Deriving preference-based single indices from non-preference based condition-specific instruments: Converting AQLQ into EQ5D indices

Suppose that one has a clinical dataset with only non-preference-based QOL data, and that one nevertheless would like to perform a cost/QALY analysis. This study reports on some efforts to establish a "mapping" relationship between AQLQ (a non-preference-based QOL instrument for asthma) and EQ5D (a preference-based generic instrument). Various methods are described in terms of associated assumptions regarding the measurement properties of the instruments. This is followed by empirical mapping, based on regressing EQ5D on AQLQ. Six main regression models and two supplementary models are identified, and the regressions carried out. Performance of each model is explored in terms of goodness of fit between observed and predicted values, and of robustness of predictions on external data. The results show that it is possible to predict mean EQ5D indices given AQLQ data. The general implications for methods of mapping non-preference-based instruments onto preference-based measures are discussed

Peripheral inflammation is associated with remote global gene expression changes in the brain

Background: Although the central nervous system (CNS) was once considered an immunologically privileged site, in recent years it has become increasingly evident that cross talk between the immune system and the CNS does occur. As a result, patients with chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease or psoriasis, are often further burdened with neuropsychiatric symptoms, such as depression, anxiety and fatigue. Despite the recent advances in our understanding of neuroimmune communication pathways, the precise effect of peripheral immune activation on neural circuitry remains unclear. Utilizing transcriptomics in a well-characterized murine model of systemic inflammation, we have started to investigate the molecular mechanisms by which inflammation originating in the periphery can induce transcriptional modulation in the brain.<p></p> Methods: Several different systemic and tissue-specific models of peripheral toll-like-receptor-(TLR)-driven (lipopolysaccharide (LPS), lipoteichoic acid and Imiquimod) and sterile (tumour necrosis factor (TNF) and 12-O-tetradecanoylphorbol-13-acetate (TPA)) inflammation were induced in C57BL/6 mice. Whole brain transcriptional profiles were assessed and compared 48 hours after intraperitoneal injection of lipopolysaccharide or vehicle, using Affymetrix GeneChip microarrays. Target gene induction, identified by microarray analysis, was validated independently using qPCR. Expression of the same panel of target genes was then investigated in a number of sterile and other TLR-dependent models of peripheral inflammation.<p></p> Results: Microarray analysis of whole brains collected 48 hr after LPS challenge revealed increased transcription of a range of interferon-stimulated genes (ISGs) in the brain. In addition to acute LPS challenge, ISGs were induced in the brain following both chronic LPS-induced systemic inflammation and Imiquimod-induced skin inflammation. Unique to the brain, this transcriptional response is indicative of peripherally triggered, interferon-mediated CNS inflammation. Similar models of sterile inflammation and lipoteichoic-acid-induced systemic inflammation did not share the capacity to trigger ISG induction in the brain.<p></p> Conclusions: These data highlight ISG induction in the brain as being a consequence of a TLR-induced type I interferon response. As considerable evidence links type I interferons to psychiatric disorders, we hypothesize that interferon production in the brain could represent an important mechanism, linking peripheral TLR-induced inflammation with behavioural changes.<p></p&gt

Deriving preference-based single indices from non-preference based condition-specific instruments: converting AQLQ into EQ5D indices

Suppose that one has a clinical dataset with only non-preference-based QOL data, and that one nevertheless would like to perform a cost/QALY analysis. This study reports on some efforts to establish a “mapping” relationship between AQLQ (a non-preference-based QOL instrument for asthma) and EQ5D (a preference-based generic instrument). Various methods are described in terms of associated assumptions regarding the measurement properties of the instruments. This is followed by empirical mapping, based on regressing EQ5D on AQLQ. Six main regression models and two supplementary models are identified, and the regressions carried out. Performance of each model is explored in terms of goodness of fit between observed and predicted values, and of robustness of predictions on external data. The results show that it is possible to predict mean EQ5D indices given AQLQ data. The general implications for methods of mapping non-preference-based instruments onto preference-based measures are discussed.EQ5D; AQLQ; mapping

Fat transforms ascorbic acid from inhibiting to promoting acid-catalysed N-nitrosation

<b>Background</b>: The major potential site of acid nitrosation is the proximal stomach, an anatomical site prone to a rising incidence of metaplasia and adenocarcinoma. Nitrite, a pre-carcinogen present in saliva, can be converted to nitrosating species and N-nitroso compounds by acidification at low gastric pH in the presence of thiocyanate. <b>Aims</b>: To assess the effect of lipid and ascorbic acid on the nitrosative chemistry under conditions simulating the human proximal stomach. <b>Methods</b>: The nitrosative chemistry was modelled in vitro by measuring the nitrosation of four secondary amines under conditions simulating the proximal stomach. The N-nitrosamines formed were measured by gas chromatography–ion-trap tandem mass spectrometry, while nitric oxide and oxygen levels were measured amperometrically. <b>Results</b>: In absence of lipid, nitrosative stress was inhibited by ascorbic acid through conversion of nitrosating species to nitric oxide. Addition of ascorbic acid reduced the amount of N-nitrosodimethylamine formed by fivefold, N-nitrosomorpholine by .1000-fold, and totally prevented the formation of N-nitrosodiethylamine and N-nitrosopiperidine. In contrast, when 10% lipid was present, ascorbic acid increased the amount of Nnitrosodimethylamine, N-nitrosodiethylamine and N-nitrosopiperidine formed by approximately 8-, 60- and 140-fold, respectively, compared with absence of ascorbic acid. <b>Conclusion</b>: The presence of lipid converts ascorbic acid from inhibiting to promoting acid nitrosation. This may be explained by nitric oxide, formed by ascorbic acid in the aqueous phase, being able to regenerate nitrosating species by reacting with oxygen in the lipid phase

Combination of gastric atrophy, reflux symptoms and histological subtype indicates two distinct aetiologies of gatric cardia cancer.

<b>INTRODUCTION</b> Atrophic gastritis is a risk factor for non-cardia gastric cancer, and gastro-oesophageal reflux disease (GORD) for oesophageal adenocarcinoma. The role of atrophic gastritis and GORD in the aetiology of adenocarcinoma of the cardia remains unclear. We have investigated the association between adenocarcinoma of the different regions of the upper gastrointestinal tract and atrophic gastritis and GORD symptoms. <b>METHODS</b> 138 patients with upper GI adenocarcinoma and age and sex matched controls were studied. Serum pepsinogen I/II was used as a marker of atrophic gastritis and categorised to five quintiles. History of GORD symptoms, smoking and H.pylori infection was incorporated in logistic regression analysis. Lauren classification of gastric cancer was used to subtype gastric and oesophageal adenocarcinoma. <b>RESULTS</b> Non-cardia cancer was associated with atrophic gastritis but not with GORD symptoms; 55% of these cancers were intestinal subtype. Oesophageal adenocarcinoma was associated with GORD symptoms, but not with atrophic gastritis; 84% were intestinal subtype. Cardia cancer was positively associated with both severe gastric atrophy [OR, 95% CI: 3.92 (1.77 – 8.67)] and with frequent GORD symptoms [OR, 95% CI: 10.08 (2.29 – 44.36)] though the latter was only apparent in the nonatrophic subgroup and in the intestinal subtype. The association of cardia cancer with atrophy was stronger for the diffuse versus intestinal subtype and this was the converse of the association observed with non-cardia cancer. <b>CONCLUSION</b> These findings indicate two distinct aetiologies of cardia cancer, one arising from severe atrophic gastritis and being of intestinal or diffuse subtype similar to non-cardia cancer, and one related to GORD and intestinal in subtype, similar to oesophageal adenocarcinoma. Gastric atrophy, GORD symptoms and histological subtype may distinguish between gastric versus oesophageal origin of cardia cancer

The gastric acid pocket is attenuated in H. pylori infected subjects

Objective Gastric acid secretory capacity in different anatomical regions, including the postprandial acid pocket, was assessed in Helicobacter pylori positive and negative volunteers in a Western population. Design We studied 31 H. pylori positive and 28 H. pylori negative volunteers, matched for age, gender and body mass index. Jumbo biopsies were taken at 11 predetermined locations from the gastro-oesophageal junction and stomach. Combined high-resolution pH metry (12 sensors) and manometry (36 sensors) was performed for 20 min fasted and 90 min postprandially. The squamocolumnar junction was marked with radio-opaque clips and visualised radiologically. Biopsies were scored for inflammation and density of parietal, chief and G cells immunohistochemically. Results Under fasting conditions, the H. pylori positives had less intragastric acidity compared with negatives at all sensors >1.1 cm distal to the peak lower oesophageal sphincter (LES) pressure (p<0.01). Postprandially, intragastric acidity was less in H. pylori positives at sensors 2.2, 3.3 and 4.4 cm distal to the peak LES pressure (p<0.05), but there were no significant differences in more distal sensors. The postprandial acid pocket was thus attenuated in H. pylori positives. The H. pylori positives had a lower density of parietal and chief cells compared with H. pylori negatives in 10 of the 11 gastric locations (p<0.05). 17/31 of the H. pylori positives were CagA-seropositive and showed a more marked reduction in intragastric acidity and increased mucosal inflammation. Conclusions In population volunteers, H. pylori positives have reduced intragastric acidity which most markedly affects the postprandial acid pocket

Contextual influences on social enterprise management in rural and urban communities

The idea that difference exists between rural and urban enterprise activity is not new, the obvious comparators are measures such as social architecture, resource availability and accessibility. However, when the concept and practice of management in social enterprise is compared in these two contexts then there is opportunity to further our understanding of the contextual challenges encountered by social enterprise. In this paper six cases studies are compared and analysed: three cases are urban social enterprises and three classified as remote rural social enterprises. The urban cases are social enterprises located around Glasgow in the west of Scotland and are compared with three remote rural location studies, one on the Scottish mainland peninsula, the other in northern Scotland and the final case on a Scottish western island. We conclude that the main differences between remote rural and urban management of social enterprise are heavily nuanced by in-migration levels in both rural and urban locations, leadership and community needs and therefore deserving of context relevant policy

Schottky Barriers on GaAs

The forward current of Schottky barriers on n-type GaAs is investigated as a function of electron concentration in the range of 8×10^17 to 8×10^18 cm^−3 at temperatures 297-4.2°K. Both vacuum-cleaved and chemically polished surfaces are used. The majority of the junctions studied are gold Schottky barriers, but tin and lead contacts are also examined. The predominant current mechanism is field emission at liquid-nitrogen temperature and below for the range of electron concentrations used. These data are in excellent quantitative agreement at 77°K with the field-emission analysis of Padovani and Stratton if one uses a two-band model for the imaginary wave number kn. At 297°K, thermionic field emission predominates, but for an electron density above 3×1018 cm−3 the field-emission mechanism with a two-band model still gives reasonable agreement

Early surgery versus initial conservative treatment in patients with traumatic intracerebral haemorrhage [STITCH(Trauma)] : the first randomized trial

Acknowledgements This project was funded by the NIHR Health Technology Assessment programme (project number 07/37/16). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health.Peer reviewedPublisher PD