Telescope to Observe Planetary Systems (TOPS): a high throughput 1.2-m visible telescope with a small inner working angle

The Telescope to Observe Planetary Systems (TOPS) is a proposed space mission to image in the visible (0.4-0.9 micron) planetary systems of nearby stars simultaneously in 16 spectral bands (resolution R~20). For the ~10 most favorable stars, it will have the sensitivity to discover 2 R_E rocky planets within habitable zones and characterize their surfaces or atmospheres through spectrophotometry. Many more massive planets and debris discs will be imaged and characterized for the first time. With a 1.2m visible telescope, the proposed mission achieves its power by exploiting the most efficient and robust coronagraphic and wavefront control techniques. The Phase-Induced Amplitude Apodization (PIAA) coronagraph used by TOPS allows planet detection at 2 lambda/d with nearly 100% throughput and preserves the telescope angular resolution. An efficient focal plane wavefront sensing scheme accurately measures wavefront aberrations which are fed back to the telescope active primary mirror. Fine wavefront control is also performed independently in each of 4 spectral channels, resulting in a system that is robust to wavefront chromaticity.Comment: 12 pages, SPIE conference proceeding, May 2006, Orlando, Florid

A Conditional Deletion of the NR1 Subunit of the NMDA Receptor in Adult Spinal Cord Dorsal Horn Reduces NMDA Currents and Injury-Induced Pain

To determine the importance of the NMDA receptor (NMDAR) in pain hypersensitivity after injury, the NMDAR1 (NR1) subunit was selectively deleted in the lumbar spinal cord of adult mice by the localized injection of an adenoassociated virus expressing Cre recombinase into floxed NR1 mice. NR1 subunit mRNA and dendritic protein are reduced by 80% in the area of the virus injection, and NMDA currents, but not AMPA currents, are reduced 86–88% in lamina II neurons. The spatial NR1 knock-out does not alter heat or cold paw-withdrawal latencies, mechanical threshold, or motor function. However, injury-induced pain produced by intraplantar formalin is reduced by 70%. Our results demonstrate conclusively that the postsynaptic NR1 receptor subunit in the lumbar dorsal horn of the spinal cord is required for central sensitization, the central facilitation of pain transmission produced by peripheral injury

Mediated Habits: Images, Networked Affect and Social Change

While many people remain hopeful that particular images of injustice will have the power to catalyse progressive transformation, there is also widespread belief in the inevitability of ‘compassion fatigue’. Bringing philosophers of habit into conversation with contemporary scholars of affect, visual culture and digital media, this article argues for a more nuanced understanding of the links between images and change – one in which political feeling and political action are complexly intertwined and repeated sensation does not necessarily lead to disaffection. When affect acts as a ‘binding technique’ compelling us to inhabit our sensorial responses to images, I suggest, we may become better attuned to everyday patterns of seeing, feeling, thinking and interacting – and hence to the possibility of change at the level of habit. This article thus contends that thinking affect and habit together as imbricated may enable us to better understand the dynamics of both individual and socio-political change today

Ensuring transparency and minimization of methodologic bias in preclinical pain research:PPRECISE considerations

Acknowledgements The authors thank Allison Lin, Dan Mellon, and LiSheng Chen for their help throughout the process of writing this article.Peer reviewedPublisher PD

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Modernism, class and colonialism in Robert Noonan’s The Ragged Trousered Philanthropists

This essay explores Robert Noonan’s 1914 novel, The Ragged Trousered Philanthropists, as a work of Irish modernist fiction. Reading its fragmented narrative as a reflection of the author’s subaltern position as an Irish republican and socialist, it interprets Noonan’s work as the product of the anticolonial and class struggles in which he was involved. Its critique of capitalist and imperial hegemony and the assertions that suffering, injustice and violence are normal, natural or inevitable phenomena reflects the author’s frustration, anger and desperation. In this way the novel counters and decentres the bourgeois-imperial dynamic that was reflected in the textual stability of Victorian realism. The Ragged Trousered Philanthropists is an uneasy text that is at once ruptured and uncertain of its own aesthetic status and conveys, through its shifting, episodic plot, the precariousness of a working-class existence permanently poised “on the brink of destitution.” © 2018 Informa UK Limited, trading as Taylor & Francis Grou

A Multicenter, Randomized, Placebo‐Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis

Objective: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. Methods: A randomized, double‐blind, placebo‐controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P 50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. Results: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient‐years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low‐density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C‐reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI −14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar. Conclusion: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists’ Collaboration meta‐analysis of statin effects in other populations

The global burden of gout: estimates from the Global Burden of Disease 2010 study

Objective: Gout is the most common cause of inflammatory arthritis in men, but has not previously been included in Global Burden of Disease (GBD) studies. As part of the GBD 2010 Study, the Musculoskeletal Disorders and Risk Factors Expert Group estimated the global burden of gout. Methods: The American Rheumatism Association 1977 case definition of primary gout was used in the study. A series of systematic reviews were conducted to gather the age-specific and sex-specific epidemiological data for gout prevalence, incidence, mortality risk and duration. Two main disabling sequelae of gout were identified; acute episode gout and chronic polyarticular gout, and used in the surveys to collect data to derive disability weights. The epidemiological data together with disability weights were then used to calculate years of life lived with disability (YLDs) for gout, for 1990 and 2010. No evidence of cause-specific mortality associated with gout was found. Gout disability-adjusted life years (DALYs), therefore, have the same value as YLDs. Results: Global prevalence of gout was 0.08% (95% uncertainty interval (UI) 0.07 to 0.08). DALYs increased from 76 000 (95% UI 48 to 112) in 1990 to 114 000 (95% UI 72 to 167) in 2010. Out of all 291 conditions studied in the GBD 2010 Study, gout ranked 138th in terms of disability as measured by YLDs, and 173rd in terms of overall burden (DALYs). Conclusions: The burden of gout is rising. With increasing ageing populations globally, this evidence is a significant prompt to optimise treatment and management of gout at individual, community and national levels