Neutrophil to lymphocyte ratio in captive olive baboons (Papio anubis): The effects of age, sex, rearing, stress, and pregnancy.

In apes and humans, neutrophil to lymphocyte ratio (NLR) can be used as a predictive indicator of a variety of clinical conditions, longevity, and physiological stress. In chimpanzees specifically, NLR systematically varies with age, rearing, sex, and premature death, indicating that NLR may be a useful diagnostic tool in assessing primate health. To date, just one very recent study has investigated NLR in old world monkeys and found lower NLR in males and nursery-reared individuals, as well as a negative relationship between NLR and disease outcomes. Given that baboons are increasingly used as research models, we aimed to characterize NLR in baboons by providing descriptive data and examinations of baboon NLR heritability, and of the relationships between NLR, age, rearing, and sex in 387 olive baboons (Papio anubis) between 6 months and 19 years of age. We found that (1) mother-reared baboons had higher NLRs than nursery-reared baboons; (2) females had higher NLRs than males; and (3) there was a quadratic relationship between NLR and age, such that middle-aged individuals had the highest NLR values. We also examined NLR as a function of transport to a new facility using a subset of the data. Baboons exhibited significantly higher transport NLRs compared to routine exam NLRs. More specifically, adult baboons had higher transport NLRs than routine NLRs, whereas juveniles showed no such difference, suggesting that younger animals may experience transport stress differently than older animals. We also found that transport NLR was heritable, whereas routine NLR was not, possibly suggesting that stress responses (as indicated in NLR) have a strong genetic component. Consistent with research in humans and chimpanzees, these findings suggest that NLR varies with important biological and life history variables and that NLR may be a useful health biomarker in baboons.

Assessing safe and personalised maternity and neonatal care through a pandemic: a case study of outcomes and experiences in two trusts in England using the ASPIRE COVID-19 framework.

BACKGROUND: The COVID-19 pandemic has resulted in profound and far-reaching impacts on maternal and newborn care and outcomes. As part of the ASPIRE COVID-19 project, we describe processes and outcome measures relating to safe and personalised maternity care in England which we map against a pre-developed ASPIRE framework to establish the potential impact of the COVID-19 pandemic for two UK trusts. METHODS: We undertook a mixed-methods system-wide case study using quantitative routinely collected data and qualitative data from two Trusts and their service users from 2019 to 2021 (start and completion dates varied by available data). We mapped findings to our prior ASPIRE conceptual framework that explains pathways for the impact of COVID-19 on safe and personalised care. RESULTS: The ASPIRE framework enabled us to develop a comprehensive, systems-level understanding of the impact of the pandemic on service delivery, user experience and staff wellbeing, and place it within the context of pre-existing challenges. Maternity services experienced some impacts on core service coverage, though not on Trust level clinical health outcomes (with the possible exception of readmissions in one Trust). Both users and staff found some pandemic-driven changes challenging such as remote or reduced antenatal and community postnatal contacts, and restrictions on companionship. Other key changes included an increased need for mental health support, changes in the availability and uptake of home birth services and changes in induction procedures. Many emergency adaptations persisted at the end of data collection. Differences between the trusts indicate complex change pathways. Staff reported some removal of bureaucracy, which allowed greater flexibility. During the first wave of COVID-19 staffing numbers increased, resolving some pre-pandemic shortages: however, by October 2021 they declined markedly. Trying to maintain the quality and availability of services had marked negative consequences for personnel. Timely routine clinical and staffing data were not always available and personalised care and user and staff experiences were poorly captured. CONCLUSIONS: The COVID-19 crisis magnified pre-pandemic problems and in particular, poor staffing levels. Maintaining services took a significant toll on staff wellbeing. There is some evidence that these pressures are continuing. There was marked variation in Trust responses. Lack of accessible and timely data at Trust and national levels hampered rapid insights. The ASPIRE COVID-19 framework could be useful for modelling the impact of future crises on routine care.

Inequalities in early marriage, childbearing and sexual debut among adolescents in sub-Saharan Africa.

BACKGROUND: Adolescent sexual and reproductive health (ASRH) is a major public health concern in sub-Saharan Africa (SSA). However, inequalities in ASRH have received less attention than many other public health priority areas, in part due to limited data. In this study, we examine inequalities in key ASRH indicators. METHODS: We analyzed national household surveys from 37 countries in SSA, conducted during 1990-2018, to examine trends and inequalities in adolescent behaviors related to early marriage, childbearing and sexual debut among adolescents using data from respondents 15-24 years. Survival analyses were conducted on each survey to obtain estimates for the ASRH indicators. Multilevel linear regression modelling was used to obtain estimates for 2000 and 2015 in four subregions of SSA for all indicators, disaggregated by sex, age, household wealth, urban-rural residence and educational status (primary or less versus secondary or higher education). RESULTS: In 2015, 28% of adolescent girls in SSA were married before age 18, declined at an average annual rate of 1.5% during 2000-2015, while 47% of girls gave birth before age 20, declining at 0.6% per year. Child marriage was rare for boys (2.5%). About 54% and 43% of girls and boys, respectively, had their sexual debut before 18. The declines were greater for the indicators of early adolescence (10-14 years). Large differences in marriage and childbearing were observed between adolescent girls from rural versus urban areas and the poorest versus richest households, with much greater inequalities observed in West and Central Africa where the prevalence was highest. The urban-rural and wealth-related inequalities remained stagnant or widened during 2000-2015, as the decline was relatively slower among rural and the poorest compared to urban and the richest girls. The prevalence of the ASRH indicators did not decline or increase in either education categories. CONCLUSION: Early marriage, childbearing and sexual debut declined in SSA but the 2015 levels were still high, especially in Central and West Africa, and inequalities persisted or became larger. In particular, rural, less educated and poorest adolescent girls continued to face higher ASRH risks and vulnerabilities. Greater attention to disparities in ASRH is needed for better targeting of interventions and monitoring of progress.

Trends in adolescent first births in sub-Saharan Africa: a tale of increasing inequity?

BACKGROUND: Single aggregate figures for adolescent pregnancy may fail to demonstrate particular population groups where rates are very high, or where progress has been slow. In addition, most indicators fail to separate younger from older adolescents. As there is some evidence that the disadvantages faced by adolescent mothers are greatest for those at the younger end of the spectrum, this is an important omission. This paper provides information on levels and trends of adolescent first births in 22 countries (at national and regional level) disaggregated by age (< 16 years, 16/17 years and 18/19 years), socio-economic status and place of residence. It highlights differences and similarities between countries in the characteristics of women who experience first birth during adolescence, as well as providing information on trends to identify groups where progress in reducing adolescent first births is poor. METHODOLOGY: In this descriptive and trend analysis study we used data from 22 low- and middle-income countries from sub-Saharan Africa that have at least three Demographic and Health Surveys (DHS) since 1990, with the most recent carried out after 2005. Adolescent first births from the most recent survey are analysed by age, wealth, and residence by country and region for women aged 20-24 years at time of survey. We also calculated annual percentage rates of change (using both short- and longer-term data) for adolescent first births disaggregated by age, family wealth and residence and examined changes in concentration indices (CI). FINDINGS: Overall percentages of adolescent first births vary considerably between countries for all disaggregated age groups. The burden of first birth among adolescents is significant, including in the youngest age group: in some countries over 20% of women gave birth before 16 years of age (e.g. Mali and Niger). Adolescent first births are more common among women who are poorer, and live in rural areas; early adolescent first births before 16 years of age are particularly concentrated in these disadvantaged groups. Progress in reducing adolescent first births has also been particularly poor amongst these vulnerable groups, leading to increasing inequity. CONCLUSIONS: Findings from this study show that adolescent births are concentrated among vulnerable groups where progress is often poorest. Strategies and programmes need to be developed to reduce adolescent pregnancies in marginalised young women in low- and middle-income countries.

Trends in adolescent first births in five countries in Latin America and the Caribbean: disaggregated data from demographic and health surveys.

BACKGROUND: Adolescents in the Latin American and Caribbean region continue to experience poor reproductive health outcomes, including high rates of first birth before the age of 20 years. Aggregate national level data fails to identify groups where progress is particularly poor. This paper explores how trends in adolescent births have changed over time in five countries (Bolivia, Colombia, Dominican Republic, Haiti, and Peru) using data disaggregated by adolescent age group, wealth and urban / rural residence. METHODS: The study draws on Demographic and Health Survey data from five countries where three surveys are available since 1990, with the most recent after 2006. It examines trends in adolescent births by wealth status and urban/rural residence. RESULTS: There has been little progress in reducing adolescent first births over the last two decades in these countries. Adolescent first births continue to be more common among the poorest and rural residents, and births among the youngest age-group (< 16 years) are particularly concentrated among these populations. CONCLUSION: Adolescent first births continue to be a major issue in these five countries, including amongst the youngest group (< 16 years), although the contexts in which it is occurring are changing over time. Efforts are needed to expand sexual education and services for adolescents and young people, as well as introduce and enforce legislation to provide effective protection from abuse or exploitation. Greater disaggregation of adolescent fertility data is needed if we are to measure progress towards the attainment of the Sustainable Development Goals to "leave no-one behind".

Living in the city: school friendships, diversity and the middle classes.

Much of the literature on the urban middle classes describes processes of both affiliation (often to the localities) and disaffiliation (often from some of the non-middle-class residents). In this paper, we consider this situation from a different position, drawing on research exploring whether and how children and adults living in diverse localities develop friendships with those different to themselves in terms of social class and ethnicity. This paper focuses on the interviews with the ethnically diverse, but predominantly white British, middle-class parent participants, considering their attitudes towards social and cultural difference. We emphasize the importance of highlighting inequalities that arise from social class and its intersection with ethnicity in analyses of complex urban populations. The paper's contribution is, first, to examine processes of clustering amongst the white British middle-class parents, particularly in relation to social class. Second, we contrast this process, and its moments of reflection and unease, with the more deliberate and purposeful efforts of one middle-class, Bangladeshi-origin mother who engages in active labour to facilitate relationships across social and ethnic difference.

Children's friendships in super-diverse localities: Encounters with social and ethnic difference.

This article explores how children make, manage, or avoid friendships in super-diverse primary school settings. We draw on interviews and pictorial data from 78 children, aged 8-9 years across three local London primary schools to identify particular friendship groupings and the extent to which they followed existing patterns of social division. Children in the study did recognise social and cultural differences, but their friendship perceptions, affections, conflicts and practices meant that the way in which difference impacted relationships was partial and unstable. Friendship practices in the routine settings of school involved interactions across difference, but also entrenchments around similarity.

Characterization of a Novel M1 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator Radioligand, [3H]PT-1284.

Selective activation of the M1 muscarinic acetylcholine receptor (mAChR) via a positive allosteric modulator (PAM) is a new approach for the treatment of the cognitive impairments associated with schizophrenia and Alzheimer's disease. Herein, we describe the characterization of an M1 PAM radioligand, 8-((1S,2S)-2-hydroxycyclohexyl)-5-((6-(methyl-t3)pyridin-3-yl)methyl)-8,9-dihydro-7H-pyrrolo[3,4-hour]quinolin-7-one ([(3)H]PT-1284), as a tool for characterizing the M1 allosteric binding site, as well as profiling novel M1 PAMs. 8-((1S,2S)-2-Hydroxycyclohexyl)-5-((6-methylpyridin-3-yl)methyl)-8,9-dihydro-7H-pyrrolo[3,4-hour]quinolin-7-one (PT-1284 ( 1: )) was shown to potentiate acetylcholine (ACh) in an M1 fluorometric imaging plate reader (FLIPR) functional assay (EC50, 36 nM) and carbachol in a hippocampal slice electrophysiology assay (EC50, 165 nM). PT-1284 ( 1: ) also reduced the concentration of ACh required to inhibit [(3)H]N-methylscopolamine ([(3)H]NMS) binding to M1, left-shifting the ACh Ki approximately 19-fold at 10 µM. Saturation analysis of a human M1 mAChR stable cell line showed that [(3)H]PT-1284 bound to M1 mAChR in the presence of 1 mM ACh with Kd, 4.23 nM, and saturable binding capacity (Bmax), 6.38 pmol/mg protein. M1 selective PAMs were shown to inhibit [(3)H]PT-1284 binding in a concentration-responsive manner, whereas M1 allosteric and orthosteric agonists showed weak affinity (>30 µM). A strong positive correlation (R(2) = 0.86) was found to exist between affinity values generated for nineteen M1 PAMs in the [(3)H]PT-1284 binding assay and the EC50 values of these ligands in a FLIPR functional potentiation assay. These data indicate that there is a strong positive correlation between M1 PAM binding affinity and functional activity, and that [(3)H]PT-1284 can serve as a tool for pharmacological investigation of M1 mAChR PAMs.

The causes of maternal mortality in adolescents in low and middle income countries: a systematic review of the literature.

BACKGROUND: While the main causes of maternal mortality in low and middle income countries are well understood, less is known about whether patterns for causes of maternal deaths among adolescents are the same as for older women. This study systematically reviews the literature on cause of maternal death in adolescence. Where possible we compare the main causes for adolescents with those for older women to ascertain differences and similarity in mortality patterns. METHODS: An initial search for papers and grey literature in English, Spanish and Portuguese was carried out using a number of electronic databases based on a pre-determined search strategy. The outcome of interest was the proportion of maternal deaths amongst adolescents by cause of death. A total of 15 papers met the inclusion criteria established in the study protocol. RESULTS: The main causes of maternal mortality in adolescents are similar to those of older women: hypertensive disorders, haemorrhage, abortion and sepsis. However some studies indicated country or regional differences in the relative magnitudes of specific causes of adolescent maternal mortality. When compared with causes of death for older women, hypertensive disorders were found to be a more important cause of mortality for adolescents in a number of studies in a range of settings. In terms of indirect causes of death, there are indications that malaria is a particularly important cause of adolescent maternal mortality in some countries. CONCLUSION: The main causes of maternal mortality in adolescents are broadly similar to those for older women, although the findings suggest some heterogeneity between countries and regions. However there is evidence that the relative importance of specific causes may differ for this younger age group compared to women over the age of 20 years. In particular hypertensive conditions make up a larger share of maternal deaths in adolescents than older women. Further, large scale studies are needed to investigate this question further.

The impact of armed conflict on adolescent transitions: a systematic review of quantitative research on age of sexual debut, first marriage and first birth in young women under the age of 20 years.

BACKGROUND: Young women in conflict-affected regions are at risk of a number of adverse outcomes as a result of violence, economic deterioration and the breakdown of community structures and services. This paper presents the findings of a systematic review of quantitative literature reporting how key sexual and reproductive health (SRH) outcomes among young women under the age of 20 years are affected by exposure to armed conflict; namely, sexual debut, first marriage and first birth. Increases in these outcomes among young women are all associated with potential negative public health consequences. It also examines and documents possible causal pathways for any changes seen. METHODS: To fit with our inclusion criteria, all reviewed studies included outcomes for comparable populations not exposed to conflict either temporally or spatially. A total of 19 studies with results from 21 countries or territories met our inclusion criteria; seven presented findings on marriage, four on fertility and eight on both of these outcomes. Only one study reporting on sexual debut met our criteria. RESULTS: Findings show clear evidence of both declines and increases in marriage and childbirth among young women in a range of conflict-affected settings. Several studies that showed increases in marriage below the age of 20 years reported that such increases were concentrated in the younger teenagers. Trends in fertility were predominantly driven by marriage patterns. Suggested causal pathways for the changes observed could be grouped into three categories: involuntary, gender and psycho-social and economic and material factors. CONCLUSION: The review reveals a paucity of literature on the impact of conflict on SRH outcomes of young women. Further quantitative and qualitative studies are needed to explore how conflict influences SRH events in young women over both the short- and longer-term.

Scratching under positive and negative arousal in common marmosets (Callithrix jacchus).

Scratching has been widely used as an indicator of anxiety in many primate species. However, a handful of studies have shown no change in scratching under anxiety-provoking circumstances. In addition, the existing literature has investigated scratching only in relation to negative arousal (i.e., anxiety), even though anxiety and excitement (positive arousal) share important physiological and behavioral correlates, including increased heart rate, blood pressure, and locomotion. In the current study, we scored all instances of scratching in 11 outdoor-housed captive common marmosets (Callithrix jacchus) during three contexts that were intended to be negatively arousing and three contexts that were intended to be positively arousing during a baseline, manipulation, and post-induction period. Summed across the three negative arousal contexts, the results showed that subjects exhibited significantly lower scratching rates during the manipulation than during either the baseline or post-induction periods, and the pattern of means was the same for all three of those contexts. Under the three contexts of positive arousal, subjects exhibited different patterns of scratching rates during the manipulation periods (play = increases, foraging = decreases, food anticipation = no change). Data from the current study, and a close examination of data from studies showing no change in scratching under anxiety-provoking circumstances, suggest that the anxiety-scratching relationship may be more complex than has been reported previously. Our results raise a potential concern about the unchallenged use of scratching as a behavioral indicator of anxiety in captive non-human primates, with important implications for welfare and management of these species.

Mapping adolescent first births within three east African countries using data from Demographic and Health Surveys: exploring geospatial methods to inform policy.

BACKGROUND: Early adolescent pregnancy presents a major barrier to the health and wellbeing of young women and their children. Previous studies suggest geographic heterogeneity in adolescent births, with clear "hot spots" experiencing very high prevalence of teenage pregnancy. As the reduction of adolescent pregnancy is a priority in many countries, further detailed information of the geographical areas where they most commonly occur is of value to national and district level policy makers. The aim of this study is to develop a comprehensive assessment of the geographical distribution of adolescent first births in Uganda, Kenya and Tanzania using Demographic and Household (DHS) data using descriptive, spatial analysis and spatial modelling methods. METHODS: The most recent Demographic and Health Surveys (DHS) among women aged 20 to 29 in Tanzania, Kenya, and Uganda were utilised. Analyses were carried out on first births occurring before the age of 20 years, but were disaggregated in to three age groups: <16, 16/17 and 18/19 years. In addition to basic descriptive choropleths, prevalence maps were created from the GPS-located cluster data utilising adaptive bandwidth kernel density estimates. To map adolescent first birth at district level with estimates of uncertainty, a Bayesian hierarchical regression modelling approach was used, employing the Integrated Nested Laplace Approximation (INLA) technique. RESULTS: The findings show marked geographic heterogeneity among adolescent first births, particularly among those under 16 years. Disparities are greater in Kenya and Uganda than Tanzania. The INLA analysis which produces estimates from smaller areas suggest "pockets" of high prevalence of first births, with marked differences between neighbouring districts. Many of these high prevalence areas can be linked with underlying poverty. CONCLUSIONS: There is marked geographic heterogeneity in the prevalence of adolescent first births in East Africa, particularly in the youngest age groups. Geospatial techniques can identify these inequalities and provide policy-makers with the information needed to target areas of high prevalence and focus scarce resources where they are most needed.

Universal health care and equity: evidence of maternal health based on an analysis of demographic and household survey data.

INTRODUCTION: The drive toward universal health coverage (UHC) is central to the post 2015 agenda, and is incorporated as a target in the new Sustainable Development Goals. However, it is recognised that an equity dimension needs to be included when progress to this goal is monitored. WHO have developed a monitoring framework which proposes a target of 80% coverage for all populations regardless of income and place of residence by 2030, and this paper examines the feasibility of this target in relation to antenatal care and skilled care at delivery. METHODOLOGY: We analyse the coverage gap between the poorest and richest groups within the population for antenatal care and presence of a skilled attendant at birth for countries grouped by overall coverage of each maternal health service. Average annual rates of improvement needed for each grouping (disaggregated by wealth quintile and urban/rural residence) to reach the goal are also calculated, alongside rates of progress over the past decades for comparative purposes. FINDINGS: Marked inequities are seen in all groups except in countries where overall coverage is high. As the monitoring framework has an absolute target countries with currently very low coverage are required to make rapid and sustained progress, in particular for the poorest and those living in rural areas. The rate of past progress will need to be accelerated markedly in most countries if the target is to be achieved, although several countries have demonstrated the rate of progress required is feasible both for the population as a whole and for the poorest. CONCLUSIONS: For countries with currently low coverage the target of 80% essential coverage for all populations will be challenging. Lessons should be drawn from countries who have achieved rapid and equitable progress in the past.

The geography of maternal and newborn health: the state of the art.

As the deadline for the millennium development goals approaches, it has become clear that the goals linked to maternal and newborn health are the least likely to be achieved by 2015. It is therefore critical to ensure that all possible data, tools and methods are fully exploited to help address this gap. Among the methods that are under-used, mapping has always represented a powerful way to 'tell the story' of a health problem in an easily understood way. In addition to this, the advanced analytical methods and models now being embedded into Geographic Information Systems allow a more in-depth analysis of the causes behind adverse maternal and newborn health (MNH) outcomes. This paper examines the current state of the art in mapping the geography of MNH as a starting point to unleashing the potential of these under-used approaches. Using a rapid literature review and the description of the work currently in progress, this paper allows the identification of methods in use and describes a framework for methodological approaches to inform improved decision-making. The paper is aimed at health metrics and geography of health specialists, the MNH community, as well as policy-makers in developing countries and international donor agencies.

Adolescent first births in East Africa: disaggregating characteristics, trends and determinants.

BACKGROUND: The use of a single national figure fails to capture the complex patterns and inequalities in early childbearing that occur within countries, as well as the differing contexts in which these pregnancies occur. Further disaggregated data that examine patterns and trends for different groups are needed to enable programmes to be focused on those most at risk. This paper describes a comprehensive analysis of adolescent first births using disaggregated data from Demographic and Household surveys (DHS) for three East African countries: Uganda, Kenya and Tanzania. METHODS: The study initially produces cross-sectional descriptive data on adolescent motherhood by age (under 16, 16-17 and 18-19 years), marital status, wealth, education, state or region, urban/rural residence and religion. Trends for two or more surveys over a period of 18-23 years are then analysed, and again disaggregated by age, wealth, urban/rural residence and marital status to ascertain which groups within the population have benefited most from reductions in adolescent first birth. In order to adjust for confounding factors we also use multinomial logistic regression to analyse the social and economic determinants of adolescent first birth, with outcomes again divided by age. FINDINGS: In all three countries, a significant proportion of women gave birth before age 16 (7%-12%). Both the bivariate analysis and logistic regression show that adolescent motherhood is strongly associated with poverty and lack of education/literacy, and this relationship is strongest among births within the youngest age group (<16 years). There are also marked differences by region, religion and urban/rural residence. Trends over time show there has been limited progress in reducing adolescent first births overall, with no reductions among the poorest. CONCLUSIONS: Adolescent first births, particularly at the youngest ages, are most common among the poorest and least educated, and progress in reducing rates within this group has not been made over the last few decades. Disaggregating data allows such patterns to be understood, and enables efforts to be better directed where needed.

Investigating the role of health care at birth on inequalities in neonatal survival: evidence from Bangladesh.

INTRODUCTION: In countries such as Bangladesh many women may only seek skilled care at birth when complications become evident. This often results in higher neonatal mortality for women who give birth in institutions than for those that give birth at home. However, we hypothesise that this apparent excess mortality is concentrated among less advantaged women. The aim of this paper is to examine the association between place of birth and neonatal mortality in Bangladesh, and how this varies by socio-economic status. METHODOLOGY: The study is based on pooled data from four Bangladesh Demographic and Household Surveys, and uses descriptive analysis and binomial multivariate logistic regression. It uses regression models stratified for place of delivery to examine the impact of socio-economic status and place of residence on neonatal mortality. RESULTS: Poor women from rural areas and those with no education who gave birth in institutions had much worse outcomes than those who gave birth at home. There is no difference for more wealthy women. There is a much stronger socio-economic gradient in neonatal mortality for women who gave birth in institutions than those who delivered at home. CONCLUSION: In Bangladesh babies from lower socio-economic groups and particularly those in rural areas have very poor outcomes if born in a facility. This suggests poorer, rural and less educated women are failing to obtain the timely access to quality maternal health care services needed to improve newborn outcomes.

Phosphodiesterase 11A in brain is enriched in ventral hippocampus and deletion causes psychiatric disease-related phenotypes.

Phosphodiesterase 11A (PDE11A) is the most recently identified family of phosphodiesterases (PDEs), the only known enzymes to break down cyclic nucleotides. The tissue expression profile of this dual specificity PDE is controversial, and little is understood of its biological function, particularly in the brain. We seek here to determine if PDE11A is expressed in the brain and to understand its function, using PDE11A(-/-) knockout (KO) mice. We show that PDE11A mRNA and protein are largely restricted to hippocampus CA1, subiculum, and the amygdalohippocampal area, with a two- to threefold enrichment in the ventral vs. dorsal hippocampus, equal distribution between cytosolic and membrane fractions, and increasing levels of protein expression from postnatal day 7 through adulthood. Interestingly, PDE11A KO mice show subtle psychiatric-disease-related deficits, including hyperactivity in an open field, increased sensitivity to the glutamate N-methyl-D-aspartate receptor antagonist MK-801, as well as deficits in social behaviors (social odor recognition memory and social avoidance). In addition, PDE11A KO mice show enlarged lateral ventricles and increased activity in CA1 (as per increased Arc mRNA), phenotypes associated with psychiatric disease. The increased sensitivity to MK-801 exhibited by PDE11A KO mice may be explained by the biochemical dysregulation observed around the glutamate alpha-amino-3-hydroxy-5-methyl-4-isozazolepropionic (AMPA) receptor, including decreased levels of phosphorylated-GluR1 at Ser845 and the prototypical transmembrane AMPA-receptor-associated proteins stargazin (gamma2) and gamma8. Together, our data provide convincing evidence that PDE11A expression is restricted in the brain but plays a significant role in regulating brain function.

The paradox of choice in the sexual and reproductive health and rights challenges of south-south migrant girls and women in Central America and Mexico: A scoping review of the literature.

The last decade has seen high levels of displacement in Central America and Mexico, with women and girls representing a growing share of this flow. Women and girls face a unique set of sexual and reproductive health risks, both as a direct result of the migration process, and as a consequence of violence, conflict and oppressive gender norms in the region. This scoping review adopts a five-stage process to search for, identify, and review selected literature to answer two questions: (1) what sexual and reproductive health and rights risks, challenges, and needs do women and girls face before and during displacement; and (2) how do issues of sexual and reproductive health and rights influence women and girls' coping mechanisms and decisions in displacement in the region? Extracted data from intersecting literature on migration, gender, and health in the corridors of migration in Central America and Mexico are mapped and analyzed against a framework adapted from the Guttmacher-Lancet Commission on components of sexual and reproductive health and rights. Many Central American and Mexican women and girls flee conditions of gang-related conflict, gender-based violence, poverty, and other situations of extreme disadvantage. Findings from this study demonstrate they face further deprivation and suffering from the denial of health and rights throughout the migratory cycle. This review finds that migrant women and girls encounter considerable barriers to accessing services of sexual and reproductive health, are vulnerable to sexually transmitted infections, and face many violations of sexual and reproductive rights. Young migrants and sex workers, who are often connected with irregular migration in border areas, appear to be particularly vulnerable. Findings also reveal that the literature tends to focus on sexual health and rights, with a relative paucity of evidence on wider reproductive health issues. Of critical importance is how women and girls must constantly balance risk and opportunity in situations of constrained choice, and how their coping strategies and decisions define and influence their migration trajectories and broader wellbeing. This review identifies a gap in the literature around comprehensive studies that define sexual and reproductive health and rights beyond the confines of disease and sexual behavior, as well as a need for greater focus on under-represented migrant groups such as adolescent girls.

Diverse pre-service midwifery education pathways in Cambodia and Malawi: A qualitative study utilising a midwifery education pathway conceptual framework.

OBJECTIVES: Educated and skilled midwives are required to improve maternal and newborn health and reduce stillbirths. There are three main approaches to the pre-service education of midwives: direct entry, post-nursing and integrated programmes combining nursing and midwifery. Within these, there can be multiple programmes of differing lengths and qualifications, with many countries offering numerous pathways. This study explores the history, rationale, benefits and disadvantages of multiple pre-service midwifery education in Malawi and Cambodia. The objectives are to investigate the differences in education, roles and deployment as well as how key informants perceive that the various pathways influence workforce, health care, and wider health systems outcomes in each country. DESIGN: Qualitative data were collected during semi-structured interviews and analysed using a pre-developed conceptual framework for understanding the development and outcomes of midwifery education programmes. The framework was created before data collection. SETTING: The setting is one Asian and one African country: Cambodia and Malawi. PARTICIPANTS: Twenty-one key informants with knowledge of maternal health care at the national level from different Government and non-governmental backgrounds. RESULTS: Approaches to midwifery education have historical origins. Different pathways have developed iteratively and are influenced by a need to fill vacancies, raise standards and professionalise midwifery. Cambodia has mostly focused on direct-entry midwifery while Malawi has a strong emphasis on dual-qualified nurse-midwives. Informants reported that associate midwifery cadres were often trained in a more limited set of competencies, but in reality were often required to carry out similar roles to professional midwives, often without supervision. While some respondents welcomed the flexibility offered by multiple cadres, a lack of coordination and harmonisation was reported in both countries. KEY CONCLUSIONS: The development of midwifery education in Cambodia and Malawi is complex and somewhat fragmented. While some midwifery cadres have been trained to fulfil a more limited role with fewer competencies, in practice they often have to perform a more comprehensive range of competencies. IMPLICATIONS FOR PRACTICE: Education of midwives in the full range of globally established competencies, and leadership and coordination between Ministries of Health, midwife educators and professional bodies are all needed to ensure midwives can have the greatest impact on maternal and newborn health and wellbeing.