Miracle-dz/UniFAR-FTUs huggingface dataset:
ADCOMS: a composite clinical outcome for prodromal Alzheimer's disease trials

Background Development of new therapies for Alzheimer's disease (AD) is increasingly focused on more mildly affected populations, and requires new assessment and outcome strategies. Patients in early stages of AD have mild cognitive decline and no, or limited, functional impairment. To respond to these assessment challenges, we developed a measurement approach based on established scale items that exhibited change in previous amnestic Mild Cognitive Impairment (aMCI) trials. Methods Partial least squares regression with a longitudinal clinical decline model identified items from commonly used clinical scales with the highest combined sensitivity to change over time in aMCI and weighted these items according to their relative contribution to detecting clinical progression in patients’ early stages of AD. The resultant AD Composite Score (ADCOMS) was assessed for its ability to detect treatment effect in aMCI/prodromal AD (pAD) clinical trial populations. Results ADCOMS consists of 4 Alzheimer's Disease Assessment Scale–cognitive subscale items, 2 Mini-Mental State Examination items, and all 6 Clinical Dementia Rating—Sum of Boxes items. ADCOMS demonstrated improved sensitivity to clinical decline over individual scales in pAD, aMCI and in mild AD dementia. ADCOMS also detected treatment effects associated with the use of cholinesterase inhibitors in these populations. Improved sensitivity predicts smaller sample size requirements when ADCOMS is used in early AD trials. Conclusions ADCOMS is proposed as new standard outcome for pAD and mild AD dementia trials, and is progressing in a CAMD-sponsored qualification process for use in registration trials of pAD.
Quantitative Analysis of Three Distinct Retinal Capillary Plexuses in Healthy Eyes Using Optical Coherence Tomography Angiography.

Purpose To identify and quantify the three distinct retinal capillary plexuses and the foveal avascular zone (FAZ) in healthy subjects according to age using optical coherence tomography angiography (OCTA) with novel projection artifact removal (PAR) software and improved segmentation. Methods All eyes in this cross-sectional study underwent OCTA imaging using RTVue XR Avanti with novel PAR AngioVue software. OCTA scans were analyzed and the three main parafoveal retinal capillary plexuses were segmented and vessel density and FAZ area were calculated. Results A total of 152 normal eyes from 95 subjects (39 males, 56 females, mean age 42 ± 25 years) were included. The mean vessel density was 15.48 ± 2.04 mm-1 in the superficial retinal capillary plexus (SCP), 15.28 ± 1.82 mm-1 in the intermediate retinal capillary plexus (ICP), and 16.33 ± 2.32 mm-1 in the deep retinal capillary plexus (DCP) for 3 × 3-mm OCTA images. Analysis of 3 × 3-mm scans yielded a mean FAZ area of 0.270 ± 0.101 mm2. The average reduction in vessel density per year of age with 3 × 3-mm OCTA scans was 0.04 mm-1 (0.22%) in the SCP, 0.05 mm-1 (0.27%) in the ICP, and 0.06 mm-1 (0.30%) in the DCP. The average increase in FAZ area per year of age was 0.0015 mm2 (0.72%). Conclusions Novel PAR software may provide improved visualization of all three major parafoveal retinal capillary plexuses including the ICP. Using this technology, SCP, ICP, and DCP vessel density decreased with increasing age while FAZ area increased with age.
Content Validity of Patient-Reported Outcome Instruments used with Pediatric Patients with Facial Differences

Objective: The aim of this systematic review was to identify patient-reported outcome (PRO) instruments used in research with children/youth with conditions associated with facial differences to identify the health concepts measured. Design: MEDLINE, EMBASE, CINAHL, and PsycINFO were searched from 2004 to 2016 to identify PRO instruments used in acne vulgaris, birthmarks, burns, ear anomalies, facial asymmetries, and facial paralysis patients. We performed a content analysis whereby the items were coded to identify concepts and categorized as positive or negative content or phrasing. Results: A total of 7,835 articles were screened; 6 generic and 11 condition-specific PRO instruments were used in 96 publications. Condition-specific instruments were for acne (four), oral health (two), dermatology (one), facial asymmetries (two), microtia (one), and burns (one). The PRO instruments provided 554 items (295 generic; 259 condition specific) that were sorted into 4 domains, 11 subdomains, and 91 health concepts. The most common domain was psychological (n = 224 items). Of the identified items, 76% had negative content or phrasing (e.g., “Because of the way my face looks I wish I had never been born”). Given the small number of items measuring facial appearance (n = 19) and function (n = 22), the PRO instruments reviewed lacked content validity for patients whose condition impacted facial function and/or appearance. Conclusions: Treatments can change facial appearance and function. This review draws attention to a problem with content validity in existing PRO instruments. Our team is now developing a new PRO instrument called FACE-Q Kids to address this problem.
A simple unsupervised MRF model based image segmentation approach

A simple technique has been suggested to obtain optimal segmentation based on tonal and textural characteristics of an image using the Markov random field (MRF) model. The technique takes an initially over segmented image as well as the original image as its inputs and defines an MRF over the region adjacency graph (RAG) of the initially segmented regions. A tonal-region based segmentation technique due to Kartikeyan and Sarkar (1989) has been used for initial segmentation. The energy function has been defined over the first order cliques of the MRF. The essence of this approach is primarily based on quantitative values of the second order statistics, on region characteristics and consequently deciding upon the action of merging neighboring regions using the F-statistic. The effectiveness of our approach is demonstrated with wide variety of real life examples viz., indoor, outdoor and satellite and a comparison of its output with that of a previous work in the literature has been provided.
Applying the SGAM methodology for rapid prototyping of smart Grid applications

In order to handle the increasing complexity of smart grid systems, detailed use case and requirements engineering has become indispensable. For this purpose the Smart Grid Reference Architecture Model (SGAM) has emerged as the major methodology. This paper presents a textual Domain Specific Language (DSL) based on SGAM, optimized for rapid prototyping of smart grid applications using a model-driven engineering approach with automatic code generation. The goal of this approach is to support the development process of smart Grid applications, from use case description to implementation. The paper presents a use case described by the DSL and shows how an IEC 61499 control application and an IEC 61850 communication configuration can be automatically generated.
Ectopic Expression Reveals a Conserved PHYB Homolog in Soybean

Phytochromes sense red/far-red light and trigger a cascade of physiological responses in plant. Here, a phytochrome B homolog, GmPHYB1, was amplified from the soybean genome, and its expression profiles were obtained for various parts of the plant and at various developmental stages. The gene was ectopically expressed in Arabidopsis thaliana, driven by CaMV 35S promoter, to study the physiological functions of the gene product. The overexpressors of GmPHYB1 behaved similarly to those of AtPHYB, but with some subtle differences with respect to the acceleration of flowering under short day conditions and the growth of the hypocotyl under certain light fluence rate. The results suggested that this soybean PHYB homolog was well conserved both at the level of sequence and physiological function.
Convergence diagnostics for stochastic gradient descent with constant step size

Many iterative procedures in stochastic optimization exhibit a transient phase followed by a stationary phase. During the transient phase the procedure converges towards a region of interest, and during the stationary phase the procedure oscillates in that region, commonly around a single point. In this paper, we develop a statistical diagnostic test to detect such phase transition in the context of stochastic gradient descent with constant learning rate. We present theory and experiments suggesting that the region where the proposed diagnostic is activated coincides with the convergence region. For a class of loss functions, we derive a closed-form solution describing such region. Finally, we suggest an application to speed up convergence of stochastic gradient descent by halving the learning rate each time stationarity is detected. This leads to a new variant of stochastic gradient descent, which in many settings is comparable to state-of-art.
A Practical Model of Quartz Crystal Microbalance in Actual Applications

A practical model of quartz crystal microbalance (QCM) is presented, which considers both the Gaussian distribution characteristic of mass sensitivity and the influence of electrodes on the mass sensitivity. The equivalent mass sensitivity of 5 MHz and 10 MHz AT-cut QCMs with different sized electrodes were calculated according to this practical model. The equivalent mass sensitivity of this practical model is different from the Sauerbrey’s mass sensitivity, and the error between them increases sharply as the electrode radius decreases. A series of experiments which plate rigid gold film onto QCMs were carried out and the experimental results proved this practical model is more valid and correct rather than the classical Sauerbrey equation. The practical model based on the equivalent mass sensitivity is convenient and accurate in actual measurements.
Probing the Druggability Limits for Enzymes of the NAD Biosynthetic Network in Glioma

The biosynthesis of NAD constitutes an important metabolic module in the cell, since NAD is an essential cofactor involved in several metabolic reactions. NAD concentrations are known to be significantly increased in several cancers, particularly in glioma, consistent with the observation of up-regulation of several enzymes of the network. Modulating NAD biosynthesis in glioma is therefore an attractive therapeutic strategy. Here we report reconstruction of a biochemical network of NAD biosynthesis consisting of 22 proteins, 36 metabolites, and 86 parameters, tuned to mimic the conditions in glioma. Kinetic simulations of the network provide comprehensive insights about the role of individual enzymes. Further, quantitative changes in the same network between different states of health and disease enable identification of drug targets, based on specific alterations in the given disease. Through simulations of enzyme inhibition titrations, we identify NMPRTase as a potential drug target, while eliminating other possible candidates NMNAT, NAPRTase, and NRK. We have also simulated titrations of both binding affinities as well as inhibitor concentrations, which provide insights into the druggability limits of the target, a novel aspect that can provide useful guidelines for designing inhibitors with optimal affinities. Our simulations suggest that an inhibitor affinity of 10 nM used in a concentration range of 0.1 to 10 μM achieves a near maximal inhibition response for NMPRTase and that increasing the affinity any further is not likely to have a significant advantage. Thus, the quantitative appreciation defines a maximal extent of inhibition possible for a chosen enzyme in the context of its network. Knowledge of this type enables an upper affinity threshold to be defined as a goal in lead screening and refinement stages in drug discovery.
Four-quadrant bidirectional operation of charging station upgraded with flywheel energy storage system

With penetration of plug-in electrical vehicles (PEV), fast charging stations (FCS) are expected to constitute be a considerable portion of total energy consumptions. This paper proposes a hybrid power coordinating control strategy implemented in a fast charging station equipped with flywheel energy storage system, in order to provide a comfortable charging circumstance for PEV as well as some ancillary services (active power and reactive power support) for grid by four-quadrate bidirectional operation. The distributed bus signaling (DBS) method is employed for coordinating the control between grid converter and flywheel converter to avoid the highly dependent on communication. Finally, the experimental results based on dSPACE1006 are presented to show the effectiveness of the proposed control structure.
Complementary microscopy techniques for surface characterisation of uncoated and mineral pigment coated paper

The quantification of surface structure is of major importance for several industry sectors. For the paper industry, the surface topography is essentially important for securing a good print quality of various paper grades. The surface affects various print quality parameters such as ink transfer, ink distribution, gloss and missing dots. It is thus important to have a detailed assessment of surface topography to be able to understand its influence on paper and print characteristics. In this study, several complementary characterisation techniques are reviewed and demonstrated, including scanners, optical microscopy, laser profilometry, scanning electron microscopy and atomic force microscopy. The techniques prove to be complementary and adequate for structural quantification at various scales, from the millimetre to the nanometre levels.
Matching Evaluation Approaches to Levels of Complexity

Background: Despite rapid advances in research on the evaluation of complex interventions, debate on evaluation methods and approaches still mainly revolves around the conventional and mostly outdated positivist–constructivist dichotomy. The lack of a clear conceptual and theoretical framework from which to choose appropriate evaluation approaches and methods means that approaches are often misused by both researchers and practitioners. Research design: Using three case studies, this article shows how different approaches should and should not be used in practice according to levels of nonlinearity. Both the theoretical development and the case studies presented in this article rely heavily on interviews conducted by the author with program management and staff, evaluation managers, heads of evaluation units, and evaluators in several countries across two continents, along with a quantitative survey. Results: This article expands the classic discussion on evaluation approaches, adapting it to current managerial demands, increased complexity, and newly developed methodologies. It suggests an operational tool for categorizing evaluations and then matching evaluation approaches to the circumstances and the evaluation objectives. Conclusion: The findings suggest that approaches which are not congruent with levels of nonlinearity may hinder attempts to accurately evaluate results, causing dissatisfaction of evaluation commissioners from the evaluation process and methods applied. In contrast, analyzing the nonlinear and structural elements of complexity separately allows an extended categorization of evaluation approaches to be matched to the nonlinearity of programs to be evaluated.
A Lifecycle Model for Web-based Application Development: Incorporating Agile and Plan-driven Methodology

For conventional software development, generic software engineering lifecycle model has proven to be very important. Though, with the evolution of Web-based applications and internet, conventional software engineering models have limited support for developing Web-based applications. In recent years Web-based applications have become more complex and new technologies are emerging at a rapid pace. Therefore, the conventional software engineering lifecycle models need to be reformed in such a way that handling the change requirements and complexity of Web-based development becomes convenient for conventional developers. However, there is a lack of any generic process model available for Web-based applications. The paper identifies and analyzes various aspects of conventional and Web-based development and proposes a lifecycle model, which incorporates the aspects of agile and plan-driven development to develop a Web-based application successfully.
Can recurrent neural networks warp time?

Successful recurrent models such as long short-term memories (LSTMs) and gated recurrent units (GRUs) use ad hoc gating mechanisms. Empirically these models have been found to improve the learning of medium to long term temporal dependencies and to help with vanishing gradient issues. We prove that learnable gates in a recurrent model formally provide quasi- invariance to general time transformations in the input data. We recover part of the LSTM architecture from a simple axiomatic approach. This result leads to a new way of initializing gate biases in LSTMs and GRUs. Ex- perimentally, this new chrono initialization is shown to greatly improve learning of long term dependencies, with minimal implementation effort.
Metrology in electricity and magnetism: EURAMET activities today and tomorrow

Metrology dedicated to electricity and magnetism has changed considerably in recent years. It encompasses almost all modern scientific, industrial, and societal challenges, e.g. the revision of the International System of Units, the profound transformation of industry, changes in energy use and generation, health, and environment, as well as nanotechnologies (including graphene and 2D materials) and quantum engineering. Over the same period, driven by the globalization of worldwide trade, the Mutual Recognition Arrangement (referred to as the CIPM MRA) was set up. As a result, the regional metrology organizations (RMOs) of national metrology institutes have grown in significance. EURAMET is the European RMO and has been very prominent in developing a strategic research agenda (SRA) and has established a comprehensive research programme. This paper reviews the highlights of EURAMET in electrical metrology within the European Metrology Research Programme and its main contributions to the CIPM MRA. In 2012 EURAMET undertook an extensive roadmapping exercise for proposed activities for the next decade which will also be discussed in this paper. This work has resulted in a new SRA of the second largest European funding programme: European Metrology Programme for Innovation and Research.
Genome Sequencing of Extended-Spectrum β-Lactamase (ESBL)-Producing Klebsiella pneumoniae Isolated from Pigs and Abattoir Workers in Cameroon

Background and objectives: Extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae is a serious public health issue globally. In this study, the antibiotic resistance genes, virulence factors, mobile genetic elements, and genetic lineages of circulating ESBL-producing K. pneumoniae strains isolated from pigs and humans in Cameroonian abattoirs were investigated using whole genome sequencing (WGS), in order to ascertain zoonotic transmission (viz. from animals to humans and/or vice-versa) in the food chain. Methods: During March–October 2016, 288 nasal and rectal pooled samples from 432 pigs as well as nasal and hand swabs from 82 humans were collected from Cameroon and South Africa. Seven ESBL-producing K. pneumoniae circulating in Cameroonian pig abattoirs were selected and their genomic DNA sequenced using an Illumina MiSeq platform. Generated reads were de novo assembled using the Qiagen CLC Genomics Workbench and SPAdes. The assembled contigs were annotated using RAST and antibiotic resistance genes, virulence factors, plasmids, and bacteriophages were identified with ResFinder, Virulence Finder, PlasmidFinder, and PHAST, respectively. Results: ESBL-producing K. pneumoniae were detected in pigs (34/158; 21.52%) and exposed workers (8/71; 11.26%) in Cameroon only. The circulating K. pneumoniae strains were dominated principally by the sequence type (ST) 14 and 39. In addition, the “high-risk” ST307 clone and two novel STs assigned ST2958 and ST2959 were detected. Genomic analysis identified various antibiotic resistance genes associated with resistance to β-lactams, aminoglycosides, fluoroquinolones, macrolide, lincosamide and streptogramins, rifampicin, sulfonamides, trimethoprim, phenicols and tetracycline. None of the ESBL-producing K. pneumoniae harbored virulence genes. Intermingled K. pneumoniae populations were observed between pig- and human-source within and across abattoirs in the country. Conclusion: Our study shows that ESBL-producing K. pneumoniae is actively disseminating in pigs and occupationally exposed workers in Cameroonian pig abattoirs and is probably underestimated in the absence of molecular epidemiological studies. It suggests pigs, abattoir workers and food products as potential reservoirs and sources of zoonotic transmission in Cameroon. Our findings underline the existence of a potential unheeded food safety and public health threat associated with these resistant strains and reinforce the crucial importance of implementing appropriate food safety measures and promoting rational antibiotic use.
Person authentication using 3D human motion

This paper presents a novel approach to identify and/or verify persons by using three-dimensional dynamic and structural features extracted from human motion depicted on image streams. These features are extracted from body landmarks which are detected and tracked when the person is asked to perform specific movements, representing the dynamics of specific parts of the body, as well as the structural traits formed by the pose of the person. Gaussian mixture model (GMM) based systems are tested on a dataset containing arm movements. Experimental results confirmed that the proposed approach is promising for person authentication tasks.
A prospective, randomized study of empirical antifungal therapy for the treatment of chemotherapy‐induced febrile neutropenia in children

Given that the rationale for empirical antifungal therapy in neutropenic children is limited and based on adult patient data, we performed a prospective, randomized, controlled trial that evaluated 110 neutropenic children with persistent fever. Those at high risk for invasive fungal infections (IFI) received caspofungin (Arm C) or liposomal amphotericinB (Arm B); those with a lower risk were randomized to receive Arm B, C, or no antifungal treatment (Arm A). Complete response to empirical antifungal therapy was achieved in 90/104 patients (86·5%): 48/56 at high risk (85·7%) [88·0% in Arm B; 83·9% in Arm C (P = 0·72)], and 42/48 at low risk (87·5%) [87·5% in control Arm A, 80·0% Arm B, 94·1% Arm C; (P = 0·41)]. None of the variables tested by multiple logistic regression analysis showed a significant effect on the probability to achieve complete response. IFI was diagnosed in nine patients (8·2%, 95% confidence interval, 3·8–15·0). This randomized controlled study showed that empirical antifungal therapy was of no advantage in terms of survival without fever and IFI in patients aged <18 years and defined with low risk of IFI. Higher risk patients, including those with relapsed cancer, appear to be the target for empirical antifungal therapy during protracted febrile neutropenia.