High intestinal cholesterol absorption is associated with cardiovascular disease and risk alleles in ABCG8 and ABO: evidence from the LURIC and YFS cohorts and from a meta-analysis.

OBJECTIVES This study sought to determine whether high intestinal cholesterol absorption represents a cardiovascular risk factor and to link ABCG8 and ABO variants to cardiovascular disease (CVD). BACKGROUND Plant sterol-enriched functional foods are widely used for cholesterol lowering. Their regular intake yields a 2-fold increase in circulating plant sterol levels that equally represent markers of cholesterol absorption. Variants in ABCG8 and ABO have been associated with circulating plant sterol levels and CVD, thereby suggesting atherogenic effects of plant sterols or of cholesterol uptake. METHODS The cholestanol-to-cholesterol ratio (CR) was used as an estimate of cholesterol absorption because it is independent of plant sterols. First, we investigated the associations of 6 single nucleotide polymorphisms in ABCG8 and ABO with CR in the LURIC (LUdwisghafen RIsk and Cardiovascular health study) and the YFS (Young Finns Study) cohorts. Second, we conducted a systematic review and meta-analysis to investigate whether CR might be related to CVD. RESULTS In LURIC, the minor alleles of rs4245791 and rs4299376 and the major alleles of rs41360247, rs6576629, and rs4953023 of the ABCG8 gene and the minor allele of rs657152 of the ABO gene were significantly associated with higher CR. Consistent results were obtained for rs4245791, rs4299376, rs6576629, and rs4953023 in YFS. The meta-analysis, including 6 studies and 4,362 individuals, found that CR was significantly increased in individuals with CVD. CONCLUSIONS High cholesterol absorption is associated with risk alleles in ABCG8 and ABO and with CVD. Harm caused by elevated cholesterol absorption rather than by plant sterols may therefore mediate the relationships of ABCG8 and ABO variants with CVD.

New online method for water isotope analysis of speleothem fluid inclusions using laser absorption spectroscopy (WS-CRDS)

A new online method to analyse water isotopes of speleothem fluid inclusions using a wavelength scanned cavity ring down spectroscopy (WS-CRDS) instrument is presented. This novel technique allows us simultaneously to measure hydrogen and oxygen isotopes for a released aliquot of water. To do so, we designed a new simple line that allows the online water extraction and isotope analysis of speleothem samples. The specificity of the method lies in the fact that fluid inclusions release is made on a standard water background, which mainly improves the δ D robustness. To saturate the line, a peristaltic pump continuously injects standard water into the line that is permanently heated to 140 °C and flushed with dry nitrogen gas. This permits instantaneous and complete vaporisation of the standard water, resulting in an artificial water background with well-known δ D and δ18O values. The speleothem sample is placed in a copper tube, attached to the line, and after system stabilisation it is crushed using a simple hydraulic device to liberate speleothem fluid inclusions water. The released water is carried by the nitrogen/standard water gas stream directly to a Picarro L1102-i for isotope determination. To test the accuracy and reproducibility of the line and to measure standard water during speleothem measurements, a syringe injection unit was added to the line. Peak evaluation is done similarly as in gas chromatography to obtain &delta D; and δ18O isotopic compositions of measured water aliquots. Precision is better than 1.5 ‰ for δ D and 0.4 ‰ for δ18O for water measurements for an extended range (−210 to 0 ‰ for δ D and −27 to 0 ‰ for δ18O) primarily dependent on the amount of water released from speleothem fluid inclusions and secondarily on the isotopic composition of the sample. The results show that WS-CRDS technology is suitable for speleothem fluid inclusion measurements and gives results that are comparable to the isotope ratio mass spectrometry (IRMS) technique.

Capability of a space-based space surveillance system to detect and track objects in GEO, MEO and LEO orbits

In this paper we present the results from the coverage and the orbit determination accuracy simulations performed within the recently completed ESA study “Assessment Study for Space Based Space Surveillance (SBSS) Demonstration System” (Airbus Defence and Space consortium). This study consisted in investigating the capability of a space based optical sensor (SBSS) orbiting in low Earth orbit (LEO) to detect and track objects in GEO (geosynchronous orbit), MEO (medium Earth orbit) and LEO and to determinate and improve initial orbits from such observations. Space based systems may achieve better observation conditions than ground based sensors in terms of astrometric accuracy, detection coverage, and timeliness. The primary observation mode of the proposed SBSS demonstrator is GEO surveillance, i.e. the systematic search and detection of unknown and known objects. GEO orbits are specific and unique orbits from dynamical point of view. A space-based sensor may scan the whole GEO ring within one sidereal day if the orbit and pointing directions are chosen properly. For an efficient survey, our goal was to develop a leak-proof GEO fence strategy. Collaterally, we show that also MEO, LEO and other (GTO,Molniya, etc.) objects would be possible to observe by the system and for a considerable number of LEO objects to down to size of 1 cm we can obtain meaningful statistical data for improvement and validation of space debris environment models

Intestinal cholesterol absorption, treatment with atorvastatin, and cardiovascular risk in hemodialysis patients.

BACKGROUND Hemodialysis patients are high absorbers of intestinal cholesterol; they benefit less than other patient groups from statin therapy, which inhibits cholesterol synthesis. OBJECTIVES This study sought to investigate whether the individual cholesterol absorption rate affects atorvastatin's effectiveness to reduce cardiovascular risk in hemodialysis patients. METHODS This post-hoc analysis included 1,030 participants in the German Diabetes and Dialysis Study (4D) who were randomized to either 20 mg of atorvastatin (n = 519) or placebo (n = 511). The primary endpoint was a composite of major cardiovascular events. Secondary endpoints included all-cause mortality and all cardiac events. Tertiles of the cholestanol-to-cholesterol ratio, which is an established biomarker of cholesterol absorption, were used to identify high and low cholesterol absorbers. RESULTS A total of 454 primary endpoints occurred. On multivariate time-to-event analyses, the interaction term between tertiles and treatment with atorvastatin was significantly associated with the risk of reaching the primary endpoint. Stratified analysis by cholestanol-to-cholesterol ratio tertiles confirmed this effect modification: atorvastatin reduced the risk of reaching the primary endpoint in the first tertile (hazard ratio [HR]: 0.72; p = 0.049), but not the second (HR: 0.79; p = 0.225) or third tertiles (HR: 1.21; p = 0.287). Atorvastatin consistently significantly reduced all-cause mortality and the risk of all cardiac events in only the first tertile. CONCLUSIONS Intestinal cholesterol absorption, as reflected by cholestanol-to-cholesterol ratios, predicts the effectiveness of atorvastatin to reduce cardiovascular risk in hemodialysis patients. Those with low cholesterol absorption appear to benefit from treatment with atorvastatin, whereas those with high absorption do not benefit.

Capability of E-Bike Tourism in Switzerland

AIM OF PAPER AND RESEARCH QUESTIONS The primary aim of this investigation was to examine, if tourism in Switzerland can be stimulated by focusing on e-bike offers. Switzerland is an attractive and manifold country for bike tourism. However, there are plenty of hilly and steep areas, where the topography is quite demanding and cycling is predestined to ambitious sportsperson. Less performance-oriented bike tourists are possibly discouraged by the challenges of the landscape. E-bikes seem to be a reasonable alterna-tive to enable less trained person to attend bike tours in steeper regions as well as to keep heterogeneous groups together. E-bikes are already popular in Switzerland for daily routes as the journey to work, but they are not very common in the tour-istic context. The presented investigation evaluates the current standing of supply and demand for e-bike tourism and asks for opportunities and threats in the future development. LITERTURE REVIEW The existing frameworks to analyse capability in the field of sport tourism are limited, because of the broad variation of sports and tourism types. Still several conceptions are valuable to evaluate the opportunities of e-bike tourism in Switzer-land. According to Higham and Hinch (2009) the potential of touristic products and destinations always depends on the interaction among the factors place, people and activity. Standeven and de Knop (1999) support this position by identify-ing the experience of place as a key component of the sport tourism experience. Bull (2005) assumes that place not only affects experience. In his opinion, the specific spatially located resources are even crucial for the existence of nature sports. He identifies four factors determining the attraction of touristic products or destination, as physical characteristics, accessibility and infrastructural arrangements, political and economic resources as well as cultural and perceptual aspects. Concerning the demand side (people) the contemporary research is guided by an individual psychological focus delivering mainly results about motives and the decision making process (e.g. Görtz & Hürten, 2011). RESEARCH DESIGN AND DATA ANALYSIS The presented study is based on a between method triangulation, consisting of qualitative interviews with important stake-holders on the supply side and a cross sectional survey on the demand side. Qualitative interviews were conducted with the first provider of touristic e-bike routes and with the manager of the leading e-bike rental company in Switzerland. The interviews were evaluated by qualitative content analysis according to Mayring (2008). The survey covered a randomized sample of 748 adult persons and focused on interests and needs of potential consumers. The concluding potentials analy-sis combined the results of the interviews and the survey with the findings of literature research. As central outcome the strengths, weaknesses, opportunities and threats were evaluated and presented by SWOT-analysis. RESULTS Results showed that the development of e-bike tourism in Switzerland was not initiated by tourism promoter, but by an innovative e-bike producer. However, also for the manufacturer the fit between landscape (place), product (activity) and visitors (people) was the crucial criterion. The first e-bike tours were offered in a demanding and rural region, in order that the experience of place was able to promote a positive overall experience. Due to the success of the first touristic e-bike products, several tourism regions started to extend their portfolio with e-bike offers. To date a nationwide network for signalised e-bike tours, rental stations and changing stations for rechargeable batteries is established. Despite the attractive offer, the demand is only moderate. The obtained results of the consumer survey pointed at a certain barrier to use e-bikes for tourism activities. The most substantial barrier is the missing affinity for bike tourism in general. Another notable group considering themselves as “fit enough for normal bike tourism”. Nevertheless 55% of the respondent are interested in tour-istic e-bike products. Looking only at people with e-bike tourism experience, even 92% are interested in further activities. DISCUSSION AN CONCLUSION The current study findings are encouraging because they suggest a superior suitability and an attractive level of e-bike tourism products in Switzerland. The results of the consumer survey indicate an increasing demand for e-bike tourism. The investigation also points at some risks, as the rivalry for bike tourism or the raised safety hazard because of the increased driving speed. Summing up, the results support the conclusion, that e-bike tourism will become more important in the com-ing years. However, to reach the goal relevant trends as the requirement for customised offers must be considered and marketing activities are supposed to be extended. REFERENCES Bull, C. (2005). Sport tourism resource analysis. In J. Higham (Ed.), Sport tourism destination: Issues, opportunities and analysis (pp. 25-38). Amsterdam: Elsevier Butterworth-Heinemann. Görtz, M., & D. Hürten (2011). Motive der Radurlauber, psychografische Merkmale und Reiseverhalten. In A. Dreyer, E. Miglbauer & R. Mühlnickel (Hrsg.), Radtourismus. Entwicklungen, Potenziale, Perspektiven (S. 36-43). München: Olden-bourg. Higham, J., & Hinch, T. (2009). Sport and Tourism. Globalization, Mobility and Identity. Amsterdam: Butterworth-Heinemann. Mayring, P. (2008). Qualitative Inhaltsanalyse. Grundlagen und Techniken (10. Aufl.). Weinheim: Beltz Verlag. Standeven, J., & De Knop, P. (1999). Sport Tourism. Campaign: Human Kinetics.

Interactions of Polyvinylpyrrolidone with Chlorin e6-Based Photosensitizers Studied by NMR and Electronic Absorption Spectroscopy

Polyvinylpyrrolidone (PVP) can act as potential drug delivery vehicle for porphyrin-based photosensitizers in photodynamic therapy (PDT) to enhance their stability and prevent porphyrin self-association. In the present study the interactions of PVP (MW 10 kDa) were probed with five different derivatives of chlorin e6 (CE6) bearing either one of the amino acids serine, lysine, tyrosine or arginine, or monoamino-hexanoic acid as substituent. All derivatives of CE6 (xCE) formed aggregates of a similar structure in aqueous buffer in the millimolar range. In the presence of PVP monomerization of all xCE aggregates could be proved by 1H NMR spectroscopy. xCE-PVP complex formation was confirmed by 1H NMR T2 relaxation and diffusion ordered spectroscopy (DOSY). 1H1H-NOESY data suggested that the xCE uptake into the PVP polymer matrix is governed by hydrophobic interactions. UV–vis absorption and fluorescence emission bands of xCE in the micromolar range revealed characteristic PVP-induced bathochromic shifts. The presented data point out the potential of PVP as carrier system for amphiphilic derivatives of chlorin e6. The capacity of PVP to monomerize xCE aggregates may enhance their efficiency as possible photosensitizers in PDT.