Julian of Norwich and her children today: Editions, translations and versions of her revelations

The viability of such concepts as "authorial intention," "the original text," "critical edition" and, above all, "scholarly editorial objectivity" is not what it was, and a study of the textual progeny of the revelations of Julian of Norwich--editions, versions, translations and selections--does little to rehabilitate them. Rather it tends to support the view that a history of reading is indeed a history of misreading or, more positively, that texts can have an organic life of their own that allows them to reproduce and evolve quite independently of their author. Julian's texts have had a more robustly continuous life than those of any other Middle English mystic. Their history--in manuscript and print, in editions more or less approximating Middle English and in translations more or less approaching Modern English--is virtually unbroken since the fifteenth century. But on this perilous journey, many and strange are the clutches into which she and her textual progeny have fallen

The development of a new measure of quality of life in the management of gastro-oesophageal reflux disease: the Reflux Questionnaire.

INTRODUCTION This paper reports on the development of a new measure of health-related quality of life for use among patients with gastro-oesophageal reflux disease (GORD), funded as part of the REFLUX trial. This is a large UK multi centre trial that aims to compare the clinical and cost effectiveness of minimal access surgery with best medical treatment for patients with GORD within the NHS. Method Potential items were identified via a series of interviews and focus groups carried out with patients who were receiving/had received medical or surgical treatment for GORD. The final measure consisted of 31 items covering 7 categories (Heartburn; Acid reflux; Wind; Eating and swallowing; Bowel movements; Sleep; Work, physical and social activities). The measure produced two outputs: a quality of life score (RQLS) and five Reflux symptom scores. Reliability (internal consistency), criterion validity with the SF-36 and, sensitivity to change in terms of relationship with reported change in prescribed medication were assessed amongst a sample of 794 patients recruited into the trial. RESULTS The measure was shown to be internally consistent, to show criterion validity with the SF-36 and sensitive to changes in patients use of prescribed medication at baseline and 3 month follow-up. DISCUSSION The Reflux questionnaire is a new self-administered questionnaire for use amongst patients with GORD. Initial findings suggest that the new measure is valid, reliable, acceptable to respondents and simple to administer in both a clinical and research context

Robust diagnostic genetic testing using solution capture enrichment and a novel variant-filtering interface.

Targeted hybridization enrichment prior to next-generation sequencing is a widespread method for characterizing sequence variation in a research setting, and is being adopted by diagnostic laboratories. However, the number of variants identified can overwhelm clinical laboratories with strict time constraints, the final interpretation of likely pathogenicity being a particular bottleneck. To address this, we have developed an approach in which, after automatic variant calling on a standard unix pipeline, subsequent variant filtering is performed interactively, using AgileExomeFilter and AgilePindelFilter (http://dna.leeds.ac.uk/agile), tools designed for clinical scientists with standard desktop computers. To demonstrate the method's diagnostic efficacy, we tested 128 patients using (1) a targeted capture of 36 cancer-predisposing genes or (2) whole-exome capture for diagnosis of the genetically heterogeneous disorder primary ciliary dyskinesia (PCD). In the cancer cohort, complete concordance with previous diagnostic data was achieved across 793 variant genotypes. A high yield (42%) was also achieved for exome-based PCD diagnosis, underscoring the scalability of our method. Simple adjustments to the variant filtering parameters further allowed the identification of a homozygous truncating mutation in a presumptive new PCD gene, DNAH8. These tools should allow diagnostic laboratories to expand their testing portfolios flexibly, using a standard set of reagents and techniques

Process evaluation of appreciative inquiry to translate pain management evidence into pediatric nursing practice

