Foxg1 is required to limit the formation of ciliary margin tissue and Wnt/β-catenin signalling in the developing nasal retina of the mouse

AbstractThe ciliary margin (CM) develops in the peripheral retina and gives rise to the iris and the ciliary body. The Wnt/β-catenin signalling pathway has been implicated in ciliary margin development. Here, we tested the hypothesis that in the developing mouse retina Foxg1 is responsible for suppressing the Wnt/β-catenin pathway and restricting CM development. We showed that there is excess CM tissue in Foxg1−/− null embryos and this expansion is more pronounced in the nasal retina where Foxg1 normally shows its highest expression levels. Results on expression of a reporter allele for Wnt/β-catenin signalling and of Lef1, a target of Wnt/β-catenin signalling, displayed significant upregulation of this pathway in Foxg1−/− nulls at embryonic days 12.5 and 14.5. Interestingly, this upregulation was observed specifically in the nasal retina, where normally very few Wnt-responsive cells are observed. These results indicate a suppressive role of Foxg1 on this signalling pathway. Our results reveal a new role of Foxg1 in limiting CM development in the nasal peripheral retina and add a new molecular player in the developmental network involved in CM specification

Love Thy Neighbor as Thyself: Community Formation and the Church

The church has played a central role in establishing and maintaining, as well as undermining, communities throughout modern history. In this paper we explore some of the mechanisms through which the church can coordinate individual behavior to achieve improvements in individual and social welfare, and reveal the ways in which the church can fail, causing established communities to founder or dissolve. In our model inherently religious individuals may become trapped in a secular equilibrium that is strictly dominated by a religious equilibrium in which individuals’ actions bestow positive external benefits on other community members. The church, via its teachings, clergy and ministries, reveals the benefits of coordinated behavior, both in this world and in the world to come, and the costs of uncoordinated behavior, separation from God and one’s fellow man, to induce community members to take actions which are both individually and socially beneficial. External forces, such as the state and secular society, and internal forces, such as doctrinal disputes, inconsistencies, and incoherence, can reduce a church’s ability to coordinate, to the detriment of all

Gluttony and Sloth: Signs of Trouble or Evidence of Bliss?

In a model of rational agent choice in which agents value consumption and leisure as well as health, we establish that individuals, unconstrained by concerns of income or time, can and will choose levels of consumption and leisure that exceed their physiological optima. By how much they exceed the optima depends on a variety of factors, most importantly, the utility cost (benefit) of achieving health. Observed positive long-run trends in adult weight, brought on by higher levels of consumption and lower levels of physical activity, often interpreted as a public health crisis in the making, can be explained by these factors. But, rather than the trend suggesting crisis, it suggests only optimal responses to altered, and perhaps improved, circumstances. While individuals today, all else equal, may weigh more than those a generation or two ago, they also may be happier

Contrasting effects of linezolid on healthy and dysfunctional human neutrophils: reducing C5a-induced injury

Background: To manage increasing demand for emergency and unscheduled care NHS England policy haspromoted services in which patients presenting to Emergency Departments (EDs) with non-urgent problems aredirected to general practitioners (GPs) and other primary care clinicians working within or alongside emergencydepartments. However, the ways that hospitals have implemented primary care services in EDs are varied. The aimof this study was to describe ED clinical leads’ experiences of implementing and delivering ‘primary care services’and ‘emergency medicine services’ where GPs were integrated into the ED team. Methods: We conducted interviews with ED clinical leads in England (n = 19) and Wales (n = 2). We usedframework analysis to analyse interview transcripts and explore differences across ‘primary care services’, ‘emergency medicine services’ and emergency departments without primary care services. Results: In EDs with separate primary care services, success was reported when having a distinct workforce ofprimary care clinicians, who improved waiting times and flow by seeing primary care-type patients in a timely way,using fewer investigations, and enabling ED doctors to focus on more acutely unwell patients. Some challengeswere: trying to align their service with the policy guidance, inconsistent demand for primary care, accessiblecommunity primary care services, difficulties in recruiting GPs, lack of funding, difficulties in agreeing governanceprotocols and establishing effective streaming pathways. Where GPs were integrated into an ED workforce successwas reported as managing the demand for both emergency and primary care and reducing admission

The psychosocial impact of microtia and ear reconstruction: A national data-linkage study

Introduction: Children with visible facial differences are believed to be at increased risk of negative psychosocial behaviours which may manifest as affective disorders. The aim of this study was to determine whether a diagnosis of microtia, and the associated surgical intervention, is associated with psychosocial implications including impaired educational attainment and a diagnosis of an affective disorder.Methods: A retrospective case-control study was conducted using data linkage to identify patients in Wales with a diagnosis of microtia. Matched controls were sought on the basis of age, gender and socioeconomic deprivation status to yield a total sample size of 709. incidence was calculated using annual and geographic birth rates. Surgical operation codes were used to classify patients into those that had no surgery, autologous reconstruction or prosthetic reconstruction. Educational attainment at 11 years of age, plus a diagnosis of depression or anxiety were used as markers of adverse psychosocial outcomes and the relative risk was attained using logistic regression analyses.Results: There were no significant associations between a diagnosis of microtia and an increased risk of adverse educational attainment or a risk of an affective disorder diagnosis. Male gender and higher deprivation scores were significantly associated with poorer educational attainment, irrespective of a diagnosis of microtia. Surgical intervention of any nature was also not associated with any increased risk of adverse educational or psychosocial outcomes in microtia patients.Discussion: Microtia patients in Wales do not appear to be at greater risk of developing affective disorders or impaired academic performance as a result of their diagnosis or associated surgical intervention. Whilst reassuring, the need for appropriate support mechanisms to maintain positive psychosocial wellbeing and academic achievement in this patient cohort is reinforced

Where Has All the Demand Gone? Challenges to Growth in a “Neo-Mercantilist Age

Extensive attention has been given to countries that run current account deficits, but little attention has been devoted to understanding why countries run large surpluses. This is surprising given that unsustainable international imbalances result from one as much as the other. We begin with a wideranging review of the literature to better understand the political and economic forces that lead to demand decreasing policies. We then demonstrate how the systemic choices made within the Bretton Woods and Post Bretton Woods periods constrained and enabled the generation of large surpluses. Next, we examine imbalances at the global level to determine whether they are getting bigger rather than trending toward external balance. We find evidence that the trend towards imbalance is strengthening. We then analyze the patterns of these surpluses in four countries noting where government policies have most prominently contributed to the surpluses, pointing out the differing motivations for and implementations of these policies across countries. This leads us to ask, finally, what these trends portend and what can be done to mitigate or reverse them if they bode ill for global economic well-being

Where Has All the Demand Gone? Challenges to Growth in a “Neo-Mercantilist Age

Extensive attention has been given to countries that run current account deficits, but little attention has been devoted to understanding why countries run large surpluses. This is surprising given that unsustainable international imbalances result from one as much as the other. We begin with a wideranging review of the literature to better understand the political and economic forces that lead to demand decreasing policies. We then demonstrate how the systemic choices made within the Bretton Woods and Post Bretton Woods periods constrained and enabled the generation of large surpluses. Next, we examine imbalances at the global level to determine whether they are getting bigger rather than trending toward external balance. We find evidence that the trend towards imbalance is strengthening. We then analyze the patterns of these surpluses in four countries noting where government policies have most prominently contributed to the surpluses, pointing out the differing motivations for and implementations of these policies across countries. This leads us to ask, finally, what these trends portend and what can be done to mitigate or reverse them if they bode ill for global economic well-being

Solution phase treatments of Sb2_2Se3_3 heterojunction photocathodes for improved water splitting performance

Antimony selenide (Sb$_2$Se$_3$) is an auspicious material for solar energy conversion that has seen rapid improvement over the past ten years, but the photovoltage deficit remains a challenge. Here, simple and low-temperature treatments of the p–n heterojunction interface of Sb$_2$Se$_3$/TiO$_2$-based photocathodes for photoelectrochemical water splitting were explored to address this challenge. The FTO/Ti/Au/Sb$_2$Se$_3$ (substrate configuration) stack was treated with (NH$_4$)$_2$S as an etching solution, followed by CuCl$_2$ treatment prior to deposition of the TiO$_2$ by atomic layer deposition. The different treatments show different mechanisms of action compared to similar reported treatments of the back Au/Sb$_2$Se$_3$ interface in superstrate configuration solar cells. These treatments collectively increased the onset potential from 0.14 V to 0.28 V vs. reversible hydrogen electrode (RHE) and the photocurrent from 13 mA cm$^{−2}$ to 18 mA cm$^{−2}$ at 0 V vs. RHE as compared to the untreated Sb$_2$Se$_3$ films. From SEM and XPS studies, it is clear that the etching treatment induces a morphological change and removes the surface Sb$_2$Se$_3$ layer, which eliminates the Fermi-level pinning that the oxide layer generates. CuCl$_2$ further enhances the performance due to the passivation of the surface defects, as supported by density functional theory molecular dynamics (DFT-MD) calculations, improving charge separation at the interface. The simple and low-cost semiconductor synthesis method combined with these facile, low-temperature treatments further increases the practical potential of Sb$_2$Se$_3$ for large-scale water splitting