Automated optimization of a reduced layer 5 pyramidal cell model based on experimental data.

The construction of compartmental models of neurons involves tuning a set of parameters to make the model neuron behave as realistically as possible. While the parameter space of single-compartment models or other simple models can be exhaustively searched, the introduction of dendritic geometry causes the number of parameters to balloon. As parameter tuning is a daunting and time-consuming task when performed manually, reliable methods for automatically optimizing compartmental models are desperately needed, as only optimized models can capture the behavior of real neurons. Here we present a three-step strategy to automatically build reduced models of layer 5 pyramidal neurons that closely reproduce experimental data. First, we reduce the pattern of dendritic branches of a detailed model to a set of equivalent primary dendrites. Second, the ion channel densities are estimated using a multi-objective optimization strategy to fit the voltage trace recorded under two conditions - with and without the apical dendrite occluded by pinching. Finally, we tune dendritic calcium channel parameters to model the initiation of dendritic calcium spikes and the coupling between soma and dendrite. More generally, this new method can be applied to construct families of models of different neuron types, with applications ranging from the study of information processing in single neurons to realistic simulations of large-scale network dynamics

Probabilistic Clustering of Time-Evolving Distance Data

We present a novel probabilistic clustering model for objects that are represented via pairwise distances and observed at different time points. The proposed method utilizes the information given by adjacent time points to find the underlying cluster structure and obtain a smooth cluster evolution. This approach allows the number of objects and clusters to differ at every time point, and no identification on the identities of the objects is needed. Further, the model does not require the number of clusters being specified in advance -- they are instead determined automatically using a Dirichlet process prior. We validate our model on synthetic data showing that the proposed method is more accurate than state-of-the-art clustering methods. Finally, we use our dynamic clustering model to analyze and illustrate the evolution of brain cancer patients over time

Video enhancement using adaptive spatio-temporal connective filter and piecewise mapping

This paper presents a novel video enhancement system based on an adaptive spatio-temporal connective (ASTC) noise filter and an adaptive piecewise mapping function (APMF). For ill-exposed videos or those with much noise, we first introduce a novel local image statistic to identify impulse noise pixels, and then incorporate it into the classical bilateral filter to form ASTC, aiming to reduce the mixture of the most two common types of noises - Gaussian and impulse noises in spatial and temporal directions. After noise removal, we enhance the video contrast with APMF based on the statistical information of frame segmentation results. The experiment results demonstrate that, for diverse low-quality videos corrupted by mixed noise, underexposure, overexposure, or any mixture of the above, the proposed system can automatically produce satisfactory results

Spatially Explicit Data: Stewardship and Ethical Challenges in Science

Scholarly communication is at an unprecedented turning point created in part by the increasing saliency of data stewardship and data sharing. Formal data management plans represent a new emphasis in research, enabling access to data at higher volumes and more quickly, and the potential for replication and augmentation of existing research. Data sharing has recently transformed the practice, scope, content, and applicability of research in several disciplines, in particular in relation to spatially specific data. This lends exciting potentiality, but the most effective ways in which to implement such changes, particularly for disciplines involving human subjects and other sensitive information, demand consideration. Data management plans, stewardship, and sharing, impart distinctive technical, sociological, and ethical challenges that remain to be adequately identified and remedied. Here, we consider these and propose potential solutions for their amelioration

Is albumin gradient or fluid to serum albumin ratio better than the pleural fluid lactate dehydroginase in the diagnostic of separation of pleural effusion?

BACKGROUND: To determine the accuracy of serum-effusion albumin gradient (SEAG) and pleural fluid to serum albumin ratio (ALBR) in the diagnostic separation of pleural effusion into transudate and exudate and to compare SEAG and ALBR with pleural fluid LDH (FLDH) the most widely used test. METHODS: Data collected from 200 consecutive patients with a known cause of pleural effusion in a United Kingdom district general hospital. RESULTS: The median and inter quartile ranges (IQR) for SEAG 93.5 (33.8 to 122.5) g/dl, ALBR 0.49 (0.42 to 0.62) and FLDH 98.5 IU/L(76.8 to 127.5) in transudates were significantly lower than the corresponding values for exudates 308.5 (171 to 692), 0.77 (0.63 to 0.85), 344 (216 to 695) all p < 0.0001. The Area Under the Curve (AUC) with 95% confidence intervals (Cl) for SEAG, ALBR and FLDH were 0.81 (0.75 to 0.87), 0.79 (0.72 to 0.86) and 0.9 (0.87 to 0.96) respectively. The positive likelihood ratios with 95%CI for FLDH, SEAG, and ALBR were: 7.3(3.5–17), 6.3(3–15) 6.2(3–14) respectively. There was a significant negative correlation between SEAG and ALBR (r= -0.89, p < 0.0001). CONCLUSION: The discriminative value for SEAG and ALBR appears to be similar in the diagnostic separation of transudates and exudates. FLDH is a superior test compared to SEAG and ALBR

The use of standardized patients for mock oral board exams in neurology: a pilot study

BACKGROUND: Mock oral board exams, fashioned after the live patient hour of the American Board of Psychiatry and Neurology exam, are commonly part of resident assessment during residency training. Exams using real patients selected from clinics or hospitals are not standardized and do not allow comparisons of resident performance across the residency program. We sought to create a standardized patient mock oral board exam that would allow comparison of residents' clinical performance. METHODS: Three cases were created and then used for this mock oral boards exercise utilizing trained standardized patients. Residents from the University of Cincinnati and Indiana University participated in the exam. Residents were scored by attending physician examiners who directly observed the encounter with the standardized patient. The standardized patient also assessed each resident. A post-test survey was administered to ascertain participant's satisfaction with the examination process. RESULTS: Resident scores were grouped within one standard deviation of the mean, with the exception of one resident who was also subjectively felt to "fail" the exam. In exams with two faculty "evaluators", scores were highly correlated. The survey showed satisfaction with the examination process in general. CONCLUSION: Standardized patients can be used for mock oral boards in the live patient format. Our initial experience with this examination process was positive. Further testing is needed to determine if this examination format is more reliable and valid than traditional methods of assessing resident competency

Second order QCD corrections to inclusive semileptonic b \to Xc l \bar \nu_l decays with massless and massive lepton

We extend previous computations of the second order QCD corrections to semileptonic b \to c inclusive transitions, to the case where the charged lepton in the final state is massive. This allows accurate description of b \to c \tau \bar \nu_\tau decays. We review techniques used in the computation of O(\alpha_s^2) corrections to inclusive semileptonic b \to c transitions and present extensive numerical studies of O(\alpha_s^2) QCD corrections to b \to c l \bar \nu_l decays, for l =e, \tau.Comment: 30 pages, 4 figures, 5 table

βB1-Crystallin: Thermodynamic Profiles of Molecular Interactions

β-Crystallins are structural proteins maintaining eye lens transparency and opacification. Previous work demonstrated that dimerization of both βA3 and βB2 crystallins (βA3 and βB2) involves endothermic enthalpy of association (∼8 kcal/mol) mediated by hydrophobic interactions.Thermodynamic profiles of the associations of dimeric βA3 and βB1 and tetrameric βB1/βA3 were measured using sedimentation equilibrium. The homo- and heteromolecular associations of βB1 crystallin are dominated by exothermic enthalpy (-13.3 and -24.5 kcal/mol, respectively).Global thermodynamics of βB1 interactions suggest a role in the formation of stable protein complexes in the lens via specific van der Waals contacts, hydrogen bonds and salt bridges whereas those β-crystallins which associate by predominately hydrophobic forces participate in a weaker protein associations

A summer heat wave decreases the immunocompetence of the mesograzer, Idotea baltica

Extreme events associated with global change will impose increasing stress on coastal organisms. How strong biological interactions such as the host–parasite arms-race are modulated by environmental change is largely unknown. The immune system of invertebrates, in particular phagocytosis and phenoloxidase activity response are key defence mechanisms against parasites, yet they may be sensitive to environmental perturbations. We here simulated an extreme event that mimicked the European heat wave in 2003 to investigate the effect of environmental change on the immunocompetence of the mesograzer Idotea baltica. Unlike earlier studies, our experiment aimed at simulation of the natural situation as closely as possible by using long acclimation, a slow increase in temperature and a natural community setting including the animals’ providence with natural food sources (Zostera marina and Fucus vesiculosus). Our results demonstrate that a simulated heat wave results in decreased immunocompetence of the mesograzer Idotea baltica, in particular a drop of phagocytosis by 50%. This suggests that global change has the potential to significantly affect host–parasite interactions

Symptomatic cerebral oedema during treatment of diabetic ketoacidosis: effect of adjuvant octreotide infusion

<p>Abstract</p> <p>Introduction</p> <p>A potentially lethal complication of diabetic ketoacidosis (DKA) in children is brain oedema, whether caused by DKA itself or by the therapeutic infusion of insulin and fluids.</p> <p>Case presentation</p> <p>A 10-year old previously healthy boy with DKA became unconscious and apnoeic due to cerebral oedema (confirmed by abnormal EEG and CT-scan) during treatment with intravenous fluids (36 ml/h) and insulin (0.1 units/kg/h). He was intubated and artificially ventilated, without impact on EEG and CT-scan. Subsequently, adjuvant infusion of octreotide was applied (3.5 μg/kg/h), suppressing growth hormone (GH) and IGF-1 production and necessitating the insulin dose to be reduced to 0.05 - 0.025 units/kg/h. The brain oedema improved and the boy made a full recovery.</p> <p>Conclusion</p> <p>Co-therapy with octreotide was associated with a favourable outcome in the present patient with DKA and cerebral oedema. Whether this could be ascribed to the effects of octreotide on the insulin requirement or on the GH/IGF-axis remains to be elucidated.</p