The influence of parental resources on the timing of the transition to marriage

This paper studies the relationship of parental resources to the marital transitions of children. It extends past research by explicitly distinguishing various dimensions of parental resources and by taking parental preferences directly into account. We test models in which parental resources have additive effects on the timing of marriage and models in which parental resources interact with parents' preferences for the timing of their children's marriages. The analysis shows that both parental financial resources and parental education influence children's marital behavior. Our analysis also demonstrates that parental preferences for their children's age at marriage do matter, but that this influence weakens as the children grow older. Finally, the analysis indicates that the effects of parent's financial resources interact with parent's preferences to affect the timing of their children's transitions to marriage.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29868/1/0000216.pd

Disease modifying and antiangiogenic activity of 2-Methoxyestradiol in a murine model of rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>A critical component of disease progression in rheumatoid arthritis (RA) involves neovascularization associated with pannus formation. 2-methoxyestradiol (2ME2) is a naturally occurring molecule with no known physiologic function, although at pharmacologic concentrations it has antiproliferative and antiangiogenic activities. We investigated the impact of orally administered 2ME2 on the initiation and development of proliferative synovitis using the anti-collagen monoclonal antibodies (CAIA) model.</p> <p>Methods</p> <p>Severe polyarticular arthritis was induced in Balb/c female mice by administration of 2 mg of a monoclonal antibody cocktail intravenously into the tail vein of mice. Twenty-four hours following monoclonal antibody administration, mice were injected with 25 μg of LPS (<it>E. coli </it>strain 0111:B4) via the intraperitoneal route. Treatment with 2ME2 (100, 75, 50, 25, 10, 1 mg/kg, p.o., daily), or vehicle control began 24 hrs following LPS challenge and continued to day 21. Hind limbs were harvested, sectioned and evaluated for DMARD activity and general histopathology by histomorphometric analysis and immunohistochemistry (vWF staining). In a separate study, different dosing regimens of 2ME2 (100 mg/kg; q.d. <it>vs </it>q.w. <it>vs </it>q.w. × 2) were evaluated. The effect of treatment with 2ME2 on gene expression of inflammatory cytokines and angiogenic growth factors in the joint space was evaluated 5 and 14 days after the induction of arthritis.</p> <p>Results</p> <p>Mice treated with 2ME2 beginning 24 hours post anti-collagen monoclonal antibody injection, showed a dose-dependent inhibition in mean arthritic scores. At study termination (day 21), blinded histomorphometric assessments of sectioned hind limbs demonstrated decreases in synovial inflammation, articular cartilage degradation, pannus formation, osteoclast activity and bone resorption. At the maximal efficacious dosing regimen (100 mg/kg/day), administration of 2ME2 resulted in total inhibition of the study parameters and prevented neovascularization into the joint. Examination of gene expression on dissected hind limbs from mice treated for 5 or 14 days with 2ME2 showed inhibition of inflammatory cytokine message for IL-1β, TNF-α, IL-6 and IL-17, as well as the angiogenic cytokines, VEGF and FGF-2.</p> <p>Conclusion</p> <p>These data demonstrate that in the CAIA mouse model of RA, 2ME2 has disease modifying activity that is at least partially attributable to the inhibition of neovascular development. Further, the data suggests new mechanistic points of intervention for 2ME2 in RA, specifically inhibition of inflammatory mediators and osteoclast activity.</p

Career guidance and the changing world of work: Contesting responsibilising notions of the future.

Career guidance is an educational activity which helps individuals to manage their participation in learning and work and plan for their futures. Unsurprisingly career guidance practitioners are interested in how the world of work is changing and concerned about threats of technological unemployment. This chapter argues that the career guidance field is strongly influenced by a “changing world of work” narrative which is drawn from a wide body of grey literature produced by think tanks, supra-national bodies and other policy influencers. This body of literature is political in nature and describes the future of work narrowly and within the frame of neoliberalism. The ‘changing world of work’ narrative is explored through a thematic analysis of grey literature and promotional materials for career guidance conferences. The chapter concludes by arguing that career guidance needs to adopt a more critical stance on the ‘changing world of work’ and to offer more emancipatory alternatives.N/

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

Zwięzła genealogia i anatomia habitusu

Retracing the philosophical origins and initial usage of habitus by Bourdieu to account for the historical disjuncture wrought by theAlgerianwar of national liberation and the postwar modernization of the French countryside allows us to clear up four recurrent misunderstandings about the concept: (1) habitus is never the replica of a single social structure but a dynamic, multiscalar, and multilayered set of schemata subject to ‘permanent revision’ in practice; (2) habitus is not necessarily coherent and unified but displays varying degrees of integration and tension; (3) because it is not always congruent with the cosmos in which it evolves, habitus is suited to analysing crisis and change no less than cohesion and perpetuation; but (4) it is not a self-sufficient mechanism for the generation of action: the dissection of dispositions must always proceed in close connection with the mapping of the system of positions that alternately excite, suppress, or redirect the socially constituted capacities and inclinations of the agent. Crucially, in Bourdieu’s hands, habitus is not an abstract concept issued from and aimed at theoretical disquisition, but a stenographic manner of designating a research posture that puts the genetic mode of thinking at the heart of social analysis.Prześledzenie filozoficznych źródeł i wczesnych zastosowań habitusu u Bourdieu – które wyjaśniały historyczne zerwania, spowodowane czy to wojną wyzwoleńczą w Algierii, czy to powojenną modernizacją francuskiej wsi – pozwala na skorygowanie czterech uporczywie powracających nieporozumień dotyczących tego pojęcia: (1) habitus nie jest nigdy repliką pojedynczej struktury społecznej, stanowi raczej, wielopoziomowy i dynamiczny zestaw schematów, który podlega „permanentnej rewizji” w praktyce; (2) habitus niekoniecznie jest koherentny i spójny, odznacza się raczej zróżnicowanymi poziomami integracji i napięcia; (3) ponieważ nie zawsze pozostaje w zgodności ze światem społecznym, w którym się rozwija, habitus jest tak samo odpowiedni do analizowania kryzysu i zmiany, jak do badań spójności i trwania; (4) nie jest samowystarczalnym mechanizmem generującym działanie: wnikliwa analiza dyspozycji musi więc przebiegać w ścisłym związku z odwzorowaniem całego systemu pozycji, które naprzemiennie pobudzają, tłumią bądź przekierowują skłonności podmiotu działającego. Co kluczowe, w ujęciu Bourdieu habitus nie jest abstrakcyjną koncepcją będącą wynikiem teoretycznych dywagacji i przeznaczoną dla tego typu rozważań; jest on przede wszystkim stenograficznym sposobem wyznaczającym postawę badawczą, który stawia w sercu analizy społecznej genetyczny sposób myślenia

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p&nbsp;&lt;.001. Over 24&nbsp;months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10&nbsp;ml/min/1.73&nbsp;m2 decrease), that was most notable in patients with eGFR &lt;30&nbsp;ml/min/1.73&nbsp;m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90&nbsp;ml/min/1.73&nbsp;m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF