Socioeconomic status as a risk factor for dementia death:individual participant meta-analysis of 86 508 men and women from the UK

Background Life-course socioeconomic factors may have a role in dementia aetiology but there is a current paucity of studies. Meta-analyses of individual participant data would considerably strengthen this evidence base. Aims To examine the association between socioeconomic status in early life and adulthood with later dementia death. Method Individual participant meta-analysis of 11 prospective cohort studies (1994-2004, n = 86 508). Results Leaving full-time education at an earlier age was associated with an increased risk of dementia death in women (fully adjusted hazard ratio (HR) for age ⩽14 v. age ⩾16: HR = 1.76, 95% CI 1.23-2.53) but not men. Occupational social class was not statistically significantly associated with dementia death in men or women. Conclusions Lower educational attainment in women was associated with an increased risk of dementia-related death independently of common risk behaviours and comorbidities

Orientation-dependent pinning and homoclinic snaking on a planar lattice

We study homoclinic snaking of one-dimensional, localized states on two-dimensional, bistable lattices via the method of exponential asymptotics. Within a narrow region of parameter space, fronts connecting the two stable states are pinned to the underlying lattice. Localized solutions are formed by matching two such stationary fronts back-to-back; depending on the orientation relative to the lattice, the solution branch may “snake” back and forth within the pinning region via successive saddle-node bifurcations. Standard continuum approximations in the weakly nonlinear limit (equivalently, the limit of small mesh size) do not exhibit this behavior, due to the resultant leading-order reaction-diffusion equation lacking a periodic spatial structure. By including exponentially small effects hidden beyond all algebraic orders in the asymptotic expansion, we find that exponentially small but exponentially growing terms are switched on via error function smoothing near Stokes lines. Eliminating these otherwise unbounded beyond-all-orders terms selects the origin (modulo the mesh size) of the front, and matching two fronts together yields a set of equations describing the snaking bifurcation diagram. This is possible only within an exponentially small region of parameter space—the pinning region. Moreover, by considering fronts orientated at an arbitrary angle ψ to the x-axis, we show that the width of the pinning region is nonzero only if tan ψ is rational or infinite. The asymptotic results are compared with numerical calculations, with good agreement

A Natural Plasmid Uniquely Encodes Two Biosynthetic Pathways Creating a Potent Anti-MRSA Antibiotic

Background Understanding how complex antibiotics are synthesised by their producer bacteria is essential for creation of new families of bioactive compounds. Thiomarinols, produced by marine bacteria belonging to the genus Pseudoalteromonas, are hybrids of two independently active species: the pseudomonic acid mixture, mupirocin, which is used clinically against MRSA, and the pyrrothine core of holomycin. Methodology/Principal Findings High throughput DNA sequencing of the complete genome of the producer bacterium revealed a novel 97 kb plasmid, pTML1, consisting almost entirely of two distinct gene clusters. Targeted gene knockouts confirmed the role of these clusters in biosynthesis of the two separate components, pseudomonic acid and the pyrrothine, and identified a putative amide synthetase that joins them together. Feeding mupirocin to a mutant unable to make the endogenous pseudomonic acid created a novel hybrid with the pyrrothine via “mutasynthesis” that allows inhibition of mupirocin-resistant isoleucyl-tRNA synthetase, the mupirocin target. A mutant defective in pyrrothine biosynthesis was also able to incorporate alternative amine substrates. Conclusions/Significance Plasmid pTML1 provides a paradigm for combining independent antibiotic biosynthetic pathways or using mutasynthesis to develop a new family of hybrid derivatives that may extend the effective use of mupirocin against MRSA

Brief of Corporate Law Professors as Amici Curie in Support of Respondents

The Supreme Court has looked to the rights of corporate shareholders in determining the rights of union members and non-members to control political spending, and vice versa. The Court sometimes assumes that if shareholders disapprove of corporate political expression, they can easily sell their shares or exercise control over corporate spending. This assumption is mistaken. Because of how capital is saved and invested, most individual shareholders cannot obtain full information about corporate political activities, even after the fact, nor can they prevent their savings from being used to speak in ways with which they disagree. Individual shareholders have no “opt out” rights or practical ability to avoid subsidizing corporate political expression with which they disagree. Nor do individuals have the practical option to refrain from putting their savings into equity investments, as doing so would impose damaging economic penalties and ignore conventional financial guidance for individual investors

Development and preliminary testing of the psychosocial adjustment to hereditary diseases scale

Background: The presence of Lynch syndrome (LS) can bring a lifetime of uncertainty to an entire family as members adjust to living with a high lifetime cancer risk. The research base on how individuals and families adjust to genetic-linked diseases following predictive genetic testing has increased our understanding of short-term impacts but gaps continue to exist in knowledge of important factors that facilitate or impede long-term adjustment. The failure of existing scales to detect psychosocial adjustment challenges in this population has led researchers to question the adequate sensitivity of these instruments. Furthermore, we have limited insight into the role of the family in promoting adjustment. Methods: The purpose of this study was to develop and initially validate the Psychosocial Adjustment to Hereditary Diseases (PAHD) scale. This scale consists of two subscales, the Burden of Knowing (BK) and Family Connectedness (FC). Items for the two subscales were generated from a qualitative data base and tested in a sample of 243 participants from families with LS. Results: The Multitrait/Multi-Item Analysis Program-Revised (MAP-R) was used to evaluate the psychometric properties of the PAHD. The findings support the convergent and discriminant validity of the subscales. Construct validity was confirmed by factor analysis and Cronbach’s alpha supported a strong internal consistency for BK (0.83) and FC (0.84). Conclusion: Preliminary testing suggests that the PAHD is a psychometrically sound scale capable of assessing psychosocial adjustment. We conclude that the PAHD may be a valuable monitoring tool to identify individuals and families who may require therapeutic interventions