Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimating steatosis and fibrosis: Comparison of acoustic structure quantification with established techniques.

AIM To compare ultrasound-based acoustic structure quantification (ASQ) with established non-invasive techniques for grading and staging fatty liver disease. METHODS Type 2 diabetic patients at risk of non-alcoholic fatty liver disease (n = 50) and healthy volunteers (n = 20) were evaluated using laboratory analysis and anthropometric measurements, transient elastography (TE), controlled attenuation parameter (CAP), proton magnetic resonance spectroscopy ((1)H-MRS; only available for the diabetic cohort), and ASQ. ASQ parameters mode, average and focal disturbance (FD) ratio were compared with: (1) the extent of liver fibrosis estimated from TE and non-alcoholic fatty liver disease (NAFLD) fibrosis scores; and (2) the amount of steatosis, which was classified according to CAP values. RESULTS Forty-seven diabetic patients (age 67.0 ± 8.6 years; body mass index 29.4 ± 4.5 kg/m²) with reliable CAP measurements and all controls (age 26.5 ± 3.2 years; body mass index 22.0 ± 2.7 kg/m²) were included in the analysis. All ASQ parameters showed differences between healthy controls and diabetic patients (P < 0.001, respectively). The ASQ FD ratio (logarithmic) correlated with the CAP (r = -0.81, P < 0.001) and (1)H-MRS (r = -0.43, P = 0.004) results. The FD ratio [CAP < 250 dB/m: 107 (102-109), CAP between 250 and 300 dB/m: 106 (102-114); CAP between 300 and 350 dB/m: 105 (100-112), CAP ≥ 350 dB/m: 102 (99-108)] as well as mode and average parameters, were reduced in cases with advanced steatosis (ANOVA P < 0.05). However, none of the ASQ parameters showed a significant difference in patients with advanced fibrosis, as determined by TE and the NAFLD fibrosis score (P > 0.08, respectively). CONCLUSION ASQ parameters correlate with steatosis, but not with fibrosis in fatty liver disease. Steatosis estimation with ASQ should be further evaluated in biopsy-controlled studies.
Impact of pharmacometrics on drug approval and labeling decisions: A survey of 42 new drug applications

The value of quantitative thinking in drug development and regulatory review is increasingly being appreciated. Modeling and simulation of data pertaining to pharmacokinetic, pharmacodynamic, and disease progression is often referred to as the pharmacometrics analyses. The objective of the current report is to assess the role of pharmacometrics at the US Food and Drug Administration (FDA) in making drug approval and labeling decisions. The New Drug Applications (NDAs) submitted between 2000 and 2004 to the Cardio-renal, Oncology, and Neuropharmacology drug products divisions were surveyed. For those NDA reviews that included a pharmacometrics consultation, the clinical pharmacology scientists ranked the impact on the regulatory decision(s). Of about a total of 244 NDAs, 42 included a pharmacometrics component. Review of NDAs involved independent, quantitative evaluation by FDA pharmacometricians, even when such analysis was not conducted by the sponsor. Pharmacometric analyses were pivotal in regulatory decision making in more than half of the 42 NDAs. Of the 14 reviews that were pivotal to approval related decisions, 5 identified the need for additional trials, whereas 6 reduced the burden of conducting additional trials. Collaboration among the FDA clinical pharmacology, medical, and statistical reviewers and effective communication with the sponsors was critical for the impact to occur. The survey and the case studies emphasize the need for early interaction between the FDA and sponsors to plan the development more efficiently by appreciating the regulatory expectations better.
Role for plasmacytoid dendritic cells in anti‐HIV innate immunity

The role of plasmacytoid dendritic cells (pDC) in anti‐HIV immunity is mostly represented by the production of type I IFN in response to HIV infection in vitro and in vivo. This production is decreased in HIV‐1 infected patients at the time of primary infection and during chronic disease in association with progression of disease. Circulating pDC counts are decreased concomitantly with type I IFN, and both factors correlate inversely overall with viral loads and positively with CD4+ T‐cell counts. These parameters might be used in clinical immunology to monitor treatment and as predictive factors of immune control of HIV‐1 replication to help decide whether to interrupt antiretroviral treatment. They may be related to control of HIV replication as well as to pathogenesis of infection, perhaps in setting the balance between immunity or tolerance to the virus. A better understanding of these parameters is required while attempts to use IFN‐α or ligands of Toll‐like receptors found on pDC are being made.
Anisotropic Foveated Self-Similarity Alessandro Foi

The foveated patch distance was shown to be a valuable feature for the assessment of nonlocal self-similarity in image filtering. The Foveated NL-means [1], which modifies the classical nonlocal means denoising filter (NL-means) [2] by computing the averaging weights based on the foveated patch distance instead of the conventional windowed patch distance, leads to a consistent improvement in the quality of the restored images according to both objective criteria and visual appearance, particularly due to better contrast and sharpness. The foveated patch distance is measured by means of foveation operators, which transform image patches through a spatially variant blur characterized by point-spread functions (PSFs) whose spread progressively increases with the spatial distance juj from the patch center. Our approach mimics the human visual system (HVS), for which visual acuity is maximal at the fixation point (imaged by the fovea, i.e. the central part of the retina, where the photoreceptor density is highest) and decreases rapidly towards the periphery of the visual field. In particular, in [1] we considered isotropic operators composed of circular-symmetric Gaussian PSFs, like those in Fig. 1(a). Unlike conventional windowing, foveation operator combines at once various multiscale features computed from the local context: the foveated patches embed pixels from fine-scale (the fixation point) to coarse-scale (pixels at the patch periphery) representations of patches.
Compensatory Adaptations, Reflex Activity, and the Brain

The authors' observations are drawn from the context of therapy with patients who sought treatment less for the discomfort of anxiety or symptom formations than from the wish to grow, change, and achieve "selfrealization. " The tendency of these patients toward expansion and complexity of adaptive capacity suggests to the authors a continuum between biological evolution and the development of ego function. The exceptional individual, one who possesses unusual synthetic and integrative capacities, is equated with the genetic mutant who emerges by natural selection. He becomes a catalyst for sociocultural change. He also forms an ideal with which others can identify to expand their individual capacities. A reciprocal interaction occurs between the psychological development of individuals and the sociocultural development of the species, each requiring adaptive changes of the other. This process forms the basis for the evolutionary "advance" of ego. Such nongenetic evolutionary advances are then transmitted to successive generations via each individual's social inheritance.
Maximum likelihood SNR estimator for coded MAPSK signals in slow fading channels

In this paper, an accurate maximum likelihood (ML) signal-to-noise ratio (SNR) estimator is proposed for coded M-ary amplitude phase shift keying (APSK) signals over a slowly time-varying fading channel. The proposed estimator significantly improves the estimation precision at low SNRs by utilizing a posteriori probabilities of coded bits provided by channel decoder. Moreover, a methodology to calculate the Cramer-Rao bound (CRB) of the proposed code-aided (CA) ML SNR estimator for coded M-APSK signals is derived. Compared with moments-based estimators and the non-data-aided (NDA) Expectation Maximization (EM) based estimator for M-APSK signals, simulation results show that the proposed estimator exploiting a posteriori information out of low-density parity-check (LDPC) decoder or Turbo decoder performs better, especially at low SNRs. It is also validated that the performances of the proposed CA-ML SNR estimator for coded 16- and 32-APSK signals can closely achieve the derived CRB.
Social and Demographic Effects of Anthropogenic Mortality: A Test of the Compensatory Mortality Hypothesis in the Red Wolf

Whether anthropogenic mortality is additive or compensatory to natural mortality in animal populations has long been a question of theoretical and practical importance. Theoretically, under density-dependent conditions populations compensate for anthropogenic mortality through decreases in natural mortality and/or increases in productivity, but recent studies of large carnivores suggest that anthropogenic mortality can be fully additive to natural mortality and thereby constrain annual survival and population growth rate. Nevertheless, mechanisms underlying either compensatory or additive effects continue to be poorly understood. Using long-term data on a reintroduced population of the red wolf, we tested for evidence of additive vs. compensatory effects of anthropogenic mortality on annual survival and population growth rates, and the preservation and reproductive success of breeding pairs. We found that anthropogenic mortality had a strong additive effect on annual survival and population growth rate at low population density, though there was evidence for compensation in population growth at high density. When involving the death of a breeder, anthropogenic mortality was also additive to natural rates of breeding pair dissolution, resulting in a net decrease in the annual preservation of existing breeding pairs. However, though the disbanding of a pack following death of a breeder resulted in fewer recruits per litter relative to stable packs, there was no relationship between natural rates of pair dissolution and population growth rate at either high or low density. Thus we propose that short-term additive effects of anthropogenic mortality on population growth in the red wolf population at low density were primarily a result of direct mortality of adults rather than indirect socially-mediated effects resulting in reduced recruitment. Finally, we also demonstrate that per capita recruitment and the proportion of adults that became reproductive declined steeply with increasing population density, suggesting that there is potential for density-dependent compensation of anthropogenically-mediated population regulation.
Attachment and Child Abuse

Defects in the bonds of attachment between parent and child are put forward as a precursor in cases of child abuse and neglect. It is suggested that therapeutic work with such families should be focussed on the re-establishment or strengthening of these bonds, if they are found to exist. Ways of determining their existence and building upon them are discussed. It is suggested that, with the safeguard of a regular and intensive contact with the family, separation can often be avoided. This allows an immediate start on the basic task of strengthening the bond, and avoids weakening it still further as a result of separation. A case example is given.
ON THE STATIONARY DISTRIBUTION OF ITERATIVE IMPUTATIONS

Iterative imputation, in which variables are imputed one at a time conditional on all the others, is a popular technique that can be convenient and flexible, as it replaces a potentially difficult multivariate modelling problem with relatively simple univariate regressions. In this paper, we begin to characterize the stationary distributions of iterative imputations and their statistical properties, accounting for the conditional models being iteratively estimated from data rather than being prespecified. When the families of conditional models are compatible, we provide sufficient conditions under which the imputation distribution converges in total variation to the posterior distribution of a Bayesian model. When the conditional models are incompatible but valid, we show that the combined imputation estimator is consistent.
Inhibitory effects of curcumin on activity of cytochrome P450 2C9 enzyme in human and 2C11 in rat liver microsomes

Abstract Cytochrome P450 2C9 (CYP2C9), one of the most important phase I drug metabolizing enzymes, could catalyze the reactions that convert diclofenanc into diclofenac 4′-hydroxylation. Evaluation of the inhibitory effects of compounds on CYP2C9 is clinically important because inhibition of CYP2C9 could result in serious drug–drug interactions. The objective of this work was to investigate the effects of curcumin on CYP2C9 in human and cytochrome P450 2C11 (CYP2C11) in rat liver microsomes. The results showed that curcumin inhibited CYP2C9 activity (10 µmol L–1 diclofenac) with half-maximal inhibition or a half-maximal inhibitory concentration (IC50) of 15.25 µmol L–1 and Ki = 4.473 µmol L–1 in human liver microsomes. Curcumin’s mode of action on CYP2C9 activity was noncompetitive for the substrate diclofenanc and uncompetitive for the cofactor NADPH. In contrast to its potent inhibition of CYP2C9 in human, diclofenanc had lesser effects on CYP2C11 in rat, with an IC50 ≥100 µmol L–1. The observations imply that curcumin has the inhibitory effects on CYP2C9 activity in human. These in vitro findings suggest that more attention should be paid to special clinical caution when intake of curcumin combined with other drugs in treatment.
Super-sensitive prostate-specific antigen (PSA) in serum of women with benign breast disease or breast cancer.

BACKGROUND Serum prostate-specific antigen (PSA) can be discovered in patients with breast cancer. We used ultrasensitive methods of PSA detection, successfully developed for early detection of PSA recurrence in prostatic-cancer patients, to study PSA in women with breast cancer and benign breast lesions before and after surgery. MATERIALS AND METHODS Blood samples of 45 women with suspect breast findings were prospectively analyzed for PSA before and after breast surgery. Supersensitive 2nd and 3rd generation DPC assays were used to measure PSA (clinical detection limit of > 0.1 and > 0.02 ng/mL, respectively) and combined with concentration of serum to improve the clinical detection limit to > 0.025 and > 0.005 ng/mL, respectively. PSA concentrations were correlated with histological findings. RESULTS The most sensitive detection was required to detect PSA preoperatively in 12 out of 45 patients, 8 (31%) out of 26 breast-cancer patients and 4 (25%) out of 16 patients with benign breast lesions. Postoperatively, 13 out of 45 patients were positive for PSA, 7 (27%) breast-cancer patients and 6 (23%) patients with benign breast lesions. CONCLUSIONS Cancer patients showed the highest concentrations of PSA measured preoperatively and a decrease after surgery that was however not significant. Women with breast lesions expressed serum PSA in one third of the cases studied. PSA expression in serum does not distinguish benign from malignant breast diseases, but it might be valuable for follow-up to analyze whether recurrent disease can be detected with quantitative ultrasensitive PSA measurement.
The Grey Paradox : How Fossil-fuels

This paper studies the distributional impacts of optimal carbon taxation on fossilfuels owners. We show that optimal carbon taxation can increase the pro ts of owners of a carbon-emitting exhaustible resource. Such phenomenon contrasts with claims from fossil-fuels owners especially from OPEC member countries that carbon taxation will undermine their pro ts. We build a theoretical model of resource extraction where a polluting exhaustible resource competes with a dirtier abundant resource and a clean backstop. The atmospheric CO2 concentration has to be kept under a carbon ceiling and the optimal extraction path is decentralized by a carbon tax. As the carbon ceiling is tightened, the exhaustible-resource rent, and thus profits, is partly captured by the tax levier (the capture e ect ), but the dirtier resource is made less competitive (the competition e ect ). We determine conditions under which pro ts increase as the ceiling falls. The role of resource endowments, pollution contents, extraction costs and demand elasticity is analyzed. Calibrating the model for the transportation sector, we nd that limiting cumulative new emissions in this sector between 322.7 and 637.5 GtCO2 increases pro ts of conventional-oil owners.
Binding cooperativity of membrane adhesion receptors

The adhesion of cells is mediated by receptors and ligands anchored in apposing membranes. A central question is how to characterize the binding affinity of these membrane-anchored molecules. For soluble molecules, the binding affinity is typically quantified by the binding equilibrium constant K3D in the linear relation [RL] = K3D[R][L] between the volume concentration [RL] of bound complexes and the volume concentrations [R] and [L] of unbound molecules. For membrane-anchored molecules, it is often assumed by analogy that the area concentration of bound complexes [RL] is proportional to the product [R][L] of the area concentrations for the unbound receptor and ligand molecules. We show here (i) that this analogy is only valid for two planar membranes immobilized on rigid surfaces, and (ii) that the thermal roughness of flexible membranes leads to cooperative binding of receptors and ligands. In the case of flexible membranes, the area concentration [RL] of receptor–ligand bonds is proportional to [R]2[L]2 for typical lengths and concentrations of receptors and ligands in cell adhesion zones. The cooperative binding helps to understand why different experimental methods for measuring the binding affinity of membrane-anchored molecules have led to values differing by several orders of magnitude.
Neuromodulation within a spinal locomotor network : Role of metabotropic glutamate receptor subtypes

2 All published papers were reproduced with permission from the publisher. ABSTRACT The metabotropic glutamate receptors, mGluRs, are G-protein coupled receptors. Eight subtypes have been cloned and divided into three groups depending on the amino acid sequence similarity, pharmacology and their signal pathways. In the lamprey spinal cord, group I mGluRs are located postsynaptically, while group II and III are presynaptic and depress synaptic transmission. The goal of this thesis has been to elucidate the mechanisms by which the two subtypes of group I mGluRs, i.e. mGluR1 and mGluR5, modulate the firing properties of single neurons, the synaptic interactions and the overall activity of the spinal locomotor network in the lamprey. mGluR1 activation by endogenously released glutamate increases the frequency of the locomotor rhythm induced by NMDA in the isolated lamprey spinal cord preparation. This increase in the frequency is the result of a number of cellular and molecular mechanisms that have been studied in detail. Firstly, mGluR1 potentiates the NMDA-induced current, and enhances NMDA-induced TTX-resistant membrane potential oscillations known to occur during locomotion. Mathematical simulations of the interaction between mGluR1 and NMDA receptors reproduce the modulation of the NMDA-induced oscillations and the increase in the locomotor frequency. Secondly, mGluR1 activation depolarizes the membrane potential of neurons and consequently induces repetitive firing. These effects are due to an inhibition of a leak current responsible for setting the resting membrane potential. Interestingly, mGluR1 activates different signaling pathways to modulate NMDA current and leak conductance. Both effects require activation of G-proteins. The mGluR1-mediated inhibition of leak current requires PLC activation and release of Ca 2+ from internal stores, as well as tyrosine kinase activation. The potentiation of NMDA current is not, however, dependent on an increase in intracellular Ca 2+ or on tyrosine kinases. Thirdly, activation of mGluR1 receptors gives rise to a synthesis and release of endocannabinoids from postsynaptic neurons. The released endocannabinoids act as retrograde messengers which bind to presynaptic receptors and reduce glycinergic synaptic transmission. The reduced inhibitory transmission will result in an increase in the locomotor frequency. Hence, mGluR1-activation triggers the release of endocannabinoids which thus contribute to the mGluR1-mediated modulation of the locomotor network operation. Finally, endogenous activation of mGluR5 during locomotion decreases the burst frequency and produces long-lasting oscillations of the intracellular Ca 2+ concentration. These oscillations are mediated through PLC and Ca 2+ release from internal stores. Furthermore, they are also dependent on Ca 2+ …
Relative Validity and Reproducibility of a Food Frequency Questionnaire Designed for French Adults

Objectives/Aims: We tested the reproducibility and relative validity of a French self-administered food frequency questionnaire (FFQ) against 24-hour dietary records (DRs). Methods: We selected 140 participants from the SU.VI. MAX study. They filled in the FFQ twice at 1-year intervals and completed monthly 24-hour DR during that year. The number of food items in the FFQ was 240. Results: Reproducibility was high. Medians of Pearson coefficients were 0.70 and 0.65 for nutrients in men and women, respectively. Medians of intraclass correlation coefficients for food were 0.62 in men and 0.65 in women. For nutrients, crude Pearson correlation coefficients for relative validity ranged from 0.28 to 0.67 in men and from 0.25 to 0.55 in women. The Spearman coefficient for alcohol was 0.78 in both genders. For food, the medians of the Spearman coefficient were 0.49 and 0.45 for men and women, respectively. Complete disagreement between the FFQ and 24-hour DRs for ranking subjects according to food consumption was low (about 4%), except for rarely consumed food groups, that is nuts, legumes and offal. Calibration coefficients were estimated by linear regression. All coefficients were lower than one. Conclusions: Acceptable reproducibility and relative validity were observed in a FFQ designed for French adults.
Human-robot interaction: Developing trust in robots

In all human-robot interaction, trust is an important element to consider because the presence or absence of trust certainly impacts the ultimate outcome of that interaction. Limited research exists that delineates the development and maintenance of this trust in various operational contexts. Our own prior research has investigated theoretical and empirically supported antecedents of human-robot trust. Here, we describe progress to date relating to the development of a comprehensive human-robot trust model based on our ongoing program of research.
CSP channels for CAN-bus connected embedded control systems

Closed loop control system typically contains multitude of sensors and actuators operated simultaneously. So they are parallel and distributed in its essence. But when mapping this parallelism to software, lot of obstacles concerning multithreading communication and synchronization issues arise. To overcome this problem, the CT kernel/library based on CSP algebra has been developed. This project (TES.5410) is about developing communication extension to the CT library to make it applicable in distributed systems. Since the library is tailored for control systems, properties and requirements of control systems are taken into special consideration. Applicability of existing middleware solutions is examined. A comparison of applicable fieldbus protocols is done in order to determine most suitable ones and CAN fieldbus is chosen to be first fieldbus used. Brief overview of CSP and existing CSP based libraries is given. Middleware architecture is proposed along with few novel ideas.