Elevated rates of horizontal gene transfer in the industrialized human microbiome.

Industrialization has impacted the human gut ecosystem, resulting in altered microbiome composition and diversity. Whether bacterial genomes may also adapt to the industrialization of their host populations remains largely unexplored. Here, we investigate the extent to which the rates and targets of horizontal gene transfer (HGT) vary across thousands of bacterial strains from 15 human populations spanning a range of industrialization. We show that HGTs have accumulated in the microbiome over recent host generations and that HGT occurs at high frequency within individuals. Comparison across human populations reveals that industrialized lifestyles are associated with higher HGT rates and that the functions of HGTs are related to the level of host industrialization. Our results suggest that gut bacteria continuously acquire new functionality based on host lifestyle and that high rates of HGT may be a recent development in human history linked to industrialization.

Ageing threatens sustainability of smallholder farming in China.

Rapid demographic ageing substantially affects socioeconomic development1-4 and presents considerable challenges for food security and agricultural sustainability5-8, which have so far not been well understood. Here, by using data from more than 15,000 rural households with crops but no livestock across China, we show that rural population ageing reduced farm size by 4% through transferring cropland ownership and land abandonment (approximately 4 million hectares) in 2019, taking the population age structure in 1990 as a benchmark. These changes led to a reduction of agricultural inputs, including chemical fertilizers, manure and machinery, which decreased agricultural output and labour productivity by 5% and 4%, respectively, further lowering farmers' income by 15%. Meanwhile, fertilizer loss increased by 3%, resulting in higher pollutant emissions to the environment. In new farming models, such as cooperative farming, farms tend to be larger and operated by younger farmers, who have a higher average education level, hence improving agricultural management. By encouraging the transition to new farming models, the negative consequences of ageing can be reversed. Agricultural input, farm size and farmer's income would grow by approximately 14%, 20% and 26%, respectively, and fertilizer loss would reduce by 4% in 2100 compared with that in 2020. This suggests that management of rural ageing will contribute to a comprehensive transformation of smallholder farming to sustainable agriculture in China.

Diminishing benefits of urban living for children and adolescents' growth and development.

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1-6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5-19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m-2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.

Increased heat risk in wet climate induced by urban humid heat.

Cities are generally warmer than their adjacent rural land, a phenomenon known as the urban heat island (UHI). Often accompanying the UHI effect is another phenomenon called the urban dry island (UDI), whereby the humidity of urban land is lower than that of the surrounding rural land1-3. The UHI exacerbates heat stress on urban residents4,5, whereas the UDI may instead provide relief because the human body can cope with hot conditions better at lower humidity through perspiration6,7. The relative balance between the UHI and the UDI-as measured by changes in the wet-bulb temperature (Tw)-is a key yet largely unknown determinant of human heat stress in urban climates. Here we show that Tw is reduced in cities in dry and moderately wet climates, where the UDI more than offsets the UHI, but increased in wet climates (summer precipitation of more than 570 millimetres). Our results arise from analysis of urban and rural weather station data across the world and calculations with an urban climate model. In wet climates, the urban daytime Tw is 0.17 ± 0.14 degrees Celsius (mean ± 1 standard deviation) higher than rural Tw in the summer, primarily because of a weaker dynamic mixing in urban air. This Tw increment is small, but because of the high background Tw in wet climates, it is enough to cause two to six extra dangerous heat-stress days per summer for urban residents under current climate conditions. The risk of extreme humid heat is projected to increase in the future, and these urban effects may further amplify the risk.

Genomic Answers for Kids: Toward more equitable access to genomic testing for rare diseases in rural populations.

Next-generation sequencing has revolutionized the speed of rare disease (RD) diagnoses. While clinical exome and genome sequencing represent an effective tool for many RD diagnoses, there is room to further improve the diagnostic odyssey of many RD patients. One recognizable intervention lies in increasing equitable access to genomic testing. Rural communities represent a significant portion of underserved and underrepresented individuals facing additional barriers to diagnosis and treatment. Primary care providers (PCPs) at local clinics, though sometimes suspicious of a potential benefit of genetic testing for their patients, have significant constraints in pursuing it themselves and rely on referrals to specialists. Yet, these referrals are typically followed by long waitlists and significant delays in clinical assessment, insurance clearance, testing, and initiation of diagnosis-informed care management. Not only is this process time intensive, but it also often requires multiple visits to urban medical centers for which distance may be a significant barrier to rural families. Therefore, providing early, "direct-to-provider" (DTP) local access to unrestrictive genomic testing is likely to help speed up diagnostic times and access to care for RD patients in rural communities. In a pilot study with a PCP clinic in rural Kansas, we observed a minimum 5.5 months shortening of time to diagnosis through the DTP exome sequencing program as compared to rural patients receiving genetic testing through the "traditional" PCP-referral-to-specialist scheme. We share our experience to encourage future partnerships beyond our center. Our efforts represent just one step in fostering greater diversity and equity in genomic studies.

Azithromycin to Reduce Mortality - An Adaptive Cluster-Randomized Trial.

BACKGROUND: Twice-yearly mass distribution of azithromycin to children is a promising intervention to reduce childhood mortality in sub-Saharan Africa. The World Health Organization recommended restricting distribution to infants 1 to 11 months of age to mitigate antimicrobial resistance, although this more limited treatment had not yet been tested. METHODS: We randomly assigned rural communities in Niger to four twice-yearly distributions of azithromycin for children 1 to 59 months of age (child azithromycin group), four twice-yearly distributions of azithromycin for infants 1 to 11 months of age and placebo for children 12 to 59 months of age (infant azithromycin group), or placebo for children 1 to 59 months of age. Census workers who were not aware of the group assignments monitored mortality twice yearly over the course of 2 years. We assessed three primary community-level mortality outcomes (deaths per 1000 person-years), each examining a different age group and pairwise group comparison. RESULTS: A total of 1273 communities were randomly assigned to the child azithromycin group (1229 were included in the analysis), 773 to the infant azithromycin group (751 included in the analysis), and 954 to the placebo group (929 included in the analysis). Among 382,586 children, 419,440 person-years and 5503 deaths were recorded. Lower mortality among children 1 to 59 months of age was observed in the child azithromycin group (11.9 deaths per 1000 person-years; 95% confidence interval [CI], 11.3 to 12.6) than in the placebo group (13.9 deaths per 1000 person-years; 95% CI, 13.0 to 14.8) (representing 14% lower mortality with azithromycin; 95% CI, 7 to 22; P<0.001). Mortality among infants 1 to 11 months of age was not significantly lower in the infant azithromycin group (22.3 deaths per 1000 person-years; 95% CI, 20.0 to 24.7) than in the placebo group (23.9 deaths per 1000 person-years; 95% CI, 21.6 to 26.2) (representing 6% lower mortality with azithromycin; 95% CI, -8 to 19). Five serious adverse events were reported: three in the placebo group, one in the infant azithromycin group, and one in the child azithromycin group. CONCLUSIONS: Azithromycin distributions to children 1 to 59 months of age significantly reduced mortality and was more effective than treatment of infants 1 to 11 months of age. Antimicrobial resistance must be monitored. (Funded by the Bill and Melinda Gates Foundation; AVENIR ClinicalTrials.gov number, NCT04224987.).

The structure and function of antagonistic ties in village social networks.

Negative or antagonistic relationships are common in human social networks, but they are less often studied than positive or friendly relationships. The existence of a capacity to have and to track antagonistic ties raises the possibility that they may serve a useful function in human groups. Here, we analyze empirical data gathered from 24,770 and 22,513 individuals in 176 rural villages in Honduras in two survey waves 2.5 y apart in order to evaluate the possible relevance of antagonistic relationships for broader network phenomena. We find that the small-world effect is more significant in a positive world with negative ties compared to an otherwise similar hypothetical positive world without them. Additionally, we observe that nodes with more negative ties tend to be located near network bridges, with lower clustering coefficients, higher betweenness centralities, and shorter average distances to other nodes in the network. Positive connections tend to have a more localized distribution, while negative connections are more globally dispersed within the networks. Analysis of the possible impact of such negative ties on dynamic processes reveals that, remarkably, negative connections can facilitate the dissemination of information (including novel information experimentally introduced into these villages) to the same degree as positive connections, and that they can also play a role in mitigating idea polarization within village networks. Antagonistic ties hold considerable importance in shaping the structure and function of social networks.

Land conflicts from overlapping claims in Brazil's rural environmental registry.

Satellite-based land use monitoring and farm-level traceability offer opportunities for targeted zero-deforestation interventions on private lands. Brazil's Rural Environmental Registry (Cadastro Ambiental Rural, or "CAR"), a land cadaster based on self-declaration of property boundaries, was created to monitor compliance with national forest laws. It has become an important enabling measure for sustainable supply chain initiatives like the Amazon Soy Moratorium. However, CAR enrollment is increasingly used to bolster illegal land claims, putting it at the heart of land grabbing dynamics. Self-declaration of properties in the CAR offers a unique situation to study land conflicts and their impact on land use decisions on a large scale. We quantified competing land claims among 846,420 registrations in the Brazilian Legal Amazon and applied a series of generalized linear mixed-effects models. We determined that CAR overlaps are more prevalent on larger registrations, in more densely settled areas, and in areas with less secure land tenure. We tested how landholders respond to land conflicts, finding significantly more deforestation and declared legal forest reserve on lands with multiple claims. CAR overlap results in an overestimation of forest reserves by up to 9.7 million hectares when considering double-counted and deforested areas of reserves, highlighting an overlooked form of Forest Code noncompliance. While the CAR continues to be used as evidence of land tenure, we conclude that the formalization of land claims through self-declarations is inadequate to decrease conflicts. CAR overlap information provides objective evidence of land conflict that authorities can leverage with field inspection to ensure peaceful occupation before issuing land titles.

How poverty is measured impacts who gets classified as impoverished.

We test whether the classification of households into poverty categories is meaningfully influenced by the poverty measurement approach that is employed. These classification techniques are widely used by governments, non-profit organizations, and development agencies for policy design and implementation. Using primary data collected in Ethiopia, Ghana, and Uganda, we find almost no agreement in how four commonly used approaches rank 16,150 households in terms of poverty status. This result holds for each country, for urban and rural households, and across the entire socio-economic distribution. Households' poverty rankings differ by an entire quartile on average. Conclusions about progress toward poverty alleviation goals may depend in large part on how poverty is measured.

Effect of a cash transfer intervention on memory decline and dementia probability in older adults in rural South Africa.

Evidence on cash transfers as a population-level intervention to support healthy cognitive aging in low-income settings is sparse. We assessed the effect of a cash transfer intervention on cognitive aging outcomes in older South African adults. We leveraged the overlap in the sampling frames of a Phase 3 randomized cash transfer trial [HIV Prevention Trial Network (HPTN) 068, 2011-2015] and an aging cohort [Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community (HAALSI), 2014-2022] in rural Mpumalanga Province, South Africa. In 2011/12, young women and their primary caregivers were randomly assigned 1:1 to receive a monthly cash transfer or control. In 2014/2015, 862 adults aged 40+ y living in trial households were enrolled in the HAALSI cohort, with cognitive data collected in three waves over 7 y. We estimated the impact of the intervention on rate of memory decline and dementia probability scores. Memory decline in the cash transfer arm was 0.03 SD units (95% CI: 0.002, 0.05) slower per year than in the control arm. Dementia probability scores were three percentage points lower in the cash transfer arm than the control arm (ß = -0.03; 95% CI: -0.05, -0.001). Effects were consistent across subgroups. A modestly sized household cash transfer delivered over a short period in mid- to later-life led to a meaningful slowing of memory decline and reduction in dementia probability 7 y later. Cash transfer programs could help stem the tide of new dementia cases in economically vulnerable populations in the coming decades.

Burden of Typhoid and Paratyphoid Fever in India.

BACKGROUND: In 2017, more than half the cases of typhoid fever worldwide were projected to have occurred in India. In the absence of contemporary population-based data, it is unclear whether declining trends of hospitalization for typhoid in India reflect increased antibiotic treatment or a true reduction in infection. METHODS: From 2017 through 2020, we conducted weekly surveillance for acute febrile illness and measured the incidence of typhoid fever (as confirmed on blood culture) in a prospective cohort of children between the ages of 6 months and 14 years at three urban sites and one rural site in India. At an additional urban site and five rural sites, we combined blood-culture testing of hospitalized patients who had a fever with survey data regarding health care use to estimate incidence in the community. RESULTS: A total of 24,062 children who were enrolled in four cohorts contributed 46,959 child-years of observation. Among these children, 299 culture-confirmed typhoid cases were recorded, with an incidence per 100,000 child-years of 576 to 1173 cases in urban sites and 35 in rural Pune. The estimated incidence of typhoid fever from hospital surveillance ranged from 12 to 1622 cases per 100,000 child-years among children between the ages of 6 months and 14 years and from 108 to 970 cases per 100,000 person-years among those who were 15 years of age or older. Salmonella enterica serovar Paratyphi was isolated from 33 children, for an overall incidence of 68 cases per 100,000 child-years after adjustment for age. CONCLUSIONS: The incidence of typhoid fever in urban India remains high, with generally lower estimates of incidence in most rural areas. (Funded by the Bill and Melinda Gates Foundation; NSSEFI Clinical Trials Registry of India number, CTRI/2017/09/009719; ISRCTN registry number, ISRCTN72938224.).

Sources of particulate-matter air pollution and its oxidative potential in Europe.

