REGENERATE-COBRA: A phase II randomized sham-controlled trial assessing the safety and efficacy of intracoronary administration of autologous bone marrow-derived cells in patients with refractory angina.

AIMS: The REGENERATE-COBRA trial (NCT05711849) will assess the safety and efficacy of an intracoronary infusion of autologous bone marrow-derived mononuclear cells in refractory angina patients with no revascularization options who are symptomatic despite optimal medical and device therapy. METHODS: REGENERATE-COBRA is a single site, blinded, randomized, sham-controlled, Phase II clinical trial enrolling 110 refractory angina patients with no revascularization options who are symptomatic despite optimal medical and device therapy. Patients will be randomized to either autologous bone marrow derived-mononuclear cells or a sham procedure. Patients in the cell-treated arm will undergo a bone marrow aspiration and an intracoronary infusion of autologous bone marrow derived-mononuclear cells. Patients in the control arm will undergo a sham bone marrow aspiration and a sham intracoronary infusion. The trial's primary endpoint is an improvement in Canadian Cardiovascular Society (CCS) angina class by 2 classes between baseline and 6 months. Secondary endpoints include change in: CCS class at 12 months, myocardial ischemic burden (as measured by perfusion imaging) at 6 months, quality of life at 6 and 12 months (as measured by EQ-5D-5L, EQ-5D-VAS and Seattle Angina Questionnaire), angina frequency at 6 and 12 months, total exercise time (as measured by a modified Bruce protocol) and major adverse cardiovascular events at 6 and 12 months. CONCLUSIONS: This is the first trial to assess the safety and efficacy of an intracoronary infusion of autologous bone marrow-derived unfractionated mononuclear cells in symptomatic refractory angina patients who have exhausted conventional therapeutic options.

The role of education in child and adolescent marriage in rural lowland Nepal.

Marriage during childhood and adolescence adversely affects maternal and child health and well-being, making it a critical global health issue. Analysis of factors associated with women marrying ≥18 years has limited utility in societies where the norm is to marry substantially earlier. This paper investigated how much education Nepali women needed to delay marriage across the range of ages from 15 to ≥18 years. Data on 6,406 women aged 23-30 years were analysed from the Low Birth Weight South Asia Trial on the early-marrying and low-educated Maithili-speaking Madhesi population in Terai, Nepal. Multivariable logistic regression models assessed the associations of women's education with marrying aged ≥15, ≥16, ≥17 and ≥18 years. Cox proportional hazards regression models quantified the hazard of marrying. Models adjusted for caste affiliation. Women married at median age of 15 years and three-quarters were uneducated. Women's primary and lower-secondary education were weakly associated with delaying marriage, whether the cut-off to define early marriage was 15, 16, 17 or 18 years, with stronger associations for secondary education. Caste associations were weak. Overall, models explained relatively little of the variance in the likelihood of marriage at different ages. The joint effects of lower-secondary and higher caste affiliation and of secondary/higher education and mid and higher caste affiliation reduced the hazard of marrying. In early-marrying and low-educated societies, changing caste-based norms are unlikely to delay women's marriage. Research on broader risk factors and norms that are more relevant for delaying marriage in these contexts is needed. Gradual increases in women's median marriage age and increased secondary education may, over time, reduce child and adolescent marriage.

A longitudinal area classification of migration in Great Britain: Testing the application of Group-Based Multi-Trajectory Modelling.

The migration of people affects the geographical distribution of the population and the demographic composition of areas over the short, medium and long terms. To recognise and respond to the corresponding needs and challenges, including consequences for service provision, social cohesion and population health, there is a continuing need to understand migration patterns of the past and present. Area classifications are a useful tool to simplify the inherently complex data on migration flows and characteristics. Yet, existing classifications often lack direct migration measures or focus solely on cross-sectional data. This study addresses these limitations by employing Group-Based Multi-Trajectory Modelling (GBMTM) to create a longitudinal, migration-specific classification of Great Britain's wards from 1981 to 2011, using six migration indicators. Using U.K. census data, we reveal six distinct migration clusters that highlight the rapid growth in studentifying neighbourhoods, the continuous influx of migrants into inner cities, and a noticeable North-South divide in terms of movers' tenure enforced by persisting income selectivity. Additionally, the geographical distribution of clusters shows a common pattern in urban areas irrespective of size or location. The longitudinal perspective of our GBMTM classification highlights trends and changes in migration patterns that are not well reflected in either the general purpose or the cross-sectional migration classification that we used as comparators. We conclude that the method presented and the classification generated offer a novel lens on migration and provide new opportunities to explore the effects of migration on a variety of outcomes and at various scales.

Differences in maternal and early child nutritional status by offspring sex in lowland Nepal.

OBJECTIVE: On average, boys grow faster than girls in early life but appear more susceptible to undernutrition. We investigated sex differences in early child growth, and whether maternal nutritional status and diet differed by offspring sex during and after pregnancy in an undernourished population. METHODS: We analyzed longitudinal data from a cluster-randomized trial from plains Nepal, stratifying results by child or gestational age. Children's outcomes (0-20 months) were weight, length, and head circumference and their z-scores relative to WHO reference data in 2-monthly intervals (n range: 24837 to 25 946). Maternal outcomes were mid-upper arm circumference (MUAC), and body mass index (BMI) during pregnancy (12-40 weeks) (n = 5550 and n = 5519) and postpartum (n = 15 710 and n = 15 356), and diet in pregnancy. We fitted unadjusted and adjusted mixed-effects linear and logistic regression models comparing boys with girls. RESULTS: Boys were larger than girls, however relative to their sex-specific reference they had lower length and head circumference z-scores from birth to 12 months, but higher weight-for-length z-scores from 0 to 6 months. Mothers of sons had higher MUAC and BMI around 36 weeks gestation but no other differences in pregnancy diets or pregnancy/postpartum maternal anthropometry were detected. Larger sex differences in children's size in the food supplementation study arm suggest that food restriction in pregnancy may limit fetal growth of boys more than girls. CONCLUSIONS: Generally, mothers' anthropometry and dietary intake do not differ according to offspring sex. As boys are consistently larger, we expect that poor maternal nutritional status may compromise their growth more than girls. Copyright © 2021 John Wiley & Sons, Ltd.

Independent associations of women's age at marriage and first pregnancy with their height in rural lowland Nepal.

OBJECTIVES: In many South Asian communities, the majority of women are married during adolescence and reproduce before 20 years. Early reproduction may adversely affect maternal nutrition and linear growth, however whether early marriage has similar effects is unknown. Shorter women might also be preferentially chosen for earlier marriage. We hypothesized that early marriage and early pregnancy may each be associated with women's shorter height, independent of any selection effects. MATERIALS AND METHODS: We analyzed cross-sectional data on 7,146 women aged 20-30 years from rural lowland Nepal. Linear regression models tested associations of early marriage and early reproduction with height, adjusting for women's education and husbands' characteristics (education and wealth) that might index preferential selection of short young women for marriage. RESULTS: Median ages at marriage and first pregnancy were 15 and 18 years, respectively, with 20% pregnant <16 years. Both early marriage and early pregnancy were independently associated with shorter stature, accounting for a decrement of 1.4 cm, which decreased to 1 cm after adjusting for women's education. Effects of early marriage and reproduction persisted after adjusting for the tendency of poorer and less educated men to marry young and short women, indicating a role for social selection. DISCUSSION: The decrements in height associated with early marriage and reproduction are indicative of broader adverse effects on maternal metabolism during a "critical period" of growth and maturation in the life-course of women. Although the magnitudes of effect are relatively small, they affect large numbers of women in this population.

Maternal physical, socioeconomic, and demographic characteristics and childbirth complications in rural lowland Nepal: Applying an evolutionary framework to understand the role of phenotypic plasticity.

OBJECTIVES: Evolutionary perspectives on human childbirth have primarily focused on characteristics of our species in general, rather than variability within and between contemporary populations. We use an evolutionary framework to explore how physical and demographic characteristics of mothers shape the risks of childbirth complications in rural lowland Nepal, where childbearing typically commences in adolescence and chronic undernutrition is widespread, though maternal overweight is increasing in association with nutrition transition. METHODS: We conducted secondary analyses of data from a cluster-randomized trial. Women aged 14-35 years were categorized by age, number of previous pregnancies, height, body mass index (BMI), husband's education, and household wealth. Multivariable logistic regression models tested whether these characteristics independently predicted risks of episiotomy and cesarean section (CS, n = 14 261), and obstructed labor (OL, n = 5185). RESULTS: Risks were greatest among first-time adolescent mothers, though associations with age varied by outcome. Independent of age and parity, short stature and high BMI increased risks of CS and OL, whereas associations were weaker for episiotomy. Male offspring had increased risk of CS and OL but not episiotomy. Wealth was not associated with OL, but lower wealth and lower husband's education were associated with lower likelihood of episiotomy and CS. CONCLUSIONS: At the individual level, the risk childbirth complications is shaped by trade-offs between fertility, growth, and survival. Some biological markers of disadvantage (early childbearing, short stature) increased the risk, whereas low socio-economic status was associated with lower risk, indicating reduced access to relevant facilities. Independent of these associations, maternal age showed complex effects.

Comprehensive analysis of the association of seasonal variability with maternal and neonatal nutrition in lowland Nepal.

OBJECTIVE: To provide a comprehensive seasonal analysis of pregnant mothers' eating behaviour and maternal/newborn nutritional status in an undernourished population from lowland rural Nepal, where weather patterns, agricultural labour, food availability and disease prevalence vary seasonally. DESIGN: Secondary analysis of cluster-randomised Low Birth Weight South Asia Trial data, applying cosinor analysis to predict seasonal patterns. OUTCOMES: Maternal mid-upper arm circumference (MUAC), BMI, dietary diversity, meals per day, eating down and food aversion in pregnancy (≥31 weeks' gestation) and neonatal z-scores of length-for-age (LAZ), weight-for-age (WAZ) and head circumference-for-age (HCAZ) and weight-for-length (WLZ). SETTING: Rural areas of Dhanusha and Mahottari districts in plains of Nepal. PARTICIPANTS: 2831 mothers aged 13-50 and 3330 neonates. RESULTS: We found seasonal patterns in newborn anthropometry and pregnant mothers' anthropometry, meal frequency, dietary diversity, food aversion and eating down. Seasonality in intake varied by food group. Offspring anthropometry broadly tracked mothers'. Annual amplitudes in mothers' MUAC and BMI were 0·27 kg/m2 and 0·22 cm, with peaks post-harvest and nadirs in October when food insecurity peaked. Annual LAZ, WAZ and WLZ amplitudes were 0·125, 0·159 and 0·411 z-scores, respectively. Neonates were the shortest but least thin (higher WLZ) in winter (December/January). In the hot season, WLZ was the lowest (May/June) while LAZ was the highest (March and August). HCAZ did not vary significantly. Food aversion and eating down peaked pre-monsoon (April/May). CONCLUSIONS: Our analyses revealed complex seasonal patterns in maternal nutrition and neonatal size. Seasonality should be accounted for when designing and evaluating public heath nutrition interventions.

Engaging Maori with qualitative healthcare research using an animated comic.

This article reports an effective strategy for recruiting patients with asthma to a qualitative study using an animated comic advertised on social media. An ad spend of NZ$432 on Facebook resulted in 101 study enquiries, and 27 participants taking part in the focus groups, of which 16 (56%) were Maori, the Indigenous Peoples of New Zealand. Representation of Maori amongst participants was over five times higher than their proportion in the local population (9.7%), resulting in data fulfilling the principle of equal explanatory power, an approach to research which can help advance Maori health development and address inequity. The success of this campaign is of particular interest for health researchers in New Zealand where Maori continue to be disproportionately affected by poorer health outcomes compared with non-Maori, particularly those with asthma. Approaches that better engage and support participation of under-represented communities in clinical research are of wider global interest. We reflect on the recruitment strategy and outcomes within a Kaupapa Maori framework, explore how this can be applied more widely in healthcare, and suggest direction for future study and implementation. Lay summary We designed an animated comic to advertise a study for patients with asthma. This was shared locally with a Facebook ad. The approach was highly engaging with the public, and resulted in rapid recruitment. Interestingly, participation of Maori (the Indigenous People of New Zealand) was over five times higher than their proportion in the local population. Maori have poorer health outcomes and increased barriers to healthcare access compared with non-Maori, particularly those with asthma. Approaches which can engage and support under-represented communities to participate in clinical research are of wider global interest. In this article, we reflect on the recruitment strategy and outcomes, and suggest direction for future study and implementation.

Why a long-term perspective is beneficial for demographers.

Although many contemporary demographers pay attention to historical demography, there is often a surprising lack of appreciation of the demographic circumstances and systems of the past, suggesting an implicit assumption that they are not relevant to the present or that the methods, data, and questions addressed by historical and contemporary demographers are different. This paper provides an overview of historical demography as published in Population Studies and how this has developed over time. Drawing on this, I demonstrate that historical and contemporary demography use similar data sources and identical methods, and they often address comparable questions. I argue that an appreciation of demographic patterns and processes is beneficial for all demographers, even those who work on the most recent time periods, and that better integration of historical and contemporary demography would be beneficial to both. The paper also considers three challenges for historical demography as it moves forward.

Revisiting the Fertility Transition in England and Wales: The Role of Social Class and Migration.

We use individual-level census data for England and Wales for the period 1851-1911 to investigate the interplay between social class and geographical context determining patterns of childbearing during the fertility transition. We also consider the effect of spatial mobility or lifetime migration on individual fertility behavior in the early phases of demographic modernization. Prior research on the fertility transition in England and Wales has demonstrated substantial variation in fertility levels and declines by different social groups; however, these findings were generally reported at a broad geographical level, disguising local variation and complicated by residential segregation along social class and occupational lines. Our findings confirm a clear pattern of widening social class differences in recent net fertility, providing strong support for the argument that belonging to a certain social group was an important determinant of early adoption of new reproductive behavior in marriage in England and Wales. However, a relatively constant effect of lower net fertility among long-distance migrants both before the transition and in the early phases of declining fertility indicates that life course migration patterns were most likely factor in explaining the differences in fertility operating through postponement of marriage and childbearing.

Adapting the Own Children Method to allow comparison of fertility between populations with different marriage regimes.

The Own Children Method (OCM) is an indirect procedure for deriving age-specific fertility rates and total fertility from children living with their mothers at a census or survey. The method was designed primarily for the calculation of overall fertility, although there are variants that allow the calculation of marital fertility. In this paper we argue that the standard variants for calculating marital fertility can produce misleading results and require strong assumptions, particularly when applied to social or spatial subgroups. We present two new variants of the method for calculating marital fertility: the first of these allows for the presence of non-marital fertility and the second also permits the more robust calculation of rates for social subgroups of the population. We illustrate and test these using full-count census data for England and Wales in 1911.

The association of maternal nutrition and children's pre-primary experience with over-age attendance in secondary school: evidence from lowland Nepal.

•Over-age attendance is increasing but remains under-studied in South Asia.•Children fall behind by entering pre-primary or primary late, and by repeating a grade during/after primary school.•Rural location, thin and uneducated mothers predicted late pre-primary entry.•Educational research and interventions need to focus on the earlier time-point of pre-primary.•Improving maternal nutrition and education may ensure timely progression of children in school.

Associations of extracurricular physical activity patterns and body composition components in a multi-ethnic population of UK children (the Size and Lung Function in Children study): a multilevel modelling analysis.

BACKGROUND: Body Mass Index (BMI) is a common outcome when assessing associations between childhood overweight and obesity and physical activity patterns. However, the fat and fat-free components of BMI, measured by the Fat Mass Index (FMI) and Fat-Free Mass Index (FFMI), may show contrasting associations with physical activity, while ethnic groups may vary in both physical activity patterns and body composition. Body composition must therefore be evaluated when assessing the associations between childhood overweight and obesity and physical activity in multi-ethnic populations. METHODS: This cross-sectional study investigated associations of BMI, FMI and FFMI z-scores with extracurricular physical activity for 2171 London primary schoolchildren (aged 5-11 years) of black, South Asian and white/other ethnicity. Multilevel mixed-effects ordered logistic modelling was used, adjusting for age, sex and family and neighbourhood socioeconomic status as potential confounders. RESULTS: Controlling for ethnicity and individual, family and neighbourhood socioeconomic confounders, actively commuting children had significantly lower Odds Ratios for being in high BMI (Odds Ratio (OR) = 0.678; 95 % Confidence Interval (CI) = 0.531 - 0.865; p - value = 0.002) and FMI z-score groups (OR = 0.679; 95 % CI = 0.499 - 0.922; p = 0.013), but not FFMI z-score groups, than passive commuters. Children doing sports less than once a week had lower Odds Ratios for being in high BMI (OR = 0.435; 95 % CI = 0.236 - 0.802; p = 0.008) and FFMI (OR = 0.455; 95 % CI = 0.214 - 0.969; p = .041) z-score categories compared to daily active children. Differences in FMI between groups did not reach the significance threshold. A trend towards statistical significance was obtained whereby children's complete inactivity was associated with higher odds for being in higher BMI (OR = 2.222 : 95 % CI = 0.977 - 5.052; p = .057) and FMI z-score groups (OR = 2.485 : 95 % CI = 0.961 - 6.429; p = .060). FFMI z-scores did not show a similar trend with complete inactivity. CONCLUSIONS: Active commuting was objectively associated with lower adiposity, while more frequent extracurricular sports participation was correlated with greater fat-free mass accretion. These relationships were independent of ethnicity and individual, family or neighbourhood socioeconomic confounding factors.

Infant feeding and child health and survival in Derbyshire in the early twentieth century.

This paper uses detailed records relating to feeding and health for a large sample of infants born in Derbyshire in the early twentieth century to provide a more detailed and nuanced picture than has previously been possible of the extent and duration of breast-feeding, reasons for ceasing to feed and the dangers of feeding in the early twentieth century. Results indicate that breast-feeding was the norm among working class British women in the early twentieth century, but the social gradient was the inverse to that found in Britain today. However this disguises much individual variation and early weaning was more common among twins, illegitimate infants, first births, and women in poor health, which placed infants at greater risk of death from many causes of death, but particularly gastro-intestinal infections. There is evidence that health visitors were successful both in promoting breast-feeding and in supporting safe hand-feeding.

Maternal phenotype, independent of family economic capital, predicts educational attainment in lowland nepalese children.

OBJECTIVES: Factors acting before children are born or reach school-going age may explain why some do not complete primary education. Many relevant factors relate to maternal phenotype, but few studies have tested for independent associations of maternal factors relative to those characterizing the family in general. METHODS: Using data from a longitudinal study of 838 children in Dhanusha, Nepal, we used logistic regression models to test whether indices of maternal somatic and educational capital, or family economic capital, were independently associated with children having had ≤2 versus 3+ years of schooling at a mean age of 8.5 years. We also tested whether maternal age, children's early growth, and urban/rural location mediated such associations. RESULTS: Children had a higher risk of completing less schooling if their mothers were short, thin, anemic, and uneducated. Independently, lower family material assets and land acreage also increased children's odds of less schooling. There was an indication of gender differences, with the risk of poor educational attainment in girls associated with low maternal somatic and educational capital, whereas in boys the relevant factors were low maternal education and family land ownership. CONCLUSIONS: Our analysis demonstrates that, independent of broader indices of family capital such as land or material assets, children's educational attainment is associated with factors embodied in maternal phenotype. Both somatic and educational maternal capital appeared important. A composite index of maternal capital could provide a new measurable proxy, prior to school entry, for identifying children at risk of completing fewer years of schooling. Am. J. Hum. Biol. 28:687-698, 2016. © 2016 Wiley Periodicals, Inc.

[Psychogenealogy and its history]. / La psychogénéalogie et son histoire.

The collective and transmittable unconscious, invisible loyalty, unconscious debts or family secrets are all concepts developed by thinkers such as Sigmund Freud, Françoise Dolto and Serge Tisseron. The genogram is a tool used by professionals to help families to identify themselves in their family constellations.

'A confession of ignorance': deaths from old age and deciphering cause-of-death statistics in Scotland, 1855-1949.

A large amount of the research undertaken in an attempt to discover the reasons underlying the late nineteenth- and early twentieth-century mortality decline in Britain has relied on the statistics published by the Registrars General. The processes by which individual causes of death are recorded and then processed in order to create the statistics are not, however, well understood. In this article, the authors build on previous work to piece together a time series of causes of death for Scotland, which removes many of the discontinuities encountered in the published statistics that result from the Registrar General deciding to update the nosology, or classification system, which was being used to compile his figures. Having regrouped individual causes of death to 'smooth' the time series, the authors use the new groups to examine the changing causes of death in Scotland for selected age groups, before turning to undertake a detailed examination of mortality amongst those aged 55 or more. The authors find that when deaths from 'old age' in the latter age group are separated from other 'ill-defined' causes, it becomes obvious that there was a 'rebranding' of cause of death. The authors then use individual-level data from two Scottish communities to further dissect the roles played by 'informants' and 'doctors' in this rebranding, in order to see how these roles may have altered over time and what the consequences might be for one's view of how mortality changed in Scotland between 1855 and 1949. Finally, the authors argue that their findings have important implications for some of historical demography's most prominent theories: the McKeown thesis and the theory of epidemiological transition.

Barriers to male involvement in contraceptive uptake and reproductive health services: a qualitative study of men and women's perceptions in two rural districts in Uganda.

BACKGROUND: Spousal communication can improve family planning use and continuation. Yet, in countries with high fertility rates and unmet need, men have often been regarded as unsupportive of their partner's use of family planning methods. This study examines men and women's perceptions regarding obstacles to men's support and uptake of modern contraceptives. METHODS: A qualitative study using 18 focus group discussions (FGDs) with purposively selected men aged 15-54 and women aged 15-49 as well as eight key informant interviews (KIIs) with government and community leaders was conducted in 2012 in Bugiri and Mpigi Districts, Uganda. Open-ended question guides were used to explore men and women's perceptions regarding barriers to men's involvement in reproductive health. All FGDs and KIIs were recorded, translated, and transcribed verbatim. Transcripts were coded and analyzed thematically using ATLAS.ti. RESULTS: Five themes were identified as rationale for men's limited involvement: (i) perceived side effects of female contraceptive methods which disrupt sexual activity, (ii) limited choices of available male contraceptives, including fear and concerns relating to vasectomy, (iii) perceptions that reproductive health was a woman's domain due to gender norms and traditional family planning communication geared towards women, (iv) preference for large family sizes which are uninhibited by prolonged birth spacing; and (v) concerns that women's use of contraceptives will lead to extramarital sexual relations. In general, knowledge of effective contraceptive methods was high. However, lack of time and overall limited awareness regarding the specific role of men in reproductive health was also thought to deter men's meaningful involvement in issues related to fertility regulation. CONCLUSION: Decision-making on contraceptive use is the shared responsibility of men and women. Effective development and implementation of male-involvement family planning initiatives should address barriers to men's supportive participation in reproductive health, including addressing men's negative beliefs regarding contraceptive services.

Exploring residential relocation- differences between newcomers and settled residents in health, travel behaviour and neighbourhood perceptions.

This study explores whether people who have recently moved to an area differ from longer-term residents in their health, travel behaviour, and perceptions of the environment. Using a large, representative sample from the UKHLS, Newcomers demonstrate significantly lower mental and physical health, reduced car commuting, and a higher likelihood of liking their neighbourhood. Area deprivation, urbanicity, household income, and age emerge as influential moderators with i.e. Newcomers in affluent areas experiencing lower physical health than Settled Residents, and rural Newcomers expressing less neighbourhood satisfaction. Our findings highlight that Newcomers' perceptions of their environment diverge and environmental influences vary among population segments, potentially impacting related health behaviours such as active travel. Furthermore, residential relocation introduces Newcomers with distinct characteristics into areas, affecting the context in which potential population health interventions aiming to influence health behaviours operate. This necessitates a deeper understanding of what influences reactions to the environment as well as ongoing adaptation of environmental interventions to respond to changing contexts within the same location over time.