bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimodal Imaging of Retired Professional Contact Sport Athletes Does Not Provide Evidence of Structural and Functional Brain Damage
Authors: Zivadinov Robert , Polak Paul , Schweser Ferdinand , Bergsland Niels , Hagemeier Jesper , Dwyer Michael G. , Ramasamy Deepa P. , Baker John G. , Leddy John J. , Willer Barry S.
Published: August 2018

Background:

Long-term consequences of playing professional football and hockey on brain function and structural neuronal integrity are unknown.

Objectives:

To investigate multimodal metabolic and structural brain magnetic resonance imaging (MRI) differences in retired professional contact sport athletes compared with noncontact sport athletes.

Methods:

Twenty-one male contact sport athletes and 21 age-matched noncontact sport athletes were scanned on a 3 tesla (3T) MRI using a multimodal imaging approach. The MRI outcomes included presence, number, and volume of focal white matter signal abnormalities, volumes of global and regional tissue-specific brain structures, diffusion-tensor imaging tract-based spatial statistics measures of mean diffusivity and fractional anisotropy, quantitative susceptibility mapping of deep gray matter, presence, number, and volume of cerebral microbleeds, MR spectroscopy N-acetyl-aspartate, glutamate, and glutamine concentrations relative to creatine and phosphor creatine of the corpus callosum, and perfusion-weighted imaging mean transit time, cerebral blood flow, and cerebral blood volume outcomes. Subjects were also classified as having mild cognitive impairment.

Results:

No significant differences were found for structural or functional MRI measures between contact sport athletes and noncontact sport athletes.

Conclusions:

This multimodal imaging study did not show any microstructural, metabolic brain tissue injury differences in retired contact versus non-contact sport athletes.
Lifetime and Recent Experiences of Violence Among College Women
Authors: Fantasia Heidi Collins , Sutherland Melissa A. , Hutchinson M. Katherine
Published: August 2018

Introduction:

Intimate partner violence (IPV) and sexual violence (SV) are serious issues for female college students. Approximately one third of women have experienced physical violence or SV in their lifetime. Female college students experience high rates of both IPV and SV. The purpose of this secondary analysis was to describe the experiences of violence and associated factors reported by college women.

Methods:

This secondary analysis included data from a cross-sectional study focused on IPV/SV screening in college health centers. Random samples of female undergraduate students, aged 18–25 years, from five participating universities in the northeastern United States were contacted via email and invited to participate in the study. Eight hundred seventy-three young women met the inclusion criteria and completed survey measures.

Results:

More than half (52%, n = 457) of female undergraduate students reported having experienced at least one episode of violence in their lifetime. Almost 12% reported experiencing IPV or SV during the preceding semester. For women reporting recent experiences of violence, forced unwanted sexual activities accounted for nearly half of all reported episodes of violence (n = 46). Heavier alcohol drinking on the weekends was correlated with reports of forced sex.

Discussion:

The results highlight the prevalence of past and recent IPV/SV and increased risk among college women. Further research is needed to identify risk factors of both victimization and perpetration and the milieu of risk on college campuses. Forensic nurses should be key stakeholders in the development and implementation of interventions for violence education, screening, and referral.
Interplay Between Socioeconomic Status and Otitis Media Disease Burden in Resource-rich and Resource-poor Nations
Authors: Guys Nicholas , Ramsey Tam , Kandinov Aron , Svider Peter F. , Jyung Robert W. , Hong Robert , Sheyn Anthony
Published: August 2018

Objectives/Hypothesis:

To characterize global differences in otitis media (OM)-related disease burden between socioeconomically advantaged and disadvantaged nations.

Methods:

Using the Global Health Data Exchange, worldwide OM burden was evaluated using age-standardized disability-adjusted life years (DALYs) per 100,000 individuals in 183 countries from 1990 to 2015. Countries were organized by socioeconomic status using Human Development Index (HDI) values collected from the United Nations Development Program. Gini coefficients and concentration indices were employed to analyze disparities in OM disease burden.

Results:

From 1990 to 2015, the mean DALY rate across all nations decreased by 21.9%. When considering disease burden in relation to socioeconomic status, age-standardized DALYs decreased as HDI values increased (p < 0.001). For both children and adults, DALY rates were significantly different between HDI groups (p < 0.01). Gini coefficients decreased from 0.821 in 1990 to 0.810 in 2015, indicating a modest reduction in international health inequality. Global disparities in OM disease burden, as measured by the concentration index, worsened from 1990 to 2010 before showing a small trend reversal in 2015.

Conclusions:

To our knowledge, this is the first analysis investigating socioeconomic-related global disparities in OM disease burden using HDI values, Gini coefficients, and concentration indices. While the overall mean decrease in DALY rate from 1990 to 2015 is encouraging, the net decrease in concentration index during this period suggests less-developed nations continue to shoulder a disproportionate burden. Greater resource allocation to resource-poor nations may be warranted, as disease burden negatively impacts these countries to a greater degree.
Advances in machine perfusion, organ preservation, and cryobiology: potential impact on vascularized composite allotransplantation
Authors: Burlage Laura C. , Tessier Shannon N. , Etra Joanna W. , Uygun Korkut , Brandacher Gerald
Published: August 2018

Purpose of review

In this review, we discuss novel strategies that allow for extended preservation of vascularized composite allografts and their potential future clinical implications for the field of vascularized composite allotransplantation (VCA).

Recent findings

The current gold standard in tissue preservation – static cold preservation on ice – is insufficient to preserve VCA grafts for more than a few hours. Advancements in the field of VCA regarding matching and allocation, desensitization, and potential tolerance induction are all within reasonable reach to achieve; these are, however, constrained by limited preservation time of VCA grafts. Although machine perfusion holds many advantages over static cold preservation, it currently does not elongate the preservation time. More extreme preservation techniques, such as cryopreservation approaches, are, however, specifically difficult to apply to composite tissues as the susceptibility to ischemia and cryoprotectant agents varies greatly by tissue type.

In the current scope of extended preservation protocols, high subzero approaches of VCA grafts will be particularly critical enabling technologies for the implementation of tolerance protocols clinically. Ultimately, advances in both preservation techniques and tolerance induction have the potential to transform the field of VCA and eventually lead to broad applications in reconstructive transplantation.
Improving Patient Flow From the Emergency Department Utilizing a Standardized Electronic Nursing Handoff Process
Authors: Potts Lisa , Ryan Catherine , Diegel-Vacek Lauren , Murchek Alisa
Published: August 2018

OBJECTIVE

The goal of this project was to decrease handoff delays from the emergency department (ED) as measured by ready to move (RTM)–to–occupied time.

BACKGROUND

ED boarding compromises the quality, safety, and experience of patient care. Lack of standardized and transparent handoff communication contributes to boarding time. This process improvement initiative implemented a standardized electronic situation, background, assessment, and recommendation (eSBAR) format-based nursing handoff process from the ED to a medical unit.

METHODS

Nursing staff were educated face-to-face regarding the initiative background, significance, and process. Outcomes were measured before and after eSBAR implementation.

RESULTS

Before implementation, the house-wide average RTM-to-occupied time was 83.6 minutes. This decreased to 49 minutes (a 41.4% decrease) 3 weeks after implementation and improved further to 47 minutes at 10 months after implementation. No related patient safety or quality issues were identified.

CONCLUSIONS

The use of an electronic, standardized handoff communication process resulted in decreased boarding time and increased bed flow efficiency.
Death and Dying Over 30 Years in the ICU: Personal Reflection
Authors: Argent Andrew C.
Published: August 2018

Objective:

To describe individual perspective over ~30 years in a PICU in Cape Town, South Africa.

Data Sources:

Personal experience and reflection, complemented by published local data.

Study Selection:

Not applicable/illustrative publications of local other data.

Data Extraction:

Not applicable/or other (as appropriate).

Data Synthesis:

Narrative, experiential reflection.
Ethical, Cultural, Social, and Individual Considerations Prior to Transition to Limitation or Withdrawal of Life-Sustaining Therapies
Authors: Kirsch Roxanne E. , Balit Corrine R. , Carnevale Franco A. , Latour Jos M. , Larcher Victor
Published: August 2018

As part of the invited supplement on Death and Dying in the PICU, we reviewed ethical, cultural, and social considerations for the bedside healthcare practitioner prior to engaging with children and families in decisions about limiting therapies, withholding, or withdrawing therapies in a PICU. Clarifying beliefs and values is a necessary prerequisite to approaching these conversations. Striving for medical consensus is important. Discussion, reflection, and ethical analysis may determine a range of views that may reasonably be respected if professional disagreements persist. Parental decisional support is recommended and should incorporate their information needs, perceptions of medical uncertainty, child’s condition, and their role as a parent. Child’s involvement in decision making should be considered, but may not be possible. Culturally attuned care requires early examination of cultural perspectives before misunderstandings or disagreements occur. Societal influences may affect expectations and exploration of such may help frame discussions. Hospital readiness for support of social media campaigns is recommended. Consensus with family on goals of care is ideal as it addresses all parties’ moral stance and diminishes the risk for superseding one group’s value judgments over another. Engaging additional supportive services early can aid with understanding or resolving disagreement. There is wide variation globally in ethical permissibility, cultural, and societal influences that impact the clinician, child, and parents. Thoughtful consideration to these issues when approaching decisions about limitation or withdrawal of life-sustaining therapies will help to reduce emotional, spiritual, and ethical burdens, minimize misunderstanding for all involved, and maximize high-quality care delivery.
Learning From Investigation After Death
Authors: Griffiths Benedict T. , Sebire Neil J. , Brierley Joe
Published: August 2018

Objectives:

The acceptability of traditional postmortem examination to bereaved families, coupled with a misguided professional view about their limited utility, has led to decrease in this ultimate investigation. Research recurrently demonstrates that postmortem examination provides clinically relevant information despite ever-improving diagnostic techniques. This review examines postmortem examination for children who die in PICU—whether consented or nonconsented (legally mandated). It explores how such investigations might provide useful information and suggests that PICU and pathology teams work together to provide information for bereaved families to either enable them to consent to postmortem interventions or understand necessary forensic processes. Newer technologies such as postmortem imaging and laparoscope-assisted/ultrasound-guided tissue sampling are reviewed, with the hope that greater acceptability to families may lead to a welcome resurgence in postmortem information for clinicians, tempered by realization that widespread acceptance of their equivalence to standard techniques by most forensic services is awaited.

Data Sources:

Literature review.

Study Selection:

Journal articles describing practices in pediatric and adult postmortem examination.

Data Extraction:

Not available.

Data Synthesis:

Not available.

Conclusions:

The PICU team have a duty to help bereaved parents understand what postmortem investigations are available, or might be mandated, after the death of their child. A thoughtful, unhurried, and compassionate discussion should be arranged with expert pathology teams and any specialists who have cared for the child to explain how investigations can provide information about what is involved—including availability and suitability of newer techniques. This should include information about when a child’s body, organs, or tissues will be available for the funeral, necessary legal procedures and how and when results will be explained to them.
Modes of Death and the Dying Process in Brazilian PICU Over the Last 30 Years: Personal Reflections
Authors: Piva Jefferson P.
Published: August 2018

This text is part of the chapter 7 of a special issue supplement called “Death and Dying in PICU” having Christopher S. Parshuram and Karen Dryden-Palmer as the guest editors. I present my personal perception regarding the modes of death and the dying process in Brazilian PICU over the last 30 years. A big change in this regard was observed in our country from the 1980s to nowadays. The PICU mortality rate decreased significantly from over 20% to below 5% as well as the modes of death being observed that the life support limitation is far the most frequent death process in the PICU. Palliative care, in the last 10 years, increased its coverage in our country and being frequently offered as a complementary care to terminal ill patients in the PICU.
Discussing Death as a Possible Outcome of PICU Care
Authors: Gilleland Jonathan C. , Parshuram Christopher S.
Published: August 2018

Objectives:

To describe practical considerations related to discussions about death or possible death of a critically ill child.

Data Sources:

Personal experience and reflection. Published English language literature.

Study Selection:

Selected illustrative studies.

Data Extraction:

Not available.

Data Synthesis:

Narrative and experiential review were used to describe the following areas benefits and potential adverse consequences of conversations about risk of death and the timing of, preparation for, and conduct of conversations about risk of death.

Conclusions:

Timely conversations about death as a possible outcome of PICU care are an important part of high-quality ICU care. Not all patients “require” these conversations; however, identifying patients for whom conversations are indicated should be an active process. Informed conversations require preparation to provide the best available objective information. Information should include distillation of local experience, incorporate the patients’ clinical trajectory, the potential impact(s) of alternate treatments, describe possible modes of death, and acknowledge the extent of uncertainty. We suggest the more factual understanding of risk of death should be initially separated from the more inherent value-laden treatment recommendations and decisions. Gathering and sharing of collective knowledge, conduct of additional investigations, and time can increase the factual content of risk of death discussions. Timely and sensitive delivery of this best available knowledge then provides foundation for high-quality treatment recommendations and decision-making.
Notes on the Development of the Slovenian Ethical Recommendations for Decision-Making on Treatment and Palliative Care of Patients at the End of Life in Intensive Care Medicine
Authors: Grosek Stefan , Orazem Miha , Groselj Urh
Published: August 2018

Objectives:

To describe the process of development of “Slovenian Ethical Recommendations for Decision-Making on Treatment and Palliative Care of Patients at the End of Life in Intensive Care Medicine” and its final outcomes.

Data Sources:

Personal experience and reflection, complemented by published data.

Study Selection:

Not applicable.

Data Extraction:

Not applicable.

Data Synthesis:

Narrative, experiential reflection, literature review.

Conclusions:

Slovenian ethical recommendations bring a small piece to a long tradition of ethical practice in a small European country. Despite the availability of informative international guiding documents on the issue, there are several specific good reasons for a small country or a region to develop its own unique guidelines (i.e., lack of local directives and legislation, unique cultural and political situation, need for development of professional expertise and terminology, and to educate healthcare providers). The authors strongly believe that our recommendations positively impact practice and will support best possible integrated palliative and end-of-life quality care with the ICU.
When a Child Dies in the PICU Despite Ongoing Life Support
Authors: Lewis-Newby Mithya , Clark Jonna D. , Butt Warwick W. , Dryden-Palmer Karen , Parshuram Christopher S. , Truog Robert D.
Published: August 2018

Objectives:

To examine the circumstance of death in the PICU in the setting of ongoing curative or life-prolonging goals.

Data Sources:

Multidisciplinary author group, international expert opinion, and use of current literature.

Data Synthesis:

We describe three common clinical scenarios when curative or life-prolonging goals of care are pursued despite a high likelihood of death. We explore the challenges to providing high-quality end-of-life care in this setting. We describe possible perspectives of families and ICU clinicians facing these circumstances to aid in our understanding of these complex deaths. Finally, we offer suggestions of how PICU clinicians might improve the care of children at the end of life in this setting.

Conclusions:

Merging curative interventions and optimal end-of-life care is possible, important, and can be enabled when clinicians use creativity, explore possibilities, remain open minded, and maintain flexibility in the provision of critical care medicine. When faced with real and perceived barriers in providing optimal end-of-life care, particularly when curative goals of care are prioritized despite a very poor prognosis, tensions and conflict may arise. Through an intentional exploration of self and others’ perspectives, values, and goals, and working toward finding commonality in order to align with each other, conflict in end-of-life care may lessen, allowing the central focus to remain on providing optimal support for the dying child and their family.
Logistics of Withdrawal of Life-Sustaining Therapies in PICU
Authors: Dryden-Palmer Karen , Haut Cathy , Murphy Samantha , Moloney-Harmon Patricia
Published: August 2018

Objectives:

To describe practical considerations and approaches to best practices for end-of-life care for critically ill children and families in the PICU.

Data Sources:

Literature review, personal experience, and expert opinion.

Study Selection:

A sampling of the foundational and current evidence related to the withdrawal of life-sustaining therapies in the context of childhood critical illness and injury was accessed.

Data Extraction:

Moderated by the authors and supported by lived experience.

Data Synthesis:

Narrative review and experiential reflection.

Conclusions:

Consequences of childhood death in the PICU extend beyond the events of dying and death. In the context of withdrawal of life-sustaining therapies, achieving a quality death is impactful both in the immediate and in the longer term for family and for the team. An individualized approach to withdrawal of life-sustaining therapies that is informed by empiric and practical knowledge will ensure best care of the child and support the emotional well-being of child, family, and the team. Adherence to the principles of holistic and compassionate end-of-life care and an ongoing commitment to provide the best possible experience for withdrawal of life-sustaining therapies can achieve optimal end-of-life care in the most challenging of circumstances.
Unusual Presentation of Hurthle Cell Carcinoma With TENIS Syndrome as Left Atrial Thrombus on 18F-FDG PET/CT
Authors: Sood Apurva , Parihar Ashwin Singh , Sood Ashwani , Kumar Rajender , Prakash Gaurav , Singhal Manphool , Gulati Ajay , Mittal Bhagwant Rai , Bahl Ajay , Singh Shashank
Published: August 2018

Differentiated thyroid cancer (DTC) with thyroglobulin elevation and negative 131I scintigraphy (TENIS) syndrome is a diagnostic and therapeutic dilemma. Treatment of differentiated thyroid cancer has an excellent outcome, but treatment options in TENIS are limited with the exception of surgically amenable disease. We present a case of TENIS syndrome with incidental detection of tumor thrombus in right pulmonary vein extending to the left atrium on 18F-FDG PET/CT and subsequently complicating as an occipital bleed. The timely detection of the thrombus facilitated early initiation of anticoagulant therapy. However, the intracranial bleed precluded the continuation of anticoagulant therapy.
A Case of Glioblastoma With Calcified Region Imaged With 18F-NaF PET/CT
Authors: Ishimura Mariko , Yamamoto Yuka , Mitamura Katsuya , Norikane Takashi , Nishiyama Yoshihiro
Published: August 2018

18F-NaF is a bone-seeking positron-emitting tracer with high sensitivity and specificity for detection of osseous lesions. We report a case of primary glial tumor that showed extraosseous uptake on 18F-NaF PET/CT. CT revealed a mass in the right parietal lobe with calcification. 18F-NaF PET/CT showed abnormal tracer uptake in the brain tumor, which was subsequently confirmed to be a glioblastoma by histologic examination.
Neurophysiological biomarkers in amyotrophic lateral sclerosis
Authors: Vucic Steve , Rutkove Seward B.
Published: August 2018

Purpose of review

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of the motor neurons, characterized by upper motor neuron (UMN) and lower motor neuron (LMN) dysfunction. There have been significant technological advances in the development of neurophysiological biomarkers of UMN and LMN dysfunction in ALS. In this review, we discuss major advances in development of neurophysiological biomarkers in ALS, critiquing their potential in diagnosis and prognosis of ALS, as well as utility in monitoring treatment effects.

Recent findings

The threshold tracking transcranial magnetic stimulation (TMS) technique has established cortical hyperexcitability as an early and specific biomarker of UMN dysfunction in ALS, and associated with neurodegeneration. In addition to establishing cortical hyperexcitability as a pathophysiological mechanism, threshold tracking TMS has enabled an earlier diagnosis of ALS and provided a means of monitoring effects of therapeutic agents. Biomarkers of LMN dysfunction, including motor unit number estimation, the neurophysiological index, electrical impedance myography and axonal excitability techniques, have all exhibited utility in monitoring disease progression.

In addition to enhancing ALS diagnosis, the development of novel neurophysiological biomarkers has implications for clinical trials research and drug development, enabling the assessment of biological efficacy of agents in early stages of drug development.
Design for data ethics: using service design approaches to operationalize ethical principles on four projects
Authors: Drew Cat
Published: August 2018

Ethical frameworks provide helpful guidance about what you should—and should not—do in relation to data projects. But they do not provide definitive yes/no answers about what an ethical data project is or is not. Indeed, research (Ipsos-MORI 2015 Public dialogue into the ethics of data science in government) conducted for the initial development of the Government's Data Ethics Framework shows that the public does not hold any clear red lines; rather, they make nuanced assessments based on a number of variables, including public good and privacy. Ethical frameworks provide a list of these variables to consider in shaping the form of the work. Some are now starting to provide more practical tools and guidance to reshape data projects and push it along those variables into a more ethical space. Alongside technical tools,
service design approaches
can help enhance the degree to which a data project is ethical, and provides a toolkit for data scientists, analysts and policymakers to take projects from ‘what should we do’ to ‘how can we do it’. This paper sets out the emergence of data science ethical frameworks within the context of the use of data for social good, and—with the recent release of the updated UK Government Data Ethics Framework—shows the recognition more practical guidance needs to be provided. The author then argues that service design approaches provide a helpful ‘wrap around’ for data projects, and draws on experience in using service design tools on four projects, as well as wider examples.

This article is part of a discussion meeting issue ‘The growing ubiquity of algorithms in society: implications, impacts and innovations’.
Algorithmic regulation and the rule of law
Authors: Hildebrandt Mireille
Published: August 2018

In this brief contribution, I distinguish between code-driven and data-driven regulation as novel instantiations of legal regulation. Before moving deeper into data-driven regulation, I explain the difference between law and regulation, and the relevance of such a difference for the rule of law. I discuss artificial legal intelligence (ALI) as a means to enable quantified legal prediction and argumentation mining which are both based on machine learning. This raises the question of whether the implementation of such technologies should count as law or as regulation, and what this means for their further development. Finally, I propose the concept of ‘agonistic machine learning’ as a means to bring data-driven regulation under the rule of law. This entails obligating developers, lawyers and those subject to the decisions of ALI to re-introduce adversarial interrogation at the level of its computational architecture.

This article is part of a discussion meeting issue ‘The growing ubiquity of algorithms in society: implications, impacts and innovations'.
The growing ubiquity of algorithms in society: implications, impacts and innovations
Authors: Olhede S. C. , Wolfe P. J.
Published: August 2018

The growing ubiquity of algorithms in society raises a number of fundamental questions concerning governance of data, transparency of algorithms, legal and ethical frameworks for automated algorithmic decision-making and the societal impacts of algorithmic automation itself. This article, an introduction to the discussion meeting issue of the same title, gives an overview of current challenges and opportunities in these areas, through which accelerated technological progress leads to rapid and often unforeseen practical consequences. These consequences—ranging from the potential benefits to human health to unexpected impacts on civil society—are summarized here, and discussed in depth by other contributors to the discussion meeting issue.

This article is part of a discussion meeting issue ‘The growing ubiquity of algorithms in society: implications, impacts and innovations'.
Motor module generalization across balance and walking is reduced after stroke
Authors: Allen Jessica L. , Kesar Trisha M. , Ting Lena H.
Published: August 2018

Here, we examined features of muscle coordination associated with reduced walking performance in chronic stroke survivors. Using motor module (a.k.a. muscle synergy) analysis, we identified differences in the modular control of overground walking and standing reactive balance in stroke survivors compared to age-similar neurotypical controls. In contrast to previous studies that demonstrated reduced motor module number post-stroke, our cohort of stroke survivors did not exhibit a reduction in motor module number compared to controls during either walking or reactive balance. Instead, the pool of motor modules common to walking and reactive balance was smaller, suggesting a reduction in generalizability of motor module function across behaviors. The motor modules common to walking and reactive balance tended to be less variable and more distinct, suggesting more reliable output compared to motor modules specific to one behavior. Indeed, higher levels of motor module generalization was associated with faster walking speeds in stroke survivors. Further, recruitment of a common independent plantarflexor module across both behaviors was associated with faster walking speeds. Our work is the first to show that motor module generalization across walking and balance may help to distinguish important and clinically-relevant differences in walking performance across stroke survivors that would have been overlooked by examining only a single behavior. Finally, as similar relationships between motor module generalization and walking performance have been demonstrated in healthy young adults and individuals with Parkinson’s disease, our work suggests that motor module generalization across walking and balance may be important for well-coordinated walking.

New and Noteworthy

Our study is the first to simultaneously examine neuromuscular control of walking and standing reactive balance in stroke survivors. We show that motor module generalization across these behaviors (i.e., recruiting common motor modules) is reduced compared to neurotypical controls, which is associated with slower walking speeds. This is true despite no difference in motor module number between groups within each behavior, suggesting that motor module generalization across walking and balance is important for well-coordinated walking.
Modeling and Cost Benefit Analysis to Guide Deployment of POC Diagnostics for Non-typhoidalSalmonellaInfections with Antimicrobial Resistance
Authors: Manore Carrie , Graham Todd , Carr Alexa , Feryn Alicia , Jakhar Shailja , Mukundan Harshini , Highlander Hannah Callender
Published: August 2018

Invasive non-typhoidalSalmonella(NTS) is among the leading causes of blood stream infections in sub-Saharan Africa and other developing regions, especially among pediatric populations. Invasive NTS can be difficult to treat and have high case-fatality rates, in part due to emergence of strains resistant to broad-spectrum antibiotics. Furthermore, improper treatment contributes to increased antibiotic resistance and death. Point of care (POC) diagnostic tests that rapidly identify invasive NTS infection, and differentiate between resistant and non-resistant strains, may greatly improve patient outcomes and decrease resistance at the community level. Here we present for the first time a model for NTS dynamics in high risk populations that can analyze the potential advantages and disadvantages of four strategies involving POC diagnostic deployment, and the resulting impact on antimicrobial treatment for patients. Our analysis strongly supports the use of POC diagnostics coupled with targeted antibiotic use for patients upon arrival in the clinic for optimal patient and public health outcomes. We show that even the use of imperfect POC diagnostics can significantly reduce total costs and number of deaths, provided that the diagnostic gives results quickly enough that patients are likely to return or stay to receive targeted treatment.
3D Tissue elongation via ECM stiffness-cued junctional remodeling
Authors: Chen Dong-Yuan , Crest Justin , Streichan Sebastian J. , Bilder David
Published: August 2018

Organs are sculpted by extracellular as well as cell-intrinsic forces, but how collective cell dynamics are orchestrated in response to microenvironmental cues is poorly understood. Here we apply advanced image analysis to reveal ECM-responsive cell behaviors that drive elongation of the Drosophila follicle, a model 3D system in which basement membrane stiffness instructs tissue morphogenesis. Throughin totomorphometric analyses of WT and ‘round egg’ mutants, we find that neither changes in average cell shape nor oriented cell division are required for appropriate organ shape. Instead, a major element is a reorientation of elongated cells at the follicle anterior. Polarized reorientation is regulated by mechanical cues from the basement membrane, which are transduced by the Src tyrosine kinase to alter junctional E-cadherin trafficking. This mechanosensitive cellular behavior represents a conserved mechanism that can elongate ‘edgeless’ tubular epithelia in a process distinct from those that elongate bounded, planar epithelia.
A computational model of loss of dopaminergic cells in Parkinson’s disease due to glutamate-induced excitotoxicity
Authors: Muddapu Vignayanandam R. , Mandali Alekhya , Chakravarthy Srinivasa V. , Ramaswamy Srikanth
Published: August 2018

