Patient and public involvement in health literacy interventions: a mapping review

Background: Health literacy is a critical mediating factor that impacts on the health of older adults. Patient and public involvement in health and social care research, policy and design of care delivery is one mechanism that can promote production of better health literacy. This mapping review looks for and describes practices, concepts and methods that have been reported involving patients, public and (non-researcher) professionals in the development and design of health literacy interventions for older people. Methods: Studies that aimed to improve health literacy were identified within a previously created compatible inventory of health behaviour studies for older people. Articles were screened for whether they addressed health literacy and featured involvement of stakeholders other than investigators and patients. Two reviewers independently read each study to identify any patient, public and professional involvement in the research process. We also noted some aspects of outcomes. Results: Twenty-two studies included patient, public and/or professional involvement in at least one research domain: design, management or evaluation. Involvement included volunteers, older people, professionals, patients, and community representatives. All studies were driven by an organisational or biomedical agenda. Conclusions: Patient, public and professional involvement wasrarely reported in studies on health literacy interventions for older people. This could help explain why some interventions fail to improve health literacy in older people. Key words – health literacy intervention research, older people, patient and public involvement, mapping revie

Enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent ZD6126

Current experimental and clinical knowledge supports the optimisation of endothelial cell targeting using a strategy combining anti-EGFR drugs with antivascular agents. The purpose of the present study was to examine the effects of the association of ZD6126, an antivascular microtubule-destabilising agent, with gefitinib and irradiation on the growth of six head and neck human cancer cell lines xenografted in nude mice and to study predictive and molecular factors responsible for antitumour effects. CAL33- and Hep-2-grafted cell lines were the most sensitive to ZD6126 treatment, with VEGF levels significantly higher (P=0.0336) in these tumour xenografts compared to Detroit 562- and CAL27-grafted cell lines with relatively low VEGF levels that were not sensitive to ZD6126. In contrast, neither IL8 levels nor EGFR expression was linked to the antitumour effects of ZD6126. ZD6126 in combination with gefitinib resulted in a synergistic cytotoxic interaction with greater antitumour effects than gefitinib alone. The synergistic interaction between ZD6126 and gefitinib was corroborated by a significant decrease in CD31 labelling. The present study may serve for future innovative clinical applications, as it suggests that VEGF tumour levels are possible predictors for ZD6126 antitumour efficacy. It also supports the notion of antitumour supra-additivity when combining gefitinib and ZD6126, and identifies neoangiogenesis as the main determinant of this synergistic combination

Clonal Population of Mycobacterium tuberculosis Strains Reside within Multiple Lung Cavities

(MTB) are localized within lung cavities of patients suffering from chronic progressive TB.Multiple cavity isolates from lung of 5 patients who had undergone pulmonary resection surgery were analyzed on the basis of their drug susceptibility profile, and genotyped by spoligotyping and 24-loci MIRU-VNTR. The patients past history including treatment was studied. Three of the 5 patients had extensive drug resistant TB. Heteroresistance was also reported within different cavity isolates of the lung. Both genotyping methods reported the presence of clonal population of MTB strain within different cavities of the each patient, even those reporting heteroresistance. Four of the 5 patients were infected with a population of the Beijing genotype. Post-surgery they were prescribed a drug regimen consisting of cycloserine, a fluoroquinolone and an injectable drug. A 6 month post-surgery follow-up reported only 2 patients with positive clinical outcome, showing sputum conversion.Identical spoligotype patterns and MIRU-VNTR profiles between multiple cavities of each patient, characterize the presence of clonal population of MTB strains (and absence of multiple MTB infection)

Actions in Practice: On details in collections

Several of the contributions to the Lynch et al. Special issue make the claim that conversation- analytic research into epistemics is ‘routinely crafted at the expense of actual, produced and constitutive detail, and what that detail may show us’. Here, we seek to address the inappositeness of this critique by tracing precisely how it is that recognizable actions emerge from distinct practices of interaction. We begin by reviewing some of the foundational tenets of conversation-analytic theory and method – including the relationship between position and composition, and the making of collections – as these appear to be primary sources of confusion for many of the contributors to the Lynch et al. Special Issue. We then target some of the specific arguments presented in the Special Issue, including the alleged ‘over-hearer’s’ writing of metrics, the provision of so- called ‘alternative’ analyses and the supposed ‘crafting’ of generalizations in epistemics research. In addition, in light of Lynch’s more general assertion that conversation analysis (CA) has recently been experiencing a ‘rapprochement’ with what he disparagingly refers to as the ‘juggernaut’ of linguistics, we discuss the specific expertise that linguists have to offer in analyzing particular sorts of interactional detail. The article as a whole thus illustrates that, rather than being produced ‘at the expense of actual, produced and constitutive detail’, conversation-analytic findings – including its work in epistemics – are unambiguously anchored in such detail. We conclude by offering our comments as to the link between CA and linguistics more generally, arguing that this relationship has long proven to be – and indeed continues to be – a mutually beneficial one

Inheriting library cards to Babel and Alexandria: Contemporary metaphors for the digital library

Librarians have been consciously adopting metaphors to describe library concepts since the nineteenth century, helping us to structure our understanding of new technologies. We have drawn extensively on these figurative frameworks to explore issues surrounding the digital library, yet very little has been written to date which interrogates how these metaphors have developed over the years. Previous studies have explored library metaphors, using either textual analysis or ethnographic methods to investigate their usage. However, this is to our knowledge the first study to use bibliographic data, corpus analysis, qualitative sentiment weighting and close reading to study particular metaphors in detail. It draws on a corpus of over 450 articles to study the use of the metaphors of the Library of Alexandria and Babel, concluding that both have been extremely useful as framing metaphors for the digital library. However, their longstanding use has seen them become stretched as metaphors, meaning that the field’s figurative framework now fails to represent the changing technologies which underpin contemporary digital libraries

TBK1 Kinase Addiction in Lung Cancer Cells Is Mediated via Autophagy of Tax1bp1/Ndp52 and Non-Canonical NF-kappa B Signalling

K-Ras dependent non-small cell lung cancer (NSCLC) cells are 'addicted' to basal autophagy that reprograms cellular metabolism in a lysosomal-sensitive manner. Here we demonstrate that the xenophagy-associated kinase TBK1 drives basal autophagy, consistent with its known requirement in K-Ras-dependent NSCLC proliferation. Furthermore, basal autophagy in this context is characterised by sequestration of the xenophagy cargo receptor Ndp52 and its paralogue Tax1bp1, which we demonstrate here to be a bona fide cargo receptor. Autophagy of these cargo receptors promotes non-canonical NF-κB signalling. We propose that this TBK1-dependent mechanism for NF-κB signalling contributes to autophagy addiction in K-Ras driven NSCLC

Communication Impairments in Mice Lacking Shank1: Reduced Levels of Ultrasonic Vocalizations and Scent Marking Behavior

Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1−/− null mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1−/− mice as compared to wildtype Shank1+/+ littermate controls. Shank1−/− pups emitted fewer vocalizations than Shank1+/+ pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1−/− males deposited fewer scent marks in proximity to female urine than Shank1+/+ males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1+/+ mice changed their calling pattern dependent on previous female interactions, while Shank1−/− mice were unaffected, indicating a failure of Shank1−/− males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1−/− mice are consistent with a phenotype relevant to social communication deficits in autism.National Institute of Mental Health (U.S.) (Intramural Research Program)Simons Foundatio

Polycomb Group Protein Bmi1 Is Required for Growth of RAF Driven Non-Small-Cell Lung Cancer

Background: We have previously described a RAF oncogene driven transgenic mouse model for non small cell lung cancer (NSCLC). Here we examine whether tumor initiation and growth requires the stem cell self-renewal factor Bmi1. Principal Findings: In order to evaluate Bmi1 function in NSCLC two founder lines that differ in incidence and latency of tumor formation were compared. Ablation of Bmi1 expression in both lines had a dramatically decreased tumor growth. As the line with shorter latency matched the life span of Bmi1 knock out mice, these mice were chosen for further study. The absence of Bmi1 did not decrease the number of tumor initiation in these mice as only the size and not the number of tumors decreased. Reduction in tumor growth resulted from an increase in cell death and decrease in cell cycle progression that corresponded with up-regulation of the p16 INK4a and p19 ARF. Significance: The data identifies Bmi1 as an important factor for expansion but not initiation of RAF driven NSCLC

Transient Reversal of Episome Silencing Precedes VP16-Dependent Transcription during Reactivation of Latent HSV-1 in Neurons

Herpes simplex virus type-1 (HSV-1) establishes latency in peripheral neurons, creating a permanent source of recurrent infections. The latent genome is assembled into chromatin and lytic cycle genes are silenced. Processes that orchestrate reentry into productive replication (reactivation) remain poorly understood. We have used latently infected cultures of primary superior cervical ganglion (SCG) sympathetic neurons to profile viral gene expression following a defined reactivation stimulus. Lytic genes are transcribed in two distinct phases, differing in their reliance on protein synthesis, viral DNA replication and the essential initiator protein VP16. The first phase does not require viral proteins and has the appearance of a transient, widespread de-repression of the previously silent lytic genes. This allows synthesis of viral regulatory proteins including VP16, which accumulate in the cytoplasm of the host neuron. During the second phase, VP16 and its cellular cofactor HCF-1, which is also predominantly cytoplasmic, concentrate in the nucleus where they assemble an activator complex on viral promoters. The transactivation function supplied by VP16 promotes increased viral lytic gene transcription leading to the onset of genome amplification and the production of infectious viral particles. Thus regulated localization of de novo synthesized VP16 is likely to be a critical determinant of HSV-1 reactivation in sympathetic neurons