Can the impact of bed closure in intensive care units be reliably monitored?

OBJECTIVE: To assess the properties of various indicators aimed at monitoring the impact on the activity and patient outcome of a bed closure in a surgical intensive care unit (ICU). DESIGN: Comparison before and after the intervention. SETTING: A surgical ICU at a university hospital. PATIENTS: All patients admitted to the unit over two periods of 10 months. INTERVENTION: Closure of one bed out of 17. MEASUREMENTS AND RESULTS: Activity and outcome indicators in the ICU and the structures upstream from it (emergency department, operative theater, recovery room) and downstream from it (intermediate care units). After the bed closure, the monthly medians of admitted patients and ICU hospital days increased from 107 (interquartile range 94-112) to 113 (106-121, P=0.07) and from 360 (325-443) to 395 (345-436, P=0.48), respectively, along with the linear trend observed in our institution. All indicators of workload, patient severity, and outcome remained stable except for SAPS II score, emergency admissions, and ICU readmissions, which increased not only transiently but also on a mid-term basis (10 months), indicating that the process of patient care delivery was no longer predictable. CONCLUSIONS: Health care systems, including ICUs, are extraordinary flexible, and can adapt to multiple external constraints without altering commonly used activity and outcome indicators. It is therefore necessary to set up multiple indicators to be able to reliably monitor the impact of external interventions and intervene rapidly when the system is no longer under control.

Communication with terminal cancer patients in palliative care: are there differences between nurses and physicians?

The aim of this study was to find whether there were interprofessional differences in specific elements of communication with terminal cancer patients and decision-making processes that concern such patients. Given that interdisciplinary team work is one of the basic values in palliative care, if there are conflicting views between professions on such important issues it is most important to know about these and to understand them. A questionnaire utilized in an earlier survey of palliative care physicians and addressing their attitudes to and beliefs about specific elements of communication and decision making was sent to a sample of palliative care nurses working in the same regions, i.e. the French-speaking parts of Switzerland, Belgium and France. After a second mailing (reminder), 135 of the 163 questionnaires (83%) were returned. There was general agreement between nurses and physicians on questions dealing with perceptions of patients' knowledge of their diagnosis and stage of disease, patients' need for information, "do not resuscitate" orders and ethical principles in decision-making processes. Statistically significant, but small, differences between professional groups were only observed for a minority of the questions. Interprofessional differences in specific elements of communication with terminal cancer patients and decision-making processes affecting these patients were not so marked that they could be called "conflicting interprofessional views."

Rhea-a manually curated resource of biochemical reactions.

Rhea (http://www.ebi.ac.uk/rhea) is a comprehensive resource of expert-curated biochemical reactions. Rhea provides a non-redundant set of chemical transformations for use in a broad spectrum of applications, including metabolic network reconstruction and pathway inference. Rhea includes enzyme-catalyzed reactions (covering the IUBMB Enzyme Nomenclature list), transport reactions and spontaneously occurring reactions. Rhea reactions are described using chemical species from the Chemical Entities of Biological Interest ontology (ChEBI) and are stoichiometrically balanced for mass and charge. They are extensively manually curated with links to source literature and other public resources on metabolism including enzyme and pathway databases. This cross-referencing facilitates the mapping and reconciliation of common reactions and compounds between distinct resources, which is a common first step in the reconstruction of genome scale metabolic networks and models.

Bayesian Networks and the Value of the Evidence for the Forensic Two-Trace Transfer Problem

Forensic scientists face increasingly complex inference problems for evaluating likelihood ratios (LRs) for an appropriate pair of propositions. Up to now, scientists and statisticians have derived LR formulae using an algebraic approach. However, this approach reaches its limits when addressing cases with an increasing number of variables and dependence relationships between these variables. In this study, we suggest using a graphical approach, based on the construction of Bayesian networks (BNs). We first construct a BN that captures the problem, and then deduce the expression for calculating the LR from this model to compare it with existing LR formulae. We illustrate this idea by applying it to the evaluation of an activity level LR in the context of the two-trace transfer problem. Our approach allows us to relax assumptions made in previous LR developments, produce a new LR formula for the two-trace transfer problem and generalize this scenario to n traces.

On the convergence of EM-like algorithms for image segmentation using Markov random fields.

Inference of Markov random field images segmentation models is usually performed using iterative methods which adapt the well-known expectation-maximization (EM) algorithm for independent mixture models. However, some of these adaptations are ad hoc and may turn out numerically unstable. In this paper, we review three EM-like variants for Markov random field segmentation and compare their convergence properties both at the theoretical and practical levels. We specifically advocate a numerical scheme involving asynchronous voxel updating, for which general convergence results can be established. Our experiments on brain tissue classification in magnetic resonance images provide evidence that this algorithm may achieve significantly faster convergence than its competitors while yielding at least as good segmentation results.

Premature atherosclerosis in patients with xanthelasma.

BACKGROUND: Only about half the patients with xanthelasma are hyperlipidemic. The clinical significance of xanthelasma as a marker of cardiovascular disease is not yet well defined. OBJECTIVE: To determine the risk of cardiovascular disease in patients with normolipidemic and hyperlipidemic xanthelasma. METHODS: Carotid ultrasonography (7 MHz using B-mode images, Advanced Technology Laboratories) was used to detect carotid plaques and measure the intima-media thickness (IMT) of the common carotid arteries. Seventeen patients with normolipidemic and hyperlipidemic xanthelasma were examined and compared with 21 age-matched normal subjects. RESULTS: The risk of cardiovascular disease was significantly increased in patients with xanthelasma. Carotid plaques were more frequent in patients with xanthelasma than in controls (64.7% and 23.8%, respectively; P = 0.020), and IMT was significantly higher (mean +/- SD: 1.1 +/- 0.1 and 0.6 +/- 0.2 mm, respectively; P < 0.001). The difference of carotid IMT between normolipidemic xanthelasma and hyperlipidemic xanthelasma was not statistically different (mean +/- SD: 1.1 +/- 0.1 and 1.1 +/- 0.2 mm, respectively; P = 0.577). CONCLUSION: Premature carotid atherosclerosis is observed in patients with normolipidemic and hyperlipidemic xanthelasma. Patients with xanthelasma should be considered to have an increased risk of cardiovascular disease independently to the level of plasma lipids. A larger number of patients is, however, needed to confirm this preliminary study.

Inferring the mode of origin of polyploid species from next-generation sequence data.

Many eukaryote organisms are polyploid. However, despite their importance, evolutionary inference of polyploid origins and modes of inheritance has been limited by a need for analyses of allele segregation at multiple loci using crosses. The increasing availability of sequence data for nonmodel species now allows the application of established approaches for the analysis of genomic data in polyploids. Here, we ask whether approximate Bayesian computation (ABC), applied to realistic traditional and next-generation sequence data, allows correct inference of the evolutionary and demographic history of polyploids. Using simulations, we evaluate the robustness of evolutionary inference by ABC for tetraploid species as a function of the number of individuals and loci sampled, and the presence or absence of an outgroup. We find that ABC adequately retrieves the recent evolutionary history of polyploid species on the basis of both old and new sequencing technologies. The application of ABC to sequence data from diploid and polyploid species of the plant genus Capsella confirms its utility. Our analysis strongly supports an allopolyploid origin of C. bursa-pastoris about 80 000 years ago. This conclusion runs contrary to previous findings based on the same data set but using an alternative approach and is in agreement with recent findings based on whole-genome sequencing. Our results indicate that ABC is a promising and powerful method for revealing the evolution of polyploid species, without the need to attribute alleles to a homeologous chromosome pair. The approach can readily be extended to more complex scenarios involving higher ploidy levels.

Spatial prediction of monthly wind speeds in complex terrain with adaptive general regression neural networks

This paper presents the general regression neural networks (GRNN) as a nonlinear regression method for the interpolation of monthly wind speeds in complex Alpine orography. GRNN is trained using data coming from Swiss meteorological networks to learn the statistical relationship between topographic features and wind speed. The terrain convexity, slope and exposure are considered by extracting features from the digital elevation model at different spatial scales using specialised convolution filters. A database of gridded monthly wind speeds is then constructed by applying GRNN in prediction mode during the period 1968-2008. This study demonstrates that using topographic features as inputs in GRNN significantly reduces cross-validation errors with respect to low-dimensional models integrating only geographical coordinates and terrain height for the interpolation of wind speed. The spatial predictability of wind speed is found to be lower in summer than in winter due to more complex and weaker wind-topography relationships. The relevance of these relationships is studied using an adaptive version of the GRNN algorithm which allows to select the useful terrain features by eliminating the noisy ones. This research provides a framework for extending the low-dimensional interpolation models to high-dimensional spaces by integrating additional features accounting for the topographic conditions at multiple spatial scales. Copyright (c) 2012 Royal Meteorological Society.

On the use of IRMS in forensic science: proposals for a methodological approach

The flourishing number of publications on the use of isotope ratio mass spectrometry (IRMS) in forensicscience denotes the enthusiasm and the attraction generated by this technology. IRMS has demonstratedits potential to distinguish chemically identical compounds coming from different sources. Despite thenumerous applications of IRMS to a wide range of forensic materials, its implementation in a forensicframework is less straightforward than it appears. In addition, each laboratory has developed its ownstrategy of analysis on calibration, sequence design, standards utilisation and data treatment without aclear consensus.Through the experience acquired from research undertaken in different forensic fields, we propose amethodological framework of the whole process using IRMS methods. We emphasize the importance ofconsidering isotopic results as part of a whole approach, when applying this technology to a particularforensic issue. The process is divided into six different steps, which should be considered for a thoughtfuland relevant application. The dissection of this process into fundamental steps, further detailed, enablesa better understanding of the essential, though not exhaustive, factors that have to be considered in orderto obtain results of quality and sufficiently robust to proceed to retrospective analyses or interlaboratorycomparisons.

Causal Warrant for Realism about Particle Physics

While scientific realism generally assumes that successful scientific explanations yield information about reality, realists also have to admit that not all information acquired in this way is equally well warranted. Some versions of scientific realism do this by saying that explanatory posits with which we have established some kind of causal contact are better warranted than those that merely appear in theoretical hypotheses. I first explicate this distinction by considering some general criteria that permit us to distinguish causal warrant from theoretical warrant. I then apply these criteria to a specific case from particle physics, claiming that scientific realism has to incorporate the distinction between causal and theoretical warrant if it is to be an adequate stance in the philosophy of particle physics.

Phylogenetic analysis of plastid and nuclear DNA sequences reveals a rapid late Miocene radiation of the temperate bamboo tribe Arundinarieae (Poaceae, Bambusoideae)

Background: Arundinarieae are a large tribe of temperate woody bamboos for which phylogenetics are poorly understood because of limited taxon sampling and lack of informative characters. Aims: This study assessed phylogenetic relationships, origins and classification of Arundinarieae. Methods: DNA sequences (plastid trnL-F; nuclear ITS) were used for parsimony and Bayesian inference including 41 woody bamboo taxa. Divergence dates were estimated using a relaxed Bayesian clock. Results: Arundinarieae were monophyletic but their molecular divergence was low compared to the tropical Bambuseae. Ancestors of the Arundinarieae lineage were estimated to have diverged from the other bamboos 23 (15-30) million years ago (Mya). However, the Arundinarieae radiation occurred 10 (6-16) Mya compared to 18 (11-25) Mya for the tropical Bambuseae. Some groups could be defined within Arundinarieae, but they do not correspond to recognised subtribes such as Arundinariinae or Shibataeinae. Conclusions: Arundinarieae are a relatively ancient bambusoid lineage that underwent a rapid radiation in the late Miocene. The radiation coincides with the continental collision of the Indo-Australian and Eurasian Plates. Arundinarieae are distributed primarily in East Asia and the Himalayas to northern Southeast Asia. It is unknown whether they were present in Asia long before their radiation, but we believe recent dispersal is a more likely scenario. Keywords: Arundinarieae; Bambuseae; internal transcribed spacer (ITS); molecular clock; phylogenetics; radiation; temperate bamboos; Thamnocalaminae; trnL-F

Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients.

Optimal vaccine strategies must be identified for improving T-cell vaccination against infectious and malignant diseases. MelQbG10 is a virus-like nano-particle loaded with A-type CpG-oligonucleotides (CpG-ODN) and coupled to peptide(16-35) derived from Melan-A/MART-1. In this phase IIa clinical study, four groups of stage III-IV melanoma patients were vaccinated with MelQbG10, given (i) with IFA (Montanide) s.c.; (ii) with IFA s.c. and topical Imiquimod; (iii) i.d. with topical Imiquimod; or (iv) as intralymph node injection. In total, 16/21 (76%) patients generated ex vivo detectable Melan-A/MART-1-specific T-cell responses. T-cell frequencies were significantly higher when IFA was used as adjuvant, resulting in detectable T-cell responses in all (11/11) patients, with predominant generation of effector-memory-phenotype cells. In turn, Imiquimod induced higher proportions of central-memory-phenotype cells and increased percentages of CD127(+) (IL-7R) T cells. Direct injection of MelQbG10 into lymph nodes resulted in lower T-cell frequencies, associated with lower proportions of memory and effector-phenotype T cells. Swelling of vaccine site draining lymph nodes, and increased glucose uptake at PET/CT was observed in 13/15 (87%) of evaluable patients, reflecting vaccine triggered immune reactions in lymph nodes. We conclude that the simultaneous use of both Imiquimod and CpG-ODN induced combined memory and effector CD8(+) T-cell responses.

Robust Estimators of the Generalized Log-Gamma Distribution

We propose robust estimators of the generalized log-gamma distribution and, more generally, of location-shape-scale families of distributions. A (weighted) Q tau estimator minimizes a tau scale of the differences between empirical and theoretical quantiles. It is n(1/2) consistent; unfortunately, it is not asymptotically normal and, therefore, inconvenient for inference. However, it is a convenient starting point for a one-step weighted likelihood estimator, where the weights are based on a disparity measure between the model density and a kernel density estimate. The one-step weighted likelihood estimator is asymptotically normal and fully efficient under the model. It is also highly robust under outlier contamination. Supplementary materials are available online.