Calibration with confidence:A principled method for panel assessment

Frequently, a set of objects has to be evaluated by a panel of assessors, but not every object is assessed by every assessor. A problem facing such panels is how to take into account different standards amongst panel members and varying levels of confidence in their scores. Here, a mathematically-based algorithm is developed to calibrate the scores of such assessors, addressing both of these issues. The algorithm is based on the connectivity of the graph of assessors and objects evaluated, incorporating declared confidences as weights on its edges. If the graph is sufficiently well connected, relative standards can be inferred by comparing how assessors rate objects they assess in common, weighted by the levels of confidence of each assessment. By removing these biases, "true" values are inferred for all the objects. Reliability estimates for the resulting values are obtained. The algorithm is tested in two case studies, one by computer simulation and another based on realistic evaluation data. The process is compared to the simple averaging procedure in widespread use, and to Fisher's additive incomplete block analysis. It is anticipated that the algorithm will prove useful in a wide variety of situations such as evaluation of the quality of research submitted to national assessment exercises; appraisal of grant proposals submitted to funding panels; ranking of job applicants; and judgement of performances on degree courses wherein candidates can choose from lists of options.Comment: 32 pages including supplementary information; 5 figure

Astronomical Spectroscopy

Spectroscopy is one of the most important tools that an astronomer has for studying the universe. This chapter begins by discussing the basics, including the different types of optical spectrographs, with extension to the ultraviolet and the near-infrared. Emphasis is given to the fundamentals of how spectrographs are used, and the trade-offs involved in designing an observational experiment. It then covers observing and reduction techniques, noting that some of the standard practices of flat-fielding often actually degrade the quality of the data rather than improve it. Although the focus is on point sources, spatially resolved spectroscopy of extended sources is also briefly discussed. Discussion of differential extinction, the impact of crowding, multi-object techniques, optimal extractions, flat-fielding considerations, and determining radial velocities and velocity dispersions provide the spectroscopist with the fundamentals needed to obtain the best data. Finally the chapter combines the previous material by providing some examples of real-life observing experiences with several typical instruments.Comment: An abridged version of a chapter to appear in Planets, Stars and Stellar Systems, to be published in 2011 by Springer. Slightly revise

Imaging of Four Planetary Nebulae in the Magellanic Clouds Using the Hubble Space Telescope Faint Object Camera

Using the Faint Object Camera on-board the Hubble Space Telescope, we have obtained images of four planetary nebulae (PNe) in the Magellanic Clouds, namely N2 and N5 in the SMC and N66 and N201 in the LMC. Each nebula was imaged through two narrow-band filters isolating [O III] λ5007 and Hβ, for a nominal exposure time of 1000 s in each filter. Significant detail is evident on the raw images and, after deconvolution using the Richardson-Lucy algorithm, structures as small as 0.06" are easily discernible. In [O III], SMC N5 shows a circular ring structure, with a peak-to-peak diameter of 0.26" and a FWHM of 0.35", while SMC N2 shows an elliptical ring structure with a peak-to-peak diameter of 0.26" x 0.21" (FWHM 0.40" x 0.35"). The expansion ages corresponding to the observed structures in SMC N2 and N5 are of the order of 3000 yr. Such low ages appear more easy to reconcile with helium-burning rather than hydrogen-burning central star evolutionary tracks. LMC N201 is very compact, with a FWHM of 0.21" in Hβ. The Type I PN LMC N66 is a multipolar nebula, with the brightest part having an extent of about 2" and with fainter structures extending over 4". The [O III] image reveals structures unprecedented for a planetary nebula, with several bright knots and faint loops visible outside the two main bright lobes

BLISS: an artificial language for learnability studies

To explore neurocognitive mechanisms underlying the human language faculty, cognitive scientists use artificial languages to control more precisely the language learning environment and to study selected aspects of natural languages. Artificial languages applied in cognitive studies are usually designed ad hoc, to only probe a specific hypothesis, and they include a miniature grammar and a very small vocabulary. The aim of the present study is the construction of an artificial language incorporating both syntax and semantics, BLISS. Of intermediate complexity, BLISS mimics natural languages by having a vocabulary, syntax, and some semantics, as defined by a degree of non-syntactic statistical dependence between words. We quantify, using information theoretical measures, dependencies between words in BLISS sentences as well as differences between the distinct models we introduce for semantics. While modeling English syntax in its basic version, BLISS can be easily varied in its internal parametric structure, thus allowing studies of the relative learnability of different parameter sets

Filamin-A Regulates Neutrophil Uropod Retraction through RhoA during Chemotaxis

Filamin-A (FLNa) has been shown to be a key cross-linker of actin filaments in the leading edge of a motile melanoma cell line, however its role in neutrophils undergoing chemotaxis is unknown. Using a murine transgenic model in which FLNa is selectively deleted in granulocytes, we report that, while neutrophils lacking FLNa show normal polarization and pseudopod extension, they exhibit obvious defects in uropod retraction. This uropod retraction defect was found to be a direct result of reduced FLNa mediated activation of the small GTPase RhoA and myosin mediated actin contraction in the FLNa null cells. This results in a neutrophil recruitment defect in FLNa null mice. The compensatory increase in FLNb levels that was observed in the FLNa null neutrophils may be sufficient to compensate for the lack of FLNa at the leading edge allowing for normal polarization, however this compensation is unable to regulate RhoA activated tail retraction at the rear of the cell

Adaptive and maladaptive consequences of “matching habitat choice:” lessons from a rapidly-evolving butterfly metapopulation

Relationships between biased dispersal and local adaptation are currently debated. Here, I show how prior work on wild butterflies casts a novel light on this topic. “Preference” is defined as the set of likelihoods of accepting particular resources after encountering them. So defined, butterfly oviposition preferences are heritable habitat adaptations distinct from both habitat preference and biased dispersal, but influencing both processes. When a butterfly emigrates after its oviposition preference begins to reduce realized fecundity, the resulting biased dispersal is analogous to that occurring when a fish emigrates after its morphological habitat adaptations reduce its feeding rate. I illustrate preference-biased dispersal with examples from metapopulations of Melitaea cinxia and Euphydryas editha. E. editha were feeding on a well-defended host, Pedicularis, when humans created patches in which Pedicularis was killed and a less-defended host, Collinsia, was rendered phenologically available. Patch-specific natural selection favoured oviposition on Collinsia in logged (“clearing”) patches and on Pedicularis in undisturbed open forest. Quantitative variation in post-alighting oviposition preference was heritable, and evolved to be consistently different between patch types. This difference was driven more by biased dispersal than by spatial variation of natural selection. Insects developing on Collinsia in clearings retained adaptations to Pedicularis in clutch size, geotaxis and oviposition preference, forcing them to choose between emigrating in search of forest habitats with Pedicularis or staying and failing to find their preferred host. Insects that stayed suffered reduction of realized fecundity after delayed oviposition on Collinsia. Those that emigrated suffered even greater fitness penalty from consistently low offspring survival on Pedicularis. Paradoxically, most emigrants reduced both their own fitness and that of the recipient populations by dispersing from a benign natal habitat to which they were maladapted into a more demanding habitat to which they were well-adapted. “Matching habitat choice” reduced fitness when evolutionary lag rendered traditional cues unreliable in a changing environment

Human metapneumovirus induces more severe disease and stronger innate immune response in BALB/c mice as compared with respiratory syncytial virus

BACKGROUND: Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are members of the Pneumovirinae subfamily of Paramyxoviridae and can cause severe respiratory disease, especially in infants and young children. Some differences in the clinical course of these infections have been described, but there are few comparative data on pathogenesis in humans and animal models. In this study, HMPV and RSV were compared for replication, pathogenesis and immune induction in BALB/c mice infected with equivalent inocula of either virus. METHODS: Viral titers in the lungs and in the nasal turbinates of mice were determined by plaque assay. Histopathological changes in the lungs as well as weight loss and levels of airway obstruction were monitored in the infected mice to record the severity of illness. Inflammatory cells recruited to the lungs were characterized by flow cytometry and by differential staining. In the case of natural killer cells, cytotoxic activity was also measured. Cytokine levels in the BAL were determined by cytometric bead array. RESULTS: RSV replicated to higher titers than HMPV in the lung and in the upper respiratory tract (URT), and virus elimination from the lungs was more rapid in HMPV-infected mice. Clinical illness as determined by airway obstruction, weight loss, and histopathology was significantly more severe after HMPV infection. A comparison of the cellular immune response revealed similar recruitment of T lymphocytes with a predominance of IFN-γ-producing CD8+ T cells. By contrast, there were obvious differences in the innate immune response. After HMPV infection, more neutrophils could be detected in the airways and there were more activated NK cells than in RSV-infected mice. This correlated with higher levels of IL-6, TNF-α and MCP-1. CONCLUSION: This study shows important differences in HMPV and RSV pathogenesis and suggests that the pronounced innate immune response observed after HMPV infection might be instrumental in the severe pathology

Persistence and compliance to antidepressant treatment in patients with depression: A chart review

<p>Abstract</p> <p>Background</p> <p>Adherence has recently been suggested to be divided into these two components: persistence (i.e., whether patients continue treatment or not) and compliance (i.e., whether patients take doses as instructed). However, no study has yet assessed these two clinically relevant components at the same time in adherence to antidepressant treatment in the clinical outpatient setting.</p> <p>Methods</p> <p>In this retrospective chart-review, 6-month adherence to antidepressants was examined in 367 outpatients with a major depressive disorder (ICD-10) (170 males; mean ± SD age 37.6 ± 13.9 years), who started antidepressant treatment from April 2006 through March 2007. Additionally, we evaluated Medication Possession Rate (MPR), defined as the total days a medication was dispensed to patients divided by the treatment period.</p> <p>Results</p> <p>Only 161 patients (44.3%) continued antidepressant treatment for 6 months. Among 252 patients who discontinued their initial antidepressant, 63.1% of these patients did so without consulting their physicians. Sertraline use was associated with a higher persistence rate at month 6 (odds ratio 2.59 in comparison with sulpiride), and the use of anxiolytic benzodiazepines had a positive effect on persistence to antidepressant treatment only at month 1 (odds ratio 2.14). An overall MPR was 0.77; 55.6% of patients were considered compliant (i.e., a MPR of ≥ 0.8).</p> <p>Conclusion</p> <p>Given a high rate of antidepressant discontinuation without consulting their physicians, closer communication between patients and their physicians should be encouraged. Although the use of anxiolytic benzodiazepines was associated with a higher persistence to antidepressant treatment at month 1, the use of these drugs should be avoided as a rule, given their well-known serious adverse effects.</p

Neutralization of (NK-cell-derived) B-cell activating factor by Belimumab restores sensitivity of chronic lymphoid leukemia cells to direct and Rituximab-induced NK lysis.

Natural killer (NK) cells are cytotoxic lymphocytes that substantially contribute to the therapeutic benefit of antitumor antibodies like Rituximab, a crucial component in the treatment of B-cell malignancies. In chronic lymphocytic leukemia (CLL), the ability of NK cells to lyse the malignant cells and to mediate antibody-dependent cellular cytotoxicity upon Fc receptor stimulation is compromised, but the underlying mechanisms are largely unclear. We report here that NK-cells activation-dependently produce the tumor necrosis factor family member 'B-cell activating factor' (BAFF) in soluble form with no detectable surface expression, also in response to Fc receptor triggering by therapeutic CD20-antibodies. BAFF in turn enhanced the metabolic activity of primary CLL cells and impaired direct and Rituximab-induced lysis of CLL cells without affecting NK reactivity per se. The neutralizing BAFF antibody Belimumab, which is approved for treatment of systemic lupus erythematosus, prevented the effects of BAFF on the metabolism of CLL cells and restored their susceptibility to direct and Rituximab-induced NK-cell killing in allogeneic and autologous experimental systems. Our findings unravel the involvement of BAFF in the resistance of CLL cells to NK-cell antitumor immunity and Rituximab treatment and point to a benefit of combinatory approaches employing BAFF-neutralizing drugs in B-cell malignancies