A basal ganglia inspired model of action selection evaluated in a robotic survival task.

The basal ganglia system has been proposed as a possible neural substrate for action selection in the vertebrate brain. We describe a robotic implementation of a model of the basal ganglia and demonstrate the capacity of this system to generate adaptive switching between several acts when embedded in a robot that has to "survive" in a laboratory environment. A comparison between this brain-inspired selection mechanism and classical "winner-takes-all" selection highlights some adaptive properties specific to the model, such as avoidance of dithering and energy-saving. These properties derive, in part, from the capacity of simulated basal ganglia-thalamo-cortical loops to generate appropriate "behavioral persistence"

Task sharing for family planning services, Burkina Faso

© 2019, World Health Organization. All rights reserved. Problem In Burkina Faso, the coverage of services for family planning is low due to shortage of qualified health staff and limited access to services. Approach Following the launch of the Ouagadougou Partnership, an alliance to catalyse the expansion of family planning services, the health ministry created a consortium of family planning stakeholders in 2011. The consortium adopted a collaborative framework to implement a pilot project for task sharing in family planning at community and primary health-care centre levels in two rural districts. Stakeholders were responsible for their areas of expertise. These areas included advocacy; monitoring and evaluation; and capacity development of community health workers (CHWs) to offer oral and injectable contraceptives to new users and of auxiliary nurses and auxiliary midwives to provide implants and intrauterine devices. The health ministry implemented supportive supervision cascades involving relevant planning and service levels. Local setting In Burkina Faso, only 15% (2563/17 087) of married women used modern contraceptives in 2010. Relevant changes Adoption of new policies and clinical care standards expanded task sharing roles in family planning. The consortium trained a total of 79 CHWs and 124 auxiliary nurses and midwives. Between January 2017 and December 2018, CHWs provided injectables to 3698 new users, and auxiliary nurses or midwives provided 726 intrauterine devices and 2574 implants to new users. No safety issues were reported. Lessons learnt The pilot project was feasible and safe, however, financial constraints are hindering scale-up efforts. Supportive supervision cascades were critical in ensuring success

Effectiveness of post-partum family planning interventions on contraceptive use and method mix at 1 year after childbirth in Kinshasa, DR Congo (Yam Daabo): a single-blind, cluster-randomised controlled trial.

BACKGROUND:In rural Burkina Faso, a package of six low-technology, post-partum contraceptive interventions (ie, refresher training for providers, a counselling tool, supportive supervision, daily availability of contraceptive services, client appointment cards, and invitation letters to attend appointments for partners), aimed at strengthening existing primary health-care services and enhancing demand for them, doubled the use of modern contraceptives at 12 months post partum (ie, 55% uptake in intervention recipients vs 29% in routine-care users). This study assessed the effect of a similar package but in urban settings of Kinshasa province, Democratic Republic of the Congo, in an effort to reduce the unmet need for post-partum family planning. METHODS:Yam Daabo was a multi-intervention, single-blinded, cluster-randomised controlled trial done in six primary health-care centres (clusters) in Kinshasa. Centres were randomly allocated to receive the six-component intervention or standard antenatal and postnatal care in matched pairs (1:1) on the basis of number of monthly births, the ratio of health workers per population in the health zone, and the urban and suburban settings. Only data analysts could be masked to cluster allocation. Health-care facilities were eligible if they provided a continuum of antenatal, delivery, and postnatal care, were well stocked with contraceptives, and were situated close to the main study centre. All pregnant women presenting to the six centres were eligible if they were in their third pregnancy trimester and had no counterindications to deliver in the facility. The main outcome was prevalence of use of modern contraceptives at 12 months after delivery. Analysis was by modified intention-to-treat using generalised linear mixed models or Fisher's exact test for small groups. Prevalence ratios were adjusted for cluster effects and baseline characteristics. This study was registered with the Pan-African Clinical Trials Registry (PACTR201609001784334). FINDINGS:From July 1, 2016, to Feb 2, 2017, eight of 52 clinics assessed for eligibility met the criteria and were randomised. Of 690 women approached, 576 (83%) women were enrolled: 286 in the four intervention clusters and 290 in the four control clusters. Of them, 519 (90%) completed the 12-month study exit interview (252 in the intervention group and 267 in the control group) and were included in the intention-to-treat analysis. At 12 months, 115 (46%) of 252 women in the intervention group and 94 (35%) of 267 in the control group were using modern contraceptives (adjusted prevalence ratio [PR] 1·58, 95% CI 0·74-3·38), with significant differences in the use of contraceptive implants (22% vs 6%; adjusted PR 4·36, 95% CI 1·96-9·70), but without difference in the use of short-acting contraceptives (23% vs 28%; 0·92, 0·29-2·98) and non-modern or inappropriate methods (7% vs 18%; 0·45, 0·13-1·54). There were no serious adverse events or maternal deaths related to the study. INTERPRETATION:The Yam Daabo intervention package did not have a significant effect on the overall use of effective modern contraceptives but significantly increased implant use in women post partum who live in urban settings in Kinshasa up to a year after childbirth. However, interferences from external family planning initiatives in the control group might have diminished differences between the services received. Such an intervention could be potentially relevant in similar contexts in DR Congo and other countries. FUNDING:Government of France; UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction

The Constitutive Lack of α7 Nicotinic Receptor Leads to Metabolic Disorders in Mouse.

