bluuebunny/crossref_metadata_2025 huggingface dataset:
Health-related quality of life in patients with uveitis
Authors: Shamdas Mohith , Bassilious Kerolos , Murray Philip Ian
Published: October 2018

Background/aims

To measure health-related quality of life (HRQOL) in patients with uveitis using time trade-off (TTO) and standard gamble (SG) methods of direct utility analysis.

Methods

Consecutive patients attending a tertiary referral uveitis clinic were administered standardised, interview-delivered TTO and SG questionnaires and completed the European Quality of Life Five Dimensions Five Level (EQ5D-5L) questionnaire. Clinical data recorded included best-corrected visual acuity, uveitis anatomical and clinical classifications, duration since diagnosis, disease activity, current medication and any ocular or systemic comorbidities.

Results

Two hundred patients with uveitis (124 female, 76 male, median age 54 years) were included. Overall mean TTO utility was 0.831 (95% CI 0.802 to 0.860); mean SG utility was 0.868 (95% CI 0.840 to 0.896) and mean EQ5D-5L utility was 0.742 (95% CI 0.702 to 0.782). There was a negative correlation between visual acuity and mean HRQOL (6/12 or better: TTO 0.86, SG 0.893; 6/15–6/60: TTO 0.662, SG 0.742; worse than 6/60: TTO 0.608, SG 0.712). Poor vision in the better- seeing eye (p=0.004), bilateral disease (p=0.047) and concurrent glaucomatous optic neuropathy (p=0.005) were predictors of poor TTO HRQOL. No correlation was found between HRQOL and duration of diagnosis, a flare of uveitis or being on systemic therapy. Patients with uveitis with poor vision have a TTO value worse than patients with end-stage renal failure on haemodialysis or those with AIDS.

Conclusion

Loss of vision resulting from uveitis is associated with reduced HRQOL. The TTO and SG utility values appear directly dependent on the degree of vision loss and not on the duration of disease or systemic medications.
Artificial intelligence and deep learning in ophthalmology
Authors: Ting Daniel Shu Wei , Pasquale Louis R , Peng Lily , Campbell John Peter , Lee Aaron Y , Raman Rajiv , Tan Gavin Siew Wei , Schmetterer Leopold , Keane Pearse A , Wong Tien Yin
Published: October 2018

Artificial intelligence (AI) based on deep learning (DL) has sparked tremendous global interest in recent years. DL has been widely adopted in image recognition, speech recognition and natural language processing, but is only beginning to impact on healthcare. In ophthalmology, DL has been applied to fundus photographs, optical coherence tomography and visual fields, achieving robust classification performance in the detection of diabetic retinopathy and retinopathy of prematurity, the glaucoma-like disc, macular oedema and age-related macular degeneration. DL in ocular imaging may be used in conjunction with telemedicine as a possible solution to screen, diagnose and monitor major eye diseases for patients in primary care and community settings. Nonetheless, there are also potential challenges with DL application in ophthalmology, including clinical and technical challenges, explainability of the algorithm results, medicolegal issues, and physician and patient acceptance of the AI ‘black-box’ algorithms. DL could potentially revolutionise how ophthalmology is practised in the future. This review provides a summary of the state-of-the-art DL systems described for ophthalmic applications, potential challenges in clinical deployment and the path forward.
Assessing the operational feasibility and acceptability of an inhalable formulation of oxytocin for improving community-based prevention of postpartum haemorrhage in Myanmar: a qualitative inquiry
Authors: Than Kyu Kyu , Oliver Victoria , Mohamed Yasmin , La Thazin , Lambert Pete , McIntosh Michelle , Luchters Stanley
Published: October 2018

Objective

This study assessed the potential operational feasibility and acceptability of a heat-stable, inhaled oxytocin (IOT) product for community-based prevention of postpartum haemorrhage in Myanmar.

Methods

A qualitative inquiry was conducted between June 2015 and February 2016 through focus group discussions and in-depth interviews. Research was conducted in South Dagon township (urban setting) and in Ngape and Thanlyin townships (rural settings) in Myanmar. Eleven focus group discussions and 16 in-depth interviews were conducted with mothers, healthcare providers and other key informants. All audio recordings were transcribed verbatim in Myanmar language and were translated into English. Thematic content analysis was done using NVivo software.

Results

Future introduction of an IOT product for community-based services was found to be acceptable among mothers and healthcare providers and would be feasible for use by lower cadres of healthcare providers, even in remote settings. Responses from healthcare providers and community members highlighted that midwives and volunteer auxiliary midwives would be key advocates for promoting community acceptance of the product. Healthcare providers perceived the ease of use and lack of dependence on cold storage as the main enablers for IOT compared with the current gold standard oxytocin injection. A single-use disposable device with clear pictorial instructions and a price that would be affordable by the poorest communities was suggested. Appropriate training was also said to be essential for the future induction of the product into community settings.

Conclusion

In Myanmar, where home births are common, access to cold storage and skilled personnel who are able to deliver injectable oxytocin is limited. Among community members and healthcare providers, IOT was perceived to be an acceptable and feasible intervention for use by lower cadres of healthcare workers, and thus may be an alternative solution for the prevention of postpartum haemorrhage in community-based settings in the future.
Is the alcohol industry doing well by ‘doing good’? Findings from a content analysis of the alcohol industry’s actions to reduce harmful drinking
Authors: Babor Thomas F , Robaina Katherine , Brown Katherine , Noel Jonathan , Cremonte Mariana , Pantani Daniela , Peltzer Raquel I , Pinsky Ilana
Published: October 2018

Objectives

The aims of this study were to: (1) describe alcohol industry corporate social responsibility (CSR) actions conducted across six global geographic regions; (2) identify the benefits accruing to the industry (‘doing well’); and (3) estimate the public health impact of the actions (‘doing good’).

Setting

Actions from six global geographic regions.

Participants

A web-based compendium of 3551 industry actions, representing the efforts of the alcohol industry to reduce harmful alcohol use, was issued in 2012. The compendium consisted of short descriptions of each action, plus other information about the sponsorship, content and evaluation of the activities. Public health professionals (n=19) rated a sample (n=1046) of the actions using a reliable content rating procedure.

Outcome measures

WHO Global strategy target area, estimated population reach, risk of harm, advertising potential, policy impact potential and other aspects of the activity.

Results

The industry actions were conducted disproportionately in regions with high-income countries (Europe and North America), with lower proportions in Latin America, Africa and Asia. Only 27% conformed to recommended WHO target areas for global action to reduce the harmful use of alcohol. The overwhelming majority (96.8%) of industry actions lacked scientific support (p<0.01) and 11.0% had the potential for doing harm. The benefits accruing to the industry (‘doing well’) included brand marketing and the use of CSR to manage risk and achieve strategic goals.

Conclusion

Alcohol industry CSR activities are unlikely to reduce harmful alcohol use but they do provide commercial strategic advantage while at the same time appearing to have a public health purpose.
Therapeutic trial design for frontotemporal dementia and related disorders
Authors: Desmarais Philippe , Rohrer Jonathan D , Nguyen Quoc Dinh , Herrmann Nathan , Stuss Donald T , Lang Anthony E , Boxer Adam L , Dickerson Bradford C , Rosen Howie , van Swieten John Cornelis , Meeter Lieke H , Borroni Barbara , Tartaglia Maria Carmela , Feldman Howard H , Black Sandra E , Masellis Mario
Published: October 2018

The frontotemporal dementia (FTD) spectrum is a heterogeneous group of neurodegenerative syndromes with overlapping clinical, molecular and pathological features, all of which challenge the design of clinical trials in these conditions. To date, no pharmacological interventions have been proven effective in significantly modifying the course of these disorders. This study critically reviews the construct and methodology of previously published randomised controlled trials (RCTs) in FTD spectrum disorders in order to identify limitations and potential reasons for negative results. Moreover, recommendations based on the identified gaps are elaborated in order to guide future clinical trial design. A systematic literature review was carried out and presented in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. A total of 23 RCTs in cohorts with diagnoses of behavioural and language variants of FTD, corticobasal syndrome and progressive supranuclear palsy syndrome were identified out of the 943 citations retrieved and were included in the qualitative review. Most studies identified were early-phase clinical trials that were small in size, short in duration and frequently underpowered. Diagnoses of populations enrolled in clinical trials were based on clinical presentation and rarely included precision-medicine tools, such as genetic and molecular testing. Uniformity and standardisation of research outcomes in the FTD spectrum are essential. Several elements should be carefully considered and planned in future clinical trials. We anticipate that precision-medicine approaches will be crucial to adequately address heterogeneity in the FTD spectrum research.
Neurite orientation and dispersion density imaging (NODDI) detects cortical and corticospinal tract degeneration in ALS
Authors: Broad Rebecca J , Gabel Matt C , Dowell Nicholas G , Schwartzman David J , Seth Anil K , Zhang Hui , Alexander Daniel C , Cercignani Mara , Leigh P Nigel
Published: October 2018

Background

Corticospinal tract (CST) degeneration and cortical atrophy are consistent features of amyotrophic lateral sclerosis (ALS). We hypothesised that neurite orientation dispersion and density imaging (NODDI), a multicompartment model of diffusion MRI, would reveal microstructural changes associated with ALS within the CST and precentral gyrus (PCG) ‘in vivo’.

Methods

23 participants with sporadic ALS and 23 healthy controls underwent diffusion MRI. Neurite density index (NDI), orientation dispersion index (ODI) and free water fraction (isotropic compartment (ISO)) were derived. Whole brain voxel-wise analysis was performed to assess for group differences. Standard diffusion tensor imaging (DTI) parameters were computed for comparison. Subgroup analysis was performed to investigate for NODDI parameter differences relating to bulbar involvement. Correlation of NODDI parameters with clinical variables were also explored. The results were accepted as significant where p<0.05 after family-wise error correction at the cluster level, clusters formed with p<0.001.

Results

In the ALS group NDI was reduced in the extensive regions of the CST, the corpus callosum and the right PCG. ODI was reduced in the right anterior internal capsule and the right PCG. Significant differences in NDI were detected between subgroups stratified according to the presence or absence of bulbar involvement. ODI and ISO correlated with disease duration.

Conclusions

NODDI demonstrates that axonal loss within the CST is a core feature of degeneration in ALS. This is the main factor contributing to the altered diffusivity profile detected using DTI. NODDI also identified dendritic alterations within the PCG, suggesting microstructural cortical dendritic changes occur together with CST axonal damage.
Suspected exaggerated reaction to dopamine infusion in a cat with increased intracranial pressure
Authors: Pascal Manuela , Kaartinen Johanna
Published: October 2018

An 11‐year 8‐month‐old, male, neutered domestic shorthair cat was presented for investigation of progressive right vestibular signs following recent ear canal surgery. The investigations showed otitis media/interna, intracranial empyema and cerebellar abscesses resulting in increased intracranial pressure and herniation of the cerebellum through the foramen magnum. During anaesthesia for ventral bulla osteotomy and total ear canal ablation, the cat developed episodes of hypotension followed by severe hypertension and tachycardia after administration of dopamine infusion. Surgery was completed and the patient recovered uneventfully. This report illustrates the challenging management of anaesthesia in a patient with intracranial pathology.
Septic monoarthritis with isolation ofP dagmatisas a monoculture in the stifle joint of a dog
Authors: Bongers Jos , van Stee Lucinda , van Bruggen Leonie , Broens Els M
Published: October 2018

A seven‐month‐old male cane corso was presented to our emergency clinic, with severe left hind lameness. The combination of history, physical examination, radiographs and cytology of the left stifle raised a suspicion of a septic monoarthritis. Bacteriology of the synovia confirmed an infection withPasteurella dagmatis. Pasteurellaspecies are frequently associated with skin disease and often isolated from dog bite wounds in humans. Isolation ofP dagmatisonly incidentally occurs and its frequency might be underestimated due to laboratory misidentification. Its pathogenicity remains unknown and is presumed to be equal to otherPasteurellaspecies. However, in humans, this organism is associated with more serious disease, which might potentially also be the case in our patient. To the author’s knowledge, this is the first case report of a monoculture ofP dagmatisisolated from the joint of a dog.
Does length of ride, gender, or nationality affect willingness to ride in a driverless ambulance?
Authors: Rice Stephen , Winter Scott R. , Mehta Rian , Keebler Joseph R. , Baugh Bradley S. , Anania Emily C. , Milner Mattie N.
Published: October 2018

Due to the frequent lack of ambulances and personnel, the purpose of this study was to examine consumers’ willingness to ride in an ambulance that was either driven by a human driver or completely automated (with no human driver) based on the gender of the participant and their nationality, either Indian or American. A two-study experimental design was utilized using over 1000 participants. In study 1, the length of the ride and the type of driver were manipulated, while in study 2, the length of the ride was manipulated across genders and nationality. Study 2 also collected affect measures to complete a mediation analysis. The findings indicate that consumers’ willingness to ride was significantly lower for longer rides when using the automated ambulance. There were significant interactions between nationality and gender and nationality, gender, and length of the ride. Affect was found to significantly mediate the relationship between willingness to ride and both nationality and gender. These findings are discussed in greater detail, along with recommendations for future research and limitations to the study.
Extended Fuller index, sky catastrophes and the Seifert conjecture
Authors: Savelyev Yasha
Published: October 2018

We extend the classical Fuller index, and use this to prove that for a certain general class of vector fields [Formula: see text] on a compact smooth manifold, if a homotopy of smooth non-singular vector fields starting at [Formula: see text] has no sky catastrophes as defined by the paper, then the time 1 limit of the homotopy has periodic orbits. This class of vector fields includes the Hopf vector field on [Formula: see text]. A sky catastrophe is a kind of bifurcation originally discovered by Fuller. This answers a natural question that existed since the time of Fuller’s foundational papers. We also put strong constraints on the kind of sky-catastrophes that may appear for homotopies of Reeb vector fields.
Spontaneous and gravitational baryogenesis
Authors: Arbuzova E. V.
Published: October 2018

Some problems of spontaneous and gravitational baryogenesis are discussed. Gravity modification due to the curvature-dependent term in gravitational baryogenesis scenario is considered. It is shown that the interaction of baryonic fields with the curvature scalar leads to strong instability of the gravitational equations of motion and as a result to noticeable distortion of the standard cosmology.
The de Sitter swampland conjecture and supersymmetric AdS vacua
Authors: Conlon Joseph P.
Published: October 2018

It has recently been conjectured that string theory does not admit de Sitter critical points. This note points out that in several cases, including KKLT or racetrack models, this statement is equivalent to the absence of supersymmetric Minkowski or AdS solutions. This equivalence arises from establishing the positivity of the potential in a large-radius limit, requiring a turnover of the potential before reaching an AdS vacuum. For example, this conjecture is incompatible with the simplest 1-modulus KKLT AdS supersymmetric solution.
Arbitrary Waveform Generators Using Current-Controlled Current Conveyor Transconductance Amplifier and Current Conveyor Analog Switches
Authors: Kumngern Montree , Nonthaputha Thanat , Khateb Fabian
Published: October 2018

This paper presents a new amplitude modulation (AM), frequency modulation (FM), amplitude shift keying (ASK), frequency shift keying (FSK), phase shift keying (PSK) and quadrature amplitude modulation (QAM) waveform generators using current current-controlled conveyor transconductance amplifier (CCCTA) and current conveyor analog switches (CCASs). The CCCTA around with capacitors and resistors are used to generate high-frequency carrier which is worked as a quadrature oscillator. The oscillating frequency of oscillator can be controlled using the bias current of CCCTA, therefore FM and FSK waveforms can be obtained by applying information signal through the bias current of CCCTA. Unlike previous waveform generators, proposed circuit uses second generation current conveyor (CCII) to work as CCAS and AM, ASK, PSK and QAM waveforms can be obtained by putting information signals to control switches that realized using CCIIs. The proposed circuit has been simulated using 0.18[Formula: see text][Formula: see text]m CMOS [Formula: see text]-well process from TSMC. The simulation results are used to confirm workability of the proposed circuit.
Maximal Defect-Free Component in Nanoscale Crossbar Circuits Amidst Stuck-Open and Stuck-Closed Faults
Authors: Kule Malay , Rahaman Hafizur , Bhattacharya Bhargab B.
Published: October 2018

We propose a technique for the analysis of manufacturing yield of nano-crossbar for the different values of defect percentage and crossbar-size. We provide an estimate of the minimum-size crossbar to be fabricated, wherein a defect-free crossbar of a given size can always be found with a guaranteed yield. Our technique is based on logical merging of two defective rows (or two columns) that emulate a defect-free row (or column). The proposed technique easily handles both the stuck-open and stuck-closed faults. Experimental results show that the proposed method provides higher defect-tolerance compared to that of previous techniques.
Applications of Bifurcation: Nonautonomous Periodically-Excited Systems
Authors: Virgin L. N. , Thompson J. M. T.
Published: October 2018

This paper reviews some examples of bifurcation in low-order, periodically driven dynamical systems. The generic loss of stability is a key component in dynamical systems theory, and provides a central pillar in assessing qualitative changes in system dynamics. Although bifurcation tends to be thought of in rather abstract, theoretical terms, we show that it also provides a compelling framework to guide laboratory-based experiments. Both local and global stability transitions and their connection are illustrated in this accessible, review-like pictorial overview of simple mechanical/structural systems driven toward instability.
Elements of Contemporary Theory of Dynamical Chaos: A Tutorial. Part I. Pseudohyperbolic Attractors
Authors: Gonchenko A. S. , Gonchenko S. V. , Kazakov A. O. , Kozlov A. D.
Published: October 2018

The paper is devoted to topical issues of modern mathematical theory of dynamical chaos and its applications. At present, it is customary to assume that dynamical chaos in finite-dimensional smooth systems can exist in three different forms. This is dissipative chaos, the mathematical image of which is a strange attractor; conservative chaos, for which the entire phase space is a large “chaotic sea” with randomly spaced elliptical islands inside it; and mixed dynamics, characterized by the principal inseparability in the phase space of attractors, repellers and conservative elements of dynamics. In the present paper (which opens a series of three of our papers), elements of the theory of pseudohyperbolic attractors of multidimensional maps and flows are presented. Such attractors, as well as hyperbolic ones, are genuine strange attractors, but they allow the existence of homoclinic tangencies. We describe two principal phenomenological scenarios for the appearance of pseudohyperbolic attractors in one-parameter families of three-dimensional diffeomorphisms, and also consider some basic examples of concrete systems in which these scenarios occur. We propagandize new methods for studying pseudohyperbolic attractors (in particular, the method of saddle charts, the modified method of Lyapunov diagrams and the so-called LMP-method for verification of pseudohyperbolicity of attractors) and test them on the above examples. We show that Lorenz-like attractors in three-dimensional generalized Hénon maps and in a nonholonomic model of Celtic stone as well as figure-eight attractors in the model of Chaplygin top are genuine (pseudohyperbolic) ones. Besides, we show an example of four-dimensional Lorenz model with a wild spiral attractor of Shilnikov–Turaev type that was found recently in [Gonchenko et al., 2018].
Exploring the Dynamics of a Third-Order Phase-Locked Loop Model
Authors: Manchein Cesar , Albuquerque Holokx A. , Mello Luis Fernando
Published: October 2018

We study the dynamics and characterize the bifurcation structure of a phase-locked loop (PLL) device modeled by a third-order autonomous differential equation with sinusoidal phase detector. The development of this work was performed using rigorous analysis and numerical experiments. Through theoretical analysis the bifurcation structures related to two fundamental equilibrium points of the system are described. By using extensive numerical experiments we investigate the intricate organization between periodic and chaotic domains in parameter space (named here parameter plane as the PLL model has only two control parameters) and obtain two following remarkable findings: (i) there are self-organized generic stable periodic structures along specific directions in parameter plane, whose periods are defined by a mathematical rule and, (ii) the existence of transient chaos phenomenon responsible for long chaotic temporal evolution preceding the asymptotic (periodic) dynamics for some particular control parameter pairs is characterized. Our theoretical and numerical results present an astonishing concordance. We believe that the present study, specially the parameter plane analysis, may have a great importance to experimental studies and general applications involving PLL devices when, for example, one would like to avoid the chaotic regimes.
Beta Chaotic Map Based Image Encryption Using Genetic Algorithm
Authors: Kaur Manjit , Kumar Vijay
Published: October 2018

In this paper, an efficient image encryption technique using beta chaotic map, nonsubsampled contourlet transform, and genetic algorithm is proposed. Initially, the nonsubsampled contourlet transform is utilized to decompose the input image into subbands. The beta chaotic map is used to develop pseudo-random key that encrypts the coefficients of subbands. However, it requires certain parameters to encrypt these coefficients. A multiobjective fitness function for genetic algorithm is designed to find the optimal parameter of beta chaotic map. The inverse of nonsubsampled contourlet transform is performed to obtain a ciphered image. The performance of the proposed technique is compared with recently developed well-known meta-heuristic based image encryption techniques. Experimental results reveal that the proposed technique provides better computational speed and high encryption intensity. The comparative analyses show effectiveness of the proposed image encryption technique.
Twelve Limit Cycles in 3D Quadratic Vector Fields with Z3 Symmetry
Authors: Guo Laigang , Yu Pei , Chen Yufu
Published: October 2018

This paper is concerned with the number of limit cycles bifurcating in three-dimensional quadratic vector fields with [Formula: see text] symmetry. The system under consideration has three fine focus points which are symmetric about the [Formula: see text]-axis. Center manifold theory and normal form theory are applied to prove the existence of 12 limit cycles with [Formula: see text]–[Formula: see text]–[Formula: see text] distribution in the neighborhood of three singular points. This is a new lower bound on the number of limit cycles in three-dimensional quadratic systems.
Bifurcations and Pattern Formation in a Predator–Prey Model
Authors: Cai Yongli , Gui Zhanji , Zhang Xuebing , Shi Hongbo , Wang Weiming
Published: October 2018

In this paper, we investigate the spatiotemporal dynamics of a Leslie–Gower predator–prey model incorporating a prey refuge subject to the Neumann boundary conditions. We mainly consider Hopf bifurcation and steady-state bifurcation which bifurcate from the constant positive steady-state of the model. In the case of Hopf bifurcation, by the center manifold theory and the normal form method, we establish the bifurcation direction and stability of bifurcating periodic solutions; in the case of steady-state bifurcation, by the local and global bifurcation theories, we prove the existence of the steady-state bifurcation, and find that there are two typical bifurcations, Turing bifurcation and Turing–Hopf bifurcation. Via numerical simulations, we find that the model exhibits not only stationary Turing pattern induced by diffusion which is dependent on space and independent of time, but also temporal periodic pattern induced by Hopf bifurcation which is dependent on time and independent of space, and spatiotemporal pattern induced by Turing–Hopf bifurcation which is dependent on both time and space. These results may enrich the pattern formation in the predator–prey model.
A Multivalued Version of the Block–Sharkovsky Theorem Applicable to Differential Equations on the Circle
Authors: Andres Jan , Pastor Karel
Published: October 2018

A multivalued version of the well-known (Sharkovsky type) Block cycle coexistence theorem is, on the basis of our former results, completed and applied to differential equations and inclusions. The deterministic results are also randomized which allows us, besides other things, to eliminate some exceptional absent periodic dynamics. In this way, instead of at most two possible deterministic exceptional cases (w.r.t. the standard Block theorem), only one possible random exception can occur, provided the forcing period [Formula: see text], [Formula: see text]. On the other hand, the application to random differential equations and inclusions is not so effective in general.
A Multiobjective Optimization Approach for Selecting Risk Response Strategies of Software Project: From the Perspective of Risk Correlations
Authors: Wu Dengsheng , Zhu Xiaoqian , Wan Jie , Bao Chunbing , Li Jianping
Published: October 2018

Studies on software risk response theories and methods play an important role in improving the success rate of software project. With the requirement of software risk management, the existing single-objective risk response strategies section model is difficult to manage software risks effectively. This paper regards software risk response cost and software risk exposure as optimization objectives and proposes a multiobjective risk response strategies optimization model for software project. Furthermore, it analyzes the risk correlation from the perspective of risk probability dependence and risk loss interaction and puts forward a multiobjective risk response strategies optimization model for software project from the perspective of risk correlation. Empirical analysis results show that there is a trade-off relationship between the software risk exposure and software risk response cost. The software manager can identify the corresponding optimal risk response strategies according to the actual risk response budget. The results also indicate that the consequence of the multiobjective risk response strategies optimization model for software project considering risk correlation can better describe the actual situation of risk management.
Rate of Angular Momentum in ZMP Using Efficient DH-Based Recursive Lagrangian
Authors: Chung Hyun-Joon , Kim Joo H. , Xiang Yujiang
Published: October 2018

Dynamic balance has to be maintained during motions of biped systems when their feet are in contact with the ground. As a necessary condition, this indicates that the calculated zero moment point (ZMP) position should be within the specified foot support region throughout the entire motion. A critical term in the ZMP formulation is the rate of angular momentum (RAM) for each link, which should be evaluated accurately and efficiently in motion planning and simulations. In this study, we propose a recursive Lagrangian method based on Denavit–Hartenberg convention to calculate the RAM for each link and the corresponding sensitivity. This method allows the evaluation of each link’s dynamic contribution to the ZMP position. The effectiveness of the proposed approach is demonstrated by simulating bipedal motions of walking and running along with their comparison against existing approaches (direct method and global force method). The accurate RAM calculation in ZMP based on the proposed approach resulted in the improved motion trajectories and reliable ground reaction forces for high-speed bipedal motion predictions.
Age and geochemistry of the Paleoproterozoic Bhatwari Gneiss of Garhwal Lesser Himalaya, NW India: implications for the pre-Himalayan magmatic history of the Lesser Himalayan basement rocks
Authors: Sen Aranya , Sen Koushik , Srivastava Hari B. , Singhal Saurabh , Phukon Purbajyoti
Published: October 2018

The Bhatwari Gneiss of Bhagirathi Valley in the Garhwal Himalaya is a Paleoproterozoic crystalline rock from the Inner Lesser Himalayan Sequence. On the basis of field and petrographic analyses, we have classified the Bhatwari Gneiss into two parts: the Lower Bhatwari Gneiss (LBG) and the Upper Bhatwari Gneiss (UBG). The geochemical signatures of these rocks suggest a monzonitic protolith for the LBG and a granitic protolith for the UBG. The UBG has a calc-alkaline S-type granitoid protolith, whereas the LBG has an alkaline I-type granitoid protolith; the UBG is more fractionated. The trace element concentrations suggest a volcanic arc setting for the LBG and a within-plate setting for the UBG. The U–Pb geochronology of one sample from the LBG gives an upper intercept age of 1988 ± 12 Ma (
n
= 10, MSWD = 2.5). One sample from the UBG gives an upper intercept age of 1895 ± 22 Ma (
n
= 15, MSWD = 0.82), whereas another sample does not give any upper intercept age, but indicates magmatism from
c.
1940 to 1840 Ma. Based on these ages, we infer that the Bhatwari Gneiss has evolved due to arc magmatism and related back-arc rifting over a time period of
c.
100 Ma during the Proterozoic. This arc magmatism is related to the formation of the Columbia supercontinent.

Supplementary material:
LA–ICP-MS calibration and adjusted major element data used for computing the isometric log-ratio transformations are available at
https://doi.org/10.6084/m9.figshare.c.4272158
Review of Power Up:
Authors: Nagaraj S.V.
Published: October 2018

Video games provide entertainment to those who play them. This book looks at the hidden mathematics behind video games. It is meant for all those who love playing video games, so that they may explore mathematical ideas in the games. It is also aimed at mathematics teachers for inspiring their students, and for all those who love mathematics and games. Even those who hate mathematics but love video games are also a part of the target audience of this book. However, this particular category of readers needs at least some familiarity with high school mathematics to benefit from the book. The author states that many people enjoy playing computer / video games but few would be indulging themselves in doing some math. He terms this a consequence of poor marketing of mathematics since time immemorial. The main purpose of the book is to highlight that mathematics can be fun and that it can be found even in the most unbelievable or unexpected places such as in computer games.
Distributed Computing Column 71
Authors: Welch Jennifer L.
Published: October 2018

Population protocols have been an active area of distributed computing for over a decade, as they are an abstract model of numerous real-world scenarios from sensor networks to biological computing paradigms. For this column, Dan Alistarh and Rati Gelashvili provide a timely overview of recent results on population protocols, focusing especially on the case when each agent in the system can have more than a constant amount of local memory. Several key building blocks are presented, followed by applications of these primitives, in an accessible way that conveys the excitement of fast-moving developments in the area.
Recent Algorithmic Advances in Population Protocols
Authors: Alistarh Dan , Gelashvili Rati
Published: October 2018

Population protocols are a popular model of distributed computing, introduced by Angluin, Aspnes, Diamadi, Fischer, and Peralta [6] a little over a decade ago. In the meantime, the model has proved a useful abstraction for modeling various settings, from wireless sensor networks [35, 26], to gene regulatory networks [17], and chemical reaction networks [21]. In a nutshell, a population protocol consists of n agents with limited local state that interact randomly in pairs, according to an underlying communication graph, and cooperate to collectively compute global predicates. From a theoretical prospective, population protocols, with the restricted communication and computational power, are probably one of the simplest distributed model one can imagine. Perhaps surprisingly though, solutions to many classical distributed tasks are still possible. Moreover, these solutions often rely on interesting algorithmic ideas for design and interesting probabilistic techniques for analysis, while known lower bound results revolve around complex combinatorial arguments.
Neuroscience and the Criminal Justice System
Authors: Greely Henry T. , Farahany Nita A.
Published: October 2018

The criminal justice system acts directly on bodies, but fundamentally it cares about minds. As neuroscience progresses, it will increasingly be able to probe the objective, physical organ of the brain and reveal secrets from the subjective mind. This is already beginning to affect the criminal justice system, a trend that will only increase. This review article cannot begin even to sketch the full scope of the new field of law and neuroscience. The first workshop on the subject was held in 2003 ( Garland 2004 ), but the field already has its own casebook ( Jones et al. 2014 ) and the MacArthur Foundation Research Network on Law and Neuroscience (2018) shows more than 1,700 publications in the area between 1984 and 2017. Greely (2009) divided the implications of law into five different categories: prediction, mind-reading, responsibility, treatment, and enhancement. This article examines only three points: the current use of neuroscience to understand and explain criminal behavior, the possibilities of relevant neuroscience-based prediction, and plausible future applications of neuroscience to the treatment of criminals. But first, we discuss the human brain and how it works.
Arrhythmogenic Right Ventricular Cardiomyopathy: Progress Toward Personalized Management
Authors: James Cynthia A. , Calkins Hugh
Published: October 2018

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease characterized by fibrofatty replacement of the ventricular myocardium, a high risk of ventricular arrhythmias, and progressive ventricular dysfunction. The clinical course is highly variable, and optimal approaches to management remain undefined. ARVC is associated with pathogenic variants in genes encoding the cardiac desmosome. Genetic testing facilitates identification of at-risk family members, but penetrance of ARVC in pathogenic variant carriers is difficult to predict. Participation in endurance exercise is a known key risk factor. However, there remains significant uncertainty about which family member will develop disease and how best to approach longitudinal screening. Our clinically focused review describes how new insights gained from natural history studies, improved understanding of pathogenic mechanisms, and appreciation of genetic and environmental modifiers have set the stage for developing personalized approaches to managing both ARVC patients and their at-risk family members.
Long-Acting HIV Drugs for Treatment and Prevention
Authors: Gulick Roy M. , Flexner Charles
Published: October 2018

Antiretroviral drugs have revolutionized the treatment and prevention of HIV infection; however, adherence is critical for sustained efficacy. Current HIV treatment consists of three-drug regimens, and current HIV pre-exposure prophylaxis (PrEP) consists of a two-drug regimen; both generally require adherence to once-daily dosing. Long-acting formulations are useful in the treatment and prevention of other conditions (e.g., contraceptives, antipsychotics) and help promote adherence. Newer long-acting formulations of approved and investigational antiretroviral drugs in existing and newer mechanistic classes are under study for HIV treatment and prevention, including some phase III trials. Although long-acting antiretroviral drugs hold promise, some clinical challenges exist, including managing side effects, drug-drug interactions, pregnancy, and long-lasting drug concentrations that could lead to the development of drug resistance. This review aims to summarize currently available information on long-acting antiretroviral drugs for HIV treatment and prevention.
PD-1 Blockade in Early-Stage Lung Cancer
Authors: Rosner Samuel , Reuss Joshua E. , Forde Patrick M.
Published: October 2018

Early-stage non–small cell lung cancer is a potentially curable disease, but with relapse rates exceeding 50% with standard treatments, this is a patient population in critical need of therapy innovation. Immunotherapy with immune checkpoint blockade has revolutionized the treatment strategy for advanced lung cancer. However, the role of this therapy in earlier-stage disease is largely unknown. The study of immunotherapy in earlier-stage disease has many advantages, including assessment of pathologic response and incorporation of translational scientific analyses to evaluate antitumor immune responses. Multiple clinical trials are currently under way, with promising early results.
Cellular and Molecular Mechanisms of Prion Disease
Authors: Sigurdson Christina J. , Bartz Jason C. , Glatzel Markus
Published: October 2018

Prion diseases are rapidly progressive, incurable neurodegenerative disorders caused by misfolded, aggregated proteins known as prions, which are uniquely infectious. Remarkably, these infectious proteins have been responsible for widespread disease epidemics, including kuru in humans, bovine spongiform encephalopathy in cattle, and chronic wasting disease in cervids, the latter of which has spread across North America and recently appeared in Norway and Finland. The hallmark histopathological features include widespread spongiform encephalopathy, neuronal loss, gliosis, and deposits of variably sized aggregated prion protein, ranging from small, soluble oligomers to long, thin, unbranched fibrils, depending on the disease. Here, we explore recent advances in prion disease research, from the function of the cellular prion protein to the dysfunction triggering neurotoxicity, as well as mechanisms underlying prion spread between cells. We also highlight key findings that have revealed new therapeutic targets and consider unanswered questions for future research.
Contribution of Wound-Associated Cells and Mediators in Orchestrating Gastrointestinal Mucosal Wound Repair
Authors: Quirós Miguel , Nusrat Asma
Published: October 2018

The gastrointestinal mucosa, structurally formed by the epithelium and lamina propria, serves as a selective barrier that separates luminal contents from the underlying tissues. Gastrointestinal mucosal wound repair is orchestrated by a series of spatial and temporal events that involve the epithelium, recruited immune cells, resident stromal cells, and the microbiota present in the wound bed. Upon injury, repair of the gastrointestinal barrier is mediated by collective migration, proliferation, and subsequent differentiation of epithelial cells. Epithelial repair is intimately regulated by a number of wound-associated cells that include immune cells and stromal cells in addition to mediators released by luminal microbiota. The highly regulated interaction of these cell types is perturbed in chronic inflammatory diseases that are associated with impaired wound healing. An improved understanding of prorepair mechanisms in the gastrointestinal mucosa will aid in the development of novel therapeutics that promote mucosal healing and reestablish the critical epithelial barrier function.
5-HT3 receptor signaling in serotonin transporter-knockout rats: a female sex-specific animal model of visceral hypersensitivity
Authors: El-Ayache Nadine , Galligan James J.
Published: October 2018

The irritable bowel syndrome (IBS) is a functional gastrointestinal motor and visceral sensation disorder that is more common in women than men. Female serotonin transporter (SERT)-gene knockout (KO) rats exhibit hypersensitivity to colorectal balloon distention (CRD) that mimics colonic hypersensitivity occurring in female IBS patients. Alosetron (5-HT3 receptor antagonist) is used to treat diarrhea-predominant IBS in female patients. Other 5-HT3 receptor antagonists are ineffective at treating IBS symptoms. The visceromotor response (VMR) to CRD in SERT-KO and wild-type (WT) rats was measured following subcutaneous (sc), intracerobroventricular (icv), or intrathecal (it) treatment with 5-HT3 receptor antagonists and an agonist. Alosetron (sc) and granisetron (antagonists) caused a paradoxical increase in the VMR to CRD in SERT-KO female rats. Alosetron (sc) increased the VMR to CRD in WT male rats. Alosetron (it) increased the VMR to CRD in SERT-KO female rats only, and the 5-HT3 receptor agonist SR-52772 increased the VMR to CRD in SERT-KO male rats. Depletion of spinal 5-HT using 5,7-dihydroxytryptamine prevented the increase in VMR to CRD in SERT-KO female and male rats treated it with alosetron and SR-52772, respectively. Alosetron (icv) did not affect the VMR to CRD in WT or KO female rats, but it increased the VMR in male SERT-KO but not WT male rats. These data suggest that 5-HT3 receptor signaling at the dorsal spinal cord mediates visceral hypersensitivity in female SERT-KO rats. Such differences could facilitate development of sex-specific drug treatments for visceral pain.

NEW & NOTEWORTHY We studied a model of female sex-specific visceral hypersensitivity using rats that had a loss of function of the serotonin transporter (SERT) caused by gene truncation. Female SERT-KO rats exhibited visceral hypersensitivity in response to colorectal balloon distention. We found that increased 5-HT signaling at dorsal spine 5-HT3 receptors was responsible for visceral hypersensitivity in female but not male SERT-KO rats.
Asymmetric cell division-dominant neutral drift model for normal intestinal stem cell homeostasis
Authors: Sei Yoshitatsu , Feng Jianying , Chow Carson C. , Wank Stephen A.
Published: October 2018

The normal intestinal epithelium is continuously regenerated at a rapid rate from actively cycling Lgr5-expressing intestinal stem cells (ISCs) that reside at the crypt base. Recent mathematical modeling based on several lineage-tracing studies in mice shows that the symmetric cell division-dominant neutral drift model fits well with the observed in vivo growth of ISC clones and suggests that symmetric divisions are central to ISC homeostasis. However, other studies suggest a critical role for asymmetric cell division in the maintenance of ISC homeostasis in vivo. Here, we show that the stochastic branching and Moran process models with both a symmetric and asymmetric division mode not only simulate the stochastic growth of the ISC clone in silico but also closely fit the in vivo stem cell dynamics observed in lineage-tracing studies. In addition, the proposed model with highest probability for asymmetric division is more consistent with in vivo observations reported here and by others. Our in vivo studies of mitotic spindle orientations and lineage-traced progeny pairs indicate that asymmetric cell division is a dominant mode used by ISCs under normal homeostasis. Therefore, we propose the asymmetric cell division-dominant neutral drift model for normal ISC homeostasis.

NEW & NOTEWORTHY The prevailing mathematical model suggests that intestinal stem cells (ISCs) divide symmetrically. The present study provides evidence that asymmetric cell division is the major contributor to ISC maintenance and thus proposes an asymmetric cell division-dominant neutral drift model. Consistent with this model, in vivo studies of mitotic spindle orientation and lineage-traced progeny pairs indicate that asymmetric cell division is the dominant mode used by ISCs under normal homeostasis.
Inflammation-induced upregulation of P2X4expression augments mucin secretion in airway epithelia
Authors: Winkelmann Veronika E. , Thompson Kristin E. , Neuland Kathrin , Jaramillo Ana M. , Fois Giorgio , Schmidt Hanna , Wittekindt Oliver H. , Han Wei , Tuvim Michael J. , Dickey Burton F. , Dietl Paul , Frick Manfred
Published: October 2018

Mucus clearance provides an essential innate defense mechanism to keep the airways and lungs free of particles and pathogens. Baseline and stimulated mucin secretion from secretory airway epithelial cells need to be tightly regulated to prevent mucus hypersecretion and mucus plugging of the airways. It is well established that extracellular ATP is a potent stimulus for regulated mucus secretion. Previous studies revealed that ATP acts via metabotropic P2Y2purinoreceptors on goblet cells. Extracellular ATP, however, is also a potent agonist for ionotropic P2X purinoreceptors. Expression of several P2X isoforms has been reported in airways, but cell type-specific expression and the function thereof remained elusive. With this study, we now provide evidence that P2X4is the predominant P2X isoform expressed in secretory airway epithelial cells. After IL-13 treatment of either human primary tracheal epithelial cells or mice, P2X4expression is upregulated in vitro and in vivo under conditions of chronic inflammation, mucous metaplasia, and hyperplasia. Upregulation of P2X4is strongest in MUC5AC-positive goblet cells. Moreover, activation of P2X4by extracellular ATP augments intracellular Ca2+signals and mucin secretion, whereas Ca2+signals and mucin secretion are dampened by inhibition of P2X4receptors. These data provide new insights into the purinergic regulation of mucin secretion and add to the emerging picture that P2X receptors modulate exocytosis of large secretory organelles and secretion of macromolecular vesicle cargo.