Assessing the impact of biomedical research in academic institutions of disparate sizes

Abstract Background The evaluation of academic research performance is nowadays a priority issue. Bibliometric indicators such as the number of publications, total citation counts and h-index are an indispensable tool in this task but their inherent association with the size of the research output may result in rewarding high production when evaluating institutions of disparate sizes. The aim of this study is to propose an indicator that may facilitate the comparison of institutions of disparate sizes. Methods The Modified Impact Index (MII) was defined as the ratio of the observed h-index (h) of an institution over the h-index anticipated for that institution on average, given the number of publications (N) it produces i.e. (α and β denote the intercept and the slope, respectively, of the line describing the dependence of the h-index on the number of publications in log10 scale). MII values higher than 1 indicate that an institution performs better than the average, in terms of its h-index. Data on scientific papers published during 2002–2006 and within 36 medical fields for 219 Academic Medical Institutions from 16 European countries were used to estimate α and β and to calculate the MII of their total and field-specific production. Results From our biomedical research data, the slope β governing the dependence of h-index on the number of publications in biomedical research was found to be similar to that estimated in other disciplines (≈0.4). The MII was positively associated with the average number of citations/publication (r = 0.653, p Conclusion The MII should complement the use of h-index when comparing the research output of institutions of disparate sizes. It has a conceptual interpretation and, with the data provided here, can be computed for the total research output as well as for field-specific publication sets of institutions in biomedicine.</p

Linear and nonlinear optical properties of realistic quantum-wire structures: The dominant role of Coulomb correlation

A systematic analysis of the linear and nonlinear optical properties of realistic quantum wires is presented. The proposed theoretical approach, based on a set of generalized semiconductor Bloch equations, provides a full three-dimensional multisubband description of carrier-carrier correlation for any profile of the confinement potential, thus allowing a direct comparison with experiments on available structures. In agreement with previous investigations based on simplified one-dimensional models, our analysis shows that, also for realistic quantum-wire structures, electron-hole Coulomb correlation completely removes the one-dimensional band-edge singularities from the linear-absorption spectra. Moreover, we find that this effect is present also at high densities (corresponding to gain regimes) and contributes significantly in suppressing the ideal sharp features of the free-carrier density of states. The multisubband nature of available state-of-the-art structures is found to play a dominant role in determining the overall spectral shape in the whole density range

Molecular gas kinematics within the central 250 pc of the Milky Way

Using spectral-line observations of HNCO, N2H+, and HNC, we investigate the kinematics of dense gas in the central ~250 pc of the Galaxy. We present SCOUSE (Semi-automated multi-COmponent Universal Spectral-line fitting Engine), a line fitting algorithm designed to analyse large volumes of spectral-line data efficiently and systematically. Unlike techniques which do not account for complex line profiles, SCOUSE accurately describes the {l, b, v_LSR} distribution of CMZ gas, which is asymmetric about Sgr A* in both position and velocity. Velocity dispersions range from 2.6 km/s28. The gas is distributed throughout several "streams", with projected lengths ~100-250 pc. We link the streams to individual clouds and sub-regions, including Sgr C, the 20 and 50 km/s clouds, the dust ridge, and Sgr B2. Shell-like emission features can be explained by the projection of independent molecular clouds in Sgr C and the newly identified conical profile of Sgr B2 in {l ,b, v_LSR} space. These features have previously invoked supernova-driven shells and cloud-cloud collisions as explanations. We instead caution against structure identification in velocity-integrated emission maps. Three geometries describing the 3-D structure of the CMZ are investigated: i) two spiral arms; ii) a closed elliptical orbit; iii) an open stream. While two spiral arms and an open stream qualitatively reproduce the gas distribution, the most recent parameterisation of the closed elliptical orbit does not. Finally, we discuss how proper motion measurements of masers can distinguish between these geometries, and suggest that this effort should be focused on the 20 km/s and 50 km/s clouds and Sgr C

Canine model of ischemic stroke with permanent middle cerebral artery occlusion: clinical and histopathological findings

The aim of the present study was to assess the clinical and histopathological findings in a canine model of ischemic stroke. Cerebral ischemic stroke was induced by middle cerebral artery occlusion in four healthy beagle dogs using silicone plugs. They showed neurological signs of forebrain dysfunction such as reduced responsiveness, head turning, circling, postural reaction deficits, perceptual deficits, and hemianopsia. These signs gradually regressed within 4 weeks without therapy. On magnetic resonance imaging, T2 hyperintensity and T1 hypointensity were found in the cerebral cortex and basal ganglia. These lesions were well-defined and sharply demarcated from adjacent brain parenchyma with a homogenous appearance. No abnormalities of the cerebrospinal fluid were observed. At necropsy, atrophic and necrotic lesions were observed in the cerebral cortex. The cerebral cortex, basal ganglia, and thalamus were partially unstained with triphenyl-tetrazolium chloride. Histopathologically, typical features of infarction were identified in cortical and thalamic lesions. This study demonstrates that our canine model resembles the conditions of real stroke patients

Molecular gas kinematics within the central 250 pc of the Milky Way

Using spectral-line observations of HNCO, N2H+, and HNC, we investigate the kinematics of dense gas in the central ~250 pc of the Galaxy. We present SCOUSE (Semi-automated multi-COmponent Universal Spectral-line fitting Engine), a line fitting algorithm designed to analyse large volumes of spectral-line data efficiently and systematically. Unlike techniques which do not account for complex line profiles, SCOUSE accurately describes the {l, b, v_LSR} distribution of CMZ gas, which is asymmetric about Sgr A* in both position and velocity. Velocity dispersions range from 2.6 km/s28. The gas is distributed throughout several "streams", with projected lengths ~100-250 pc. We link the streams to individual clouds and sub-regions, including Sgr C, the 20 and 50 km/s clouds, the dust ridge, and Sgr B2. Shell-like emission features can be explained by the projection of independent molecular clouds in Sgr C and the newly identified conical profile of Sgr B2 in {l ,b, v_LSR} space. These features have previously invoked supernova-driven shells and cloud-cloud collisions as explanations. We instead caution against structure identification in velocity-integrated emission maps. Three geometries describing the 3-D structure of the CMZ are investigated: i) two spiral arms; ii) a closed elliptical orbit; iii) an open stream. While two spiral arms and an open stream qualitatively reproduce the gas distribution, the most recent parameterisation of the closed elliptical orbit does not. Finally, we discuss how proper motion measurements of masers can distinguish between these geometries, and suggest that this effort should be focused on the 20 km/s and 50 km/s clouds and Sgr C

Bilateral effects of unilateral cerebellar lesions as detected by voxel based morphometry and diffusion imaging

Over the last decades, the importance of cerebellar processing for cortical functions has been acknowledged and consensus was reached on the strict functional and structural cortico-cerebellar interrelations. From an anatomical point of view strictly contralateral interconnections link the cerebellum to the cerebral cortex mainly through the middle and superior cerebellar peduncle. Diffusion MRI (dMRI) based tractography has already been applied to address cortico-cerebellar-cortical loops in healthy subjects and to detect diffusivity alteration patterns in patients with neurodegenerative pathologies of the cerebellum. In the present study we used dMRI-based tractography to determine the degree and pattern of pathological changes of cerebellar white matter microstructure in patients with focal cerebellar lesions. Diffusion imaging and high-resolution volumes were obtained in patients with left cerebellar lesions and in normal controls. Middle cerebellar peduncles and superior cerebellar peduncles were reconstructed by multi fiber diffusion tractography. From each tract, measures of microscopic damage were assessed, and despite the presence of unilateral lesions, bilateral diffusivity differences in white matter tracts were found comparing patients with normal controls. Consistently, bilateral alterations were also evidenced in specific brain regions linked to the cerebellum and involved in higher-level functions. This could be in line with the evidence that in the presence of unilateral cerebellar lesions, different cognitive functions can be affected and they are not strictly linked to the side of the cerebellar lesion

Dynamic, Large-Scale Profiling of Transcription Factor Activity from Live Cells in 3D Culture

phenotypes. Taken together, our objective was to develop cellular arrays for dynamic, large-scale quantification of TF activity as cells organized into spherical structures within 3D culture.TF-specific and normalization reporter constructs were delivered in parallel to a cellular array containing a well-established breast cancer cell line cultured in Matrigel. Bioluminescence imaging provided a rapid, non-invasive, and sensitive method to quantify luciferase levels, and was applied repeatedly on each sample to monitor dynamic activity. Arrays measuring 28 TFs identified up to 19 active, with 13 factors changing significantly over time. Stimulation of cells with β-estradiol or activin A resulted in differential TF activity profiles evolving from initial stimulation of the ligand. Many TFs changed as expected based on previous reports, yet arrays were able to replicate these results in a single experiment. Additionally, arrays identified TFs that had not previously been linked with activin A.This system provides a method for large-scale, non-invasive, and dynamic quantification of signaling pathway activity as cells organize into structures. The arrays may find utility for investigating mechanisms regulating normal and abnormal tissue growth, biomaterial design, or as a platform for screening therapeutics

Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households

Background: There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza. We implemented a study of the feasibility and efficacy of face masks and hand hygiene to reduce influenza transmission among Hong Kong household members. Methodology/Principal Findings: We conducted a cluster randomized controlled trial of households (composed of at least 3 members) where an index subject presented with influenza-like-illness of <48 hours duration. After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test, the household of the index subject was randomised to 1) control or 2) surgical face masks or 3) hand hygiene. Households were visited within 36 hours, and 3, 6 and 9 days later. Nose and throat swabs were collected from index subjects and all household contact at each home visit and tested by viral culture. The primary outcome measure was laboratory culture confirmed influenza in a household contact; the secondary outcome was clinically diagnosed influenza (by self-reported symptoms). We randomized 198 households and completed follow up home visits in 128; the index cases in 122 of those households had laboratory-confirmed influenza. There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6%. Clinical secondary attack ratios varied from 5% to 18% depending on case definitions. The laboratory-based or clinical secondary attack ratios old not significantly differ across the intervention arms. Adherence to interventions was variable. Conclusions/Significance: The secondary attack ratios were lower than anticipated, and lower than reported in other countries, perhaps due to differing patterns of susceptibility, lack of significant antigenic drift in circulating influenza virus strains recently, and/or issues related to the symptomatic recruitment design. Lessons learn from this pilot have informed changes for the main study in 2008.published_or_final_versio

The role of kinetic context in apparent biased agonism at GPCRs

Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usually inferred from pharmacological data with the assumption that the confounding influences of observational (that is, assay dependent) and system (that is, cell background dependent) bias are excluded by experimental design and analysis. Here we reveal that ‘kinetic context’, as determined by ligand-binding kinetics and the temporal pattern of receptor-signalling processes, can have a profound influence on the apparent bias of a series of agonists for the dopamine D2 receptor and can even lead to reversals in the direction of bias. We propose that kinetic context must be acknowledged in the design and interpretation of studies of biased agonism