample comprised 6053 adolescents (Mage = 12.7, SD = 0.5; 50.6% male‐identifying). The mean parental monitoring score was 20.1/24 (SD = 4.76) for males and 21.9/24 (SD = 3.37) for females. Compared to adolescents who perceived lower levels of parental monitoring, adolescents reporting higher parental monitoring had higher odds of insufficient fruit (OR = 1.03; 95% CI = 1.02–1.05) and excessive SSB (OR = 1.07; 95% CI = 1.06–1.09) intake, but lower odds of excessive junk food (OR = 0.96; 95% CI = 0.95–0.98) and insufficient vegetable (OR = 0.97, 95% CI = 0.96–0.99) intake. Adolescent dietary intake is associated with higher perceived parental monitoring; however, these associations for fruit and SSB differ to junk food and vegetable intake. This study may have implications for prevention interventions for parents, identifying how this modifiable parenting factor is related to adolescent diet has highlighted how complex the psychological and environmental factors contributing to dietary intake are. Key messages: Little research has been conducted on adolescent‐perceived parental monitoring, which is a factor contributing to overall parenting styles, and its relationship with adolescent's dietary intake. This study found that perceived parental monitoring is significantly associated with adolescent dietary intake, despite the increased autonomy and independence over food choices at this age.Our findings indicated that higher perceived parental monitoring is significantly associated with fruit, vegetable, sugar‐sweetened beverage and junk food intake in different ways, highlighting how complex the psychological and environmental factors contributing to dietary intake are.Further research is needed incorporating parents' own diet and different parenting practices from both an adolescent and parents' perspective to help better depict the most recommended style for the optimum diet during adolescence. [ABSTRACT FROM AUTHOR]

Candidate glaciovolcanic landforms have been identified across Mars, suggesting that volcano‐ice interactions may have been relatively widespread in areas that once contained extensive surface and near‐surface ice deposits. To better constrain the detection of glaciovolcanism in Mars' geological record, this study has investigated and characterized the petrology, geochemistry, and mineralogy of three intraglacial volcanoes and an interglacial volcano in the Þórisjökull area of southwest Iceland. Our results show that glaciovolcanism creates abundant, variably altered hyaloclastite and hyalotuff that is sufficiently geochemically and mineralogically distinctive from subaerially erupted lava for identification using instruments available on Mars rovers and landers. Due to the lower gravity and atmospheric pressure at the surface of Mars, hyaloclastite and hyalotuff are also more likely to form in greater abundance in Martian glaciovolcanoes. Our results support that magmatism following deglaciation likely triggers decompression melting of the shallow mantle beneath Iceland, creating systematic changes in geochemistry and mineralogy. Glaciation can also suppress magmatism at its peak, encouraging the formation of shallow fractionated magma chambers. As such, it is possible for the crustal loading of an ice cap to enhance igneous diversity on a planet without plate tectonism, creating glass‐rich, altered, and mineralogically diverse deposits such as those discovered in Gale crater by the Curiosity rover. However, as the eroded products of glaciovolcanism are similar to those formed through hydrovolcanism, the presence of a glaciovolcanic landform at the source is required to confirm whether volcano‐ice interactions occurred at the sediment source. Plain Language Summary: The ancient Martian climate has been long debated with scientists hypothesizing that the river channels and lake beds preserved on the surface today formed in either a warm and wet environment or a cold and icy environment, with heating events driving large‐scale melting. One such heating event includes volcanism. This study investigated the chemical and mineralogical impact of volcano‐ice interactions in Iceland using techniques available to Mars rovers and landers to improve the detection of these deposits on Mars. Our results show that deposits rich in glass and the early products of low temperature alteration (palagonite, clays, zeolites) are likely to be more prevalent on Mars compared to the Earth due to differences in gravity between the two planets. Furthermore, the presence of a thick ice cap on Mars may encourage a diversity of lava compositions to form in shallow magma chambers as the weight of a thick ice cap can suppress volcanism. These types of deposits are identifiable using Mars rover and lander techniques, but due to their similarities to other volcanic units that may have erupted in the presence of water, a candidate glaciovolcanic landform is needed to confirm that these deposits are from volcano‐ice interactions. Key Points: Glaciovolcanism creates large deposits of altered fragmented volcanic glass distinct from subaerial volcanismGlaciation can suppress magmatism, driving geochemical and mineralogical diversity in an area once deglaciation startsGlaciovolcanism may have occurred on Mars with explosive phreatomagmatic units more likely under Mars' planetary conditions [ABSTRACT FROM AUTHOR]

Background: Monte Carlo simulations have been considered for a long time the gold standard for dose calculations in conventional radiotherapy and are currently being applied for the same purpose in innovative radiotherapy techniques such as targeted radionuclide therapy (TRT). Purpose: We present in this work a benchmarking study of the latest version of the Transport d'Ions Lourds Dans l'Aqua & Vivo (TILDA‐V) Monte Carlo track structure code, highlighting its capabilities for describing the full slowing down of α$\alpha$‐particles in water and the energy deposited in cells by α$\alpha$‐emitters in the context of TRT. Methods: We performed radiation transport simulations of α$\alpha$‐particles (10 keV u−1${\rm u}^{-1}$–100 MeV u−1${\rm u}^{-1}$) in water with TILDA‐V and the Particle and Heavy Ion Transport code System (PHITS) version 3.33. We compared the predictions of each code in terms of track parameters (stopping power, range and radial dose profiles) and cellular S‐values of the promising radionuclide astatine‐211 (211At$^{211}{\rm At}$). Additional comparisons were made with available data in the literature. Results: The stopping power, range and radial dose profiles of α$\alpha$‐particles computed with TILDA‐V were in excellent agreement with other calculations and available data. Overall, minor differences with PHITS were ascribed to phase effects, that is, related to the use of interaction cross sections computed for water vapor or liquid water. However, important discrepancies were observed in the radial dose profiles of monoenergetic α$\alpha$‐particles, for which PHITS results showed a large underestimation of the absorbed dose compared to other codes and experimental data. The cellular S‐values of 211At$^{211}{\rm At}$ computed with TILDA‐V agreed within 4% with the values predicted by PHITS and MIRDcell. Conclusions: The validation of the TILDA‐V code presented in this work opens the possibility to use it as an accurate simulation tool for investigating the interaction of α$\alpha$‐particles in biological media down to the nanometer scale in the context of medical research. The code may help nuclear medicine physicians in their choice of α$\alpha$‐emitters for TRT. Further research will focus on the application of TILDA‐V for quantifying radioinduced damage on the deoxyribonucleic acid (DNA) molecule. [ABSTRACT FROM AUTHOR]

Against the background of the rise in higher‐education participation rates, this paper examines the spatial redistribution of undergraduates across the United Kingdom resulting from moves to and from university. Drawing on the Graduate Outcomes Surveys of 2017/2018 and 2018/2019, address data coded to 53 subregions (SRs) are used to track those enrolled on degree courses by age 20 from domicile to university and workplace 15 months after graduation. The paper begins by examining how university‐ward migration serves to concentrate this group geographically and the way in which subsequent job‐related moves tend to reinforce this process. Each person is then classified on the basis of their migration trajectories between domicile and workplace, enabling a set of migration accounts to be produced for each SR. Applying cluster analysis to these accounts, a six‐way grouping of SRs is used to gauge change between their domicile and workplace populations in both overall numbers and qualitative characteristics, the latter being measured in terms of educational qualifications preuniversity and occupational status 15 months after graduation. These analyses demonstrate how the different types of SRs fare in these exchanges of students/graduates, with more subregions suffering the 'double whammy' of losing out in both quantitative and qualitative terms than gaining from this process, with challenging implications for central government's current 'levelling‐up' agenda. [ABSTRACT FROM AUTHOR]

Peptidoglycan is a major constituent of the bacterial cell wall. Its integrity as a polymeric edifice is critical for bacterial survival and, as such, it is a preeminent target for antibiotics. The peptidoglycan is a dynamic crosslinked polymer that undergoes constant biosynthesis and turnover. The soluble lytic transglycosylase (Slt) of Pseudomonas aeruginosa is a periplasmic enzyme involved in this dynamic turnover. Using amber‐codon‐suppression methodology in live bacteria, we incorporated a fluorescent chromophore into the structure of Slt. Fluorescent microscopy shows that Slt populates the length of the periplasmic space and concentrates at the sites of septation in daughter cells. This concentration persists after separation of the cells. Amber‐codon‐suppression methodology was also used to incorporate a photoaffinity amino acid for the capture of partner proteins. Mass‐spectrometry‐based proteomics identified 12 partners for Slt in vivo. These proteomics experiments were complemented with in vitro pulldown analyses. Twenty additional partners were identified. We cloned the genes and purified to homogeneity 22 identified partners. Biophysical characterization confirmed all as bona fide Slt binders. The identities of the protein partners of Slt span disparate periplasmic protein families, inclusive of several proteins known to be present in the divisome. Notable periplasmic partners (KD < 0.5 μM) include PBPs (PBP1a, KD = 0.07 μM; PBP5 = 0.4 μM); other lytic transglycosylases (SltB2, KD = 0.09 μM; RlpA, KD = 0.4 μM); a type VI secretion system effector (Tse5, KD = 0.3 μM); and a regulatory protease for alginate biosynthesis (AlgO, KD < 0.4 μM). In light of the functional breadth of its interactome, Slt is conceptualized as a hub protein within the periplasm. [ABSTRACT FROM AUTHOR]

Background: The high maternal and neonatal mortality rate in sub‐Saharan Africa could be reduced by using navigation by means of mobile devices to increase the number of women who choose to give birth in a health center (HC) with a skilled healthcare practitioner. Methods: A quasi‐experimental design was used to test a midwife‐delivered navigation by means of mobile phone. A total of 208 women were randomized to two groups (intervention and control). Women in the intervention group received up to three navigation calls from midwives. Women in the control group received usual antenatal education during prenatal visits. Data were collected using semistructured questionnaires. Childbirth location was determined through medical records. Results: Overall, 180 (87%) women gave birth in a HC with a 3% advantage for the intervention group. A total of 86% (88/102) of the control group gave birth in a HC versus 89% (92/103) for the intervention group (Χ2 = 0.44, p‐value = 0.51), with an unadjusted odds ratio of 1.33 (95% CI: 0.57, 3.09). Among those with personal phones, 91% (138/152) had a birth in a HC versus 79% (42/53) in those without a personal phone (Χ2 = 4.89, p‐value = 0.03). Conclusions: The results of this study indicate that it is feasible to deliver phone‐based navigation to support birth in a HC; personal phone ownership may be a factor in the success of this strategy. [ABSTRACT FROM AUTHOR]

Background: Pregnancy in kidney transplant recipients has become increasingly common. However, pregnancy carries higher risks to these patients compared to the general population. Aims: To describe pregnancy outcomes in kidney transplant recipients. Materials and Methods: We conducted a single‐centre retrospective cohort study of kidney transplant recipients who delivered after 20 weeks gestation at a quaternary hospital in Victoria, Australia, between 2000 and 2022 inclusive. Results: The study included 37 pregnancies from 27 patients, accounting for 38 infants. Over half of recorded pregnancies occurred in the past five years (56.8%, n = 21). There were high rates of pre‐existing hypertension (75.7%, n = 28). Pregnancy‐induced hypertension and pre‐eclampsia were common antenatal complications (21.6%, n = 8 and 48.6%, n = 18 respectively). Soluble fms‐like tyrosine kinase‐1 / placental growth factor ratios were elevated in all patients who developed severe pre‐eclampsia (16.2%, n = 6). The median gestational age at birth was 36.4 weeks (range 20–40.4, Q1 32.9, Q3 37.6) and 59.5% (n = 22) of births were preterm. Unplanned caesarean without labour was the most common mode of birth (35.1%, n = 13). The overall caesarean rate was 62.1% (n = 23). Post‐partum haemorrhage complicated over half of pregnancies (56.8%, n = 21). Fifty percent (n = 19) of infants were admitted for neonatal care, in particular neonatal intensive care, and had low birthweights under 2500 g. While there was a transient deterioration in kidney function, there was no graft rejection within one year of birth. Conclusions: Clinicians should consider the high rates of pre‐existing hypertension, preterm birth, and caesarean birth when counselling and managing pregnant kidney transplant recipients. [ABSTRACT FROM AUTHOR]

This document provides a summary of a hackathon event organized by the Ministry of Justice (MoJ) and Aon, a reinsurance company, to explore the social impacts of climate change. The hackathon focused on developing consistent scenarios for future climate risk, understanding uncertainties in European windstorm modeling, and providing real-time context for extreme weather events. The teams developed tools and methodologies to assess the severity and potential impact of extreme events on insured losses. The collaboration between the MoJ, Aon, and participants from various institutions aims to further research and develop papers and grant proposals in these areas. [Extracted from the article]

Objective: Maxillomandibular advancement (MMA) is an effective surgical treatment for obstructive sleep apnea (OSA); however, it is unclear how many patients who are referred for MMA actually undergo surgery. This study aims to determine follow‐up rates for patients referred for MMA and the reasons behind their choices. Methods: Via retrospective review, we assessed consecutive patients with OSA intolerant to continuous positive airway pressure (CPAP) who underwent drug induced sleep endoscopy (DISE) between 2018 and 2020 at our institution. Patients recommended for MMA based on DISE and other findings were included. Patients were then contacted and administered an IRB‐approved survey in present time. Results: One hundred and fifty nine patients were referred to oral maxillofacial surgery (OMFS) for MMA consult. Seventy seven patients (48%) followed up with OMFS and 29 (18%) underwent MMA. Sixty two (40%) patients resumed CPAP. Fifty eight patients (36.5%) were lost to follow up. Seventy three patients (46%) completed our survey. Of those patients, 37 (51%) followed up with OMFS and 17 (23%) underwent MMA. Patients who did not follow up with OMFS cited the invasiveness of the surgery (39%), recovery time (17%), or both (31%) as reasons. Those who pursued consultation cited inability to tolerate CPAP (73%), not being a candidate for inspire (14%), and desire to learn about alternative treatments (14%) as reasons. Of those who did not undergo MMA, 28.6% are not using OSA treatment. Conclusion: Less than half of patients referred for MMA followed up, and less than half of those patients underwent MMA. Most patients cited concerns about the invasiveness of the surgery and recovery process. Level of Evidence: 4 Laryngoscope, 134:2964–2969, 2024 [ABSTRACT FROM AUTHOR]

Purpose: Software has a substantial impact on quantitative perfusion MRI values. The lack of generally accepted implementations, code sharing and transparent testing reduces reproducibility, hindering the use of perfusion MRI in clinical trials. To address these issues, the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI) aimed to establish a community‐led, centralized repository for sharing open‐source code for processing contrast‐based perfusion imaging, incorporating an open‐source testing framework. Methods: A repository was established on the OSIPI GitHub website. Python was chosen as the target software language. Calls for code contributions were made to OSIPI members, the ISMRM Perfusion Study Group, and publicly via OSIPI websites. An automated unit‐testing framework was implemented to evaluate the output of code contributions, including visual representation of the results. Results: The repository hosts 86 implementations of perfusion processing steps contributed by 12 individuals or teams. These cover all core aspects of DCE‐ and DSC‐MRI processing, including multiple implementations of the same functionality. Tests were developed for 52 implementations, covering five analysis steps. For T1 mapping, signal‐to‐concentration conversion and population AIF functions, different implementations resulted in near‐identical output values. For the five pharmacokinetic models tested (Tofts, extended Tofts‐Kety, Patlak, two‐compartment exchange, and two‐compartment uptake), differences in output parameters were observed between contributions. Conclusions: The OSIPI DCE‐DSC code repository represents a novel community‐led model for code sharing and testing. The repository facilitates the re‐use of existing code and the benchmarking of new code, promoting enhanced reproducibility in quantitative perfusion imaging. [ABSTRACT FROM AUTHOR]

Thrombotic microangiopathy (TMA) reflects a syndrome of endothelial injury characterised by microangiopathic haemolytic anaemia (nonimmune), thrombocytopenia, and often end-organ dysfunction. TMA disorders are well-recognised in kidney transplant recipients, often due to an underlying genetic predisposition related to complement dysregulation, or de novo due to infection, immunosuppression toxicity, or antibody-mediated rejection. In pregnancy, TMA disorders are most commonly due to severe pre-eclampsia or HELLP, but may also be due to thrombotic thrombocytopenic purpura (TTP) or complement-mediated (atypical) haemolytic uremic syndrome (aHUS). Complement dysregulation is being recognised as playing a role in the development of preeclampsia and HELLP syndrome in addition to aHUS. Due to overlapping clinical and laboratory features, diagnosis can be difficult and delays in treatment can be life-threatening for both mother and fetus. This report describes a 32 year-old female who had two successive wanted pregnancies. The first pregnancy was terminated at 22 weeks gestation due to presumed severe preeclampsia and fetal growth restriction in the context of known chronic kidney failure due to reflux nephropathy. A living-related kidney transplant was performed to improve the chances of pregnancy resulting in a live birth. A subsequent pregnancy was complicated by progressive kidney impairment and hypertension at 22 weeks gestation. Kidney biopsy showed TMA, but the etiology was unclear. This report highlights the diagnostic dilemma of TMA in a pregnant kidney transplant recipient and a role for the anti-C5 terminal complement blockade monoclonal antibody eculizumab, in pregnancy-associated TMA, especially at a peri-viable gestation. [ABSTRACT FROM AUTHOR]

Summary: This study investigated how changing or maintaining parent‐set bedtimes over time relates to adolescents' sleep timing, latency, and duration. Adolescents (n = 2509; Mage = 12.6 [0.5] years; 47% m) self‐reported their sleep patterns, and whether they had parent‐set bedtimes on two separate occasions in 2019 (T1; 12.6 years) and 2020 (T2; 13.7 years). We identified four groups based on parent‐set bedtimes: (1) bedtime rules at both T1 and T2 (46%, n = 1155), (2) no bedtime rules at T1 nor T2 (26%, n = 656), (3) bedtime rules at T1 but not T2 (19%, n = 472), (4) no bedtime rules at T1 but a parent‐set bedtime at T2 (9%, n = 226). As expected, the entire sample showed that bedtimes generally became later and sleep duration shorter across adolescence, but the change differed among the groups. Adolescents whose parents introduced bedtime rules at T2 reported earlier bedtimes and longer sleep duration (~20 min) compared with adolescents with no bedtime rules at T2. Importantly, they no longer differed from adolescents who consistently had bedtimes across T1 and T2. There was no significant interaction for sleep latency, which declined at a similar rate for all groups. These results are the first to suggest that maintaining or re‐introducing a parent‐set bedtime may be possible and beneficial for adolescents' sleep. [ABSTRACT FROM AUTHOR]

Objective: To investigate incorporating a ready‐to‐use 2.5:1 ratio liquid feed into a ketogenic diet (KD) in children and adults with drug‐resistant epilepsy. Methods: Following a three‐day baseline, patients (n = 19; age: 19 years [SD 13], range: 8–46 years) followed a KD for 28 days (control period), then incorporated ≥200 mL/day of a ready‐to‐use liquid feed, made with a ratio of 2.5 g of fat to 1 g of protein plus carbohydrate and including medium chain triglycerides ([MCTs]; 25.6% of total fat/100 mL) for 28 days as part of their KD (intervention period). Outcome measures (control vs intervention period) included gastrointestinal (GI) tolerance, adherence to KD and intervention feed, dietary intake, blood ß‐hydroxybutyrate (BHB) concentration, seizure outcomes, health‐related quality of life (HRQoL), acceptability and safety. Results: Compared to the control period, during the intervention period, the percentage of patients reporting no GI symptoms increased (+5% [SD 5], p = 0.02); adherence to the KD prescription was similar (p = 0.92) but higher in patients (n = 5) with poor adherence (<50%) to KD during the control period (+33% [SD 26], p = 0.049); total MCT intake increased (+12.1 g/day [SD 14.0], p = 0.002), driven by increases in octanoic (C8; +8.3 g/day [SD 6.4], p < 0.001) and decanoic acid (C10; +5.4 g/day [SD 5.4], p < 0.001); KD ratio decreased (p = 0.047), driven by a nonsignificant increase in protein intake (+11 g/day [SD 44], p = 0.29); seizure outcomes were similar (p ≥ 0.63) but improved in patients (n = 6) with the worst seizure outcomes during the control period (p = 0.04); and HRQoL outcomes were similar. The intervention feed was well adhered to (96% [SD 8]) and accepted (≥88% of patients confirmed). Significance: These findings provide an evidence‐base to support the effective management of children and adults with drug‐resistant epilepsy following a KD with the use of a ready‐to‐use, nutritionally complete, 2.5:1 ratio feed including MCTs. Plain language summary: This study examined the use of a ready‐to‐use, nutritionally complete, 2.5:1 ratio (2.5 g of fat to 1 g of protein plus carbohydrate) liquid feed, including medium chain triglycerides (MCTs), into a ketogenic diet (KD) in children and adults with drug‐resistant epilepsy. The results show that the 2.5:1 ratio feed was well tolerated, adhered to, and accepted in these patients. Increases in MCT intake (particularly C8 and C10) and improvements in seizure outcomes (reduced seizure burden and intensity) and KD adherence also occurred with the 2.5:1 ratio feed in patients with the worst seizures and adherence, respectively. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to measure the effectiveness of an on‐line, neuroscience‐based harm reduction intervention (The Illicit Project) on substance use, harms and knowledge over a 12‐month period. Design: We used a two‐arm cluster‐randomized controlled trial. Setting: The study was conducted at eight secondary schools across New South Wales, Australia. Participants: A total of 950 (mean age = 15.9; standard deviation = 0.68) in grades 10–12 at participating schools in 2020 took part. Intervention and comparator: The Illicit Project intervention group (schools = five, n = 681) received an on‐line, universal substance use and harm reduction programme over three classes. The active control group (schools = three, n = 269) received school‐based health education as usual. Measurements Self‐report questionnaires assessed primary [alcohol, nicotine, cannabis, 3,4‐methylenedioxymethamphetamine (MDMA), cocaine and prescription drug misuse] and secondary outcomes (alcohol‐related harms and drug literacy) at baseline and the 6‐ and 12‐month follow‐up assessment. Findings Approximately 63% (n = 595) of the sample completed the 12‐month follow‐up assessment, including 58% of the intervention group (n = 396/679) and 66% of the active control group (n = 179/271). Participants in the intervention group had slower annual increases in binge drinking [odds ratio (OR) = 0.33, 95% confidence interval (CI) = 0.12–0.89], nicotine use (OR = 0.80, 95% CI = 0.52–1.23), MDMA use (OR = 0.14, 95% CI = 0.02–1.00), cocaine use (OR = 0.06, 95% CI = 0.01–0.64) and prescription drug misuse (OR = 0.07, 95% CI = 0.01–0.54) compared with the active control group. There was limited evidence of an intervention effect on cannabis use and alcohol‐related harm (P > 0.5). The secondary outcomes showed that the intervention group maintained higher levels of drug literacy knowledge (β = 3.71, 95% CI = 1.86–5.56) and harm reduction help‐seeking skills (β = 1.55, 95% CI = 0.62–2.48) compared with the active control group. Conclusion: The Illicit Project (an on‐line, neuroscience‐based substance use harm reduction intervention) was effective in slowing the uptake of risky substance use and improving drug literacy skills among late secondary school students in Australia, compared with school‐based health education as usual. [ABSTRACT FROM AUTHOR]

The Lizard ophiolite, Cornwall, South-West England, is the largest and best-preserved ophiolite within the Variscan orogenic belt. It forms part of the Rheic-Rhenohercynian suture zone, and was obducted northwestward onto the passive continental margin of Avalonia (Laurussia) during the Middle Devonian. It comprises an almost complete thrust slice of oceanic crust with sheeted dykes, gabbros, Moho transition sequence, and upper-mantle peridotites, underlain by a metamorphic sole. Despite the importance of the Lizard ophiolite in understanding Variscan tectonics, the origin and age of the Lizard ophiolite are debated. We present new field observations, structural maps and cross-sections of the Lizard ophiolite from extensive re-mapping, integrated with U--Pb geochronology, petrology, thermobarometry, and whole rock geochemistry. We report new U--Pb zircon (CA-ID-TIMS and LA-ICPMS) ages of 386.80 ± 0.25/0.31/0.52 Ma (Givetian) from a plagiogranite dyke intruding the Crousa Gabbros at Porthoustock, and 395.08 ± 0.14/0.22/0.47 Ma (Emsian) from partial melts of the metamorphic sole Landewednack Amphibolites at Mullion Cove. These ages, respectively, precisely date the formation of the Lizard ophiolite oceanic crust, and the age of cooling post peakmetamorphism of the sole. Petrological modeling on the Landewednack Amphibolites suggests peak metamorphic conditions of 10 ± 2 kbar and 600 ± 75°C. We demonstrate that the Lizard ophiolite formed as a supra-subduction zone ophiolite overlying an inverted metamorphic sole, and we combine our observations and data into a new geodynamic model for the formation and obduction of the ophiolite. The current data supports an induced subduction initiation model. [ABSTRACT FROM AUTHOR]

Climate‐driven environmental change is increasingly impacting global fisheries and marine resource use. Fisheries provide a broad range of economic, social and cultural benefits while delivering essential contributions to nutrient security and human health. Despite this, little is known about how climate change will impact the availability and quality of seafood‐derived nutrients. Here, we quantified spatial and temporal changes in the nutritional quality of the commercially harvested eastern school whiting, Sillago flindersi, sampled throughout the south‐east Australian ocean warming hotspot. Several nutrients measured in S. flindersi, including protein, ash, polyunsaturated fatty acids (PUFA) and the omega‐3 PUFA–docosahexaenoic acid (DHA, 22:6ɷ3), were related to one or more environmental factors (sea bottom temperature, depth and chlorophyll). We also detected seasonal variability in DHA and ash composition throughout the species' commercially harvested distribution. Historical and future spatial modelling predicted a decrease in DHA of up to 6% with increasing ocean temperature under future Representative Concentration Pathway (RCP) 4.5 and 8.5 emission scenarios. Overall, our results identified S. flindersi as a rich source of protein and essential PUFAs for human consumers and supported emerging evidence that reductions in seafood‐derived essential nutrients may occur under future ocean warming, specifically reductions in omega‐3 fatty acids. The development of nutritional quality forecasting tools for seafood holds the potential to inform fishers and managers of locations and times of the year to target species with optimal nutritional quality. [ABSTRACT FROM AUTHOR]

Background and aims: Early alcohol use may predict later alcohol problems, but the magnitude of this effect and impact of delayed onset remain uncertain. This study measured age‐based differences in progression from first full alcoholic drink to hazardous drinking in one of the largest and most recent prospective cohorts of Australian adolescents. Design, settings, participants and measurement: A 7‐year (2012–19) prospective longitudinal cohort of 2082 Australian adolescents was established from the Climate and Preventure (cohort 1) and Climate Schools Combined (cohort 2) studies. Participants completed surveys annually from ages 13 to 20 years. Interval censored survival analyses were conducted with first episode of hazardous drinking [three or more on proxy Alcohol Use Disorders Identification Test (AUDIT‐C)] as the survival end‐point, controlling for age, sex and mental health symptomatology. Onset of hazardous drinking was expressed as hazard ratios (HRs), and median survival time (years) was used to model first onset of hazardous alcohol use in survival curves. Findings: Compared with those aged 15 or older, those who had their first full drink at 12 or younger had significantly elevated risk of hazardous drinking onset during the study period [log (HR): 9.3; 95% confidence interval (CI) = 7.0–12.0, P < 0.001]. Compared with those who had their first full drink at ages 13–14, those who delayed until 15 or older had significantly later onset of hazardous drinking; 1.63 years for males (95% CI = 1.31–1.92, P < 0.001) and 1.50 for females (95% CI = 1.15–1.81, P < 0.001), resulting in a median age of onset of hazardous drinking of > 19 for both sexes (male: 19.05 years, 95% CI = 18.74–19.38; female: 19.47 years, 95% CI = 19.19–19.75). First drink at ages 13–14 was associated with the earliest onset of hazardous drinking (males: 17.43 years; females: 17.98 years). Conclusions: In Australia, alcohol initiation prior to age 15 appears to be associated with an earlier onset of hazardous drinking than initiation after age 15. [ABSTRACT FROM AUTHOR]

The hippocampal subfield prosubiculum (ProS), is a conserved neuroanatomic region in mouse, monkey, and human. This area lies between CA1 and subiculum (Sub) and particularly lacks consensus on its boundaries; reports have varied on the description of its features and location. In this report, we review, refine, and evaluate four cytoarchitectural features that differentiate ProS from its neighboring subfields: (1) small neurons, (2) lightly stained neurons, (3) superficial clustered neurons, and (4) a cell sparse zone. ProS was delineated in all cases (n = 10). ProS was examined for its cytoarchitectonic features and location rostrocaudally, from the anterior head through the body in the hippocampus. The most common feature was small pyramidal neurons, which were intermingled with larger pyramidal neurons in ProS. We quantitatively measured ProS pyramidal neurons, which showed (average, width at pyramidal base = 14.31 µm, n = 400 per subfield). CA1 neurons averaged 15.57 µm and Sub neurons averaged 15.63 µm, both were significantly different than ProS (Kruskal–Wallis test, p <.0001). The other three features observed were lightly stained neurons, clustered neurons, and a cell sparse zone. Taken together, these findings suggest that ProS is an independent subfield, likely with distinct functional contributions to the broader interconnected hippocampal network. Our results suggest that ProS is a cytoarchitecturally varied subfield, both for features and among individuals. This diverse architecture in features and individuals for ProS could explain the long‐standing complexity regarding the identification of this subfield. [ABSTRACT FROM AUTHOR]

Although alcohol use disorder (AUD) is associated with a high disease burden due to medical consequences, people with AUD often do not receive appropriate treatment or community health service support. Peer‐support services, intended to bridge the gap between patients with AUD and mental health providers have produced successful results. However, the number of studies on peer supporters in South Korea, especially those with AUD, is limited. Therefore, research on the effectiveness or challenges faced by AUD peer supporters in Korea is required to meet the challenges posed by increases in the numbers and capabilities of peer supporters in the mental health field. This qualitative study (N = 13), included focus group interviews of AUD peer supporters (n = 7), and supervisors of peer supporters (n = 6). Focus group data were analysed using thematic analysis methods. These analyses identified themes including 'Life before AUD peer supporters: The moment of change', 'Effects of peer support services: Working as peer supporters changed our lives', 'Challenges of peer supporter services: Things experienced as a team' and 'Future directions: How we can improve peer support services'? Findings indicate that healthcare professionals, educated to maintain clear boundaries, are discouraged from disclosing personal information or developing personal relationships with patients. On the other hand, peer supporters discuss personal histories and prioritize personal connections. By acting as comrades, peer supporters have positive effects. By sharing their experiences, peer supporters formed appropriate relationships with AUD patients and families resulting in more active engagement in treatment programmes and increased numbers of patients receiving outpatient treatment. [ABSTRACT FROM AUTHOR]

Summary: An 11‐month‐old Arabian filly was presented for chronic diarrhoea, ill‐thrift and intermittent colic. Abdominal ultrasonography revealed multifocal regions of marked colonic wall thickening. Exploratory laparotomy confirmed multifocal, multi‐sized nodular and segmental intramural mass‐like lesions affecting the right ventral and transverse colon, respectively. Locally extensive regions of mural thickening in the aborad transverse colon resulted in severe luminal restriction (<2.5 cm) and subsequent obstruction of the orad transverse and right dorsal colons with impacted feed material. The lesions were unresectable and full‐thickness biopsy samples were submitted for histopathological evaluation. The filly was subsequently diagnosed with transmural intestinal ganglioneuromatosis of the right ventral and transverse colons. The filly was successfully conservatively managed over a 24‐month follow‐up duration. Management consisted of long‐term dietary modifications in the form of a low‐bulk diet, as well as enteral laxatives and a tapering course of corticosteroids postoperatively. This is the first case of intestinal ganglioneuromatosis in veterinary literature that was (1) diagnosed in a juvenile horse, (2) successfully medically managed and (3) followed up for more than 12 months. [ABSTRACT FROM AUTHOR]

Investigating interindividual variability is a major field of interest in neuroscience. The entorhinal cortex (EC) is essential for memory and affected early in the progression of Alzheimer's disease (AD). We combined histology ground‐truth data with ultrahigh‐resolution 7T ex vivo MRI to analyze EC interindividual variability in 3D. Further, we characterized (1) entorhinal shape as a whole, (2) entorhinal subfield range and midpoints, and (3) subfield architectural location and tau burden derived from 3D probability maps. Our results indicated that EC shape varied but was not related to demographic or disease factors at this preclinical stage. The medial intermediate subfield showed the highest degree of location variability in the probability maps. However, individual subfields did not display the same level of variability across dimensions and outcome measure, each providing a different perspective. For example, the olfactory subfield showed low variability in midpoint location in the superior–inferior dimension but high variability in anterior–posterior, and the subfield entorhinal intermediate showed a large variability in volumetric measures but a low variability in location derived from the 3D probability maps. These findings suggest that interindividual variability within the entorhinal subfields requires a 3D approach incorporating multiple outcome measures. This study provides 3D probability maps of the individual entorhinal subfields and respective tau pathology in the preclinical stage (Braak I and II) of AD. These probability maps illustrate the subfield average and may serve as a checkpoint for future modeling. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) can undergo either a latent or a lytic infection in cells of the myeloid lineage. Whilst the molecular mechanisms which determine the outcome of infection are far from clear, it is well established that a key factor is the differential regulation of the major immediate early promoter (MIEP) responsible for driving lytic immediate early gene expression. Using a myelomonocytic cell line stably transduced with a GFP reporter under the control of the MIEP, which recapitulates MIEP regulation in the context of virus infection, we have used an unbiased CRISPR‐Cas9 sub‐genomic, epigenetic library screen to identify novel cellular factors involved in MIEP repression during establishment and maintenance of latency in myeloid cells. One such cellular factor identified was MORC3. Consistent with MORC3 being a robust repressor of the MIEP, we show that THP1 cells devoid of MORC3 fail to establish latency. We also show that MORC3 is induced during latent infection, recruited to the MIEP and forms MORC3 nuclear bodies (MORC3‐NBs) which, interestingly, co‐localize with viral genomes. Finally, we show that the latency‐associated functions of MORC3 are regulated by the deSUMOylase activity of the viral latency‐associated LUNA protein likely to prevent untimely HCMV reactivation. [ABSTRACT FROM AUTHOR]

Using cross‐cultural dialogue pieces from this issue, Nyoni outlines factors to consider when trying to balance voices between south and north. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has potentially altered the system of population movement around the world. As COVID‐19 hit cities the hardest in the wake of the pandemic, apocalyptic headlines anticipated the 'death of cities'. Yet, little was known about the impact of the COVID‐19 pandemic on cities and the ways it has shaped the patterns of internal population movement in and out of cities. This virtual special issue aims to consolidate our knowledge of the impacts of the COVID‐19 pandemic on internal migration, discuss key lessons we have learnt so far, and identify areas for future enquiry. It brings together evidence from six different countries: Australia, Germany, Japan, Spain, Sweden and the United Kingdom, covering the pandemic in varying temporal lengths. Systematic patterns emerge. A first commonality is an overall reduction of internal migration rates during the early days of the pandemic but to a lesser degree than expected. Second, the impacts of COVID‐19 leading to out‐migration from cities seem to have been temporary, though evidence from Spain and Britain points to scarring effects with persistent losses in highly dense areas. Third, changes in internal migration generated small impacts on the population structure of cities but large‐scale changes in small, rural and low‐density areas. [ABSTRACT FROM AUTHOR]

Sea urchins can cause extensive damage to kelp forests, and their overgrazing can create extensive barren areas, leading to a loss of biodiversity. Barrens may persist when the recruitment of kelp, which occurs through the microscopic haploid gametophyte stage, is suppressed. However, the ecology of kelp gametophytes is poorly understood, and here we investigate if grazing by juvenile urchins on kelp gametophytes can suppress kelp recruitment and if this is exacerbated by climate change. We compared grazing of Ecklonia radiata gametophytes by two species of juvenile urchins, the tropical Tripneustes gratilla and the temperate Centrostephanus rodgersii, at winter (19°C), summer (23°C), and ocean warming (26°C) temperatures for the low‐latitude range edge of E. radiata, which is vulnerable to ocean warming. We examined the rate of recovery of gametophytes following grazing and determined whether they survived and formed sporophytes after ingestion by sea urchins. Both T. gratilla and C. rodgersii grazed E. radiata gametophytes, reducing their abundance compared to no grazing controls. Surprisingly, temperature did not influence grazing rates, but gametophytes did not recover from grazing in the ocean warming (26°C) treatment. Gametophytes survived ingestion by both species of sea urchin and formed sporophytes after ingestion by T. gratilla, but not C. rodgersii. These results suggest complex grazer–gametophyte interactions, in which both negative (reduced abundance and poor recovery with warming) and positive (facilitated recruitment) effects are possible. Small grazers may play a more important role in kelp ecosystem function than previously thought and should be considered in our understanding of alternate stable states. [ABSTRACT FROM AUTHOR]

The 11 lytic transglycosylases of Pseudomonas aeruginosa have overlapping activities in the turnover of the cell‐wall peptidoglycan. Rare lipoprotein A (RlpA) is distinct among the 11 by its use of only peptidoglycan lacking peptide stems. The spatial localization of RlpA and its interactome within P. aeruginosa are unknown. We employed suppression of introduced amber codons at sites in the rlpA gene for the introduction of the unnatural‐amino‐acids Νζ‐[(2‐azidoethoxy)carbonyl]‐l‐lysine (compound 1) and Nζ‐[[[3‐(3‐methyl‐3H‐diazirin‐3‐yl)propyl]amino]carbonyl]‐l‐lysine (compound 2). In live P. aeruginosa, full‐length RlpA incorporating compound 1 into its sequence was fluorescently tagged using strained‐promoted alkyne‐azide cycloaddition and examined by fluorescence microscopy. RlpA is present at low levels along the sidewall length of the bacterium, and at higher levels at the nascent septa of replicating bacteria. In intact P. aeruginosa, UV photolysis of full‐length RlpA having compound 2 within its sequence generated a transient reactive carbene, which engaged in photoaffinity capture of neighboring proteins. Thirteen proteins were identified. Three of these proteins—PBP1a, PBP5, and MreB—are members of the bacterial divisome. The use of the complementary methodologies of non‐canonical amino‐acid incorporation, photoaffinity proximity analysis, and fluorescent microscopy confirm a dominant septal location for the RlpA enzyme of P. aeruginosa, as a divisome‐associated activity. This accomplishment adds to the emerging recognition of the value of these methodologies for identification of the intracellular localization of bacterial proteins. [ABSTRACT FROM AUTHOR]

Purpose: To obtain better microstructural integrity, interstitial fluid, and microvascular images from multi‐b‐value diffusion MRI data by using a physics‐informed neural network (PINN) fitting approach. Methods: Test–retest whole‐brain inversion recovery diffusion‐weighted images with multiple b‐values (IVIM: intravoxel incoherent motion) were acquired on separate days for 16 patients with cerebrovascular disease on a 3.0T MRI system. The performance of the PINN three‐component IVIM (3C‐IVIM) model fitting approach was compared with conventional fitting approaches (i.e., non‐negative least squares and two‐step least squares) in terms of (1) parameter map quality, (2) test–retest repeatability, and (3) voxel‐wise accuracy. Using the in vivo data, the parameter map quality was assessed by the parameter contrast‐to‐noise ratio (PCNR) between normal‐appearing white matter and white matter hyperintensities, and test–retest repeatability was expressed by the coefficient of variation (CV) and intraclass correlation coefficient (ICC). The voxel‐wise accuracy of the 3C‐IVIM parameters was determined by 10,000 computer simulations mimicking our in vivo data. Differences in PCNR and CV values obtained with the PINN approach versus conventional fitting approaches were assessed using paired Wilcoxon signed‐rank tests. Results: The PINN‐derived 3C‐IVIM parameter maps were of higher quality and more repeatable than those of conventional fitting approaches, while also achieving higher voxel‐wise accuracy. Conclusion: Physics‐informed neural networks enable robust voxel‐wise estimation of three diffusion components from the diffusion‐weighted signal. The repeatable and high‐quality biological parameter maps generated with PINNs allow for visual evaluation of pathophysiological processes in cerebrovascular disease. [ABSTRACT FROM AUTHOR]

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Climate change is driving the poleward redistribution of coral species, but the rate and magnitude of future range extensions within temperate regions are rarely quantified. A better understanding of the likely future distribution of corals is needed to anticipate the resulting social, economic and environmental implications. Here, we project the rate and magnitude of extensions of suitable thermal conditions for hard coral communities along the east Australian coastline, using data on coral community presence, in conjunction with historical and projected ocean temperatures. Our projections indicate that temperatures will be suitable for coral communities dominated by the subtropical coral Pocillopora aliciae, currently found off Sydney, to extend their range poleward by 80 (RCP 2.6) to 450 km (RCP 8.5) by 2100, corresponding to a rate of 0.9–5.0 km year−1. Similarly, thermal conditions will be such that diverse coral communities, such as those currently occurring in the Solitary Islands, may extend their range by 130 (RCP 2.6) to 580 km (RCP 8.5) by 2100, at a rate of 1.4–6.4 km year−1. These projections are similar to those forecast for coral species in other parts of the world. Newly establishing coral communities in temperate regions may provide a range of novel local economic opportunities, particularly for marine tourism. [ABSTRACT FROM AUTHOR]

Intravoxel incoherent motion (IVIM) imaging and diffusion tensor imaging (DTI) facilitate noninvasive quantification of tissue perfusion and diffusion. Both are promising biomarkers in various diseases and a combined acquisition is therefore desirable. This comes with challenges, including noisy parameter maps and long scan times, especially for the perfusion fraction f and pseudo‐diffusion coefficient D*. A model‐based reconstruction has the potential to overcome these challenges. As a first step, our goal was to develop a model‐based reconstruction framework for IVIM and combined IVIM‐DTI parameter estimation. The IVIM and IVIM‐DTI models were implemented in the PyQMRI model‐based reconstruction framework and validated with simulations and in vivo data. Commonly used voxel‐wise nonlinear least‐squares fitting was used as the reference. Simulations with the IVIM and IVIM‐DTI models were performed with 100 noise realizations to assess accuracy and precision. Diffusion‐weighted data were acquired for IVIM reconstruction in the liver (n = 5), as well as for IVIM‐DTI in the kidneys (n = 5) and lower‐leg muscles (n = 6) of healthy volunteers. The median and interquartile range (IQR) values of the IVIM and IVIM‐DTI parameters were compared to assess bias and precision. With model‐based reconstruction, the parameter maps exhibited less noise, which was most pronounced in the f and D* maps, both in the simulations and in vivo. The bias values in the simulations were comparable between model‐based reconstruction and the reference method. The IQR was lower with model‐based reconstruction compared with the reference for all parameters. In conclusion, model‐based reconstruction is feasible for IVIM and IVIM‐DTI and improves the precision of the parameter estimates, particularly for f and D* maps. [ABSTRACT FROM AUTHOR]

The development of subunit vaccine platforms has been of considerable interest due to their good safety profile and ability to be adapted to new antigens, compared to other vaccine typess. Nevertheless, subunit vaccines often lack sufficient immunogenicity to fully protect against infectious diseases. A wide variety of subunit vaccines have been developed to enhance antigen immunogenicity by increasing antigen multivalency, as well as stability and delivery properties, via presentation of antigens on protein nanoparticles. Increasing multivalency can be an effective approach to provide a potent humoral immune response by more strongly engaging and clustering B cell receptors (BCRs) to induce activation, as well as increased uptake by antigen presenting cells and their subsequent T cell activation. Proper orientation of antigen on protein nanoparticles is also considered a crucial factor for enhanced BCR engagement and subsequent immune responses. Therefore, various strategies have been reported to decorate highly repetitive surfaces of protein nanoparticle scaffolds with multiple copies of antigens, arrange antigens in proper orientation, or combinations thereof. In this review, we describe different chemical bioconjugation methods, approaches for genetic fusion of recombinant antigens, biological affinity tags, and enzymatic conjugation methods to effectively present antigens on the surface of protein nanoparticle vaccine scaffolds. [ABSTRACT FROM AUTHOR]

Coade stone has played a significant role in architectural and ornamental design since its inception in the early 18th century. It is well known that earlier, experimental, architectural stoneware products existed, but few of these have been studied in detail scientifically, and only one major analytical study of Coade stone has appeared in the literature. This paper presents a new spectroscopic analysis of Coade stone along with that of a newly discovered sample from Oxnead Hall in Norfolk where it known that Sir Clement Paston experimented with artificial stone in the late 16th century. The results demonstrate that it is possible to differentiate between the two variants on the basis of both the raw materials used and the different phases formed in their production processes. [ABSTRACT FROM AUTHOR]

Background: Encephaloceles are neural tube defects characterized by herniation of meninges, neural tissue and cerebrospinal fluid, while atretic cephaloceles denote a rudimentary connection to the intracranial space with absence of herniated neural tissue and represent an infrequent dermatopathologic diagnosis. Limited reports of these entities confound the challenge in their histopathologic distinction. Accurate classification is important given associated anomalies and neurologic manifestations that impact prognosis. Methods: We describe the clinicopathological and immunohistochemical [glial fibrillary acidic protein (GFAP), S100, epithelial membrane antigen (EMA), and somatostatin receptor subtype 2A (SSTR2A)] features in a retrospective series encountered at a single institution between 1994 and 2020. Results: We identified 13 cases classified as atretic cephalocele (n = 11) and encephalocele (n = 2). Hamartomatous changes and multinucleated cells were unique to atretic cephaloceles while myxoid areas were unique to encephaloceles. At least focal staining for SSTRA was seen in all atretic cephaloceles with the majority (87.5%) staining for EMA; negative staining for GFAP and S100 confirmed absence of neural tissue. Encephaloceles were GFAP and S100 positive, and negative for SSTR2 and EMA. Atretic cephaloceles had a favorable prognosis compared to encephaloceles, with severe morbidity present in both encephalocele cases. Conclusion: Our study raises awareness of atretic cephalocele and encephalocele among dermatopathologists and reveals a mutually exclusive immunophenotype that facilitates their distinction for prognostication and management. [ABSTRACT FROM AUTHOR]