Obesity is the major risk factor for metabolic syndrome and through it diabetes as well as cardiovascular disease. Visceral fat (VF) rather than subcutaneous fat (SF) is the major predictor of ...adverse events. Currently, the reference standard for measuring VF is abdominal X‐ray computed tomography (CT) or magnetic resonance imaging (MRI), requiring highly used clinical equipment. Dual‐energy X‐ray absorptiometry (DXA) can accurately measure body composition with high‐precision, low X‐ray exposure, and short‐scanning time. The purpose of this study was to validate a new fully automated method whereby abdominal VF can be measured by DXA. Furthermore, we explored the association between DXA‐derived abdominal VF and several other indices for obesity: BMI, waist circumference, waist‐to‐hip ratio, and DXA‐derived total abdominal fat (AF), and SF. We studied 124 adult men and women, aged 18–90 years, representing a wide range of BMI values (18.5–40 kg/m2) measured with both DXA and CT in a fasting state within a one hour interval. The coefficient of determination (r2) for regression of CT on DXA values was 0.959 for females, 0.949 for males, and 0.957 combined. The 95% confidence interval for r was 0.968 to 0.985 for the combined data. The 95% confidence interval for the mean of the differences between CT and DXA VF volume was −96.0 to −16.3 cm3. Bland‐Altman bias was +67 cm3 for females and +43 cm3 for males. The 95% limits of agreement were −339 to +472 cm3 for females and −379 to +465 cm3 for males. Combined, the bias was +56 cm3 with 95% limits of agreement of −355 to +468 cm3. The correlations between DXA‐derived VF and BMI, waist circumference, waist‐to‐hip ratio, and DXA‐derived AF and SF ranged from poor to modest. We conclude that DXA can measure abdominal VF precisely in both men and women. This simple noninvasive method with virtually no radiation can therefore be used to measure VF in individual patients and help define diabetes and cardiovascular risk.
Next-generation sequencing approaches used to characterize microbial communities are subject to technical caveats that can lead to major distortion of acquired data. Determining the optimal sample ...handling protocol is essential to minimize the bias for different sample types. Using a mock community composed of 22 bacterial strains of even concentration, we studied a combination of handling conditions to determine the optimal conditions for swab material. Examining a combination of effects simulates the reality of handling environmental samples and may thus provide a better foundation for the standardization of protocols. We found that the choice of storage buffer and extraction kit affects the detected bacterial composition, while different 16S rRNA amplification methods only had a minor effect. All bacterial genera present in the mock community were identified with minimal levels of contamination independent of the choice of sample processing. Despite this, the observed bacterial profile for all tested conditions were significantly different from the expected abundance. This highlights the need for proper validation and standardization for each sample type using a mock community and blank control samples, to assess the bias in the protocol and reduce variation across the datasets.
This paper reviews the different concepts of measuring activities of multinational corporations. It aims at working out the economic relationships that theoretically exist between these measures ...under general economic assumptions and then empirically investigates to which extent such relationships exist in the data. As a main conclusion, foreign direct investment (FDI) stock data is indeed a good proxy for measuring most real economic activities of multinational firms. Discrepancies between FDI stock and other data can to a large extent be given a reasonable economic meaning, but observed asset‐to‐employment patterns in multinational production also call for more thorough future research.
The induction of ischemic tolerance by preconditioning provides a platform to elucidate endogenous mechanisms of stroke protection. In these studies, we characterize the relationship between ...hypoxia‐inducible factor (HIF), sphingosine kinase 2 (SphK2), and chemokine (C–C motif) ligand 2 (CCL2) in models of hypoxic or pharmacological preconditioning‐induced ischemic tolerance. A genetics‐based approach using SphK2‐ and CCL2‐null mice showed both SphK2 and CCL2 to be necessary for the induction of ischemic tolerance following preconditioning with hypoxia, the hypoxia‐mimetic cobalt chloride, or the sphingosine‐1‐phosphate (S1P) agonist FTY720. A pharmacological approach confirmed the necessity of HIF signaling for all three preconditioning stimuli, and showed that the SphK/S1P pathway transduces tolerance via the S1P1 receptor. In addition, our data suggest significant cross‐talk between HIF and SphK2‐produced S1P signaling, which together act to up‐regulate CCL2 expression. Overall, HIF, SphK, S1P, and CCL2 participate in a signaling cascade to induce the gene expression responsible for the stroke‐tolerant phenotype established by hypoxic and FTY720 preconditioning. The identification of these common molecular mediators involved in signaling the genomic response to multiple preconditioning stimuli provides several targets for therapeutic manipulation.
Signaling the preconditioning genomic response
Preconditioning for stroke tolerance with hypoxia, cobalt, and FTY720 requires HIF activity and SphK2‐generated S1P signaling via the S1P1 receptor. In turn, cross‐talk/feedback between HIF and S1P signaling up‐regulates CCL2 expression to induce this epigenetic response. The identification herein of multiple upstream mediators of ischemic tolerance provides several targets of translational relevance for preconditioning in humans.
Transduction of endothelial cells (EC) with a vector that expresses apolipoprotein A-I (APOAI) reduces atherosclerosis in arteries of fat-fed rabbits. However, the effects on atherosclerosis are ...partial and might be enhanced if APOAI expression could be increased. With a goal of developing an expression cassette that generates higher levels of APOAI mRNA in EC, we tested 4 strategies, largely in vitro: addition of 2 types of enhancers, addition of computationally identified EC-specific cis-regulatory modules (CRM), and insertion of the rabbit APOAI gene at the transcription start site (TSS) of sequences cloned from genes that are highly expressed in cultured EC. Addition of a shear stress-responsive enhancer did not increase APOAI expression. Addition of 2 copies of a Mef2c enhancer increased APOAI expression from a moderately active promoter/enhancer but decreased APOAI expression from a highly active promoter/enhancer. Of the 11 CRMs, 3 increased APOAI expression from a moderately active promoter (2-7-fold; P < 0.05); none increased expression from a highly active promoter/enhancer. Insertion of the APOAI gene into the TSS of highly expressed EC genes did not increase expression above levels obtained with a moderately active promoter/enhancer. New strategies are needed to further increase APOAI transgene expression in EC.
The Identification of Relevant Attributes for Liver Cancer Therapies (IRALCT) project is intended to provide new insights into the relevant utility attributes regarding therapy choices for malignant ...primary and secondary liver tumors from the perspective of those who are involved in the decision-making process. It addresses the potential value of taking patients' expectations and preferences into account during the decision-making and, when possible, adapting therapies according to these preferences. Specifically, it is intended to identify the relevant clinical attributes that influence the patients', medical laymen's, and medical professionals' decisions and compare the three groups' preferences. We conducted maximum difference (MaxDiff) scaling among 261 participants (75 physicians, 97 patients with hepatic malignancies, and 89 medical laymen) to rank the importance of 14 attributes previously identified through a literature review. We evaluated the MaxDiff data using count analysis and hierarchical Bayes estimation (HB). Physicians, patients, and medical laymen assessed the same 7 attributes as the most important: probability (certainty) of a complete removal of the tumor, probability of reoccurrence of the disease, pathological evidence of tumor removal, possible complications during the medical intervention, welfare after the medical intervention, duration and intensity of the pain, and degree of difficulty of the medical intervention. The cumulative relative importance of these 7 attributes was 88.3%. Our results show that the physicians', patients', and medical laymen's preferences were very similar and stable.Trial registration DRKS-ID of the study: DRKS00013304, Date of Registration in DRKS: 2017/11/16.
Purpose High resolution flat-panel computed tomography arthrography (FPCT-A) and magnetic resonance arthrography (MR-A) are well suited to evaluate osteochondral lesions. The current study compares ...the performance of FPCT-A versus MR-A in an experimental setting. Methods Fourteen cadaveric ankles were prepared with artificial osteochondral defects of various sizes in four separate talar locations. After intra-articular contrast injection, FPCT-A and 3-T MR-A were acquired. Each defect was then filled with synthetic pallets. The resulting cast was used as reference. Two independent radiologists measured the dimensions of all defects with FPCT-A and MR-A. Intra-class correlation coefficients (ICC) were calculated. Data were compared using t-tests and Bland-Altman plots. Results The correlation for FPCT-A and cast was higher compared to MR-A and cast (ICC 0.876 vs. 0.799 for surface length x width; ICC 0.887 vs. 0.866 for depth, p<0.001). Mean differences between FPCT-A and cast measurements were -1.1 mm for length (p<0.001), -0.7 mm for width (p0.05). Depth measurements were significantly smaller by MR-A (mean difference -1.1 mm, p<0.001). There was no bias between the different modalities. Conclusions Ex vivo FPCT-A and MR-A both deliver high diagnostic accuracy for the evaluation of osteochondral defects. FPCT-A was slightly more accurate than MR-A, which was most significant when measuring lesion depth.
Cell and gene therapy is a promising and disruptive new field of medicine for diseases lacking effective treatments. Collaboration among stakeholders has become critically important as investigators, ...health care providers, manufacturers, couriers, data registries, regulators and payers all become more invested in the success of this field. Many organizations have collaborated with each other to increase clarity, advocate for improvements and share lessons learned. These efforts appear to be making an impact, although the potential for duplicative efforts could slow progress. The second Regenerative Medicine InterCHANGE, hosted by the Foundation for the Accreditation of Cellular Therapy, took place at the Phacilitate Leaders World/World Stem Cell Summit conference in Miami, Florida, on January 24, 2020. Participants from several organizations outlined needs to advance cell and gene therapies. Efforts to address these include standardization, workforce development and advocacy. This article summarizes the major challenges and opportunities discussed during the InterCHANGE.
The purpose of the present study was to integrate an interactive gradient-based needle navigation system and to evaluate the feasibility and accuracy of the system for real-time MR guided needle ...puncture in a multi-ring phantom and in vivo in a porcine model. The gradient-based navigation system was implemented in a 1.5T MRI. An interactive multi-slice real-time sequence was modified to provide the excitation gradients used by two sets of three orthogonal pick-up coils integrated into a needle holder. Position and orientation of the needle holder were determined and the trajectory was superimposed on pre-acquired MR images. A gel phantom with embedded ring targets was used to evaluate accuracy using 3D distance from needle tip to target. Six punctures were performed in animals to evaluate feasibility, time, overall error (target to needle tip) and system error (needle tip to the guidance needle trajectory) in vivo. In the phantom experiments, the overall error was 6.2±2.9 mm (mean±SD) and 4.4±1.3 mm, respectively. In the porcine model, the setup time ranged from 176 to 204 seconds, the average needle insertion time was 96.3±40.5 seconds (min: 42 seconds; max: 154 seconds). The overall error and the system error was 8.8±7.8 mm (min: 0.8 mm; max: 20.0 mm) and 3.3±1.4 mm (min: 1.8 mm; max: 5.2 mm), respectively.
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