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The European Marriage Pattern (EMP), in place in NW Europe for perhaps 500 years, substantially limited fertility. But how could such limitation persist when some individuals who deviated from the EMP norm had more children? If their children inherited their deviant behaviors, their descendants would quickly become the majority of later generations. This puzzle has two possible solutions. The first is that all those that deviated actually had lower net fertility over multiple generations. We show, however, no fertility penalty to future generations from higher initial fertility. Instead the EMP survived because even though the EMP persisted at the social level, children did not inherit their parents' individual fertility choices. In the paper we show evidence consistent with lateral, as opposed to vertical, transmission of EMP fertility behaviors., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

This paper investigates health impacts at the end of adolescence of prenatal exposure to multiple shocks, by exploiting the unique natural experiment of the Dutch Hunger Winter. At the end of World War II, a famine occurred abruptly in the Western Netherlands (November 1944-May 1945), pushing the previously and subsequently well-nourished Dutch population to the brink of starvation. We link high-quality military recruits data with objective health measurements for the cohorts born in the years surrounding WWII with newly digitised historical records on calories and nutrient composition of the war rations, daily temperature, and warfare deaths. Using difference-in-differences and triple differences research designs, we first show that the cohorts exposed to the Dutch Hunger Winter since early gestation have a higher Body Mass Index and an increased probability of being obese at age 18. We then find that this effect is partly moderated by warfare exposure and a reduction in energy-adjusted protein intake. Lastly, we account for selective mortality using a copula-based approach and newly-digitised data on survival rates, and find evidence of both selection and scarring effects. These results emphasise the complexity of the mechanisms at play in studying the consequences of early conditions., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Despite being one of the deadliest viruses in history, there is limited information on the socioeconomic factors that affected mortality rates during the Great Influenza Pandemic. In this study, we use occupation-province level data to investigate the relationship between influenza excess mortality rates and occupation-related status in Spain. We obtain three main results. Firstly, individuals in low-income occupations experienced the highest excess mortality, pointing to a notable income gradient. Secondly, professions that involved more social interaction were associated with a higher excess of mortality, regardless of income. Finally, we observe a substantial rural mortality penalty, even after controlling for income-related occupational groups. Based on this evidence, it seems that the high number of deaths was caused by not self-isolating. Some individuals did not quarantine themselves because they could not afford to miss work. In rural areas, home confinement was likely more limited because their inhabitants did not have immediate access to information about the pandemic or fully understand its impact due to their limited experience handling influenza outbreaks., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Portugal's real income per head grew by a factor of eight during the second half of the twentieth century, a period of fast convergence towards Western European living standards. We use a new sample of about 3,400 infants and children living in Lisbon to document trends in the prevalence of stunting and wasting between 1906 and 1994. We find that stunting and wasting fell quickly from around 1950, for both males and females. We additionally use a sample of more than 26,000 young adult males covering the entire country, which shows a consistent decrease in wasting and stunting with the expected time lag. We discuss these trends in relation to changes in income and public policy, which affected the ontogenetic environment of children. Sustained progress began well before the introduction of democracy., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Monoclonal antibody (mAb)-based therapies have been a major advance in oncology patient care, even though they represent a significant healthcare cost. Biosimilars, launched in Europe in 2004 are an economically attractive alternative to expensive originator biological drugs. They also increase the competitiveness of pharmaceutical development. This article focuses on the case of Erbitux® (cetuximab). This anti-EGFR (Epidermal Growth Factor Receptor) monoclonal antibody is indicated for metastatic colorectal cancer (2004) and squamous cell carcinoma of the head and neck (2006). However, despite the expiration of the patent in Europe in 2014 and estimated annual sales of 1.681 million US dollars in 2022, Erbitux® has not yet faced any approved biosimilar challenges in the United States or in Europe. Here, we outline the unique structural complexity of this antibody highlighted by advanced orthogonal analytical characterization strategies resulting in risks to demonstrate biosimilarity, which may explain the lack of Erbitux® biosimilars in the European and US markets to date. The development of Erbitux® biobetters are also discussed as alternative strategies to biosimilars. These biologics offer expected additional safety and potency benefits over the reference product but require a full pharmaceutical and clinical development as for New Molecular Entities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Human cysteine cathepsins form a family of eleven proteases (B, C, F, H, K, L, O, S, V, W, X/Z) that play important roles in a considerable number of biological and pathophysiological processes. Among them, cathepsin V, also known as cathepsin L2, is a lysosomal enzyme, which is mainly expressed in cornea, thymus, heart, brain, and skin. Cathepsin V is a multifunctional endopeptidase that is involved in both the release of antigenic peptides and the maturation of MHC class II molecules and participates in the turnover of elastin fibrils as well in the cleavage of intra- and extra-cellular substrates. Moreover, there is increasing evidence that cathepsin V may contribute to the progression of diverse diseases, due to the dysregulation of its expression and/or its activity. For instance, increased expression of cathepsin V is closely correlated with malignancies (breast cancer, squamous cell carcinoma, or colorectal cancer) as well vascular disorders (atherosclerosis, aortic aneurysm, hypertension) being the most prominent examples. This review aims to shed light on current knowledge on molecular aspects of cathepsin V (genomic organization, protein structure, substrate specificity), its regulation by protein and non-protein inhibitors as well to summarize its expression (tissue and cellular distribution). Then the core biological and pathophysiological roles of cathepsin V will be depicted, raising the question of its interest as a valuable target that can open up pioneering therapeutic avenues., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The funding sources had no role in the writing of the manuscript., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Using 1975-2005 Dutch time-diary data covering over 10,000 respondents for 7 consecutive days each, we show that sleep time exhibits non-constant variability, or volatility, characterized by stationary autoregressive conditional heteroscedasticity: The absolute values of deviations from a person's average sleep on one day are positively correlated with those on adjacent days. Sleep is more variable on weekends and among younger people, those without young children, or with less education. Volatility is greater among parents with young children, slightly greater among men, but independent of other demographics. Economic incentives to minimize the dispersion of sleep imply higher-wage workers will exhibit less dispersion, which we observe. Sleep volatility spills over onto volatility in other personal activities, with no reverse causation onto sleep. The results illustrate a novel dimension of inequality among people and could be applied to a wide variety of human behavior and biological processes., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Global population growth remains one of the major challenges of the twenty-first century. This is particularly true for African countries which have been undergoing their demographic transitions. To investigate whether predicted increasing population density and urbanization can help to stabilize African population, we construct a database for 84 georeferenced Demographic and Health Survey (DHS) samples including 947,191 individuals in sub-Saharan Africa and match each location with gridded population density from NASA. We apply a proportional hazard model to evaluate the quantitative impact of local population density on the transitions from childlessness to motherhood, and from celibacy to marriage. Moving from the 5th to the 95th percentile of population density increases the median age at first birth by 2.2 years. This roughly decreases completed fertility by half a child. The same increase in population density increases the median age at first marriage by 3.3 years. These findings contribute to the understanding of why fertility has not dropped in Africa as fast as expected. One part of the answer is that population density remains low. Yet the total effect of increased density on fertility remains limited and counting on it to stabilize the population would be unrealistic., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

This article traces inequality and numeracy development in the regions of Chile during the 19th and early 20th century. Inequality, measured with anthropometric methods, was associated with a lower speed of human capital formation. Not all talents received the necessary education to make full use of their talent for the regional economy, especially in the south in the early period. However, Chile became slightly less unequal over time and more numerate during the late 19th century. In addition, we study the correlates of low-intensity immigration in Chile. Regions with a relatively high share of North European migrants developed faster in terms of numeracy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This paper studies the effect of passive smoking on child development. We use data from a time when the adverse effects of smoking on health were not known and when tobacco was not an inferior good. This allows us to disentangle the effect on foetuses and infants of smoking from that of other indicators of social and economic conditions. We exploit a set of unique longitudinal historical datasets defined at a detailed level of geographical disaggregation, namely the 69 Italian provinces. The datasets record precise information on the per capita consumption of tobacco products, the heights of twenty-year old conscripts in the second half of the 19th century Italy, and other relevant controls. We find a strong negative effect of smoking in the period immediately before and after birth on the height at age 20. Results are robust to changes in specification and consistent across the height distribution., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Covid-19 has demonstrated again that epidemics can affect minorities more than the population in general. We consider one of the last major epidemics in the United States: HIV/AIDS from ca. 1980-2000. We calculate life expectancy and lifespan disparity (a measure of variance in age at death) for thirty US states, finding noticeable differences both between states and between the black and white communities. Lifespan disparity allows us to examine distributional effects, and, using decomposition methods, we find that for six states lifespan disparity for blacks increased between 1980 and 1990, while life expectancy increased less than for whites. We find that we can attribute most of this to the impact of HIV/AIDS., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This work here presented provides insights over a novel biodegradable polymeric nanosystem made of hyaluronic acid and polyarginine for diaminocyclohexane-platinum (DACHPt) encapsulation. Using mild conditions based on ionic gelation technique, monodispersed blank and DACHPt-loaded nanoparticles (NP) with a size of around 200 nm and negative ζ potential (-35 mV) were obtained. The freeze-drying process was optimized to improve the stability and shelf-life of the developed nanoparticles. After reconstitution, nanoparticles maintained their size showing an association efficiency of around 70% and a high drug loading (8%). In vitro cytotoxicity studies revealed that DACHPt-loaded nanoparticles had a superior anticancer activity compared with oxaliplatin solution. The IC50 was reduced by a factor of two in HT-29 cells (IC50 39 µM vs 74 µM, respectively), and resulted almost 1.3 fold lower in B6KPC3 cells (18 µM vs 23 µM respectively). Whereas toxic effects of both drug and DACHPt-loaded nanoparticles were comparable in the A549 cell line (IC50 11 µM vs 12 µM). DACHPt-loaded nanoparticles were also able to modulate immunogenic cell death (ICD) in vitro. After incubation with B6KPC3 cells, an increase in HMGB1 (high-mobility group box 1) production associated with ATP release occurred. Then, in vivo pharmacokinetic studies were performed after intravenous injection (IV) of DACHPt-loaded nanoparticles and oxaliplatin solution in healthy mice (35.9 µg of platinum equivalent/mouse). An AUC six times higher (24 h * mg/L) than the value obtained following the administration of oxaliplatin solution (3.76 h * mg/L) was found. C max was almost five times higher than the control (11.4 mg/L for NP vs 2.48 mg/L). Moreover, the reduction in volume of distribution and clearance clearly indicated a more limited tissue distribution. A simulated repeated IV regimen was performed in silico and showed no accumulation of platinum from the nanoparticles. Overall, the proposed approach discloses a novel nano-oncological treatment based on platinum derivative with improved antitumor activity in vitro and in vivo stability as compared to the free drug., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Lung cysteine cathepsin S (CatS) that is a potent elastase plays a deleterious role in alveolar remodeling during smoke-induced emphysema. Despite the presence of a reactive nucleophilic cysteine (Cys25) within its active site, most of its elastinolytic activity is preserved after exposure to cigarette smoke extract (CSE), a major source of sulfhydryl oxidants. This result led us to decipher CatS resistance to major and representative CSE oxidants: hydrogen peroxide, formaldehyde, acrolein and peroxynitrite. CatS was inactivated by hydrogen peroxide, peroxynitrite and acrolein in a time- and dose-dependent manner, while formaldehyde was a weaker oxidant. Hydrogen peroxide, but not CSE, formaldehyde, and peroxynitrite impaired the autocatalytic maturation of pro-CatS, whereas acrolein prevented the formation of mature CatS without hindering the initial step of the two-step autocatalytic process. Far-UV CD spectra analysis supported that oxidation by CSE and hydrogen peroxide did not led to a structural alteration of CatS, despite a notable increase of protein carbonylation, a major hallmark of oxidative damage. Evaluation of the oxidation status of Cys25 by specific biotinylated redox sensing probes suggested the formation of sulfenic acid followed by a slower conversion to sulfinic acid after incubation with hydrogen peroxide. Addition of reducing reagents (dithiothreitol, glutathione and N-acetyl cysteine) led to a partial recovery of CatS activity following incubation with CSE, hydrogen peroxide and peroxynitrite. Current results provide some mechanistic evidence of CatS stability and activity in the presence of CSE, supporting its harmful contribution to the pathophysiology of emphysema., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We study the relationship between harsh parenting strategies, including psychological and physical aggressions that do not constitute abuse, on early childhood cognitive and socio-emotional development. We estimate a value-added model that controls for a rich set of child, mother, and family characteristics, from a nationally representative sample of Chilean children aged 52-83 months. We find harsh parenting is significantly associated with lower verbal skills (Peabody Picture Vocabulary Test) of a magnitude of 0.06 standard deviations, and with increased behavioral problems (Child Behavior Check List), by 0.11 standard deviations, including internalization, externalization, and sleep problems. We also find that the more systematic (persistent) harsh parenting is, the stronger the association; the association is similar for boys and girls; reaches its peak at about 5 years of age; and it is stronger for children with less educated mothers., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We study height trends among Chinese, South Korean, and Taiwanese groups during the rapid economic growth period of the 1960s to the 1980s. Heights rose strongly as income grew. Did rapid income growth also cause a decline in gender inequality? Or did it rise because the gains were unevenly distributed? Gender inequality is particularly interesting given the traditionally strong son preference in the region. For mainland China, we find that gender inequality was relatively modest in the pre-reform period (before the 1980s). Especially in comparison to the early 20th century, female heights grew faster than male heights. In contrast, the 1980s transition period to an economic system with market elements was characterized by increasing gender inequality in China. This was the case to an even greater extent in South Korea, where gender dimorphism noticeably increased during the 1980s, paralleling a similar increase in sex-selective abortions. Moreover, we also study other inequality patterns in the three countries, focusing on socioeconomic, regional, and educational differences between groups., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Scandinavian countries currently have very high values of female autonomy. Was this already the case in Viking Times? In this study, we trace the roots of gender equality in the Scandinavian periphery over the past two millennia. We evaluate and recommend a new measure of early gender equality: relative enamel hypoplasia values of males and females. This new indicator allows us to trace relative health and nutritional equality, using archaeological evidence. We find that Scandinavian women in the rural periphery already had relatively good health and nutritional values during the Viking era and the medieval period thereafter. The corresponding value is 0.8 equality advantage for Scandinavian women, whereas in the rest of Europe most values fall in a band around 1.2 ratio units. This suggests that the currently high gender equality had a precedence during the Middle Ages., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This paper considers the long-term effects of smoking on disability retirement in Sweden. Smoking is known to have damaging effects on health, but there is limited evidence on how the effects of smoking translate into worse labour market outcomes, such as the inability to work. In contrast to the few previous studies on smoking and disability retirement, we use a large population sample with registry information on smoking, which is recorded for all women who give birth in Sweden. Thanks to these comprehensive data, we are able to account for a much broader range of potential confounders. In particular, by the use of sibling and twin fixed effects, we account for unobserved heterogeneity in childhood environment and family characteristics. Given that smoking is often initiated in adolescence, one would suspect such factors to play important roles. Among individuals aged 50-64 in 2011, a simple model suggested smokers to have a 5 percentage point higher probability of receiving (full) disability pension, making them more than twice as likely as non-smokers to receive this. However, in a model with sibling fixed effects, the size of the effect was reduced by more than a third. The results point to the importance of confounders, such as childhood circumstances or behaviours, which were not accounted for by previous studies. We also consider effects on disability due to different health conditions. In relative terms, effects are the largest for circulatory conditions and tumours. Results are largely driven by health problems severe enough to merit hospitalization, and there is no evidence of a role played by financial incentives., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The Nobel laureate Angus Deaton concentrated his work on puzzling developments and phenomena in economics. Puzzles are exciting elements in economics, because readers feel challenged by the question of how they can be solved. Among the puzzles analyzed by Deaton are: (1) Mortality increase of white, U.S. non-Hispanic men (2000 to today); (2) Why are height and income sometimes closely correlated, but not always?; (3) Height inequality among males and females; and (4) The Indian puzzle of declining consumption of calories during overall expenditure growth. This article reviews these "puzzles" and the main insights that Deaton derived from their discussion insofar as they pertain to the biological aspects of human development. I will focus on the field of this journal, Economics and Human Biology, in which Deaton has been very active over the last two decades. I will also document some of the responses by other scholars and their contributions to these puzzles, as they relate to the field of economics and human biology., (Copyright © 2016 Elsevier B.V. All rights reserved.)

It is well known that a substantial part of income and education is passed on from parents to children, generating substantial persistence in socioeconomic status across generations. In this paper, we examine whether another form of human capital, health, is also largely transmitted from generation to generation. Using data from the NLSY, we first present new evidence on intergenerational transmission of health outcomes in the U.S., including weight, height, the body mass index (BMI), asthma and depression for both natives and immigrants. We show that between 50% and 70% of the mothers' health status persists in both native and immigrant children, and that, on average, immigrants experience higher persistence than natives in BMI. We also find that the longer immigrants remain in the U.S., the less intergenerational persistence there is and the more immigrants look like native children. Unfortunately, the more generations immigrant families remain in the U.S., the more children of immigrants resemble natives' higher BMI., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

While recent research has found that birth order affects outcomes such as education and earnings, the evidence for effects on health is more limited. This paper uses a large Norwegian dataset to focus on the relationship between birth order and a range of health and health-related behaviors, outcomes not previously available in datasets of this magnitude. Interestingly, we find complicated effects of birth order. First-borns are more likely to be overweight, to be obese, and to have high blood pressure and high triglycerides. For example, compared to fifth-borns, first-borns are about 5% points more likely to be obese and 7% points more likely to have high blood pressure. So, unlike education or earnings, there is no clear first-born advantage in health. However, first-borns are about 13% points less likely to smoke daily than fifth-borns and are more likely to report good physical and mental health. Later-borns also score lower on well-being with fifth-borns being about 9% points less likely than first-borns to report that they are happy. Our findings are generally monotonic with middle-borns having outcomes that are intermediate between first- and fifth-borns. We find that these effects are largely unaffected by conditioning on education and earnings, suggesting that these are not the only important pathways to health differentials by birth order. When we explore possible mechanisms, we find that early maternal investment may play a role in birth order effects on health., (Copyright © 2016 Elsevier B.V. All rights reserved.)

This paper uses information about prime age individuals living in Amsterdam to study the patterns of use of ecstasy and cocaine. The information was collected in surveys in 1994, 1997 and 2001. The analysis shows that the use of ecstasy and cocaine is mainly influenced by calendar year, family situation, and parental cannabis use. Individuals that are more likely to use cocaine are also more likely to use ecstasy. The entrance of ecstasy in the Amsterdam drugs market in the course of the 1990s did not reduce the use of cocaine.