The locus coeruleus-noradrenergic (LC-NA) neuromodulatory system has been implicated in a broad array of cognitive processes, yet scope for investigating this system's function in humans is currently limited by an absence of reliable non-invasive measures of LC activity. Although pupil diameter has been employed as a proxy measure of LC activity in numerous studies, empirical evidence for a relationship between the two is lacking. In the present study, we sought to rigorously probe the relationship between pupil diameter and BOLD activity localized to the human LC. Simultaneous pupillometry and fMRI revealed a relationship between continuous pupil diameter and BOLD activity in a dorsal pontine cluster overlapping with the LC, as localized via neuromelanin-sensitive structural imaging and an LC atlas. This relationship was present both at rest and during performance of a two-stimulus oddball task, with and without spatial smoothing of the fMRI data, and survived retrospective image correction for physiological noise. Furthermore, the spatial extent of this pupil/LC relationship guided a volume-of-interest analysis in which we provide the first demonstration in humans of a fundamental characteristic of animal LC activity: phasic modulation by oddball stimulus relevance. Taken together, these findings highlight the potential for utilizing pupil diameter to achieve a more comprehensive understanding of the role of the LC-NA system in human cognition.

We present evidence from the first large-scale randomized-controlled trial of a land formalization program. We examine the link between land demarcation and investment in rural Benin in light of a model of agricultural production under insecure tenure. The demarcation process involved communities in the mapping and attribution of land rights; cornerstones marked parcel boundaries and offered lasting landmarks. The tenure security improvement through demarcation induces a 23 to 43 percent shift toward long-term investment on treated parcels. We explore gender and parcel location as relevant dimensions of heterogeneity. We find that female-managed landholdings in treated villages are more likely to be left fallow-an important soil fertility investment. Women respond to an exogenous tenure security change by shifting investment away from relatively secure, demarcated land and toward less secure land outside the village to guard those parcels.

The success of cell‐based therapies to restore joint cartilage requires an optimal source of reparative progenitor cells and tight control of their differentiation into a permanent cartilage phenotype. Bone morphogenetic protein 2 (BMP‐2) has been extensively shown to promote mesenchymal cell differentiation into chondrocytes in vitro and in vivo. Conversely, developmental studies have demonstrated decreased chondrocyte maturation by Wingless‐Type MMTV Integration Site Family, Member 5A (Wnt5a). Thus, we hypothesized that treatment of human embryonic stem cell (hESC)‐derived chondroprogenitors with BMP‐2 followed by Wnt5a may control the maturational progression of these cells into a hyaline‐like chondrocyte phenotype. We examined the effects of sustained exposure of hESC‐derived mesenchymal‐like progenitors to recombinant Wnt5a or BMP‐2 in vitro. Our data indicate that BMP‐2 promoted a strong chondrogenic response leading to terminal maturation, whereas recombinant Wnt5a induced a mild chondrogenic response without promoting hypertrophy. Moreover, Wnt5a suppressed BMP‐2‐mediated chondrocyte maturation, preventing the formation of fibrocartilaginous tissue in high‐density cultures treated sequentially with BMP‐2 and Wnt5a. Implantation of scaffoldless pellets of hESC‐derived chondroprogenitors pretreated with BMP‐2 followed by Wnt5a into rat chondral defects induced an articular‐like phenotype in vivo. Together, the data establish a novel role for Wnt5a in controlling the progression from multipotency into an articular‐like cartilage phenotype in vitro and in vivo. Stem Cells Translational Medicine 2017;6:40–50

Publié par l'Équipe d'assistance à la recherche La série des documents de travail consacrés à la recherche sur les politiques diffuse les conclusions des travaux en cours pour encourager l'échange d'idées sur les questions de développement. Elle a pour objectif de publier les résultats rapidement, même si la présentation n'en est pas définitive. Les études portent le nom de leurs auteurs qui doivent donc être cités. Les rapports portent le nom de leurs auteurs et doivent être cités en conséquence. Les observations, interprétations et conclusions présentées ici n'engagent que leurs auteurs et ne sauraient être attribuées à la Banque internationale pour la reconstruction et le développement/Banque mondiale et ses organisations affiliées, à des membres du Conseil des Administrateurs, ni aux pays qu'ils représentent Document de travail 7435 consacré à la recherche sur les politiques Ce rapport a été produit par la Région Afrique et le Groupe de recherche de Balnque Mondiale. Il s'inscrit dans le cadre d'une initiative de plus grande envergure lancée par la Banque mondiale pour donner libre accès à ses travaux de recherche et contribuer aux discussions consacrées aux politiques de développement dans le monde entier. Les documents de travail consacrés à la recherche sur les politiques sont également affichés sur le web à http://econ.worldbank.org. Il est également possible de contacter les auteurs aux adresses suivantes :

Background: Depression and poor mental health are known to be negative predictors of patient-reported outcomes after total joint arthroplasty. Although previous studies have examined these risk factors in isolation to each other, they are, in reality, closely related, and yet each represents a different aspect of one’s psychological well-being. The objective of this study was to investigate the association between depression and patient-reported outcomes, taking into account patients’ baseline mental health. Methods: Our prospective, institutional joint registry was queried for patients who had undergone primary elective total joint arthroplasty and had a minimum follow-up of 1 year. Baseline mental health was measured by the Short Form-12 Mental Component Summary (SF-12 MCS). Four cohorts were analyzed on the basis of the presence or absence of depression and patients’ SF-12 MCS scores at the time of the surgical procedure, which were categorized as either poor or good on the basis of previously defined cutoffs. The primary outcomes were the net changes in SF-12 MCS, SF-12 Physical Component Summary (PCS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at 4 and 12 months postoperatively. Univariate and mixed-effects model analyses were performed to control for potential confounding factors. Results: Patients with depression but good baseline mental health achieved gains in patient-reported outcomes that were comparable with those of normal controls (p > 0.05). Patients with poor baseline mental health achieved significant gains in all patient-reported outcomes, but the changes were largest for those without depression (p < 0.05). Only patients with depression and poor baseline mental health did not cross the threshold for good mental health at the time of the latest follow-up despite achieving similar gains in physical function compared with their counterparts who did not have depression. Conclusions: The effect of depression on patient-reported outcomes is more complex but less pessimistic than previously thought. Patients with depression undergoing total joint arthroplasty may have significant improvements in their patient-reported outcomes, but the net gains are modulated by their mental health at the time of the surgical procedure. Preoperative screening of patients with depression using the SF-12 MCS may help to identify those who are at risk for attaining suboptimal patient-reported outcomes and may benefit from counseling or psychiatric referral for optimization before undergoing a surgical procedure. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

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Across the European Union, an increase in life expectancy is commonly reported with women outliving men (Eurostat, 2019). In the Republic of Ireland, the mean age of death in the general population in 2001 was 73 years and by 2016, this had increased to 76 years, although for women the mean age of death was 79 years and for males, 74 years (CSO, personal communication). However, increases in life expectancy were not uniform across the population. Lower life expectancy was found among persons living in more socially deprived areas, in urban settings, in rented accommodation provided by local authorities, and for people who were single and less educated (CSO, 2010).Internationally, for people with intellectual disability, their mean age of death is notably lower than for the general population. A systematic review of 27 studies concluded that a gap of around 20 years exists with greater inequality for women with intellectual disability than for men (O'Leary et al., 2018). It is unclear the extent to which the gap has reduced in recent years due mainly to a dearth of longitudinal studies. Nevertheless a study of deaths of people with intellectual disability in one English city over a 33 year period up to 2012 suggested that the gap persisted although there were increases in the life expectancy of people with intellectual disability (Emerson et al., 2014).Two previous studies have reported deaths of Irish people with intellectual disability. In the period 1996 to 2001, the mean age of