Effects of ursodeoxycholic acid on synthesis of cholesterol and bile acids in healthy subjects

Background/Aims: Ursodeoxycholic acid ( UDCA) decreases biliary secretion of cholesterol and is therefore used for the dissolution of cholesterol gallstones. It remains unclear whether these changes in biliary cholesterol excretion are associated with changes in cholesterol synthesis and bile acid synthesis. We therefore studied the activities of rate-limiting enzymes of cholesterol synthesis and bile acid synthesis, 3-hydroxy-3-methyl-glutarylcoenzyme A reductase and cholesterol 7alpha-hydroxylase, respectively, in normal subjects during UDCA feeding. Methods: UDCA was given to 8 healthy volunteers ( 5 men, 3 women; age 24-44 years) in a single dose of 10-15 mg/kg body weight for 40 days. Before and during ( days 3, 5, 10, 20, 30 and 40) UDCA treatment, urinary excretion of mevalonic acid and serum concentrations of 7alpha-hydroxy-4-cholesten-3-one (7alpha-HCO) were determined as markers of cholesterol and bile acid synthesis, respectively. The Wilcoxon signed rank test and Spearman's rank correlation coefficient were used for statistical analysis. Results: Cholesterol synthesis and serum lipid concentrations remained unchanged during UDCA treatment for 40 days. However, synthesis of bile acids increased during long-term treatment with UDCA as reflected by an increase in 7alpha-HCO serum concentrations from 39.7 +/- 21.3 ng/ml (median 32.8 ng/ml) before treatment to 64.0 +/- 30.4 ng/ml (median 77.5 ng/ml) at days 30-40 of UDCA treatment ( p < 0.05). Conclusions: UDCA treatment does not affect cholesterol synthesis in the liver, but does increase bile acid synthesis after prolonged treatment. This may represent a compensatory change following decreased absorption of endogenous bile acids as observed with UDCA therapy

Pixelated Geiger-Mode Avalanche Photo-Diode Characterization through Dark Current Measurement

PIXELATED geiger-mode avalanche photodiodes(PPDs), often called silicon photomultipliers (SiPMs) are emerging as an excellent replacement for traditional photomultiplier tubes (PMTs) in a variety of detectors, especially those for subatomic physics experiments, which requires extensive test and operation procedures in order to achieve uniform responses from all the devices. In this paper, we show for two PPD brands, Hamamatsu MPPC and SensL SPM, that the dark noise rate, breakdown voltage and rate of correlated avalanches can be inferred from the sole measure of dark current as a function of operating voltage, hence greatly simplifying the characterization procedure. We introduce a custom electronics system that allows measurement for many devices concurrently, hence allowing rapid testing and monitoring of many devices at low cost. Finally, we show that the dark current of Hamamastu Multi-Pixel Photon Counter (MPPC) is rather independent of temperature at constant operating voltage, hence the current measure cannot be used to probe temperature variations. On the other hand, the MPPC current can be used to monitor light source conditions in DC mode without requiring strong temperature stability, as long as the integrated source brightness is comparable to the dark noise rate.Comment: 8 pages, 9 figures. Submitted to IEEE Transaction in Nuclear Scienc

The North American Journals of Prince Maximilian of Wied, volume 3, September 1833-August 1834

Review of: "The North American Journals of Prince Maximilian of Wied, volume 3, September 1833-August 1834," edited by Stephen S. Witte and Marsha V. Gallagher and translated by Dieter Karch

Shouldering responsibility for sustainable peace: exploring Afghan ownership of peacebuilding activities in Afghanistan

The international community has followed up its 2001 invasion of Afghanistan with a complex multi-faceted peacebuilding project. However, informed observers believe the Western-led mission in Afghanistan has failed to address the inherent peacebuilding needs of Afghanistan and has hindered the formation of a locally experienced sustainable peace. In response, emerging peacebuilding theory and rhetoric has pointed to an urgent need for revised peacebuilding paradigms and strategies that hold local (Afghan) ownership of peacebuilding activities as a central concern. This research project utilised a qualitative grounded theory methodology to explore perceptions of Afghan ownership of peacebuilding activities in Afghanistan. Research data was gathered in early 2011 through face-to-face semi-structured interviews with 63 local and international peacebuilding leaders in two Afghan urban centres. The participants included persons from the United Nations, the Afghan and foreign governments, local and international NGOs, a broad range of civil society groups, international donors, and the international military forces. Analysis of the interview narratives revealed several dilemmas on the journey towards increased Afghan ownership of peacebuilding. First, participants believed that the international community is performing important roles in Afghanistan, but is struggling to ensure Afghan ownership of peacebuilding activities. Second, international and Afghan peacebuilding actors have struggled to define who should be owning peacebuilding in at least two respects: (1) civil society or government; and (2) traditional- informal or democratic-formal institutions. Third, grassroots populations and Afghan civil society felt virtually no ownership of upper-level peace processes, and described a distinct lack of locally owned grassroots-level peace process activities. And fourth, inappropriate external forces and processes, the militarisation and politicisation of peacebuilding activities, local aid dependency, and inadequate local control over peacebuilding coordination have hindered the international-domestic inter-relationship in Afghanistan. However, the dilemmas of local ownership do not need to be viewed as unworkable barriers but can be re-conceptualised as holding constructive potential in designing sustainable peacebuilding solutions. To this end, this research study proposed the creation of a locally owned, broadly participatory, and strategic dispute resolution system that might transform international-local relations and forge the necessary space in which the transition to local authority and ownership might occur.October 201

The Indianization of Lewis and Clark

Review of: "The Indianization of Lewis and Clark," by William R. Swagerty

The North American Journals of Prince Maximilian of Wied, volume 3, September 1833-August 1834

Review of: "The North American Journals of Prince Maximilian of Wied, volume 3, September 1833-August 1834," edited by Stephen S. Witte and Marsha V. Gallagher and translated by Dieter Karch

Social pedagogy as relational attachment practice

The utility of social pedagogy as an approach to building resiliency and developing positive relationships with children and youth is currently underdeveloped in North America. However, there are signs of growth in this field. For example, one youth project in British Columbia, Canada, employs relationship building, collaboration and creativity in terms of music- or art-based community interventions as part of its programme. The findings from a recent evaluation report on this youth project will be used to explore the potential for a social pedagogical approach being deployed more widely, and possibly more effectively, than current youth-focused practice. Specifically, the importance of relational practice, underpinned by aspects of attachment theory will be used to explore the utility of social pedagogical practices and examine the possibility of its development within a number of professional contexts

safety, feasibility, and metabolic response

Background Intensive care unit (ICU)-acquired weakness in critically ill patients is a common and significant complication affecting the course of critical illness. Whole-body vibration is known to be effective muscle training and may be an option in diminishing weakness and muscle wasting. Especially, patients who are immobilized and not available for active physiotherapy may benefit. Until now whole-body vibration was not investigated in mechanically ventilated ICU patients. We investigated the safety, feasibility, and metabolic response of whole-body vibration in critically ill patients. Methods We investigated 19 mechanically ventilated, immobilized ICU patients. Passive range of motion was performed prior to whole-body vibration therapy held in the supine position for 15 minutes. Continuous monitoring of vital signs, hemodynamics, and energy metabolism, as well as intermittent blood sampling, took place from the start of baseline measurements up to 1 hour post intervention. We performed comparative longitudinal analysis of the phases before, during, and after intervention. Results Vital signs and hemodynamic parameters remained stable with only minor changes resulting from the intervention. No application had to be interrupted. We did not observe any adverse event. Whole-body vibration did not significantly and/or clinically change vital signs and hemodynamics. A significant increase in energy expenditure during whole-body vibration could be observed. Conclusions In our study the application of whole-body vibration was safe and feasible. The technique leads to increased energy expenditure. This may offer the chance to treat patients in the ICU with whole-body vibration. Further investigations should focus on the efficacy of whole-body vibration in the prevention of ICU- acquired weakness. Trial registration Applicability and Safety of Vibration Therapy in Intensive Care Unit (ICU) Patients. ClinicalTrials.gov NCT01286610. Registered 28 January 2011

Evidence for the Rare Decay B -> K*ll and Measurement of the B -> Kll Branching Fraction

We present evidence for the flavor-changing neutral current decay $B\to K^*\ell^+\ell^-$ and a measurement of the branching fraction for the related process $B\to K\ell^+\ell^-$, where $\ell^+\ell^-$ is either an $e^+e^-$ or $\mu^+\mu^-$ pair. These decays are highly suppressed in the Standard Model, and they are sensitive to contributions from new particles in the intermediate state. The data sample comprises $123\times 10^6$ $\Upsilon(4S)\to B\bar{B}$ decays collected with the Babar detector at the PEP-II $e^+e^-$ storage ring. Averaging over $K^{(*)}$ isospin and lepton flavor, we obtain the branching fractions ${\mathcal B}(B\to K\ell^+\ell^-)=(0.65^{+0.14}_{-0.13}\pm 0.04)\times 10^{-6}$ and ${\mathcal B}(B\to K^*\ell^+\ell^-)=(0.88^{+0.33}_{-0.29}\pm 0.10)\times 10^{-6}$, where the uncertainties are statistical and systematic, respectively. The significance of the $B\to K\ell^+\ell^-$ signal is over $8\sigma$, while for $B\to K^*\ell^+\ell^-$ it is $3.3\sigma$.Comment: 7 pages, 2 postscript figues, submitted to Phys. Rev. Let