Late steps of ribosome assembly in E. coli are sensitive to a severe heat stress but are assisted by the HSP70 chaperone machine†

The late stages of 30S and 50S ribosomal subunits biogenesis have been studied in a wild-type (wt) strain of Escherichia coli (MC4100) subjected to a severe heat stress (45–46°C). The 32S and 45S ribosomal particles (precursors to 50S subunits) and 21S ribosomal particles (precursors to 30S subunits) accumulate under these conditions. They are authentic precursors, not degraded or dead-end particles. The 21S particles are shown, by way of a modified 3′5′ RACE procedure, to contain 16S rRNA unprocessed, or processed at its 5′ end, and not at the 3′ end. This implies that maturation of 16S rRNA is ordered and starts at its 5′-terminus, and that the 3′-terminus is trimmed at a later step. This observation is not limited to heat stress conditions, but it also can be verified in bacteria growing at a normal temperature (30°C), supporting the idea that this is the general pathway. Assembly defects at very high temperature are partially compensated by plasmid-driven overexpression of the DnaK/DnaJ chaperones. The ribosome assembly pattern in wt bacteria under a severe heat stress is therefore reminiscent of that observed at lower temperatures in E. coli mutants lacking the chaperones DnaK or DnaJ

Globalization, North-South Industrial Location and Environmental Competition

Relying on a North-South model of economic geography, our paper attempts to discuss the management of global pollution issues such as greenhouse gas emissions. As firms are increasingly mobile, they become sensitive to differences in environmental standards across countries and subject the regulatory power of a country to the rule of competition. In this context, we first evaluate the consequences of a passive ecological dumping from the South. We find that the Northern region undergoes a phenomenon of industrial relocation with a fall in its real income. In addition, the outcomes on global pollution abatement appear ambiguous. Globalization of the world economy, by changing the location decisions of firms, can make global pollution even worse. This calls for international cooperation between the North and the South. We then turn to investigate the outcomes of a harmonization of environmental policies. Although better from an ecological point of view, this second scenario harms the South both in terms of industrial relocation and real income.Economic geography, Global pollution, Environmental competition

The Association Between Depression and Medication Non-Adherence in Type 2 Diabetes: A Population-Based Cohort Study

Background: Depression has been correlated with suboptimal adherence to antidiabetic drug (AD) treatment in many studies. However, most of them were cross-sectional and the association and directionality of this relationship has not yet been established. Purpose: To measure the association between depression and non-adherence to AD treatment. Methods: We performed a population-based cohort study using the administrative data from the Quebec health insurance board (RAMQ) among adults newly using ADs. Depression was determined using a validated algorithm. To avoid immortal time bias, we carried out a depression diagnosis-time distribution matching by assigning a random fictive date of depression to individuals without depression. Non-adherence to AD treatment (i.e. <90% of days covered by at least 1 AD) in the 1-year period following depression diagnosis (real or fictive) was the main outcome. To estimate the effect of depression on AD treatment non-adherence, we conducted a multivariate logistic regression analysis, adjusting for baseline adherence and other potential confounders. Results: Between 2000 and 2006 we identified 3106 patients with a diagnosis of depression matched to 70,633 patients without depression. Among patients with depression, 52.0% were subsequently non-adherent with their AD treatment vs. 49% of patients without depression. Patients with depression were 24% more likely to be non-adherent to their AD treatment (adjusted odds ratio=1.24, 95% confidence interval: 1.13 to 1.37). Conclusions: Results suggest that depression is an independent risk factor of non-adherence to AD treatment. Patients with type 2 diabetes might benefit from regular detection for depression and adherence-enhancing interventions

The creation of the Global Scales for Early Development (GSED) for children aged 0-3 years: Combining subject matter expert judgements with big data

Introduction With the ratification of the Sustainable Development Goals, there is an increased emphasis on early childhood development (ECD) and well-being. The WHO led Global Scales for Early Development (GSED) project aims to provide population and programmatic level measures of ECD for 0-3 years that are valid, reliable and have psychometrically stable performance across geographical, cultural and language contexts. This paper reports on the creation of two measures: (1) the GSED Short Form (GSED-SF) - a caregiver reported measure for population-evaluation - self-administered with no training required and (2) the GSED Long Form (GSED-LF) - a directly administered/observed measure for programmatic evaluation - administered by a trained professional. Methods We selected 807 psychometrically best-performing items using a Rasch measurement model from an ECD measurement databank which comprised 66 075 children assessed on 2211 items from 18 ECD measures in 32 countries. From 766 of these items, in-depth subject matter expert judgements were gathered to inform final item selection. Specifically collected were data on (1) conceptual matches between pairs of items originating from different measures, (2) developmental domain(s) measured by each item and (3) perceptions of feasibility of administration of each item in diverse contexts. Prototypes were finalised through a combination of psychometric performance evaluation and expert consensus to optimally identify items. Results We created the GSED-SF (139 items) and GSED-LF (157 items) for tablet-based and paper-based assessments, with an optimal set of items that fit the Rasch model, met subject matter expert criteria, avoided conceptual overlap, covered multiple domains of child development and were feasible to implement across diverse settings. Conclusions State-of-the-art quantitative and qualitative procedures were used to select of theoretically relevant and globally feasible items representing child development for children aged 0-3 years. GSED-SF and GSED-LF will be piloted and validated in children across diverse cultural, demographic, social and language contexts for global use

Protocol for validation of the Global Scales for Early Development (GSED) for children under 3 years of age in seven countries

Introduction Children's early development is affected by caregiving experiences, with lifelong health and well-being implications. Governments and civil societies need population-based measures to monitor children's early development and ensure that children receive the care needed to thrive. To this end, the WHO developed the Global Scales for Early Development (GSED) to measure children's early development up to 3 years of age. The GSED includes three measures for population and programmatic level measurement: (1) short form (SF) (caregiver report), (2) long form (LF) (direct administration) and (3) psychosocial form (PF) (caregiver report). The primary aim of this protocol is to validate the GSED SF and LF. Secondary aims are to create preliminary reference scores for the GSED SF and LF, validate an adaptive testing algorithm and assess the feasibility and preliminary validity of the GSED PF. Methods and analysis We will conduct the validation in seven countries (Bangladesh, Brazil, Côte d'Ivoire, Pakistan, The Netherlands, People's Republic of China, United Republic of Tanzania), varying in geography, language, culture and income through a 1-year prospective design, combining cross-sectional and longitudinal methods with 1248 children per site, stratified by age and sex. The GSED generates an innovative common metric (Developmental Score: D-score) using the Rasch model and a Development for Age Z-score (DAZ). We will evaluate six psychometric properties of the GSED SF and LF: concurrent validity, predictive validity at 6 months, convergent and discriminant validity, and test-retest and inter-rater reliability. We will evaluate measurement invariance by comparing differential item functioning and differential test functioning across sites. Ethics and dissemination This study has received ethical approval from the WHO (protocol GSED validation 004583 20.04.2020) and approval in each site. Study results will be disseminated through webinars and publications from WHO, international organisations, academic journals and conference proceedings. Registration details Open Science Framework https://osf.io/ on 19 November 2021 (DOI 10.17605/OSF.IO/KX5T7; identifier: osf-registrations-kx5t7-v1)