Do not attempt resuscitation : the importance of consensual decisions

Aims: To describe the involvement and input of physicians and nurses in cardiopulmonary resuscitation (cpr / do not attempt resuscitation (dnar) decisions; to analyse decision patterns; and understand the practical implications. Design: A qualitative grounded theory study using one-time open-ended interviews with 40 volunteer physicians and 52 nurses drawn from acute care wards with mixes of heterogeneous cases in seven different hospitals in German-speaking Switzerland. Results: Establishing dnar orders in the best interests of patients was described as a challenging task requiring the leadership of senior physicians and nurses. Implicit decisions in favour of cpr predominated at the beginning of hospitalisation; depending on the context, they were relieved/superseded by explicit dnar decisions. Explicit decisions were the result of hierarchical medical expertise, of multilateral interdisciplinary expertise, of patient autonomy and/or of negotiated patient autonomy. Each type of decision, implicit or explicit, potentially represented a team consensus. Non-consensual decisions were prone to precipitate personal or team conflicts, and, occasionally, led to non-compliance. Conclusion: Establishing dnar orders is a demanding task. Reaching a consensus is of crucial importance in guaranteeing teamwork and good patient care. Communication and negotiation skills, professional and personal life experience and empathy for patients and colleagues are pivotal. Therefore, leadership by experienced senior physicians and nurses is needed and great efforts should be made with regard to multidisciplinary education

Structural dissimilarity of large-scale structures in turbulent flows over wavy walls

Turbulent flows over a wavy wall are investigated in channels with a wavy bottom and a flat top with different channel heights. Flow structures are determined from proper orthogonal decompositions of velocity fields measured with particle image velocimetry. Three different channel heights are considered, which are characterized by blockage ratios β (half channel height to wave amplitude ratio) 3.3, 6.7, and 10. Measurements are evaluated at comparable Reynolds numbers (Re) around 10 000. Structural similarity of large-scale structures, which is valid at β = 6.7 and 10, no longer holds at β = 3.3. Furthermore, characteristic regions of flows over wavy walls exhibit different locations in the case of the smallest channel height

Impact of loss of high-molecular-weight von Willebrand factor multimers on blood loss after aortic valve replacement

Background Severe aortic stenosis is associated with loss of the largest von Willebrand factor (vWF) multimers, which could affect primary haemostasis. We hypothesized that the altered multimer structure with the loss of the largest multimers increases postoperative bleeding in patients undergoing aortic valve replacement. Methods We prospectively included 60 subjects with severe aortic stenosis. Before and after aortic valve replacement, vWF antigen, activity, and multimer structure were determined and platelet function was measured by impedance aggregometry. Blood loss from mediastinal drainage and the use of blood and haemostatic products were evaluated perioperatively. Results Before operation, the altered multimer structure was present in 48 subjects (80%). Baseline characteristics and laboratory data were similar in all subjects. The median blood loss after 6 h was 250 (105-400) and 145 (85-240) ml in the groups with the altered and normal multimer structures, respectively (P=0.182). After 24 h, the cumulative loss was 495 (270-650) and 375 (310-600) ml in the groups with the altered and normal multimer structures, respectively (P=0.713). Multivariable analysis revealed no significant influence of multimer structure and platelet function on bleeding volumes after 6 and 24 h. After 24 h, there was no obvious difference in vWF antigen, activity, and multimer structure in subjects with and without the altered multimer structure before operation or in subjects with and without perioperative plasma transfusion. Conclusions The altered vWF multimer structure before operation was not associated with increased bleeding after aortic valve replacement. Our findings might be explained by perioperative release of vWF and rapid recovery of the largest vWF multimer

ESS Target Moderator Cryogenic Plant : Process Design

The European Spallation Source (ESS) project is a neutron spallation source facility currently under construction outside Lund, Sweden. The ESS accelerator will deliver a 5 MW proton beam to a spallation target at 2.0 GeV with a nominal current of 62.5 mA to generate fast neutrons. The cooling of the spallation target with liquid hydrogen circulating in the cryogenic moderator system (CMS) transforms these fast neutrons to slow neutrons which compose the useful radiation. The liquid hydrogen itself is cooled by a helium refrigeration cycle, the target moderator cryogenic plant (TMCP) providing cooling capacity in a wide range of 2.3-31.8 kW at 15-20 K. TMCP\u27s maximum cooling capacity of 31.8 kW will make it the world\u27s largest plant of its kind. The TMCP project is challenging in many ways. The heat load of the CMS has to be removed precisely all the time by the TMCP. In addition the TMCP has to meet highly dynamic requirements as the heat load ceases quickly in case the proton beam trips off. Furthermore transitions within the wide cooling capacity range have to be achieved seamlessly. In this talk the progress of the TMCP engineering is summarized. Process design, control strategies, machine concept and layout are presented

Telomerase activity in human leukemic cells with or without monosomy 7 or 7q-

BACKGROUND: In bone marrow material from patients with various leukemias we noted that samples with either a deletion on the long arm of one chromosome 7 (7q-) or a monosomy 7 had a higher telomerase activity. Considering that introduction of a chromosome 7 into a cancer cell line had been reported to eliminate telomerase activity, that 7q- is a common negative prognostic finding in cancers, and that the deleted segment (band 7q31) contains an unidentified tumor suppressor gene, we wondered if this gene might be a telomerase inhibitor. RESULTS: We found no significant difference in telomerase activity between the three groups of patient samples. In contrast to reports on tumor cell lines we observed no amplification of the telomerase genes. METHODS: We analyzed telomerase activity and copy number of the telomerase genes hTERT and hTR in frozen archival bone marrow samples from leukemia patients with a referral diagnosis of AML, and either a monosomy for chromosome 7, a deletion on the long arm of chromosome 7 (7q-), or none of these aberrations. Telomerase activity was measured with a commercially available kit, and the copy number of the telomerase genes was tested by FISH. CONCLUSIONS: We found no evidence of a telomerase inhibitor in band 7q31. The lack of telomerase gene amplification found in cell lines from solid tumors could reflect that this amplification is a property of solid tumors, not of hematological cancers

Cell-cycle-dependent transcriptional and translational DNA-damage response of 2 ribonucleotide reductase genes in S. cerevisiae

The ribonucleotide reductase (RNR) enzyme catalyzes an essential step in the production of deoxyribonucleotide triphosphates (dNTPs) in cells. Bulk biochemical measurements in synchronized Saccharomyces cerevisiae cells suggest that RNR mRNA production is maximal in late G1 and S phases; however, damaged DNA induces RNR transcription throughout the cell cycle. But such en masse measurements reveal neither cell-to-cell heterogeneity in responses nor direct correlations between transcript and protein expression or localization in single cells which may be central to function. We overcame these limitations by simultaneous detection of single RNR transcripts and also Rnr proteins in the same individual asynchronous S. cerevisiae cells, with and without DNA damage by methyl methanesulfonate (MMS). Surprisingly, RNR subunit mRNA levels were comparably low in both damaged and undamaged G1 cells and highly induced in damaged S/G2 cells. Transcript numbers became correlated with both protein levels and localization only upon DNA damage in a cell cycle-dependent manner. Further, we showed that the differential RNR response to DNA damage correlated with variable Mec1 kinase activity in the cell cycle in single cells. The transcription of RNR genes was found to be noisy and non-Poissonian in nature. Our results provide vital insight into cell cycle-dependent RNR regulation under conditions of genotoxic stress.Massachusetts Institute of Technology. Center for Environmental Health Sciences (deriving from NIH P30-ES002109)National Institutes of Health (U.S.) (grant R01-CA055042)National Institutes of Health (U.S.) (grant DP1-OD006422)Massachusetts Institute of Technology (CSBi Merck-MIT Fellowship

Effect of promoter architecture on the cell-to-cell variability in gene expression

According to recent experimental evidence, the architecture of a promoter, defined as the number, strength and regulatory role of the operators that control the promoter, plays a major role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effort that addresses the question of how changes in promoter architecture affect noise in gene expression in a systematic rather than case-by-case fashion. In this article, we make such a systematic investigation, based on a simple microscopic model of gene regulation that incorporates stochastic effects. In particular, we show how operator strength and operator multiplicity affect this variability. We examine different modes of transcription factor binding to complex promoters (cooperative, independent, simultaneous) and how each of these affects the level of variability in transcription product from cell-to-cell. We propose that direct comparison between in vivo single-cell experiments and theoretical predictions for the moments of the probability distribution of mRNA number per cell can discriminate between different kinetic models of gene regulation.Comment: 35 pages, 6 figures, Submitte

Assessment of dosimetric errors induced by deformable image registration methods in 4D pencil beam scanned proton treatment planning for liver tumours

PURPOSE: Respiratory impacts in pencil beam scanned proton therapy (PBS-PT) are accounted by extensive 4D dose calculations, where deformable image registration (DIR) is necessary for estimating deformation vector fields (DVFs). We aim here to evaluate the dosimetric errors induced by different DIR algorithms in their resulting 4D dose calculations by using ground truth(GT)-DVFs from 4DMRI. MATERIALS AND METHODS: Six DIR methods: ANACONDA, Morfeus, B-splines, Demons, CT Deformable, and Total Variation, were respectively applied to nine 4DCT-MRI liver data sets. The derived DVFs were then used as input for 4D dose calculation. The DIR induced dosimetric error was assessed by individually comparing the resultant 4D dose distributions to those obtained with GT-DVFs. Both single-/three-field plans and single/rescanned strategies were investigated. RESULTS: Differences in 4D dose distributions among different DIR algorithms, and compared to the results using GT-DVFs, were pronounced. Up to 40 % of clinically relevant dose calculation points showed dose differences of 10 % or more between the GT. Differences in V95(CTV) reached up to 11.34 ± 12.57 %. The dosimetric errors became in general less substantial when applying multiple-field plans or using rescanning. CONCLUSION: Intrinsic geometric errors by DIR can influence the clinical evaluation of liver 4D PBS-PT plans. We recommend the use of an error bar for correctly interpreting individual 4D dose distributions