bluuebunny/crossref_metadata_2025 huggingface dataset:
Packaged peristaltic micropump for controlled drug delivery application
Authors: Vinayakumar K. B. , Nadiger Girish , R. Shetty Vikas , Dinesh N. S. , Nayak M. M. , Rajanna K.
Published: January 2017

Micropump technology has evolved significantly in the last two decades and is finding a variety of applications ranging from μTAS (micro Total Analysis System) to drug delivery. However, the application area of the micropump is limited owing to: simple pumping mechanism, ease of handling, controlled (microliter to milliliter) delivery, continuous delivery, and accuracy in flow rate. Here, the author presents the design, development, characterization, and precision flow controlling of a DC-motor driven peristaltic pump for controlled drug delivery application. All the micropump components were fabricated using the conventional fabrication technique. The volume flow variation of the pump has been characterized for different viscous fluids. The change in volume flow due to change in back pressure has been presented in detail. The fail-safe mode operation of the pump has been tested and leak rate was measured (∼0.14% leak for an inlet pressure of 140 kPa) for different inlet pressures. The precision volume flow of the pump has been achieved by measuring the pinch cam position and load current. The accuracy in the volume flow has been measured after 300 rotations. Finally, the complete system has been integrated with the necessary electronics and an android application has been developed for the self-administration of bolus and basal delivery of insulin.
The band gap variation of a two dimensional binary locally resonant structure in thermal environment
Authors: Li Zhen , Wang Xian , Li Yue-ming
Published: January 2017

In this study, the numerical investigation of thermal effect on band gap dynamical characteristic for a two-dimensional binary structure composed of aluminum plate periodically filled with nitrile rubber cylinder is presented. Initially, the band gap of the binary structure variation trend with increasing temperature is studied by taking the softening effect of thermal stress into account. A breakthrough is made which found the band gap being narrower and shifting to lower frequency in thermal environment. The complete band gap which in higher frequency is more sensitive to temperature that it disappears with temperature increasing. Then some new transformed models are created by changing the height of nitrile rubber cylinder from 1mm to 7mm. Simulations show that transformed model can produce a wider band gap (either flexure or complete band gap). A proper forbidden gap of elastic wave can be utilized in thermal environment although both flexure and complete band gaps become narrower with temperature. Besides that, there is a zero-frequency flat band appearing in the first flexure band, and it becomes broader with temperature increasing. The band gap width decreases trend in thermal environment, as well as the wider band gap induced by the transformed model with higher nitrile rubber cylinder is useful for the design and application of phononic crystal structures in thermal environment.
Influence of particle arrangement on the permittivity of an elastomeric composite
Authors: Tsai Peiying J. , Nayak Suchitra , Ghosh Suvojit , Puri Ishwar K.
Published: January 2017

Elastomers are used as dielectric layers contained between the parallel conductive plates of capacitors. The introduction of filler particles into an elastomer changes its permittivity ε. When particle organization in a composite is intentionally varied, this alters its capacitance. Using numerical simulations, we examine how conductive particle chains introduced into polydimethylsiloxane (PDMS) alter ε. The effects of filler volume fraction ψ, interparticle d and interchain spacing a, zigzag angle θ between adjacent particles and overall chain orientation, particle size r, and clearance h between particles and the conductive plates are characterized. When filler particles are organized into chainlike structures rather than being just randomly distributed in the elastomer matrix, ε increases by as much as 85%. When particles are organized into chainlike forms, ε increases with increasing ψ and a, but decreases with increasing d and θ. A composite containing smaller particles has a higher ε when ψ<9% while larger particles provide greater enhancement when ψ is larger than that value. To enhance ε, adjacent particles must be interconnected and the overall chain direction should be oriented perpendicular to the conductive plates. These results are useful for additive manufacturing on electrical applications of elastomeric composites.
Brønsted Base-Mediated Aziridination of 2-Alkyl-Substituted-1,3-Dicarbonyl Compounds and 2-Acyl-Substituted-1,4-Dicarbonyl Compounds by Iminoiodanes
Authors: Tejo Ciputra , Tirtorahardjo Davin , Day David Philip , Ma Dik-Lung , Leung Chung-Hang , Chan Philip Wai Hong
Published: January 2017

The synthesis of α,α-diacylaziridines and α,α,β-triacylaziridines from reaction of 2-alkyl-substituted-1,3-dicarbonyl compounds and 2-acyl-substituted-1,4-dicarbonyl compounds with arylsulfonyliminoiodinanes (ArSO2N=IPh) under Brønsted base-mediated atmospheric conditions is described. The reaction mechanism is thought to involve the formal oxidation of the substrate followed by aziridination of the ensuing α,β-unsaturated intermediate by the hypervalent iodine(iii) reagent.
Accuracy and computational efficiency of genomic selection with high-density SNP and whole-genome sequence data.
Authors: Wang TingTing Wang TingTing , Chen YiPing [Chen Y. P. P. ] , Hayes B.
Published: January 2017

The prediction of complex or quantitative traits from single nucleotide polymorphism (SNP) genotypes has transformed livestock and plant breeding, and is also playing an increasingly important role in prediction of human disease. Genomic predictions are made using a prediction equation derived from regressing the phenotypes of the individuals in a reference population on all available SNP simultaneously. Genomic selection is then selection of animals or plants for breeding based on these genomic predictions. As the rate of genetic gain that can be achieved with genomic selection is proportional to the accuracy of the genomic predictions, a key focus is now to increase the accuracy of genomic predictions. This can be achieved by increasing the size of the reference set, using denser markers, and using appropriate genomic prediction models. A wide range of genomic prediction models have been proposed, some of which use marker selection and either linear or non-linear Bayesian models for regression. The non-linear Bayesian models give higher accuracy of genomic prediction for some traits, particularly as marker density increases, but at the cost of high computational burden. Strategies to improve computational efficiency of the non-linear Bayesian methods are becoming more important, as the ultimate marker density is whole-genome sequence, and this is increasingly affordable in many species. In this paper, we review the performance of alternative models for genomic prediction. Strategies that have been proposed to improve the computational efficiency of implementing these models are evaluated. Finally, we outline what is required to enable genomic prediction from whole-genome sequence data.
Culture of honour and the blaming of women in cases of rape / La cultura del honor y la inculpación de la mujer en casos de violación
Authors: Canto Jesús M. , Perles Fabiola , San Martín Jesús
Published: January 2017

The main objective of this research was to examine the influence of the culture of honour on victim blaming according to three types of rape scenarios involving the rape of a married woman (stranger rape vs. acquaintance rape vs. marital rape). A total of 262 university students (120 men and 142 women) participated in this study. Our results confirmed the influence of the culture of honour on the acquaintance rape scenario in the degree of victim blaming, followed by the marital rape scenario. In both scenarios the behaviour of the victim challenged the codes of the culture of honour. The results confirmed that the participants’ answers depended on the interaction of situational variables of a rape (type of scenarios) and the variables concerning the observer (the culture of honour).
A Refined Electrofishing Technique for Collecting Silver Carp: Implications for Management
Authors: Bouska Wesley W. , Glover David C. , Bouska Kristen L. , Garvey James E.
Published: January 2017

Detecting nuisance species at low abundance or in newly established areas is critical to developing pest management strategies. Due to their sensitivity to disturbance and erratic jumping behavior, Silver Carp Hypophthalmichthys molitrix can be difficult to collect with traditional sampling methods. We compared catch per unit effort (CPUE) of all species from a Long Term Resource Monitoring (LTRM) electrofishing protocol to an experimental electrofishing technique designed to minimize Silver Carp evasion through tactical boat maneuvering and selective application of power. Differences in CPUE between electrofishing methods were detected for 2 of 41 species collected across 2 years of sampling at 20 sites along the Illinois River. The mean catch rate of Silver Carp using the experimental technique was 2.2 times the mean catch rate of the LTRM electrofishing technique; the increased capture efficiency at low relative abundance emphasizes the utility of this method for early detection. The experimental electrofishing also collected slightly larger Silver Carp (mean: 510.7 mm TL versus 495.2 mm TL), and nearly four times as many Silver Carp independently jumped into the boat during experimental transects. Novel sampling approaches, such as the experimental electrofishing technique used in this study, should be considered to increase probability of detection for aquatic nuisance species.

Received June 9, 2016; accepted September 19, 2016 Published online January 3, 2017
Contact Selectivity for Four Fish Species Sampled with North American Standard Gill Nets
Authors: Smith Bradley J. , Blackwell Brian G. , Wuellner Melissa R. , Graeb Brian D. S. , Willis David W.
Published: January 2017

The American Fisheries Society (AFS) has recommended standard gears and methods for collecting North American freshwater fish data, but selectivity of these gears, including gill nets, is poorly described for most species. We calculated contact selectivity for species commonly collected with AFS standard gill nets in lakes and reservoirs of North America, including Black Bullhead Ameiurus melas, Channel Catfish Ictalurus punctatus, Walleye Sander vitreus, and Yellow Perch Perca flavescens. The normal selectivity curve provided the best fit to empirical catch data for all species. Inclusion of a tangle factor improved model fit for Black Bullhead, Channel Catfish, and Walleye, indicating that tangling is an important means of capture for these species. Channel Catfish were more susceptible to tangling than the closely related Black Bullhead, likely because larger Channel Catfish are more vulnerable to tangling by spines in the smallest meshes, whereas Black Bullhead in the same meshes were wedged. Failure to include a tangle factor for Channel Catfish and Walleye would have underestimated peak length of captured fish by 80 and 40 mm, respectively. Tangling was not an important factor in Yellow Perch capture. Total selectivity curves for each species captured with the AFS standard gill net were calculated, and relative selectivity values are provided as correction factors for size-selectivity bias. Our correction factors and modeled selectivity curves for Channel Catfish, Walleye, and Yellow Perch corroborate previous studies that modeled selectivity of the AFS standard gill net for Channel Catfish, Walleye, and Yellow Perch, but our study provided novel information on Black Bullhead. Improved selectivity information for the AFS standard gill net may help to promote further voluntary adoption of AFS standard gears and methods.

Received July 15, 2016; accepted October 24, 2016 Published online January 3, 2017
Electrochemical direct writing and erasing of silver nanostructures on phosphate glass using atomic force microscopy
Authors: Barna Shama F , Jacobs Kyle E , Mensing Glennys A , Ferreira Placid M
Published: January 2017

This paper reports a liquid-free, mask-less electrochemical direct-write lithographic technique using an atomic force microscopy (AFM) probe for writing silver nanostructures in minutes on an optically transparent substrate. Under ambient conditions, silver is locally and controllably extracted to the surface of superionic (AgI)0.25 (AgPO3)0.75 glass by bringing a conductive AFM probe tip in contact with it, biasing the probe with a negative voltage, and regulating the resulting current. The growth mechanism of the resulting nanostructure is explored by extracting silver with a stationary AFM tip on the surface of the silver. A moving tip was then used to produce continuous lines, solid films and discrete dots of silver by implementing continuous and pulsed current writing approaches. The line dimensions depend on writing speed and current flowing in the electrochemical circuit, while the size and spacing of the dots depend on the parameters (magnitude, duration and frequency) of the current pulses and the writing speed of the AFM tip. Line-widths in the ∼100 nm range are demonstrated. Our investigation also shows that a threshold potential must be overcome to be able to draw and reduce silver ions on the glass surface. When polarity between the electrodes is reversed, the patterned silver ionizes back into the glass, thus offering the capability to erase and rewrite Ag patterns on the glass surface.
Social‐Optimal Household Food Waste: Taxes and Government Incentives
Authors: Katare Bhagyashree , Serebrennikov Dmytro , Wang H. Holly , Wetzstein Michael
Published: January 2017

In 2010, 21% of the total food available for consumption in the United States was wasted at the household level. In response to this waste, a number of counties and U.S. localities have instituted policies (disposal taxes) directed toward reducing this waste. However, currently there is no federal food‐waste disposal tax. The aim of this paper is to establish a theoretical foundation for household food waste, and based on this theory, to determine the social‐optimal food‐waste (disposal) tax, along with a government incentive. The theory unravels the interrelation between social food insecurity and external environmental costs, which is not generally considered by households when they waste food. A social‐optimal disposal tax and government incentive involve Pigovian mechanisms and governmental expenditures. For a zero level of food waste, the social‐optimal disposable tax and government incentive approach infinity.
Increased Expression of Macrophage Migration Inhibitory Factor in the Nucleus of the Solitary Tract Attenuates Renovascular Hypertension in Rats
Authors: Barbosa Rafaela Moreira , Speretta Guilherme F. , Dias Daniel Penteado Martins , Ruchaya Prashant Jay , Li Hongwei , Menani José Vanderlei , Sumners Colin , Colombari Eduardo , Colombari Débora S. A.
Published: January 2017

BACKGROUND

Macrophage migration inhibitory factor (MIF) is an intracellular inhibitory regulator of the actions of angiotensin II in the central nervous system. Renovascular hypertensive 2-kidney, 1-clip (2K1C) rats have an increased activity of the renin–angiotensin system and a decrease in baroreflex function compared to normotensive (NT) rats. In the present study, we tested the effects of MIF overexpression within the nucleus of the solitary tract (NTS), a key brainstem region for cardiovascular regulation, on the development of hypertension, on baroreflex function, and on water and food intake in 2K1C rats.

METHODS

Holtzman NT rats received a silver clip around the left renal artery to induce 2K1C hypertension. Three weeks later, rats were microinjected in the NTS with AAV2-CBA-MIF, to increase the expression of MIF, or with the control vector AAV2-CBA-enhanced green fluorescent protein. Mean arterial pressure (MAP) and heart rate were recorded by telemetry. Baroreflex function was tested, and water and food intake were also measured.

RESULTS

Increasing MIF expression in the NTS of 2K1C rats attenuated the development of hypertension, reversed the impairment of baroreflex function, and reduced the increase in water intake. In contrast to 2K1C rats, similar increases in MIF expression in the NTS of NT rats produced no changes in baseline MAP, baroreflex function, or water intake.

CONCLUSIONS

These results indicate that an increased expression of MIF within the NTS attenuates the development of hypertension and restores the baroreflex function in 2K1C rats.
The cost of Lyme borreliosis
Authors: van den Wijngaard Cees. C. , Hofhuis Agnetha , Wong Albert , Harms Margriet G. , de Wit G. Ardine , Lugnér Anna K. , Suijkerbuijk Anita W. M. , Mangen Marie-Josée J. , van Pelt Wilfrid
Published: January 2017

Background: Lyme borreliosis (LB) is the most frequently reported tick-borne infection in Europe and North America. The aim of this study was to estimate the cost-of-illness of LB in the Netherlands. Methods: We used available incidence estimates from 2010 for tick bite consultations and three symptomatic LB outcomes: erythema migrans (EM), disseminated LB and Lyme-related persisting symptoms. The cost was estimated using these incidences and the average cost per patient as derived from a patient questionnaire. We estimated the cost from a societal perspective, including healthcare cost, patient cost and production loss, using the friction cost method and a 4% annual discount rate. Results: Tick bites and LB in 2010 led to a societal cost of €19.3 million (95% CI 15.6–23.4; 16.6 million population) for the Netherlands. Healthcare cost and production loss each constituted 48% of the total cost (€9.3 and €9.2 million/year), and patient cost 4% (€0.8 million/year). Of the total cost, 37% was related to disseminated LB, followed by 27% for persisting symptoms, 22% for tick bites and 14% for EM. Per outcome, for an individual case the mean cost of disseminated LB and Lyme-related persisting symptoms was both around €5700; for EM and GP consultations for tick bites this was €122 and €53. As an alternative to the friction cost method, the human capital method resulted in a total cost of €23.5 million/year. Conclusion: LB leads to a substantial societal cost. Further research should therefore focus on additional preventive interventions.
Analysis of professional competencies for the clinical research data management profession: implications for training and professional certification
Authors: Zozus Meredith N , Lazarov Angel , Smith Leigh R , Breen Tim E , Krikorian Susan L , Zbyszewski Patrick S , Knoll Shelly K , Jendrasek Debra A , Perrin Derek C , Zambas Demetris N , Williams Tremaine B , Pieper Carl F
Published: January 2017

Objective: To assess and refine competencies for the clinical research data management profession.

Materials and Methods: Based on prior work developing and maintaining a practice standard and professional certification exam, a survey was administered to a captive group of clinical research data managers to assess professional competencies, types of data managed, types of studies supported, and necessary foundational knowledge.

Results: Respondents confirmed a set of 91 professional competencies. As expected, differences were seen in job tasks between early- to mid-career and mid- to late-career practitioners. Respondents indicated growing variability in types of studies for which they managed data and types of data managed.

Discussion: Respondents adapted favorably to the separate articulation of professional competencies vs foundational knowledge. The increases in the types of data managed and variety of research settings in which data are managed indicate a need for formal education in principles and methods that can be applied to different research contexts (ie, formal degree programs supporting the profession), and stronger links with the informatics scientific discipline, clinical research informatics in particular.

Conclusion: The results document the scope of the profession and will serve as a foundation for the next revision of the Certified Clinical Data ManagerTM exam. A clear articulation of professional competencies and necessary foundational knowledge could inform the content of graduate degree programs or tracks in areas such as clinical research informatics that will develop the current and future clinical research data management workforce.
Development and validation of a structured query language implementation of the Elixhauser comorbidity index
Authors: Epstein Richard H , Dexter Franklin
Published: January 2017

Objective: Comorbidity adjustment is often performed during outcomes and health care resource utilization research. Our goal was to develop an efficient algorithm in structured query language (SQL) to determine the Elixhauser comorbidity index.

Materials and Methods: We wrote an SQL algorithm to calculate the Elixhauser comorbidities from Diagnosis Related Group and International Classification of Diseases (ICD) codes. Validation was by comparison to expected comorbidities from combinations of these codes and to the 2013 Nationwide Readmissions Database (NRD).

Results: The SQL algorithm matched perfectly with expected comorbidities for all combinations of ICD-9 or ICD-10, and Diagnosis Related Groups. Of 13 585 859 evaluable NRD records, the algorithm matched 100% of the listed comorbidities. Processing time was ∼0.05 ms/record.

Discussion: The SQL Elixhauser code was efficient and computationally identical to the SAS algorithm used for the NRD.

Conclusions: This algorithm may be useful where preprocessing of large datasets in a relational database environment and comorbidity determination is desired before statistical analysis. A validated SQL procedure to calculate Elixhauser comorbidities and the van Walraven index from ICD-9 or ICD-10 discharge diagnosis codes has been published.
Genomic decision support needs in pediatric primary care
Authors: Pennington Jeffrey W , Karavite Dean J , Krause Edward M , Miller Jeffrey , Bernhardt Barbara A , Grundmeier Robert W
Published: January 2017

Clinical genome and exome sequencing can diagnose pediatric patients with complex conditions that often require follow-up care with multiple specialties. The American Academy of Pediatrics emphasizes the role of the medical home and the primary care pediatrician in coordinating care for patients who need multidisciplinary support. In addition, the electronic health record (EHR) with embedded clinical decision support is recognized as an important component in providing care in this setting. We interviewed 6 clinicians to assess their experience caring for patients with complex and rare genetic findings and hear their opinions about how the EHR currently supports this role. Using these results, we designed a candidate EHR clinical decision support application mock-up and conducted formative exploratory user testing with 26 pediatric primary care providers to capture opinions on its utility in practice with respect to a specific clinical scenario. Our results indicate agreement that the functionality represented by the mock-up would effectively assist with care and warrants further development.
Acute circulatory failure–chronic liver failure–sequential organ failure assessment score: a novel scoring model for mortality risk prediction in critically ill cirrhotic patients with acute circulatory failure
Authors: Zhou Xiao-Dong , Chen Qin-Fen , Wang Zheng-Xian , Liu Wen-Yue , Van Poucke Sven , Mao Zhi , Wu Sheng-Jie , Huang Wei-Jian , Zheng Ming-Hua
Published: January 2017

Background and aim

Acute circulatory failure (ACF) is associated with high mortality rates in critically ill cirrhotic patients. Only a few accurate scoring models exist specific to critically ill cirrhotic patients with acute circulatory failure (CICCF) for mortality risk assessment. The aim was to develop and evaluate a novel model specific to CICCF.

Patients and methods

This study collected and analyzed the data on CICCF from the Multiparameter Intelligent Monitoring in Intensive Care-III database. The acute circulatory failure–chronic liver failure–sequential organ failure assessment (ACF–CLIF–SOFA) score was derived by Cox’s proportional hazards regression. Performance analysis of ACF–CLIF–SOFA against CLIF–SOFA and model for end-stage liver disease systems was completed using area under the receiver operating characteristic curve.

Results

ACF–CLIF–SOFA identified six independent factors: mean arterial pressure [hazard ratio (HR)=0.984, 95% confidence interval (CI): 0.978–0.990, P<0.001], vasopressin (HR=1.548, 95% CI: 1.273–1.883, P<0.001), temperature (HR=0.764, 95% CI: 0.694–0.840, P<0.001), bilirubin (HR=1.031, 95% CI: 1.022–1.041, P<0.001), lactate (HR=1.113, 95% CI: 1.084–1.142, P<0.001), and urine output (HR=0.854, 95% CI: 0.767–0.951, P=0.004). ACF–CLIF–SOFA showed a better predictive performance than CLIF–SOFA and model for end-stage liver disease in terms of predicting mortality (0.769 vs. 0.729 vs. 0.713 at 30 days, 0.757 vs. 0.707 vs. 0.698 at 90 days, 0.733 vs. 0.685 vs. 0.691 at 1 year, respectively, all P<0.05).

Conclusion

ACF–CLIF–SOFA, as the first model specific to CICCF, enables a more accurate prediction at 30-day, 90-day, and 1-year follow-up periods than other existing scoring systems.
Reliability, precision, and clinically important change of the Nine-Hole Peg Test in individuals with multiple sclerosis
Authors: Hervault Mario , Balto Julia M. , Hubbard Elizabeth A. , Motl Robert W.
Published: January 2017

This study evaluated the reliability, precision, and clinically important change of the Nine-Hole Peg Test (9-HPT) over a 1-week period. Sixty-nine patients with multiple sclerosis completed the 9-HPT on two occasions 1 week apart. Test–retest reliability was based on intraclass correlation coefficient, and precision was based on standard error of measurement and coefficient of variation. Clinically important change was based on the minimal detectable change. Intraclass correlation coefficients exceed 0.90 for all 9-HPT metrics. Standard error of measurements for dominant (DH) and nondominant (NDH) hand time were 1.58 and 2.69 s, and 0.03 peg/s for both DH and nondominant NDH speed, respectively. Coefficient of variations for DH and NDH time were 4.3 and 3.8%, and 4.5 and 4.6% for DH and NDH speed. Minimal detectable changes for DH and NDH time were 19.4 and 29.1%, and 18.6 and 20.5% for DH and NDH speed. These data provide evidence on reliability, precision, and clinically important change of the 9-HPT over a 1-week period in multiple sclerosis for clinicians and researchers.
Auditory and visual scene analysis: an overview
Authors: Kondo Hirohito M. , van Loon Anouk M. , Kawahara Jun-Ichiro , Moore Brian C. J.
Published: January 2017

We perceive the world as stable and composed of discrete objects even though auditory and visual inputs are often ambiguous owing to spatial and temporal occluders and changes in the conditions of observation. This raises important questions regarding where and how ‘scene analysis’ is performed in the brain. Recent advances from both auditory and visual research suggest that the brain does not simply process the incoming scene properties. Rather, top-down processes such as attention, expectations and prior knowledge facilitate scene perception. Thus, scene analysis is linked not only with the extraction of stimulus features and formation and selection of perceptual objects, but also with selective attention, perceptual binding and awareness. This special issue covers novel advances in scene-analysis research obtained using a combination of psychophysics, computational modelling, neuroimaging and neurophysiology, and presents new empirical and theoretical approaches. For integrative understanding of scene analysis beyond and across sensory modalities, we provide a collection of 15 articles that enable comparison and integration of recent findings in auditory and visual scene analysis.

This article is part of the themed issue ‘Auditory and visual scene analysis’.
Modelling auditory attention
Authors: Kaya Emine Merve , Elhilali Mounya
Published: January 2017

Sounds in everyday life seldom appear in isolation. Both humans and machines are constantly flooded with a cacophony of sounds that need to be sorted through and scoured for relevant information—a phenomenon referred to as the ‘cocktail party problem’. A key component in parsing acoustic scenes is the role of attention, which mediates perception and behaviour by focusing both sensory and cognitive resources on pertinent information in the stimulus space. The current article provides a review of modelling studies of auditory attention. The review highlights how the term attention refers to a multitude of behavioural and cognitive processes that can shape sensory processing. Attention can be modulated by ‘bottom-up’ sensory-driven factors, as well as ‘top-down’ task-specific goals, expectations and learned schemas. Essentially, it acts as a selection process or processes that focus both sensory and cognitive resources on the most relevant events in the soundscape; with relevance being dictated by the stimulus itself (e.g. a loud explosion) or by a task at hand (e.g. listen to announcements in a busy airport). Recent computational models of auditory attention provide key insights into its role in facilitating perception in cluttered auditory scenes.

This article is part of the themed issue ‘Auditory and visual scene analysis’.
A roadmap for the study of conscious audition and its neural basis
Authors: Dykstra Andrew R. , Cariani Peter A. , Gutschalk Alexander
Published: January 2017

How and which aspects of neural activity give rise to subjective perceptual experience—i.e. conscious perception—is a fundamental question of neuroscience. To date, the vast majority of work concerning this question has come from vision, raising the issue of generalizability of prominent resulting theories. However, recent work has begun to shed light on the neural processes subserving conscious perception in other modalities, particularly audition. Here, we outline a roadmap for the future study of conscious auditory perception and its neural basis, paying particular attention to how conscious perception emerges (and of which elements or groups of elements) in complex auditory scenes. We begin by discussing the functional role of the auditory system, particularly as it pertains to conscious perception. Next, we ask: what are the phenomena that need to be explained by a theory of conscious auditory perception? After surveying the available literature for candidate neural correlates, we end by considering the implications that such results have for a general theory of conscious perception as well as prominent outstanding questions and what approaches/techniques can best be used to address them.

This article is part of the themed issue ‘Auditory and visual scene analysis’.
Is predictability salient? A study of attentional capture by auditory patterns
Authors: Southwell Rosy , Baumann Anna , Gal Cécile , Barascud Nicolas , Friston Karl , Chait Maria
Published: January 2017

In this series of behavioural and electroencephalography (EEG) experiments, we investigate the extent to which repeating patterns of sounds capture attention. Work in the visual domain has revealed attentional capture by statistically predictable stimuli, consistent with predictive coding accounts which suggest that attention is drawn to sensory regularities. Here, stimuli comprised rapid sequences of tone pips, arranged in regular (REG) or random (RAND) patterns. EEG data demonstrate that the brain rapidly recognizes predictable patterns manifested as a rapid increase in responses to REG relative to RAND sequences. This increase is reminiscent of the increase in gain on neural responses to attended stimuli often seen in the neuroimaging literature, and thus consistent with the hypothesis that predictable sequences draw attention. To study potential attentional capture by auditory regularities, we used REG and RAND sequences in two different behavioural tasks designed to reveal effects of attentional capture by regularity. Overall, the pattern of results suggests that regularity does not capture attention.

This article is part of the themed issue ‘Auditory and visual scene analysis’.
Cat and mouse search: the influence of scene and object analysis on eye movements when targets change locations during search
Authors: Hillstrom Anne P. , Segabinazi Joice D. , Godwin Hayward J. , Liversedge Simon P. , Benson Valerie
Published: January 2017

We explored the influence of early scene analysis and visible object characteristics on eye movements when searching for objects in photographs of scenes. On each trial, participants were shown sequentially either a scene preview or a uniform grey screen (250 ms), a visual mask, the name of the target and the scene, now including the target at a likely location. During the participant's first saccade during search, the target location was changed to: (i) a different likely location, (ii) an unlikely but possible location or (iii) a very implausible location. The results showed that the first saccade landed more often on the likely location in which the target re-appeared than on unlikely or implausible locations, and overall the first saccade landed nearer the first target location with a preview than without. Hence, rapid scene analysis influenced initial eye movement planning, but availability of the target rapidly modified that plan. After the target moved, it was found more quickly when it appeared in a likely location than when it appeared in an unlikely or implausible location. The findings show that both scene gist and object properties are extracted rapidly, and are used in conjunction to guide saccadic eye movements during visual search.

This article is part of the themed issue ‘Auditory and visual scene analysis’.
Interindividual variability in auditory scene analysis revealed by confidence judgements
Authors: Pelofi C. , de Gardelle V. , Egré P. , Pressnitzer D.
Published: January 2017

Because musicians are trained to discern sounds within complex acoustic scenes, such as an orchestra playing, it has been hypothesized that musicianship improves general auditory scene analysis abilities. Here, we compared musicians and non-musicians in a behavioural paradigm using ambiguous stimuli, combining performance, reaction times and confidence measures. We used ‘Shepard tones’, for which listeners may report either an upward or a downward pitch shift for the same ambiguous tone pair. Musicians and non-musicians performed similarly on the pitch-shift direction task. In particular, both groups were at chance for the ambiguous case. However, groups differed in their reaction times and judgements of confidence. Musicians responded to the ambiguous case with long reaction times and low confidence, whereas non-musicians responded with fast reaction times and maximal confidence. In a subsequent experiment, non-musicians displayed reduced confidence for the ambiguous case when pure-tone components of the Shepard complex were made easier to discern. The results suggest an effect of musical training on scene analysis: we speculate that musicians were more likely to discern components within complex auditory scenes, perhaps because of enhanced attentional resolution, and thus discovered the ambiguity. For untrained listeners, stimulus ambiguity was not available to perceptual awareness.

This article is part of the themed issue ‘Auditory and visual scene analysis’.
Resolving the neural dynamics of visual and auditory scene processing in the human brain: a methodological approach
Authors: Cichy Radoslaw Martin , Teng Santani
Published: January 2017

In natural environments, visual and auditory stimulation elicit responses across a large set of brain regions in a fraction of a second, yielding representations of the multimodal scene and its properties. The rapid and complex neural dynamics underlying visual and auditory information processing pose major challenges to human cognitive neuroscience. Brain signals measured non-invasively are inherently noisy, the format of neural representations is unknown, and transformations between representations are complex and often nonlinear. Further, no single non-invasive brain measurement technique provides a spatio-temporally integrated view. In this opinion piece, we argue that progress can be made by a concerted effort based on three pillars of recent methodological development: (i) sensitive analysis techniques such as decoding and cross-classification, (ii) complex computational modelling using models such as deep neural networks, and (iii) integration across imaging methods (magnetoencephalography/electroencephalography, functional magnetic resonance imaging) and models, e.g. using representational similarity analysis. We showcase two recent efforts that have been undertaken in this spirit and provide novel results about visual and auditory scene analysis. Finally, we discuss the limits of this perspective and sketch a concrete roadmap for future research.

This article is part of the themed issue ‘Auditory and visual scene analysis’.
Animal models for auditory streaming
Authors: Itatani Naoya , Klump Georg M.
Published: January 2017

Sounds in the natural environment need to be assigned to acoustic sources to evaluate complex auditory scenes. Separating sources will affect the analysis of auditory features of sounds. As the benefits of assigning sounds to specific sources accrue to all species communicating acoustically, the ability for auditory scene analysis is widespread among different animals. Animal studies allow for a deeper insight into the neuronal mechanisms underlying auditory scene analysis. Here, we will review the paradigms applied in the study of auditory scene analysis and streaming of sequential sounds in animal models. We will compare the psychophysical results from the animal studies to the evidence obtained in human psychophysics of auditory streaming, i.e. in a task commonly used for measuring the capability for auditory scene analysis. Furthermore, the neuronal correlates of auditory streaming will be reviewed in different animal models and the observations of the neurons’ response measures will be related to perception. The across-species comparison will reveal whether similar demands in the analysis of acoustic scenes have resulted in similar perceptual and neuronal processing mechanisms in the wide range of species being capable of auditory scene analysis.

This article is part of the themed issue ‘Auditory and visual scene analysis’.
Surveillance to Establish Elimination of Transmission and Freedom from Dog-mediated Rabies
Authors: Hampson Katie , Abela-Ridder Bernadette , Brunker Kirstyn , Bucheli S. Tamara M. , Carvalho Mary , Caldas Eduardo , Changalucha Joel , Cleaveland Sarah , Dushoff Jonathan , Gutierrez Veronica , Fooks Anthony R , Hotopp Karen , Haydon Daniel T , Lugelo Ahmed , Lushasi Kennedy , Mancy Rebecca , Marston Denise A , Mtema Zac , Rajeev Malavika , Dourado Lúcia R. Montebello P , Gonzalez Roldan J. F. , Rysava Kristyna , Rocha Silene Manrique , Sambo Maganga , Sikana Lwitiko , Vigilato Marco , Del Rio Vilas Victor
Published: January 2017

Background

With a global target set for zero human deaths from dog-mediated rabies by 2030 and some regional programmes close to eliminating canine rabies, there is an urgent need for enhanced surveillance strategies suitable for declaring freedom from disease and elimination of transmission with known confidence.

Methods

Using exhaustive contact tracing across settings in Tanzania we generated detailed data on rabies incidence, rabid dog biting behaviour and health-seeking behaviour of bite victims. Using these data we compared case detection of sampling-based and enhanced surveillance methodologies and investigated elimination verification procedures.

Findings

We demonstrate that patients presenting to clinics with bite injuries are sensitive sentinels for identifying dog rabies cases. Triage of patients based on bite history criteria and investigation of suspicious incidents can confirm >10% of dog rabies cases and is an affordable approach that will enable validation of disease freedom following two years without case detection. Approaches based on sampling the dog population without using bite-injury follow-up were found to be neither sensitive nor cost-effective.

Interpretation

The low prevalence of rabies, and short window in which disease can be detected, preclude sampling-based surveillance. Instead, active case finding guided by bite-patient triage is needed as elimination is approached. Our proposed methodology is affordable, practical and supports the goal of eliminating human rabies deaths by improving administration of lifesaving post-exposure prophylaxis for genuinely exposed but untreated contacts. Moreover, joint investigations by public health and veterinary workers will strengthen intersectoral partnerships and capacity for control of emerging zoonoses.
α7 nicotinic acetylcholine receptor signaling modulates the inflammatory and iron homeostasis in fetal brain microglia
Authors: Cortes M. , Cao M. , Liu H.L. , Moore C.S. , Durosier L.D. , Burns P. , Fecteau G. , Desrochers A. , Barreiro L.B. , Antel J.P. , Frasch M.G.
Published: January 2017

Neuroinflammationin uteromay result in life-long neurological disabilities. Microglia play a pivotal role, but the mechanisms are poorly understood. No early postnatal treatment strategies exist to enhance neuroprotective potential of microglia. We hypothesized that agonism on α7 nicotinic acetylcholine receptor (α7nAChR) in fetal microglia will augment their neuroprotective transcriptome profile, while the antagonistic stimulation of α7nAChR will achieve the opposite. Using anin vivo-in vitromodel of developmental programming of neuroinflammation induced by lipopolysaccharide (LPS), we validated this hypothesis in primary fetal sheep microglia cultures re-exposed to LPS in presence of a selective α7nAChR agonist or antagonist. Our RNAseq and protein level findings show that a pro-inflammatory microglial phenotype acquiredin vitroby LPS stimulation is reversed with α7nAChR agonistic stimulation. Conversely, antagonistic α7nAChR stimulation potentiates the pro-inflammatory microglial phenotype. Surprisingly, under conditions of LPS double-hit an interference of a postulated α7nAChR - ferroportin signaling pathway may impede this mechanism. These results suggest a therapeutic potential of α7nAChR agonists in early re-programming of microglia in neonates exposed toin uteroinflammation via an endogenous cerebral cholinergic anti-inflammatory pathway. Future studies will assess the role of interactions between inflammation-triggered microglial iron sequestering and α7nAChR signaling in neurodevelopment.
Modeling HIV disease progression and transmission at population-level: The potential impact of modifying disease progression in HIV treatment programs
Authors: Ross Jennifer M. , Ying Roger , Celum Connie L. , Baeten Jared M. , Thomas Katherine K. , Murnane Pamela M. , van Rooyen Heidi , Hughes James P , Barnabas Ruanne
Published: January 2017

Introduction

Mathematical models of HIV transmission that incorporate the dynamics of disease progression can estimate the potential impact of adjunctive strategies to antiretroviral therapy (ART) for HIV treatment and prevention. Suppressive treatment of HIV-positive persons co-infected with herpes simplex virus-2 (HSV-2) with valacyclovir, a medication directed against HSV-2, can lower HIV viral load, but the impact of valacyclovir on population HIV transmission has not been estimated.

Methods

We applied data on CD4 and viral load progression in ART-naïve persons studied in two HIV clinical trials to a novel, discrete-time Markov model. We validated our disease progression estimates using data from a trial of home-based HIV counseling and testing in KwaZulu-Natal, South Africa. Finally, we applied our disease progression estimates to a dynamic transmission model estimating the impact of providing valacyclovir to ART-naïve individuals to reduce onward transmission of HIV in three scenarios of different ART and valacyclovir population coverage. We assumed that valacyclovir reduced HIV viral load by 1.23 log copies/μL, and that persons treated with valacyclovir initiated ART more rapidly when their CD4 fell below 500 due to improved retention in pre-ART care.

Results

The average duration of HIV infection following acute infection was 9.5 years. The duration of disease after acute infection and before reaching CD4 200 cells/μL was 2.53 years longer for females than males. Relative to a baseline of community HIV testing and counseling and ART initiation at CD4 <=500 cells/μL, valacyclovir with increased linkage to care resulted in 166,000 fewer HIV infections over ten years, with an incremental cost-effectiveness ratio (ICER) of $4,696 per HIV infection averted. The Test and Treat scenario with 70% ART coverage and no valacyclovir resulted in 202,000 fewer HIV infections at an ICER of $6,579.

Conclusion

Even when compared with initiation of valacyclovir, a safe drug that reduces HIV viral load, universal treatment for HIV is the optimal strategy for averting new infections and increasing public health benefit. Universal HIV treatment should be pursued by all countries to most effectively and efficiently reduce the HIV burden.
Joint genetic analysis using variant sets reveals polygenic gene-context interactions
Authors: Casale Francesco Paolo , Horta Danilo , Rakitsch Barbara , Stegle Oliver
Published: January 2017

Joint genetic models for multiple traits have helped to enhance association analyses. Most existing multi-trait models have been designed to increase power for detecting associations, whereas the analysis of interactions has received considerably less attention. Here, we propose iSet, a method based on linear mixed models to test for interactions between sets of variants and environmental states or other contexts. Our model generalizes previous interaction tests and in particular provides a test for local differences in the genetic architecture between contexts. We first use simulations to validate iSet before applying the model to the analysis of genotype-environment interactions in an eQTL study. Our model retrieves a larger number of interactions than alternative methods and reveals that up to 20% of cases show context-specific configurations of causal variants. Finally, we apply iSet to test for sub-group specific genetic effects in human lipid levels in a large human cohort, where we identify a gene-sex interaction for C-reactive protein that is missed by alternative methods.

Author summary

Genetic effects on phenotypes can depend on external contexts, including environment. Statistical tests for identifying such interactions are important to understand how individual genetic variants may act in different contexts. Interaction effects can either be studied using measurements of a given phenotype in different contexts, under the same genetic backgrounds, or by stratifying a population into subgroups. Here, we derive a method based on linear mixed models that can be applied to both of these designs. iSet enables testing for interactions between context and sets of variants, and accounts for polygenic effects. We validate our model using simulations, before applying it to the genetic analysis of gene expression studies and genome-wide association studies of human blood lipid levels. We find that modeling interactions with variant sets offers increased power, thereby uncovering interactions that cannot be detected by alternative methods.