Markov State Models and Molecular Dynamics Simulations Reveal the Conformational Transition of the Intrinsically Disordered Hypervariable Region of K-Ras4B to the Ordered Conformation.

K-Ras4B, the most frequently mutated Ras isoform in human tumors, plays a vital part in cell growth, differentiation, and survival. Its tail, the C-terminal hypervariable region (HVR), is involved in anchoring K-Ras4B at the cellular plasma membrane and in isoform-specific protein-protein interactions and signaling. In the inactive guanosine diphosphate-bound state, the intrinsically disordered HVR interacts with the catalytic domain at the effector-binding region, rendering K-Ras4B in its autoinhibited state. Activation releases the HVR from the catalytic domain, with its ensemble favoring an ordered α-helical structure. The large-scale conformational transition of the HVR from the intrinsically disordered to the ordered conformation remains poorly understood. Here, we deploy a computational scheme that integrates a transition path-generation algorithm, extensive molecular dynamics simulation, and Markov state model analysis to investigate the conformational landscape of the HVR transition pathway. Our findings reveal a stepwise pathway for the HVR transition and uncover several key conformational substates along the transition pathway. Importantly, key interactions between the HVR and the catalytic domain are unraveled, highlighting the pathogenesis of K-Ras4B mild mutations in several congenital developmental anomaly syndromes. Together, these findings provide a deeper understanding of the HVR transition mechanism and the regulation of K-Ras4B activity at an atomic level.

Costoefectividad del régimen combinado de mirabegron/solifenacina en el tratamiento del síndrome de vejiga hiperactiva en Colombia / Cost-effectiveness of the Combined Regimen of Mirabegron/Solifenacin in the Treatment of Overactive Bladder Syndrome in Colombia

Objetivo Evaluar la costoefectividad incremental del régimen combinado de mirabegron/solifenacina en comparación con el uso temprano de toxina botulínica, desde la perspectiva del sistema de salud colombiano, para el tratamiento de adultos con vejiga hiperactiva. Métodos Se empleó un modelo de Markov en que se comparan dos secuencias de tratamiento, una con y otra sin mirabegron/solifenacina, para evaluar la costoefectividad en un horizonte temporal de cinco años. Debido a la perspectiva de análisis, sólo se tuvieron en cuenta los costos médicos directos. La eficacia del tratamiento evaluado y su comparador fue medida en términos de la reducción de episodios diarios de incontinencia y de la frecuencia de micciones. Los costos fueron expresados en pesos colombianos de 2019, y se aplicó una tasa de descuento de 5% tanto para desenlaces como para costos. Resultados Para el caso base, el costo del tratamiento en la secuencia que incluye mirabegron/solifenacina fue mayor, pero generó un mayor número de años de vida ajustados por calidad, y así e obtuvo una razón de costoefectividad incremental de $13.637,184 si se considera el desenlace de reducción de episodios diarios de incontinencia de 50%, y de $29.313,848 si se considera el del 100%. Conclusiones De acuerdo con los resultados de esta evaluación, para un horizonte de análisis de cinco años, la secuencia de tratamiento con mirabegron/solifenacina es una alternativa costoefectiva, si se considera un umbral de disposición a pagar de tres veces el producto interno bruto (PIB) per cápita.

Aim To evaluate the incremental cost-effectiveness of the combined regimen of mirabegron/solifenacin compared with the early use of botulinum toxin, from the perspective of the Colombian health system, for the treatment of adults with overactive bladder. Methods A Markov model comparing two treatment sequences, one with and one without mirabegron/solifenacin, was used to assess cost-effectiveness over a five-year period. Due to the perspective of the analysis, only direct medical costs were considered. The efficacy of the evaluated treatment and its comparator was measured in terms of the reduction in the daily incontinence episodes and the frequency of micturition. The costs were expressed in Colombian pesos of 2019, and a discount rate of 5% was applied for both outcomes and costs. Results For the base case, the cost of the treatment in the sequence that includes mirabegron/solifenacin was higher, but it generated a greater number of quality-adjusted years of life, thus obtaining an incremental cost-effectiveness ratio of $13,637,184 when considering the outcome of 50% of reduction in the daily incontinence episodes, and $29,313,848 when considering 100%. Conclusions According to the results of the present assessment, for a five-year period of analysi, the mirabegron/solifenacin treatment sequence is a cost-effective alternative when considering a threshold of willingness to pay three times the per capita gross domestic product (GDP).

Spatiotemporal Trends of Malaria in Relation to Economic Development and Cross-Border Movement along the China-Myanmar Border in Yunnan Province.

The heterogeneity and complexity of malaria involves political and natural environments, socioeconomic development, cross-border movement, and vector biology; factors that cannot be changed in a short time. This study aimed to assess the impact of economic growth and cross-border movement, toward elimination of malaria in Yunnan Province during its pre-elimination phase. Malaria data during 2011-2016 were extracted from 18 counties of Yunnan and from 7 villages, 11 displaced person camps of the Kachin Special Region II of Myanmar. Data of per-capita gross domestic product (GDP) were obtained from Yunnan Bureau of Statistics. Data were analyzed and mapped to determine spatiotemporal heterogeneity at county and village levels. There were a total 2,117 malaria cases with 85.2% imported cases; most imported cases came from Myanmar (78.5%). Along the demarcation line, malaria incidence rates in villages/camps in Myanmar were significantly higher than those of the neighboring villages in China. The spatial and temporal trends suggested that increasing per-capita GDP may have an indirect effect on the reduction of malaria cases when observed at macro level; however, malaria persists owing to complex, multi-faceted factors including poverty at individual level and cross-border movement of the workforce. In moving toward malaria elimination, despite economic growth, cooperative efforts with neighboring countries are critical to interrupt local transmission and prevent reintroduction of malaria via imported cases. Cross-border workers should be educated in preventive measures through effective behavior change communication, and investment is needed in active surveillance systems and novel diagnostic and treatment services during the elimination phase.

Cigarette affordability in the Eastern Mediterranean Region.

BACKGROUND: The World Health Organization Eastern Mediterranean Region is the only WHO region with increasing male prevalence of smoking tobacco products observed and predicted. There is no regional analysis of cigarette affordability in the literature. AIMS: This study aimed to compare the affordability of the cheapest, most sold and premium brands of cigarettes between countries of the Eastern Mediterranean Region (EMR) and countries in the rest of the world by income group in 2008 and 2018. METHODS: Affordability was defined as the percentage of GDP per capita needed to purchase 2000 cigarette sticks. A simple average and 95% confidence interval of affordability was calculated by income group for EMR countries and for the rest of the world. RESULTS: Historically, the cheapest, most sold and premium brands of cigarettes have on average been more affordable in the EMR compared to the same brands in the rest of the world in every income group. This pattern persists despite some convergence between the affordability of cigarettes in the EMR and in countries in the rest of the world. CONCLUSION: The historic and persisting higher affordability of cigarettes in the EMR relative to the rest of the world could offer an explanation to the tobacco prevalence trends in the region. Continued implementation of Article 6 of the WHO Framework Convention on Tobacco Control is needed.

Early life environment and adult height: The case of Chile.

In this paper, we analyze the relationship between adult height and early-life disease environment, proxied by the infant mortality rate (IMR) in the first year of life, using cohort-region level data for Chile for 1960-1989. IMRs show a remarkable reduction of 100 points per thousand over this thirty-year period, declining from 119.4 to 21.0 per thousand. We also document a 0.96 cm increase in height per decade.We find that the drop in IMRs observed among our cohorts explains almost all of the long-term trend in rising adult heights, and that per capita GDP does not appear to have any predictive power in this context. Results are robust in a variety of specifications, which include area and cohort dummies, an adjustment for internal migration, and urbanization rates. Our results point to the long-term effect of a public health policy.

Avaliação de custo-efetividade e impacto orçamentário do tratamento adicional de omalizumabe em pacientes com asma alérgica grave não controlada / Cost-effectiveness and budget impact analysis of additional treatment of omalizumab in patients with severe uncontrolled allergic asthma

Objetivo: Avaliar a custo-efetividade e o impacto orçamentário da adição do omalizumabe (Oma) ao tratamento padrão [corticosteroide inalatório [CI] em dose média/alta e agente beta 2-agonista de longa ação (LABA)] no tratamento da asma alérgica grave não controlada, sob a perspectiva do sistema privado de saúde no Brasil. Método: Na análise econômica, utilizou-se o modelo de Markov baseado na evolução da asma, considerando os seguintes desfechos clínicos: exacerbações graves clinicamente significantes (EGCS) e exacerbações não graves clinicamente significantes (ECS), além de taxa de mortalidade por asma e uso de recursos e custos com o tratamento. Calculou-se razões de custo-efetividade incremental (RCEI) e o impacto orçamentário, com base em dados da saúde suplementar sobre população elegível e horizonte de 5 anos. Resultados: A análise de custoefetividade realizada mostrou que o tratamento com Oma teve maior benefício, se comparado ao tratamento padrão, e gerou uma RCEI de R$ 60.293,00 por ano de vida salvo, que é três vezes inferior ao produto interno bruto (PIB) per capita no Brasil. A análise de sensibilidade, para avaliar o impacto da incerteza dos parâmetros sobre o resultado encontrado, demonstrou que os resultados permanecem estáveis a favor do Oma. A análise do impacto orçamentário apontou um custo por beneficiário de R$ 0,40 no primeiro ano, chegando a R$ 1,80 no quinto ano. Conclusão: A análise econômica demonstrou que a combinação do tratamento com Oma com o padrão para asma alérgica grave não controlada é custo-efetivo no cenário nacional, e a sua incorporação na saúde suplementar é viável.

Objective: To evaluate the cost-effectiveness and budgetary impact of adding omalizumab (Oma) to standard treatment (medium/highdose inhaled corticosteroid [ICS] and long-acting beta 2-agonist [LABA]) in the treatment of severe uncontrolled allergic asthma, from the perspective of the Brazilian private health system (PHS). Method: In economic analysis, the Markov model was used based on the progression of asthma considering the following clinical outcomes: clinically significant severe exacerbations (CSSE) and clinically significant non-severe exacerbations (CSNSE), as well as asthma mortality rate and use of resources and costs of treatment. Incremental cost-effectiveness ratios (ICER) and budgetary impact were calculated based on PHS data regarding eligible population and 5-year horizon scanning. Results: The cost-effectiveness analysis showed that treatment with Oma provided greater benefit compared to the standard treatment and generated an ICER of BRL 60,293 per life-years saved, corresponding to less than three times the gross domestic product (GDP) per capita in Brazil. A sensitivity analysis to evaluate the impact of parameter uncertainty showed that results still favor Oma. The budget impact analysis showed a cost of BRL 0.40 per recipient in the first year, reaching BRL 1.80 in the fifth year. Conclusion: The economic analysis demonstrated that combined Oma treatment and standard treatment of uncontrolled severe allergic asthma is cost-effective in the national setting and its incorporation into PHS is feasible.

Omalizumabe no tratamento da urticária crônica espontânea: análise de custo-efetividade e impacto orçamentário / Omalizumab in the treatment of chronic spontaneous urticaria: cost-effectiveness analysis and budgetary impact

Objetivos: Determinar a relação custo-efetividade da adição do omalizumabe (Oma) no tratamento da urticária crônica espontânea (UCE) refratária aos tratamentos convencionais, bem como o impacto orçamentário no contexto da saúde suplementar (SS) no Brasil. Métodos: Na análise econômica, utilizou-se o modelo de Markov baseado no Urticaria Activity Score for 7 days (UAS7), considerando- se os desfechos clínicos: anos de vida salvos com doença controlada (UAS7 = 0 ou UAS7 ≤ 6), e anos de vida ajustados à qualidade (QALY). Três razões de custo-efetividade incremental (RCEI) foram calculadas. O impacto orçamentário foi calculado com base em dados da SS, população elegível e o horizonte de 5 anos. Resultados: As RCEI calculadas para o desfecho anos de vida salvos com doença controlada nos horizontes de 3 e 5 anos foram R$ 108.935,42 e R$ 166.977,29, respectivamente. O impacto orçamentário, do primeiro ao quinto ano, da incorporação do Oma à SS para o tratamento de pacientes com UCE refratária variou entre R$ 65 milhões e R$ 157 milhões, que equivaleria a R$ 1,38/assistido no primeiro ano incorporação. Sendo assim, ao analisar os custos adicionais por desfecho adicional salvo, nota-se que a RCEI também se mostrou menor que três vezes o PIB per capita no Brasil, podendo-se dizer que o tratamento com Oma é custo-efetivo em comparação ao tratamento atual também neste desfecho. Conclusão: A análise econômica demonstrou que o tratamento com Oma da UCE refratária ao tratamento com antihistamínicos H1 em doses elevadas é custo-efetivo no cenário nacional, e a sua incorporação na SS é viável.

Objectives: To determine the cost-effectiveness of adding omalizumab (Oma) to the treatment of chronic spontaneous urticaria (CSU) refractory to conventional treatments, as well as its budgetary impact in the context of private health insurance (PHI) in Brazil. Methods: In the economic analysis, the Markov model based on the Urticaria Activity Score over 7 days (UAS7) was used considering the following clinical outcomes: life years saved with controlled disease (UAS7 = 0 or UAS7 ≤ 6) and quality-adjusted life years (QALYs). Three incremental cost-effectiveness ratios (ICERs) were calculated. The budgetary impact was calculated using PHI data, eligible population, and 5-year horizon. Results: The estimated ICERs for life years saved with controlled disease in 3- and 5-year horizons were R$ 108,935.42 and R$ 166,977.29, respectively. The budgetary impact from the first to the fifth year of the incorporation of Oma into PHI for the treatment of patients with refractory CSU ranged from R$ 65 million to R$ 157 million, equivalent to R$ 1.38/assisted patient in the first year of incorporation. When additional costs were analyzed per additional outcome saved, ICER was shown to be less than three times the GDP per capita in Brazil. Thus, Oma is cost-effective compared to the current treatment in this outcome as well. Conclusion: The economic analysis demonstrated that treatment with Oma of CSU refractory to the treatment with H1 antihistamines in high doses is cost-effective in the Brazilian setting and its incorporation into the PHI system is feasible.

Network influences on policy implementation: Evidence from a global health treaty.

This paper examines whether country implementation of a public health treaty is influenced by the implementation behaviors of other countries to which they have network ties. We examine implementation of the Framework Convention on Tobacco Control (FCTC) adopted by the World Health Organization in 2003 and ratified by approximately 94% of countries as of 2016. We constructed five networks: (1) geographic distance, (2) general trade, (3) tobacco trade, (4) GLOBALink referrals, and (5) GLOBALink co-subscriptions. Network exposure terms were constructed from these networks based on the implementation scores for six articles of the FCTC treaty. We estimate effects using a lagged Type 1 Tobit model. Results show that network effects were significant: (a) across all networks for article 6 (pricing and taxation), (b) distance, general trade, GL referrals, and GL co-subscriptions for article 8 (second hand smoke), (c) distance, general trade, and GL co-subscriptions for article 11 (packaging and labeling), and (d) distance and GL co-subscription for article 13 (promotion and advertising), (e) tobacco trade and GL co-subscriptions for article 14 (cessation). These results indicate that diffusion effects were more prevalent for pricing and taxation as well as restrictions on smoking in public places and packaging and labeling. These results suggest that network influences are possible in domains that are amenable to control by national governments but unlikely to occur in domains established by existing regulatory systems. Implications for future studies of policy implementation are discussed.

Simulation of spontaneous G protein activation reveals a new intermediate driving GDP unbinding.

Activation of heterotrimeric G proteins is a key step in many signaling cascades. However, a complete mechanism for this process, which requires allosteric communication between binding sites that are ~30 Å apart, remains elusive. We construct an atomically detailed model of G protein activation by combining three powerful computational methods: metadynamics, Markov state models (MSMs), and CARDS analysis of correlated motions. We uncover a mechanism that is consistent with a wide variety of structural and biochemical data. Surprisingly, the rate-limiting step for GDP release correlates with tilting rather than translation of the GPCR-binding helix 5. ß-Strands 1 - 3 and helix 1 emerge as hubs in the allosteric network that links conformational changes in the GPCR-binding site to disordering of the distal nucleotide-binding site and consequent GDP release. Our approach and insights provide foundations for understanding disease-implicated G protein mutants, illuminating slow events in allosteric networks, and examining unbinding processes with slow off-rates.

Assessment of mutation probabilities of KRAS G12 missense mutants and their long-timescale dynamics by atomistic molecular simulations and Markov state modeling.

A mutated KRAS protein is frequently observed in human cancers. Traditionally, the oncogenic properties of KRAS missense mutants at position 12 (G12X) have been considered as equal. Here, by assessing the probabilities of occurrence of all KRAS G12X mutations and KRAS dynamics we show that this assumption does not hold true. Instead, our findings revealed an outstanding mutational bias. We conducted a thorough mutational analysis of KRAS G12X mutations and assessed to what extent the observed mutation frequencies follow a random distribution. Unique tissue-specific frequencies are displayed with specific mutations, especially with G12R, which cannot be explained by random probabilities. To clarify the underlying causes for the nonrandom probabilities, we conducted extensive atomistic molecular dynamics simulations (170 µs) to study the differences of G12X mutations on a molecular level. The simulations revealed an allosteric hydrophobic signaling network in KRAS, and that protein dynamics is altered among the G12X mutants and as such differs from the wild-type and is mutation-specific. The shift in long-timescale conformational dynamics was confirmed with Markov state modeling. A G12X mutation was found to modify KRAS dynamics in an allosteric way, which is especially manifested in the switch regions that are responsible for the effector protein binding. The findings provide a basis to understand better the oncogenic properties of KRAS G12X mutants and the consequences of the observed nonrandom frequencies of specific G12X mutations.

Signatures of a macroscopic switching transition for a dynamic microtubule.

Characterising complex kinetics of non-equilibrium self-assembly of bio-filaments is of general interest. Dynamic instability in microtubules, consisting of successive catastrophes and rescues, is observed to occur as a result of the non-equilibrium conversion of GTP-tubulin to GDP-tubulin. We study this phenomenon using a model for microtubule kinetics with GTP/GDP state-dependent polymerisation, depolymerisation and hydrolysis of subunits. Our results reveal a sharp switch-like transition in the mean velocity of the filaments, from a growth phase to a shrinkage phase, with an associated co-existence of the two phases. This transition is reminiscent of the discontinuous phase transition across the liquid-gas boundary. We probe the extent of discontinuity in the transition quantitatively using characteristic signatures such as bimodality in velocity distribution, variance and Binder cumulant, and also hysteresis behaviour of the system. We further investigate ageing behaviour in catastrophes of the filament, and find that the multi-step nature of catastrophes is intensified in the vicinity of the switching transition. This assumes importance in the context of Microtubule Associated Proteins which have the potential of altering kinetic parameter values.

The Role of Policy and Institutions on Health Spending.

This paper investigates the impact of policies and institutions on health expenditures for a large panel of Organisation for Economic Co-operation and Development countries for the period of 2000-2010. A set of 20 policy and institutional indicators developed by the Organisation for Economic Co-operation and Development are integrated into a theoretically motivated econometric framework, alongside control variables related to demographic (dependency ratio) and non-demographic (income, prices and technology) drivers of health expenditures per capita. Although a large share of cross-country differences in public health expenditures can be explained by demographic and economic factors (around 71%), cross-country variations in policies and institutions also have a significant influence, explaining most of the remaining difference in public health spending (23%). Copyright © 2016 John Wiley & Sons, Ltd.

Carbon emissions, logistics volume and GDP in China: empirical analysis based on panel data model.

This paper studies the relationship among carbon emissions, GDP, and logistics by using a panel data model and a combination of statistics and econometrics theory. The model is based on the historical data of 10 typical provinces and cities in China during 2005-2014. The model in this paper adds the variability of logistics on the basis of previous studies, and this variable is replaced by the freight turnover of the provinces. Carbon emissions are calculated by using the annual consumption of coal, oil, and natural gas. GDP is the gross domestic product. The results showed that the amount of logistics and GDP have a contribution to carbon emissions and the long-term relationships are different between different cities in China, mainly influenced by the difference among development mode, economic structure, and level of logistic development. After the testing of panel model setting, this paper established a variable coefficient model of the panel. The influence of GDP and logistics on carbon emissions is obtained according to the influence factors among the variables. The paper concludes with main findings and provides recommendations toward rational planning of urban sustainable development and environmental protection for China.

The great recession, youth unemployment and inequalities in psychological health complaints in adolescents: a multilevel study in 31 countries.

OBJECTIVES: Little is known about the impact of recessions on young people's socioeconomic inequalities in health. This study investigates the impact of the economic recession in terms of youth unemployment on socioeconomic inequalities in psychological health complaints among adolescents across Europe and North America. METHODS: Data from the WHO collaborative 'Health Behaviour in School-aged Children' (HBSC) study were collected in 2005/06 (N = 160,830) and 2009/10 (N = 166,590) in 31 European and North American countries. Logistic multilevel models were used to assess the contribution of youth unemployment in 2009/10 (enduring recession) and the change in youth unemployment (2005-2010) to adolescent psychological health complaints and socioeconomic inequalities in complaints in 2009/10. RESULTS: Youth unemployment during the recession is positively related to psychological health complaints, but not to inequalities in complaints. Changes in youth unemployment (2005-2010) were not associated with adolescents' psychological health complaints, whereas greater inequalities in complaints were found in countries with greater increases in youth unemployment. CONCLUSIONS: This study highlights the need to tackle the impact of increasing unemployment on adolescent health and health inequalities during economic recessions.

Agricultural vulnerability over the Chinese Loess Plateau in response to climate change: Exposure, sensitivity, and adaptive capacity.

Understanding how the vulnerability of agricultural production to climate change can differ spatially has practical significance to sustainable management of agricultural systems worldwide. Accordingly, this study developed a conceptual framework to assess the agricultural vulnerability of 243 rural counties on the Chinese Loess Plateau. Indicators representing the climate/agriculture interface were selected to describe exposure and sensitivity, while stocks of certain capitals were used to describe adaptive capacity. A vulnerability index for each county was calculated and the spatial distribution was mapped. Results showed that exposure, sensitivity, and adaptive capacity occur independently, with most contributing indicator values concentrated in a narrow range after normalization. Within the 49 most vulnerable counties, which together encompass 81 % of the vulnerability index range, 42 were characterized by high exposure and sensitivity but low adaptive capacity. The most vulnerable area was found to be located in the central northeast-southwest belt of Loess Plateau. Adaptation measures for both ecological restoration and economic development are needed and potential adaptation options need further investigation.

Trends and structural shifts in health tourism: evidence from seasonal time-series data on health-related travel spending by Canada during 1970-2010.

There has been a growing interest in better understanding the trends and determinants of health tourism activities. While much of the expanding literature on health tourism offers theoretical or qualitative discussion, empirical evidences has been lacking. This study employs Canada's outbound health tourism activities as an example to examine the trends in health tourism and its association with changing domestic health care market characteristics. A time-series model that accounts for potential structural changes in the trend is employed to analyze the quarterly health-related travel spending series reported in the Balance of Payments Statistics (BOPS) during 1970-2010 (n = 156). We identified a structural shift point which marks the start of an accelerated growth of health tourism and a flattened seasonality in such activities. We found that the health tourism activities of Canadian consumers increase when the private investment in medical facilities declines or when the private MPI increases during the years following the structural-change. We discussed the possible linkage of the structural shift to the General Agreement on Trade in Services (GATS), which went into effect in January, 1995.

Unemployment and Suicide Mortality: Evidence from Regional Panel Data in Europe.

This paper addresses the influence of economic activity on suicide mortality in Europe. To this end, it employs a new panel data set of 275 regions in 29 countries over the period 1999-2010. The results suggest that unemployment does have a significantly positive influence on suicides. In line with economic theory, this influence varies among gender and age groups. Men of working age are particularly sensitive, while old-age suicide mortality (older than 65 years old) hardly responds to unemployment. Moreover, real economic growth negatively affects the suicide rates of working-age men. The results withstand several robustness checks, such as sample variations, and after controlling for serial and spatial autocorrelation.

Social capital and health: evidence that ancestral trust promotes health among children of immigrants.

This paper presents evidence that generalized trust promotes health. Children of immigrants in a broad set of European countries with ancestry from across the world are studied. Individuals are examined within country of residence using variation in trust across countries of ancestry. The approach addresses reverse causality and concerns that the trust measure picks up institutional factors in the individual's contextual setting. There is a significant positive estimate of ancestral trust in explaining self-assessed health. The finding is robust to accounting for individual, parental, and extensive ancestral country characteristics. Individuals with higher ancestral trust are also less likely to be hampered by health problems in their daily life, providing evidence of trust influencing real life outcomes. Individuals with high trust feel and act healthier, enabling a more productive life.

The role of nutrition and genetics as key determinants of the positive height trend.

The aim of this study was to identify the most important variables determining current differences in physical stature in Europe and some of its overseas offshoots such as Australia, New Zealand and USA. We collected data on the height of young men from 45 countries and compared them with long-term averages of food consumption from the FAOSTAT database, various development indicators compiled by the World Bank and the CIA World Factbook, and frequencies of several genetic markers. Our analysis demonstrates that the most important factor explaining current differences in stature among nations of European origin is the level of nutrition, especially the ratio between the intake of high-quality proteins from milk products, pork meat and fish, and low-quality proteins from wheat. Possible genetic factors such as the distribution of Y haplogroup I-M170, combined frequencies of Y haplogroups I-M170 and R1b-U106, or the phenotypic distribution of lactose tolerance emerge as comparably important, but the available data are more limited. Moderately significant positive correlations were also found with GDP per capita, health expenditure and partly with the level of urbanization that influences male stature in Western Europe. In contrast, male height correlated inversely with children's mortality and social inequality (Gini index). These results could inspire social and nutritional guidelines that would lead to the optimization of physical growth in children and maximization of the genetic potential, both at the individual and national level.