Particulate matter is a component of ambient air pollution that has been linked to millions of annual premature deaths globally1-3. Assessments of the chronic and acute effects of particulate matter on human health tend to be based on mass concentration, with particle size and composition also thought to play a part4. Oxidative potential has been suggested to be one of the many possible drivers of the acute health effects of particulate matter, but the link remains uncertain5-8. Studies investigating the particulate-matter components that manifest an oxidative activity have yielded conflicting results7. In consequence, there is still much to be learned about the sources of particulate matter that may control the oxidative potential concentration7. Here we use field observations and air-quality modelling to quantify the major primary and secondary sources of particulate matter and of oxidative potential in Europe. We find that secondary inorganic components, crustal material and secondary biogenic organic aerosols control the mass concentration of particulate matter. By contrast, oxidative potential concentration is associated mostly with anthropogenic sources, in particular with fine-mode secondary organic aerosols largely from residential biomass burning and coarse-mode metals from vehicular non-exhaust emissions. Our results suggest that mitigation strategies aimed at reducing the mass concentrations of particulate matter alone may not reduce the oxidative potential concentration. If the oxidative potential can be linked to major health impacts, it may be more effective to control specific sources of particulate matter rather than overall particulate mass.

Air pollution and suicide in rural and urban America: Evidence from wildfire smoke.

Air pollution poses well-established risks to physical health, but little is known about its effects on mental health. We study the relationship between wildfire smoke exposure and suicide risk in the United States in 2007 to 2019 using data on all deaths by suicide and satellite-based measures of wildfire smoke and ambient fine particulate matter (PM2.5) concentrations. We identify the causal effects of wildfire smoke pollution on suicide by relating year-over-year fluctuations in county-level monthly smoke exposure to fluctuations in suicide rates and compare the effects across local areas and demographic groups that differ considerably in their baseline suicide risk. In rural counties, an additional day of smoke increases monthly mean PM2.5 by 0.41 µg/m3 and suicide deaths by 0.11 per million residents, such that a 1-µg/m3 (13%) increase in monthly wildfire-derived fine particulate matter leads to 0.27 additional suicide deaths per million residents (a 2.0% increase). These effects are concentrated among demographic groups with both high baseline suicide risk and high exposure to outdoor air: men, working-age adults, non-Hispanic Whites, and adults with no college education. By contrast, we find no evidence that smoke pollution increases suicide risk among any urban demographic group. This study provides large-scale evidence that air pollution elevates the risk of suicide, disproportionately so among rural populations.

Low Genetic Impact of the Roman Occupation of Britain in Rural Communities.

The Roman period saw the empire expand across Europe and the Mediterranean, including much of what is today Great Britain. While there is written evidence of high mobility into and out of Britain for administrators, traders, and the military, the impact of imperialism on local, rural population structure, kinship, and mobility is invisible in the textual record. The extent of genetic change that occurred in Britain during the Roman military occupation remains underexplored. Here, using genome-wide data from 52 ancient individuals from eight sites in Cambridgeshire covering the period of Roman occupation, we show low levels of genetic ancestry differentiation between Romano-British sites and indications of larger populations than in the Bronze Age and Neolithic. We find no evidence of long-distance migration from elsewhere in the Empire, though we do find one case of possible temporary mobility within a family unit during the Late Romano-British period. We also show that the present-day patterns of genetic ancestry composition in Britain emerged after the Roman period.

Magnitude of urban heat islands largely explained by climate and population.

Urban heat islands (UHIs) exacerbate the risk of heat-related mortality associated with global climate change. The intensity of UHIs varies with population size and mean annual precipitation, but a unifying explanation for this variation is lacking, and there are no geographically targeted guidelines for heat mitigation. Here we analyse summertime differences between urban and rural surface temperatures (ΔTs) worldwide and find a nonlinear increase in ΔTs with precipitation that is controlled by water or energy limitations on evapotranspiration and that modulates the scaling of ΔTs with city size. We introduce a coarse-grained model that links population, background climate, and UHI intensity, and show that urban-rural differences in evapotranspiration and convection efficiency are the main determinants of warming. The direct implication of these nonlinearities is that mitigation strategies aimed at increasing green cover and albedo are more efficient in dry regions, whereas the challenge of cooling tropical cities will require innovative solutions.

New insights from uncultivated genomes of the global human gut microbiome.

The genome sequences of many species of the human gut microbiome remain unknown, largely owing to challenges in cultivating microorganisms under laboratory conditions. Here we address this problem by reconstructing 60,664 draft prokaryotic genomes from 3,810 faecal metagenomes, from geographically and phenotypically diverse humans. These genomes provide reference points for 2,058 newly identified species-level operational taxonomic units (OTUs), which represents a 50% increase over the previously known phylogenetic diversity of sequenced gut bacteria. On average, the newly identified OTUs comprise 33% of richness and 28% of species abundance per individual, and are enriched in humans from rural populations. A meta-analysis of clinical gut-microbiome studies pinpointed numerous disease associations for the newly identified OTUs, which have the potential to improve predictive models. Finally, our analysis revealed that uncultured gut species have undergone genome reduction that has resulted in the loss of certain biosynthetic pathways, which may offer clues for improving cultivation strategies in the future.

Rising rural body-mass index is the main driver of the global obesity epidemic in adults.

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities1,2. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3-6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.