Reading, Trauma and Literary Caregiving 1914-1918: Helen Mary Gaskell and the War Library

This article is about the relationship between reading, trauma and responsive literary caregiving in Britain during the First World War. Its analysis of two little-known documents describing the history of the War Library, begun by Helen Mary Gaskell in 1914, exposes a gap in the scholarship of war-time reading; generates a new narrative of "how," "when," and "why" books went to war; and foregrounds gender in its analysis of the historiography. The Library of Congress's T. W. Koch discovered Gaskell's ground-breaking work in 1917 and reported its successes to the American Library Association. The British Times also covered Gaskell's library, yet researchers working on reading during the war have routinely neglected her distinct model and method, skewing the research base on war-time reading and its association with trauma and caregiving. In the article's second half, a literary case study of a popular war novel demonstrates the extent of the "bitter cry for books." The success of Gaskell's intervention is examined alongside H. G. Wells's representation of textual healing. Reading is shown to offer sick, traumatized and recovering combatants emotional and psychological caregiving in ways that she could not always have predicted and that are not visible in the literary/historical record

Hospital Mental Health Admissions in Women after Unsuccessful Infertility Treatment and In Vitro Fertilization: An Australian Population-Based Cohort Study

Objective - To examine the association between in vitro fertilization (IVF) and later admission to hospital with a mental health diagnosis in women who remained childless after infertility treatment. Methods - This was a population-based cohort study using linked administrative hospital and registry data. The study population included all women commencing hospital treatment for infertility in Western Australia between the years 1982 and 2002 aged 20–44 years at treatment commencement who did not have a recorded birth by the end of follow-up (15 August 2010) and did not have a hospital mental health admission prior to the first infertility admission (n=6,567). Of these, 2,623 women had IVF and 3,944 did not. We used multivariate Cox regression modeling of mental health admissions and compared women undergoing IVF treatment with women having infertility treatment but not IVF. Results - Over an average of 17 years of follow-up, 411 women in the cohort were admitted to hospital with a mental health diagnosis; 93 who had IVF and 318 who did not. The unadjusted hazard ratio (HR) for a hospital mental health admission comparing women who had IVF with those receiving other infertility treatment was 0.50 (95% confidence interval [CI] 0.40–0.63). After adjustment for age, calendar year and socio-economic status the HR was 0.56 (95% CI 0.44–0.71). Conclusions - IVF treatment is associated with a reduced risk of hospital mental health admissions in women after unsuccessful infertility treatment. This may be explained by the healthy cohort effect

A Phase II Trial of Prexasertib (LY2606368) in Patients With Extensive-Stage Small-Cell Lung Cancer

Patients with extensive-stage small-cell lung cancer (ED-SCLC) need improved outcomes in the relapsed/refractory setting. This phase II study evaluated the safety and efficacy of prexasertib, a checkpoint kinase 1 inhibitor, in platinum-sensitive and platinum-refractory ED-SCLC. Prexasertib demonstrated response rates of 5.2% in platinum-sensitive and 0% in platinum-refractory ED-SCLC. Prexasertib did not show prespecified efficacy as monotherapy in ED-SCLC. Background: This study assessed the checkpoint kinase 1 inhibitor prexasertib in patients with extensive-stage smallcell lung cancer (ED-SCLC).Patients and Methods: This was a parallel-cohort phase II study of 105 mg/m2 prexasertib once every 14 days for patients who progressed after no more than two prior therapies and had platinum-sensitive (Cohort 1) or platinum-resistant/platinum-refractory (Cohort 2) disease. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics. Exploratory endpoints included biomarker identification and assessment of an alternative regimen (Cohort 3: 40 mg/m2 days 1-3, 14-day cycle). Results: In Cohort 1 (n = 58), ORR was 5.2%; DCR, 31%; median PFS, 1.41 months (95% confidence interval [CI], 1.31-1.64); and median OS, 5.42 months (95% CI, 3.75-8.51). In Cohort 2 (n = 60), ORR was 0%; DCR, 20%; median PFS, 1.36 months (95% CI, 1.25-1.45); and median OS, 3.15 months (95% CI, 2.27-5.52). The most frequent all-grade, related, treatment-emergent adverse events were decreased neutrophil count (Cohort 1, 69.6%; Cohort 2, 73.3%), decreased platelet count (Cohort 1, 51.8%; Cohort 2, 50.0%), decreased white blood cell count (Cohort 1, 28.6%; Cohort 2, 40.0%), and anemia (Cohort 1, 39.3%; Cohort 2, 28.3%). Eleven patients (19.6%) in Cohort 1 and one patient (1.7%) in Cohort 2 experienced grade ≥3 febrile neutropenia. Prexasertib pharmacokinetics were consistent with prior studies. Cohort 3 outcomes were similar to those of Cohorts 1 and 2. No actionable biomarkers were identified. Conclusion: Prexasertib did not demonstrate activity to warrant future development as monotherapy in ED-SCLC

A Large Polysaccharide Produced by <i>Helicobacter hepaticus</i> Induces an Anti-inflammatory Gene Signature in Macrophages

Interactions between the host and its microbiota are of mutual benefit and promote health. Complex molecular pathways underlie this dialog, but the identity of microbe-derived molecules that mediate the mutualistic state remains elusive. Helicobacter hepaticus is a member of the mouse intestinal microbiota that is tolerated by the host. In the absence of an intact IL-10 signaling, H. hepaticus induces an IL-23-driven inflammatory response in the intestine. Here we investigate the interactions between H. hepaticus and host immune cells that may promote mutualism, and the microbe-derived molecule(s) involved. Our results show that H. hepaticus triggers early IL-10 induction in intestinal macrophages and produces a large soluble polysaccharide that activates a specific MSK/CREB-dependent anti-inflammatory and repair gene signature via the receptor TLR2. These data identify a host-bacterial interaction that promotes mutualistic mechanisms at the intestinal interface. Further understanding of this pathway may provide novel prevention and treatment strategies for inflammatory bowel disease.We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics for the generation of the Sequencing data. F.F. was supported by Cancer Research UK (OCRC-DPhil13-FF) and N.E.I. by the Kennedy Trust (KENN 15 16 03). M.M.-L. received a fellowship from the Spanish Ministry of Education, Culture, and Sport. This work was funded by the Wellcome Trust UK (095688/Z/11/Z), an ERC grant (Advanced Grant Ares(2013)3687660), and the Fondation Louis JeantetS

Cluster K Mycobacteriophages: Insights into the Evolutionary Origins of Mycobacteriophage TM4

Five newly isolated mycobacteriophages –Angelica, CrimD, Adephagia, Anaya, and Pixie – have similar genomic architectures to mycobacteriophage TM4, a previously characterized phage that is widely used in mycobacterial genetics. The nucleotide sequence similarities warrant grouping these into Cluster K, with subdivision into three subclusters: K1, K2, and K3. Although the overall genome architectures of these phages are similar, TM4 appears to have lost at least two segments of its genome, a central region containing the integration apparatus, and a segment at the right end. This suggests that TM4 is a recent derivative of a temperate parent, resolving a long-standing conundrum about its biology, in that it was reportedly recovered from a lysogenic strain of Mycobacterium avium, but it is not capable of forming lysogens in any mycobacterial host. Like TM4, all of the Cluster K phages infect both fast- and slow-growing mycobacteria, and all of them – with the exception of TM4 – form stable lysogens in both Mycobacterium smegmatis and Mycobacterium tuberculosis; immunity assays show that all five of these phages share the same immune specificity. TM4 infects these lysogens suggesting that it was either derived from a heteroimmune temperate parent or that it has acquired a virulent phenotype. We have also characterized a widely-used conditionally replicating derivative of TM4 and identified mutations conferring the temperature-sensitive phenotype. All of the Cluster K phages contain a series of well conserved 13 bp repeats associated with the translation initiation sites of a subset of the genes; approximately one half of these contain an additional sequence feature composed of imperfectly conserved 17 bp inverted repeats separated by a variable spacer. The K1 phages integrate into the host tmRNA and the Cluster K phages represent potential new tools for the genetics of M. tuberculosis and related species

Pass a Law, Any Law, Fast! State Legislative Responses to the Kelo Backlash

The Supreme Court in Kelo v. City of New London left protection of property against takings for economic development to the states. Since Kelo, thirty-seven states have enacted legislation to update their eminent domain laws. This paper is the first to theoretically and empirically analyze the factors that influence whether, in what manner, and how quickly states change their laws through new legislation. Fourteen of the thirty-seven new laws offer only weak protections against development takings. The legislative response to Kelo was responsive to measures of the backlash but only in the binary decision whether to pass any new law. The decision to enact a meaningful restriction was more a function of relevant political economy measures. States with more economic freedom, greater value of new housing construction, and less racial and income inequality are more likely to have enacted stronger restrictions, and sooner. Of the thirteen states that have not updated, Arkansas, Oklahoma and Mississippi are highly likely to do so in the future. Hawaii, Massachusetts and New York are unlikely to update ever if at all

Interstitial cell migration: integrin-dependent and alternative adhesion mechanisms

Adhesion and migration are integrated cell functions that build, maintain and remodel the multicellular organism. In migrating cells, integrins are the main transmembrane receptors that provide dynamic interactions between extracellular ligands and actin cytoskeleton and signalling machineries. In parallel to integrins, other adhesion systems mediate adhesion and cytoskeletal coupling to the extracellular matrix (ECM). These include multifunctional cell surface receptors (syndecans and CD44) and discoidin domain receptors, which together coordinate ligand binding with direct or indirect cytoskeletal coupling and intracellular signalling. We review the way that the different adhesion systems for ECM components impact cell migration in two- and three-dimensional migration models. We further discuss the hierarchy of these concurrent adhesion systems, their specific tasks in cell migration and their contribution to migration in three-dimensional multi-ligand tissue environments

Opportunities and Challenges for Molecular Understanding of Ciliopathies-The 100,000 Genomes Project.

Cilia are highly specialized cellular organelles that serve multiple functions in human development and health. Their central importance in the body is demonstrated by the occurrence of a diverse range of developmental disorders that arise from defects of cilia structure and function, caused by a range of different inherited mutations found in more than 150 different genes. Genetic analysis has rapidly advanced our understanding of the cell biological basis of ciliopathies over the past two decades, with more recent technological advances in genomics rapidly accelerating this progress. The 100,000 Genomes Project was launched in 2012 in the UK to improve diagnosis and future care for individuals affected by rare diseases like ciliopathies, through whole genome sequencing (WGS). In this review we discuss the potential promise and medical impact of WGS for ciliopathies and report on current progress of the 100,000 Genomes Project, reviewing the medical, technical and ethical challenges and opportunities that new, large scale initiatives such as this can offer