Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved detection of resistance at failure to a tenofovir, emtricitabine and efavirenz regimen by ultradeep sequencing.

OBJECTIVES Resistant minority variants present before ART can be a source of virological failure. This has been shown for NRTIs, NNRTIs and CCR5 inhibitors. However, very few data are available for the detection of such minority resistant variants that could be selected at virological failure and not detected using classical Sanger sequencing. METHODS We studied 26 patients treated with tenofovir, emtricitabine and efavirenz with their first virological failure (defined as two consecutive viral loads >50 copies/mL). We performed standard Sanger sequencing and ultradeep sequencing (UDS; Roche 454(®) Life Sciences) in plasma at failure. For UDS, mutations >1% were considered. We compared the presence of reverse transcriptase mutations between the two techniques, using the latest ANRS algorithm. RESULTS UDS detected more resistance mutations in 38.5% of cases (10/26 patients) and the genotypic sensitivity score (GSS) was reduced for 6 of them (23.1%). The GSS was impacted more often for NRTIs than for NNRTIs, for which most mutations were already detected by Sanger sequencing. Resistant minority variants were detected even in patients with low viral load at failure. CONCLUSIONS These results strongly argue for the use of next-generation sequencing in patients failing on an NRTI+NNRTI regimen, as UDS has the potential to modify the choice of the subsequent regimen.
Discriminable spatial patterns of activation for faces and bodies in the fusiform gyrus

Functional neuroimaging studies consistently report that the visual perception of faces and bodies strongly activates regions within ventral occipitotemporal cortex (VOTC) and, in particular, within the mid-lateral fusiform gyrus. One unresolved issue is the degree to which faces and bodies activate discrete or overlapping cortical regions within this region. Here, we examined VOTC activity to faces and bodies at high spatial resolution, using univariate and multivariate analysis approaches sensitive to differences in both the strength and spatial pattern of activation. Faces and bodies evoked substantially overlapping activations in the fusiform gyrus when each was compared to the control category of houses. No discrete regions of activation for faces and bodies in the fusiform gyrus survived a direct statistical comparison using standard univariate statistics. However, multi-voxel pattern analysis differentiated faces and bodies in regions where univariate analysis found no significant difference in the strength of activation. Using a whole-brain multivariate searchlight approach, we also found that extensive regions in VOTC beyond those defined as fusiform face and body areas using standard criteria where the spatial pattern of activation discriminated faces and bodies. These findings provide insights into the spatial distribution of face- and body-specific activations in VOTC and the identification of functionally specialized regions.
Effects of Message Framing and Past Experience on Intentions to Prevent Human–Coyote Conflicts

ABSTRACT To test the effects of message framing on intentions to participate in seven behaviors to prevent coyote problems, we randomly assigned 461 participants to a control (no message) group or one of four experimental (message) conditions, as part of a 2 (gain versus loss) x 2 (family-referencing versus community-referencing) between-subjects factorial design. We found a significant three-way interaction between gain versus loss framing, point of reference, and past experience with coyotes on intentions to prevent human–coyote conflicts. For people who had encountered coyotes before, the family-referencing, gain-framed message had superior persuasive power; the family-referencing, loss-framed message was more effective in stimulating problem-prevention behavioral intentions for those who had not encountered coyotes. In addition, fear fully mediated the relationship between the three-way interaction and behavioral intentions. Tailoring messages to audiences based on prior experience with coyote problems may improve the efficacy of communication campaigns designed to reduce problem interactions with coyotes.
Hierarchical Contract, Firm Size, and Pay Sensitivity

We present a moral-hazard-based hierarchical contracting model, where investors contract the top manager and the top manager contracts all middle managers. We compare effects of hierarchical contracting on managerial contract sensitivities with those of a direct contracting benchmark where investors directly contract all managers. We argue that under hierarchical contracting, the top manager shifts his compensation risk to middle managers by providing middle managers with higher-powered incentive contracts than would be desired by investors under direct contracting. It is striking that this top managerial risk-shifting behavior motivates investors to design the top managerial contract in such a way that the top-managerial hierarchical contract sensitivity approaches either the first best or zero, as the firm size grows. However, under some reasonable conditions such as correlated managerial effort outcomes, the top managerial sensitivity quickly approaches zero as the firm size increases, and consequently, the sensitivity for large firms can be far lower than predicted by the standard agency theory. This result can serve as an explanation of widely observed firm-size effects on CEO compensations, namely, lower pay sensitivities for large firms than those for small firms. We also argue that even when investors are risk-neutral and then individual performance outcomes of nonexecutive employees may be very weakly correlated to the total outcome of the firm, company-wide bonus plans for nonexecutive employees can still be justified under hierarchical contracting.
Final version : July 2003 To appear in the Review of Economic Studies

We examine an oligopoly model where some consumers engage in costly non-sequential search to discover prices. There are three distinct price-dispersed equilibria characterized by low, moderate and high search intensity. The effects of an increase in the number of firms on search behavior, expected prices, price dispersion and welfare are sensitive (i) to the equilibrium consumers’ search intensity, and (ii) to the status quo number of firms. For instance, when consumers search with low intensity, an increase in the number of firms reduces search, does not affect expected price, leads to greater price dispersion and reduces welfare. In contrast, when consumers search with high intensity, increased competition results in more search and lower prices when the number of competitors in the market is low to begin with, but in less search and higher prices when the number of competitors is large. Duopoly yields identical expected price and price dispersion but higher welfare than an infinite number of firms.
ISOPERIMETRIC PROFILE OF SUBGROUPS AND PROBABILITY OF RETURN OF RANDOM WALKS ON GEOMETRICALLY ELEMENTARY SOLVABLE GROUPS

We study a large class of amenable locally compact groups containing all solvable algebraic groups over a local field and their discrete subgroups. We show that the isoperimetric profile of these groups is in some sense optimal among amenable groups. We use this fact to compute the probability of return of symmetric random walks, and to derive various other geometric properties which are likely to be only satisfied by these groups.
Absence of Spatial Tuning in the Orbitofrontal Cortex

There is limited data in the literature to explicitly support the notion that neurons in OFC are truly action-independent in their coding. We set out to specifically test the hypothesis that OFC value-related neurons in area 13 m of the monkey do not carry information about the action required to obtain that reward – that activity in this area represents reward values in an abstract and action-independent manner. To accomplish that goal we had two monkeys select and execute saccadic eye movements to 81 locations in the visual field for three different kinds of juice rewards. Our detailed analysis of the response fields indicates that these neurons are insensitive to the amplitude or direction of the saccade required to obtain these rewards. Our data thus validate earlier proposals that neurons of 13 m in the OFC encode subjective value independent of the saccadic action required to obtain that reward.
Differentiation and transdifferentiation potentials of cancer stem cells

Tumor cells actively contribute to constructing their own microenvironment during tumorigenesis and tumor progression. The tumor microenvironment contains multiple types of stromal cells that work together with the extracellular matrix and local and systemic factors to coordinately contribute to tumor initiation and progression. Tumor cells and their stromal compartments acquire many genetic and/or epigenetic alternations to facilitate tumor growth and metastasis. The cancer stem cell (CSC) concept has been widely applied to interpreting tumor initiation, growth, metastasis, dormancy and relapse. CSCs have differentiation abilities to generate the original lineage cells that are similar to their normal stem cell counterparts. Interestingly, recent evidence demonstrates that CSCs also have the potential to transdifferentiate into vascular endothelial cells and pericytes, indicating that CSCs can transdifferentiate into other lineage cells for promoting tumor growth and metastasis in some tissue contexts instead of only recruiting stromal cells from local or distant tissues. Although the transdifferentiation of CSCs into tumor stromal cells provides a new dimension that explains tumor heterogeneity, many aspects of CSC transdifferentiation remain elusive. In this review, we summarize the multi-lineage differentiation and transdifferentiation potentials of CSCs as well as discuss their potential contributions to tumor heterogeneity and tumor microenvironment in tumor progression.
The homotopy type of a topological stack

The notion of the \emph{homotopy type} of a topological stack has been around in the literature for some time. The basic idea is that an atlas $X \to \mathfrak{X}$ of a stack determines a topological groupoid $\mathbb{X}$ with object space $X$. The homotopy type of $\mathfrak{X}$ should be the classifying space $B \mathbb{X}$. The choice of an atlas is not part of the data of a stack and hence it is not immediately clear why this construction of a homotopy type is well-defined, let alone functorial. The purpose of this note is to give an elementary construction of such a homotopy-type functor.
Examining the Robustness of Competing Explanations of Slow Growth in African Countries

Abstract This research examines previous findings regarding the robustness of the African growth dummy by (i) expanding the list of variables to include those suggested by Easterly and Levine (1998) and Sachs and Warner (1997b) and (ii) with a modelling strategy that allows explicitly for model uncertainty. Using the Bayesian Averaging of Classical Estimates approach, this paper concludes that the African growth dummy does not appear to be robustly related to growth. This supports the interpretation that the significance of the African dummy may be attributable to omitted variable bias. The paper also contributes to the debate on growth strategies for Africa by assessing the robustness of divergent perspectives offered in the recent literature
Translating flowcharts to non-deterministic languages

Modeling languages are used to verify software and can be classified into deterministic modeling languages and non-deterministic modeling languages. Deterministic modeling languages have a single thread of control whereas non-deterministic ones have a multitude of threads of control and are more amenable for program transformations and analyses. However, deterministic languages such as control-flow graphs are pre-dominantly used in programming language tools. In this work, we translate programs in a deterministic flowchart language to a non-deterministic algebraic modelling language. For the translation, we employ the technique of converting a finite state automata to a regular expression. The states of the finite state automata represent states in the control-flow graph, and the edges represent the edges in the control-flowgraph. We construct a homomorphism to show that the translation is sound, i.e., we prove that the semantics of the program in the deterministic flowchart language is preserved in the translation. Experiments on our implemented algorithm are conducted on the SPEC benchmark suite.
Automatic 1-D inversion of magnetotelluric data: Finding the simplest possible model that fits the data

We demonstrate that automatic layered inversion of plane‐wave electromagnetic data can be carried out by modifying standard least‐squares inversion schemes. The modifications include a logarithmic reparameterization of the unknown model parameters, whereby all layer parameters are forced to remain within given bounds. However, the most important modification to help the optimization process find the best model and to avoid local minima is to split the data into several subbands, starting from the highest frequencies. By this stripping procedure, the shallower part of the model becomes well estimated first. As more data are introduced, more layers may be required to improve the data fit. The new inversion procedure has been applied to many sets of theoretical data representing increasingly complicated layering that is often found in near‐surface studies. The main result of these simulations is that there is a very strong coupling between the resolution power of plane‐wave data and their random errors. Part.
Trimetazidine: a meta-analysis of randomised controlled trials in heart failure

Objective To explore whether trimetazidine could improve symptoms, cardiac functions and clinical outcomes in patients with heart failure (HF). Methods A systematic literature search was conducted to identify randomised controlled trials (RCT) of trimetazidine for HF between 1966 and May 2010 in Pubmed, the Cochrane Central Registry of Clinical Trials and EMBASE. Reports of trials were sought that compared trimetazidine with placebo control for chronic HF in adults, with outcomes including all-cause mortality, hospitalisation, cardiovascular events, changes in cardiac function parameters and exercise capacity. Results 17 trials with data for 955 patients were identified by the literature search. Trimetazidine therapy was associated with a significant improvement in left ventricular ejection fraction in patients with both ischaemic (weighted mean difference (WMD) with placebo 7.37%; 95% CI 6.05 to 8.70; p<0.01) and non-ischaemic HF (WMD 8.72%; 95% CI 5.51 to 11.92; p<0.01). With trimetazidine therapy, left ventricular end-systolic volume was significantly reduced (WMD 10.37 ml; 95% CI 15.46 to 5.29; p<0.01) and New York Heart Association classification was improved (WMD 0.41; 95% CI 0.51 to 0.31; p<0.01) as was exercise duration (WMD, 30.26 s; 95% CI 8.77 to 51.75; p<0.01). More importantly, trimetazidine had a significant protective effect for all-cause mortality (RR 0.29; 95% CI 0.17 to 0.49; p<0.00001) and cardiovascular events and hospitalisation (RR 0.42; 95% CI 0.30 to 0.58; p<0.00001). Conclusion Trimetazidine might be an effective strategy for treating HF. More studies, especially larger multicentre RCT, are warranted to clarify the effect of trimetazidine on HF.
Using design thinking to engage autistic students in participatory design of an online toolkit to help with transition into higher education

Purpose – The purpose of this paper is to reflect on engaging young autistic people in the participatory design of the Autism & Uni online toolkit. The purpose of the toolkit is to provide autistic students with information and strategies for dealing with the challenges they may encounter when entering higher education. The study adds to existing research on participatory design by considering the specific needs and contributions of autistic people who are of average or higher intelligence, academically competent and generally articulate, a group that has received limited attention hitherto. Design/methodology/approach – The research used a five-step design thinking approach and engaged multiple stakeholders at different points. The paper covers the whole process, paying particular attention to the final two steps of prototyping and testing. During three participatory design workshops, autistic people acted as co-designers and co-creators. Findings – The workshops were effective in engaging participants i.
Rapidly Escalating Hepcidin and Associated Serum Iron Starvation Are Features of the Acute Response to Typhoid Infection in Humans

Background Iron is a key pathogenic determinant of many infectious diseases. Hepcidin, the hormone responsible for governing systemic iron homeostasis, is widely hypothesized to represent a key component of nutritional immunity through regulating the accessibility of iron to invading microorganisms during infection. However, the deployment of hepcidin in human bacterial infections remains poorly characterized. Typhoid fever is a globally significant, human-restricted bacterial infection, but understanding of its pathogenesis, especially during the critical early phases, likewise is poorly understood. Here, we investigate alterations in hepcidin and iron/inflammatory indices following experimental human typhoid challenge. Methodology/Principal Findings Fifty study participants were challenged with Salmonella enterica serovar Typhi and monitored for evidence of typhoid fever. Serum hepcidin, ferritin, serum iron parameters, C-reactive protein (CRP), and plasma IL-6 and TNF-alpha concentrations were measured during the 14 days following challenge. We found that hepcidin concentrations were markedly higher during acute typhoid infection than at baseline. Hepcidin elevations mirrored the kinetics of fever, and were accompanied by profound hypoferremia, increased CRP and ferritin, despite only modest elevations in IL-6 and TNF-alpha in some individuals. During inflammation, the extent of hepcidin upregulation associated with the degree of hypoferremia. Conclusions/Significance We demonstrate that strong hepcidin upregulation and hypoferremia, coincident with fever and systemic inflammation, are hallmarks of the early innate response to acute typhoid infection. We hypothesize that hepcidin-mediated iron redistribution into macrophages may contribute to S. Typhi pathogenesis by increasing iron availability for macrophage-tropic bacteria, and that targeting macrophage iron retention may represent a strategy for limiting infections with macrophage-tropic pathogens such as S. Typhi.
‘Cashing In’ on curiosity and spectacle: the forensic patient and news media

Abstract Health and social care professionals are gatekeepers to, and custodians of, confidential service user information. In the United Kingdom (UK), police investigations have unveiled cases of payments being made to public service officials by journalists in return for service user information. The purpose of this discussion is to investigate such cases in the context of high-security forensic care. This paper provides a discussion drawing upon two UK-based case studies of prosecutions of public service workers relating to the sale of confidential information. The analysis presented here illuminates upon the salient and connected issues at work that have led to the transgression of legal obligations and professional responsibilities/principles of confidentiality. A fuller reading of the context in which these transgressions occur, and motivations that exist, may well serve to inform policy, training, guidance or vigilance in relation to the preserving of service user information in the future.
SUBGROUPS AND QUOTIENTS OF AUTOMORPHISM GROUPS OF RAAGS

We study subgroups and quotients of outer automorphsim groups of rightangled Artin groups (RAAGs). We prove that for all RAAGs, the outer automorphism group is residually finite and, for a large class of RAAGs, it satisfies the Tits alternative. We also investigate which of these automorphism groups contain non-abelian solvable subgroups.
Spin foam models for quantum gravity

In this topical review, we review the present status of the spin foam formulation of non-perturbative (background-independent) quantum gravity. The topical review is divided into two parts. In the first part, we present a general introduction to the main ideas emphasizing their motivation from various perspectives. Riemannian three-dimensional gravity is used as a simple example to illustrate conceptual issues and the main goals of the approach. The main features of the various existing models for four-dimensional gravity are also presented here. We conclude with a discussion of important questions to be addressed in four dimensions (gauge invariance, discretization independence, etc). In the second part, we concentrate on the definition of the Barrett–Crane model. We present the main results obtained in this framework from a critical perspective. Finally, we review the combinatorial formulation of spin foam models based on the dual group field theory technology. We present the Barrett–Crane model in this framework and review the finiteness results obtained for both its Riemannian and its Lorentzian variants.
Response of Midbrain Pain Receptors in a Rodent Model of Radiculopathy

Response of Midbrain Pain Receptors in a Rodent Model of Radiculopathy by Priscilla Y Hwang Department of Biomedical Engineering Duke University Date:___________________________ Approved: _____________________________ Lori A Setton, Supervisor ______________________________ Warren M Grill _____________________________ David F Katz An abstract of a thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in the Department of Biomedical Engineering in the Graduate School of Duke University 2012 Copyright by Priscilla Y Hwang 2012
Importance of the Time Interval between Bowel Preparation and Colonoscopy in Determining the Quality of Bowel Preparation for Full-Dose Polyethylene Glycol Preparation

Background/Aims The quality of bowel preparation (QBP) is the important factor in performing a successful colonoscopy. Several factors influencing QBP have been reported; however, some factors, such as the optimal preparation-to-colonoscopy time interval, remain controversial. This study aimed to determine the factors influencing QBP and the optimal time interval for full-dose polyethylene glycol (PEG) preparation. Methods A total of 165 patients who underwent colonoscopy from June 2012 to August 2012 were prospectively evaluated. The QBP was assessed using the Ottawa Bowel Preparation Scale (Ottawa) score according to several factors influencing the QBP were analyzed. Results Colonoscopies with a time interval of 5 to 6 hours had the best Ottawa score in all parts of the colon. Patients with time intervals of 6 hours or less had the better QBP than those with time intervals of more than 6 hours (p=0.046). In the multivariate analysis, the time interval (odds ratio, 1.897; 95% confidence interval, 1.006 to 3.577; p=0.048) was the only significant contributor to a satisfactory bowel preparation. Conclusions The optimal time was 5 to 6 hours for the full-dose PEG method, and the time interval was the only significant contributor to a satisfactory bowel preparation.
Variance Risk Premia

We propose a direct and robust method for quantifying the variance risk premium on financial assets. We theoretically and numerically show that the risk-neutral expected value of the return variance, also known as the variance swap rate, is well approximated by the value of a particular portfolio of options. Ignoring the small approximation error, the difference between the realized variance and this synthetic variance swap rate quantifies the variance risk premium. Using a large options data set, we synthesize variance swap rates and investigate the historical behavior of variance risk premia on five stock indexes and 35 individual stocks.