Neurocognitive profiles of 22q11.2 and 16p11.2 deletions and duplications.

Rare recurrent copy number variants (CNVs) at chromosomal loci 22q11.2 and 16p11.2 are genetic disorders with lifespan risk for neuropsychiatric disorders. Microdeletions and duplications are associated with neurocognitive deficits, yet few studies compared these groups using the same measures to address confounding measurement differences. We report a prospective international collaboration applying the same computerized neurocognitive assessment, the Penn Computerized Neurocognitive Battery (CNB), administered in a multi-site study on rare genomic disorders: 22q11.2 deletions (n = 492); 22q11.2 duplications (n = 106); 16p11.2 deletion (n = 117); and 16p11.2 duplications (n = 46). Domains examined include executive functions, episodic memory, complex cognition, social cognition, and psychomotor speed. Accuracy and speed for each domain were included as dependent measures in a mixed-model repeated measures analysis. Locus (22q11.2, 16p11.2) and Copy number (deletion/duplication) were grouping factors and Measure (accuracy, speed) and neurocognitive domain were repeated measures factors, with Sex and Site as covariates. We also examined correlation with IQ. We found a significant Locus × Copy number × Domain × Measure interaction (p = 0.0004). 22q11.2 deletions were associated with greater performance accuracy deficits than 22q11.2 duplications, while 16p11.2 duplications were associated with greater specific deficits than 16p11.2 deletions. Duplications at both loci were associated with reduced speed compared to deletions. Performance profiles differed among the groups with particularly poor memory performance of the 22q11.2 deletion group while the 16p11.2 duplication group had greatest deficits in complex cognition. Average accuracy on the CNB was moderately correlated with Full Scale IQ. Deletions and duplications of 22q11.2 and 16p11.2 have differential effects on accuracy and speed of neurocognition indicating locus specificity of performance profiles. These profile differences can help inform mechanistic substrates to heterogeneity in presentation and outcome, and can only be established in large-scale international consortia using the same neurocognitive assessment. Future studies could aim to link performance profiles to clinical features and brain function.

In vivo evidence of microstructural hypo-connectivity of brain white matter in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome, or 22q11.2DS, is a genetic syndrome associated with high rates of schizophrenia and autism spectrum disorders, in addition to widespread structural and functional abnormalities throughout the brain. Experimental animal models have identified neuronal connectivity deficits, e.g., decreased axonal length and complexity of axonal branching, as a primary mechanism underlying atypical brain development in 22q11.2DS. However, it is still unclear whether deficits in axonal morphology can also be observed in people with 22q11.2DS. Here, we provide an unparalleled in vivo characterization of white matter microstructure in participants with 22q11.2DS (12-15 years) and those undergoing typical development (8-18 years) using a customized magnetic resonance imaging scanner which is sensitive to axonal morphology. A rich array of diffusion MRI metrics are extracted to present microstructural profiles of typical and atypical white matter development, and provide new evidence of connectivity differences in individuals with 22q11.2DS. A recent, large-scale consortium study of 22q11.2DS identified higher diffusion anisotropy and reduced overall diffusion mobility of water as hallmark microstructural alterations of white matter in individuals across a wide age range (6-52 years). We observed similar findings across the white matter tracts included in this study, in addition to identifying deficits in axonal morphology. This, in combination with reduced tract volume measurements, supports the hypothesis that abnormal microstructural connectivity in 22q11.2DS may be mediated by densely packed axons with disproportionately small diameters. Our findings provide insight into the in vivo white matter phenotype of 22q11.2DS, and promote the continued investigation of shared features in neurodevelopmental and psychiatric disorders.

Borrelia bavariensis in Questing Ixodes ricinus Ticks, United Kingdom.

We detected Borrelia bavariensis in Ixodes ricinus ticks collected near 2 towns in the United Kingdom. Human B. bavariensis infections have not been reported previously in the country, underscoring the value of tick surveillance to warn of emerging human disease. B. bavariensis should be considered in patients with suspected neuroborreliosis.

Differential reward in "male" versus "female" pollen of functionally dioecious Solanum.

PREMISE: Five to six percent of angiosperm species exhibit a dioecious sexual system, with unisexual "male" or "female" flowers borne on separate plants. The consequent need for inter-individual pollen exchange is a special challenge for taxa where pollen is the sole pollinator reward. Dioecious Australian Solanum assure visits from pollen-foraging bees via production of inaperturate pollen in functionally female (morphologically bisexual) flowers. Biochemical composition of pollen from Australian Solanum has not been assessed nor compared to porate pollen from staminate flowers to reveal whether these flowers differ in their pollinator reward potential. METHODS: Porate pollen from male flowers and inaperturate pollen from functionally female flowers of two functionally dioecious Australian species were compared for protein and amino acid content. We also assessed pollen from bisexual and staminate flowers of a closely related andromonoecious species, in which all pollen is porate, as a comparison across co-occurring sexual systems. RESULTS: In both functionally dioecious species, porate pollen grains from staminate flowers had significantly higher levels of proteins and amino acids than inaperturate pollen grains from functionally female flowers. Levels of proteins and amino acids were highest in bisexual and staminate flowers of the andromonoecious species. CONCLUSIONS: Higher levels of proteins and amino acids in porate pollen of "male" flowers in our functionally dioecious Solanum species suggests a greater nutritive reward for bees foraging on "male" plants than for those foraging on functionally "female" plants. Greater reward in porate pollen (including andromonoecious species) may be connected to the potential to generate a pollen tube.

The Potential for Cloth Masks to Protect Health Care Clinicians From SARS-CoV-2: A Rapid Review.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has led at times to a scarcity of personal protective equipment, including medical masks, for health care clinicians, especially in primary care settings. The objective of this review was to summarize current evidence regarding the use of cloth masks to prevent respiratory viral infections, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), among health care clinicians. METHODS: We searched 5 databases, the Centers for Disease Control and Prevention website, and the reference lists of identified articles on April 3, 2020. All identified publications were independently screened by 2 reviewers. Two authors independently extracted data and graded the studies. Randomized control trials (RCTs) were graded using the Consolidated Standards of Reporting Trials (CONSORT) checklist, and observational and nonhuman subject studies were graded using 11 domains common across frequently used critical appraisal tools. All discrepancies were resolved by consensus. RESULTS: Our search identified 136 original publications. Nine studies met inclusion criteria. We performed a qualitative synthesis of the data from these studies. Four nonrandomized trials, 3 laboratory studies, 1 single-case experiment, and 1 RCT were identified. The laboratory studies found that cloth materials provided measurable levels of particle filtration but were less efficacious at blocking biologic material than medical masks. The RCT found that cloth masks were associated with significantly more viral infections than medical masks. CONCLUSIONS: The current literature suggests that cloth materials are somewhat efficacious in filtering particulate matter and aerosols but provide a worse fit and inferior protection compared to medical masks in clinical environments. The quality and quantity of literature addressing this question are lacking. Cloth masks lack evidence for adequate protection of health care clinicians against respiratory viral infections.

Antenatal and intrapartum consent: Implications of the NSW Consent Manual 2020.

The provision of informed consent for antenatal and intrapartum care remains a contentious issue among healthcare professionals and has been the topic of controversies in the pages of this journal. Recently, the New South Wales (NSW) Department of Health has fundamentally changed the ground rules for the provision of maternity care within the state. In this opinion piece, we try to provide guidance to clinicians to help them deal with the medicolegal environment created by this document which is likely to affect practitioners not just in NSW.

Interaction of the N terminus of ADP-ribosylation factor with the PH domain of the GTPase-activating protein ASAP1 requires phosphatidylinositol 4,5-bisphosphate.

Arf GAP with Src homology 3 domain, ankyrin repeat, and pleckstrin homology (PH) domain 1 (ASAP1) is a multidomain GTPase-activating protein (GAP) for ADP-ribosylation factor (ARF)-type GTPases. ASAP1 affects integrin adhesions, the actin cytoskeleton, and invasion and metastasis of cancer cells. ASAP1's cellular function depends on its highly-regulated and robust ARF GAP activity, requiring both the PH and the ARF GAP domains of ASAP1, and is modulated by phosphatidylinositol 4,5-bisphosphate (PIP2). The mechanistic basis of PIP2-stimulated GAP activity is incompletely understood. Here, we investigated whether PIP2 controls binding of the N-terminal extension of ARF1 to ASAP1's PH domain and thereby regulates its GAP activity. Using [Δ17]ARF1, lacking the N terminus, we found that PIP2 has little effect on ASAP1's activity. A soluble PIP2 analog, dioctanoyl-PIP2 (diC8PIP2), stimulated GAP activity on an N terminus-containing variant, [L8K]ARF1, but only marginally affected activity on [Δ17]ARF1. A peptide comprising residues 2-17 of ARF1 ([2-17]ARF1) inhibited GAP activity, and PIP2-dependently bound to a protein containing the PH domain and a 17-amino acid-long interdomain linker immediately N-terminal to the first ß-strand of the PH domain. Point mutations in either the linker or the C-terminal α-helix of the PH domain decreased [2-17]ARF1 binding and GAP activity. Mutations that reduced ARF1 N-terminal binding to the PH domain also reduced the effect of ASAP1 on cellular actin remodeling. Mutations in the ARF N terminus that reduced binding also reduced GAP activity. We conclude that PIP2 regulates binding of ASAP1's PH domain to the ARF1 N terminus, which may partially regulate GAP activity.

Extracellular vesicles from young women's breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach.

BACKGROUND: Extracellular vesicles (EVs) are small membrane particles that contribute to cancer progression and metastases by transporting biologically significant proteins and nucleic acids. They may also serve as biomarkers of various disease states or important therapeutic targets. Breast cancer EVs have the potential to change the behavior of other cells in their microenvironment. However, the proteomic content of EVs isolated from young women's breast cancer patients and the mechanisms underlying the influence of EVs on tumor cell behavior have not yet been reported. METHODS: In our current translational studies, we compared the proteomic content of EVs isolated from invasive breast cancer cell lines and plasma samples from young women's breast cancer (YWBC) patients and age-matched healthy donors using mass spectrometry. We analyzed the functionality of EVs in two dimensional tumor cell invasion assays and the gene expression changes in tumor cells after incubation with EVs. RESULTS: We found that treatment with EVs from both invasive breast cancer cell lines and plasma of YWBC patients altered the invasive properties of non-invasive breast cancer cells. Proteomics identified differences between EVs from YWBC patients and healthy donors that correlated with their altered function. Further, we identified gene expression changes in non-invasive breast cancer cells after treatment with EVs that implicate the Focal Adhesion Kinase (FAK) signaling pathway as a potential targetable pathway affected by breast cancer-derived EVs. CONCLUSIONS: Our results suggest that the proteome of EVs from breast cancer patients reflects their functionality in tumor motility assays and may help elucidate the role of EVs in breast cancer progression.

The effect of replacing vacuum with forceps in operative vaginal delivery: an observational study.

INTRODUCTION AND HYPOTHESIS: An increase in vaginal delivery with forceps may increase rates of pelvic floor trauma. This study was designed to predict trauma rates resulting from policies preferencing forceps. METHODS: This is an observational cohort study utilizing data from 660 primiparae enrolled in an RCT in two tertiary obstetric units in Sydney, Australia. Participants were assessed clinically and with 4D translabial ultrasound in the late third trimester and again at 3-6 months postpartum. Incidence of trauma associated with mode of delivery was adjusted to reflect change associated with a conversion of vacuum to forceps delivery. Primary outcome measures were third-/fourth-degree tear, levator avulsion (LA) and external anal sphincter (EAS) trauma diagnosed sonographically. RESULTS: Five hundred four women were seen at a mean of 5.1 (2.3-24.3) months postpartum. After exclusion of 21 because of missing data, 483 women were analysed: 112 (23%) had a CS, 268 (55%) a normal vaginal delivery (NVD), 69 (14%) a vacuum (VD) and 34 (7%) a forceps (FD). One hundred fifty-two women had EAS trauma and/or LA; 17 sustained both. After VD, 32/69 (46%) women suffered LA and/or EAS trauma; after FD, it was 33/34 (97%). Converting VD to FD was estimated to result in an increase in trauma from 152/483 (31%) to 187/483 (39%). A formula can be generated based on local obstetric and ultrasound data to estimate trauma incidence. CONCLUSIONS: A change in obstetric practice resulting in the conversion of primary VD to primary FD would be expected to substantially increase the likelihood of pelvic floor trauma.

Contributing factors in forceps associated pelvic floor trauma.

INTRODUCTION AND HYPOTHESIS: Levator avulsion occurs in 10-35% of women after a first vaginal delivery, with forceps being the main risk factor. Three mechanisms have been proposed to account for the high risk of trauma: the additional space requirement, increased speed of distension, and/ or greater force. This study examines the additional space requirements associated with forceps to determine any associated increase in avulsion risk. METHODS: This was an in vitro simulation study of spatial requirements for delivery of a fetal head by forceps, with mathematical modelling of spatial requirements using data from a local observational study. A balloon device was used to model head circumferences through the range of expected measurements at term, with measurements taken after application of three different types of forceps. Each measurement was performed in triplicate. RESULTS: On average, forceps increased the circumference of the fetal head by 1.01 cm for Wrigley's, 1.04 cm for Kielland's, and 1.64 cm for Neville-Barnes forceps, resulting in an estimated increase in the diameter of the fetal head by 0.32 cm, 0.33 cm, and 0.52 cm, respectively. This increase was linear throughout the tested range. In 534 singleton pregnancies at term, we determined an odds ratio (OR) of 1.11 per centimeter head circumference for avulsion. Hence, the additional space requirement due to forceps explains ORs of 1.11, 1.12, and 1.19 for avulsion, depending on forceps type. CONCLUSIONS: The effect of forceps on avulsion risk is not fully explained by the increase in space requirement alone. Other factors, such as shortened time to maximum distension and/or increased peak force applied may contribute to the excess risk.

Is vaginal flatus related to pelvic floor functional anatomy?

INTRODUCTION AND HYPOTHESIS: Vaginal flatus is an embarrassing condition that can impair women's quality of life. The underlying pathophysiology is unclear. We aimed to evaluate the association between vaginal flatus and pelvic floor anatomy. METHODS: Retrospective observational study on women seen in a tertiary urogynaecological service. All had undergone a standardised interview, clinical examination and four-dimensional transperineal ultrasound. Offline analysis of volume data was performed blinded against clinical data. RESULTS: Datasets of 570 women were analysed. Five hundred twelve (90%) were vaginally parous. Vaginal flatus was reported by 190 (33%). Mean bother score was 4.2 (SD 3.4, range 0-10). One hundred eighty-five reported frequency of vaginal flatus: it occurred < once a month in 25 (14%), once a month in 70 (38%), once a week in 47 (25%), once daily in 28 (15%) and > once daily in 15 (8%). One hundred two women identified the following precipitating factors: intercourse in 72 (71%), postural change in 22 (22%) and physical activities in 9 (9%). Vaginal birth, central and posterior compartment prolapse, anal incontinence, higher levator resting tone and younger age were associated with vaginal flatus. The latter was moderately correlated with symptom bother (correlation coefficient - 0.21). CONCLUSIONS: Vaginal flatus is a prevalent and bothersome condition affecting one-third of our study population. The condition is associated with pelvic floor functional anatomy. A higher resting tone may confer a higher resistance against which trapped air is expelled during physical activities. Younger age was moderately correlated with symptom bother.

Factors influencing sedentary behaviours after stroke: findings from qualitative observations and interviews with stroke survivors and their caregivers.

BACKGROUND: Stroke survivors are more sedentary than healthy, age-matched controls, independent of functional capacity. Interventions are needed to encourage a reduction in overall sedentary time, and regular breaks in prolonged periods of sedentary behaviour. This study captured the views and experiences of stroke survivors and their caregivers related to sedentary behaviour after stroke, to inform the development of an intervention to reduce sedentary behaviour. METHODS: Mixed-methods qualitative study. Non-participant observations were completed in two stroke services, inclusive of inpatient and community settings in the United Kingdom. Semi-structured interviews were conducted with stroke survivors and their caregivers (if available) at six- or nine-months post-stroke. Underpinned by the capability, opportunity and motivation (COM-B) model of behaviour change, observational data (132 h) were analysed thematically and interview data (n = 31 stroke survivors, n = 12 caregivers) were analysed using the Framework approach. RESULTS: Observation participants differed in functional ability whereas stroke survivor interviewees were all ambulant. Six themes related to sedentary behaviour after stroke were generated: (1) sedentary behaviour levels and patterns after stroke; (2) the physical and social environment in the stroke service and in the home; (3) standing and movement capability after stroke; (4) emotion and motivation after stroke; (5) caregivers' influence on, and role in influencing stroke survivors' sedentary behaviour; and (6) intervening to reduce sedentary behaviour after stroke. Capability, opportunity and motivation were influenced by the impact of the stroke and caregivers' inclination to support sedentary behaviour reduction. Stroke survivors reported being more sedentary than they were pre-stroke due to impaired balance and co-ordination, increased fatigue, and reduced confidence in mobilising. Caregivers inclination to support stroke survivors to reduce sedentary behaviour depended on factors including their willingness to withdraw from the caregiver role, and their perception of whether the stroke survivor would act on their encouragement. CONCLUSIONS: Many stroke survivors indicate being open to reducing sedentary behaviour, with appropriate support from stroke service staff and caregivers. The findings from this study have contributed to an intervention development process using the Behaviour Change Wheel (BCW) approach to develop strategies to reduce sedentary behaviour after stroke.

Predictors of successful ring pessary use in women with pelvic organ prolapse.

BACKGROUND: Pelvic organ prolapse (POP) is a common chronic health issue. Pessary rings are used for conservative management. To date, there is little evidence on objective anatomical findings as predictors of successful ring pessary management. AIM: To determine any association between history, clinical and four-dimensional translabial ultrasound (TLUS)/pelvic floor ultrasound examination and pessary success. MATERIALS AND METHODS: From November 2013 to November 1015, all new patients presenting with symptomatic prolapse to a tertiary urogynaecological unit underwent an assessment including interview, clinical examination, that is, International Continence Society POPQ (pelvic organ prolapse quantification) and TLUS. Women with symptomatic prolapse were offered conservative management with a ring pessary. Those who agreed had a ring inserted that day. Successful trial of pessary use was defined as continued use for at least three months. Retrospective analysis of imaging data was performed blinded to other data. Statistical analysis was performed to assess the relationship between history, examination and imaging and pessary success. RESULTS: Of 525 patients seen during the inclusion period, 177 had symptomatic prolapse. One hundred and twenty-eight were offered a pessary, 89 accepted. Five had incomplete data, leaving 84. Forty- Two (50%) were still using the pessary at a three-month follow-up. Predictors associated with failure included being pre-menopausal (P = 0.031), a previous hysterectomy (P = 0.051), increasing genital hiatus and perineal body (Gh + Pb) (P = 0.013), posterior compartment prolapse (P = 0.027) and a larger hiatal area on Valsalva on TLUS (P = 0.049). Pre-menopausal status (P = 0.003), increasing Gh + Pb (P = 0.011) and previous hysterectomy (P = 0.001) remained significant on multivariate analysis. CONCLUSIONS: A history of previous hysterectomy is a predictor of pessary failure as are Gh+Pb on Valsalva and premenopausal status.

Analysis of spermatogenesis and fertility in adult mice with a hypomorphic mutation in the Mtrr gene.

Recent research has focussed on the significance of folate metabolism in male fertility. Knocking down the mouse gene Mtrr impedes the progression of folate and methionine metabolism and results in hyperhomocysteinaemia, dysregulation of DNA methylation and developmental phenotypes (e.g. neural tube, heart and placenta defects). The Mtrrgt mouse line is a model of transgenerational epigenetic inheritance (TEI), the hypothesised cause of which is the inheritance of a yet-to-be determined epigenetic factor via the germline. We investigated Mtrrgt/gt testes and sperm function compared with control C57Bl/6J testes to explore potential defects that might confound our understanding of TEI in the Mtrrgt model. Histological analysis revealed that adult Mtrrgt/gt testes are more spherical in shape than C57Bl/6J testes, though serum testosterone levels were normal and spermatogenesis progressed in a typical manner. Spermatozoa collected from the cauda epididymis showed normal morphology, counts, and viability in Mtrrgt/gt males. Correspondingly, Mtrrgt spermatozoa contributed to normal pregnancy rates. Similar parameters were assessed in Mtrr+/+ and Mtrr+/gt males, which were normal compared with controls. Overall, our data showed that the Mtrrgt allele is unlikely to alter spermatogenesis or male fertility. Therefore, it is improbable that these factors confound the mechanistic study of TEI in Mtrrgt mice.

The impact of variations in obstetric practice on maternal birth trauma.

INTRODUCTION AND HYPOTHESIS: Forceps delivery and length of second stage are risk factors of maternal birth trauma, i.e., levator ani muscle (LAM) avulsion and anal sphincter trauma. The cesarean section (CS) rate has recently become the key performance indicator because of its increase worldwide. Attempts to reduce CS rates seem to have led to an increase in forceps deliveries and longer second stages. This study aimed to determine the association between variations in obstetric practice (between hospitals) and maternal birth trauma. METHODS: This was a retrospective ancillary analysis involving 660 nulliparous women carrying an uncomplicated singleton term pregnancy in a prospective perinatal intervention trial at two Australian tertiary obstetric units. They had been seen antenatally and at 3-6 months postpartum for a standardized clinical assessment between 2007 and 2014. Primary outcome measures were sonographically diagnosed LAM and external anal sphincter (EAS) trauma. RESULTS: The incidence of LAM avulsion (11.5% vs. 21.3%, P = 0.01) and composite trauma, i.e., LAM avulsion ± EAS injury (29.2% vs. 39.7%, P = 0.03) were higher in one of the two hospitals, where the forceps delivery rate was also higher (10.9% vs. 2.6%, P < 0.001). BMI (OR 0.9, P = 0.02), length of second stage (OR 1.01, P = 0.02) and forceps delivery (OR 5.24, P < 0.001) were significant predictors of the difference in LAM avulsion incidence between the hospitals. Maternal age (OR 1.06, P < 0.04) and forceps delivery (OR 8.66, P < 0.001) were significant predictors for composite trauma. CONCLUSIONS: A higher incidence of LAM avulsion and composite trauma in one of the two hospitals was largely explained by a higher forceps delivery rate.

Supporting carers of stroke survivors to reduce carer burden: development of the Preparing is Caring intervention using Intervention Mapping.

BACKGROUND: Burden is well documented among carers of stroke survivors, yet current evidence is insufficient to determine if any strategies reduce this negative outcome. Existing interventions for carers of stroke survivors typically involve supporting carers according to their individual needs through face-to-face interactions and provision of information including workbooks or educational guides. To date, no interventions have been developed using a method which systematically incorporates evidence, behaviour change theories, and stakeholder involvement to change the behaviours of carers and relevant individuals who support carers. This study aimed to develop a programme plan for a theory and evidence-based intervention to reduce burden in carers of stroke survivors. METHODS: Informed by evidence from two systematic reviews and 33 qualitative interviews, the first four stages of Intervention Mapping were used to guide the intervention development process: 1) needs assessment; 2) identifying outcomes and objectives; 3) selecting theoretical methods and practical applications; and 4) creating a programme plan. Structured and facilitated involvement from stakeholders, including carers, researchers, and professionals from health and community services was integral to the intervention development process. Stakeholders helped to prioritise the focus of the intervention, develop the goals, outcomes and objectives for the programme, and generate and refine intervention ideas. RESULTS: Stakeholders prioritised the need for carers to feel prepared before and during the transition from hospital to home as key to reducing burden. The proposed intervention 'Preparing is Caring' targets this need and involves providing and signposting carers to relevant information and support for practical and emotional needs. This is to be delivered before, during, and immediately after the stroke survivor's transition from hospital to home by a person taking on a single point of contact role. It is comprised of multiple theory-based components including: training packages for information and support providers working with carers and wider staff teams, plus elements to support carers to feel prepared. CONCLUSIONS: We have developed a comprehensive programme plan for a multiple-component, theory and evidence informed behaviour change intervention aimed at preparing carers before and during the transition from hospital to home. Future work is required to refine, implement and evaluate the Preparing is Caring intervention.

Atraumatic normal vaginal delivery: how many women get what they want?

BACKGROUND: Trauma to the perineum, levator ani complex, and anal sphincter is common during vaginal childbirth, but often clinically underdiagnosed, and many women are unaware of the potential for long-term damage. OBJECTIVE: In this study we use transperineal ultrasound to identify how many women will achieve a normal vaginal delivery without substantial damage to the levator ani or anal sphincter muscles, and to create a model to predict patient characteristics associated with successful atraumatic normal vaginal delivery. STUDY DESIGN: This is a retrospective, secondary analysis of data sets gathered in the context of an interventional perinatal imaging study. A total of 660 primiparas, carrying an uncomplicated singleton pregnancy, underwent an antepartum and postpartum interview, vaginal exam (Pelvic Organ Prolapse Quantification), and 4-dimensional translabial ultrasound. Ultrasound data were analyzed for levator trauma and/or overdistention and residual sphincter defects. Postprocessing analysis of ultrasound volumes was performed blinded against clinical data and analyzed against obstetric data retrieved from the local maternity database. Levator avulsion was diagnosed if the muscle insertion at the inferior pubic ramus at the plane of minimal hiatal dimensions and within 5 mm above this plane on tomographic ultrasound imaging was abnormal, ie the muscle was disconnected from the inferior pubic ramus. Hiatal overdistensibility (microtrauma) was diagnosed if there was a peripartum increase in hiatal area on Valsalva by >20% with the resultant area ≥25 cm2. A sphincter defect was diagnosed if a gap of >30 degrees was seen in ≥4 of 6 tomographic ultrasound imaging slices bracketing the external anal sphincter. Two models were tested: a first model that defines severe pelvic floor trauma as either obstetric anal sphincter injury or levator avulsion, and a second, more conservative model, that also included microtrauma. RESULTS: A total of 504/660 women (76%) returned for postpartum follow-up as described previously. In all, 21 patients were excluded due to inadequate data or intercurrent pregnancy, leaving 483 women for analysis. Model 1 defined nontraumatic vaginal delivery as excluding operative delivery, obstetric anal sphincter injuries, and sonographic evidence of levator avulsion or residual sphincter defect. Model 2 also excluded microtrauma. Of 483 women, 112 (23%) had a cesarean delivery, 103 (21%) had an operative vaginal delivery, and 17 (4%) had a third-/fourth-degree tear, leaving 251 women who could be said to have had a normal vaginal delivery. On ultrasound, in model 1, 27 women (6%) had an avulsion and 31 (6%) had a residual defect, leaving 193/483 (40%) who met the criteria for atraumatic normal vaginal delivery. In model 2, an additional 33 women (7%) had microtrauma, leaving only 160/483 (33%) women who met the criteria for atraumatic normal vaginal delivery. On multivariate analysis, younger age and earlier gestation at time of delivery remained highly significant as predictors of atraumatic normal vaginal delivery in both models, with increased hiatal area on Valsalva also significant in model 2 (all P ≤ .035). CONCLUSION: The prevalence of significant pelvic floor trauma after vaginal child birth is much higher than generally assumed. Rates of obstetric anal sphincter injury are often underestimated and levator avulsion is not included as a consequence of vaginal birth in most obstetric text books. In this study less than half (33-40%) of primiparous women achieved an atraumatic normal vaginal delivery.

Social marketing and community mobilisation to reduce underage alcohol consumption in Australia: A cluster randomised community trial.

BACKGROUND AND AIMS: In many countries adolescent alcohol use is a major health problem. To supplement national policies, it is important to trial community interventions as a potential strategy to prevent adolescent alcohol use. METHODS: This study evaluated a multicomponent community intervention that included community mobilisation, social marketing, and the monitoring of alcohol sales to minors. Evaluation was a clustered randomised trial design with 14 intervention and 14 control communities. Prior to randomisation, communities were matched on socioeconomic status and location. Intervention communities were not blinded. PARTICIPANTS: 3545 Year 8 students (M = 12 years) were surveyed at baseline from 75 schools; 3377 students were surveyed post intervention in 2013 from 54 schools. OUTCOMES: It was hypothesised that the primary outcome, individual alcohol consumption in last 30 days, after the intervention would be 15% lower in intervention communities. Secondary outcomes were consumption in the past year and intention not to drink before age 18. RESULTS: The intervention communities showed larger relative reductions compared to the controls in last 30-day consumption and past year (10%), but not significantly different. A significantly lower proportion of participants in the intervention community (63%), compared to the controls (71%), reported intending to drink before 18 years old. Subgroup analysis identified regional and state differences for some secondary measures. CONCLUSIONS: Intervention assignment was associated with lower adolescent intention to drink before the age of 18. However, more intensive and longer-term intervention may be required to measure significant differences in behaviour change. TRIAL REGISTRATION: ACTRN12612000384853. PROTOCOL: Rowland B, Toumbourou JW, Osborn A, et al. BMJ Open 2013;3:e002423. doi:10.1136/bmjopen-2012-002423.

Can pelvic floor trauma be predicted antenatally?

INTRODUCTION: Levator trauma is a risk factor for the development of pelvic organ prolapse. We aimed to identify antenatal predictors for significant damage to the levator ani muscle during a first vaginal delivery. MATERIAL AND METHODS: A retrospective observational study utilizing data from two studies with identical inclusion criteria and assessment protocols between 2005 and 2014. A total of 1148 primiparae with an uncomplicated singleton pregnancy were recruited and assessed with translabial ultrasound at 36 weeks antepartum and 871 (76%) returned for reassessment 3-6 months postpartum. The ultrasound data of vaginally parous women were analyzed for levator avulsion and microtrauma. The former was diagnosed if the muscle insertion at the inferior pubic ramus in the plane of minimal hiatal dimensions and within 5 mm above were abnormal on tomographic ultrasound imaging. Microtrauma was diagnosed in women with an intact levator and if there was a postpartum increase in hiatal area on Valsalva by >20% with the resultant area ≥25 cm2 . RESULTS: The complete datasets of 844 women were analyzed. Among them, 609 delivered vaginally: by normal vaginal delivery in 452 (54%), a vacuum birth in 102 (12%) and a forceps delivery in 55 (6%). Levator avulsion was diagnosed in 98 and microtrauma in 97. On multivariate analysis, increasing maternal age, lower body mass index and lower bladder neck descent were associated with avulsion. Increased bladder neck descent and a family history of cesarean section (CS) were associcated with microtrauma. CONCLUSIONS: Maternal age, body mass index, bladder neck descent and family history of CS are antenatal predictors for levator trauma.

Distributional learning aids linguistic category formation in school-age children.

The goal of this study was to determine if typically developing children could form grammatical categories from distributional information alone. Twenty-seven children aged six to nine listened to an artificial grammar which contained strategic gaps in its distribution. At test, we compared how children rated novel sentences that fit the grammar to sentences that were ungrammatical. Sentences could be distinguished only through the formation of categories of words with shared distributional properties. Children's ratings revealed that they could discriminate grammatical and ungrammatical sentences. These data lend support to the hypothesis that distributional learning is a potential mechanism for learning grammatical categories in a first language.