Alzheimer's disease and age-related macular degeneration have different genetic models for complement gene variation

Alzheimer's disease (AD) and age-related macular degeneration (AMD) are both neurodegenerative disorders which share common pathological and biochemical features of the complement pathway. The aim of this study was to investigate whether there is an association between well replicated AMD genetic risk factors and AD. A large cohort of AD (n = 3898) patients and controls were genotyped for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), the Age-related maculopathy susceptibility protein 2 (ARMS2) the complement component 2 (C2), the complement factor B (CFB), and the complement component 3 (C3) genes. While significant but modest associations were identified between the complement factor H, the age-related maculopathy susceptibility protein 2, and the complement component 3 single nucleotide polymorphisms and AD, these were different in direction or genetic model to that observed in AMD. In addition the multilocus genetic model that predicts around a half of the sibling risk for AMD does not predict risk for AD. Our study provides further support to the hypothesis that while activation of the alternative complement pathway is central to AMD pathogenesis, it is less involved in AD.

The Role of Variation at AβPP, PSEN1, PSEN2, and MAPT in Late Onset Alzheimer's Disease

Rare mutations in AßPP, PSEN1, and PSEN2 cause uncommon early onset forms of Alzheimer's disease (AD), and common variants in MAPT are associated with risk of other neurodegenerative disorders. We sought to establish whether common genetic variation in these genes confer risk to the common form of AD which occurs later in life (>65 years). We therefore tested single-nucleotide polymorphisms at these loci for association with late-onset AD (LOAD) in a large case-control sample consisting of 3,940 cases and 13,373 controls. Single-marker analysis did not identify any variants that reached genome-wide significance, a result which is supported by other recent genome-wide association studies. However, we did observe a significant association at the MAPT locus using a gene-wide approach (p = 0.009). We also observed suggestive association between AD and the marker rs9468, which defines the H1 haplotype, an extended haplotype that spans the MAPT gene and has previously been implicated in other neurodegenerative disorders including Parkinson's disease, progressive supranuclear palsy, and corticobasal degeneration. In summary common variants at AßPP, PSEN1, and PSEN2 and MAPT are unlikely to make strong contributions to susceptibility for LOAD. However, the gene-wide effect observed at MAPT indicates a possible contribution to disease risk which requires further study.

Encouraging lifestyle behaviour change in mild cognitive impairment patients:development of appropriate educational material

Objectives: A healthy lifestyle may help maintain cognitive function and reduce the risk of developing dementia. This study employed a focus group approach in order to gain insight into opinions of mild cognitive impairment (MCI) patients, caregivers (CG) and health professionals (HP) regarding lifestyle and its relationship with cognition. The qualitative data were used to design, develop and pilot test educational material (EM) to help encourage lifestyle behaviour change. Method: Data gathering phase: structured interviews were conducted with HP (n = 10), and focus groups with MCI patients (n = 24) and CG (n = 12). EM was developed and pilot tested with a new group of MCI patients (n = 21) and CG (n = 6). Results: HP alluded to the lack of clinical trial evidence for a lifestyle and MCI risk link. Although they felt that lifestyle modifications should be recommended to MCI patients, they appeared hesitant in communicating this information and discussions were often patient-driven. MCI patients lacked awareness of the lifestyle cognition link. Participants preferred EM to be concise, eye-catching and in written format, with personal delivery of information favoured. Most pilot testers approved of the EM but were heterogeneous in terms of lifestyle, willingness to change and support needed to change. Conclusion: MCI patients need to be made more aware of the importance of lifestyle for cognition. EM such as those developed here, which are specifically tailored for this population would be valuable for HP who, currently, appear reticent in initiating lifestyle-related discussions. Following further evaluation, the EM could be used in health promotion activities targeting MCI patients.

Growth and adrenal suppression in asthmatic children treated with high-dose fluticasone propionate

Background: Fluticasone propionate was introduced in 1993 in the UK as a potentially safer inhaled corticosteroid than those already in use. The efficacy and safety of fluticasone has been established at recommended doses of 200 µg/day, but not at the higher doses that are often used.

Methods: Growth retardation was observed in six severely asthmatic children after introduction of high-dose fluticasone propionate treatment (dry powder). Assessment of cortisol response was by insulin-induced hypoglycaemia in three cases, by short tetracosactrin test in two, and by low-dose tetracosactrin and 24-hour urinary cortisol/creatinine ratio in one.

Findings: Six children with growth retardation noted after treatment with high-dose fluticasone propionate were found to have adrenal suppression. In one case the growth rate and cortisol response returned to normal 9 months after the fluticasone dose was reduced to 500 µg/day.

Interpretation: When high doses of fluticasone propionate are used, growth may be retarded and adrenal suppression may occur.

Insulin-like growth factor binding protein-3 mediates vascular repair by enhancing nitric oxide generation

Insulin-like growth factor binding protein (IGFBP)-3 modulates vascular development by regulating endothelial progenitor cell (EPC) behavior, specifically stimulating EPC cell migration. This study was undertaken to investigate the mechanism of IGFBP-3 effects on EPC function and how IGFBP-3 mediates cytoprotection following vascular injury.

DONUTS: A Science Frame Autoguiding Algorithm with Sub-Pixel Precision, Capable of Guiding on Defocused Stars

We present the DONUTS autoguiding algorithm, designed to fix stellar positions at the sub-pixel level for high-cadence time-series photometry, and also capable of autoguiding on defocused stars. DONUTS was designed to calculate guide corrections from a series of science images and recentre telescope pointing between each exposure. The algorithm has the unique ability of calculating guide corrections from undersampled to heavily defocused point spread functions. We present the case for why such an algorithm is important for high precision photometry and give our results from off and on-sky testing. We discuss the limitations of DONUTS and the facilities where it soon will be deployed.

Germany and the New Global History of Secularism: Questioning the Postcolonial Genealogy

Secularism has emerged as a central category of twenty-first century political thought that in many ways has replaced the theory of secularization. According to postcolonial scholars, neither the theory nor the practice of secularization was politically neutral. They define secularism as the set of discourses, policies, and constitutional arrangements whereby modern states and liberal elites have sought to unify nations and divide colonial populations. This definition is quite different from the original meaning of secularism, as an immanent scientific worldview linked to anticlericalism. Anthropologist Talal Asad has connected nineteenth-century worldview secularism to twenty-first century political secularism through a genealogical account that stresses continuities of liberal hegemony. This essay challenges this account. It argues that liberal elites did not merely subsume worldview secularism in their drive for state secularization. Using the tools of conceptual history, the essay shows that one reason that “secularization” only achieved its contemporary meaning in Germany after 1945 was that radical freethinkers and other anticlerical secularists had previously resisted liberal hegemony. The essay concludes by offering an agenda for research into the discontinuous history of these two types of secularism.

A European Culture War in the Twentieth Century? Antic-Catholicism and Anti-Bolshevism between Moscow, Berlin, and the Vatican 1922 to 1933

The term “culture war” has become a generic expression for secular-catholic conflicts across nineteenth-century Europe. Yet, if measured by acts of violence, anticlericalism peaked in the years between 1927 and 1939, when thousands of Catholic priests and believers were imprisoned or executed and hundreds of churches razed in Mexico, Spain and Russia. This essay argues that not only in these three countries, but indeed across Europe a culture war raged in the interwar period. It takes, as a case study, the interaction of communist and Catholic actors located in the Vatican, the Soviet Union, and Germany in the period between the beginning of the Pontificate of Pius XI in 1922 and Hitler’s appointment as chancellor of Germany in 1933. Using correspondence and reports from the Vatican archives, this essay shows how Papal officials and communist leaders each sought to mobilize the German populace to achieve their own diplomatic ends. German Catholics and communists gladly responded to the call to arms that sounded from Rome and Moscow in 1930, but they did so also to further their own domestic goals. The case study shows how national contexts inflected the transnational dynamics of radical anti-Catholicism in interwar Europe. In the end, agitation against “godlessness” did not lead to the return of a “Christian State” desired by many conservative Christians. Instead, the culture war further destabilized the republic and added a religious dimension to a landscape well suited to National Socialist efforts to reach a Christian population otherwise mistrustful of its völkisch and anticlerical elements.

Freethought

Essay on the history of German Freethought in the twentieth century.