bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating dietitians into primary health care: benefits for patients, dietitians and the general practice team
Authors: Beckingsale Louise , Fairbairn Kirsty , Morris Caroline
Published: September 2018

ABSTRACT INTRODUCTION Dietetic service delivery in primary health care is an emerging area of dietetic practice in New Zealand. AIM This paper aims to describe the dietetic services being delivered in this setting and dietitians’ perceptions of the factors that have an effect on their ability to deliver an optimal service. METHODS Individual, qualitative, semi-structured, face-to-face interviews were conducted with 12 primary healthcare dietitians from a range of age, ethnicity and professional backgrounds. Interviews were audio-recorded, transcribed verbatim and analysed using inductive thematic analysis. RESULTS Participants were delivering a range of services including: providing nutrition care directly to patients, helping to upskill other primary health care professionals in nutrition, and delivering health promotion initiatives to their local community. Three key factors were identified that participants perceived as having an effect on their ability to deliver effective dietetic services in primary health care: being part of a multidisciplinary general practice team, having flexible service delivery contracts appropriate for the setting and that supported integration, and having an adequate level of dietetic experience. DISCUSSION Dietitians working in primary health care recognise the importance of being well integrated into a multidisciplinary general practice team. This enables them to deliver more collaborative and coordinated nutrition care alongside their colleagues, to benefit patient care. Establishing flexible dietetic service delivery contracts, which support integration and take into account funding and workforce capacity requirements, may help ensure that the unique skill set of a dietitian is utilised to best effect.
A taboo topic? How General Practitioners talk about overweight and obesity in New Zealand
Authors: Gray Lesley , Stubbe Maria , Macdonald Lindsay , Tester Rachel , Hilder Jo , Dowell Anthony C.
Published: September 2018

ABSTRACT INTRODUCTION Obesity is overtaking tobacco smoking in New Zealand as the leading potentially modifiable risk to health. International obesity guidelines recommend that health professionals opportunistically encourage weight management with their patients. However, research shows consistently low rates of weight management discussion, suggesting that health professionals may not be realising their full potential to address obesity. AIM To identify communication strategies used by General Practitioners (GPs) to open the topic of weight and weight management in routine consultations. METHODS A secondary analysis was conducted of 36 video-recorded consultations in general practices, selected for relevance from a database of 205 consultations. Content and interactional analysis was conducted in the context of the entire consultation. RESULTS The topic of weight was initiated more often by GPs than patients and was raised mostly once or twice in a consultation and occasionally as many as six times. GPs employed opportunistic strategies twice as often as they used structured strategies. DISCUSSION This study of naturally occurring consultations confirmed GPs do engage in opportunistic discussions about weight. However, such discussions are challenging and interactionally delicate. Highlighting the clinical relevance of weight appears to be effective. The high frequency of patient contact with GPs provides opportunity to reach and work with people at risk of chronic conditions associated with excess weight. Further research is required to identify suitable training and brief intervention tools for use in routine consultations that may be beneficial for both GPs and patients.
Why grit requires perseverance and passion to positively predict performance
Authors: Jachimowicz Jon M. , Wihler Andreas , Bailey Erica R. , Galinsky Adam D.
Published: September 2018

Prior studies linking grit—defined as perseverance and passion for long-term goals—to performance are beset by contradictory evidence. As a result, commentators have increasingly declared that grit has limited effects. We propose that this inconsistent evidence has occurred because prior research has emphasized perseverance and ignored, both theoretically and empirically, the critical role of passion, which we define as a strong feeling toward a personally important value/preference that motivates intentions and behaviors to express that value/preference. We suggest that combining the grit scale—which only captures perseverance—with a measure that assesses whether individuals attain desired levels of passion will predict performance. We first metaanalyzed 127 studies (
n
= 45,485) that used the grit scale and assessed performance, and found that effect sizes are larger in studies where participants were more passionate for the performance domain. Second, in a survey of employees matched to supervisor-rated job performance (
n
= 422), we found that the combination of perseverance, measured through the grit scale, and passion attainment, measured through a new scale, predicted higher performance. A final study measured perseverance and passion attainment in a sample of students (
n
= 248) and linked these to their grade-point average (GPA), finding that the combination of perseverance and passion attainment predicted higher GPAs in part through increased immersion. The present results help resolve the mixed evidence of grit’s relationship with performance by highlighting the important role that passion plays in predicting performance. By adequately measuring both perseverance and passion, the present research uncovers grit’s true predictive power.
Functional profiling of circulating tumor cells with an integrated vortex capture and single-cell protease activity assay
Authors: Dhar Manjima , Lam Jeffrey Nam , Walser Tonya , Dubinett Steven M. , Rettig Matthew B. , Di Carlo Dino
Published: September 2018

Significance

The current paradigm in liquid biopsies focuses on circulating tumor cell (CTC) count and genomics to provide clinically actionable information. We push beyond current capabilities to introduce a functional assay that quantifies protease secretion from live CTCs with single-cell resolution. In this assay, an integrated microfluidic device captures CTCs from blood and washes and encapsulates them into nanoliter-scale droplets with fluorogenic substrates within minutes, maintaining physiologic conditions. Our data support the presence of outlier CTCs with high protease activity that may drive metastasis or immune evasion. We reveal an intriguing correlation between CTC protease activity and metastatic progression. Such functional liquid biopsy approaches provide avenues to understand the metastatic process and potential for companion diagnostics.
Multi-verb constructions in Old Chinese and Middle Chinese
Authors: Li Wenchao
Published: September 2018

Multiple verb constructions have been studied intensively in Chinese. However, given the typological differences between the
Indo-European languages and Chinese, it is no surprise that the application of a ‘Western’ notion, namely ‘serial verb
construction’ (SVC), has caused much debate. This study provides a working definition of ‘SVC’ in Old Chinese and then turns to
diachronic issues, for example, the combinatorial possibilities of multiple verbs in Old Chinese, pre-Middle Chinese, and Middle
Chinese, clarifying which kind of complex constructions may be regarded as verb serialising and which as verb compounding. With
this in place, the study approaches an understanding of the evolution of multiple verb formations in Chinese. The finding reveals
that multiple verbs in Old Chinese are combined via verb serialisation. Six combinatorial possibilities are confirmed: (a)
unergative V + unergative V; (b) transitive V + unaccusative V; (c) unaccusative V + unaccusative V (change of state); (d)
unergative V + unaccusative V; (e) transitive V + transitive V; (f) unaccusative V + unaccusative V (motion). These can be further
classified into two groups: Group I: (a)–(d) are successive SVCs; Group II: (e)–(f) are
coordinate SVCs. In pre-Middle Chinese, there are signs of verb compounding. The occurrence of disyllabic
word roots in the Early Han Dynasty as well as (de)grammaticalisation may be responsible for this. In Middle Chinese, the
grammaticalisation of transitive change-of-state verbs, and the degrammaticalisation of motion verbs, led to three different
lexical categories: (a) partial intransitive change-of-state verbs turned into resultative complements (resulting in [transitive
V + unaccusative V] SVC transiting into predicate-complement V-V (change-of-state)); (b) partial motion verbs degrammaticalised
and turned into directional complements (resulting in [unergative V + unaccusative V] SVC transiting into predicate-complement V-V
(motion)); and (c) the first verb in [coordinate SVC] receives preverbalisation (giving rise to modifier-predicate V-V).
The role of educational factors in the development of lexical splits
Authors: Lin Yuhan
Published: September 2018

While variationist literature on sound change has mostly focused on chain shifts and mergers, much less is written about splits (Labov, 1994,2010). Previous literature shows that the acquisition of splits is unlikely unless motivated by social factors (Labov, 1994). The current study presents an apparent time analysis on the development of two phonemic splits, the initial /s/-/ʂ/ contrast and the initial /ɻ/-/l/ contrast, in Xiamen Mandarin, a contact variety ofPutonghua, the official language in China. Statistical results showed similar patterns for both variables: younger speakers and female speakers are leading the change; the distinction between two phonemes are more distinct in wordlist than in the sociolinguistic interview. By examining the sociolinguistic situation in Xiamen, the paper discusses two potential factors that have led to these sound changes: the regional campaign for Putonghua and the emphasis ofPinyin, a phonetically-based orthography, in the education system.
From sharing food to sharing information
Authors: Burkart Judith , Guerreiro Martins Eloisa , Miss Fabia , Zürcher Yvonne
Published: September 2018

Language is a cognitively demanding human trait, but it is also a fundamentally cooperative enterprise that rests on the motivation to share information. Great apes possess many of the cognitive prerequisites for language, but largely lack the motivation to share information. Callitrichids (including marmosets and tamarins) are highly vocal monkeys that are more distantly related to humans than great apes are, but like humans, they are cooperative breeders and all group members help raising offspring. Among primates, this rearing system is correlated with proactive prosociality, which can be expressed as motivation to share information. We therefore propose that the unique coincidence of these two components in humans set the stage for language evolution: The cognitive component inherited from our great ape-like ancestors, and the motivational one added convergently as a result of cooperative breeding. We evaluate this scenario based on a review of callitrichd vocal communication and show that furthermore, they possess many of the mechanistic elements emphasized by the mirror system hypothesis of language evolution. We end by highlighting how more systematic phylogenetic comparisons will enable us to further promote our understanding of the role of cooperative breeding during language evolution.
Pantomime and imitation in great apes
Authors: Russon Anne E.
Published: September 2018

This paper assesses great apes’ abilities for pantomime and action imitation, two communicative abilities proposed as key contributors to language evolution. Modern great apes, the only surviving nonhuman hominids, are important living models of the communicative platform upon which language evolved. This assessment is based on 62 great ape pantomimes identified via data mining plus published reports of great ape action imitation. Most pantomimes were simple, imperative, and scaffolded by partners’ relationship and scripts; some resemble declaratives, some were sequences of several inter-related elements. Imitation research consistently shows great apes perform action imitation at low fidelity, but also that action imitation may not represent a distinct process or function. Discussion focuses on how findings may advance reconstruction of the evolution of language, including what great apes may contribute to understanding ‘primitive’ forms of pantomime and imitation and how to improve their study.
The evolutionary roots of human imitation, action understanding and symbols
Authors: Myowa-Yamakoshi Masako
Published: September 2018

This paper focuses on how human complex imitation and its developmental processes are related to the abilities for action representation, acquisition of symbols, and language. After overviewing the characteristics of imitation in chimpanzees and humans, I propose a model of imitation emphasizing how these two species differ in the ways they process visual-motor information. These differences may in turn contribute to core interspecies differences in higher-order cognitive functions, not only for bodily imitation but for action understanding through complex referential information from faces, sharing symbols, and language. This ‘developmental-comparative’ approach reveals the development of species-specific intelligences, and shows what is shared and not shared between humans and other primates. In doing so, we can obtain a more complete understanding of the emergence of the ‘language-ready brain’ in relation to its biological and evolutionary foundations.
Computational challenges of evolving the language-ready brain
Authors: Arbib Michael A.
Published: September 2018

A theory of evolving the language-ready brain requires a theory of what it is that evolved. We offer the TCG (Template Construction Grammar) model of comprehension and production of utterances to exhibit hypotheses on how utterances may link to “what language is about.” A key subsystem of TCG is the SemRep system for semantic representation of a visual scene. We offer an account of how it may have evolved as an expansion of the ventral pathway supporting the planning of manual actions, complemented by a dorsal pathway for articulation. The Mirror System Hypothesis (MSH) claims that earlyHomo sapienshad protolanguage but not language and that cultural evolution yielded the social structures within which children could indeed acquire language. The article poses the challenge of understanding how a brain system could be innately specified that could develop into a TCG-like form, posing a range of questions for future research.
Mind the gap – moving beyond the dichotomy between intentional gestures and emotional facial and vocal signals of nonhuman primates
Authors: Liebal Katja , Oña Linda
Published: September 2018

Despite the variety of theories suggesting how human language might have evolved, very few consider the potential role of emotions in such scenarios. The few existing theories jointly highlight that gaining control over the production of emotional communication was crucial for establishing and maintaining larger social groups. This in turn resulted in the development of more complex social emotions and the corresponding sophisticated socio-cognitive skills to understand others’ communicative behavior, providing the grounds for language to emerge. Importantly, these theories propose that the ability of controlling emotional communication is a uniquely human trait, an assumption that we will challenge. By taking a comparative approach, we discuss recent findings from behavioral and neurobiological studies from our closest relatives, the non-human primates, on the extent of control over their gestural, facial and vocal signals. This demonstrates that research foci differ drastically across these modalities, which further enhances the traditional dichotomy between emotional, involuntary facial and vocal expressions in contrast to intentionally, voluntarily produced gestures. Based on this brief overview, we point to gaps of knowledge in primate communication research and suggest how investigating emotional expressions in our closest relatives might enrich the road map towards the evolution of human language.
The evolution of enhanced conceptual complexity and of Broca’s area
Authors: Schoenemann P. Thomas
Published: September 2018

Evolutionary change occurs most often through the modification of pre-existing structures. What were the pre-existing circuits in our primate ancestors that paved the way for human language, and how did they change in the lineages leading to our present condition? Among the neural modifications that were critical for human language, there are two of special interest: The origin and evolution of the remarkably rich conceptual world that humans share to the exclusion of other primates (which made possible increasingly sophisticated communication systems), and the origin of neural circuitry that underlies various sequential and hierarchical aspects of language, as utilized for example in syntax and word morphology. The fossil record of brain evolution and the archaeological record provide intriguing clues about these processes.
The comparative neuroprimatology 2018 (CNP-2018) road map for research on How the Brain Got Language
Authors: Arbib Michael A. , Aboitiz Francisco , Burkart Judith M. , Corballis Michael , Coudé Gino , Hecht Erin , Liebal Katja , Myowa-Yamakoshi Masako , Pustejovsky James , Putt Shelby , Rossano Federico , Russon Anne E. , Schoenemann P. Thomas , Seifert Uwe , Semendeferi Katerina , Sinha Chris , Stout Dietrich , Volterra Virginia , Wacewicz Sławomir , Wilson Benjamin
Published: September 2018

We present a new road map for research on “How the Brain Got Language” that adopts an EvoDevoSocio perspective and highlights comparative neuroprimatology – the comparative study of brain, behavior and communication in extant monkeys and great apes – as providing a key grounding for hypotheses on the last common ancestor of humans and monkeys (LCA-m) and chimpanzees (LCA-c) and the processes which guided the evolution LCA-m → LCA-c → protohumans → H. sapiens. Such research constrains and is constrained by analysis of the subsequent, primarily cultural, evolution of H. sapiens which yielded cultures involving the rich use of language.
Isozyme-Specific Role of SAD-A in Neuronal Migration During Development of Cerebral Cortex
Authors: Nakanishi Keiko , Niida Hiroyuki , Tabata Hidenori , Ito Tsuyoshi , Hori Yuki , Hattori Madoka , Johmura Yoshikazu , Yamada Chisato , Ueda Takashi , Takeuchi Kosei , Yamada Kenichiro , Nagata Koh-ichi , Wakamatsu Nobuaki , Kishi Masashi , Pan Y Albert , Ugawa Shinya , Shimada Shoichi , Sanes Joshua R , Higashi Yujiro , Nakanishi Makoto
Published: September 2018

SAD kinases regulate presynaptic vesicle clustering and neuronal polarization. A previous report demonstrated that Sada−/− and Sadb−/− double-mutant mice showed perinatal lethality with a severe defect in axon/dendrite differentiation, but their single mutants did not. These results indicated that they were functionally redundant. Surprisingly, we show that on a C57BL/6N background, SAD-A is essential for cortical development whereas SAD-B is dispensable. Sada−/− mice died within a few days after birth. Their cortical lamination pattern was disorganized and radial migration of cortical neurons was perturbed. Birth date analyses with BrdU and in utero electroporation using pCAG-EGFP vector showed a delayed migration of cortical neurons to the pial surface in Sada−/− mice. Time-lapse imaging of these mice confirmed slow migration velocity in the cortical plate. While the neurites of hippocampal neurons in Sada−/− mice could ultimately differentiate in culture to form axons and dendrites, the average length of their axons was shorter than that of the wild type. Thus, analysis on a different genetic background than that used initially revealed a nonredundant role for SAD-A in neuronal migration and differentiation.
Automated extraction of quality indicators for treatment of children with complex developmental disorders: A feasibility study using the example of attention-deficit/hyperactivity disorder
Authors: Borusiak Peter , Hameister Karin A , Jozwiak Dennis , Saatz Inga M , Mathea Lutz , Schilling Stephan , Buckard Johannes , Wegener Armin
Published: September 2018

Quality issue

Quality assessment is challenging in children with developmental disorders. Previously, a set of quality indicators (QIs) was developed and analyzed in terms of feasibility of use with patients with attention-deficit/hyperactivity disorder (ADHD). QI assessment turned out to be possible but highly complex. Thus, we compared different technologies for automated extraction of data for assessment of QIs.

Choice of solution

Four automated extraction technologies (regular expressions, Apache Solr, Apache Mahout, Apache OpenNLP) were compared with respect to their properties regarding the complexity of implementing the QI, the complexity of implementing a check module, the reliability and quality of results, the complexity of preparation of interdisciplinary medical reports, and the complexity of deployment and installation.

Implementation

Twenty medical reports from different institutions were reviewed for compliance with three QIs by these technologies and compared with expert opinions.

Evaluation

Among the four technologies, Apache Solr had the best overall performance. For manual extraction of the three QIs, at least 77 s were necessary per medical report, whereas the prototype evaluated and extracted the QIs automatically in 8 s on average. Unexpectedly, different assessments of the degree of compliance by the experts turned out to be one of the stumbling blocks. An in-depth evaluation compared results on a semantic level.

Lessons learned

It is possible to extract QIs by post-processing automated technologies. This approach can also be applied to other developmental disorders. However, a more uniform documentation throughout institutions involved will be necessary in order to implement this method in daily practice.
Is a modified Global Trigger Tool method using automatic trigger identification valid when measuring adverse events?
Authors: Mevik Kjersti , Hansen Tonje E , Deilkås Ellen C , Ringdal Alexander M , Vonen Barthold
Published: September 2018

Objectives

To evaluate a modified Global Trigger Tool (GTT) method with manual review of automatic triggered records to measure adverse events.

Design

A cross-sectional study was performed using the original GTT method as gold standard compared to a modified GTT method.

Setting

Medium size hospital trust in Northern Norway.

Participants

One thousand two hundred thirty-three records selected between March and December 2013.

Main outcome measure

Records with triggers, adverse events and number of adverse events identified. Recall (sensitivity), precision (positive predictive value), specificity and Cohen’s kappa with 95 % confidence interval were calculated.

Results

Both methods identified 35 adverse events per 1000 patient days. The modified GTT method with manual review of 658 automatic triggered records identified adverse events (n = 214) in 189 records and the original GTT method identified adverse events (n = 216) in 186 records. One hundred and ten identical records were identified with adverse events by both methods. Recall, precision, specificity and reliability for records identified with adverse events were respectively 0.59, 0.58, 0.92 and 0.51 for the modified GTT method. The total manual review time in the modified GTT method was 23 h while the manual review time using the original GTT method was 411 h.

Conclusions

The modified GTT method is as good as the original GTT method that complies with the GTTs aim monitoring the rate of adverse events. Resources saved by using the modified GTT method enable for increasing the sample size. The automatic trigger identification system may be developed to assess triggers in real-time to mitigate risk of adverse events.
Leveraging mobile health applications for biomedical research and citizen science: a scoping review
Authors: Schmitz Hannah , Howe Carol L , Armstrong David G , Subbian Vignesh
Published: September 2018

Objective

This systematic review aims to analyze current capabilities, challenges, and impact of self-directed mobile health (mHealth) research applications such as those based on the ResearchKit platform.

Materials and Methods

A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. English publications were included if: 1) mobile applications were used in the context of large-scale collection of data for biomedical research, and not as medical or behavioral intervention of any kind, and 2) all activities related to participating in research and data collection methods were executed remotely without any face-to-face interaction between researchers and study participants.

Results

Thirty-six unique ResearchKit apps were identified. The majority of the apps were used to conduct observational studies on general citizens and generate large datasets for secondary research. Nearly half of the apps were focused on chronic conditions in adults.

Discussion

The ability to generate large biomedical datasets on diverse populations that can be broadly shared and re-used was identified as a promising feature of mHealth research apps. Common challenges were low participation retention, uncertainty regarding how use patterns influence data quality, need for data validation, and privacy concerns.

Conclusion

ResearchKit and other mHealth-based studies are well positioned to enhance development and validation of novel digital biomarkers as well as generate new biomedical knowledge through retrospective studies. However, in order to capitalize on these benefits, mHealth research studies must strive to improve retention rates, implement rigorous data validation strategies, and address emerging privacy and security challenges.
Taking preventative health messages into the wider caring professions: the views of housing staff and tenants
Authors: Blank Lindsay , Holding Eleanor , Crowder Mary , Butterworth Sally , Ferrari Ed , Goyder Elizabeth
Published: September 2018

Background

In order to harness the potential impact of the wider public health workforce, innovative services are providing opportunities for social housing staff to extend their public health role. This study explored the views of housing professionals and social housing residents on the delivery of preventative health messages by housing staff in the context of the evaluation of the roll-out of a new service.

Methods

We conducted semi structured interviews with 21 neighbourhood housing officers, 4 managers and 30 social housing tenants to understand their views on the widening role and the potential impact on the preventative healthcare messages being delivered.

Results

Neighbourhood officers were willing to discuss existing health conditions with tenants; but they often did not feel comfortable discussing their lifestyle choices. Most tenants also reported that they would feel discussions around lifestyle behaviours to be intrusive and outside the remit of housing staff.

Conclusions

Resistance to discussions of lifestyle topics during home visits was found among both housing staff and tenants. Appropriate staff training and the development of strong and trusting relationships between officers and tenants is needed, if similar programmes to extend the role of housing staff are to succeed in terms of health impact.
Preservation of Monilinia fructicola Genotype Diversity Within Fungal Cankers
Authors: Dowling Madeline E. , Bridges William C. , Cox Brodie M. , Sroka Tommy , Wilson Jennifer R. , Schnabel Guido
Published: September 2018

Monilinia fructicola is a destructive pathogen causing brown rot on stone fruits worldwide. Though it is best known as a fruit rot pathogen, M. fructicola also causes blossom blight and, subsequently, twig cankers in the spring. Orchard management strategies often overlook cankers as an inoculum source, though they are an inoculum source of both blossom and fruit infections. In this study, we analyzed the role of cankers as storage structures for diverse genotypes of M. fructicola, examining whether multiple genotypes can be transmitted from blossom to canker. Fungal spores from blossoms, and 2 months later from their corresponding cankers, were collected from a conventional and an unsprayed orchard in 2015 and 2016. Simple sequence repeat markers were used to genotype 10 to 20 single spores from each of four blossom/canker pairs per orchard. Individual blossoms and cankers were detected containing up to four and five genotypes, respectively. The average number of genotypes in blossoms and corresponding cankers were not significantly different (P = 0.690) across both years and farms, showing that a bottleneck for genetic diversity was not generated during the transition from blossom to canker. The average number of genotypes unique to blossom or canker was not significantly different (P = 0.569) and no significant effect of farm (P = 0.961) or year (P = 0.520) was observed, although blossoms had a numerically greater number of unique genotypes in both cases. In conclusion, a single blossom may be infected by one or more genotypes of M. fructicola, and this diversity is being preserved in the corresponding canker. This information implicates M. fructicola cankers as diversity storehouses, and may also apply to other Monilinia spp. and fungal diseases that initiate in reproductive tissue.
Dynamics of constrained many body problems in constant curvature two-dimensional manifolds
Authors: Maciejewski Andrzej J. , Przybylska Maria
Published: September 2018

In this paper, we investigate systems of several point masses moving in constant curvature two-dimensional manifolds and subjected to certain holonomic constraints. We show that in certain cases these systems can be considered as rigid bodies in Euclidean and pseudo-Euclidean three-dimensional spaces with points which can move along a curve fixed in the body. We derive the equations of motion which are Hamiltonian with respect to a certain degenerated Poisson bracket. Moreover, we have found several integrable cases of described models. For one of them, we give the necessary and sufficient conditions for the integrability.

This article is part of the theme issue ‘Finite dimensional integrable systems: new trends and methods’.
Relations in the cohomology ring of the moduli space of flatSO(2n + 1)-connections on a Riemann surface
Authors: Adina Gamse Elisheva , Weitsman Jonathan
Published: September 2018

We consider the moduli space of flatSO(2n + 1)-connections (up to gauge transformations) on a Riemann surface, with fixed holonomy around a marked point. There are natural line bundles over this moduli space; we construct geometric representatives for the Chern classes of these line bundles, and prove that the ring generated by these Chern classes vanishes below the dimension of the moduli space, generalizing a conjecture of Newstead.

This article is part of the theme issue ‘Finite dimensional integrable systems: new trends and methods’.
Modeling sensory-motor decisions in natural behavior
Authors: Zhang Ruohan , Zhang Shun , Tong Matthew H. , Cui Yuchen , Rothkopf Constantin A. , Ballard Dana H. , Hayhoe Mary M.
Published: September 2018

Although a standard reinforcement learning model can capture many aspects of reward-seeking behaviors, it may not be practical for modeling human natural behaviors because of the richness of dynamic environments and limitations in cognitive resources. We propose a modular reinforcement learning model that addresses these factors. Based on this model, a modular inverse reinforcement learning algorithm is developed to estimate both the rewards and discount factors from human behavioral data, which allows predictions of human navigation behaviors in virtual reality with high accuracy across different subjects and with different tasks. Complex human navigation trajectories in novel environments can be reproduced by an artificial agent that is based on the modular model. This model provides a strategy for estimating the subjective value of actions and how they influence sensory-motor decisions in natural behavior.

Author summary

It is generally agreed that human actions can be formalized within the framework of statistical decision theory, which specifies a cost function for actions choices, and that the intrinsic value of actions is controlled by the brain’s dopaminergic reward machinery. Given behavioral data, the underlying subjective reward value for an action can be estimated through a machine learning technique called inverse reinforcement learning. Hence it is an attractive method for studying human reward-seeking behaviors. Standard reinforcement learning methods were developed for artificial intelligence agents, and incur too much computation to be a viable model for real-time human decision making. We propose an approach called modular reinforcement learning that decomposes a complex task into independent decision modules. This model includes a frequently overlooked variable called the discount factor, which controls the degree of impulsiveness in seeking future reward. We develop an algorithm called modular inverse reinforcement learning that estimates both the reward and the discount factor. We show that modular reinforcement learning may be a useful model for natural navigation behaviors. The estimated rewards and discount factors explain human walking direction decisions in a virtual-reality environment, and can be used to train an artificial agent that can accurately reproduce human navigation trajectories.
Investigating the conformational response of the Sortilin receptor upon binding endogenous peptide- and protein ligands by HDX-MS
Authors: Trabjerg Esben , Abu-Asad Nadia , Wan Ziqian , Kartberg Fredrik , Christensen Søren , Rand Kasper D.
Published: September 2018

Sortilin is a multifunctional transmembrane neuronal receptor involved in sorting of neurotrophic factors and apoptosis signalling. So far, structural characterization of Sortilin and its endogenous ligands has been limited to crystallographic studies of Sortilin in complex with the neuropeptide Neurotensin. Here, we use hydrogen/deuterium exchange mass spectrometry to investigate the conformational response of Sortilin to binding biological ligands including the peptides Neurotensin and the Sortilin propeptide and the proteins Progranulin and pro-Nerve growth factor-β. The results show that the ligands employ two binding sites inside the cavity of the β-propeller of Sortilin. However, ligands have distinct differences in their conformational impact on the receptor. Interestingly, the protein ligands induce conformational stabilization in a remote membrane-proximal domain, hinting at an unknown conformational link between the ligand binding region and this membrane-proximal region of Sortilin. Our findings improves our molecular understanding of Sortilin and how it mediates diverse ligand-dependent functions important in neurobiology.
Stability and sensitivity of structural connectomes: effect of thresholding and filtering and demonstration in neurodegeneration
Authors: McColgan Peter , Blom Tessel , Rees Geraint , Seunarine Kiran K , Gregory Sarah , Johnson Eileanoir , Durr Alexandra , Roos Raymund AC , Scahill Rachael I , Clark Chris A , Tabrizi Sarah J , Razi Adeel ,   the Track-HD Investigators
Published: September 2018

Structural connectomes derived using diffusion tractography are increasingly used to investigate white matter connectivity in neurological diseases. However inherent biases in diffusion tractography algorithms may lead to both false negatives and false positives in connectome construction. A range of graph thresholding approaches and more recently several streamline filtering algorithms have been developed to address these issues. However there is no consensus in the literature regarding the best available approach. Using a cohort of Huntington’s disease patients and healthy controls we compared the effect of several graph thresholding strategies: proportional, absolute, consensus and consistency thresholding, with and without streamline filtering, using Spherical Deconvolution Informed Filtering of tractograms (SIFT2) algorithm. We examined the effect of thresholding strategies on the stability of graph theory metrics and the sensitivity of these measures in neurodegeneration. We show that while a number of graph thresholding procedures result in stable metrics across thresholds, the detection of group differences is highly variable. We also showed that the application of streamline filtering using SIFT2 resultes in better detection of group differences and stronger clinical correlations. We therefore conclude that the application of SIFT2 streamline filtering without graph thresholding may be sufficient for structural connectome construction.
Membrane capacitance recordings resolve dynamics and complexity of receptor-mediated endocytosis in Wnt signalling
Authors: Bandmann Vera , Mirsanaye Ann Schirin , Schäfer Johanna , Thiel Gerhard , Holstein Thomas , Mikosch-Wersching Melanie
Published: September 2018

Receptor-mediated endocytosis is an essential process in signaling pathways for an activation of intracellular signaling cascades. One example is the Wnt signaling pathway, which seems to depend on endocytosis of the ligand-receptor complex for initiation of Wnt signal transduction. So far, the role of different endocytic pathways in Wnt signaling, the molecular players and the kinetics of this process are unclear. Here, we monitor endocytosis in Wnt3a and Wnt5a mediated signaling by membrane capacitance recordings of HEK293 cells. Our measurements revealed a fast and substantial increase in the number of endocytic vesicles. This endocytotic activity is specifically elicited by extracellular Wnt ligands; it starts immediately upon ligand binding and ceases over a period of ten minutes. By using specific inhibitors, we can dissect Wnt induced endocytosis into two independent pathways, where canonical Wnt3a is taken up mainly by clathrin-independent endocytosis and Wnt5a exclusively by clathrin-mediated endocytosis.
Quantitative proteomics reveals key roles for post-transcriptional gene regulation in the molecular pathology of FSHD
Authors: Jagannathan Sujatha , Ogata Yuko , Gafken Philip R. , Tapscott Stephen J. , Bradley Robert K.
Published: September 2018

DUX4 is a transcription factor whose misexpression in skeletal muscle causes facioscapulohumeral muscular dystrophy (FSHD). While DUX4’s transcriptional activity has been extensively characterized, the DUX4-induced proteome remains undescribed. Here, we report concurrent measurement of RNA and protein levels in DUX4-expressing cells via RNA-seq and quantitative mass spectrometry. DUX4 transcriptional targets were robustly translated, confirming the likely clinical relevance of proposed FSHD biomarkers. However, a multitude of mRNAs and proteins exhibited discordant expression changes upon DUX4 expression. Our dataset revealed unexpected proteomic, but not transcriptomic, dysregulation of diverse molecular pathways, including Golgi apparatus fragmentation, as well as extensive post-transcriptional buffering of stress response genes. Key components of RNA degradation machineries, including UPF1, UPF3B, and XRN1, exhibited suppressed protein, but not mRNA, levels, explaining the build-up of aberrant RNAs that characterizes DUX4-expressing cells. Our results provide a resource for the FSHD community and illustrate the importance of post-transcriptional processes to DUX4-induced pathology.
Phylogeny, evidence for a cryptic plastid, and distribution of Chytriodinium parasites (Dinophyceae) infecting copepods
Authors: Strassert Jürgen F. H. , Hehenberger Elisabeth , del Campo Javier , Okamoto Noriko , Kolisko Martin , Richards Thomas A. , Worden Alexandra Z. , Santoro Alyson E. , Keeling Patrick J.
Published: September 2018

Spores of the dinoflagellate Chytriodinium are known to infest copepod eggs causing their lethality. Despite the potential to control the population of such an ecologically important host, knowledge about Chytriodinium parasites is limited: we know little about phylogeny, parasitism, abundance, or geographical distribution. We carried out genome sequence surveys on four manually isolated sporocytes from the same sporangium to analyse the phylogenetic position of Chytriodinium based on SSU and concatenated SSU/LSU rRNA gene sequences, and also characterize two genes related to the plastidial heme pathway, hemL and hemY. The results suggest the presence of a cryptic plastid in Chytriodinium and a photosynthetic ancestral state of the parasitic Chytriodinium/Dissodinium clade. Finally, by mapping Tara Oceans V9 SSU amplicon data to the recovered SSU rRNA gene sequences from the sporocytes, we show that globally, Chytriodinium parasites are most abundant within the pico/nano- and mesoplankton of the surface ocean and almost absent within microplankton, a distribution indicating that they generally exist either as free-living spores or host-associated sporangia.
Reward-driven changes in striatal pathway competition shape evidence evaluation in decision-making
Authors: Dunovan Kyle , Vich Catalina , Clapp Matthew , Verstynen Timothy , Rubin Jonathan
Published: September 2018

Cortico-basal-ganglia-thalamic (CBGT) networks are critical for adaptive decision-making, yet how changes to circuit-level properties impact cognitive algorithms remains unclear. Here we explore how dopaminergic plasticity at corticostriatal synapses alters competition between striatal pathways, impacting the evidence accumulation process during decision-making. Spike-timing dependent plasticity simulations showed that dopaminergic feedback based on rewards modified the ratio of direct and indirect corticostriatal weights within opposing action channels. Using the learned weight ratios in a full spiking CBGT network model, we simulated neural dynamics and decision outcomes in a reward-driven decision task and fit them with a drift diffusion model. Fits revealed that the rate of evidence accumulation varied with inter-channel differences in direct pathway activity while boundary height varied with overall indirect pathway activity. This multi-level modeling approach demonstrates how complementary learning and decision computations can emerge from corticostriatal plasticity.

Author summary

Cognitive process models such as reinforcement learning (RL) and the drift diffusion model (DDM) have helped to elucidate the basic algorithms underlying error-corrective learning and the evaluation of accumulating decision evidence leading up to a choice. While these relatively abstract models help to guide experimental and theoretical probes into associated phenomena, they remain uninformative about the actual physical mechanics by which learning and decision algorithms are carried out in a neurobiological substrate during adaptive choice behavior. Here we present an “upwards mapping” approach to bridging neural and cognitive models of value-based decision-making, showing how dopaminergic feedback alters the network-level dynamics of cortico-basal-ganglia-thalamic (CBGT) pathways during learning to bias behavioral choice towards more rewarding actions. By mapping “up” the levels of analysis, this approach yields specific predictions about aspects of neuronal activity that map to the quantities appearing in the cognitive decision-making framework.
Inverse occlusion, a binocularly motivated treatment for amblyopia
Authors: Zhou Jiawei , Wu Yidong , Chen Yiya , Chen Xiaoxin , Liang Yunjie , Mao Yu , Yao Zhimo , He Zhifen , Lu Fan , Qu Jia , Hess Robert F.
Published: September 2018

Recent laboratory finding suggest that short-term patching the amblyopic eye (i.e., inverse occlusion) results in a larger and more sustained improvement in the binocular balance compared with normal controls. In this study, we investigate the cumulative effects of the short-term inverse occlusion in adults and old children with amblyopia. A prospective cohort study of 18 amblyopes (10-35 years old; 3 with strabismus) who have been subjected to 2 hours/day of inverse occlusion for 2 months. Patients who required refractive correction or whose refractive correction needed updating were given a 2-month period of refractive adaptation. The primary outcome measure was the binocular balance which was measured using a phase combination task, the secondary outcome measures were the best corrected visual acuity which was measured with a Tumbling E acuity chart and convert to logMAR units and the stereo acuity which was measured with the Random-dot preschool stereotest. The averaged binocular gain was 0.11 in terms of the effective contrast ratio (z = −2.344, p = 0.019, 2-tailed Related samples Wilcoxon Signed Ranks Test). The average acuity gain was 0.14 logMAR equivalent (t(17) = 0.13, p < 0.001, 2-tailed paired samples t-test). The averaged stereo acuity gain was 253 arc seconds (z = −2.689, p = 0.007). Based on more recent research concerning adult ocular dominance plasticity, contrary to current practice, patching the amblyopic eye makes more sense; comparable acuity benefits, better compliance, better binocular outcome and applicable to adults as well as old children.
Probing variability in a cognitive map using manifold inference from neural dynamics
Authors: Low Ryan J. , Lewallen Sam , Aronov Dmitriy , Nevers Rhino , Tank David W.
Published: September 2018

Hippocampal neurons fire selectively in local behavioral contexts such as the position in an environment or phase of a task,1-3and are thought to form a cognitive map of task-relevant variables.1,4,5However, their activity varies over repeated behavioral conditions,6such as different runs through the same position or repeated trials. Although widely observed across the brain,7-10such variability is not well understood, and could reflect noise or structure, such as the encoding of additional cognitive information.6,11-13Here, we introduce a conceptual model to explain variability in terms of underlying, population-level structure in single-trial neural activity. To test this model, we developed a novel unsupervised learning algorithm incorporating temporal dynamics, in order to characterize population activity as a trajectory on a nonlinear manifold—a space of possible network states. The manifold’s structure captures correlations between neurons and temporal relationships between states, constraints arising from underlying network architecture and inputs. Using measurements of activity over time but no information about exogenous behavioral variables, we recovered hippocampal activity manifolds during spatial and non-spatial cognitive tasks in rats. Manifolds were low-dimensional and smoothly encoded task-related variables, but contained an extra dimension reflecting information beyond the measured behavioral variables. Consistent with our model, neurons fired as a function of overall network state, and fluctuations in their activity across trials corresponded to variation in the underlying trajectory on the manifold. In particular, the extra dimension allowed the system to take different trajectories despite repeated behavioral conditions. Furthermore, the trajectory could temporarily decouple from current behavioral conditions and traverse neighboring manifold points corresponding to past, future, or nearby behavioral states. Our results suggest that trial-to-trial variability in the hippocampus is structured, and may reflect the operation of internal cognitive processes. The manifold structure of population activity is well-suited for organizing information to support memory,1,5,14planning,12,15,16and reinforcement learning.17,18In general, our approach could find broader use in probing the organization and computational role of circuit dynamics in other brain regions.