47 research outputs found
Introduction : exploring forgiveness in nineteenth-century poetry
This essay serves as an introduction to the essays collected in the âNineteenth-century Poetry and Forgivenessâ cluster. It takes as its foundation the recent turn to questions of hospitality, forgiveness and gift in the intra-disciplinary field of religion, philosophy and literature and highlights the centrality of these issues for reading nineteenth-century poetry. The essay argues that nineteenth-century poetry attempts to figure forgiveness as poetic sound and rhythm as a way of thinking reciprocal forgiving relationships between people. Part I contextualizes this argument and argues for an understanding of forgiveness through emotion. Part II offers an overview of the field of forgiveness scholarship and explores its relevance for nineteenth-century debate on the topic. Part III offers a way into thinking forgiveness as sound and rhythm in Wordsworth's poem âAirey-Force Valleyâ through Martin Heidegger's reading of poetics and being
Investigating the viability of genetic screening/testing for RA susceptibility using combinations of five confirmed risk loci
Objective. Five lociâthe shared epitope (SE) of HLA-DRB1, the PTPN22 gene, a locus on 6q23, the STAT4 gene and a locus mapping to the TRAF1/C5 genetic regionâhave now been unequivocally confirmed as conferring susceptibility to RA. The largest single effect is conferred by SE. We hypothesized that combinations of susceptibility alleles may increase risk over and above that of any individual locus alone
Earth: Atmospheric Evolution of a Habitable Planet
Our present-day atmosphere is often used as an analog for potentially
habitable exoplanets, but Earth's atmosphere has changed dramatically
throughout its 4.5 billion year history. For example, molecular oxygen is
abundant in the atmosphere today but was absent on the early Earth. Meanwhile,
the physical and chemical evolution of Earth's atmosphere has also resulted in
major swings in surface temperature, at times resulting in extreme glaciation
or warm greenhouse climates. Despite this dynamic and occasionally dramatic
history, the Earth has been persistently habitable--and, in fact,
inhabited--for roughly 4 billion years. Understanding Earth's momentous changes
and its enduring habitability is essential as a guide to the diversity of
habitable planetary environments that may exist beyond our solar system and for
ultimately recognizing spectroscopic fingerprints of life elsewhere in the
Universe. Here, we review long-term trends in the composition of Earth's
atmosphere as it relates to both planetary habitability and inhabitation. We
focus on gases that may serve as habitability markers (CO2, N2) or
biosignatures (CH4, O2), especially as related to the redox evolution of the
atmosphere and the coupled evolution of Earth's climate system. We emphasize
that in the search for Earth-like planets we must be mindful that the example
provided by the modern atmosphere merely represents a single snapshot of
Earth's long-term evolution. In exploring the many former states of our own
planet, we emphasize Earth's atmospheric evolution during the Archean,
Proterozoic, and Phanerozoic eons, but we conclude with a brief discussion of
potential atmospheric trajectories into the distant future, many millions to
billions of years from now. All of these 'Alternative Earth' scenarios provide
insight to the potential diversity of Earth-like, habitable, and inhabited
worlds.Comment: 34 pages, 4 figures, 4 tables. Review chapter to appear in Handbook
of Exoplanet
Oral Abstracts 7: RA ClinicalO37.âLong-Term Outcomes of Early RA Patients Initiated with Adalimumab Plus Methotrexate Compared with Methotrexate Alone Following a Targeted Treatment Approach
Background: This analysis assessed, on a group level, whether there is a long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially treated with placebo (PBO) + MTX who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was a 78- week, randomized, controlled trial of ADA + MTX vs PBO + MTX in MTX-naĂŻve early (<1 year) RA patients. Therapy was adjusted at week 26: ADA + MTX-responders (R) who achieved DAS28 (CRP) <3.2 at weeks 22 and 26 (Period 1, P1) were re-randomized to withdraw or continue ADA and PBO + MTX-R continued randomized therapy for 52 weeks (P2); IR-patients received open-label (OL) ADA + MTX during P2. This post hoc analysis evaluated the proportion of patients at week 78 with DAS28 (CRP) <3.2, HAQ-DI <0.5, and/or ÎmTSS â€0.5 by initial treatment. To account for patients who withdrew ADA during P2, an equivalent proportion of R was imputed from ADA + MTX-R patients. Results: At week 26, significantly more patients had low disease activity, normal function, and/or no radiographic progression with ADA + MTX vs PBO + MTX (Table 1). Differences in clinical and functional outcomes disappeared following additional treatment, when PBO + MTX-IR (n = 348/460) switched to OL ADA + MTX. Addition of OL ADA slowed radiographic progression, but more patients who received ADA + MTX from baseline had no radiographic progression at week 78 than patients who received initial PBO + MTX. Conclusions: Early RA patients treated with PBO + MTX achieved comparable long-term clinical and functional outcomes on a group level as those who began ADA + MTX, but only when therapy was optimized by the addition of ADA in PBO + MTX-IR. Still, ADA + MTX therapy conferred a radiographic benefit although the difference did not appear to translate to an additional functional benefit. Disclosures: P.E., AbbVie, Merck, Pfizer, UCB, Roche, BMSâProvided Expert Advice, Undertaken Trials, AbbVieâAbbVie sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. R.F., AbbVie, Pfizer, Merck, Roche, UCB, Celgene, Amgen, AstraZeneca, BMS, Janssen, Lilly, NovartisâResearch Grants, Consultation Fees. S.F., AbbVieâEmployee, Stocks. A.K., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, UCBâResearch Grants, Consultation Fees. H.K., AbbVieâEmployee, Stocks. S.R., AbbVieâEmployee, Stocks. J.S., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, GlaxoSmithKline, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCBâResearch Grants, Consultation Fees. R.V., AbbVie, BMS, GlaxoSmithKline, Human Genome Sciences, Merck, Pfizer, Roche, UCB PharmaâConsultation Fees, Research Support. Table 1.Week 78 clinical, functional, and radiographic outcomes in patients who received continued ADA + MTX vs those who continued PBO + MTX or added open-label ADA following an inadequate response ADA + MTX, n/N (%)a PBO + MTX, n/N (%)b Outcome Week 26 Week 52 Week 78 Week 26 Week 52 Week 78 DAS28 (CRP) <3.2 246/466 (53) 304/465 (65) 303/465 (65) 139/460 (30)*** 284/460 (62) 300/460 (65) HAQ-DI <0.5 211/466 (45) 220/466 (47) 224/466 (48) 150/460 (33)*** 203/460 (44) 208/460 (45) ÎmTSS â€0.5 402/462 (87) 379/445 (86) 382/443 (86) 330/459 (72)*** 318/440 (72)*** 318/440 (72)*** DAS28 (CRP) <3.2 + ÎmTSS â€0.5 216/462 (47) 260/443 (59) 266/443 (60) 112/459 (24)*** 196/440 (45) 211/440 (48)*** DAS28 (CRP) <3.2 + HAQ-DI <0.5 + ÎmTSS â€0.5 146/462 (32) 168/443 (38) 174/443 (39) 82/459 (18)*** 120/440 (27)*** 135/440 (31)** aIncludes patients from the ADA Continuation (n = 105) and OL ADA Carry On (n = 259) arms, as well as the proportional equivalent number of responders from the ADA Withdrawal arm (n = 102). bIncludes patients from the MTX Continuation (n = 112) and Rescue ADA (n = 348) arms. Last observation carried forward: DAS28 (CRP) and HAQ-DI; Multiple imputations: ÎmTSS. ***P < 0.001 and **iP < 0.01, respectively, for differences between initial treatments from chi-squar
A genome-wide association study identifies risk alleles in plasminogen and P4HA2 associated with giant cell arteritis
Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analysed in 2,134 cases and 9,125 unaffected controls from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, P = 1.94E-54, per-allele OR = 1.79; and rs9275592, P = 1.14E-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, P = 1.23E-10, OR = 1.28; and rs128738, P = 4.60E-09, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis
The Impact of Obstructive Sleep Apnea on Aortic Disease in Marfan's Syndrome
Background: Aortic dissection is a life-threatening manifestation of Marfan's syndrome. Preliminary evidence suggests that obstructive sleep apnea (OSA) is associated with aortic disease in Marfan's syndrome. Objectives: To study the effect of OSA on aortic events in Marfan's syndrome. Methods: In patients with Marfan's syndrome, a sleep study was performed at baseline and OSA was defined as >5 events of apnea/hypopnea (A+H) per hour in bed. Operation because of progressive aortic dilatation and death because of aortic rupture were defined as 'aortic events'. Kaplan-Meier survival analyses were used to compare event-free survival in patients with and without OSA. Cox regression models were used to explore the effects of covariates on event-free survival. Results: Data from 44 patients (mean age 37.4 years, 30 females) were available for analysis; 15 patients (34.1%) had OSA. The median follow-up time was 29 (interquartile range 24-36) months. Five patients had an aortic event within the follow-up time. Median event-free survival was 51.6 months. Event-free survival was significantly shorter in patients with OSA compared to patients without OSA (p = 0.012). In univariate analysis, A+H was associated with aortic events [hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.01-1.18, p = 0.023]. Taking the interaction between BMI and A+H into account increased the HR for A+H (HR 1.75, 95% CI 1.003-3.048, p = 0.049). This association was no longer significant when other covariates were forced into the multivariate analysis. Conclusions: These data suggest that aortic event-free survival may be shorter in patients with Marfan's syndrome and OSA compared to patients without OSA, but more data from well-designed studies are needed to prove this association
A Highly Dependable Computing Architecture for Safety-Critical Control Applications
. More and more technical systems are supervised, controlled and regulated by programmable electronic systems. The dependability of the entire system depends heavily on the safety of the embedded software. But the technological trend to entrust software with tasks of growing complexity and safety relevance conflicts with the lacking acceptance of rigorous proofs of software safety. Based on an international standard for higher level programming languages for programmable logic controllers (PLC, IEC 1131-3), a mathematically based method for validating the behavioral correctness and the functional safety of graphical designs of safe-critical control applications is introduced. The design elements taken from a domain specific module library are proven correct and safe only once. The functional correctness and satifaction of safety requirements of new application graphical programs can then be shown effectively by reference to the proven properties of the library components used. This app..