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Groundwater is the most ubiquitous source of liquid freshwater globally, yet its role in supporting diverse ecosystems is rarely acknowledged1,2. However, the location and extent of groundwater-dependent ecosystems (GDEs) are unknown in many geographies, and protection measures are lacking1,3. Here, we map GDEs at high-resolution (roughly 30 m) and find them present on more than one-third of global drylands analysed, including important global biodiversity hotspots4. GDEs are more extensive and contiguous in landscapes dominated by pastoralism with lower rates of groundwater depletion, suggesting that many GDEs are likely to have already been lost due to water and land use practices. Nevertheless, 53% of GDEs exist within regions showing declining groundwater trends, which highlights the urgent need to protect GDEs from the threat of groundwater depletion. However, we found that only 21% of GDEs exist on protected lands or in jurisdictions with sustainable groundwater management policies, invoking a call to action to protect these vital ecosystems. Furthermore, we examine the linkage of GDEs with cultural and socio-economic factors in the Greater Sahel region, where GDEs play an essential role in supporting biodiversity and rural livelihoods, to explore other means for protection of GDEs in politically unstable regions. Our GDE map provides critical information for prioritizing and developing policies and protection mechanisms across various local, regional or international scales to safeguard these important ecosystems and the societies dependent on them.

BACKGROUND: Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis. METHODS: Using a data-driven approach, a PRS for ALC was generated using a meta-genome-wide association study of ALC (N=4305) and an independent cohort of heavy drinkers with ALC and without significant liver disease (N=3037). It was validated in 2 additional independent cohorts from the UK Biobank with diagnosed ALC (N=467) and high-risk drinking controls (N=8981) and participants in the Indiana Biobank Liver cohort with alcohol-associated liver disease (N=121) and controls without liver disease (N=3239). RESULTS: A 20-single-nucleotide polymorphisms PRS for ALC (PRSALC) was generated that stratified risk for ALC comparing the top and bottom deciles of PRS in the 2 validation cohorts (ORs: 2.83 [95% CI: 1.82 -4.39] in UK Biobank; 4.40 [1.56 -12.44] in Indiana Biobank Liver cohort). Furthermore, PRSALC improved the prediction of ALC risk when added to the models of clinically known predictors of ALC risk. It also stratified the risk for metabolic dysfunction -associated steatotic liver disease -cirrhosis (3.94 [2.23 -6.95]) in the Indiana Biobank Liver cohort -based exploratory analysis. CONCLUSIONS: PRSALC incorporates 20 single-nucleotide polymorphisms, predicts increased risk for ALC, and improves risk stratification for ALC compared with the models that only include clinical risk factors. This new score has the potential for early detection of heavy drinking patients who are at high risk for ALC.

Debate remains around the anatomical origins of specific brain cell subtypes and lineage relationships within the human forebrain1-7. Thus, direct observation in the mature human brain is critical for a complete understanding of its structural organization and cellular origins. Here we utilize brain mosaic variation within specific cell types as distinct indicators for clonal dynamics, denoted as cell-type-specific mosaic variant barcode analysis. From four hemispheres and two different human neurotypical donors, we identified 287 and 780 mosaic variants, respectively, that were used to deconvolve clonal dynamics. Clonal spread and allele fractions within the brain reveal that local hippocampal excitatory neurons are more lineage-restricted than resident neocortical excitatory neurons or resident basal ganglia GABAergic inhibitory neurons. Furthermore, simultaneous genome transcriptome analysis at both a cell-type-specific and a single-cell level suggests a dorsal neocortical origin for a subgroup of DLX1+ inhibitory neurons that disperse radially from an origin shared with excitatory neurons. Finally, the distribution of mosaic variants across 17 locations within one parietal lobe reveals that restriction of clonal spread in the anterior-posterior axis precedes restriction in the dorsal-ventral axis for both excitatory and inhibitory neurons. Thus, cell-type-resolved somatic mosaicism can uncover lineage relationships governing the development of the human forebrain.

Structured liquids stabilized by interfacial assemblies enable spatial control over chemical systems. To prescribe a lifetime for structured liquids requires that the interfacially trapped material eventually reverts to molecularly dissolved species. Here, we show that poly(acrylic acid) fueled with carbodiimide segregates to an oil-water interface and forms assemblies of aggregates, solidifying the interface. When the fuel is consumed, the assembly dissipates into soluble polymer chains, destroying any out-of-equilibrium structure imparted to the liquid. We exploit this phenomenon to control liquid compartment temporal stability. Using interfacial rheology, we identify crossover points in the interfacial storage and loss moduli at times commensurate with the fuel concentration, evidencing transitions from solid-like to liquid-like assemblies that cause compartmentalized liquids to burst. These solid-like assemblies demonstrate reduced permeability to dye, showing the potential of this system for timed partitioning or release of chemical species. This work opens a pathway to time- and shape-programmable chemical systems.

BACKGROUND: A rapid and affordable point-of-care test is a priority for Neisseria gonorrhoeae control. WHO and Foundation for Innovative New Diagnostics (FIND) have a target product profile for a non-molecular N gonorrhoeae rapid point-of-care test that requires a clinical sensitivity of greater than 80% and a specificity over 95% to be considered useful in syndromic management; test turnaround time should be 30 min or under, and the test should cost less than US$3. A novel lateral flow assay (LFA) was developed to achieve that profile. METHODS: In this cross-sectional study we evaluated the performance of the novel N gonorrhoeae lateral flow assay (NG-LFA) at the primary health-care level in South Africa. Male patients with urethral discharge syndrome and female patients with vaginal discharge syndrome were recruited from five primary health-care facilities in the Buffalo City Metropolitan Municipality health district of South Africa. First-void urine specimens and nurse-collected vaginal swabs were tested in-facility with the NG-LFA and Xpert CT/NG PCR assay. N gonorrhoeae multi-antigen sequence typing (NG-MAST) was performed on all LFA positive specimens. FINDINGS: Between March 7, and Sept 19, 2022, we enrolled 200 male patients with urethral discharge and 200 female patients with vaginal discharge. The median age of male patients was 24 years (IQR 21-31 years), and the median age of female patients was 25 years (IQR 21-32 years). In addition, 23 male patients and 12 female patients who presented at the facility with a partner notification slip were enrolled of whom one (4%) and five (42%) were symptomatic, respectively. NG-LFA and Xpert results were available for all participants. In urine specimens, NG-LFA sensitivity was 96·1% (Wilson 95% CI 91·2-98·3; 123 LFA-positive among 128 PCR-positive specimens) and 91·7% in vaginal swab specimens (78·2-97·1; 33 LFA-positive among 36 PCR-positive). The specificity was 97·2% in urine specimens (90·4-99·2; 70 LFA-negative among 72 PCR-negative) and 96·3% in vaginal specimens (92·2-98·3; 158 LFA-negative among 164 PCR-negative). In 156 LFA-positive specimens, NG-MAST showed 93 different sequence types. INTERPRETATION: The novel NG-LFA had excellent clinical sensitivity and specificity in symptomatic male and female patients. The test met the optimal requirement for sensitivity and the minimal requirement for specificity specified in the target product profile. NG-LFA could provide an important tool to optimise clinical management and reduce excess antibiotic use in settings without direct access to laboratory testing. FUNDING: Global Antimicrobial Resistance Innovation Fund (GAMRIF) via FIND and National Institutes of Health.

The muscle isoform of clathrin heavy chain, CHC22, has 85% sequence identity to the ubiquitously expressed CHC17, yet its expression pattern and function appear to be distinct from those of well-characterized clathrin-coated vesicles. In mature muscle CHC22 is preferentially concentrated at neuromuscular and myotendinous junctions, suggesting a role at sarcolemmal contacts with extracellular matrix. During myoblast differentiation, CHC22 expression is increased, initially localized with desmin and nestin and then preferentially segregated to the poles of fused myoblasts. CHC22 expression is also increased in regenerating muscle fibers with the same time course as embryonic myosin, indicating a role in muscle repair. CHC22 binds to sorting nexin 5 through a coiled-coil domain present in both partners, which is absent in CHC17 and coincides with the region on CHC17 that binds the regulatory light-chain subunit. These differential binding data suggest a mechanism for the distinct functions of CHC22 relative to CHC17 in membrane traffic during muscle development, repair, and at neuromuscular and myotendinous junctions.

This paper explores how students participating in a co-curricular scholarship programme in a large Australian university develop their employability. It seeks to add to recent literature regarding different approaches to graduate employability through examining how participating students' capital acquisition is shaped by and internalised within the structure and culture of the scholarship. The paper also offers an example of how comprehensive and integrated co-curricular scholarship programmes can facilitate graduate employability. It suggests that despite curricular intentions to promote comprehensive and processual approaches to employability, students' employability internalisations are influenced by possessive and positional messages and cultural cues within the scholarship programme. These insights serve as important considerations for higher education institutions seeking to instigate or improve their employability curricula.

Increasingly, there are expectations internationally that schools will use research to inform their improvement initiatives. Within this context, this paper brings together findings from two large-scale Australian studies - the Monash Q Project and the University of Newcastle's Quality Teaching Rounds Project - to explore educators' patterns of engagement with research. The combination of these studies provides data from a larger and more diverse sample (n = 774) than other recent Australian studies, and integrates insights from direct and indirect approaches to investigating educators' research engagement. The analysis highlights several common themes associated with educators' research use including: the perceived credibility of different sources; the relevance and usability of research; and affordances of access to research and time to use it well in practice. Newer and more nuanced insights include: the interrelationships between collaborative and directed research use; the need for research to be convenient in terms of access and usability; the role of trusted colleagues in helping to bridge gaps between research and practice; and educators' distrust of research itself. The paper argues that these insights provide important cues as to how systems and school leaders can help educators to increase and improve their use of research in practice.

Professional learning (PL) in education is thought to be a key mechanism for improving classroom instruction and student achievement. Yet despite decades of research into PL, the impact of this investment is not well understood, with reports of limited change in both research and practice. As part of a large-scale investigation focusing on practitioner use of evidence in education, the authors undertook a rapid review to understand what is known about effective PL for K-12 school-based educators. Based on analysis and synthesis of 12 included studies, the review identified eight features of effective PL: collaboration; active learning and reflection; content and pedagogy in context; sustained duration; coaching; external expertise; models and modelling; and, audience and alignment. It also highlighted additional considerations for effective PL, including workplace conditions, PL providers, and online and blended approaches. This paper argues that though there is a consensus around effective PL features, there is a need to go beyond 'effective approaches' and consider the broader conditions and methodological limitations that impact improved and sustained change. Overall, this paper has implications for understanding the research landscape around effective PL, and applying an evidence-informed approach to designing PL programmes.

The planned integration of Catholic social teaching (CST) across the curriculum was the primary focus of the 'Identity and Curriculum in Catholic Education' (2013-2018) initiative in Catholic schools in the state of Queensland. Initial reconnaissance involved a survey of teachers' views regarding the identity, purposes and characteristics of Catholic schools. This was followed by action research with some thirty teachers in seven schools where various CST principles were integrated in particular Units across a range of learning areas. Strong evidence emerged for the effectiveness and feasibility of such integration. Participating teachers identified positive student interest and outcomes, while acknowledging the 'good fit' between certain aspects of the Australian Curriculum and CST principles such as common good, human dignity, and stewardship of creation. At a time when neo-liberalism and market values are dominant, the potential of such counter-cultural opportunities must be considered by Catholic schools internationally.

Assessment is often described as the tail that wags the curriculum dog. Curriculum has featured more prominently than assessment in Irish scholarship. Drawing on relevant policy documents and interviews with senior National Council for Curriculum and Assessment (NCCA) and State Examinations Commission (SEC) officers, and relevant documentation, the author attempts to redress this imbalance. The Irish curriculum/ assessment relationship was characterised by strict Department of Education control for some sixty years. The education partners became involved during the 1980s, culminating in the establishment of the statutory NCCA in 2002. Meanwhile, the Department of Education's Examinations Branch was replaced by the statutory SEC. Issues arising from these developments and from the changing external environment are considered, including: increased NCCA/SEC collaboration; the evolution of curriculum culture including the shift from subject syllabuses (focused on subject content), to curriculum specifications (focusing on learning outcomes); assessment criteria; content and performance standards; marking schemes and assessment grids; pre-ordained grade boundaries and the use of attainment referencing to maintain standards from year to year. The discussion considers the pros and cons of learning outcomes, the impact of high-stakes examinations on student learning, and the role of the teacher as professional in the assessment of students for national certification.

Somatic mosaicism is defined as an occurrence of two or more populations of cells having genomic sequences differing at given loci in an individual who is derived from a single zygote. It is a characteristic of multicellular organisms that plays a crucial role in normal development and disease. To study the nature and extent of somatic mosaicism in autism spectrum disorder, bipolar disorder, focal cortical dysplasia, schizophrenia, and Tourette syndrome, a multi-institutional consortium called the Brain Somatic Mosaicism Network (BSMN) was formed through the National Institute of Mental Health (NIMH). In addition to genomic data of affected and neurotypical brains, the BSMN also developed and validated a best practices somatic single nucleotide variant calling workflow through the analysis of reference brain tissue. These resources, which include >400 terabytes of data from 1087 subjects, are now available to the research community via the NIMH Data Archive (NDA) and are described here.

Abstract: Understanding cascading processes on complex network topologies is paramount for modelling how diseases, information, fake news and other media spread. In this article, we extend the multi-type branching process method developed in Keating et al., (2022), which relies on networks having homogenous node properties, to a more general class of clustered networks. Using a model of socially inspired complex contagion we obtain results, not just for the average behaviour of the cascades but for full distributions of the cascade properties. We introduce a new method for the inversion of probability generating functions to recover their underlying probability distributions; this derivation naturally extends to higher dimensions. This inversion technique is used along with the multi-type branching process to obtain univariate and bivariate distributions of cascade properties. Finally, using clique-cover methods, we apply the methodology to synthetic and real-world networks and compare the theoretical distribution of cascade sizes with the results of extensive numerical simulations.

Brain somatic mosaicism is linked to several neurological disorders, thought to arise post-zygotically. The recent study by Miller et al. suggests prezygotic aneuploidy followed by postzygotic partial reversion leads to a recurrent form of brain mosaicism-related epilepsy.

Abstract: LNPK encodes a conserved membrane protein that stabilizes the junctions of the tubular endoplasmic reticulum network playing crucial roles in diverse biological functions. Recently, homozygous variants in LNPK were shown to cause a neurodevelopmental disorder (OMIM#618090) in four patients displaying developmental delay, epilepsy, and non-specific brain malformations including corpus callosum hypoplasia and variable impairment of cerebellum. We sought to delineate the molecular and phenotypic spectrum of LNPK-related disorder. Exome or genome sequencing was carried out in eleven families. Thorough clinical and neuroradiological evaluation was performed for all the affected individuals, including review of previously reported patients. We identified twelve distinct homozygous loss-of-function variants in sixteen individuals presenting with moderate to profound developmental delay, cognitive impairment, regression, refractory epilepsy and a recognizable neuroimaging pattern consisting of corpus callosum hypoplasia and signal alterations of the forceps minor (“ear-of-the-lynx” sign), variably associated with substantia nigra signal alterations, mild brain atrophy, short midbrain, and cerebellar hypoplasia/atrophy. In summary, we define the core phenotype of LNPK-related disorder and expand the list of neurological disorders presenting with the “ear of the lynx” sign suggesting a possible common underlying mechanism related to endoplasmic reticulum-phagy dysfunction.

BRAT1 biallelic variants are associated with rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL), and neurodevelopmental disorder associating cerebellar atrophy with or without seizures syndrome (NEDCAS). To date, forty individuals have been reported in the literature. We collected clinical and molecular data from 57 additional cases allowing us to study a large cohort of 97 individuals and draw phenotype-genotype correlations. Fifty-nine individuals presented with BRAT1-related RMFSL phenotype. Most of them had no psychomotor acquisition (100%), epilepsy (100%), microcephaly (91%), limb rigidity (93%), and died prematurely (93%). Thirty-eight individuals presented a non-lethal phenotype of BRAT1-related NEDCAS phenotype. Seventy-six percent of the patients in this group were able to walk and 68% were able to say at least a few words. Most of them had cerebellar ataxia (82%), axial hypotonia (79%) and cerebellar atrophy (100%). Genotype-phenotype correlations in our cohort revealed that biallelic nonsense, frameshift or inframe deletion/insertion variants result in the severe BRAT1-related RMFSL phenotype (46/46; 100%). In contrast, genotypes with at least one missense were more likely associated with NEDCAS (28/34; 82%). The phenotype of patients carrying splice variants was variable: 41% presented with RMFSL (7/17) and 59% with NEDCAS (10/17).