Popular Theology from Popular Scientists: Assessing the Legacy of Eddington and Jeans as Apologists

This thesis asserts and demonstrates that the current historical evaluation of the significance of Arthur Eddington and James Jeans is inadequate. Not only has their importance in the years between the two World Wars been forgotten, but their transitional role in the science and religion debate post-Darwin is now largely unrecognised. Both had a major influence on subsequent popular apologists and Eddington in particular influenced post war academic theologians as diverse as Thomas Torrance and Eric Mascall. It is generally accepted that the apologetic writings of Eddington and Jeans were widely read and were adept at conveying their message. They have, however, been increasingly ignored by historians and theologians. This thesis argues that their work post-Darwin on the new physics of the early twentieth century was significant in steering the science and religion dialogue in the United Kingdom away from the more conflict-based approaches such as the beginnings of creationism in the United States. Further their deployment of metaphor, ability to engage in dialogue with the public through the press and the new technology of the wireless were innovative and left a legacy for apologetics and the science and religion dialogue. By an examination of three key texts, a new account is given of the authors’ importance and of the reactions of contemporary theologians, philosophers and scientists. Their work brought the latest science to bear on important areas of traditional theological debate in an accessible way and to a good apologetic end. The role of intuition and ‘seeking’ in relation to Eddington’s writing shows a fresh Quaker-influenced approach to apologetics and the science and religion debate. The widely-accepted role of Susan Stebbing in the post-war decline of Eddington and Jeans is examined and dismissed as simplistic. A new analysis of the reasons for their decline and neglect is made. Jeans and Eddington remind us that the importance of general cultural trends and contemporary events in the science and religion debate is often overlooked. The history of the reception of their apologetic work and the pattern of their continuing significance illustrate the connectedness of theology with current events

Amici Curiae Brief of the International Municipal Lawyers Association and Legal Scholars in Support of Defendants-Appellees in Portland Pipe Line Corporation, et al. v. City of South Portland, et al.

This brief to the Maine Supreme Judicial Court was filed in support of the City of South Portland by the Amici Curiae, including the International Municipal Lawyers Association and legal scholars, to provide the Court with a background on the role of local governments in land use planning, and to explain why the City of South Portland’s Clear Skies Ordinance falls easily within the City’s authority and was not preempted by state legislation.After studying the potential for bulk loading of crude oil within its boundaries, the City of South Portland concluded that the infrastructure requirements and environmental impacts of the activity posed a threat to public health and welfare and were incompatible with the community’s vision of itself for the future. The City therefore decided to enact the Clear Skies Ordinance, which prohibits the storing and handling of petroleum or petroleum products for the bulk loading of crude oil onto any marine tank vessel in specified zoning districts. Litigation followed, with plaintiffs arguing that the City lacked authority to enact the Ordinance and that, even if it had such authority in the first instance, that authority had been preempted by other state law. Defendants prevailed on summary judgment in the U.S. District Court for the District of Maine, and during the course of an appeal to the United States Court of Appeals for the First Circuit, the Circuit certified several questions to the Maine Supreme Judicial Court. This brief was filed in support of the City with regard to those certified questions.The brief begins by discussing how central the role of local governments is in making land use decisions, emphasizing the highly localized impacts of land use decisions for public health and welfare. It then describes the zoning mechanisms by which local governments exercise their land use power, and discusses why the zoning power is so important for protecting public health and environmental quality, and responding to the changing needs of communities.Next, the brief explains the legal underpinnings of the City of South Portland’s home rule authority. The Constitution of the State of Maine contains a broad grant of home rule authority that is further strengthened by a statutorily imposed rebuttable presumption of validity for exercises of that authority. Local exercises of zoning authority are consistent within this home rule grant, and the brief discusses why the Clear Skies Ordinance falls squarely within the local zoning power. Finally, the brief explains why the Ordinance has not been expressly or impliedly preempted by state law. For all of those reasons, the brief concludes that the City’s enactment of the Ordinance was valid in the first instance and should not be overturned

Differential Drug Survival of Biologic Therapies for the Treatment of Psoriasis: A Prospective Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR)

Drug survival reflects a drug’s effectiveness, safety, and tolerability. We assessed the drug survival of biologics used to treat psoriasis in a prospective national pharmacovigilance cohort (British Association of Dermatologists Biologic Interventions Register (BADBIR)). The survival rates of the first course of biologics for 3,523 biologic-naive patients with chronic plaque psoriasis were compared using survival analysis techniques and predictors of discontinuation analyzed using a multivariate Cox proportional hazards model. Data for patients on adalimumab (n=1,879), etanercept (n=1,098), infliximab (n=96), and ustekinumab (n=450) were available. The overall survival rate in the first year was 77%, falling to 53% in the third year. Multivariate analysis showed that female gender (hazard ratio (HR) 1.22; 95% confidence interval (CI): 1.09–1.37), being a current smoker (HR 1.19; 95% CI: 1.03–1.38), and a higher baseline dermatology life quality index (HR 1.01; 95% CI: 1.00–1.02) were predictors of discontinuation. Presence of psoriatic arthritis (HR 0.82; 95% CI: 0.71–0.96) was a predictor for drug survival. As compared with adalimumab, patients on etanercept (HR 1.63; 95% CI: 1.45–1.84) or infliximab (HR 1.56; 95% CI: 1.16–2.09) were more likely to discontinue therapy, whereas patients on ustekinumab were more likely to persist (HR 0.48; 95% CI: 0.37–0.62). After accounting for relevant covariates, ustekinumab had the highest first-course drug survival. The results of this study will aid clinical decision making when choosing biologic therapy for psoriasis patients

Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes

Risk of major cardiovascular events in patients with psoriasis receiving biologic therapies: a prospective cohort study

Background: The cardiovascular safety profile of biologic therapies used for psoriasis is unclear. Objectives: To compare the risk of major cardiovascular events (CVEs; acute coronary syndrome, unstable angina, myocardial infarction and stroke) in patients with chronic plaque psoriasis treated with adalimumab, etanercept or ustekinumab in a large prospective cohort. Methods: Prospective cohort study examining the comparative risk of major CVEs was conducted using the British Association of Dermatologists Biologics and Immunomodulators Register. The main analysis compared adults with chronic plaque psoriasis receiving ustekinumab with tumour necrosis‐α inhibitors (TNFi: etanercept and adalimumab), whilst the secondary analyses compared ustekinumab, etanercept or methotrexate against adalimumab. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using overlap weights by propensity score to balance baseline covariates among comparison groups. Results: We included 5468 biologic‐naïve patients subsequently exposed (951 ustekinumab; 1313 etanercept; and 3204 adalimumab) in the main analysis. The secondary analyses also included 2189 patients receiving methotrexate. The median (p25–p75) follow‐up times for patients using ustekinumab, TNFi, adalimumab, etanercept and methotrexate were as follows: 2.01 (1.16–3.21), 1.93 (1.05–3.34), 1.94 (1.09–3.32), 1.92 (0.93–3.45) and 1.43 (0.84–2.53) years, respectively. Ustekinumab, TNFi, adalimumab, etanercept and methotrexate groups had 7, 29, 23, 6 and 9 patients experiencing major CVEs, respectively. No differences in the risk of major CVEs were observed between biologic therapies [adjusted HR for ustekinumab vs. TNFi: 0.96 (95% CI 0.41–2.22); ustekinumab vs. adalimumab: 0.81 (0.30–2.17); etanercept vs. adalimumab: 0.81 (0.28–2.30)] and methotrexate against adalimumab [1.05 (0.34–3.28)]. Conclusions: In this large prospective cohort study, we found no significant differences in the risk of major CVEs between three different biologic therapies and methotrexate. Additional studies, with longer term follow‐up, are needed to investigate the potential effects of biologic therapies on incidence of major CVEs

Development and validation of a multivariable risk prediction model for serious infection in patients with psoriasis receiving systemic therapy

BACKGROUND: Patients with psoriasis are often concerned about the risk of serious infection associated with systemic psoriasis treatments. OBJECTIVES: To develop and externally validate a prediction model for serious infection in patients with psoriasis within 1 year of starting systemic therapies. METHODS: The risk prediction model was developed using the British Association of Dermatologists Biologic Interventions Register (BADBIR), and the German Psoriasis Registry PsoBest was used as the validation dataset. Model discrimination and calibration were assessed internally and externally using the C-statistic, the calibration slope and the calibration in the large. RESULTS: Overall 175 (1·7%) out of 10 033 participants from BADBIR and 41 (1·7%) out of 2423 participants from PsoBest developed a serious infection within 1 year of therapy initiation. Selected predictors in a multiple logistic regression model included nine baseline covariates, and starting infliximab was the strongest predictor. Evaluation of model performance showed a bootstrap optimism-corrected C-statistic of 0·64 [95% confidence interval (CI) 0·60-0·69], calibration in the large of 0·02 (95% CI -0·14 to 0·17) and a calibration slope of 0·88 (95% CI 0·70-1·07), while external validation performance was poor, with C-statistic 0·52 (95% CI 0·42-0·62), calibration in the large 0·06 (95% CI -0·25 to 0·37) and calibration slope 0·36 (95% CI -0·24 to 0·97). CONCLUSIONS: We present the first results of the development of a multivariable prediction model. This model may help patients and dermatologists in the U.K. and the Republic of Ireland to identify modifiable risk factors and inform therapy choice in a shared decision-making process

Intentional and unintentional medication non-adherence in psoriasis: The role of patients’ medication beliefs and habit strength

Medication non-adherence is a missed opportunity for therapeutic benefit. We assessed “real-world” levels of self-reported non-adherence to conventional and biologic systemic therapies used for psoriasis and evaluated psychological and biomedical factors associated with non-adherence using multivariable analyses. Latent profile analysis was used to investigate whether patients can be categorized into groups with similar medication beliefs. Latent profile analysis categorizes individuals with similar profiles on a set of continuous variables into discrete groups represented by a categorical latent variable. Eight hundred and eleven patients enrolled in the British Association of Dermatologists Biologic Interventions Register were included. Six hundred and seventeen patients were using a self-administered systemic therapy; 22.4% were classified as “non-adherent” (12% intentionally and 10.9% unintentionally). Patients using an oral conventional systemic agent were more likely to be non-adherent compared to those using etanercept or adalimumab (29.2% vs. 16.4%; P ≤ 0.001). Latent profile analysis supported a three-group model; all groups held strong beliefs about their need for systemic therapy but differed in levels of medication concerns. Group 1 (26.4% of the sample) reported the strongest concerns, followed by Group 2 (61%), with Group 3 (12.6%) reporting the weakest concerns. Group 1 membership was associated with intentional non-adherence (odds ratio = 2.27, 95% confidence interval = 1.16−4.47) and weaker medication-taking routine or habit strength was associated with unintentional non-adherence (odds ratio = 0.92, 95% confidence interval = 0.89−0.96). Medication beliefs and habit strength are modifiable targets for strategies to improve adherence in psoriasis

HelioSwarm: A Multipoint, Multiscale Mission to Characterize Turbulence

HelioSwarm (HS) is a NASA Medium-Class Explorer mission of the Heliophysics Division designed to explore the dynamic three-dimensional mechanisms controlling the physics of plasma turbulence, a ubiquitous process occurring in the heliosphere and in plasmas throughout the universe. This will be accomplished by making simultaneous measurements at nine spacecraft with separations spanning magnetohydrodynamic and sub-ion spatial scales in a variety of near-Earth plasmas. In this paper, we describe the scientific background for the HS investigation, the mission goals and objectives, the observatory reference trajectory and instrumentation implementation before the start of Phase B. Through multipoint, multiscale measurements, HS promises to reveal how energy is transferred across scales and boundaries in plasmas throughout the universe

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis