The Effectiveness of an App-Based Nurse-Moderated Program for New Mothers With Depression and Parenting Problems (eMums Plus):Pragmatic Randomized Controlled Trial

Background: Postnatal depression and caregiving difficulties adversely affect mothers, infants, and later childhood development. In many countries, resources to help mothers and infants are limited. Online group-based nurse-led interventions have the potential to help address this problem by providing large numbers of mothers with access to professional and peer support during the postnatal period. Objective: This study tested the effectiveness of a 4-month online group-based nurse-led intervention delivered when infants were aged 2 to 6 months as compared with standard care outcomes. Methods: The study was a block randomized control trial. Mothers were recruited at the time they were contacted for the postnatal health check offered to all mothers in South Australia. Those who agreed to participate were randomly assigned to the intervention or standard care. The overall response rate was 63.3% (133/210). Primary outcomes were the level of maternal depressive symptoms assessed with the Edinburgh Postnatal Depression Scale (EPDS) and quality of maternal caregiving assessed using the Parenting Stress Index (PSI; competence and attachment subscales), the Parenting Sense of Competence Scale (PSCS), and the Nursing Child Assessment Satellite Training Scale. Assessments were completed at baseline (mean child age 4.9 weeks [SD 1.4]) and again when infants were aged 8 and 12 months. Results: Outcomes were evaluated using linear generalized estimating equations adjusting for postrandomization group differences in demographic characteristics and the outcome score at baseline. There were no significant differences in the intervention and standard care groups in scores on the PSI competence subscale (P=.69) nor in the PSCS (P=.11). Although the group by time interaction suggested there were differences over time between the EPDS and PSI attachment subscale scores in the intervention and standard care groups (P=.001 and P=.04, respectively), these arose largely because the intervention group had stable scores over time whereas the standard care group showed some improvements between baseline and 12 months. Mothers engaged well with the intervention with at least 60% (43/72) of mothers logging-in once per week during the first 11 weeks of the intervention. The majority of mothers also rated the intervention as helpful and user-friendly. Conclusions: Mothers reported that the intervention was helpful, and the app was described as easy to use. As such, it appears that support for mothers during the postnatal period, provided using mobile phone technology, has the potential to be an important addition to existing services. Possible explanations for the lack of differences in outcomes for the 2 groups in this study are the failure of many mothers to use key components of the intervention and residual differences between the intervention and standard care groups post randomization.Alyssa Sawyer, Amy Kaim, Huynh-Nhu Le, Denise McDonald, Murthy Mittinty, John Lynch, Michael Sawye

Mechanical feedback through E-cadherin promotes direction sensing during collective cell migration.

E-cadherin is a major homophilic cell-cell adhesion molecule that inhibits motility of individual cells on matrix. However, its contribution to migration of cells through cell-rich tissues is less clear. We developed an in vivo sensor of mechanical tension across E-cadherin molecules, which we combined with cell-type-specific RNAi, photoactivatable Rac, and morphodynamic profiling, to interrogate how E-cadherin contributes to collective migration of cells between other cells. Using the Drosophila ovary as a model, we found that adhesion between border cells and their substrate, the nurse cells, functions in a positive feedback loop with Rac and actin assembly to stabilize forward-directed protrusion and directionally persistent movement. Adhesion between individual border cells communicates direction from the lead cell to the followers. Adhesion between motile cells and polar cells holds the cluster together and polarizes each individual cell. Thus, E-cadherin is an integral component of the guidance mechanisms that orchestrate collective chemotaxis in vivo

Protocol for economic evaluation alongside the SHINE (Supporting Healthy Image, Nutrition and Exercise) cluster randomised controlled trial

INTRODUCTION: Limited evidence exists on the cost-effectiveness of interventions to prevent obesity and promote healthy body image in adolescents. The SHINE (Supporting Healthy Image, Nutrition and Exercise) study is a cluster randomised control trial (cRCT) aiming to deliver universal education about healthy nutrition and physical activity to adolescents, as well as targeted advice to young people with body image concerns who are at risk of developing disordered eating behaviours. This paper describes the methods for the economic evaluation of the SHINE cRCT, to determine whether the intervention is cost-effective as an obesity prevention measure. METHODS AND ANALYSIS: A public payer perspective will be adopted, with intervention costs collected prospectively. Within-trial cost-effectiveness analysis (CEA) and cost-utility analysis (CUA) will quantify the incremental costs and health gains of the intervention as compared with usual practice (ie, teacher-delivered curriculum). CEA will present results as cost per body mass index unit saved. CUA will present results as cost per quality-adjusted life year gained. A modelled CUA will extend the target population, time horizon and decision context to provide valuable information to policymakers on the potential for incremental cost offsets attributable to disease prevention arising from intervention. Intervention costs and effects will be extrapolated to the population of Australian adolescents in Grade 7 of secondary school (approximate age 13 years) and modelled over the cohort\u27s lifetime. Modelled CUA results will be presented as health-adjusted life years saved and healthcare cost-savings of diseases averted. Incremental cost-effectiveness ratios will be calculated as the difference in costs between the intervention and comparator divided by the difference in benefit. Semi-structured interviews with key intervention stakeholders will explore the potential impact of scalability on cost-effectiveness. These data will be thematically analysed to inform sensitivity analysis of the base case economic evaluation, such that cost-effectiveness evidence is reflective of the potential for scalability. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Deakin University Human Research Ethics Committee (#2017-269) and the Victorian Department of Education and Training (#2018_003630). Study findings will be disseminated through peer-reviewed academic papers and participating schools will receive annual reports over the 3 years of data collection. TRIAL REGISTRATION NUMBER: ACTRN 12618000330246; Pre-results

Meaning making as an interactional accomplishment: a temporal analysis of intentionality and improvisation in classroom dialogue

In this paper we offer a significant development of Baldry and Thibault’s (2006) notion of a ‘meaning-making trajectory’ to explore the collective, and often improvisational, interactional processes of meaning making in classroom dialogue. We report a sociocultural discourse analysis (Mercer, 2004) of a series of history lessons with a class of 6-7 year-old children, which utilises the notion of ‘meaning potential’: to highlight the valuable distinction and flexible interplay between a teacher’s intended meaning-making trajectory, and the meaning-making trajectories that are instantiated in interaction with pupils through dialogic interaction. We argue that where disparities are identified, often through pupils’ unexpected questions or contributions, there can be valuable teaching-and-learning opportunities for collaboratively constructing and appropriating common knowledge

Here Comes Grosz

Program for the eighth annual RISD Cabaret held in Cellar at the top of the Waterman Building. Publicity, posters, cartoons and program designed by Yoon Cho, Yu-Kyung Chung,Arther Jones, Scott King, Richard Lloyd and Polly Spencer.https://digitalcommons.risd.edu/liberalarts_cabaret_programs/1007/thumbnail.jp

Modular Approach to Therapy for Anxiety, Depression, Trauma, or Conduct Problems in outpatient child and adolescent mental health services in New Zealand: study protocol for a randomized controlled trial

Background: Mental health disorders are common and disabling for young people because of the potential to disrupt key developmental tasks. Implementation of evidence-based psychosocial therapies in New Zealand is limited, owing to the inaccessibility, length, and cost of training in these therapies. Furthermore, most therapies address one problem area at a time, although comorbidity and changing clinical needs commonly occur in practice. A more flexible approach is needed. The Modular Approach to Therapy for Children with Anxiety, Depression, Trauma, or Conduct Problems (MATCH-ADTC) is designed to overcome these challenges; it provides a range of treatment modules addressing different problems, within a single training program. A clinical trial of MATCH-ADTC in the USA showed that MATCH-ADTC outperformed usual care and standard evidence-based treatment on several clinical measures. We aim to replicate these findings and evaluate the impact of providing training and supervision in MATCH-ADTC to: (1) improve clinical outcomes for youth attending mental health services; (2) increase the amount of evidence-based therapy content; (3) increase the efficiency of service delivery. Methods: This is an assessor-blinded multi-site effectiveness randomized controlled trial. Randomization occurs at two levels: (1) clinicians (≥60) are randomized to intervention or usual care; (2) youth participants (7–14 years old) accepted for treatment in child and adolescent mental health services (with a primary disorder that includes anxiety, depression, trauma-related symptoms, or disruptive behavior) are randomly allocated to receive MATCH-ADTC or usual care. Youth participants are recruited from ‘mainstream’, Māori-specific, and Pacific-specific child and adolescent mental health services. We originally planned to recruit 400 youth participants, but this has been revised to 200 participants. Centralized computer randomization ensures allocation concealment. The primary outcome measures are: (i) the difference in trajectory of change of clinical severity between groups (using the parent-rated Brief Problem Monitor); (ii) clinicians’ use of evidence-based treatment procedures during therapy sessions; (iii) total time spent by clinicians delivering therapy. Discussion: If MATCH-ADTC demonstrates effectiveness it could offer a practical efficient method to increase access to evidence-based therapies, and improve outcomes for youth attending secondary care services

Genetic Editing of HBV DNA by Monodomain Human APOBEC3 Cytidine Deaminases and the Recombinant Nature of APOBEC3G

Hepatitis B virus (HBV) DNA is vulnerable to editing by human cytidine deaminases of the APOBEC3 (A3A-H) family albeit to much lower levels than HIV cDNA. We have analyzed and compared HBV editing by all seven enzymes in a quail cell line that does not produce any endogenous DNA cytidine deaminase activity. Using 3DPCR it was possible to show that all but A3DE were able to deaminate HBV DNA at levels from 10−2 to 10−5 in vitro, with A3A proving to be the most efficient editor. The amino terminal domain of A3G alone was completely devoid of deaminase activity to within the sensitivity of 3DPCR (∼10−4 to 10−5). Detailed analysis of the dinucleotide editing context showed that only A3G and A3H have strong preferences, notably CpC and TpC. A phylogenic analysis of A3 exons revealed that A3G is in fact a chimera with the first two exons being derived from the A3F gene. This might allow co-expression of the two genes that are able to restrict HIV-1Δvif efficiently

Ancient genomes reveal a high diversity of Mycobacterium leprae in medieval Europe.

Studying ancient DNA allows us to retrace the evolutionary history of human pathogens, such as Mycobacterium leprae, the main causative agent of leprosy. Leprosy is one of the oldest recorded and most stigmatizing diseases in human history. The disease was prevalent in Europe until the 16th century and is still endemic in many countries with over 200,000 new cases reported annually. Previous worldwide studies on modern and European medieval M. leprae genomes revealed that they cluster into several distinct branches of which two were present in medieval Northwestern Europe. In this study, we analyzed 10 new medieval M. leprae genomes including the so far oldest M. leprae genome from one of the earliest known cases of leprosy in the United Kingdom-a skeleton from the Great Chesterford cemetery with a calibrated age of 415-545 C.E. This dataset provides a genetic time transect of M. leprae diversity in Europe over the past 1500 years. We find M. leprae strains from four distinct branches to be present in the Early Medieval Period, and strains from three different branches were detected within a single cemetery from the High Medieval Period. Altogether these findings suggest a higher genetic diversity of M. leprae strains in medieval Europe at various time points than previously assumed. The resulting more complex picture of the past phylogeography of leprosy in Europe impacts current phylogeographical models of M. leprae dissemination. It suggests alternative models for the past spread of leprosy such as a wide spread prevalence of strains from different branches in Eurasia already in Antiquity or maybe even an origin in Western Eurasia. Furthermore, these results highlight how studying ancient M. leprae strains improves understanding the history of leprosy worldwide

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups