bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Exposure Problem and Market Design
Authors: Goeree Jacob K , Lindsay Luke 
Published: September 2019

AbstractMarkets have an exposure problem when getting to the optimal allocation requires a sequence of transactions which if started but not completed leaves at least one trader with losses. We use laboratory experiments to evaluate the effect of the exposure problem on alternative market mechanisms. The continuous double auction performs poorly: efficiency is only 20% when exposure is high and 55% when it is low. A package market effectively eliminates the exposure problem: in low and high-exposure treatments efficiency is 82% and 89%, respectively. Building on stability notions from matching theory we introduce the concept of mechanism stability. A model of trade that combines mechanism stability with noisy best responses and imperfect foresight explains the difference in market performance. Finally, decentralized bargaining with contingent contracts performs well with perfect information and communication but not in the more realistic case when traders’ preferences are privately known.
Externalities and Benefit Design in Health Insurance
Authors: Starc Amanda , Town Robert J 
Published: September 2019

Abstract
Insurance benefit design has important implications for consumer welfare. In this article, we model insurer behaviour in the Medicare prescription drug coverage market and show that strategic private insurer incentives impose a fiscal externality on the traditional Medicare program. We document that plans covering medical expenses have more generous drug coverage than plans that are only responsible for prescription drug spending, which translates into higher drug utilization by enrolees. The effect is driven by drugs that reduce medical expenditure and treat chronic conditions. Our equilibrium model of benefit design endogenizes plan characteristics and accounts for asymmetric information; the model estimates confirm that differential incentives to internalize medical care offsets can explain disparities across plans. Counterfactuals show that strategic insurer incentives are as important as asymmetric information in determining benefit design.
Cardiopulmonary exercise testing in a combined screening approach to individuate pulmonary arterial hypertension in systemic sclerosis
Authors: Santaniello Alessandro , Casella Rosa , Vicenzi Marco , Rota Irene , Montanelli Gaia , De Santis Maria , Bellocchi Chiara , Lombardi Federico , Beretta Lorenzo 
Published: September 2019

Abstract

Objectives
The DETECT algorithm has been developed to identify SSc patients at risk for pulmonary arterial hypertension (PAH) yielding high sensitivity but low specificity, and positive predictive value. We tested whether cardiopulmonary exercise testing (CPET) could improve the performance of the DETECT screening strategy.

Methods
Consecutive SSc patients over a 30-month period were screened with the DETECT algorithm and positive subjects were referred for CPET before the execution of right-heart catheterization. The predictive performance of CPET on top of DETECT was evaluated and internally validated via bootstrap replicates.

Results
Out of 314 patients, 96 satisfied the DETECT application criteria and 54 were positive. PAH was ascertained in 17 (31.5%) and pre-capillary pulmonary hypertension in 23 (42.6%) patients. Within CPET variables, the slope of the minute ventilation to carbon dioxide production relationship (VE/VCO2 slope) had the best performance to predict PAH at right-heart catheterization [median (interquartile range) of specificity 0.778 (0.714–0.846), positive predictive value 0.636 (0.556–0.750)]; exploratory analysis on pre-capillary yielded a specificity of 0.714 (0.636–0.8) and positive predictive value of 0.714 (0.636–0.8).

Conclusion
In association with the DETECT algorithm, CPET may be considered as a useful tool in the workup of SSc-related pulmonary hypertension. The sequential determination of the VE/VCO2 slope in DETECT-positive subjects may reduce the number of unnecessary invasive procedures without any loss in the capability to capture PAH. This strategy had also a remarkable performance in highlighting the presence of pre-capillary pulmonary hypertension.
Adaptive mechanisms driving maladaptive pain: how chronic ongoing activity in primary nociceptors can enhance evolutionary fitness after severe injury
Authors: Walters Edgar T. 
Published: September 2019

Chronic pain is considered maladaptive by clinicians because it provides no apparent protective or recuperative benefits. Similarly, evolutionary speculations have assumed that chronic pain represents maladaptive or evolutionarily neutral dysregulation of acute pain mechanisms. By contrast, the present hypothesis proposes that chronic pain can be driven by mechanisms that evolved to reduce increased vulnerability to attack from predators and aggressive conspecifics, which often target prey showing physical impairment after severe injury. Ongoing pain and anxiety persisting long after severe injury continue to enhance vigilance and behavioural caution, decreasing the heightened vulnerability to attack that results from motor impairment and disfigurement, thereby increasing survival and reproduction (fitness). This hypothesis is supported by evidence of animals surviving and reproducing after traumatic amputations, and by complex specializations that enable primary nociceptors to detect local and systemic signs of injury and inflammation, and to maintain low-frequency discharge that can promote ongoing pain indefinitely. Ongoing activity in nociceptors involves intricate electrophysiological and anatomical specializations, including inducible alterations in the expression of ion channels and receptors that produce persistent hyperexcitability and hypersensitivity to chemical signals of injury. Clinically maladaptive chronic pain may sometimes result from the recruitment of this powerful evolutionary adaptation to severe bodily injury.
This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Comparative studies of endocannabinoid modulation of pain
Authors: Paulsen Riley T. , Burrell Brian D. 
Published: September 2019

Cannabinoid-based therapies have long been used to treat pain, but there remain questions about their actual mechanisms and efficacy. From an evolutionary perspective, the cannabinoid system would appear to be highly conserved given that the most prevalent endogenous cannabinoid (endocannabinoid) transmitters, 2-arachidonyl glycerol and anandamide, have been found throughout the animal kingdom, at least in the species that have been analysed to date. This review will first examine recent findings regarding the potential conservation across invertebrates and chordates of the enzymes responsible for endocannabinoid synthesis and degradation and the receptors that these transmitters act on. Next, comparisons of how endocannabinoids modulate nociception will be examined for commonalities between vertebrates and invertebrates, with a focus on the medicinal leechHirudo verbana. Evidence is presented that there are distinct, evolutionarily conserved anti-nociceptive and pro-nociceptive effects. The combined studies across various animal phyla demonstrate the utility of using comparative approaches to understand conserved mechanisms for modulating nociception.This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
An assay for chemical nociception inDrosophilalarvae
Authors: Lopez-Bellido Roger , Himmel Nathaniel J. , Gutstein Howard B. , Cox Daniel N. , Galko Michael J. 
Published: September 2019

Chemically induced nociception has not yet been studied intensively in genetically tractable models. Hence, our goal was to establish aDrosophilaassay that can be used to study the cellular and molecular/genetic bases of chemically induced nociception.Drosophilalarvae exposed to increasing concentrations of hydrochloric acid (HCl) produced an increasingly intense aversive rolling response. HCl (0.5%) was subthreshold and provoked no response. All classes of peripheral multidendritic (md) sensory neurons (classes I–IV) are required for full responsiveness to acid, with class IV making the largest contribution. At the cellular level, classes IV, III and I showed increases in calcium following acid exposure. In the central nervous system, Basin-4 second-order neurons are the key regulators of chemically induced nociception, with a slight contribution from other types. Finally, chemical nociception can be sensitized by tissue damage. Subthreshold HCl provoked chemical allodynia in larvae 4 h after physical puncture wounding. Pinch wounding and UV irradiation, which do not compromise the cuticle, did not cause chemical allodynia. In sum, we developed a novel assay to study chemically induced nociception inDrosophilalarvae. This assay, combined with the high genetic resolving power ofDrosophila,should improve our basic understanding of fundamental mechanisms of chemical nociception.This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
An evolutionary medicine perspective on pain and its disorders
Authors: Nesse Randolph M. , Schulkin Jay 
Published: September 2019

Enormous progress in understanding the mechanisms that mediate pain can be augmented by an evolutionary medicine perspective on how the capacity for pain gives selective advantages, the trade-offs that shaped the mechanisms, and evolutionary explanations for the system's vulnerability to excessive and chronic pain. Syndromes of deficient pain document tragically the utility of pain to motivate escape from and avoidance of situations causing tissue damage. Much apparently excessive pain is actually normal because the cost of more pain is often vastly less than the cost of too little pain (the smoke detector principle). Vulnerability to pathological pain may be explained in part because natural selection has shaped mechanisms that respond adaptively to repeated tissue damage by decreasing the pain threshold and increasing pain salience. The other half of an evolutionary approach describes the phylogeny of pain mechanisms; the apparent independence of different kinds of pain is of special interest. Painful mental states such as anxiety, guilt and low mood may have evolved from physical pain precursors. Preliminary evidence for this is found in anatomic and genetic data. Such insights from evolutionary medicine may help in understanding vulnerability to chronic pain.This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
The neuroscience of vision and pain: evolution of two disciplines
Authors: Finlay Barbara L. 
Published: September 2019

Research in the neuroscience of pain perception and visual perception has taken contrasting paths. The contextual and the social aspects of pain judgements predisposed pain researchers to develop computational and functional accounts early, while vision researchers tended to simple localizationist or descriptive approaches first. Evolutionary thought was applied to distinct domains, such as game-theoretic approaches to cheater detection in pain research, versus vision scientists' studies of comparative visual ecologies. Both fields now contemplate current motor or decision-based accounts of perception, particularly predictive coding. Vision researchers do so without the benefit of earlier attention to social and motivational aspects of vision, while pain researchers lack a comparative behavioural ecology of pain, the normal incidence and utility of responses to tissue damage. Hybrid hypotheses arising from predictive coding as used in both domains are applied to some perplexing phenomena in pain perception to suggest future directions. The contingent and predictive interpretation of complex sensations, in such domains as ‘runner's high’, multiple cosmetic procedures, self-harm and circadian rhythms in pain sensitivity is one example. The second, in an evolutionary time frame, considers enhancement of primary perception and expression of pain in social species, when expressions of pain might reliably elicit useful help.This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Pain in dinosaurs: what is the evidence?
Authors: Hearn Les , Williams Amanda C. de C. 
Published: September 2019

How far back can we trace behaviour associated with pain? Behaviour is not preserved in the palaeontological record, so, for dinosaurs, we are restricted to what we can deduce from fossilized bones and tracks. This review is a thought experiment using circumstantial evidence from dinosaur fossils and from the behaviour of their extant relatives to describe probable responses of dinosaurs to serious injuries. Searches yielded 196 papers and chapters with: reports of healed serious injuries, and limping gait and injured feet in trackways; information about physiology and behaviour relevant to healing; evidence of evolutionary connections with birds and crocodilians, and their behaviour; and information about relevant aspects of evolution. Clearly, many dinosaurs survived injuries that would have seriously hampered mobility, impairing hunting or escape from predators, and affecting social interactions. Recovery from severe injuries implies pain-mediated responses. Rates of healing seem faster than for other reptiles, possibily aided by warm-bloodedness. Nesting was often communal, raising the possibility of parental and group protection for injured young. The existence of family groups, packs or herds raises the possibility of protection or feeding from pack kills. This is the first study, to our knowledge, of possible pain behaviour and responses to injury in dinosaurs.
This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Demonstration of a portable intracortical brain-computer interface
Authors: Weiss Jeffrey M. , Gaunt Robert A. , Franklin Robert , Boninger Michael , Collinger Jennifer L. 
Published: September 2019

AbstractWhile recent advances in intracortical brain-computer interfaces (iBCI) have demonstrated the ability to restore motor and communication functions, such demonstrations have generally been confined to controlled experimental settings and have required bulky laboratory hardware. Here, we developed and evaluated a self-contained portable iBCI that enabled the user to interact with various computer programs. The iBCI, which weighs 1.5 kg, consists of digital headstages, a small signal processing hub, and a tablet PC. A human participant tested the portable iBCI in laboratory and home settings under an FDA Investigational Device Exemption (NCT01894802). The participant successfully completed 96% of trials in a 2D cursor center-out task with the portable iBCI, a rate indistinguishable from that achieved with the standard laboratory iBCI. The participant also completed a variety of free-form tasks, including drawing, gaming, and typing.
Rate and predictors of Treatment Failure among pediatric population taking Highly Active Antiretroviral Therapy in Ethiopia
Authors: Getaneh Yimam , Yizengaw Ajanaw , Likie Agajie , Getahun Mulusew , Feleke Altaye , Kidane Eleni , Yilma Amelework , Mulugeta Achamyeleh , Moshago Tezera , Assefa Yibeltal 
Published: September 2019

AbstractBackgroundThough the unprecedented global effort at scaling up universal access to antiretroviral therapy (ART) has decreased the progression of HIV, treatment failure (TF) among pediatric patients receiving ART against human immunodeficiency virus (HIV) is becoming a global public health concern which may impact on treatment outcome. Thus, the aim of this study was to determine the rate and predictors of treatment failure (TF) among HIV-infected pediatric patients taking ART in Ethiopia.MethodsA prospective and retrospective follow-up study was conducted from March 2016 to 2017. Retrospective clinical and laboratory data were captured from patients’ medical record. Socio-demographics and explanatory variables of participants were collected using pre-tested structured questionnaire and study participants were followed for three to six month after baseline viral load has been done to classify virologic failure (VF). TF was ascertained from population who virally failed with the denominator of population taking ART. Chi-square test and multiple logistic regressions were conducted to assess predictors TF. Statistical significance was set at P-value less than 0.05.ResultsA total of 554 pediatrics patients taking ART from 40 selected health facilities were included in the study. Viral load suppression (VLS) (VL<1000 copies/ml) among pediatric population taking ART in Ethiopia were found to be 344 (62.1%). From those who was not virally suppressed at baseline of the study 210 (37.9%), 99 (51.6%) were re-suppressed after three to six month of enhanced adherence and counseling, leading the overall virologic failure (VF) among pediatric population taking ART in Ethiopia to be 93 (17.3%). The mean CD4 count was improved from 490 cells/ml at ART initiation to 921 cells/ml after 80 months of ART exposure. Moreover, the clinical outcome was improved from 42% to 89% at ART initiation and after 80 month of ART experience. CD4 count, clinical stage, Hemoglobin and weight were found to be predictors of VF. Moreover; family HIV and disclosure status, duration on ART, age, being orphan, stigma and medication adherence have significant association with VF.ConclusionsThe low level of VLS (62.1%) and the high level of VF (18.3%) could explain the challenge on the national ART program among pediatric population. The significant improvement on immunologic and clinical outcome could indicate the success of ART on treatment outcome among pediatric population. CD4 count, clinical stage, Hemoglobin and weight could be good predictors of TF among pediatric population. Improving disclosure status, stigma and medication adherence could improve the treatment outcome of pediatric population taking ART in Ethiopia.
Excess Pneumonia Mortality During a Legionnaires’ Disease Outbreak in Flint, Michigan
Authors: Binney ZO , Nelson KN , Chamberlain AT 
Published: September 2019

AbstractIntroductionFrom June 2014-October 2015, the Michigan Department of Health and Human Services (MDHHS) reported a Legionnaires’ disease (LD) outbreak in Genesee County, Michigan, of which Flint is the county seat. MDHHS’ final case count for the outbreak was 90 cases, including 10 deaths among Genesee County residents. As LD is not routinely tested for as a cause of community-acquired pneumonia, the size of the outbreak may have been underestimated. Specifically, some LD cases may have been classified as pneumonias of other or unexplained etiologies.ObjectiveTo estimate excess pneumonia deaths in Genesee County during the 2014-15 LD outbreak and compare this with reported deaths due to LD.MethodsWe used data from the CDC WONDER database, which contains monthly county-level counts of death certificates, on all pneumonia deaths among residents of Genesee and a set of similar counties from 2011-2017. We calculated excess pneumonia deaths in Genesee during the period of the LD outbreak (May 2014-October 2015). We used data from the Genesee County Vital Records Division to map pneumonia deaths by census tract to assess geographic overlap with reported LD cases.ResultsWe estimated 70.0 excess pneumonia deaths (90% uncertainty interval (UI): 36 to 103) in Genesee County during the LD outbreak. This is substantially higher than the 10 LD deaths among Genesee County residents reported by MDHHS. Areas of high pneumonia mortality overlapped with those with high LD incidence and were primarily located in western Flint and northwestern non-Flint Genesee County.ConclusionsThese findings are consistent with the hypothesis that the LD outbreak was larger than reported. Earlier detection and response to this outbreak may have facilitated identification of these additional cases.
medExtractR: A medication extraction algorithm for electronic health records using the R programming language
Authors: Weeks Hannah L. , Beck Cole , McNeer Elizabeth , Bejan Cosmin A. , Denny Joshua C. , Choi Leena 
Published: September 2019

ABSTRACTObjectiveWe developed medExtractR, a natural language processing system to extract medication dose and timing information from clinical notes. Our system facilitates creation of medication-specific research datasets from electronic health records.Materials and MethodsWritten using the R programming language, medExtractR combines lexicon dictionaries and regular expression patterns to identify relevant medication information (‘drug entities’). The system is designed to extract particular medications of interest, rather than all possible medications mentioned in a clinical note. MedExtractR was developed on notes from Vanderbilt University’s Synthetic Derivative, using two medications (tacrolimus and lamotrigine) prescribed with varying complexity, and with a third drug (allopurinol) used for testing generalizability of results. We evaluated medExtractR and compared it to three existing systems: MedEx, MedXN, and CLAMP.ResultsOn 50 test notes for each development drug and 110 test notes for the additional drug, medExtractR achieved high overall performance (F-measures > 0.95). This exceeded the performance of the three existing systems across all drugs, with the exception of a couple specific entity-level evaluations including dose amount for lamotrigine and allopurinol.DiscussionMedExtractR successfully extracted medication entities for medications of interest. High performance in entity-level extraction tasks provides a strong foundation for developing robust research datasets for pharmacological research. However, its targeted approach provides a narrower scope compared with existing systems.ConclusionMedExtractR (available as an R package) achieved high performance values in extracting specific medications from clinical text, leading to higher quality research datasets for drug-related studies than some existing general-purpose medication extraction tools.
Mammalian RAD51 prevents non-conservative alternative end-joining and single strand annealing through non-catalytic mechanisms
Authors: So Ayeong , Muhammad Ali , Chailleux Catherine , Sanz Laura Sesma , Ragu Sandrine , Le Cam Eric , Canitrot Yvan , Masson Jean Yves , Dupaigne Pauline , Lopez Bernard S. , Guirouilh-Barbat Josée 
Published: September 2019

AbstractThe selection of the DNA double-strand breaks (DSBs) repair pathway is decisive for genetic stability/instability. We proposed that it acts according to two successive steps: 1-canonical non-homologous end-joining (C-NHEJ)versussingle-strand DNA (ssDNA) resection; 2- on ssDNA, gene conversion (GC)versusnon-conservative single-strand annealing (SSA) or alternative end-joining (A-EJ).Using intramolecular substrates, we systematically analysed the equilibrium between the different DSB repair pathways. We show that ablation of RAD51 stimulated both SSA and A-EJ but did not stimulate C-NHEJ, validating the two-step model. Moreover, we found that two ATP-mutant dominant-negative forms of RAD51 that stimulated non-conservative repair, failed to load into damaged chromatin, clarifying the role of ATP in RAD51-mediated HR, also. In contrast, another dominant-negative form of RAD51, which retains its DNA binding capacities, repressed SSA and A-EJ, revealing two separable functions of RAD51 i.e. GC and non-conservative repair inhibition. In vitroassays show that the binding of RAD51 on both complementary ssDNA is required to block both spontaneous and RAD52-induced strand annealing. Therefore, RAD51 represses non-conservative repair (SSA and A-EJ), by inhibiting the annealing step through ssDNA occupancy, independently of the catalytic strand-exchange activity required for GC.