Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical efficacy and mechanistic evaluation of aflibercept for proliferative diabetic retinopathy (acronym CLARITY): a multicentre phase IIb randomised active-controlled clinical trial

Introduction Proliferative diabetic retinopathy (PDR) is the main cause of severe visual loss in people with diabetes mellitus. The standard treatment for this condition is panretinal photocoagulation (PRP). This laser treatment is inherently destructive, with predictable adverse effects on visual function, and a safer alternative is required. Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors can induce short-term regression of retinal neovascularisation. The aim of this randomised controlled trial is to determine the efficacy, safety and cost-effectiveness of intravitreal aflibercept, an inhibitor of VEGF-A, VEGF-B and placental growth factor (PLGF), in PDR, and to investigate the impact on local oxygenation. Methods and analysis This is a phase IIb randomised controlled single-masked multicentre clinical trial to determine the impact of repeated intravitreal aflibercept injections in the treatment and prevention of PDR. 220 participants with treatment-naïve or treated but active retinal neovascularisation in at least one eye will be randomly allocated 1:1 to intravitreal aflibercept injections or PRP for a period of 52 weeks. The primary outcome is the change in best-corrected visual acuity in the study eye at 52 weeks. Secondary outcomes include changes from baseline in other visual functions, anatomical changes and cost-effectiveness. Ocular and non-ocular adverse events will also be reported over 52 weeks. Ethics and dissemination The study has been approved by the National Research Ethics Service (NRES) committee with respect to scientific content and compliance with applicable research and human subjects’ regulations. Findings will be reported through scientific publications and research conferences. The results of this study will provide clinical evidence for the feasibility, efficacy safety and cost-effectiveness of intravitreal aflibercept for PDR. Trial registration number ISRCTN 32207582.
Analysis and optimization of pilot symbol-assisted Rake receivers for DS-CDMA systems

The effect of imperfect channel estimation (CE) on the performance of pilot-symbol-assisted modulation (PSAM) and MRC Rake reception over time- or frequency-selective fading channels with either a uniform power delay profile (UPDP) or a nonuniform power delay profile (NPDP) is investigated. For time-selective channels, a Wiener filter or linear minimum mean square error (LMMSE) filter for CE is considered, and a closed-form asymptotic expression for the mean square error (MSE) when the number of pilots used for CE approaches infinity is derived. In high signal-to-noise ratio (SNR), the MSE becomes independent of the channel Doppler spectrum. A characteristic function method is used to derive new closed-form expressions for the bit error rate (BER) of Rake receivers in UPDP and NPDP channels. The results are extended to two-dimensional (2-D) Rake receivers. The pilot-symbol spacing and pilot-to-data power ratio are optimized by minimizing the BER. For UPDP channels, elegant results are obtained in the asymptotic case. Furthermore, robust spacing design criteria are derived for the maximum Doppler frequency
Post‐intensive care syndrome: its pathophysiology, prevention, and future directions

Expanding elderly populations are a major social challenge in advanced countries worldwide and have led to a rapid increase in the number of elderly patients in intensive care units (ICUs). Innovative advances in medical technology have enabled lifesaving of patients in ICUs, but there remain various problems to improve their long‐term prognoses. Post‐intensive care syndrome (PICS) refers to physical, cognition, and mental impairments that occur during ICU stay, after ICU discharge or hospital discharge, as well as the long‐term prognosis of ICU patients. Its concept also applies to pediatric patients (PICS‐p) and the mental status of their family (PICS‐F). Intensive care unit‐acquired weakness, a syndrome characterized by acute symmetrical limb muscle weakness after ICU admission, belongs to physical impairments in three domains of PICS. Prevention of PICS requires performance of the ABCDEFGH bundle, which incorporates the prevention of delirium, early rehabilitation, family intervention, and follow‐up from the time of ICU admission to the time of discharge. Diary, nutrition, nursing care, and environmental management for healing are also important in the prevention of PICS. This review outlines the pathophysiology, prevention, and future directions of PICS.
DEFINING MARKETS FOR NEW MATERIALS Engineering Methodology with Case Application

An engineering methodology to identify profitable market segments for the use of new materials is presented and illustrated by application to the automobile industry. The method has three parts: empirical, statistical and analytical. The first measures company preferences for the important attributes of a use of a material, applying single-attribute utility functions. The second identifies market segments, by determining significant differences between measured preferences with t-tests. The third estimates the premium these market segments would pay for a product made of a new material, using multiattribute utilities, and thus determines profitable market segments. The case study of valve trains containing ceramic components defined two market segments: companies with either a broad world market or a narrow specialty. The immediate buyers of these valve trains are likely to be producers of high-value, six-cylinder automobiles, who seem prepared to pay a significant premium for this product.
Steatosis and Steatohepatitis: Complex Disorders

Non-alcoholic fatty liver disease (NAFLD) which includes steatosis and steatohepatitis, in particular non-alcoholic steatohepatitis (NASH), is a rising health problem world-wide and should be separated from alcoholic steatohepatitis (ASH). NAFLD is regarded as hepatic manifestation of the metabolic syndrome (MetSy), being tightly linked to obesity and type 2 diabetes mellitus (T2DM). Development of steatosis, liver fibrosis and cirrhosis often progresses towards hepatocellular carcinogenesis and frequently results in the indication for liver transplantation, underlining the clinical significance of this disease complex. Work on different murine models and several human patients studies led to the identification of different molecular key players as well as epigenetic factors like miRNAs and SNPs, which have a promoting or protecting function in AFLD/ASH or NAFLD/NASH. To which extent they might be translated into human biology and pathogenesis is still questionable and needs further investigation regarding diagnostic parameters, drug development and a better understanding of the genetic impact. In this review we give an overview about the currently available knowledge and recent findings regarding the development and progression of this disease.
No Evidence That Experiencing Physical Warmth Promotes Interpersonal Warmth: Two Failures to Replicate Williams and Bargh (2008)

Williams and Bargh (2008) reported that holding a hot cup of coffee caused participants to judge a person’s personality as warmer and that holding a therapeutic heat pad caused participants to choose rewards for other people rather than for themselves. These experiments featured large effects (r = .28 and .31), small sample sizes (41 and 53 participants), and barely statistically significant results. We attempted to replicate both experiments in field settings with more than triple the sample sizes (128 and 177) and double-blind procedures, but found near-zero effects (r = −.03 and .02). In both cases, Bayesian analyses suggest there is substantially more evidence for the null hypothesis of no effect than for the original physical warmth priming hypothesis.
Business process modeling for post execution analysis and improvement

Evaluation and analysis of business processes are important for improvement of business processes. Business process modeling is used as a medium of communication between stakeholders. Most of the research in business process modeling is focused on alignment of information technology services and business operations. Existing process models lack the representation of performance data for evaluation and analysis. The process models conceived for information system development are not sufficient for such representation. This paper discusses the challenges of business process modeling in the post execution analysis context and describes the characteristics of an analytical modeling language. Furthermore, we also extend an existing modeling language and explain the proposed extensions with the help of a case study.
XocR, a LuxR solo required for virulence in Xanthomonas oryzae pv. oryzicola

Xanthomonas oryzae pv. oryzicola (Xoc) causes bacterial leaf streak (BLS) in rice, a serious bacterial disease of rice in Asia and parts of Africa. The virulence mechanisms of Xoc are not entirely clear and control measures for BLS are poorly developed. The solo LuxR proteins are widespread and shown to be involved in virulence in some plant associated bacteria (PAB). Here, we have cloned and characterized a PAB LuxR solo from Xoc, named as XocR. Mutation of xocR almost completely impaired the virulence ability of Xoc on host rice, but did not alter the ability to trigger HR (hypersensitive response, a programmed cell death) on non-host (plant) tobacco, suggesting the diversity of function of xocR in host and non-host plants. We also provide evidence to show that xocR is involved in the regulation of growth-independent cell motility in response to a yet-to-be-identified rice signal, as mutation of xocR impaired cell swimming motility of wild-type Rs105 in the presence but not absence of rice macerate. We further found that xocR regulated the transcription of two characterized virulence-associated genes (recN and trpE) in the presence of rice macerate. The promoter regions of recN and trpE possessed a potential binding motif (an imperfect pip box-like element) of XocR, raising the possibility that XocR might directly bind the promoter regions of these two genes to regulate their transcriptional activity. Our studies add a new member of PAB LuxR solos and also provide new insights into the role of PAB LuxR solo in the virulence of Xanthomonas species.
COPD management: role of symptom assessment in routine clinical practice

Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms that significantly impair health-related quality of life. Despite this, COPD treatment and its management are mainly based on lung function assessments. There is increasing evidence that conventional lung function measures alone do not correlate well with COPD symptoms and their associated impact on patients’ everyday lives. Instead, symptoms should be assessed routinely, preferably by using patient-centered questionnaires that provide a more accurate guide to the actual burden of COPD. Numerous questionnaires have been developed in an attempt to find a simple and reliable tool to use in everyday clinical practice. In this paper, we review three such patient-reported questionnaires recommended by the latest Global Initiative for Chronic Obstructive Lung Disease guidelines, ie, the modified Medical Research Council questionnaire, the clinical COPD questionnaire, and the COPD Assessment Test, as well as other symptom-specific questionnaires that are currently being developed.
Papering over the cracks: The effects of introducing best practices on the web security ecosystem

Hypertext Transfer Protocol Secure (HTTPS) is the de facto standard for secure end-to-end web communication. However, numerous flaws discovered during recent years, such as Apple's "goto fail" bug, and cryptographic weaknesses as illustrated by the Poodlebleed vulnerability, have brought the efficiency of the mostly self-regulated web security market into question. In this cross-disciplinary paper, the authors survey some 160.000 HTTPS-enabled servers among popular web sites over a time period of three years. The research question is what effect the introduction of best practices and vulnerability publication have on web server security in the form of protocol support. Main findings include that (i) insecure configurations, although well known, can remain widespread for over a decade, (ii) the introduction of best practices affect the decline of insecure configurations only moderately, whereas highly publicized security flaws have a significant impact, and (iii) economic incentives for website owners to provide secure services are weak, motivating such other levers of influence as legislation or blocking of noncompliant sites.
Information and Self-Organization of Behavior

The goal of Guided Self-Organization (GSO) is to leverage the strengths of selforganization while still being able to direct the outcome of the self-organizing process. GSO typically has the following features: (i) an increase in organization (structure and/or functionality) over some time; (ii) the local interactions are not explicitly guided by any external agent; and (iii) task-independent objectives are combined with task-dependent constraints. Over the last few years a mathematical framework has started to form around these features, promising to provide common organizational and guidance principles across multiple scales and contexts. This process is far from being complete, and every year an International GSO Workshop showcases new breakthroughs that diversify and reshape the field. Nevertheless, some themes and ideas withstand the test of time, maintaining the core of the GSO research. One of these themes is the role of information (understood as Shannon information, i.e. “reduction in uncertainty”) in guiding a self-organizing process. In particular, a lot of progress has been achieved in studying various aspects of information structure and information processing during self-organization of behavior (molecular, neural, cognitive, social, etc.). For example, several principles based on information flows through the perception-action loops of embodied cognitive systems were recently developed (Ay et al., 2012). These principles related GSO to the notion that adaptive behaviors emerge from interactions between brain, body, and environment while optimizing task-independent objective functions. Having a language that describes interactions is essential for a non-reductionist science (Gershenson and Heylighen, 2005). And so another common GSO trend is the use of graph theory in representing and analyzing interactions within a system, be it a cell, the brain, a social network, an ecological web, or a power grid. Several graph-theoretical measures have been devised and put to use in tracing various self-organization processes developing within networks, as well as in relating connectivity of the self-organizing systems to their function (Rubinov and Sporns, 2010; Gershenson, 2012). This topical issue presents a selection of papers following two GSO Workshops (Bloomington, Indiana, USA, in 2010 and Hertfordshire, UK, in 2011). These papers are grouped into three sections. The first section contains three studies characterizing neural dynamics with model-free techniques. It is followed
Exploring novel paths towards protein signatures of chronic pain

Pain is a major symptom of many medical conditions and the worldwide number one reason for people to seek medical assistance. It affects the quality of life of patients and poses a heavy financial burden on society with high costs of treatment and lost productivity. Furthermore, the treatment of chronic pain presents a big challenge as pain therapeutics often lack efficacy and exhibit minimal safety profiles. The latter can be largely attributed to the fact that current therapies target molecules with key physiological functions throughout the body. In light of these difficulties, the identification of proteins specifically involved in chronic pain states is of paramount importance for designing selective interventions. Several profiling efforts have been employed with the aim to dissect the molecular underpinnings of chronic pain, both on the level of the transcriptome and proteome. However, generated results are often inconsistent and non-overlapping, which is largely due to inherent technical constraints. A potential solution may be offered by emerging strategies capable of performing standardized and reproducible proteome analysis, such as data-independent acquisition-mass spectrometry (DIA-MS). We have recently demonstrated the applicability of DIA-MS to interrogate chronic pain-related proteome alterations in mice. Based on our results, we aim to provide an overview on DIA-MS and its potential to contribute to the comprehensive characterization of molecular signatures underlying pain pathologies.
Phosphine Resistance in the Rust Red Flour Beetle, Tribolium castaneum (Coleoptera: Tenebrionidae): Inheritance, Gene Interactions and Fitness Costs

The recent emergence of heritable high level resistance to phosphine in stored grain pests is a serious concern among major grain growing countries around the world. Here we describe the genetics of phosphine resistance in the rust red flour beetle Tribolium castaneum (Herbst), a pest of stored grain as well as a genetic model organism. We investigated three field collected strains of T. castaneum viz., susceptible (QTC4), weakly resistant (QTC1012) and strongly resistant (QTC931) to phosphine. The dose-mortality responses of their test- and inter-cross progeny revealed that most resistance was conferred by a single major resistance gene in the weakly (3.2×) resistant strain. This gene was also found in the strongly resistant (431×) strain, together with a second major resistance gene and additional minor factors. The second major gene by itself confers only 12–20× resistance, suggesting that a strong synergistic epistatic interaction between the genes is responsible for the high level of resistance (431×) observed in the strongly resistant strain. Phosphine resistance is not sex linked and is inherited as an incompletely recessive, autosomal trait. The analysis of the phenotypic fitness response of a population derived from a single pair inter-strain cross between the susceptible and strongly resistant strains indicated the changes in the level of response in the strong resistance phenotype; however this effect was not consistent and apparently masked by the genetic background of the weakly resistant strain. The results from this work will inform phosphine resistance management strategies and provide a basis for the identification of the resistance genes.
Sovereign CDS and Bond Pricing Dynamics in Emerging Markets: Does the Cheapest-to-Deliver Option Matter?

We examine the relationships between credit default swap (CDS) premiums and bond yield spreads for nine emerging market sovereign borrowers. We find that these two measures of credit risk deviate considerably in the short run, due to factors such as liquidity and contract specifications, but we estimate a stable long-term equilibrium relationship for most countries. In particular, CDS premiums tend to move more than one-for-one with yield spreads, which we show is broadly consistent with the presence of a significant "cheapest-to-deliver" (CTD) option. In addition, we find a variety of cross-sectional evidence of a CTD option being incorporated into CDS premiums. In our analysis of the short-term dynamics, we find that CDS premiums often move ahead of the bond market. However, we also find that bond spreads lead CDS premiums for emerging market sovereigns more often than has been found for investment-grade corporate credits, consistent with the CTD option impeding CDS liquidity for our riskier set of borrowers. Furthermore, the CDS market is less likely to lead for sovereigns that have issued more bonds, suggesting that the relative liquidity of the two markets is a key determinant of where price discovery occurs.
Roles and strategies of learning analytics in the e-publication era

E-books have been introduced to educational institutions in many countries. The use of e-books in traditional classrooms enables the recording of learning logs. Recently, researchers have begun to carry out learning analytics on the learning logs of e-books. However, there has been limited attention devoted to understanding the types of learning strategies that students employ when they read e-books. In this paper, using e-book learning logs, we examine the learning strategies that students employed when reading e-books. In this paper, we will introduce how to identify learning strategies from e-book learning logs with two case studies. One is “Identifying Learning Strategies Using Clustering” and the other is “Examining Learning Strategies Using Sequential Analysis. ”
Systematic Review and Meta-analysis of Therapeutic Management of Upper-Limb Dysfunction in Children With Congenital Hemiplegia

CONTEXT. Rehabilitation for children with congenital hemiplegia to improve function in the impaired upper limb and enhance participation may be time-consuming and costly. OBJECTIVES. To systematically review the efficacy of nonsurgical upper-limb therapeutic interventions for children with congenital hemiplegia. METHODS. The Cochrane Central Register of Controlled Trials, Medline, CINAHL (Cumulative Index to Nursing and Allied Health Literature), AMED (Allied and Complementary Medicine), Embase, PsycINFO, and Web of Science were searched up to July 2008. Data sources were randomized or quasi-randomized trials and systematic reviews. RESULTS. Twelve studies and 7 systematic reviews met our criteria. Trials had strong methodologic quality (Physiotherapy Evidence Database [PEDro] scale ≥ 5), and systematic reviews rated strongly (AMSTAR [Assessment of Multiple Systematic Reviews] score ≥ 6). Four interventions were identified: intramuscular botulinum toxin A combined with upper-limb training; constraint-induced movement therapy; hand-arm bimanual intensive training; and neurodevelopmental therapy. Data were pooled for upper-limb, self-care, and individualized outcomes. There were small-to-medium treatment effects favoring intramuscular botulinum toxin A and occupational therapy, neurodevelopmental therapy and casting, constraint-induced movement therapy, and hand-arm bimanual intensive training on upper-limb outcomes. There were large treatment effects favoring intramuscular botulinum toxin A and upper-limb training for individualized outcomes. No studies reported participation outcomes. CONCLUSIONS. No one treatment approach seems to be superior; however, injections of botulinum toxin A provide a supplementary benefit to a variety of upper-limb–training approaches. Additional research is needed to justify more-intensive approaches such as constraint-induced movement therapy and hand-arm bimanual intensive training.
Indoor navigation for mobile robots using predictive fields

A predictive field based path planner for mobile robot navigation in indoor areas is described. Predictive fields are used for incorporating moving obstacle information into the navigation function framework. Navigation functions have been limited by geometric restrictions for robot workspaces and cannot easily be used in everyday environments. A methodical description of indoor workspaces such that they follow the constraints of a navigation function based path planner is proposed. Typical use of navigation function based path planners as a gradient based control input requires large scaling factors in practical use. A direction based control input, which eliminates the scaling factor altogether, is proposed and its stability and convergence is proved using Lyapunov-type analysis. The proposed algorithm improves the practicability of navigation functions and makes it possible to envisage a person following mobile robot operating in indoor environments using predictive field navigation.