An inverse analysis for determination of space-dependent heat flux in heat conduction problems in the presence of variable thermal conductivity

Translator disclaimer Full Article Figures & data References Citations Metrics Reprints & Permissions Get accessAbstractThis article presents an inverse problem of determination of a space-dependent heat flux in steady-state heat conduction problems. The thermal conductivity of a heat conducting body depends on the temperature distribution over the body. In this study, the simulated measured temperature distribution on part of the boundary is related to the variable heat flux imposed on a different part of the boundary through incorporating the variable thermal conductivity components into the sensitivity coefficients. To do so, a body-fitted grid generation technique is used to mesh the two-dimensional irregular body and solve the direct heat conduction problem. An efficient, accurate, robust, and easy to implement method is presented to compute the sensitivity coefficients through derived expressions. Novelty of the study is twofold: (1) Boundary-fitted grid-based sensitivity analysis in which all sensitivities can be obtained in only one direct solution (at each iteration), irrespective of the number of unknown parameters, and (2) the way the measured temperatures on part of boundary are related to a variable heat flux applied on another part of boundary through components of a variable thermal conductivity. The conjugate gradient method along with the discrepancy principle is used in the inverse analysis to minimize the objective function and achieve the desired solution

GABA-ergic Dynamics in Human Frontotemporal Networks Confirmed by Pharmaco-Magnetoencephalography.

To bridge the gap between preclinical cellular models of disease and in vivo imaging of human cognitive network dynamics, there is a pressing need for informative biophysical models. Here we assess dynamic causal models (DCM) of cortical network responses, as generative models of magnetoencephalographic observations during an auditory oddball roving paradigm in healthy adults. This paradigm induces robust perturbations that permeate frontotemporal networks, including an evoked 'mismatch negativity' response and transiently induced oscillations. Here, we probe GABAergic influences in the networks using double-blind placebo-controlled randomized-crossover administration of the GABA reuptake inhibitor, tiagabine (oral, 10 mg) in healthy older adults. We demonstrate the facility of conductance-based neural mass mean-field models, incorporating local synaptic connectivity, to investigate laminar-specific and GABAergic mechanisms of the auditory response. The neuronal model accurately recapitulated the observed magnetoencephalographic data. Using parametric empirical Bayes for optimal model inversion across both drug sessions, we identify the effect of tiagabine on GABAergic modulation of deep pyramidal and interneuronal cell populations. We found a transition of the main GABAergic drug effects from auditory cortex in standard trials to prefrontal cortex in deviant trials. The successful integration of pharmaco- magnetoencephalography with dynamic causal models of frontotemporal networks provides a potential platform on which to evaluate the effects of disease and pharmacological interventions.SIGNIFICANCE STATEMENT Understanding human brain function and developing new treatments require good models of brain function. We tested a detailed generative model of cortical microcircuits that accurately reproduced human magnetoencephalography, to quantify network dynamics and connectivity in frontotemporal cortex. This approach identified the effect of a test drug (GABA-reuptake inhibitor, tiagabine) on neuronal function (GABA-ergic dynamics), opening the way for psychopharmacological studies in health and disease with the mechanistic precision afforded by generative models of the brain

Spontaneous Neutrophil Migration Patterns during Sepsis after Major Burns

Finely tuned to respond quickly to infections, neutrophils have amazing abilities to migrate fast and efficiently towards sites of infection and inflammation. Although neutrophils ability to migrate is perturbed in patients after major burns, no correlations have yet been demonstrated between altered migration and higher rate of infections and sepsis in these patients when compared to healthy individuals. To probe if such correlations exist, we designed microfluidic devices to quantify the neutrophil migration phenotype with high precision. Inside these devices, moving neutrophils are confined in channels smaller than the neutrophils and forced to make directional decisions at bifurcations and around posts. We employed these devices to quantify neutrophil migration across 18 independent parameters in 74 blood samples from 13 patients with major burns and 3 healthy subjects. Blinded, retrospective analysis of clinical data and neutrophil migration parameters revealed that neutrophils isolated from blood samples collected during sepsis migrate spontaneously inside the microfluidic channels. The spontaneous neutrophil migration is a unique phenotype, typical for patients with major burns during sepsis and often observed one or two days before the diagnosis of sepsis is confirmed. The spontaneous neutrophil migration phenotype is rare in patients with major burns in the absence of sepsis, and is not encountered in healthy individuals. Our findings warrant further studies of neutrophils and their utility for early diagnosing and monitoring sepsis in patients after major burns

Multi-Parameter Entanglement in Femtosecond Parametric Down-Conversion

A theory of spontaneous parametric down-conversion, which gives rise to a quantum state that is entangled in multiple parameters, such as three-dimensional wavevector and polarization, allows us to understand the unusual characteristics of fourth-order quantum interference in many experiments, including ultrafast type-II parametric down-conversion, the specific example illustrated in this paper. The comprehensive approach provided here permits the engineering of quantum states suitable for quantum information schemes and new quantum technologies.Comment: to appear in Physical Review

GABAergic cortical network physiology in frontotemporal lobar degeneration.

The clinical syndromes caused by frontotemporal lobar degeneration are heterogeneous, including the behavioural variant frontotemporal dementia (bvFTD) and progressive supranuclear palsy. Although pathologically distinct, they share many behavioural, cognitive and physiological features, which may in part arise from common deficits of major neurotransmitters such as γ-aminobutyric acid (GABA). Here, we quantify the GABAergic impairment and its restoration with dynamic causal modelling of a double-blind placebo-controlled crossover pharmaco-magnetoencephalography study. We analysed 17 patients with bvFTD, 15 patients with progressive supranuclear palsy, and 20 healthy age- and gender-matched controls. In addition to neuropsychological assessment and structural MRI, participants undertook two magnetoencephalography sessions using a roving auditory oddball paradigm: once on placebo and once on 10 mg of the oral GABA reuptake inhibitor tiagabine. A subgroup underwent ultrahigh-field magnetic resonance spectroscopy measurement of GABA concentration, which was reduced among patients. We identified deficits in frontotemporal processing using conductance-based biophysical models of local and global neuronal networks. The clinical relevance of this physiological deficit is indicated by the correlation between top-down connectivity from frontal to temporal cortex and clinical measures of cognitive and behavioural change. A critical validation of the biophysical modelling approach was evidence from parametric empirical Bayes analysis that GABA levels in patients, measured by spectroscopy, were related to posterior estimates of patients' GABAergic synaptic connectivity. Further evidence for the role of GABA in frontotemporal lobar degeneration came from confirmation that the effects of tiagabine on local circuits depended not only on participant group, but also on individual baseline GABA levels. Specifically, the phasic inhibition of deep cortico-cortical pyramidal neurons following tiagabine, but not placebo, was a function of GABA concentration. The study provides proof-of-concept for the potential of dynamic causal modelling to elucidate mechanisms of human neurodegenerative disease, and explains the variation in response to candidate therapies among patients. The laminar- and neurotransmitter-specific features of the modelling framework, can be used to study other treatment approaches and disorders. In the context of frontotemporal lobar degeneration, we suggest that neurophysiological restoration in selected patients, by targeting neurotransmitter deficits, could be used to bridge between clinical and preclinical models of disease, and inform the personalized selection of drugs and stratification of patients for future clinical trials

Surgical site infection following surgery for hand trauma: a systematic review and meta-analysis

Surgical site infection is the most common healthcare-associated infection. Surgical site infection after surgery for hand trauma is associated with increased antibiotic prescribing, re-operation, hospital readmission and delayed rehabilitation, and in severe cases may lead to amputation. As the risk of surgical site infection after surgery for hand trauma remains unclear, we performed a systematic review and meta-analysis of all primary studies of hand trauma surgery, including randomized controlled trials, cohort studies, case-control studies and case series. A total of 8836 abstracts were screened, and 201 full studies with 315,618 patients included. The meta-analysis showed a 10% risk of surgical site infection in randomized control trials, with an overall risk of 5% when all studies were included. These summary statistics can be used clinically for informed consent and shared decision making, and for power calculations for future clinical trials of antimicrobial interventions in hand trauma

Molecular Spiders in One Dimension

Molecular spiders are synthetic bio-molecular systems which have "legs" made of short single-stranded segments of DNA. Spiders move on a surface covered with single-stranded DNA segments complementary to legs. Different mappings are established between various models of spiders and simple exclusion processes. For spiders with simple gait and varying number of legs we compute the diffusion coefficient; when the hopping is biased we also compute their velocity.Comment: 14 pages, 2 figure