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Antimicrobial resistance (AMR) remains a major threat to global health. To date, tractable approaches that decipher how AMR emerges within a bacterial population remain limited. Here, we developed a framework that exploits genetic diversity from environmental bacterial populations to decode emergent phenotypes such as AMR. OmpU is a porin that can make up to 60% of the outer membrane of Vibrio cholerae , the cholera pathogen. This porin is directly associated with the emergence of toxigenic clades and confers resistance to numerous host antimicrobials. In this study, we examined naturally occurring allelic variants of OmpU in environmental V . cholerae and established associations that connected genotypic variation with phenotypic outcome. We covered the landscape of gene variability and found that the porin forms two major phylogenetic clusters with striking genetic diversity. We generated 14 isogenic mutant strains, each encoding a unique ompU allele, and found that divergent genotypes lead to convergent antimicrobial resistance profiles. We identified and characterized functional domains in OmpU unique to variants conferring AMR-associated phenotypes. Specifically, we identified four conserved domains that are linked with resistance to bile and host-derived antimicrobial peptides. Mutant strains for these domains exhibit differential susceptibility patterns to these and other antimicrobials. Interestingly, a mutant strain in which we exchanged the four domains of the clinical allele for those of a sensitive strain exhibits a resistance profile closer to a porin deletion mutant. Finally, using phenotypic microarrays, we uncovered novel functions of OmpU and their connection with allelic variability. Our findings highlight the suitability of our approach towards dissecting the specific protein domains associated with the emergence of AMR and can be naturally extended to other bacterial pathogens and biological processes.

PurposeInstitutional environment plays a crucial role in determining the nature of entrepreneurship that prevails in an economy. In this paper, the authors address how business, labour and credit regulations contribute differently to both the overall prevalence of opportunity-driven entrepreneurship (ODE) and its gender gap in high-income and emerging economies.Design/methodology/approachOn the basis of an unbalanced panel of 41 countries over the period 2005–2016, the authors estimate system generalised method of moment models. The authors also perform an ordinary least square analysis to address gender differences in ODE.FindingsThe authors find that higher credit market liberalisation is especially associated with more entrepreneurship by opportunity. Nevertheless, while credit market regulation stands out as a key element to promote opportunity-based entrepreneurship in both high-income and emerging countries, in the emerging world business regulation is also largely related to the prevalence of opportunity entrepreneurship. In terms of gender gap, business and labour market freedom seem to exert an equalising effect on the divide in entrepreneurship by opportunity, specifically in emerging economies.Originality/valueFindings allow the identification of regulatory policy reform priorities to enhance the prevalence of ODE depending on the level of a country's development. They also identify which specific areas of economic regulation would speed up closing the gender gap in opportunity entrepreneurship.

This paper assesses the effectiveness of social benefit programs on children who had prior experience with poverty across 27 European countries in the years following the Great Recession (2012–2015). Even though social benefit functions might contribute to alleviating child poverty, our findings highlight that child poverty differs not only across social benefit functions, but also between children with and without previous experience in poverty. While living in a country with comparatively high family/children’s benefits is associated with lower child poverty risk, these benefits do not significantly prevent children from being poor when they have been in poverty in the past year. By contrast, old-age/survivor benefits appear to be strongly associated with a lower risk of poverty for children with previous experience in poverty. This is particularly noticeable in multigenerational households, especially in countries that provide limited support for families with children and allocate significant expenditure to pension benefits. This finding remains consistent even when using lower poverty thresholds.

This research examines the extent to which labor regulatory context matters for entrepreneurial activity under a gender perspective, using institutional economics and feminist theories as the analytical framework. We conduct a panel data analysis for 86 countries during the period 2004–2018 by differentiating between high-income and developing economies. Our findings highlight that while the links between labor regulation and entrepreneurial activity seem negligible in high-income economies, in developing economies labor flexibility is closely associated with female entrepreneurship. However, unlike the market-oriented view on the positive association between labor market flexibility and entrepreneurship, our results point out that in these economies more flexible labor regulation is related to lower early-stage female entrepreneurial activity, even though this relationship tends to vanish as the level of economic development of the country increases. This study contributes theoretically, helping to advance the analysis of gender differences in entrepreneurial activity from an institutional approach, and practically, providing evidence to policy makers on possible gender differences in the application of country-level labor market regulation in terms of entrepreneurial activity.Plain English SummaryOur analysis reveals that the application of labor regulation, apparently formulated in a gender-neutral manner, might lead to gender differences in entrepreneurial activity, especially in developing countries. We find that the link between labor market regulation and entrepreneurship tend to weaken for men and women as the country’s level of economic development increases, becoming negligible in high-income countries. However, in developing countries more flexible labor regulation is closely related to lower female early-stage entrepreneurial activity. This is because women’s greater opportunity costs and risk aversion, along with gender biases that usually characterize labor markets in numerous developing economies, might prevent them from taking advantage of their capabilities and opportunities for new ventures. Consequently, improving labor regulation in these countries in aspects such as minimum wages, laws inhibiting layoffs, severity requirements, and restraints on hiring and hours worked might be particularly advisable in terms of female entrepreneurship, rather than the traditional prescription of increasing labor flexibility suggested by the liberal paradigm.

