Exploring differential item functioning in the SF-36 by demographic, clinical, psychological and social factors in an osteoarthritis population

The SF-36 is a very commonly used generic measure of health outcome in osteoarthritis (OA). An important, but frequently overlooked, aspect of validating health outcome measures is to establish if items work in the same way across subgroup of a population. That is, if respondents have the same 'true' level of outcome, does the item give the same score in different subgroups or is it biased towards one subgroup or another. Differential item functioning (DIF) can identify items that may be biased for one group or another and has been applied to measuring patient reported outcomes. Items may show DIF for different conditions and between cultures, however the SF-36 has not been specifically examined in an osteoarthritis population nor in a UK population. Hence, the aim of the study was to apply the DIF method to the SF-36 for a UK OA population. The sample comprised a community sample of 763 people with OA who participated in the Somerset and Avon Survey of Health. The SF-36 was explored for DIF with respect to demographic, social, clinical and psychological factors. Well developed ordinal regression models were used to identify DIF items. Results: DIF items were found by age (6 items), employment status (6 items), social class (2 items), mood (2 items), hip v knee (2 items), social deprivation (1 item) and body mass index (1 item). Although the impact of the DIF items rarely had a significant effect on the conclusions of group comparisons, in most cases there was a significant change in effect size. Overall, the SF-36 performed well with only a small number of DIF items identified, a reassuring finding in view of the frequent use of the SF-36 in OA. Nevertheless, where DIF items were identified it would be advisable to analyse data taking account of DIF items, especially when age effects are the focus of interest

Using an Ishikawa diagram as a tool to assist memory and retrieval of relevant medical cases from the medical literature

<p>Abstract</p> <p>Studying medical cases is an effective way to enhance clinical reasoning skills and reinforce clinical knowledge. An Ishikawa diagram, also known as a cause-and-effect diagram or fishbone diagram, is often used in quality management in manufacturing industries.</p> <p>In this report, an Ishikawa diagram is used to demonstrate how to relate potential causes of a major presenting problem in a clinical setting. This tool can be used by teams in problem-based learning or in self-directed learning settings.</p> <p>An Ishikawa diagram annotated with references to relevant medical cases and literature can be continually updated and can assist memory and retrieval of relevant medical cases and literature. It could also be used to cultivate a lifelong learning habit in medical professionals.</p

The antisaccade task as an index of sustained goal activation in working memory: modulation by nicotine

The antisaccade task provides a laboratory analogue of situations in which execution of the correct behavioural response requires the suppression of a more prepotent or habitual response. Errors (failures to inhibit a reflexive prosaccade towards a sudden onset target) are significantly increased in patients with damage to the dorsolateral prefrontal cortex and patients with schizophrenia. Recent models of antisaccade performance suggest that errors are more likely to occur when the intention to initiate an antisaccade is insufficiently activated within working memory. Nicotine has been shown to enhance specific working memory processes in healthy adults. MATERIALS AND METHODS: We explored the effect of nicotine on antisaccade performance in a large sample (N = 44) of young adult smokers. Minimally abstinent participants attended two test sessions and were asked to smoke one of their own cigarettes between baseline and retest during one session only. RESULTS AND CONCLUSION: Nicotine reduced antisaccade errors and correct antisaccade latencies if delivered before optimum performance levels are achieved, suggesting that nicotine supports the activation of intentions in working memory during task performance. The implications of this research for current theoretical accounts of antisaccade performance, and for interpreting the increased rate of antisaccade errors found in some psychiatric patient groups are discussed

Differential regulation of NF-κB activation and function by topoisomerase II inhibitors

BACKGROUND: While many common chemotherapeutic drugs and other inducers of DNA-damage result in both NF-κB nuclear translocation and DNA-binding, we have previously observed that, depending on the precise stimulus, there is great diversity of the function of NF-κB. In particular, we found that treatment of U-2 OS osteosarcoma cells with the anthracycine daunorubicin or with ultraviolet (UV-C) light resulted in a form of NF-κB that repressed rather than induced NF-κB reporter plasmids and the expression of specific anti-apoptotic genes. Anthracyclines such as daunorubicin can induce DNA-damage though inhibiting topoisomerase II, intercalating with DNA and undergoing redox cycling to produce oxygen free radicals. In this study we have investigated other anthracyclines, doxorubicin and aclarubicin, as well as the anthracenedione mitoxantrone together with the topoisomerase II inhibitor ICRF-193, which all possess differing characteristics, to determine which of these features is specifically required to induce both NF-κB DNA-binding and transcriptional repression in U-2 OS cells. RESULTS: The use of mitoxantrone, which does not undergo redox cycling, and the reducing agent epigallocatechingallate (EGCG) demonstrated that oxygen free radical production is not required for induction of NF-κB DNA-binding and transcriptional repression by these agents and UV-C. In addition, the use of aclarubicin, which does not directly inhibit topoisomerase II and ICRF-193, which inhibits topoisomerase II but does not intercalate into DNA, demonstrated that topoisomerase II inhibition is not sufficient to induce the repressor form of NF-κB. CONCLUSION: Induction of NF-κB DNA-binding and transcriptional repression by topoisomerase II inhibitors was found to correlate with an ability to intercalate into DNA. Although data from our and other laboratories indicates that topoisomerase II inhibition and oxygen free radicals do regulate NF-κB, they are not required for the particular ability of NF-κB to repress rather than activate transcription. Together with our previous data, these results demonstrate that the nature of the NF-κB response is context dependent. In a clinical setting such effects could profoundly influence the response to chemotherapy and suggest that new methods of analyzing NF-κB function could have both diagnostic and prognostic value

Microdevices for extensional rheometry of low viscosity elastic liquids : a review

Extensional flows and the underlying stability/instability mechanisms are of extreme relevance to the efficient operation of inkjet printing, coating processes and drug delivery systems, as well as for the generation of micro droplets. The development of an extensional rheometer to characterize the extensional properties of low viscosity fluids has therefore stimulated great interest of researchers, particularly in the last decade. Microfluidics has proven to be an extraordinary working platform and different configurations of potential extensional microrheometers have been proposed. In this review, we present an overview of several successful designs, together with a critical assessment of their capabilities and limitations

From working collections to the World Germplasm Project: agricultural modernization and genetic conservation at the Rockefeller Foundation

This paper charts the history of the Rockefeller Foundation’s participation in the collection and long-term preservation of genetic diversity in crop plants from the 1940s through the 1970s. In the decades following the launch of its agricultural program in Mexico in 1943, the Rockefeller Foundation figured prominently in the creation of world collections of key economic crops. Through the efforts of its administrators and staff, the foundation subsequently parlayed this experience into a leadership role in international efforts to conserve so-called plant genetic resources. Previous accounts of the Rockefeller Foundation’s interventions in international agricultural development have focused on the outcomes prioritized by foundation staff and administrators as they launched assistance programs and especially their characterization of the peoples and ‘‘problems’’ they encountered abroad. This paper highlights instead how foundation administrators and staff responded to a newly emergent international agricultural concern—the loss of crop genetic diversity. Charting the foundation’s responses to this concern, which developed only after agricultural modernization had begun and was understood to be produced by the successes of the foundation’s own agricultural assistance programs, allows for greater interrogation of how the foundation understood and projected its central position in international agricultural research activities by the 1970s.Research for this article was supported in part by a grant-in-aid from the Rockefeller Archive Center

Inflammatory cytokines, goblet cell hyperplasia and altered lung mechanics in Lgl1+/- mice

<p>Abstract</p> <p>Background</p> <p>Neonatal lung injury, a leading cause of morbidity in prematurely born infants, has been associated with arrested alveolar development and is often accompanied by goblet cell hyperplasia. Genes that regulate alveolarization and inflammation are likely to contribute to susceptibility to neonatal lung injury. We previously cloned <it>Lgl1</it>, a developmentally regulated secreted glycoprotein in the lung. In rat, O₂toxicity caused reduced levels of <it>Lgl1</it>, which normalized during recovery. We report here on the generation of an <it>Lgl1 </it>knockout mouse in order to determine whether deficiency of <it>Lgl1 </it>is associated with arrested alveolarization and contributes to neonatal lung injury.</p> <p>Methods</p> <p>An <it>Lgl1 </it>knockout mouse was generated by introduction of a neomycin cassette in exon 2 of the <it>Lgl1 </it>gene. To evaluate the pulmonary phenotype of <it>Lgl1</it>^+/-mice, we assessed lung morphology, <it>Lgl1 </it>RNA and protein, elastin fibers and lung function. We also analyzed tracheal goblet cells, and expression of mucin, interleukin (IL)-4 and IL-13 as markers of inflammation.</p> <p>Results</p> <p>Absence of <it>Lgl1 </it>was lethal prior to lung formation. Postnatal <it>Lgl1</it>^+/-lungs displayed delayed histological maturation, goblet cell hyperplasia, fragmented elastin fibers, and elevated expression of T_H2 cytokines (IL-4 and IL-13). At one month of age, reduced expression of <it>Lgl1 </it>was associated with elevated tropoelastin expression and altered pulmonary mechanics.</p> <p>Conclusion</p> <p>Our findings confirm that <it>Lgl1 </it>is essential for viability and is required for developmental processes that precede lung formation. <it>Lgl1</it>^+/-mice display a complex phenotype characterized by delayed histological maturation, features of inflammation in the post-natal period and altered lung mechanics at maturity. <it>Lgl1 </it>haploinsufficiency may contribute to lung disease in prematurity and to increased risk for late-onset respiratory disease.</p

HSPVdb—the Human Short Peptide Variation Database for improved mass spectrometry-based detection of polymorphic HLA-ligands

T cell epitopes derived from polymorphic proteins or from proteins encoded by alternative reading frames (ARFs) play an important role in (tumor) immunology. Identification of these peptides is successfully performed with mass spectrometry. In a mass spectrometry-based approach, the recorded tandem mass spectra are matched against hypothetical spectra generated from known protein sequence databases. Commonly used protein databases contain a minimal level of redundancy, and thus, are not suitable data sources for searching polymorphic T cell epitopes, either in normal or ARFs. At the same time, however, these databases contain much non-polymorphic sequence information, thereby complicating the matching of recorded and theoretical spectra, and increasing the potential for finding false positives. Therefore, we created a database with peptides from ARFs and peptide variation arising from single nucleotide polymorphisms (SNPs). It is based on the human mRNA sequences from the well-annotated reference sequence (RefSeq) database and associated variation information derived from the Single Nucleotide Polymorphism Database (dbSNP). In this process, we removed all non-polymorphic information. Investigation of the frequency of SNPs in the dbSNP revealed that many SNPs are non-polymorphic “SNPs”. Therefore, we removed those from our dedicated database, and this resulted in a comprehensive high quality database, which we coined the Human Short Peptide Variation Database (HSPVdb). The value of our HSPVdb is shown by identification of the majority of published polymorphic SNP- and/or ARF-derived epitopes from a mass spectrometry-based proteomics workflow, and by a large variety of polymorphic peptides identified as potential T cell epitopes in the HLA-ligandome presented by the Epstein–Barr virus cells