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

Luxury retailers’ entry and expansion strategies in China

Purpose The purpose of this paper is to examine internationalising luxury fashion retailers’ entry and post-entry expansion strategies in mainland China. Design/methodology/approach The study adopts a pragmatic mixed-methods research approach, including a quantitative mail survey and qualitative face-to-face in-depth executive interviews. Findings Different from initial single entry methods, multiple methods are increasingly popular for luxury fashion retailers’ post-entry expansion in mainland China. Although directly controlled expansion strategies have become significant, local partnerships are still important and omnichannel distribution strategies are rapidly growing. Research limitations/implications The findings were generated in mainland China only. Originality/value This work provides an understanding of luxury fashion retailers’ activities in the Chinese market from both macro and micro perspectives. It examines luxury fashion retailers’ initial entry strategies, as well as their post-entry expansion strategies in mainland China. Few studies in the area of international luxury fashion retailing have employed a mixed-methods approach with this number of participants

A universal size classification system for landslides

Size is a fundamental property of landslides, but it is described inconsistently within the scientific literature. There is currently no widely adopted size classification system applicable to all landslide types. A Scopus database search shows the most used landslide size descriptor is the term large, used to refer to landslides with volumes spanning ten orders of magnitude. Some size descriptors are unintuitive or potentially misleading (e.g. the term massive which describes a material property). We argue that a formal size classification scheme would encourage more consistent and logical usage of size descriptors and improve landslide science communication. To that end, we propose a size classification scheme suitable for all landslide types. The scheme provides a log scale of size classes for volume and area, with base units of cubic metre and square metre, respectively. In theory, there is no limit to the number of size classes possible. Six size descriptors are suggested, each spanning 3 orders of magnitude: very small (10−3–100 m3), small (10–103 m3), medium (103–106 m3), large (106–109 m3), giant (109–1012 m3), and monster (1012–1015 m3). Our system does not replace existing (or preclude future) classification systems for specific landslide types (e.g. snow avalanche) that use numerical size classes, and it maintains consistency with some commonly used descriptors. Whatever system is used, we encourage people to define the terms they use and to quantify size where possible, so that clearer meaning is given to the words used to describe landslide sizes

Response to Crocetti et al.

No abstract available

Hong Kong, a Gateway for Mainland China? An examination of the impact of luxury fashion retailers’ ownership structures on expansion strategies

Purpose: The purpose of this paper is to examine luxury fashion retailers’ ownership structures at their internationalisation strategies in Hong Kong and mainland China. Design/methodology/approach: This study adopts a pragmatic mixed methods approach, comprising a quantitative mail survey and ten qualitative executive interviews. Findings: This study found that group-owned luxury fashion retailers usually encounter fewer difficulties when internationalising into mainland China than their individually owned counterparts because of parenting advantage, particularly functional and service support. However, the success of some individually owned brands has demonstrated that branding strategies, management culture, international experience, financial power and local partners’ know-how are as important as parent company support and although the luxury market in mainland China has become developed, many foreign luxury fashion retailers still enter Hong Kong prior to mainland China. However, in relation to post-entry management and expansion strategies, the importance of Hong Kong has weakened because the emergence of capital cities, the growth of the middle class and fewer political restrictions. Research limitations/implications: The research findings are generated in the context of Hong Kong and mainland China, they are therefore limited in explaining luxury fashion retailers’ internationalisation strategies in other markets. Despite the challenge of the sample size, 63 out of 130 survey respondents (48.5 per cent response rate) and ten interview participants are felt to be sufficient to represent the market. Practical implications: This research can be used by practitioners when assessing appropriate entry strategies to the Chinese luxury fashion market. Originality/value: This is a pioneering study of the Chinese luxury market from the perspective of international retail strategies. It differentiates between Greater China (including Hong Kong, Macau and Taiwan) and mainland China, and examines the impact of luxury fashion retailers’ ownership structures on their internationalisation strategies

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