Background Sialic acids comprise a family of nine-carbon amino sugars that are prevalent in mucus rich environments. Sialic acids from the human host are used by a number of pathogens as an energy source. Here we explore the evolution of the genes involved in the catabolism of sialic acid. Results The cluster of genes encoding the enzymes N -acetylneuraminate lyase (NanA), epimerase (NanE), and kinase (NanK), necessary for the catabolism of sialic acid (the Nan cluster), are confined 46 bacterial species, 42 of which colonize mammals, 33 as pathogens and 9 as gut commensals. We found a putative sialic acid transporter associated with the Nan cluster in most species. We reconstructed the phylogenetic history of the NanA, NanE, and NanK proteins from the 46 species and compared them to the species tree based on 16S rRNA. Within the NanA phylogeny, Gram-negative and Gram-positive bacteria do not form distinct clades. NanA from Yersinia and Vibrio species was most closely related to the NanA clade from eukaryotes. To examine this further, we reconstructed the phylogeny of all NanA homologues in the databases. In this analysis of 83 NanA sequences, Bacteroidetes, a human commensal group formed a distinct clade with Verrucomicrobia, and branched with the Eukaryotes and the Yersinia/Vibrio clades. We speculate that pathogens such as V. cholerae may have acquired NanA from a commensal aiding their colonization of the human gut. Both the NanE and NanK phylogenies more closely represented the species tree but numerous incidences of incongruence are noted. We confirmed the predicted function of the sialic acid catabolism cluster in members the major intestinal pathogens Salmonella enterica, Vibrio cholerae, V. vulnificus, Yersinia enterocolitica and Y. pestis . Conclusion The Nan cluster among bacteria is confined to human pathogens and commensals conferring them the ability to utilize a ubiquitous carbon source in mucus rich surfaces of the human body. The Nan region shows a mosaic evolution with NanA from Bacteroidetes, Vibrio and Yersinia branching closely together with NanA from eukaryotes.

ObjectiveTo identify individual and initial prescription-related factors associated with an increased risk for opioid-related misuse, poisoning and dependence (MPD) in patients with non-cancer pain.MethodsCohort study linking several databases covering 5 million inhabitants of the region of Valencia, Spain, including all adults initiating prescription opioids in the period 2012–2018. To ascertain the association between the characteristics of the initial prescription choice and the risk of opioid MPD, we used shared frailty Cox regression models. We additionally considered death as a competing risk in sensitivity analyses.Results958 019 patients initiated opioid prescription from 2012 to 2018, of which 0.13% experienced MPD. Most patients were prescribed tramadol as initial opioid (76.7%) followed by codeine (16.3%), long-acting opioids (6.7%), short-acting opioids (0.2%) and ultrafast opioids (0.1%). Initiation with ultrafast (HR 7.2; 95% CI 4.1 to 12.6), short-acting (HR 4.8; 95% CI 2.3 to 10.2) and long-acting opioids (HR 1.5; 95% CI 1.2 to 1.9) were associated with a higher risk of MPD when compared with tramadol. Initial prescriptions covering 4–7 days (HR 1.3; 95% CI 1.0 to 1.8), 8–14 days (HR 1.4; 95% CI 1.0 to 1.9), 15–30 days (HR 1.7; 95% CI 1.2 to 2.3) and more than one a month (HR 1.8; 95% CI 1.3 to 2.5) were associated with more MPD risk than initial prescriptions for 1–3 days. Treatments with >120 daily morphine milligram equivalents (MME) increased MPD risk (vs <50 MME, HR 1.6; 95% CI 1.1 to 2.2). Main individual factors associated with increased risk of MPD risk were male sex (HR 2.4; 95% CI 2.1 to 2.7), younger age (when compared with patients aged 18–44 years, patients aged 45–64 years, HR 0.4; 95% CI 0.4 to 0.5; patients aged 65–74 years, HR 0.4; 95% CI 0.3 to 0.5 and patients aged 75 years old and over, HR 0.7; 95% CI 0.6 to 0.8), lack of economic resources (2.1; 95% CI 1.8 to 2.5) and registered misuse of alcohol (2.9; 95% CI 2.4 to 3.5). Sensitivity analyses yielded overall comparable results.ConclusionsOur study identifies riskier patterns of opioid prescription initiation for non-cancer indications, as well as patient subgroups with higher risk of misuse, poisoning and dependence.

Printing functional devices on flexible substrates requires printing of high conductivity metallic patterns. To prevent deformation and damage of the polymeric substrate, the processing (printing) and post-processing (annealing) temperature of the metal patterns must be lower than the glass transition temperature of the substrate. Here, a hybrid process including deposition of a sacrificial blanket thin film, followed by room environment nozzle-based electrodeposition, and subsequent etching of the blanket film is demonstrated to print pure and nanocrystalline metallic (Ni and Cu) patterns on flexible substrates (PI and PET). Microscopy and spectroscopy showed that the printed metal is nanocrystalline, solid with no porosity and with low impurities. Electrical resistivity close to the bulk (~2-time) was obtained without any thermal annealing. Mechanical characterization confirmed excellent cyclic strength of the deposited metal, with limited degradation under high cyclic flexure. Several devices including radio frequency identification (RFID) tag, heater, strain gauge, and temperature sensor are demonstrated.

This paper provides an analytical framework for the study of spatial income dynamics using the classical measures of σ -convergence (reduction in dispersion) and β -convergence (poor areas grow more quickly than rich ones) linked by a re-ranking metric and reinterpreted based on the ‘leave no one behind’ principle. Our approach allows identifying the contribution of each territorial unit to each of the three facets of distributional change ( σ -convergence, β -convergence, and re-ranking), as well as gauging the part of each component of distributional change that corresponds to geographically neighbouring and non-neighbouring units. We illustrate our proposal by examining convergence across the census tracts of Malaga – the sixth most populated city of Spain – before and after the COVID-19 pandemic. We find that while income convergence across Malaga’s census tracts tended to improve over the period 2015–2019, this process was interrupted during the first year of the pandemic, affecting some specific census tracts. We examine our outcomes by grouping the results into deciles and districts made up of specific census tracts. Finally, we analyse the impact of neighbours on regional convergence and each of its components. This spatial decomposition highlights the crucial role of the spatial component in the convergence process.

Physical exercise is known to be beneficial for breast cancer survivors (BCS). However, avoiding nonfunctional overreaching is crucial in this population, as they are in physiological dysregulation. These factors could decrease their exercise capacity or facilitate nonfunctional overreaching, which can increase their risk of additional morbidities and even all-cause mortality. The focus of this study is to evaluate the reliability and validity of the ATOPE+ mHealth system to estimate autonomic balance and specific wellness parameters associated with BCS’ perceived load, thereby informing nonlinear prescriptions in individualized physical exercise programs for BCS.Twenty-two BCS were included in the reliability and validity analysis. Measures were taken for four days, including morning autonomic balance by heart rate variability, self-reported perception of recovery from exercise, sleep satisfaction, emotional distress and fatigue after exertion. Measures were taken utilizing the ATOPE+ mHealth system application. The results of these measures were compared with criterion instruments to assess validity.The reliability results indicated that the intraclass correlation coefficient (ICC) showed an excellent correlation for recovery (0.93; 95% CI 0.85–0.96) and distress (0.94, 95% CI 0.89–0.97) as well as good correlation for the natural logarithm of the mean square root differences of the standard deviation (LnRMSSD) (0.87; 95% CI 0.74–0.94). Sleep satisfaction also showed an excellent correlation with a weighted kappa of 0.83. The validity results showed no significant differences, except for fatigue. ATOPE+ is reliable and valid for remotely assessing autonomic balance, perception of recovery, sleep satisfaction and emotional distress in BCS; however, it is not for fatigue. This highlights that ATOPE+ could be an easy and efficient system used to assess readiness in BCS, and could help to improve their health by supporting the prescription of optimal and safe physical exercise. Trial registration NCT03787966 ClinicalTrials.gov, December 2019 [ATOPE project]. https://clinicaltrials.gov/ct2/show/NCT03787966 .

One of the most challenging gender gaps in the Global South remains in the economic sphere. This paper examines how public institutions affect the gender gap in economic participation and opportunities in 74 developing and emerging countries during the period 2006–2016. We find that the public institutional environment is closely related to the economic gender gap. Specifically, the protection of property rights and guaranteeing security seem to be two key factors associated to lower economic gender inequality. Nevertheless, public institutions do not matter equally throughout economically backward countries. Whereas in emerging countries, particularly in Latin America and the Caribbean, a broad variety of institutional aspects, including undue influence on judicial and government decisions, are closely related to the economic gender gap, in low-income developing countries, such as Sub-Saharan countries, the problems of ethics and corruption stand out as a particularly remarkable element against economic gender equality. Some significant policy implications are derived from our findings regarding the potential of public institution reforms to reduce the economic gender gap.