Type 2 diabetes (T2D) occurs by deterioration in pancreatic β-cell function and/or progressive loss of pancreatic β-cell mass under the context of insulin resistance. α7 nicotinic acetylcholine receptor (nAChR) may contribute to insulin sensitivity but its role in the pathogenesis of T2D remains undefined. We investigated whether the systemic lack of α7 nAChR was sufficient to impair glucose homeostasis. We used an α7 nAChR knock-out (α7 <sup>-/-</sup> ) mouse model fed a standard chow diet. The effects of the lack of α7 nAChR on islet mass, insulin secretion, glucose and insulin tolerance, body composition, and food behaviour were assessed in vivo and ex vivo experiments. Young α7 <sup>-/-</sup> mice display a chronic mild high glycemia combined with an impaired glucose tolerance and a marked deficit in β-cell mass. In addition to these metabolic disorders, old mice developed adipose tissue inflammation, elevated plasma free fatty acid concentrations and presented glycolytic muscle insulin resistance in old mice. Finally, α7 <sup>-/-</sup> mice, fed a chow diet, exhibited a late-onset excessive gain in body weight through increased fat mass associated with higher food intake. Our work highlights the important role of α7 nAChR in glucose homeostasis. The constitutive lack of α7 nAChR suggests a novel pathway influencing the pathogenesis of T2D

Effectiveness of a package of postpartum family planning interventions on the uptake of contraceptive methods until twelve months postpartum in Burkina Faso and the Democratic Republic of Congo: The YAM DAABO study protocol

© 2018 The Author(s). Background: Postpartum family planning (PPFP) information and services can prevent maternal and child morbidity and mortality in low-resource countries, where high unmet need for PPFP remains despite opportunities offered by routine postnatal care visits. This study aims to identify a package of PPFP interventions and determine its effectiveness on the uptake of contraceptive methods during the first year postpartum. We hypothesize that implementing a PPFP intervention package that is designed to strengthen existing antenatal and postnatal care services will result in an increase in contraceptive use. Methods: This is an operational research project using a complex intervention design with three interacting phases. The pre-formative phase aims to map study sites to establish a sampling frame. The formative phase employs a participatory approach using qualitative methodology to identify barriers and catalysts to PPFP uptake to inform the design of a PPFP intervention package. The intervention phase applies a cluster randomized-controlled trial design based at the primary healthcare level, with the experimental group implementing the PPFP package, and the control group implementing usual care. The primary outcome is modern contraceptive method uptake at twelve months postpartum. Qualitative research is embedded in the intervention phase to understand the operational reasons for success or failure of PPFP services. Discussion: Designing, testing, and scaling-up effective, affordable, and sustainable health interventions in low-resource countries is critical to address the high unmet need for PPFP. Due to socio-cultural complexities surrounding contraceptive use, this research assumes that this is more effectively accomplished by engaging key stakeholders, including adolescents, women, men, key community members, service providers, and policy-makers. At the individual level, knowledge, attitudes, and behaviors of women and couples toward PPFP will likely be influenced by a set of low-cost interventions. At the health service delivery level, the implementation of this trial will probably require a shift in behavior and accountability of providers regarding the systematic integration of PPFP into their clinical practice, as well as the optimization of health service organization to ensure the availability of competent staff and contraceptive supplies. Trial registration: Retrospectively registered in the Pan African Clinical Trials Registry (PACTR201609001784334, 27 September 2016)

Time to Long-Acting Reversible Contraceptive Uptake Over Twelve Months Postpartum: Findings of the Yam Daabo Cluster Randomized-Controlled Trial in Burkina Faso and the Democratic Republic of the Congo.

Purpose: An earlier adoption of contraceptive methods during the postpartum period could help women to extend the inter-pregnancy interval. This article aimed to determine and compare the timing of long-acting reversible contraceptives (LARC) use (ie, intrauterine device and implant) in Burkina Faso (BF) and DR Congo (DRC) between the intervention and control groups. Patients and Methods: A total of 1120 postpartum women were enrolled and followed up to 12 months postpartum. We used Yam-Daabo trial data which was a multi-intervention, single-blinded, cluster-randomised controlled trial done in primary health-care centres (clusters) in both countries. Centres were randomly allocated to receive the six-component intervention or standard antenatal and postnatal care in matched pairs (1:1). We did a secondary analysis using Royston-Parmar’s semi-parametric model to estimate the effect of the interventions on the median time of LARC uptake. Results: Our analysis included 567 postpartum women in BF (284 in the intervention group and 283 in the control group) and 553 in the DRC (274 in the intervention group and 279 in the control group). After showing an increase in family planning use in these two African countries, Yam Daabo’s interventions showed a reduction of the median time of LARCs adoption in the intervention group compared to the control group in both countries (difference of 39 days in Burkina Faso; difference of 86 days in the DR Congo). Conclusion: The Yam Daabo intervention package resulted in increased and earlier adoption of LARC in rural settings in Burkina Faso and urban settings in DR Congo. Such an intervention could be relevant in similar contexts in Sub-Saharan Africa with very high fertility rates and high unmet needs for contraception

Participatory action research to identify a package of interventions to promote postpartum family planning in Burkina Faso and the Democratic Republic of Congo

© 2018 The Author(s). Background: The YAM DAABO study ("your choice" in Mooré) takes place in Burkina Faso and the Democratic Republic of Congo. It has the objective to identify a package of postpartum family planning (PPFP) interventions to strengthen primary healthcare services and determine its effectiveness on contraceptive uptake during the first year postpartum. This article presents the process of identifying the PPFP interventions and its detailed contents. Methods: Based on participatory action research principles, we adopted an inclusive process with two complementary approaches: a bottom-up formative approach and a circular reflective approach, both of which involved a wide range of stakeholders. For the bottom-up component, we worked in each country in three formative sites and used qualitative methods to identify barriers and catalysts to PPFP uptake. The results informed the package design which occurred during the circular reflective approach - a research workshop gathering service providers, members of both country research teams, and the WHO coordination team. Results: As barriers and catalysts were found to be similar in both countries and with the view to scaling up our strategy to other comparable settings, we identified a common package of six low-cost, low-technology, and easily-scalable interventions that addressed the main service delivery obstacles related to PPFP: (1) refresher training of service providers, (2) regularly scheduled and strengthened supportive supervision of service providers, (3) enhanced availability of services 7 days a week, (4) a counseling tool, (5) appointment cards for women, and (6) invitation letters for partners. Conclusions: Our research strategy assumes that postpartum contraceptive uptake can be increased by supporting providers, enhancing the availability of services, and engaging women and their partners. The package does not promote any modern contraceptive method over another but prioritizes the importance of women's right to information and choice regarding postpartum fertility options. The effectiveness of the package will be studied in the experimental phase. If found to be effective, this intervention package may be relevant to and scalable in other parts of Burkina Faso and the DRC, and possibly other Sub-Saharan countries

Discontinuation and switching of postpartum contraceptive methods over twelve months in Burkina Faso and the Democratic Republic of the Congo: a secondary analysis of the Yam Daabo trial.

IntroductionWomen who use contraceptive methods sometimes stop early, use methods intermittently, or switched contraceptive methods. All these events (discontinuations and switching) contribute to the occurrence of unwanted and close pregnancies. This study aimed to explore contraceptive discontinuation and switching during the Yam-Daabo project to measure the effect of interventions on the continuation of contraceptive methods use.MethodsWe conducted a secondary analysis of the Yam-Daabo trial data. We choose the discontinuation and switching of a modern contraceptive method as outcome measures. We performed a survival analysis using the Stata software package to estimate the effect of the interventions on contraceptive discontinuation. We also studied the main reasons for discontinuation and switching.ResultsIn total, 637 out of the 1120 women used at least one contraceptive method (of any type), with 267 women in the control and 370 in the intervention group. One hundred seventy-nine women of the control group used modern methods compared to 279 women of the intervention group with 24 and 32 who discontinued, respectively. We observed no statistically significant association between interventions and modern methods discontinuation and switching. However, modern methods' discontinuation was higher in pills and injectables users than implants and IUDs users. The pooled data comparison showed that, in reference to the women who had not switched while using a modern method, the likelihood of switching to a less or equal effectiveness method among the women of the control group was 3.8(95% CI: 1.8-8.0) times the likelihood of switching to a less or equal effectiveness method among the women of the intervention group. And this excess was statistically significant (p ConclusionThe results of this study show no statistically significant association between interventions and modern methods discontinuation. Discontinuation is more related to the methods themselves than to any other factor. It is also essential to set up specific actions targeting women's partners and influential people in the community to counter inhibiting beliefs.Trial registrationPan African Clinical Trials Registry (PACTR201609001784334, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=1784 )

Dnmt2/Trdmt1 as mediator of RNA polymerase II transcriptional activity in cardiac growth

Dnmt2/Trdmt1 is a methyltransferase, which has been shown to methylate tRNAs. Deficient mutants were reported to exhibit various, seemingly unrelated, defects in development and RNA-mediated epigenetic heredity. Here we report a role in a distinct developmental regulation effected by a noncoding RNA. We show that Dnmt2-deficiency in mice results in cardiac hypertrophy. Echocardiographic measurements revealed that cardiac function is preserved notwithstanding the increased dimensions of the organ due to cardiomyocyte enlargement. Mechanistically, activation of the P-TEFb complex, a critical step for cardiac growth, results from increased dissociation of the negatively regulating Rn7sk non-coding RNA component in Dnmt2-deficient cells. Our data suggest that Dnmt2 plays an unexpected role for regulation of cardiac growth by modulating activity of the P-TEFb complex. © 2016 Ghanbarian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited