The Ghosts of Bindings Past: Micro-Computed X-Ray Tomography for the Study of Bookbinding

This essay describes the results of a new application of micro-computed X-ray tomography (µCT) to conduct nondestructive investigations of the binding structures of premodern books. This application addresses a twofold challenge in the study of historic bindings and their construction. Few premodern books survive in their original bindings. Moreover, until recently, when books were rebound, the original structures were rarely documented, and the remains were usually discarded. Where original bindings do remain in situ, much of their structure is, by design, hidden. Particulars of construction may be surmised; but without destructive disbinding, little can be proven. µCT enables an exploratory, multilinear approach to codicological investigations that makes bindings accessible in the form of tractable volumetric data

Phylogenomics of the Reproductive Parasite Wolbachia pipientis wMel: A Streamlined Genome Overrun by Mobile Genetic Elements

The complete sequence of the 1,267,782 bp genome of Wolbachia pipientis wMel, an obligate intracellular bacteria of Drosophila melanogaster, has been determined. Wolbachia, which are found in a variety of invertebrate species, are of great interest due to their diverse interactions with different hosts, which range from many forms of reproductive parasitism to mutualistic symbioses. Analysis of the wMel genome, in particular phylogenomic comparisons with other intracellular bacteria, has revealed many insights into the biology and evolution of wMel and Wolbachia in general. For example, the wMel genome is unique among sequenced obligate intracellular species in both being highly streamlined and containing very high levels of repetitive DNA and mobile DNA elements. This observation, coupled with multiple evolutionary reconstructions, suggests that natural selection is somewhat inefficient in wMel, most likely owing to the occurrence of repeated population bottlenecks. Genome analysis predicts many metabolic differences with the closely related Rickettsia species, including the presence of intact glycolysis and purine synthesis, which may compensate for an inability to obtain ATP directly from its host, as Rickettsia can. Other discoveries include the apparent inability of wMel to synthesize lipopolysaccharide and the presence of the most genes encoding proteins with ankyrin repeat domains of any prokaryotic genome yet sequenced. Despite the ability of wMel to infect the germline of its host, we find no evidence for either recent lateral gene transfer between wMel and D. melanogaster or older transfers between Wolbachia and any host. Evolutionary analysis further supports the hypothesis that mitochondria share a common ancestor with the α-Proteobacteria, but shows little support for the grouping of mitochondria with species in the order Rickettsiales. With the availability of the complete genomes of both species and excellent genetic tools for the host, the wMel–D. melanogaster symbiosis is now an ideal system for studying the biology and evolution of Wolbachia infections

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Mesh versus non-mesh for inguinal and femoral hernia repair

BackgroundThis is an update of a Cochrane Review first published in 2001.Hernias are protrusions of all or part of an organ through the body wall that normally contains it. Groin hernias include inguinal (96%) and femoral (4%) hernias, and are often symptomatic with discomfort. They are extremely common, with an estimated lifetime risk in men of 27%. Occasionally they may present as emergencies with complications such as bowel incarceration, obstruction and strangulation. The definitive treatment of all hernias is surgical repair, inguinal hernia repair being one of the most common surgical procedures performed. Mesh (hernioplasty) and the traditional non-mesh repairs (herniorrhaphy) are commonly used, with an increasing preference towards mesh repairs in high-income countries.ObjectivesTo evaluate the benefits and harms of different inguinal and femoral hernia repair techniques in adults, specifically comparing closure with mesh versus without mesh. Outcomes include hernia recurrence, complications (including neurovascular or visceral injury, haematoma, seroma, testicular injury, infection, postoperative pain), mortality, duration of operation, postoperative hospital stay and time to return to activities of daily living.Search methodsWe searched the following databases on 9 May 2018: Cochrane Colorectal Cancer Group Specialized Register, Cochrane Central Register of Controlled Trials (Issue 1), Ovid MEDLINE (from 1950), Ovid Embase (from 1974) and Web of Science (from 1900). Furthermore, we checked the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for trials. We applied no language or publication restrictions. We also searched the reference lists of included trials and review articles.Selection criteriaWe included randomised controlled trials of mesh compared to non-mesh inguinal or femoral hernia repairs in adults over the age of 18 years.Data collection and analysisWe used standard methodological procedures expected by Cochrane. Where available, we collected information on adverse effects. We presented dichotomous data as risk ratios, and where possible we calculated the number needed to treat for an additional beneficial outcome (NNTB). We presented continuous data as mean difference. Analysis of missing data was based on intention-to-treat principles, and we assessed heterogeneity using an evaluation of clinical and methodological diversity, Chi(2) test and I-2 statistic. We used GRADE to assess the quality of evidence for each outcome.Main resultsWe included 25 studies (6293 participants) in this review. All included studies specified inguinal hernias, and two studies reported that femoral hernias were included.Mesh repair probably reduces the risk of hernia recurrence compared to non-mesh repair (21 studies, 5575 participants; RR 0.46, 95% CI 0.26 to 0.80, I-2 = 44%, moderate-quality evidence). In absolute numbers, one hernia recurrence was prevented for every 46 mesh repairs compared with non-mesh repairs. Twenty-four studies (6293 participants) assessed a wide range of complications with varying follow-up times. Neurovascular and visceral injuries were more common in non-mesh repair groups (RR 0.61, 95% CI 0.49 to 0.76, I-2 = 0%, NNTB = 22, high-quality evidence). Wound infection was found slightly more commonly in the mesh group (20 studies, 4540 participants; RR 1.29, 95% CI 0.89 to 1.86, I-2 = 0%, NNTB = 200, low-quality evidence). Mesh repair reduced the risk of haematoma compared to non-mesh repair (15 studies, 3773 participants; RR 0.88, 95% CI 0.68 to 1.13, I-2 = 0%, NNTB = 143, low-quality evidence). Seromas probably occur more frequently with mesh repair than with non-mesh repair (14 studies, 2640 participants; RR 1.63, 95% CI 1.03 to 2.59, I-2 = 0%, NNTB = 72, moderate-quality evidence), as does wound swelling (two studies, 388 participants; RR 4.56, 95% CI 1.02 to 20.48, I-2 = 33%, NNTB = 72, moderate-quality evidence). The comparative effect on wound dehiscence is uncertain due to wide confidence intervals (two studies, 329 participants; RR 0.55, 95% CI 0.12 to 2.48, I-2 = 37% NNTB = 77, low-quality evidence). Testicular complications showed nearly equivocal results; they probably occurred slightly more often in the mesh group however the confidence interval around the effect was wide (14 studies, 3741 participants; RR 1.06, 95% CI 0.63 to 1.76, I-2 = 0%, NNTB = 2000, low-quality evidence). Mesh reduced the risk of postoperative urinary retention compared to non-mesh (eight studies, 1539 participants; RR 0.53, 95% CI 0.38 to 0.73, I-2 = 56%, NNTB = 16, moderate-quality evidence).Postoperative and chronic pain could not be compared due to variations in measurement methods and follow-up time (low-quality evidence).No deaths occurred during the follow-up periods reported in the seven studies (2546 participants) reporting this outcome (high-quality evidence).The average operating time was longer for non-mesh repairs by a mean of 4 minutes 22 seconds, despite wide variation across the studies regarding size and direction of effect, thus this result is uncertain (20 studies, 4148 participants; 95% CI -6.85 to -1.60, I-2 = 97%, very low-quality evidence). Hospital stay may be shorter with mesh repair, by 0.6 days (12 studies, 2966 participants; 95% CI -0.86 to -0.34, I-2 = 98%, low-quality evidence), and participants undergoing mesh repairs may return to normal activities of daily living a mean of 2.87 days sooner than those with non-mesh repair (10 studies, 3183 participants; 95% CI -4.42 to -1.32, I-2 = 96%, low-quality evidence), although the results of both these outcomes are also limited by wide variation in the size and direction of effect across the studies.Authors' conclusionsMesh and non-mesh repairs are effective surgical approaches in treating hernias, each demonstrating benefits in different areas. Compared to non-mesh repairs, mesh repairs probably reduce the rate of hernia recurrence, and reduce visceral or neurovascular injuries, making mesh repair a common repair approach. Mesh repairs may result in a reduced length of hospital stay and time to return to activities of daily living, but these results are uncertain due to variation in the results of the studies. Non-mesh repair is less likely to cause seroma formation and has been favoured in low-income countries due to low cost and reduced availability of mesh materials. Risk of bias in the included studies was low to moderate and generally handled well by study authors, with attention to details of allocation, blinding, attrition and reporting

RAD Collaboration in the Writing Center: An Impact Study of Course-Embedded Writing Center Support on Student Writing in a Criminological Theory Course

Given numerous calls within the writing center community for replicable, aggregable, and data-driven (RAD) research, this article presents findings from a study of course-embedded writing center impact on student writing in a writing-intensive criminological theory course. The research team analyzed papers from two semesters of the same course: one where students were given extra credit for self-selecting to work with the writing center and one where course-embedded writing center support was implemented. A total of 162 papers were analyzed using two taxonomies in order to study writing center impact on (a) grammatical correctness (mechanics, relationships between words, clauses, and the whole paper), as well as (b) student engagement with and comprehension of course content. Findings show that students in the semester with course-embedded writing center support had fewer grammatical errors in three out of the four subcategories analyzed, but also showed that GPA was the strongest predictor of grammatical correctness. Findings also indicate that course-embedded writing center support was the strongest predictor of students’ engagement with and comprehension of course content for the first of two theories in each of their papers, but that the student’s GPA coming into the course was a stronger predictor of student’s engagement and comprehension of a second theory in each of their papers.University Writing Cente

astropy/SPISEA: v2.1.11

Bugfix to RedLawFritz11 so that paths work regardless of operating system used (from Winston Zhang

Effects of wearing gumboots and leather lace-up boots on lower limb muscle activity when walking on simulated underground coal mine surfaces

This study aimed to investigate the effects of wearing two standard underground coal mining work boots (a gumboot and a leather lace-up boot) on lower limb muscle activity when participants walked across simulated underground coal mining surfaces. Quadriceps (rectus femoris, vastus medialis, vastus lateralis) and hamstring (biceps femoris, semitendinosus) muscle activity were recorded as twenty male participants walked at a self-selected pace around a circuit while wearing each boot type. The circuit consisted of level, inclined and declined surfaces composed of rocky gravel and hard dirt. Walking in a leather lace-up boot, compared to a gumboot, resulted in increased vastus lateralis and increased biceps femoris muscle activity when walking on sloped surfaces. Increased muscle activity appears to be acting as a slip and/or trip prevention strategy in response to challenging surfaces and changing boot features