Objective To disseminate the portable sequencer MinION in developing countries for the main purpose of battling infectious diseases, we found a consortium called Global Research Alliance in Infectious Diseases (GRAID). By holding and inviting researchers both from developed and developing countries, we aim to train the participants with MinION’s operations and foster a collaboration in infectious diseases researches. As a real-life example in which resources are limited, we describe here a result from a training course, a metagenomics analysis from two blood samples collected from a routine cattle surveillance in Kulan Progo District, Yogyakarta Province, Indonesia in 2019. Results One of the samples was successfully sequenced with enough sequencing yield for further analysis. After depleting the reads mapped to host DNA, the remaining reads were shown to map to Theileria orientalis using BLAST and OneCodex. Although the reads were also mapped to Clostridium botulinum, those were found to be artifacts derived from the cow genome. An effort to construct a consensus sequence was successful using a reference-based approach with Pomoxis. Hence, we concluded that the asymptomatic cow might be infected with T. orientalis and showed the usefulness of sequencing technology, specifically the MinION platform, in a developing country.
Background Unbalanced iron homeostasis in pregnancy is associated with an increased risk of adverse birth and childhood health outcomes. DNA methylation has been suggested as a potential underlying mechanism linking environmental exposures such as micronutrient status during pregnancy with offspring health. We performed a meta-analysis on the association of maternal early-pregnancy serum ferritin concentrations, as a marker of body iron stores, and cord blood DNA methylation. We included 1286 mother–newborn pairs from two population-based prospective cohorts. Serum ferritin concentrations were measured in early pregnancy. DNA methylation was measured with the Infinium HumanMethylation450 BeadChip (Illumina). We examined epigenome-wide associations of maternal early-pregnancy serum ferritin and cord blood DNA methylation using robust linear regression analyses, with adjustment for confounders and performed fixed-effects meta-analyses. We additionally examined whether associations of any CpGs identified in cord blood persisted in the peripheral blood of older children and explored associations with other markers of maternal iron status. We also examined whether similar findings were present in the association of cord blood serum ferritin concentrations with cord blood DNA methylation. Results Maternal early-pregnancy serum ferritin concentrations were inversely associated with DNA methylation at two CpGs (cg02806645 and cg06322988) in PRR23A and one CpG (cg04468817) in PRSS22 . Associations at two of these CpG sites persisted at each of the follow-up time points in childhood. Cord blood serum ferritin concentrations were not associated with cord blood DNA methylation levels at the three identified CpGs. Conclusion Maternal early-pregnancy serum ferritin concentrations were associated with lower cord blood DNA methylation levels at three CpGs and these associations partly persisted in older children. Further studies are needed to uncover the role of these CpGs in the underlying mechanisms of the associations of maternal iron status and offspring health outcomes.
The relevance of the human oral microbiome to our understanding of human health has grown in recent years as microbiome studies continue to develop. Given the links of the oral cavity with the digestive, respiratory and circulatory systems, the composition of the oral microbiome is relevant beyond just oral health, impacting systemic processes across the body. However, we still have a very limited understanding about intrinsic and extrinsic factors that shape the composition of the healthy oral microbiome. Here, we followed a citizen-science approach to assess the relative impact on the oral microbiome of selected biological, social, and lifestyle factors in 1648 Spanish individuals. We found that the oral microbiome changes across age, with middle ages showing a more homogeneous composition, and older ages showing more diverse microbiomes with increased representation of typically low abundance taxa. By measuring differences within and between groups of individuals sharing a given parameter, we were able to assess the relative impact of different factors in driving specific microbial compositions. Chronic health disorders present in the analyzed population were the most impactful factors, followed by smoking and the presence of yeasts in the oral cavity. Finally, we corroborate findings in the literature that relatives tend to have more similar oral microbiomes, and show for the first time a similar effect for classmates. Multiple intrinsic and extrinsic factors jointly shape the oral microbiome. Comparative analysis of metabarcoding data from a large sample set allows us to disentangle the individual effects.
Background Sleep is important for healthy functioning in children. Numerous genetic and environmental factors, from conception onwards, may influence this phenotype. Epigenetic mechanisms such as DNA methylation have been proposed to underlie variation in sleep or may be an early-life marker of sleep disturbances. We examined if DNA methylation at birth or in school age is associated with parent-reported and actigraphy-estimated sleep outcomes in children. Methods We meta-analysed epigenome-wide association study results. DNA methylation was measured from cord blood at birth in 11 cohorts and from peripheral blood in children (4–13 years) in 8 cohorts. Outcomes included parent-reported sleep duration, sleep initiation and fragmentation problems, and actigraphy-estimated sleep duration, sleep onset latency and wake-after-sleep-onset duration. Results We found no associations between DNA methylation at birth and parent-reported sleep duration (n = 3658), initiation problems (n = 2504), or fragmentation (n = 1681) (p values above cut-off 4.0 × 10–8). Lower methylation at cg24815001 and cg02753354 at birth was associated with longer actigraphy-estimated sleep duration (p = 3.31 × 10–8, n = 577) and sleep onset latency (p = 8.8 × 10–9, n = 580), respectively. DNA methylation in childhood was not cross-sectionally associated with any sleep outcomes (n = 716–2539). Conclusion DNA methylation, at birth or in childhood, was not associated with parent-reported sleep. Associations observed with objectively measured sleep outcomes could be studied further if additional data sets become available.
Designed to set limits to air pollutant emissions, EU Directive 2008/50/EG has pushed city administrations to strengthen their commitment to environmental protection with mixed results. However, the effectiveness of these policies remains suboptimal. Within this context, this paper provides original empirical evidence on the naturemand evolution of the debate over air pollution in the EU that helps readers understand how the interplay among discourse coalitions across levels of governance relates to the implementation of air pollution directives in Europe. To provide this evidence, we apply the discourse‑coalition framework to a multi‑level governance context by comparing debates over air pollution and examining their evolution in different contexts through the use of discourse network analysis. Our results show that the debate in the EU institutions is largely dominated by pro‑environmental coalitions, whereas discussions in Stuttgart and Berlin show different degrees of permeability to such arguments. Hence, the relative prominence of certain actors and levels of governance in the local discourse helps explain the extent to which debates at the local level align with the arguments put forward by the EU institutions. For their part, governmental organizations have a tendency to act as bridges between discourse coalitions. This novel empirical evidence provides clues that help make sense of the varying levels of implementation of EU air pollution directives at the local level. In this regard, the ability of supranational and national bodies to align their discourse with those of local organizations might facilitate a common understanding and the successful implementation of EU policies. Policymakers aiming to improve air quality at the local level may want to consider engaging actively with this debate by reinforcing the arguments of pro‑environmental coalitions. They may also want to make a special effort to ensure that the messages conveyed to supranational and national bodies are also effectively conveyed to lower levels of governance.
Energy poverty (EP) is becoming an increasingly important problem in the urban contexts of southern Europe. In Barcelona, EP indicators are higher than those of the European Union and are strongly associated with poor health status and high use of health services and medication, becoming a major public health problem. EP is unevenly distributed in the population of Barcelona, according to axes of social stratification. However, its geographic distribution at the small-area level remains unknown because it cannot be directly estimated with the available information sources and commonly used methods. Therefore, the aim of this study was to analyze geographical inequalities in EP in Barcelona by estimating reliable small-area EP indicators and a composite indicator (index). We used a novel method that allowed us to obtain 6 EP indicators for the 73 Barcelona neighborhoods and an EP index from a principal component analysis of these indicators. We found major geographical inequalities in the distribution of EP in Barcelona. Many neighborhoods had significantly higher EP than the city average, and these areas made up 3 well-defined spatial clusters. Therefore, the estimated small-area indicators and index allowed identification of the most affected neighborhoods. These results indicate the need to prioritize these areas for local interventions to alleviate EP, and could also be used for policy making.
In 1980, a few years after its democratization process, Spain raised the minimum working age from 14 to 16, while the compulsory education age remained at 14. This reform changed the within-cohort incentives to remain in the educational system. We use a difference-in-differences approach, where our treated and control individuals only differ in their month of birth, to analyze the gender asymmetries in mortality generated by this change. The reform decreased mortality at ages 14–29 among men by 6.4% and women by 8.9%, mainly from a reduction in deaths due to traffic accidents. However, the reform also increased mortality for women ages 30–45 by 7%. This is driven by increases in HIV mortality, as well as by diseases related to the nervous and circulatory systems. We show that women’s health habits deteriorated as a consequence of the reform, while this was not the case for men. The gender differences in the impact of the reform on smoking and drinking should be understood in the context of the gender equalization process that affected women were experiencing when the reform took place. All in all, these patterns help explain the narrowing age gap in life expectancy between women and men in many developed countries while, at the same time, they provide important policy implications for middle-income countries that are undergoing those gender equalization processes right now.
China implemented the first phase of its National Healthy Cities pilot program from 2016-20. Along with related urban health governmental initiatives, the program has helped put health on the agenda of local governments while raising public awareness. Healthy City actions taken at the municipal scale also prepared cities to deal with the COVID-19 pandemic. However, after intermittent trials spanning the past two decades, the Healthy Cities initiative in China has reached a crucial juncture. It risks becoming inconsequential given its overlap with other health promotion efforts, changing public health priorities in response to the pandemic, and the partial adoption of the Healthy Cities approach advanced by the World Health Organization (WHO). We recommend aligning the Healthy Cities initiative in China with strategic national and global level agendas such as Healthy China 2030 and the Sustainable Development Goals (SDGs) by providing an integrative governance framework to facilitate a coherent intersectoral program to systemically improve population health. Achieving this alignment will require leveraging the full spectrum of best practices in Healthy Cities actions and expanding assessment efforts. Funding Tsinghua-Toyota Joint Research Fund “Healthy city systems for smart cities” program.
Introduction High levels of cotinine in non-smokers indicate passive exposure to tobacco smoke. This study aims to evaluate variations in salivary cotinine cut-offs to discriminate smokers and non-smokers before and after the implementation of smoke-free legislation (Law 28/2005 and Law 42/2010) in a sample of the adult population of Barcelona, Spain. Methods This longitudinal study analyzes salivary cotinine samples and self-reported information from a representative sample (n = 676) of the adult population from Barcelona before and after the approval of smoke-free legislation. We calculated the receiver operating characteristic (ROC) curves, to obtain optimal cotinine cut-off points to discriminate between smokers and non-smokers overall, by sex and age, and their corresponding sensitivity, specificity, and area under the curve. We used linear mixed-effects models, with individuals as random effects, to model the percentage change of cotinine concentration before and after the implementation of both laws. Results The mean salivary cotinine concentration was significantly lower post-2010 law (−85.8%, p < 0.001). The ROC curves determined that the optimal cotinine cut-off points for discriminating non-smokers and smokers were 10.8 ng/mL (pre-2005 law) and 5.6 ng/mL (post-2010 law), with a post-2010 law sensitivity of 92.6%, specificity of 98.4%, and an area under the curve of 97.0%. The post-2010 law cotinine cut-off points were 5.6 ng/mL for males and 1.9 ng/mL for females. Conclusion The implementation of Spanish smoke-free legislation was effective in reducing secondhand smoke exposure and, therefore, also in reducing the cut-off point for salivary cotinine concentration. This value should be used to better assess tobacco smoke exposure in this population.
Trace elements such as cadmium, arsenic, zinc or selenium increase or decrease risk of a wide range of human diseases. Their levels in toenails may provide a measure of mid-term intake of trace elements for studies in humans. However, in biologically and clinically aggressive diseases as pancreatic cancer, the progression of the disease could modify such concentrations and produce reverse causation bias. The aim was to analyze the influence of specific time intervals between several clinical events and the collection of toenails upon concentrations of trace elements in patients with pancreatic cancer. Subjects were 118 incident cases of pancreatic adenocarcinoma prospectively recruited in eastern Spain. Toenails were collected at cancer diagnosis, and soon thereafter interviews were conducted. Information on cancer signs and symptoms was obtained from medical records and patient interviews. Levels of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. General linear models adjusting for potential confounders were applied to analyze relations between log concentrations of trace elements and the time intervals, including the interval from first symptom of cancer to toenail collection (iST). Toenail concentrations of the 12 trace elements were weakly or not influenced by the progression of the disease or the diagnostic procedures. Concentrations of aluminum were slightly higher in subjects with a longer iST (age, sex and stage adjusted geometric means: 11.44 vs. 7.75 µg/g for iST > 120 days vs. ≤ 40 days). There was a weak inverse relation of iST with concentrations of zinc and selenium (maximum differences of about 20 and 0.08 µg/g, respectively). Conclusions: concentrations of the trace elements were weakly or not influenced by the development of the disease before toenail collection. Only concentrations of aluminum increased slightly with increasing iST, whereas levels of zinc and selenium decreased weakly. Even in an aggressive disease as pancreatic cancer, toenail concentrations of trace elements may provide a valid measure of mid-term intake of trace elements, unaffected by clinical events and disease progression. Supplementary information: The online version contains supplementary material available at 10.1007/s12403-021-00436-2.
The consonant bias is evidenced by a greater reliance on consonants over vowels in lexical processing. Although attested during adulthood for most Roman and Germanic languages (e.g., French, Italian, English, Dutch), evidence on its development suggests that the native input modulates its trajectory. French and Italian learners exhibit an early switch from a higher reliance on vowels at 5 and 6 months of age to a consonant bias by the end of the first year. This study investigated the developmental trajectory of this bias in a third Romance language unexplored so far—Spanish. In a central visual fixation procedure, infants aged 5, 8½, and 12 months were tested in a word recognition task. In Experiment 1, infants preferred listening to frequent words (e.g., leche, milk) over nonwords (e.g., machi) at all ages. Experiment 2 assessed infants’ listening times to consonant and vowel alterations of the words used in Experiment 1. Here, 5-month-olds preferred listening to consonant alterations, whereas 12-month-olds preferred listening to vowel alterations, suggesting that 5-month-olds’ recognition performance was more affected by a vowel alteration (e.g., leche →lache), whereas 12-month-olds’ recognition performance was more affected by a consonant alteration (e.g., leche →keche). These findings replicate previous findings in Italian and French and generalize them to a third Romance language (Spanish). As such, they support the idea that specific factors common to Romance languages might be driving an early consonant bias in lexical processing.
The most economically important centellosides, madecassoside and asiaticoside, are produced in very low amounts in Centella asiatica (L.) Urban roots. With the aim of overcoming this limitation, in this work we compared the effect of different elicitors on centelloside production in hairy root cultures established by Agrobacterium rhizogenes infection. Additionally, elicitor-induced changes in the expression of key biosynthetic genes were studied to shed light on the regulation of the triterpene metabolic pathway. The elicitors tested were coronatine and methyl jasmonate, added separately or together, and salicylic acid. The content of the four main centellosides (asiaticoside, madecassoside, asiatic acid and madecassic acid) was determined by HPLC/DAD, and the expression level of genes after elicitation was analyzed by real-time quantitative polymerase chain reaction. The greatest increase in the production of centellosides, especially madecassoside, was achieved with coronatine, applied alone or with methyl jasmonate. This treatment also enhanced the expression of the target genes, particularly at the start of elicitation. By far the most highly expressed were those involved in oxidations, indicating that the tested elicitors did not act specifically on key genes in the centelloside biosynthetic pathway. These results support that hairy roots are a promising biotechnological platform for improved centelloside production and that this approach warrants further research.
Purpose of Review Maternal tobacco smoking during pregnancy is of public health concern, and understanding the biological mechanisms can help to promote smoking cessation campaigns. This non-systematic review focuses on the effects of maternal smoking during pregnancy on offspring’s epigenome, consistent in chemical modifications of the genome that regulate gene expression. Recent Findings Recent meta-analyses of epigenome-wide association studies have shown that maternal smoking during pregnancy is consistently associated with offspring’s DNA methylation changes, both in the placenta and blood. These studies indicate that effects on blood DNA methylation can persist for years, and that the longer the duration of the exposure and the higher the dose, the larger the effects. Hence, DNA methylation scores have been developed to estimate past exposure to maternal smoking during pregnancy as biomarkers. Summary There is robust evidence for DNA methylation alterations associated with maternal smoking during pregnancy; however, the role of sex, ethnicity, and genetic background needs further exploration. Moreover, there are no conclusive studies about exposure to low doses or during the preconception period. Similarly, studies on tissues other than the placenta and blood are scarce, and cell-type specificity within tissues needs further investigation. In addition, biological interpretation of DNA methylation findings requires multi-omics data, poorly available in epidemiological settings. Finally, although several mediation analyses link DNA methylation changes with health outcomes, they do not allow causal inference. For this, a combination of data from multiple study designs will be essential in the future to better address this topic.
Lexical ambiguity is pervasive in language, and often systematic. For instance, the Spanish word dedo can refer to a toe or a finger, that is, these two meanings colexify in Spanish; and they do so as well in over one hundred other languages. Previous work shows that related meanings are more likely to colexify. This is attributed to cognitive pressure towards simplicity in language, as it makes lexicons easier to learn and use. The present study examines the interplay between this pressure and the competing pressure for languages to support accurate information transfer. We hypothesize that colexification follows a Goldilocks principle that balances the two pressures: meanings are more likely to attach to the same word when they are related to an optimal degree—neither too much, nor too little. We find support for this principle in data from over 1200 languages and 1400 meanings. Our results thus suggest that universal forces shape the lexicons of natural languages. More broadly, they contribute to the growing body of evidence suggesting that languages evolve to strike a balance between competing functional and cognitive pressures.
How should policymakers respond to the risk of technological unemployment that automation brings? First, I develop a procedure for answering this question that consults, rather than usurps, individuals’ own attitudes and ambitions towards that risk. I call this the insurance argument. A distinctive virtue of this view is that it dispenses with the need to appeal to a class of controversial reasons about the value of employment, and so is consistent with the demands of liberal political morality. Second, I appeal to the insurance argument to show that governments ought not simply to provide those who are displaced by machines with unemployment benefits. Instead, it must offer re-training programmes, as well as enact more general macroeconomic policies that create new opportunities for employment. My contribution is important not only because it helps us to resolve a series of urgent policy disputes—disputes that have been discussed extensively by labour market economists and policymakers, but less so by political philosophers—but also because my analysis sheds light on more general philosophical controversies relating to risk.
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