SHOULD WE DIFFERENTIATE BETWEEN BUSINESS AND PRIVATE CUSTOMERS?

The literature on how customers make their service-provider choices largely distinguishes between private and business customers, and companies’ offerings have been separated accordingly. This study takes a closer look at the possible differences between these two customer categories. The results are explorative and based on both qualitative and quantitative studies focusing on customers’ actual behavior. The findings show that it is not only job-related aspects such as “being able to work” that influence business travel, and that private matters such as “time with the family” are clearly of equal significance in the choice situation. Price perception is important, but only when it is set against the appropriate social costs. The contradiction appears in the airlines’ offers to these customers, which are generally specifically job related. The results of the present study show that most business customers are, in fact, “private customers”.air travel, customer relationships, business-to-business relationships, preferences, choice, service

Critical incident techniques

Critical incident techniques Towards a framework for analysing the criticality of critical incident

Accounting Problems Under the Excess Profits Tax

DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.Funding Agencies|Research Council of Norway; Odd Fellow</p

Automated workflow-based exploitation of pathway databases provides new insights into genetic associations of metabolite profiles

Background: Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) that associate with clinical phenotypes, but these SNPs usually explain just a small part of the heritability and have relatively modest effect sizes. In contrast, SNPs that associate with metabolite levels generally explain a higher percentage of the genetic variation and demonstrate larger effect sizes. Still, the discovery of SNPs associated with metabolite levels is challenging since testing all metabolites measured in typical metabolomics studies with all SNPs comes with a severe multiple testing penalty. We have developed an automated workflow approach that utilizes prior knowledge of biochemical pathways present in databases like KEGG and BioCyc to generate a smaller SNP set relevant to the metabolite. This paper explores the opportunities and challenges in the analysis of GWAS of metabolomic phenotypes and provides novel insights into the genetic basis of metabolic variation through the re-analysis of published GWAS datasets. Results: Re-analysis of the published GWAS dataset from Illig et al. (Nature Genetics, 2010) using a pathway-based workflow (http://www.myexperiment.org/packs/319.html), confirmed previously identified hits and identified a new locus of human metabolic individuality, associating Aldehyde dehydrogenase family1 L1 (ALDH1L1) with serine/glycine ratios in blood. Replication in an independent GWAS dataset of phospholipids (Demirkan et al., PLoS Genetics, 2012) identified two novel loci supported by additional literature evidence: GPAM (Glycerol-3 phosphate acyltransferase) and CBS (Cystathionine beta-synthase). In addition, the workflow approach provided novel insight into the affected pathways and relevance of some of these gene-metabolite pairs in disease development and progression. Conclusions: We demonstrate the utility of automated exploitation of background knowledge present in pathway databases for the analysis of GWAS datasets of metabolomic phenotypes. We report novel loci and potential biochemical mechanisms that contribute to our understanding of the genetic basis of metabolic variation and its relationship to disease development and progression

Peripheral Artery Disease in Acute Ischemic Stroke Patients Treated With Endovascular Thrombectomy; Results From the MR CLEAN Registry

Background and Purpose: Though peripheral artery disease (PAD) is a well-known risk factor for ischemic events, better outcomes have been described in acute ischemic stroke patients with co-existing PAD. This paradoxical association has been attributed to remote ischemic preconditioning (RIPC) and might be related to better collateral blood flow. The aim of this study is to compare outcomes after endovascular thrombectomy (EVT) in acute stroke patients with and without PAD and to assess the relation between PAD and collateral grades. Methods: We analyzed acute ischemic stroke patients treated with EVT for an anterior circulation large artery occlusion, included in the Dutch, prospective, multicenter MR CLEAN Registry between March 2014 and November 2017. Collaterals were scored on CT angiography, using a 4-point collateral score. We used logistic regression analysis to estimate the association of PAD with collateral grades and functional outcome, assessed with the modified Rankin Scale (mRS) at 90 days. Safety outcomes included mortality at 90 days, symptomatic intracranial hemorrhage, and stroke progression. Results: We included 2,765 patients for analysis, of whom 254 (9.2%) had PAD. After adjustment for potential confounders, multivariable regression analysis showed no association of PAD with functional outcome [mRS cOR 0.90 (95% CI, 0.7-1.2)], collateral grades (cOR 0.85, 95% CI 0.7-1.1), or safety outcomes. Conclusion: In the absence of an association between the presence of PAD and collateral scores or outcomes after EVT, it may be questioned whether PAD leads to RIPC in patients with acute ischemic stroke due to large vessel occlusion

MR CLEAN-LATE, a multicenter randomized clinical trial of endovascular treatment of acute ischemic stroke in The Netherlands for late arrivals:study protocol for a randomized controlled trial

BACKGROUND: Endovascular therapy (EVT) for acute ischemic stroke due to proximal occlusion of the anterior intracranial circulation, started within 6 h from symptom onset, has been proven safe and effective. Recently, EVT has been proven effective beyond the 6-h time window in a highly selected population using CT perfusion or MR diffusion. Unfortunately, these imaging modalities are not available in every hospital, and strict selection criteria might exclude patients who could still benefit from EVT. The presence of collaterals on CT angiography (CTA) may offer a more pragmatic imaging criterion that predicts possible benefit from EVT beyond 6 h from time last known well. The aim of this study is to assess the safety and efficacy of EVT for patients treated between 6 and 24 h from time last known well after selection based on the presence of collateral flow. METHODS: The MR CLEAN-LATE trial is a multicenter, randomized, open-label, blinded endpoint trial, aiming to enroll 500 patients. We will investigate the efficacy of EVT between 6 and 24 h from time last known well in acute ischemic stroke due to a proximal intracranial anterior circulation occlusion confirmed by CTA or MRA. Patients with any collateral flow (poor, moderate, or good collaterals) on CTA will be included. The inclusion of poor collateral status will be restricted to a maximum of 100 patients. In line with the current Dutch guidelines, patients who fulfill the characteristics of included patients in DAWN and DEFUSE 3 will be excluded as they are eligible for EVT as standard care. The primary endpoint is functional outcome at 90 days, assessed with the modified Rankin Scale (mRS) score. Treatment effect will be estimated with ordinal logistic regression (shift analysis) on the mRS at 90 days. Secondary endpoints include clinical stroke severity at 24 h and 5-7 days assessed by the NIHSS, symptomatic intracranial hemorrhage, recanalization at 24 h, follow-up infarct size, and mortality at 90 days, DISCUSSION: This study will provide insight into whether EVT is safe and effective for patients treated between 6 and 24 h from time last known well after selection based on the presence of collateral flow on CTA. TRIAL REGISTRATION: NL58246.078.17 , ISRCTN19922220 , Registered on 11 December 2017

Effect of atrial fibrillation on endovascular thrombectomy for acute ischemic stroke. A meta-analysis of individual patient data from six randomised trials: Results from the HERMES collaboration

Background: Atrial fibrillation is an important risk factor for ischemic stroke, and is associated with an increased risk of poor outcome after ischemic stroke. Endovascular thrombectomy is safe and effective in acute ischemic stroke patients with large vessel occlusion of the anterior circulation. This meta-analysis aims to investigate whether there is an interaction between atrial fibrillation and treatment effect of endovascular thrombectomy, and secondarily whether atrial fibrillation is associated with worse outcome in patients with ischemic stroke due to large vessel occlusion. Methods: Individual patient data were from six of the recent randomised clinical trials (MR CLEAN, EXTEND-IA, REVASCAT, SWIFT PRIME, ESCAPE, PISTE) in which endovascular thrombectomy plus standard care was compared to standard care alone. Primary outcome measure was the shift on the modified Rankin scale (mRS) at 90 days. Secondary outcomes were functional independence (mRS 0–2) at 90 days, National Institutes of Health Stroke Scale score at 24 h, symptomatic intracranial hemorrhage and mortality at 90 days. The primary effect parameter was the adjusted common odds ratio, estimated with ordinal logistic regression (shift analysis); treatment effect modification of atrial fibrillation was assessed with a multiplicative interaction term. Results: Among 1351 patients, 447 p

Expanding the Versatility of Phage Display II: Improved Affinity Selection of Folded Domains on Protein VII and IX of the Filamentous Phage

Background: Phage display is a leading technology for selection of binders with affinity for specific target molecules. Polypeptides are normally displayed as fusions to the major coat protein VIII (pVIII) or the minor coat protein III (pIII). Whereas pVIII display suffers from drawbacks such as heterogeneity in display levels and polypeptide fusion size limitations, toxicity and infection interference effects have been described for pIII display. Thus, display on other coat proteins such as pVII or pIX might be more attractive. Neither pVII nor pIX display have gained widespread use or been characterized in detail like pIII and pVIII display. Methodology/Principal Findings: Here we present a side-by-side comparison of display on pIII with display on pVII and pIX. Polypeptides of interest (POIs) are fused to pVII or pIX. The N-terminal periplasmic signal sequence, which is required for phage integration of pIII and pVIII and that has been added to pVII and pIX in earlier studies, is omitted altogether. Although the POI display level on pIII is higher than on pVII and pIX, affinity selection with pVII and pIX display libraries is shown to be particularly efficient. Conclusions/Significance: Display through pVII and/or pIX represent platforms with characteristics that differ from those of the pIII platform. We have explored this to increase the performance and expand the use of phage display. In the paper, we describe effective affinity selection of folded domains displayed on pVII or pIX. This makes both platforms more attractive alternatives to conventional pIII and pVIII display than they were before. © 2011 Wälchli et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Meat, vegetables and genetic polymorphisms and the risk of colorectal carcinomas and adenomas

<p>Abstract</p> <p>Background</p> <p>The risk of sporadic colorectal cancer (CRC) is mainly associated with lifestyle factors, particularly dietary factors. Diets high in red meat and fat and low in fruit and vegetables are associated with an increased risk of CRC. The dietary effects may be modulated by genetic polymorphisms in biotransformation genes. In this study we aimed to evaluate the role of dietary factors in combination with genetic factors in the different stages of colorectal carcinogenesis in a Norwegian population.</p> <p>Methods</p> <p>We used a case-control study design (234 carcinomas, 229 high-risk adenomas, 762 low-risk adenomas and 400 controls) to test the association between dietary factors (meat versus fruit, berries and vegetables) genetic polymorphisms in biotransformation genes (<it>GSTM1</it>, <it>GSTT1</it>, <it>GSTP1 </it>Ile¹⁰⁵Val, <it>EPHX1 </it>Tyr¹¹³His and <it>EPHX1 </it>His¹³⁹Arg), and risk of colorectal carcinomas and adenomas. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression.</p> <p>Results</p> <p>A higher ratio of total meat to total fruit, berry and vegetable intake was positively associated with both high and low-risk adenomas, with approximately twice the higher risk in the 2^ndquartile compared to the lowest quartile. For the high-risk adenomas this positive association was more obvious for the common allele (Tyr allele) of the <it>EPHX1 </it>codon 113 polymorphism. An association was also observed for the <it>EPHX1 </it>codon 113 polymorphism in the low-risk adenomas, although not as obvious.</p> <p>Conclusion</p> <p>Although, the majority of the comparison groups are not significant, our results suggest an increased risk of colorectal adenomas in individuals for some of the higher ratios of total meat to total fruit, berry and vegetable intake. In addition the study supports the notion that the biotransformation enzymes GSTM1, GSTP1 and EPHX1 may modify the effect of dietary factors on the risk of developing colorectal carcinoma and adenoma.</p