Weak Gravitational Lensing by a Sample of X-ray Luminous Clusters of Galaxies -- III. Serendipitous Weak Lensing Detections of Dark and Luminous Mass Concentrations

In the course of a weak gravitational lensing survey of 39 clusters of galaxies,covering a total sky area of ~1 square degree, we have serendipitously discovered mass concentrations in the fields of A1705 and A1722 which are most probably not associated with the main cluster target. By combining weak lensing information with two-color galaxy photometry in fields centered on our sample clusters, we identify a new cluster candidate at z~0.5 in the field of A1705. This cluster candidate also displays strong lensing in the form of a giant luminous arc. The new mass concentration in the field of A1722 also seems to be associated with an optically luminous cluster of galaxies at z~0.5, but in this case there is some evidence for additional structures along the line of sight that may contribute to the lensing signal. A third cluster, A959, has a dark sub-clump which shows interesting morphological evidence in the mass map for being associated with the main cluster. This is the first case where there is any significant evidence for a physical association between a dark sub-clump (discovered from weak lensing) and a normal cluster. Analysis of archival X-ray data shows that the three new mass concentrations are not firmly detected in X-rays and that they are X-ray underluminous.Comment: 14 pages, 10 figures, version accepted by ApJ. See http://www.nordita.dk/~dahle/paper3.ps.gz for a version with high-resolution figures and Fig.5 in colo

Experimental model for CAPD studies in the rabbit

An animal model suitable for bioeompatibility studies of peritoneal dialysis solutions is presented. It permits fluid exchanges to be performed 3 times a day for at least 28 days. thus simulating Continuous Ambulatory Peritoneal Dialysis (CAPD) in humans.The surgical procedure is lenient, without omentectomy and nephrectomy. A closed, subcutaneous placed eatheter-system permits the animals to thrive well and move freely between dialysis-fluid exchanges. A Y-shaped dialysis equipment whichprevents air- and over-infusion was developed and is presented.The surgical procedure and the implanted catheter caused only minor histological changes of the peritoneum. No catheter-tunnel infections were observed.Our findings suggest that a slight peritoneal irritation is caused by the C:\PD-solutions, as non-infected, dialysed animals had a slightly higher body-temperature than controls and as the LD content of the dialysate was high probably indicatingcell-lysis.Though peritonitis was not avoided this experimental model using rabbits was found suitable for long term CAPD studies

A systematic approach for evaluating the role of surface-exposed loops in trypsin-like serine proteases applied to the 170 loop in coagulation factor VIIa

Proteases play a major role in many vital physiological processes. Trypsin-like serine proteases (TLPs), in particular, are paramount in proteolytic cascade systems such as blood coagulation and complement activation. The structural topology of TLPs is highly conserved, with the trypsin fold comprising two β-barrels connected by a number of variable surface-exposed loops that provide a surprising capacity for functional diversity and substrate specificity. To expand our understanding of the roles these loops play in substrate and co-factor interactions, we employ a systematic methodology akin to the natural truncations and insertions observed through evolution of TLPs. The approach explores a larger deletion space than classical random or directed mutagenesis. Using FVIIa as a model system, deletions of 1–7 amino acids through the surface exposed 170 loop, a vital allosteric regulator, was introduced. All variants were extensively evaluated by established functional assays and computational loop modelling with Rosetta. The approach revealed detailed structural and functional insights recapitulation and expanding on the main findings in relation to 170 loop functions elucidated over several decades using more cumbersome crystallization and single deletion/mutation methodologies. The larger deletion space was key in capturing the most active variant, which unexpectedly had a six-amino acid truncation. This variant would have remained undiscovered if only 2–3 deletions were considered, supporting the usefulness of the methodology in general protease engineering approaches. Our findings shed further light on the complex role that surface-exposed loops play in TLP function and supports the important role of loop length in the regulation and fine-tunning of enzymatic function throughout evolution

Detailed statistical analysis plan for the Danish Palliative care trial (DanPaCT)

Acknowledgements We wish to thank the students who sent out the questionnaires, who entered and compared all data, help with data management, made material blind to the investigators, and were/will be outcome assessors of interventions given. They were: Nicla Rohde Christensen, Ellen Lundorff, Marc Klee Olsen, Charlotte Lund Rasmussen, and Nete Skjødt. This work was funded by the Tryg Foundation [journal number 7-10-0838A] and the Danish Cancer Society [journal number R16-A695]. Other than funding the trial, the funding body had no role in the design, conduct, analysis, or reporting of the present trial.Peer reviewedPublisher PD

Making a Difference: A Qualitative Study on Care and Priority Setting in Health Care

The focus of the study is the conflict between care and concern for particular patients, versus considerations that take impartial considerations of justice to be central to moral deliberations. To examine these questions we have conducted qualitative interviews with health professionals in Norwegian hospitals. We found a value norm that implicitly seemed to overrule all others, the norm of ‘making a difference for the patients’. We will examine what such a statement implies, aiming to shed some light over moral dilemmas interwoven in bedside rationing

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations