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Activation of the transcription factor NF-kappa B appears to be involved in different stages of atherogenesis. In this paper we investigate the role of NF-kappa B inhibitor I kappa B alpha in atherosclerosis. Myeloid-specific deletion of I kappa B alpha results in larger and more advanced lesions in LDL-R-deficient mice without affecting the compositional phenotype of the plaques or systemic inflammatory markers in the plasma. We show that I kappa B alpha-deleted macrophages display enhanced adhesion to an in vitro endothelial cell layer, coinciding with an increased expression of the chemokine CCL5. Also, in vivo we found that I kappa B alpha(del) mice had more leukocytes adhering to the luminal side of the endothelial cell layers that cover the atherosclerotic plaques. Moreover, we introduce ER-MP58 in this paper as a new immunohistochemical tool for quantifying newly recruited myeloid cells in the atherosclerotic lesion. This staining confirms that in I kappa B alpha(del) mice more leukocytes are attracted to the plaques. In conclusion, we show that I kappa B alpha deletion in myeloid cells promotes atherogenesis, probably through an induced leukocyte recruitment to plaques.

__Introduction:__ Inconsistency in the time trade-off (TTO) task in EQ-5D-5L occurs when a respondent gives a higher value to a logically worse health state, the occurrence of inconsistency compromises the quality of the data. It is not yet clear which factors are associated with individual level inconsistency. Relating inconsistency to the characteristics of the respondent, interviewer, and the interview process could be helpful in understanding the causes of inconsistency. The objective of this paper is to discover the factors associated with individual level inconsistencies. __Methods:__ Twenty interviewers interviewed 1,296 respondents and each respondent valued 10 health states using the EQ-VT platform in 5 cities in China. At the respondent level, inconsistency was identified in terms of severity and quantity and related to the respondent’s background characteristics, the time and iterations spent on the wheelchair example task, and the formal TTO tasks, using multilevel multinomial regression analyses. Interviewers’ impact on inconsistencies was analyzed using single level multinomial regression analyses. __Results:__ In the full dataset, slight inconsistency was more related to the interview process (Time spent on TTO task: RRR = 1.246 with 95%CI: 1.076,1.441; time spent on Wheelchair example: RRR = 0.815 with 95%CI:0.699,0.952) while severe inconsistency was more related to respondent’s gender (Gender: RRR = 2.347 with 95%CI:1.429,3.855). One Interviewer (Interviewer 7: RRR = 7.335 with 95%CI:1.908,28.195) and interviewer’s experience (Sequence: RRR = 0.511 with 95%CI:0.385,0.678) in general showed strong influence over inconsistency in the TTO task. __Conclusion:__ In conclusion, logical inconsistency in the valuation of EQ-5D-5L health states is associated not only with respondents’ characteristics but also with interviewers’ performance and the interview process. The role of interviewers and the importance of interviewer training may be more crucial than hitherto believed. This finding could be generalizable to other interviewer-administered health-state valuation study.

textabstractBackground: Italy has a population of 60 million and a universal coverage single-payer healthcare system, which mandates collection of healthcare administrative data in a uniform fashion throughout the country. On the other hand, organization of the health system takes place at the regional level, and local initiatives generate natural experiments. This is happening in particular in primary care, due to the need to face the growing burden of chronic diseases. Health services research can compare and evaluate local initiatives on the basis of the common healthcare administrative data.However reliability of such data in this context needs to be assessed, especially when comparing different regions of the country. In this paper we investigated the validity of healthcare administrative databases to compute indicators of compliance with standards of care for diabetes, ischaemic heart disease (IHD) and heart failure (HF). Methods: We compared indicators estimated from healthcare administrative data collected by Local Health Authorities in five Italian regions with corresponding estimates from clinical data collected by General Practitioners (GPs). Four indicators of diagnostic follow-up (two for diabetes, one for IHD and one for HF) and four indicators of appropriate therapy (two each for IHD and HF) were considered. Results: Agreement between the two data sources was very good, except for indicators of laboratory diagnostic follow-up in one region and for the indicator of bioimaging diagnostic follow-up in all regions, where measurement with administrative data underestimated quality. Conclusion: According to evidence presented in this study, estimating compliance with standards of care for diabetes, ischaemic heart disease and heart failure from healthcare databases is likely to produce reliable results, even though completeness of data on diagnostic procedures should be assessed first. Performing studies comparing regions using such indicators as outcomes is a promising development with potential to improve quality governance in the Italian healthcare system.

In small animal imaging studies, when the locations of the micro-structures of interest are unknown a priori, there is a simultaneous need for full-body coverage and high resolution. In MRI, additional requirements to image contrast and acquisition time will often make it impossible to acquire such images directly. Recently, a resolution enhancing post-processing technique called super-resolution reconstruction (SRR) has been demonstrated to improve visualization and localization of micro-structures in small animal MRI by combining multiple low-resolution acquisitions. However, when the field-of-view is large relative to the desired voxel size, solving the SRR problem becomes very expensive, in terms of both memory requirements and computation time. In this paper we introduce a novel local approach to SRR that aims to overcome the computational problems and allow researchers to efficiently explore both global and local characteristics in whole-body small animal MRI. The method integrates state-of-the-art image processing techniques from the areas of articulated atlas-based segmentation, planar reformation, and SRR. A proof-of-concept is provided with two case studies involving CT, BLI, and MRI data of bone and kidney tumors in a mouse model. We show that local SRR-MRI is a computationally efficient complementary imaging modality for the precise characterization of tumor metastases, and that the method provides a feasible high-resolution alternative to conventional MRI.

Programs that monitor local, national, and regional levels of transmitted HIV-1 drug resistance inform treatment guidelines and provide feedback on the success of HIV-1 treatment and prevention programs. To accurately compare transmitted drug resistance rates across geographic regions and times, the World Health Organization has recommended the adoption of a consensus genotypic definition of transmitted HIV-1 drug resistance. In January 2007, we outlined criteria for developing a list of mutations for drug-resistance surveillance and compiled a list of 80 RT and protease mutations meeting these criteria (surveillance drug resistance mutations; SDRMs). Since January 2007, several new drugs have been approved and several new drug-resistance mutations have been identified. In this paper, we follow the same procedures described previously to develop an updated list of SDRMs that are likely to be useful for ongoing and future studies of transmitted drug resistance. The updated SDRM list has 93 mutations including 34 NRTI-resistance mutations at 15 RT positions, 19 NNRTI-resistance mutations at 10 RT positions, and 40 PI-resistance mutations at 18 protease positions.