Miracle-dz/UniFAR-FTUs huggingface dataset:
A comparison of denominator degrees of freedom methods for multiple observer ROC analysis

There are several methods available for analysing multireader ROC studies that generalize results to both the reader and case populations. Two of these methods—the Dorfman–Berbaum–Metz (DBM) method and the Obuchowki–Rockette (OR) method—appear to be quite different in their original formulations. However, recently it has been shown that the DBM and OR procedures yield the same test statistic when based on the same accuracy measure and covariance estimation method, but inferences can vary depending on which denominator degrees of freedom (ddf) method, DBM or OR, is used. I show in simulations that there are problems with both ddf methods: OR is ultraconservative with significance levels considerably below the nominal level, and DBM can result in extremely wide confidence intervals because the ddf can be close to zero. I propose a new ddf method that overcomes both of these problems and can be used with either the OR or DBM procedure. Copyright © 2006 John Wiley & Sons, Ltd.
Hypoxia-inducible factor-1 mediates adaptive developmental plasticity of hypoxia tolerance in zebrafish, Danio rerio

In recent years, natural and anthropogenic factors have increased aquatic hypoxia the world over. In most organisms, the cellular response to hypoxia is mediated by the master regulator hypoxia-inducible factor-1 (HIF-1). HIF-1 also plays a critical role in the normal development of the cardiovascular system of vertebrates. We tested the hypothesis that hypoxia exposures which resulted in HIF-1 induction during embryogenesis would be associated with enhanced hypoxia tolerance in subsequent developmental stages. We exposed zebrafish (Danio rerio) embryos to just 4 h of severe hypoxia or total anoxia at 18, 24 and 36 h post-fertilization (hpf). Of these, exposure to hypoxia at 24 and 36 hpf as well as anoxia at 36 hpf activated the HIF-1 cellular pathway. Zebrafish embryos that acutely upregulated the HIF-1 pathway had an increased hypoxia tolerance as larvae. The critical window for hypoxia sensitivity and HIF-1 signalling was 24 hpf. Adult male fish had a lower critical oxygen tension (Pcrit) compared with females. Early induction of HIF-1 correlated directly with an increased proportion of males in the population. We conclude that mounting a HIF-1 response during embryogenesis is associated with long-term impacts on the phenotype of later stages which could influence both individual hypoxia tolerance and population dynamics.
Housing Consumption and Level of Development: A Cross-National Comparison

While housing issues in developing countries, after years of benign neglect, have become major items of public policy, the design and analysis of appropriate development plans are handicapped by the state of current knowledge of housing consumption patterns and their variations among countries and over time. This paper presents the notion that changes in housing consumption in a country reflect its level of development. Evidence has been found to support this hypothesis that income elasticities are low in early development, increase rapidly during middle levels of development, and begin to decline at very high levels of development.
Fault activation by hydraulic fracturing in western Canada

Triggered quakes get unconventional The big earthquakes induced by human activity are mostly linked with disposal of wastewater. However, Bao and Eaton implicate hydraulic fracturing (or fracking) as the culprit in western Canada (see the Perspective by Elsworth). Fracking near Fox Creek, Alberta, reactivated faults, clustering earthquakes along the old fault traces. Fracking does not appear to cause large earthquakes in many other areas that are prone to induced seismicity. Understanding the underlying causes of seismicity in different localities is vital for developing sound regulation to limit damaging earthquakes. Science, this issue p. 1406; see also p. 1380 Hydraulic fracturing reactivated faults, inducing an earthquake of magnitude > 4 in western Canada. Hydraulic fracturing has been inferred to trigger the majority of injection-induced earthquakes in western Canada, in contrast to the Midwestern United States, where massive saltwater disposal is the dominant triggering mechanism. A template-based earthquake catalog from a seismically active Canadian shale play, combined with comprehensive injection data during a 4-month interval, shows that earthquakes are tightly clustered in space and time near hydraulic fracturing sites. The largest event [moment magnitude (MW) 3.9] occurred several weeks after injection along a fault that appears to extend from the injection zone into crystalline basement. Patterns of seismicity indicate that stress changes during operations can activate fault slip to an offset distance of >1 km, whereas pressurization by hydraulic fracturing into a fault yields episodic seismicity that can persist for months.
Emergency Conditions in Horses: Opinions and Decision Making of Livery Yard Owners

Objective: The aim of this study was to evaluate equine livery yard owners’ opinions of emergency conditions, and to identify factors influencing emergency decision making in the horse. Background: There is limited data on horse owners’ opinions and decision making in emergency conditions. Evidentiary value: An online questionnaire was distributed to UK livery yard owners accredited with the British Horse Society. There were 104 survey participants, who represented experienced owners with responsibility for care of a number of horses. Methods: The questionnaire consisted of open and closed questions on participants’ demographics, their experiences and opinions of the most common equine emergency conditions, and emergency decision making. Descriptive data analysis included frequency ranking and categorisation of free text responses. Results: The majority of respondents had kept horses for more than 10 years (97%), and reported previous experience of emergency conditions (99%), predominantly colic (96%) and wounds (92%). Participants considered that the most common emergency conditions were colic (98%), wounds (49%) and fractures (22%), and the most concerning conditions were colic (94%), lameness (36%) and wounds (21%). Factors believed to be important in emergency decision making were: degree of pain, likelihood of condition resolving, and severity of disease. Conclusion: This study highlights the importance of colic and wounds as emergency conditions in the horse, and describes factors considered important in emergency decision making. Application: The outcomes identify where research and clinical resources should be targeted to improve emergency care for horses. The results were used to inform a survey of the wider horse population.
Systolic Blood Pressure and Mortality in Chronic Hemodialysis Patients: Results of a Nationwide Italian Study

Studies on the relationship between blood pressure (BP) and mortality among hemodialysis patients have yielded conflicting results. Reports have come mostly from North America and have dealt with dialysis patients as a homogenous population and differed in methods and time of BP measurement and the optimal BP target. In a prospective nationwide study in 3674 unselected Caucasian patients with end‐stage renal disease undergoing chronic hemodialysis from 73 dialysis units, the authors sought to examine the relationship between the different measurements of BP and mortality according to antihypertensive treatment. The mean age of patients was 67.2±14.1 years and the prevalence of diabetes was 19.5%. During follow‐up (26.5±10.5 months), 977 deaths were recorded. In the whole cohort, BP was not associated with mortality. After grouping the patients according to antihypertensive treatment, the analysis showed that only in patients who did not take antihypertensive medications (1613) was there an inverse relationship between postdialysis systolic BP and mortality. These patients differed from the others in BP, dialysis vintage, prevalence of diabetes, and type of dialysis technique. This study suggests that with respect to the relationship of BP with mortality, dialysis patients are not a homogenous population. Differences in demographic characteristics and in dialysis technique may therefore explain the reported variability of previous results.
On Auditors And The Courts In An Adverse Selection Setting

Most models of auditing in the accounting literature may be classified as agency models or signaling models. ' The emphasis in an agency model is on a single firm; the auditor is typically modeled as a utility-maximizing player who is hired by a firm's owner to better control a manager as well as to improve their risk-sharing arrangement. A signaling model, on the other hand, includes a larger set of players, and it focuses on the interrelationships among the various players in a market setting. The auditor is usually modeled as a mechanistic monitor; the output (report) of an auditor, and/or the act of hiring an auditor, is used by an informed party (e.g., an owner) to signal its private information (e.g., the firm's risk characteristics) to an uninformed party (e.g., an investor). In this paper we incorporate a utility-maximizing auditor, as found in agency models, into a simple signaling setting composed of firms of unobservable risk types requiring loans, lenders of capital to the firms, auditors, and a court system. We consider how litigation against auditors affects the prevailing equilibria as well as the resulting welfare of the different participants when the endogenously determined interest rates
Health and economic impact of PHiD-CV in Canada and the UK: a Markov modelling exercise

Abstract Objective: The spectrum of diseases caused by Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) represents a large burden on healthcare systems around the world. Meningitis, bacteraemia, community-acquired pneumonia (CAP), and acute otitis media (AOM) are vaccine-preventable infectious diseases that can have severe consequences. The health economic model presented here is intended to estimate the clinical and economic impact of vaccinating birth cohorts in Canada and the UK with the 10-valent, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) compared with the newly licensed 13-valent pneumococcal conjugate vaccine (PCV-13). Methods: The model described herein is a Markov cohort model built to simulate the epidemiological burden of pneumococcal- and NTHi-related diseases within birth cohorts in the UK and Canada. Base-case assumptions include estimates of vaccine efficacy and NTHi infection rates that are based on published literature. Results: The model predicts that the two vaccines will provide a broadly similar impact on all-cause invasive disease and CAP under base-case assumptions. However, PHiD-CV is expected to provide a substantially greater reduction in AOM compared with PCV-13, offering additional savings of Canadian $9.0 million and £4.9 million in discounted direct medical costs in Canada and the UK, respectively. Limitations: The main limitations of the study are the difficulties in modelling indirect vaccine effects (herd effect and serotype replacement), the absence of PHiD-CV- and PCV-13-specific efficacy data and a lack of comprehensive NTHi surveillance data. Additional limitations relate to the fact that the transmission dynamics of pneumococcal serotypes have not been modelled, nor has antibiotic resistance been accounted for in this paper. Conclusion: This cost-effectiveness analysis suggests that, in Canada and the UK, PHiD-CV’s potential to protect against NTHi infections could provide a greater impact on overall disease burden than the additional serotypes contained in PCV-13.
In silico prediction and segregation analysis of putative virus defense genes based on SSR markers in sweet potato F1 progenies of cultivars New Kawogo and Resisto

In sweet potato, an anti-virus defense mechanism termed reversion has been postulated to lead to virus freedom from once infected plants. The objectives of this study were to identify anti-virus defense genes and evaluate their segregation in progenies. Reference genes from different plant species were used to assemble transcript sequences of each sweet potato defense gene in silico. Sequences were used for evaluate phylogenetic relationships with similar genes from different plant species, mining respective defense genes and thereafter developing simple sequence repeats (SSRs) for segregation analysis. Eight potential defense genes were identified: RNA dependent RNA polymerases 1, 2, 5, and 6; Argonaute 1, and Dicer-like 1, 2, and 4. Identified genes were differentially related to those of other plants and were observed on different chromosomes. The defense genes contained mono-, di-, tri-, tetra, penta-, and hexa-nucleotide repeat motifs. The SSR markers within progenies were segregated in disomic, co-segregation, nullisomic, monosomic, and trisomic modes. These findings indicate the possibility of deriving and utilizing SSRs using published genomic information. Furthermore, and given that the SSR markers were derived from known genes on defined chromosomes, this work will contribute to future molecular breeding and development of resistance gene analogs in this economically important crop. Key words: In silico, segregation, simple sequence repeats (SSR) markers, sweet potato defense genes, virus.
What outcome measures are commonly used for Complex Regional Pain Syndrome clinical trials? A systematic review of the literature

Complex Regional Pain Syndrome (CRPS) is a chronic pain condition, often triggered by trauma to a limb and characterized by sensory, motor, autonomic and trophic changes within the affected limb. Due to the multi‐faceted nature of the condition there are a wide range of potential health outcome measures for use within CRPS related clinical trials. This aim of this systematic literature review was to identify which patient or health professional questionnaire format outcome measures have been used in CRPS specific clinical trials, and which of these have been developed specifically for use in CRPS populations. Information gained from this review will inform an international consortium project to define a Core Outcome measurement set for CRPS Clinical trials.
Insulin-sensitisers in the treatment of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine condition with reproductive and metabolic implications. In the current setting there is an evolving, yet inadequate, understanding of the pathophysiology, long-term health implications and ideal therapies for women with PCOS. Insulin resistance, secondary to both genetic and lifestyle factors, is integrally involved in the pathogenesis, the metabolic and clinical features and the long-term sequelae of PCOS in a majority of patients. Therapeutic strategies targeting insulin resistance ameliorate clinical features and may reduce long-term sequelae of PCOS, including diabetes. The main benefit of improved insulin resistance is to improve fertility and potentially to improve clinical features of hyperandrogenism and lower androgen levels. Insulin sensitisers also have the potential to delay the development of diabetes and cardiovascular disease in PCOS. Lifestyle therapy is indicated as the first intervention; however, metformin as an insulin sensitising agent has a role in first-line medical therapy in women with PCOS. Further research is needed to define the role of insulin sensitisers in PCOS and to determine the long-term risks and benefits of these therapies.
Small-Cost Asymptotics for Long-Term Growth Rates in Incomplete Markets

This article provides a rigorous asymptotic analysis of long-term growth rates under both proportional and Morton-Pliska transaction costs. We consider a general incomplete financial market with an unspanned Markov factor process that includes the Heston stochastic volatility model and the Kim-Omberg stochastic excess return model as special cases. Using a dynamic programming approach, we determine the leading-order expansions of long-term growth rates and explicitly construct strategies that are optimal at the leading order. We further analyze the asymptotic performance of Morton-Pliska strategies in settings with proportional transaction costs. We find that the performance of the optimal Morton-Pliska strategy is the same as that of the optimal one with costs increased by a factor of √2. Finally, we demonstrate that our strategies are in fact pathwise optimal, in the sense that they maximize the long-run growth rate path by path. All our results are substantiated by verification arguments.
Representing the States Before the U.S. Supreme Court: State Amicus Brief Participation, the Policy-making Environment, and the Fourth Amendment

State attorneys general, situated at the intersection of the state and federal governments, are increasingly the subject of scholarly inquiry. Yet, little work examines what prompts them to participate as amici. The decision to participate as amici reveals important information about how state actors attempt to shape outcomes at the federal level. We investigate how the broader policy-making environment facilitates and constrains AG amicus brief initiation and joining. Analyzing all orally argued Fourth Amendment cases from 1970 to 2009, we find the characteristics of the policy-making environment shape AG amicus activity. Initiation is predicted by institutional resources; whereas joining is the product of legal case facts and institutional resources. Because prior research notes larger attorney general coalitions are more successful, we highlight the complexity of amicus participation by state actors and speak to the conditions under which state actors can mobilize large coalitions to shape federal search and seizure case law.
Behavioral Observations of Parents With ADHD During Parent Training

Objective: Several studies suggest that parental ADHD impedes behavioral parent training (BPT) outcomes. Parental ADHD symptoms exhibited during BPT may interfere with the acquisition of new skills. This study explored the observed behavior of parents with ADHD during BPT. Method: Parents of children with ADHD attending group BPT completed self-ratings of their ADHD symptoms. Parents indicating a moderate level of ADHD symptoms were administered a clinical interview, and 37.3% of parents met ADHD criteria based on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) clinician-rated symptom counts. Results: Parents with high ADHD symptoms displayed more total and off-task violations compared with parents with low ADHD symptoms, although no significant differences emerged for other behaviors (i.e., working quietly, using materials appropriately, and remaining in seat), absences, or tardiness. Conclusion: Parental ADHD symptoms were manifested during BPT. Future research should clarify the nature of parental behavior in BPT as a possible mechanism explaining the relation between parental ADHD and impaired BPT outcomes.
Autologous Platelets Have No Effect on the Healing of Human Achilles Tendon Ruptures

Background: Animal studies have shown that local application of platelet-rich plasma (PRP) stimulates tendon repair. Preliminary results from a retrospective case series have shown faster return to sports. Hypothesis: Autologous PRP stimulates healing of acute Achilles tendon ruptures. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: Thirty patients were recruited consecutively. During surgery, tantalum beads were implanted in the Achilles tendon proximal and distal to the rupture. Before skin suture, randomization was performed, and 16 patients were injected with 10mL PRP (10 times higher platelet concentration than peripheral blood) whereas 14 were not. With 3-dimensional radiographs (roentgen stereophotogrammetric analysis; RSA), the distance between the beads was measured at 7, 19, and 52 weeks while the patient resisted different dorsal flexion moments over the ankle joint, thereby estimating tendon strain per load. An estimate of elasticity modulus was calculated using callus dimensions from computed tomography. At 1 year, functional outcome was evaluated, including the heel raise index and Achilles Tendon Total Rupture Score. The primary effect variables were elasticity modulus at 7 weeks and heel raise index at 1 year. Results: The mechanical variables showed a large degree of variation between patients that could not be explained by measuring error. No significant group differences in elasticity modulus could be shown. There was no significant difference in heel raise index. The Achilles Tendon Total Rupture Score was lower in the PRP group, suggesting a detrimental effect. There was a correlation between the elasticity modulus at 7 and 19 weeks and the heel raise index at 52 weeks. Conclusion: The results suggest that PRP is not useful for treatment of Achilles tendon ruptures. The variation in elasticity modulus provides biologically relevant information, although it is unclear how early biomechanics is connected to late clinical results.
A comprehensive review of recent studies on pharmacokinetics of traditional Chinese medicines (2014–2017) and perspectives

Abstract Traditional Chinese medicines (TCMs) have a long history for safely treating human diseases. Unlike western medicine, TCMs usually contain multiple components synergistically and holistically acting on the diseases. It remains a big challenge to represent rationally the in vivo process of multiple components of TCMs for understanding the relationship between administration and therapeutic effects. For years, efforts were always made to face the challenge, and the achievements were obvious. Here, we give an comprehensive overview of the recent investigation progress (from 2015 to 2017, except the part of ‘integrated pharmacokinetics of TCMs’ from 2014 to 2017 and the part of ‘reverse pharmacokinetics in drug discovery from natural medicines’ in 2014) on pharmacokinetics of TCMs, mainly referring to the following six aspects: (1) classical pharmacokinetic studies on TCMs; (2) absorbed components and metabolites identification of TCMs; (3) pharmacokinetic herb–drug interactions and herb–herb interactions with TCMs; (4) integrated pharmacokinetics of TCMs; (5) pharmacokinetic and pharmacodynamic combination studies to dissect the action mechanisms of TCMs; and (6) reverse pharmacokinetics in drug discovery from natural medicines. Finally, based on the insights from the recent progress and our latest efforts, we propose new perspectives on the integrated pharmacokinetics of TCMs.
A Model of Training Policies in an Imperfectly Labour Market

According to human capital theory training underinvestment can arise in case of imperfect competition in the labour markets and when workers are credit constrained. In both cases training policies have to be considered in order to increase the amount of training and to alleviate the consequences of underinvestment. The model developed in this paper puts in evidence the structure of costs and benefits on which the decisions of investment in human capital by firms and workers depend under the hypothesis of imperfect labour markets. Several options of training policy are analysed through the model and their outcomes compared for what concerns the level of training and other features like the distribution of costs and benefits and wage differentials between trainees and trained workforce. The second section draws a theoretical scheme of evaluation of training policies effectiveness in connection with the structural characteristics of the markets. The third section develops the model of analysis of the enterprises' choices relative to training under the hypothesis of an imperfect labour market and in the presence of different policies and of collective wage bargaining. The last section synthesizes main results and indicates some prospects of further research.