Fast global oscillations in networks of integrate-and-fire neurons with low firing rates

We study analytically the dynamics of a network of sparsely connected inhibitory integrate-and-fire neurons in a regime where individual neurons emit spikes irregularly and at a low rate. In the limit when the number of neurons N tends to infinity,the network exhibits a sharp transition between a stationary and an oscillatory global activity regime where neurons are weakly synchronized. The activity becomes oscillatory when the inhibitory feedback is strong enough. The period of the global oscillation is found to be mainly controlled by synaptic times, but depends also on the characteristics of the external input. In large but finite networks, the analysis shows that global oscillations of finite coherence time generically exist both above and below the critical inhibition threshold. Their characteristics are determined as functions of systems parameters, in these two different regimes. The results are found to be in good agreement with numerical simulations.Comment: 45 pages, 11 figures, to be published in Neural Computatio

Development of an in vitro cell system from zebrafish suitable to study bone cell differentiation and extracellular matrix mineralization

Mechanisms of bone formation and skeletal development have been successfully investigated in zebrafish using a variety of in vivo approaches, but in vitro studies have been hindered due to a lack of homologous cell lines capable of producing an extracellular matrix (ECM) suitable for mineral deposition. Here we describe the development and characterization of a new cell line termed ZFB1, derived from zebrafish calcified tissues. ZFB1 cells have an epithelium-like phenotype, grow at 28 degrees C in a regular L-15 medium supplemented with 15% of fetal bovine serum, and are maintained and manipulated using standard methods (e.g., trypsinization, cryopreservation, and transfection). They can therefore be propagated and maintained easily in most cell culture facilities. ZFB1 cells show aneuploidy with 2n=78 chromosomes, indicative of cell transformation. Furthermore, because DNA can be efficiently delivered into their intracellular space by nucleofection, ZFB1 cells are suitable for gene targeting approaches and for assessing gene promoter activity. ZFB1 cells can also differentiate toward osteoblast or chondroblast lineages, as demonstrated by expression of osteoblast- and chondrocyte-specific markers, they exhibit an alkaline phosphatase activity, a marker of bone formation in vivo, and they can mineralize their ECM. Therefore, they represent a valuable zebrafish-derived in vitro system for investigating bone cell differentiation and extracellular matrix mineralization.FISHCELL project [PTDC/MAR/105313/2008]; Portuguese Science and Technology Foundation (FCT); European Regional Development Fund (ERDF) through the COMPETE Program; National Fund through FCT [PEst-C/MAR/LA0015/2011]; FCT [SFRH/BPD/39189/2007]; Association of European Marine Biological Laboratories through the ASSEMBLE project [FP7/227799]info:eu-repo/semantics/publishedVersio

Analyzing Ideological Communities in Congressional Voting Networks

We here study the behavior of political party members aiming at identifying how ideological communities are created and evolve over time in diverse (fragmented and non-fragmented) party systems. Using public voting data of both Brazil and the US, we propose a methodology to identify and characterize ideological communities, their member polarization, and how such communities evolve over time, covering a 15-year period. Our results reveal very distinct patterns across the two case studies, in terms of both structural and dynamic properties

Acceptability and Preliminary Efficacy of a Web- and Telephone-Based Personalised Exercise Intervention for Individuals with Metastatic Prostate Cancer: The ExerciseGuide Pilot Randomised Controlled Trial.

Preliminary research has shown the effectiveness of supervised exercise-based interventions in alleviating sequela resulting from metastatic prostate cancer. However, many individuals encounter barriers that limit the uptake of face-to-face exercise. Technology-enabled interventions offer a distance-based alternative. This pilot study aimed to explore the acceptability, safety and preliminary efficacy of a web-based exercise intervention (ExerciseGuide) in individuals with metastatic prostate cancer. Forty participants (70.2 ± 8.5 years) with metastatic prostate cancer were randomised into the 8-week intervention (N = 20) or a wait-list control (N = 20). The intervention arm had access to a computer-tailored website, personalised exercise prescription and remote supervision. ExerciseGuide was deemed acceptable with a score ≥20 on the client satisfaction questionnaire; however, the usability score was just below the pre-specified score of ≥68 on the software usability scale. There were no serious adverse events reported. Moderate-to-vigorous physical activity levels between baseline and follow-ups were significantly higher (10.0 min per day; 95% CI = (1.3-18.6); p = 0.01) in the intervention group compared to wait-list control. There were also greater improvements in step count (1332; 95% CI = (159-2505); p = 0.02) and identified motivation (0.4, 95% CI = (0.0, 0.7); p = 0.04). Our findings provide preliminary evidence that ExerciseGuide is acceptable, safe and efficacious among individuals with metastatic prostate cancer

F-theory and Neutrinos: Kaluza-Klein Dilution of Flavor Hierarchy

We study minimal implementations of Majorana and Dirac neutrino scenarios in F-theory GUT models. In both cases the mass scale of the neutrinos m_nu ~ (M_weak)^2/M_UV arises from integrating out Kaluza-Klein modes, where M_UV is close to the GUT scale. The participation of non-holomorphic Kaluza-Klein mode wave functions dilutes the mass hierarchy in comparison to the quark and charged lepton sectors, in agreement with experimentally measured mass splittings. The neutrinos are predicted to exhibit a "normal" mass hierarchy, with masses m_3,m_2,m_1 ~ .05*(1,(alpha_GUT)^(1/2),alpha_GUT) eV. When the interactions of the neutrino and charged lepton sectors geometrically unify, the neutrino mixing matrix exhibits a mild hierarchical structure such that the mixing angles theta_23 and theta_12 are large and comparable, while theta_13 is expected to be smaller and close to the Cabibbo angle: theta_13 ~ theta_C ~ (alpha_GUT)^(1/2) ~ 0.2. This suggests that theta_13 should be near the current experimental upper bound.Comment: v2: 83 pages, 10 figures, references adde

Triangle Counting in Dynamic Graph Streams

Estimating the number of triangles in graph streams using a limited amount of memory has become a popular topic in the last decade. Different variations of the problem have been studied, depending on whether the graph edges are provided in an arbitrary order or as incidence lists. However, with a few exceptions, the algorithms have considered {\em insert-only} streams. We present a new algorithm estimating the number of triangles in {\em dynamic} graph streams where edges can be both inserted and deleted. We show that our algorithm achieves better time and space complexity than previous solutions for various graph classes, for example sparse graphs with a relatively small number of triangles. Also, for graphs with constant transitivity coefficient, a common situation in real graphs, this is the first algorithm achieving constant processing time per edge. The result is achieved by a novel approach combining sampling of vertex triples and sparsification of the input graph. In the course of the analysis of the algorithm we present a lower bound on the number of pairwise independent 2-paths in general graphs which might be of independent interest. At the end of the paper we discuss lower bounds on the space complexity of triangle counting algorithms that make no assumptions on the structure of the graph.Comment: New version of a SWAT 2014 paper with improved result

Qualitative study of the impact of an authentic electronic portfolio in undergraduate medical education

Background Portfolios are increasingly used in undergraduate and postgraduate medical education. Four medical schools have collaborated with an established NHS electronic portfolio provider to develop and implement an authentic professional electronic portfolio for undergraduate students. We hypothesized that using an authentic portfolio would have significant advantages for students, particularly in familiarizing them with the tool many will continue to use for years after graduation. This paper describes the early evaluation of this undergraduate portfolio at two participating medical schools. Methods To gather data, a questionnaire survey with extensive free text comments was used at School 1, and three focus groups were held at School 2. This paper reports thematic analysis of students’ opinions expressed in the free text comments and focus groups. Results Five main themes, common across both schools were identified. These concerned the purpose, use and acceptability of the portfolio, advantages of and barriers to the use of the portfolio, and the impacts on both learning and professional identity. Conclusions An authentic portfolio mitigated some of the negative aspects of using a portfolio, and had a positive effect on students’ perception of themselves as becoming past of the profession. However, significant barriers to portfolio use remained, including a lack of understanding of the purpose of a portfolio and a perceived damaging effect on feedback

Serum procalcitonin for the early recognition of nosocomial infection in the critically ill patients: a preliminary report

<p>Abstract</p> <p>Background</p> <p>The usefulness of procalcitonin (PCT) measurement in critically ill medical patients with suspected nosocomial infection is unclear. The aim of the study was to assess PCT value for the early diagnosis of bacterial nosocomial infection in selected critically ill patients.</p> <p>Methods</p> <p>An observational cohort study in a 15-bed intensive care unit was performed. Seventy patients with either proven (n = 47) or clinically suspected but not confirmed (n = 23) nosocomial infection were included. Procalcitonin measurements were obtained the day when the infection was suspected (D0) and at least one time within the 3 previous days (D-3 to D0). Patients with proven infection were compared to those without. The diagnostic value of PCT on D0 was determined through the construction of the corresponding receiver operating characteristic (ROC) curve. In addition, the predictive value of PCT variations preceding the clinical suspicion of infection was assessed.</p> <p>Results</p> <p>PCT on D0 was the best predictor of proven infection in this population of ICU patients with a clinical suspicion of infection (AUROCC = 0.80; 95% CI, 0.68–0.91). Thus, a cut-off value of 0.44 ng/mL provides sensitivity and specificity of 65.2% and 83.0%, respectively. Procalcitonin variation between D-1 and D0 was calculated in 45 patients and was also found to be predictive of nosocomial infection (AUROCC = 0.89; 95% CI, 0.79–0.98) with a 100% positive predictive value if the +0.26 ng/mL threshold value was applied. Comparable results were obtained when PCT variation between D-2 and D0, or D-3 and D0 were considered. In contrast, CRP elevation, leukocyte count and fever had a poor predictive value in our population.</p> <p>Conclusion</p> <p>PCT monitoring could be helpful in the early diagnosis of nosocomial infection in the ICU. Both absolute values and variations should be considered and evaluated in further studies.</p

Exploiting inflammation for therapeutic gain in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with &#60;5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC