Moral preferences in helping dilemmas expressed by matching and forced choice

This paper asks whether moral preferences in eight medical dilemmas change as a function of how preferences are expressed, and how people choose when they are faced with two equally attractive help projects. In two large-scale studies, participants first read dilemmas where they “matched” two suggested helping projects (which varied on a single attribute) so that they became equally attractive. They did this by filling in a missing number (e.g., how many male patients must Project M save in order to be equally attractive as Project F which can save 100 female patients). Later, the same participants were asked to choose between the two equally attractive projects. We found robust evidence that people do not choose randomly, but instead tend to choose projects that help female (vs. male), children (vs. adult), innocent (vs. non-innocent), ingroup (vs. outgroup) and existing (vs. future) patients, and imply no (vs. some) risk of a harmful side-effect, even when these projects have been matched as equally attractive as, and save fewer patients than the contrasting project. We also found that some moral preferences are hidden when expressed with matching but apparent when expressed with forced choice. For example, 88–95% of the participants expressed that female and male patients are equally valuable when doing the matching task, but over 80% of them helped female patients in the choice task

Relativistic quantum clocks

The conflict between quantum theory and the theory of relativity is exemplified in their treatment of time. We examine the ways in which their conceptions differ, and describe a semiclassical clock model combining elements of both theories. The results obtained with this clock model in flat spacetime are reviewed, and the problem of generalizing the model to curved spacetime is discussed, before briefly describing an experimental setup which could be used to test of the model. Taking an operationalist view, where time is that which is measured by a clock, we discuss the conclusions that can be drawn from these results, and what clues they contain for a full quantum relativistic theory of time.Comment: 12 pages, 4 figures. Invited contribution for the proceedings for "Workshop on Time in Physics" Zurich 201

Elucidating an amorphous form stabilization mechanism of tenapanor hydrochloride: crystal structure analysis using Xray diffraction, NMR crystallography and molecular modelling

By the combined use of powder and single crystal X-ray diffraction, solid-state NMR, and molecular modelling, the crystal structures of two systems containing the unusually large tenapanor drug molecule have been determined: the free form, ANHY and a dihydrochloride salt form, 2HCl. Dynamic nuclear polarization (DNP) assisted solid-state NMR (SSNMR) crystallography investigations were found essential for the final assignment, and were used to validate the crystal structure of ANHY. From the structural informatics analysis of ANHY and 2HCl, conformational ring differences in one part of the molecule were observed which influences the relative orientation of a methyl group on a ring nitrogen and thereby impacts the crystallizability of the dihydrochloride salt. From quantum chemistry calculations, the dynamics between different ring conformations in tenapanor is predicted to be fast. Addition of HCl to tenapanor results in general in a mixture of protonated ring conformers and hence a statistical mix of diastereoisomers which builds up the amorphous form, a-2HCl. This was qualitatively verified by 13C CP/MAS NMR investigations of the amorphous form. Thus, to form any significant amount of the crystalline material 2HCl, which originates from the minor (i.e., energetically less stable) ring conformations, one needs to involve nitrogen deprotonation to allow exchange between minor and major conformations of ANHY in solution. Thus, by controlling the solution pH value to well below the pKa of ANHY, the equilibrium between ANHY and 2HCl can be controlled and by this mechanism the crystallization of 2HCl can be avoided and the amorphous form of the dichloride salt can therefore be stabilized

PR3-ANCA:a promising biomarker in primary sclerosing cholangitis (PSC)

BACKGROUND AND AIMS:The only recognized biomarker for primary sclerosing cholangitis (PSC) is atypical anti-neutrophil cytoplasmic antibodies (aANCA), which, in addition to having low sensitivity and specificity, is an indirect immunofluorescence (IIF) test lacking the advantages of high throughput and objectivity. Recent reports have shown that antibodies to proteinase-3 (PR3-ANCA) might add diagnostic value in inflammatory bowel disease (IBD), specifically in ulcerative colitis (UC). As PSC is associated with IBD, the objective of this study was to evaluate the frequency and clinical significance of PR3-ANCA in a large cohort of patients. METHODS:A total of 244 PSC and 254 control [autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), hepatitis C viral infection (HCV), hepatitis B viral infection (HBV), and healthy controls] sera and their clinical correlations were retrospectively analyzed for PR3-ANCA determined by ELISA and a new chemiluminescence immunoassay (CIA). Testing was also performed for aANCA by IIF. RESULTS:When measured by CIA, PR3-ANCA was detected in 38.5% (94/244) of PSC patients compared to 10.6% (27/254) controls (p<0.0001). By ELISA, PR3-ANCA was detected in 23.4% (57/244) of PSC patients compared to 2.7% (6/254) controls (p<0.0001). PR3-ANCA in PSC patients was not associated with the presence or type of underlying IBD, and, in fact, it was more frequent in Crohn's disease (CD) patients with PSC than previously reported in CD alone. PR3-ANCA in PSC measured by CIA correlated with higher liver enzymes. CONCLUSION:PR3-ANCA is detected in a significant proportion of PSC patients compared to other liver diseases including PBC and AIH. PR3-ANCA is associated with higher liver enzyme levels in PSC, and is not solely related to underlying IBD

Integrating isotopes and documentary evidence : dietary patterns in a late medieval and early modern mining community, Sweden

We would like to thank the Archaeological Research Laboratory, Stockholm University, Sweden and the Tandem Laboratory (Ångström Laboratory), Uppsala University, Sweden, for undertaking the analyses of stable nitrogen and carbon isotopes in both human and animal collagen samples. Also, thanks to Elin Ahlin Sundman for providing the δ13C and δ15N values for animal references from Västerås. This research (Bäckström’s PhD employment at Lund University, Sweden) was supported by the Berit Wallenberg Foundation (BWS 2010.0176) and Jakob and Johan Söderberg’s foundation. The ‘Sala project’ (excavations and analyses) has been funded by Riksens Clenodium, Jernkontoret, Birgit and Gad Rausing’s Foundation, SAU’s Research Foundation, the Royal Physiographic Society of Lund, Berit Wallenbergs Foundation, Åke Wibergs Foundation, Lars Hiertas Memory, Helge Ax:son Johnson’s Foundation and The Royal Swedish Academy of Sciences.Peer reviewedPublisher PD

A prospective study of Helicobacter pylori in relation to the risk for pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>The relationship between <it>Helicobacter pylori </it>infection and pancreatic cancer has been investigated in three previous studies with contradictory results. The aim of the present study was to investigate the association between <it>H. pylori </it>seropositivity and the risk for pancreatic cancer in a nested case-control study within a population based cohort.</p> <p>Methods</p> <p>Selected birth-year cohorts (born 1921–1949) of residents in Malmö, Sweden, were invited to a health screening investigation. A total of 33 346 subjects participated. Cases with pancreatic cancer (n = 87) were matched to controls (n = 263) using age, sex and time for baseline investigation as matching variables. <it>H. pylori </it>serology was analysed in stored serum samples using an enzyme-linked immunosorbent assay. Odds ratios (OR) for pancreatic cancer were calculated with 95% confidence intervals (CI) using logistic regression.</p> <p>Results</p> <p><it>H. pylori </it>seropositivity was not associated with pancreatic cancer in the total cohort (adjusted OR 1.25 (0.75–2.09)). However, a statistically significant association was found in never smokers (OR 3.81 (1.06–13.63) adjusted for alcohol consumption) and a borderline statistically significant association was found in subjects with low alcohol consumption (OR 2.13 (0.97–4.69) adjusted for smoking).</p> <p>Conclusion</p> <p>We conclude that no association between <it>H. pylori </it>infection and the risk for pancreatic cancer was found in the total cohort. However, in never smokers and in subjects with low risk alcohol consumption, a positive <it>H. pylori </it>serology was associated with an increased risk for pancreatic cancer. These findings should be interpreted cautiously due to the limited number of cases in these subgroups.</p

Change and continuity in managerialism: 100 years of administrative history at the International Museum of Ceramics in Faenza

This paper offers a long-term perspective on the debate on managerial transformations in the public sector: how public sector organisations actually arrived at such changes, what processes, discourses and practices are transformed and how. This is investigated through archival research and a longitudinal analysis of 100 years of the administrative history of an Italian museum. Taking a historical perspective allows us to account for organisational changes that occurred over time, including major reforms in the governance structure and the dynamics of some core managerial features. Such an approach enables a more in-depth, empirically grounded and historically aware discussion on the so-called rise of managerial issues in the public secto

Activation of Latent HIV Using Drug-Loaded Nanoparticles

Antiretroviral therapy is currently only capable of controlling HIV replication rather than completely eradicating virus from patients. This is due in part to the establishment of a latent virus reservoir in resting CD4+ T cells, which persists even in the presence of HAART. It is thought that forced activation of latently infected cells could induce virus production, allowing targeting of the cell by the immune response. A variety of molecules are able to stimulate HIV from latency. However no tested purging strategy has proven capable of eliminating the infection completely or preventing viral rebound if therapy is stopped. Hence novel latency activation approaches are required. Nanoparticles can offer several advantages over more traditional drug delivery methods, including improved drug solubility, stability, and the ability to simultaneously target multiple different molecules to particular cell or tissue types. Here we describe the development of a novel lipid nanoparticle with the protein kinase C activator bryostatin-2 incorporated (LNP-Bry). These particles can target and activate primary human CD4+ T-cells and stimulate latent virus production from human T-cell lines in vitro and from latently infected cells in a humanized mouse model ex vivo. This activation was synergistically enhanced by the HDAC inhibitor sodium butyrate. Furthermore, LNP-Bry can also be loaded with the protease inhibitor nelfinavir (LNP-Bry-Nel), producing a particle capable of both activating latent virus and inhibiting viral spread. Taken together these data demonstrate the ability of nanotechnological approaches to provide improved methods for activating latent HIV and provide key proof-of-principle experiments showing how novel delivery systems may enhance future HIV therapy