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Autism Spectrum Disorder (ASD) is a heterogeneous disorder that is often accompanied with many co-morbidities. Recent genetic studies have identified various pathways from hundreds of candidate risk genes with varying levels of association to ASD. However, it is unknown which pathways are specific to the core symptoms or which are shared by the co-morbidities. We hypothesised that critical ASD candidates should appear widely across different scoring systems, and that comorbidity pathways should be constituted by genes expressed in the relevant tissues. We analysed the Simons Foundation for Autism Research Initiative (SFARI) database and four independently published scoring systems and identified 292 overlapping genes. We examined their mRNA expression using the Genotype-Tissue Expression (GTEx) database and validated protein expression levels using the human protein atlas (HPA) dataset. This led to clustering of the overlapping ASD genes into 2 groups; one with 91 genes primarily expressed in the central nervous system (CNS geneset) and another with 201 genes expressed in both CNS and peripheral tissues (CNS+PT geneset). Bioinformatic analyses showed a high enrichment of CNS development and synaptic transmission in the CNS geneset, and an enrichment of synapse, chromatin remodelling, gene regulation and endocrine signalling in the CNS+PT geneset. Calcium signalling and the glutamatergic synapse were found to be highly interconnected among pathways in the combined geneset. Our analyses demonstrate that 2/3 of ASD genes are expressed beyond the brain, which may impact peripheral function and involve in ASD co-morbidities, and relevant pathways may be explored for the treatment of ASD co-morbidities.

Concern has been expressed globally over rising caesarean birth rates. Recently, the International Federation of Gynaecology and Obstetrics (FIGO) called for help from governmental bodies, professional organisations, women's groups, and other stakeholders to reduce unnecessary caesareans. As part of a wider research initiative, we conducted an overview of systematic reviews of antenatal and intrapartum interventions, and reports of evidence based recommendations, to identify and highlight those that have been shown to be effective for reducing caesarean birth, promoting vaginal birth and reducing fear of childbirth. Following registration of the review protocol, (PROSPERO 2018 CRD42018090681), we searched The Cochrane Database of Systematic Reviews, PubMed, CINAHL and EMBASE (Jan 2000-Jan 2018) and searched for grey literature in PROSPERO, and on websites of health professional and other relevant bodies. Screening and selection of reviews, quality appraisal using AMSTAR-2, and data extraction were performed independently by pairs of at least two reviewers. Excluding reviews assessed as 'critically low' on AMSTAR-2 (n = 54), 101 systematic reviews, and 10 reports of evidence based recommendations were included in the overview. Narrative synthesis was performed, due to heterogeneity of review methodology and topics. The results highlight twenty-five interventions, across 17 reviews, that reduced the risk of caesarean, nine interventions across eight reviews that increased the risk of caesarean, eight interventions that reduced instrumental vaginal birth, four interventions that increased spontaneous vaginal birth, and two interventions that reduced fear of childbirth. This overview of reviews identifies and highlights interventions that have been shown to be effective for reducing caesarean birth, promoting vaginal births and reducing fear of childbirth. In recognising that clinical practices change over time, this overview includes reviews published from 2000 onwards only, thus providing contemporary evidence, and a valuable resource for clinicians when making decisions on practices that should be implemented for reducing unnecessary caesarean births safely. Protocol Registration: PROSPERO 2018 CRD42018090681. Available from: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018090681.

As the water-energy-food (WEF) nexus becomes an increasingly common framework for bridging science and policy, there is a growing need to unpack and make explicit many of the methods and assumptions being used to operationalize the nexus. In this paper, we focus on two common approaches to nexus research, quantitative modeling and futures thinking, and the ways that each set of methodological tools address uncertainty. We first review the underlying assumptions of each approach with a focus on sources of and ability to measure uncertainty, and potential complementarities. Quantitative modeling takes a probabilistic approach to predicting the likelihood of a specific outcome or future state based on estimates of current system dynamics. In contrast, futures thinking approaches, such as scenario processes, explore novel changes that cannot be fully predicted or even anticipated based on current understandings of the nexus. We then examine a set of applied nexus projects that bridge science and policy-making contexts to better understand practitioner experiences with different methodological tools and how they are utilized to navigate uncertainty. We explore one nexus case study, LIVES Cambodia, in-depth, to better understand the opportunities and challenges associated with participatory modelling and stakeholder engagement with uncertainty in a policy-making context. Across the cases, practitioners identify the complementarity between modeling and futures thinking approaches, and those projects that integrated both into the planning process experienced benefits from having multiple angles on uncertainty within the nexus. In particular, stakeholder engagement provided critical opportunities to address some types of uncertainties (e.g. data gaps) through the use of local knowledge. Explicit discussions of model uncertainty and use of scenario processes also enabled stakeholders to deepen their understandings of uncertainties and envision policy pathways that would be robust to uncertainty. In many senses, models became boundary objects that encouraged critical thinking and questioning of assumptions across diverse stakeholders. And, for some nexus projects, confronting uncertainty in explicit and transparent ways build capacity for policy flexibility and adaptiveness. We conclude with a discussion of when and how these benefits can be fully realized through the strategic use of appropriate approaches to characterizing and navigating nexus uncertainty.

Background Controversy exists regarding ankyloglossia (tongue-tie) and its clinical impact on breastfeeding, including the benefits, or otherwise, of tongue-tie release (frenotomy). As exclusive breastfeeding rates in Ireland are already considerably low (46% on discharge home from the maternity unit following birth in 2014), it is imperative to protect and support breastfeeding, including identifying the associated effects that frenotomy might have on breastfeeding variables. Objective To determine the associated effects of frenotomy on breastfeeding variables in infants with ankyloglossia. Methods A prospective before and after cohort study was conducted. Following ethical approval, two self-reported questionnaires were administered to women whose infants were undergoing frenotomy at seven healthcare clinics in the Republic of Ireland. Data on breastfeeding variables prior to the frenotomy procedure and at 1-month post-frenotomy were collected and compared. Descriptive statistics (frequencies and proportions) were used to analyse, separately, the pre- and post-frenotomy data. Inferential statistics (z-test scores for differences between proportions (alpha <0.05) and mean differences (MD) with 95% confidence intervals (CI)) were used for pre- and post-frenotomy comparative analyses. Results Ninety-eight women returned the baseline questionnaire, and, of these, 89 returned the follow-up questionnaire. The most common reason for seeking a frenotomy was difficulty with latch (38%). Private lactation consultants were the main person recommending a frenotomy (31%). Rates of exclusive breastfeeding remained similar pre- and post-frenotomy (58% versus 58%), although rates of formula feeding increased two-fold at follow-up. Infants’ ability to extend their tongues to the lower lip after frenotomy was significantly increased ( p  < 0.0001) . Almost all participants (91%) reported an overall improvement in breastfeeding post-frenotomy. Pain on breastfeeding was significantly reduced post-frenotomy (MD 2.90, 95% CI 3.75 to 2.05) and overall LATCH scale scores were significantly increased (MD -0.50, 95% CI -0.67 to −0.33). Conclusions This study supports the hypothesis that frenotomy has a positive effect on breastfeeding variables in infants with ankyloglossia. These findings, however, are based on a relatively small number of participants from one country only where breastfeeding rates are low. Further, larger studies are required to substantiate these findings.

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. 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. 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. 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.

Background: This review aimed to find relevant published studies on the co-morbidity of autism and Asperger’s syndrome with psychotic, anxiety and/or mood disorders, assess them, synthesize the findings, present an overview and make recommendations for future research. Methods: Systematic literature searches were performed using several databases. Selected articles had to describe an original study that provided prevalence and/or incidence estimates on autism and/or Asperger’s syndrome co-morbidity with psychotic, anxiety and/or mood disorders. Results and Conclusion: There is conflicting evidence regarding the frequency of schizophrenia in this population. Depression appears to be common, although most individuals with autism do not have sufficient language skills to verbalize changes in mood. Anxiety disorders represent the most common psychiatric co-morbidity in this population.

Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder associated with a characteristic behavioral phenotype that includes severe hyperphagia and a variety of other behavioral challenges such as temper outbursts and anxiety. These behaviors have a significant and dramatic impact on the daily functioning and quality of life for the person with PWS and their families. To date, effective therapies addressing these behavioral challenges have proven elusive, but several potential treatments are on the horizon. However, a limiting factor for treatment studies in PWS is the lack of consensus in the field regarding how to best define and measure the complex and interrelated behavioral features of this syndrome. The International PWS Clinical Trials Consortium (PWS-CTC, www.pwsctc.org ) includes expert PWS scientists, clinicians, and patient advocacy organization representatives focused on facilitating clinical trials in this rare disease. To address the above gap in the field, members of the PWS-CTC “Behavior Outcomes Working Group” sought to develop a unified understanding of the key behavioral features in PWS and build a consensus regarding their definition and description. The primary focus of this paper is to present consensus definitions and descriptions of key phenotypic PWS behaviors including hyperphagia, temper outbursts, anxiety, obsessive–compulsive behaviors, rigidity, and social cognition deficits. Patient vignettes are provided to illustrate the interrelatedness and impact of these behaviors. We also review some available assessment tools as well as new instruments in development which may be useful in measuring these behavioral features in PWS.

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.

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.

Abnormalities in frontostriatal circuitry potentially underlie the two core deficits in Autism Spectrum Disorder (ASD); social interaction and communication difficulties and restricted interests and repetitive behaviors. Whilst a few studies have examined connectivity within this circuitry in ASD, no previous study has examined both functional and structural connectivity within the same population. The present study provides the first exploration of both functional and structural frontostriatal connectivity in ASD. Twenty-eight right-handed Caucasian male ASD (17.28 ± 3.57 years) and 27 right-handed male, age and IQ matched controls (17.15 ± 3.64 years) took part in the study. Resting state functional connectivity was carried out on 21 ASD and control participants, and tractography was carried out on 22 ASD and 24 control participants, after excluding subjects for excessive motion and poor data quality. Functional connectivity analysis was carried out between the frontal cortex and striatum after which tractography was performed between regions that showed significant group differences in functional connectivity. The ASD group showed increased functional connectivity between regions in the frontal cortex [anterior cingulate cortex (ACC), middle frontal gyrus (MFG), paracingulate gyrus (Pcg) and orbitofrontal cortex (OFC)], and striatum [nucleus accumbens (NAcc) and caudate]. Increased functional connectivity between ACC and caudate was associated with deactivation to social rewards in the caudate, as previously reported in the same participants. Greater connectivity between the right MFG and caudate was associated with higher restricted interests and repetitive behaviors and connectivity between the bilateral Pcg and NAcc, and the right OFC and NAcc, was negatively associated with social and communicative deficits. Although tracts were reliably constructed for each subject, there were no group differences in structural connectivity. Results are in keeping with previously reported increased corticostriatal functional connectivity in ASD.