Vortex fluidics-mediated DNA rescue from formalin-fixed museum specimens.

DNA from formalin-preserved tissue could unlock a vast repository of genetic information stored in museums worldwide. However, formaldehyde crosslinks proteins and DNA, and prevents ready amplification and DNA sequencing. Formaldehyde acylation also fragments the DNA. Treatment with proteinase K proteolyzes crosslinked proteins to rescue the DNA, though the process is quite slow. To reduce processing time and improve rescue efficiency, we applied the mechanical energy of a vortex fluidic device (VFD) to drive the catalytic activity of proteinase K and recover DNA from American lobster tissue (Homarus americanus) fixed in 3.7% formalin for >1-year. A scan of VFD rotational speeds identified the optimal rotational speed for recovery of PCR-amplifiable DNA and while 500+ base pairs were sequenced, shorter read lengths were more consistently obtained. This VFD-based method also effectively recovered DNA from formalin-preserved samples. The results provide a roadmap for exploring DNA from millions of historical and even extinct species

Dialogue on 'Institutional complementarity and political economy'

"Martin Höpner's paper was written to structure discussions at a workshop of the 'Complementarity Project', which was held in Paris, 26-27 September 2003. The project was organized by Bruno Amable and Robert Boyer, Colin Crouch, Martin Höpner and Wolfgang Streeck. The subject of the workshop was the complementarity, real or imagined, of financial markets and industrial relations in present-day 'varieties of capitalism'. Apart from the organizers, participants included Patrick Le Gales, Peter Hall, Gregory Jackson, Bruce Kogut, David Marsden and Pascal Petit. In the follwing we document short excerpts from five out of nine 'reaction papers' written by participants in advance of the workshop." (author's abstract

ABCC9/SUR2 in the Brain: Implications for Hippocampal Sclerosis of Aging and a Potential Therapeutic Target

The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“K ATP ”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The K ATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is a result of ABCC9 mutations; we discuss neurologic manifestations of this genetic syndrome. More common brain disorders linked to ABCC9 gene variants include hippocampal sclerosis of aging (HS-Aging), sleep disorders, and depression. HS-Aging is a prevalent neurological disease with pathologic features of both neurodegenerative (aberrant TDP-43) and cerebrovascular (arteriolosclerosis) disease. As to potential therapeutic intervention, the human pharmacopeia features both SUR2 agonists and antagonists, so ABCC9 /SUR2 may provide a “druggable target”, relevant perhaps to both HS-Aging and Alzheimer\u27s disease. We conclude that more work is required to better understand the roles of ABCC9 /SUR2 in the human brain during health and disease conditions

Titania-doped tantala/silica coatings for gravitational-wave detection

Reducing thermal noise from optical coatings is crucial to reaching the required sensitivity in next generation interferometric gravitational-wave detectors. Here we show that adding TiO2 to Ta2O5 in Ta2O5/SiO2 coatings reduces the internal friction and in addition present data confirming it reduces thermal noise. We also show that TiO2-doped Ta2O5/SiO2 coatings are close to satisfying the optical absorption requirements of second generation gravitational-wave detectors

'A feminine touch’: gender, design and the ocean liner

This article offers an interdisciplinary account of gender in relation to ocean liner interior design. It outlines a case study of what the discipline of design history can bring to gender and maritime history. A historiography of the subject is followed by an analysis of the ways in which the spaces on board British ocean liners were conceived of, designed and used in terms of gender. Some spaces on board were designated as female only and other spaces understood to be male only – particularly the smoking room. The concluding part of the article considers the role of women designers within the patriarchal world of ship design and construction, by investigating the contributions of Elsie Mackay at P & O and the Zinkeisen sisters on the Queen Mary. Using primary sources, including visual evidence, the article considers a range of liners, from the Hindostan (1842) through to the Orontes (1929; refitted 1948). This bridges the gap between design history, gender and maritime history and adds to debates around gender and maritime history with a consideration of the overlooked area of design and its histories

Intravesical rAd-IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study.

Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10(11) viral particles (vp)/mL or 3 × 10(11) vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd-IFNα/Syn3 (1 × 10(11) vp/mL, n = 21; 3 × 10(11) vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd-IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd-IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy

Correspondence: Are Cognitive Functions Localizable? Colin Camerer et al. versus Marieke van Rooij and John G. Holden

The Fall 2011 issue of this journal published a two-paper section on “Neuroeconomics.” One paper, by Ernst Fehr and Antonio Rangel, clearly and concisely summarized a small part of the fast-growing literature. The second paper, “It’s about Space, It’s about Time, Neuroeconomics, and the Brain Sublime,” by Marieke van Rooij and Guy Van Orden, is beautifully written and enjoyable to read, but misleading in many critical ways. A number of economists and neuroscientists working at the intersection of the two fields shared our reaction and have signed this letter, as shown below. Some of the paper’s descriptions of empirical findings and methods in neuroeconomics are incomplete, badly out of date, or flatly wrong. In studies the authors describe in detail, their skeptical interpretations have often been refuted by published data, old and new, that they overlook

Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke : a secondary analysis of an individual patient data meta-analysis

Background Randomised trials have shown that alteplase improves the odds of a good outcome when delivered within 4.5 h of acute ischaemic stroke. However, alteplase also increases the risk of intracerebral haemorrhage; we aimed to determine the proportional and absolute effects of alteplase on the risks of intracerebral haemorrhage, mortality, and functional impairment in different types of patients. Methods We used individual patient data from the Stroke Thrombolysis Trialists' (STT) meta-analysis of randomised trials of alteplase versus placebo (or untreated control) in patients with acute ischaemic stroke. We prespecified assessment of three classifications of intracerebral haemorrhage: type 2 parenchymal haemorrhage within 7 days; Safe Implementation of Thrombolysis in Stroke Monitoring Study's (SITS-MOST) haemorrhage within 24-36 h (type 2 parenchymal haemorrhage with a deterioration of at least 4 points on National Institutes of Health Stroke Scale [NIHSS]); and fatal intracerebral haemorrhage within 7 days. We used logistic regression, stratified by trial, to model the log odds of intracerebral haemorrhage on allocation to alteplase, treatment delay, age, and stroke severity. We did exploratory analyses to assess mortality after intracerebral haemorrhage and examine the absolute risks of intracerebral haemorrhage in the context of functional outcome at 90-180 days. Findings Data were available from 6756 participants in the nine trials of intravenous alteplase versus control. Alteplase increased the odds of type 2 parenchymal haemorrhage (occurring in 231 [6.8%] of 3391 patients allocated alteplase vs 44 [1.3%] of 3365 patients allocated control; odds ratio [OR] 5.55 [95% CI 4.01-7.70]; absolute excess 5.5% [4.6-6.4]); of SITS-MOST haemorrhage (124 [3.7%] of 3391 vs 19 [0.6%] of 3365; OR 6.67 [4.11-10.84]; absolute excess 3.1% [2.4-3.8]); and of fatal intracerebral haemorrhage (91 [2.7%] of 3391 vs 13 [0.4%] of 3365; OR 7.14 [3.98-12.79]; absolute excess 2.3% [1.7-2.9]). However defined, the proportional increase in intracerebral haemorrhage was similar irrespective of treatment delay, age, or baseline stroke severity, but the absolute excess risk of intracerebral haemorrhage increased with increasing stroke severity: for SITS-MOST intracerebral haemorrhage the absolute excess risk ranged from 1.5% (0.8-2.6%) for strokes with NIHSS 0-4 to 3.7% (2.1-6.3%) for NIHSS 22 or more (p=0.0101). For patients treated within 4.5 h, the absolute increase in the proportion (6.8% [4.0% to 9.5%]) achieving a modified Rankin Scale of 0 or 1 (excellent outcome) exceeded the absolute increase in risk of fatal intracerebral haemorrhage (2.2% [1.5% to 3.0%]) and the increased risk of any death within 90 days (0.9% [-1.4% to 3.2%]). Interpretation Among patients given alteplase, the net outcome is predicted both by time to treatment (with faster time increasing the proportion achieving an excellent outcome) and stroke severity (with a more severe stroke increasing the absolute risk of intracerebral haemorrhage). Although, within 4.5 h of stroke, the probability of achieving an excellent outcome with alteplase treatment exceeds the risk of death, early treatment is especially important for patients with severe stroke.Peer reviewe