Australian, Irish, and Swedish women's comfort levels when breastfeeding in public.

BACKGROUND: Despite a flux of global initiatives to increase and sustain breastfeeding rates, challenges persist. The decision to commence and sustain breastfeeding is influenced by multiple, complex factors. Feelings of social embarrassment, shame, fear of judgement, and lack of confidence when breastfeeding in public, compound women's decisions to breastfeed and may result in formula feeding or early cessation of breastfeeding. A greater understanding of where and how women feel most comfortable when breastfeeding in public can assist in designing interventions to support the initiation and continuation of breastfeeding. METHODS: A cross-sectional survey was conducted with women living in Australia (n = 10,910), Sweden (n = 1,520), and Ireland (n = 1,835), who were currently breastfeeding or who had breastfed within the previous two years. Our aim was to explore where, and how often women breastfeed in public and to compare their levels of comfort when breastfeeding in public. Data were collected in 2018 using an anonymous online survey over a four-week period in Ireland, Australia, and Sweden, and were analyzed using SPSS Version 25. RESULTS: Most respondents were highly educated, with over 70% in each country reporting having a university or college degree. Observing women breastfeeding in public was more commonly reported to be a weekly or daily occurrence in Sweden (24.5%) and Australia (28%), than in Ireland (13.3%). Women in the participating countries reported breastfeeding in public most commonly whenever their babies needed feeding. Very few women never or rarely breastfed publicly. Coffee shops/cafes, restaurants, and parks were the most popular locations. In all three countries, partners were reported to be very supportive of breastfeeding in public, which enhanced breastfeeding women's comfort levels. When asked to score out of a maximum comfort level of 10, women reported higher mean levels of comfort when breastfeeding in front of strangers (Ireland M = 7.33, Australia M = 6.58, Sweden M = 6.75) than with those known to them, particularly in front of their father-in-law (Ireland M = 5.44, Australia M = 5.76, Sweden M = 6.66 out of 10), who scored lowest in terms of women's comfort levels. CONCLUSION: This study offers important insights into the experiences and comfort levels of women breastfeeding in public. Limitations include the anonymous nature of the surveys, thus preventing follow-up, and variances in terminology used to describe locations across the three settings. Recommendations are made for research to determine the relationships between the frequency of breastfeeding in public and breastfeeding women's perceived comfort levels, the influence of family members' perceptions of breastfeeding in public and women's experiences, and the experience of women who feel uncomfortable while breastfeeding in public, with a view to developing support measures.

Bridge-building between communities: Imagining the future of biomedical autism research.

A paradigm shift in research culture is required to ease perceived tensions between autistic people and the biomedical research community. As a group of autistic and non-autistic scientists and stakeholders, we contend that through participatory research, we can reject a deficit-based conceptualization of autism while building a shared vision for a neurodiversity-affirmative biomedical research paradigm.

Women's perceptions of factors needed to encourage a culture of public breastfeeding: a cross-sectional study in Sweden, Ireland and Australia.

BACKGROUND: Breastfeeding in the public sphere is known to be experienced as a problem for many women. It has been shown to arouse negative feelings among the public, depending on the attitude of those in the immediate surroundings. This contributes to the fact that many women hesitate to breastfeed in public and prepare themselves for potential adverse comments. METHODS: An online survey was used for an international cross-sectional study including women living in Sweden (n = 1252), Australia (n = 7602) and Ireland (n = 1597). Women who had breastfed within the previous two years were invited to participate through Facebook. One key open-ended question was presented, inviting women to respond to: "What do you think is important or needed to encourage a breastfeeding culture where breastfeeding in public is seen as normal?" During 2018, data were collected during a four-week period. A thematic analysis of women's responses was conducted separately in each country and then comparison and negotiation occurred once similarities between themes and subthemes were confirmed. Frequencies of subthemes were then determined and compared between the three countries. RESULTS: Seven subthemes developed from the data; 'Make breastfeeding visible in society'; 'Healthcare professionals support and knowledge regarding breastfeeding'; 'Education of the public'; 'Inviting environment'; 'Zero tolerance to other's unwanted opinions'; 'Focusing on the needs and rights of the breastfeeding dyad'; and 'Desexualize breastfeeding and women's' bodies in society'. Subthemes were integrated under two themes; 'Active supportive interventions needed for breastfeeding' and 'The obvious right of breastfeeding women and children to take a seat in the public sphere'. CONCLUSION: The common experience that exists today regarding public breastfeeding requires change towards normalization. Further collaborative research is recommended to meet the expressed requirements from women who wish to breastfeed in public.

Bridging the translational gap: what can synaptopathies tell us about autism?

Multiple molecular pathways and cellular processes have been implicated in the neurobiology of autism and other neurodevelopmental conditions. There is a current focus on synaptic gene conditions, or synaptopathies, which refer to clinical conditions associated with rare genetic variants disrupting genes involved in synaptic biology. Synaptopathies are commonly associated with autism and developmental delay and may be associated with a range of other neuropsychiatric outcomes. Altered synaptic biology is suggested by both preclinical and clinical studies in autism based on evidence of differences in early brain structural development and altered glutamatergic and GABAergic neurotransmission potentially perturbing excitatory and inhibitory balance. This review focusses on the NRXN-NLGN-SHANK pathway, which is implicated in the synaptic assembly, trans-synaptic signalling, and synaptic functioning. We provide an overview of the insights from preclinical molecular studies of the pathway. Concentrating on NRXN1 deletion and SHANK3 mutations, we discuss emerging understanding of cellular processes and electrophysiology from induced pluripotent stem cells (iPSC) models derived from individuals with synaptopathies, neuroimaging and behavioural findings in animal models of Nrxn1 and Shank3 synaptic gene conditions, and key findings regarding autism features, brain and behavioural phenotypes from human clinical studies of synaptopathies. The identification of molecular-based biomarkers from preclinical models aims to advance the development of targeted therapeutic treatments. However, it remains challenging to translate preclinical animal models and iPSC studies to interpret human brain development and autism features. We discuss the existing challenges in preclinical and clinical synaptopathy research, and potential solutions to align methodologies across preclinical and clinical research. Bridging the translational gap between preclinical and clinical studies will be necessary to understand biological mechanisms, to identify targeted therapies, and ultimately to progress towards personalised approaches for complex neurodevelopmental conditions such as autism.

A review of the cognitive impact of neurodevelopmental and neuropsychiatric associated copy number variants.

The heritability of intelligence or general cognitive ability is estimated at 41% and 66% in children and adults respectively. Many rare copy number variants are associated with neurodevelopmental and neuropsychiatric conditions (ND-CNV), including schizophrenia and autism spectrum disorders, and may contribute to the observed variability in cognitive ability. Here, we reviewed studies of intelligence quotient or cognitive function in ND-CNV carriers, from both general population and clinical cohorts, to understand the cognitive impact of ND-CNV in both contexts and identify potential genotype-specific cognitive phenotypes. We reviewed aggregate studies of sets ND-CNV broadly linked to neurodevelopmental and neuropsychiatric conditions, and genotype-first studies of a subset of 12 ND-CNV robustly associated with schizophrenia and autism. Cognitive impacts were observed across ND-CNV in both general population and clinical cohorts, with reports of phenotypic heterogeneity. Evidence for ND-CNV-specific impacts were limited by a small number of studies and samples sizes. A comprehensive understanding of the cognitive impact of ND-CNVs would be clinically informative and could identify potential educational needs for ND-CNV carriers. This could improve genetic counselling for families impacted by ND-CNV, and clinical outcomes for those with complex needs.

CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions.

BACKGROUND: Heterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services. METHODS: Using a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N = 1275 individuals with ASD/NDD (age = 11.0 ± 3.6 years; n females = 277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups. RESULTS: Clustering revealed four subgroups. One subgroup-broad symptom worsening only (20%)-included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup. LIMITATIONS: Notable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic. CONCLUSIONS: Concomitantly assessing variation in changes of symptoms and service access during the first phase of the pandemic revealed differential outcome profiles in ASD/NDD youth. Subgroups were characterized by distinct prediction patterns across a set of pre- and pandemic-related experiences/contexts. Results may inform recovery efforts and preparedness in future crises; they also underscore the critical value of international data-sharing and collaborations to address the needs of those most vulnerable in times of crisis.

Sex and gender in neurodevelopmental conditions.

Health-related conditions often differ qualitatively or quantitatively between individuals of different birth-assigned sexes and gender identities, and/or with different gendered experiences, requiring tailored care. Studying the moderating and mediating effects of sex-related and gender-related factors on impairment, disability, wellbeing and health is of paramount importance especially for neurodivergent individuals, who are diagnosed with neurodevelopmental conditions with uneven sex/gender distributions. Researchers have become aware of the myriad influences that sex-related and gender-related variables have on the manifestations of neurodevelopmental conditions, and contemporary work has begun to investigate the mechanisms through which these effects are mediated. Here we describe topical concepts of sex and gender science, summarize current knowledge, and discuss research and clinical challenges related to autism, attention-deficit/hyperactivity disorder and other neurodevelopmental conditions. We consider sex and gender in the context of epidemiology, behavioural phenotypes, neurobiology, genetics, endocrinology and neighbouring disciplines. The available evidence supports the view that sex and gender are important contributors to the biological and behavioural variability in neurodevelopmental conditions. Methodological caveats such as frequent conflation of sex and gender constructs, inappropriate measurement of these constructs and under-representation of specific demographic groups (for example, female and gender minority individuals and people with intellectual disabilities) limit the translational potential of research so far. Future research and clinical implementation should integrate sex and gender into next-generation diagnostics, mechanistic investigations and support practices.

Pregnancy, birth and neonatal outcomes associated with reduced fetal movements: A systematic review and meta-analysis of non-randomised studies.

PROBLEM: Maternal perception of reduced fetal movements (RFM) is identified as an important alarm signal for possible risk of impending adverse perinatal outcomes. BACKGROUND: Perinatal outcomes associated with RFM are increasingly being investigated in non-randomised studies with several associated outcomes, including stillbirth, preterm birth, fetal growth restriction and neonatal death being reported. Findings from studies, however, are conflicting. AIM: To synthesise the findings of published studies regarding pregnancy, birth and neonatal outcomes in women who presented with RFM. METHODS: PubMed, EMBASE, CINAHL complete, Maternity and Infant Care, PsycINFO, and Science Citation Index databases were searched up to 8th July 2021 and updated again on 8th September 2022. Non-randomised studies involving pregnant women ≥24 weeks' gestation, who presented with a primary complaint of RFM compared to women who did not present with RFM were included. Data were meta-analysed using a random-effects model and presented as Odds Ratios (OR) or Standard Mean Differences (SMD) with 95% Confidence Intervals (CI). FINDINGS: Thirty-nine studies were included. Women with RFM had increased odds of stillbirth (OR 3.44, 95% CI 2.02-5.88) and small for gestational age (OR 1.37, 95% CI 1.16-1.61) when compared with women who did not have RFM. Associations were also found for induction of labor, instrumental birth and caesarean section but not for preterm birth (OR 0.92, 95% CI 0.71-1.19) or neonatal death (OR 0.99; 95% CI 0.52-1.90). CONCLUSION: This review revealed that RFM is associated with increased odds of stillbirth, small for gestational age, induction of labor, instrumental birth and caesarean section but not preterm birth or neonatal death.

Brief Report: Evaluating the Diagnostic Yield of Commercial Gene Panels in Autism.

Autism is a prevalent neurodevelopmental condition, highly heterogenous in both genotype and phenotype. This communication adds to existing discussion of the heterogeneity of clinical sequencing tests, "gene panels", marketed for application in autism. We evaluate the clinical utility of available gene panels based on existing genetic evidence. We determine that diagnostic yields of these gene panels range from 0.22% to 10.02% and gene selection for the panels is variable in relevance, here measured as percentage overlap with SFARI Gene and ranging from 15.15% to 100%. We conclude that gene panels marketed for use in autism are currently of limited clinical utility, and that sequencing with greater coverage may be more appropriate.

What would reduce caesarean section rates?-Views from pregnant women and clinicians in Ireland.

BACKGROUND: Caesarean section rates continue to rise in most parts of the world. While CS is a lifesaving procedure there is evidence that, beyond a certain threshold, CS rates may contribute to increased maternal and perinatal morbidity. This study aimed to elicit the views of pregnant women's and clinicians' on how CS rates might be reduced. METHODS: Pregnant women and their partners, and clinicians working with pregnant women in a maternity hospital in the Republic of Ireland of Ireland, were invited to participate in focus groups. Eligibility criteria included all women attending antenatal classes and clinicians working with pregnant women. A convenience sample was used and interviews were audio recorded, transcribed, and analysed using thematic analysis. RESULTS: Four focus group interviews were conducted with 30 clinicians and 15 pregnant women and two partners participated in three focus groups. A further two women were interviewed individually. Participants expressed a view that rising CS rates were impacted by a societal perception that CS had become a 'normal mode of birth'. Suggestions for reducing CS rates were offered by clinicians and pregnant women and their partners. CONCLUSIONS: Clinicians and pregnant women consider that CS rates can be reduced if a shared philosophy supporting normal birth is prioritised alongside adequate resourcing. Women and their partners also believe that enhanced communication with clinicians is central to reducing CS rates.

The Synaptic Gene Study: Design and Methodology to Identify Neurocognitive Markers in Phelan-McDermid Syndrome and NRXN1 Deletions.

Synaptic gene conditions, i.e., "synaptopathies," involve disruption to genes expressed at the synapse and account for between 0.5 and 2% of autism cases. They provide a unique entry point to understanding the molecular and biological mechanisms underpinning autism-related phenotypes. Phelan-McDermid Syndrome (PMS, also known as 22q13 deletion syndrome) and NRXN1 deletions (NRXN1ds) are two synaptopathies associated with autism and related neurodevelopmental disorders (NDDs). PMS often incorporates disruption to the SHANK3 gene, implicated in excitatory postsynaptic scaffolding, whereas the NRXN1 gene encodes neurexin-1, a presynaptic cell adhesion protein; both are implicated in trans-synaptic signaling in the brain. Around 70% of individuals with PMS and 43-70% of those with NRXN1ds receive a diagnosis of autism, suggesting that alterations in synaptic development may play a crucial role in explaining the aetiology of autism. However, a substantial amount of heterogeneity exists between conditions. Most individuals with PMS have moderate to profound intellectual disability (ID), while those with NRXN1ds have no ID to severe ID. Speech abnormalities are common to both, although appear more severe in PMS. Very little is currently known about the neurocognitive underpinnings of phenotypic presentations in PMS and NRXN1ds. The Synaptic Gene (SynaG) study adopts a gene-first approach and comprehensively assesses these two syndromic forms of autism. The study compliments preclinical efforts within AIMS-2-TRIALS focused on SHANK3 and NRXN1. The aims of the study are to (1) establish the frequency of autism diagnosis and features in individuals with PMS and NRXN1ds, (2) to compare the clinical profile of PMS, NRXN1ds, and individuals with 'idiopathic' autism (iASD), (3) to identify mechanistic biomarkers that may account for autistic features and/or heterogeneity in clinical profiles, and (4) investigate the impact of second or multiple genetic hits on heterogeneity in clinical profiles. In the current paper we describe our methodology for phenotyping the sample and our planned comparisons, with information on the necessary adaptations made during the global COVID-19 pandemic. We also describe the demographics of the data collected thus far, including 25 PMS, 36 NRXN1ds, 33 iASD, and 52 NTD participants, and present an interim analysis of autistic features and adaptive functioning.

Maternal Immune Activation and Interleukin 17A in the Pathogenesis of Autistic Spectrum Disorder and Why It Matters in the COVID-19 Era.

Autism spectrum disorder (ASD) is the commonest neurodevelopmental disability. It is a highly complex disorder with an increasing prevalence and an unclear etiology. Consensus indicates that ASD arises as a genetically modulated, and environmentally influenced condition. Although pathogenic rare genetic variants are detected in around 20% of cases of ASD, no single factor is responsible for the vast majority of ASD cases or that explains their characteristic clinical heterogeneity. However, a growing body of evidence suggests that ASD susceptibility involves an interplay between genetic factors and environmental exposures. One such environmental exposure which has received significant attention in this regard is maternal immune activation (MIA) resulting from bacterial or viral infection during pregnancy. Reproducible rodent models of ASD are well-established whereby induction of MIA in pregnant dams, leads to offspring displaying neuroanatomical, functional, and behavioral changes analogous to those seen in ASD. Blockade of specific inflammatory cytokines such as interleukin-17A during gestation remediates many of these observed behavioral effects, suggesting a causative or contributory role. Here, we review the growing body of animal and human-based evidence indicating that interleukin-17A may mediate the observed effects of MIA on neurodevelopmental outcomes in the offspring. This is particularly important given the current corona virus disease-2019 (COVID-19) pandemic as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy is a potent stimulator of the maternal immune response, however the long-term effects of maternal SARS-CoV-2 infection on neurodevelopmental outcomes is unclear. This underscores the importance of monitoring neurodevelopmental outcomes in children exposed to SARS-CoV-2-induced MIA during gestation.

Midwives' views of an evidence-based intervention to reduce caesarean section rates in Ireland.

PROBLEM: A worldwide increase of caesarean section (CS) rates has been estimated at a rate of 4% per year and numerous interventions to reduce the rates have not been successful, perhaps because they are not acceptable to clinicians. BACKGROUND: A caesarean section (CS) can be a life-saving operation, but has been associated with short- and long-term risk factors and shown to affect subsequent pregnancies. AIM: To explore midwives' views on CS rates and evaluate the feasibility and acceptability of an evidence-based intervention programme (REDUCE) designed to decrease overall CS rates in Ireland by 7%. METHODS: Following ethical approval, a qualitative exploratory design was used to seek midwives' views of the evidence-based intervention. A total of 28 midwives from one large tertiary maternity hospital took part in four focus group interviews. Data were analysed using thematic analysis. FINDINGS: Five themes emerged, illustrating the midwives' views of what could be improved in the present system and how CS rates could be reduced in future. The themes included: (i) Induction of labour; (ii) Education; (iii) Auditing of practice; (iv) Clinical practice; (v) Midwife-Obstetrician collaboration. DISCUSSION: This study noted a rising CS rate year on year, with a rate of 37% at the time of the study, and the midwives voiced their very real concerns over the increased high rates. CONCLUSION: The study provided support for the evidence based 'REDUCE' intervention, which now needs to be tested empirically within this Irish population.

Subtly altered topological asymmetry of brain structural covariance networks in autism spectrum disorder across 43 datasets from the ENIGMA consortium.

Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously been characterized. Inter-regional morphological covariance analysis can capture network connectivity between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1455 individuals with ASD and 1560 controls, across 43 independent datasets of the ENIGMA consortium's ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered average asymmetry of networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, involving higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve executive functions, language-related and sensorimotor processes. These findings provide a network-level characterization of altered left-right brain asymmetry in ASD, based on a large combined sample. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.

Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder: The ENIGMA adventure.

Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA-ADHD and ENIGMA-ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA-ADHD and -ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case-control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case-control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow-up analyses continue that include more imaging modalities (diffusion MRI and resting-state functional MRI), collaborations with other large databases, and samples with dual diagnoses.

How does genetic variation modify ND-CNV phenotypes?

Rare copy-number variants (CNVs) associated with neurodevelopmental disorders (NDDs), i.e., ND-CNVs, provide an insight into the neurobiology of NDDs and, potentially, a link between biology and clinical outcomes. However, ND-CNVs are characterised by incomplete penetrance resulting in heterogeneous carrier phenotypes, ranging from non-affected to multimorbid psychiatric, neurological, and physical phenotypes. Recent evidence indicates that other variants in the genome, or 'other hits', may partially explain the variable expressivity of ND-CNVs. These may be other rare variants or the aggregated effects of common variants that modify NDD risk. Here we discuss the recent findings, current questions, and future challenges relating to other hits research in the context of ND-CNVs and their potential for improved clinical diagnostics and therapeutics for ND-CNV carriers.

NRXN1α+/- is associated with increased excitability in ASD iPSC-derived neurons.

BACKGROUND: NRXN1 deletions are identified as one of major rare risk factors for autism spectrum disorder (ASD) and other neurodevelopmental disorders. ASD has 30% co-morbidity with epilepsy, and the latter is associated with excessive neuronal firing. NRXN1 encodes hundreds of presynaptic neuro-adhesion proteins categorized as NRXN1α/ß/γ. Previous studies on cultured cells show that the short NRXN1ß primarily exerts excitation effect, whereas the long NRXN1α which is more commonly deleted in patients involves in both excitation and inhibition. However, patient-derived models are essential for understanding functional consequences of NRXN1α deletions in human neurons. We recently derived induced pluripotent stem cells (iPSCs) from five controls and three ASD patients carrying NRXN1α+/- and showed increased calcium transients in patient neurons. METHODS: In this study we investigated the electrophysiological properties of iPSC-derived cortical neurons in control and ASD patients carrying NRXN1α+/- using patch clamping. Whole genome RNA sequencing was carried out to further understand the potential underlying molecular mechanism. RESULTS: NRXN1α+/- cortical neurons were shown to display larger sodium currents, higher AP amplitude and accelerated depolarization time. RNASeq analyses revealed transcriptomic changes with significant upregulation glutamatergic synapse and ion channels/transporter activity including voltage-gated potassium channels (GRIN1, GRIN3B, SLC17A6, CACNG3, CACNA1A, SHANK1), which are likely to couple with the increased excitability in NRXN1α+/- cortical neurons. CONCLUSIONS: Together with recent evidence of increased calcium transients, our results showed that human NRXN1α+/- isoform deletions altered neuronal excitability and non-synaptic function, and NRXN1α+/- patient iPSCs may be used as an ASD model for therapeutic development with calcium transients and excitability as readouts.

Scientists' warning on extreme wildfire risks to water supply.

2020 is the year of wildfire records. California experienced its three largest fires early in its fire season. The Pantanal, the largest wetland on the planet, burned over 20% of its surface. More than 18 million hectares of forest and bushland burned during the 2019-2020 fire season in Australia, killing 33 people, destroying nearly 2500 homes, and endangering many endemic species. The direct cost of damages is being counted in dozens of billion dollars, but the indirect costs on water-related ecosystem services and benefits could be equally expensive, with impacts lasting for decades. In Australia, the extreme precipitation ("200 mm day -1 in several location") that interrupted the catastrophic wildfire season triggered a series of watershed effects from headwaters to areas downstream. The increased runoff and erosion from burned areas disrupted water supplies in several locations. These post-fire watershed hazards via source water contamination, flash floods, and mudslides can represent substantial, systemic long-term risks to drinking water production, aquatic life, and socio-economic activity. Scenarios similar to the recent event in Australia are now predicted to unfold in the Western USA. This is a new reality that societies will have to live with as uncharted fire activity, water crises, and widespread human footprint collide all-around of the world. Therefore, we advocate for a more proactive approach to wildfire-watershed risk governance in an effort to advance and protect water security. We also argue that there is no easy solution to reducing this risk and that investments in both green (i.e., natural) and grey (i.e., built) infrastructure will be necessary. Further, we propose strategies to combine modern data analytics with existing tools for use by water and land managers worldwide to leverage several decades worth of data and knowledge on post-fire hydrology.