Background Appreciative inquiry (AI) is an innovative knowledge translation (KT) intervention that is compatible with the Promoting Action on Research in Health Services (PARiHS) framework. This study explored the innovative use of AI as a theoretically based KT intervention applied to a clinical issue in an inpatient pediatric care setting. The implementation of AI was explored in terms of its acceptability, fidelity, and feasibility as a KT intervention in pain management. Methods A mixed-methods case study design was used. The case was a surgical unit in a pediatric academic-affiliated hospital. The sample consisted of nurses in leadership positions and staff nurses interested in the study. Data on the AI intervention implementation were collected by digitally recording the AI sessions, maintaining logs, and conducting individual semistructured interviews. Data were analysed using qualitative and quantitative content analyses and descriptive statistics. Findings were triangulated in the discussion. Results Three nurse leaders and nine staff members participated in the study. Participants were generally satisfied with the intervention, which consisted of four 3-hour, interactive AI sessions delivered over two weeks to promote change based on positive examples of pain management in the unit and staff implementation of an action plan. The AI sessions were delivered with high fidelity and 11 of 12 participants attended all four sessions, where they developed an action plan to enhance evidence-based pain assessment documentation. Participants labeled AI a 'refreshing approach to change' because it was positive, democratic, and built on existing practices. Several barriers affected their implementation of the action plan, including a context of change overload, logistics, busyness, and a lack of organised follow-up. Conclusions Results of this case study supported the acceptability, fidelity, and feasibility of AI as a KT intervention in pain management. The AI intervention requires minor refinements (e.g., incorporating continued follow-up meetings) to enhance its clinical utility and sustainability. The implementation process and effectiveness of the modified AI intervention require evaluation in a larger multisite study

Tuning of Human Modulation Filters Is Carrier-Frequency Dependent

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Postherpetic Neuralgia: Role of Gabapentin and Other Treatment Modalities

Postherpetic neuralgia (PHN) is a chronic and painful condition that may occur after a herpes zoster infection. The frequency of PHN after untreated zoster varies widely. Age is the most important risk factor for development of PHN. The condition occurs in an estimated 50% of patients older than 50 years. The pain of PHN can be severe and debilitating and is frequently associated with allodynia. Although in most patients pain remits within the first year, it may persist for a lifetime. Tricyclic antidepressants (TCAs), topical agents, opioids, and gabapentin, a structural Γ-amino butyric acid (GABA) analogue, are the only agents that have demonstrated efficacy in randomized clinical trials for treatment of both the shooting and the burning form of pain associated with PHN. TCAs are among the most commonly used classes of agents for treating PHN and are effective in a significant proportion of patients. However, various adverse events can limit treatment. These side effects tend to be more acute in the elderly, the population most likely to suffer from PHN. Topical agents have led to mild to moderate improvement in patients with PHN but are usually ineffective as monotherapy for this condition. Until recently, carbamazepine was the only antiepileptic drug evaluated for the treatment of PHN. Over the past few years, however, gabapentin has received increasing attention as a useful treatment for neuropathic pain. Gabapentin lacks significant drug-drug interactions and has a favorable safety profile, which makes it particularly useful for treatment of PHN.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65597/1/j.1528-1157.1999.tb00933.x.pd

Projections from the paralemniscal nucleus to the spinal cord in the mouse

The present study investigated the projection from the paralemniscal nucleus (PL) to the spinal cord in the mouse by injecting the retrograde tracer fluoro-gold to different levels of the spinal cord and injecting the anterograde tracer biotinylated dextran amine into PL. We found that PL projects to the entire spinal cord with obvious contralateral predominance—420 neurons projected to the contralateral cervical cord and 270 to the contralateral lumbar cord. Fibers from PL descended in the dorsolateral funiculus on the contralateral side and terminated in laminae 5, 6, 7, and to a lesser extent in the dorsal and ventral horns. A smaller number of fibers also descended in the ventral funiculus on the ipsilateral side and terminated in laminae 7, 8 and, to a lesser extent in lamina 9. The present study is the first demonstration of the PL fiber termination in the spinal cord in mammals. The PL projection to the spinal cord may be involved in vocalization and locomotion

Multilevel Deconstruction of the In Vivo Behavior of Looped DNA-Protein Complexes

Protein-DNA complexes with loops play a fundamental role in a wide variety of cellular processes, ranging from the regulation of DNA transcription to telomere maintenance. As ubiquitous as they are, their precise in vivo properties and their integration into the cellular function still remain largely unexplored. Here, we present a multilevel approach that efficiently connects in both directions molecular properties with cell physiology and use it to characterize the molecular properties of the looped DNA-lac repressor complex while functioning in vivo. The properties we uncover include the presence of two representative conformations of the complex, the stabilization of one conformation by DNA architectural proteins, and precise values of the underlying twisting elastic constants and bending free energies. Incorporation of all this molecular information into gene-regulation models reveals an unprecedented versatility of looped DNA-protein complexes at shaping the properties of gene expression.Comment: Open Access article available at http://www.plosone.org/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.000035