Parkinson’s disease (PD) is a neurodegenerative disease associated with progressive and inexorable loss of dopaminergic cells in Substantia Nigra pars compacta (SNc). A full understanding of the underlying pathogenesis of this cell loss is unavailable, though a number of mechanisms have been indicated in the literature. A couple of these mechanisms, however, show potential for the development of radical and promising PD therapeutics. One of these mechanisms is the peculiar metabolic vulnerability of SNc cells by virtue of their excessive energy demands; the other is the excitotoxicity caused by excessive glutamate release onto SNc by an overactive Subthalamic Nucleus (STN). To investigate the latter hypothesis computationally, we developed a spiking neuron network model of the SNc-STN-GPe system. In the model, prolonged stimulation of SNc cells by an overactive STN leads to an increase in a ‘stress’ variable; when the stress in a SNc neuron exceeds a stress threshold the neuron dies. The model shows that the interaction between SNc and STN involves a positive feedback due to which, an initial loss of SNc cells that crosses a threshold causes a runaway effect that leads to an inexorable loss of SNc cells, strongly resembling the process of neurodegeneration. The model further suggests a link between the two aforementioned PD mechanisms: metabolic vulnerability and glutamate excitotoxicity. Our simulation results show that the excitotoxic cause of SNc cell loss in PD might be initiated by weak excitotoxicity mediated by energy deficit, followed by strong excitotoxicity, mediated by a disinhibited STN. A variety of conventional therapies are simulated in the model to test their efficacy in slowing down or arresting SNc cell loss. Among the current therapeutics, glutamate inhibition, dopamine restoration, subthalamotomy and deep brain stimulation showed superior neuroprotective effects in the proposed model.
Comparison of environmental, biological and anthropogenic causes of wildlife–vehicle collisions among three large herbivore species
Authors: Christine Saint-Andrieux , Clément Calenge , Christophe Bonenfant
Published: August 2018

Wildlife–vehicle collisions are of increasing concern with regards to the continuous and accelerating anthropogenic development. Preventing and mitigating collisions with wildlife will require a better understanding of the environmental and biological drivers of collision risks. Because species of large mammals differ in terms of food requirements, habitat selection and movement behaviours we tested at the management unit level if the density of collisions with red deer, roe deer and wild boar differed in terms of spatial distribution and explanatory factors. From 20,275 documented collisions in France between years 1990 and 2006, we found marked differences in the most influential environmental factors accounting for the density of collisions among the three species. The effect of road density was higher for the red deer than for the two other species and did not level off at our spatial-scale of observation. As expected, the annual hunting harvest – interpreted as a proxy of population abundance – was positively associated with the density of collisions for all species, being the strongest for red deer. While the collision density decreased with the proportion of forest in a management unit for wild boar, it increased with the fragmentation of forests for red deer that commute among forest patches between day and night. To reduce the number of wildlife– vehicle collisions, our results suggest to generalise road fencing and/or a control of abundance of large herbivore populations. Mitigation measures should target units where the collision risk is the highest for the most problematic species.
Deciphering the roles of N-glycans on collagen-platelet interactions
Authors: Toonstra Christian , Hu Yingwei , Zhang Hui
Published: August 2018

Collagen is a potent agonist for platelet activation, presenting itself as a key contributor to coagulation via interactions with platelet glycoproteins. The fine-details dictating platelet-collagen interactions are poorly understood. In particular, glycosylation could be a key determinant in the platelet-collagen interaction. Here we report an affinity purification coupled to mass spectrometry-based approach to elucidate the function of N-glycans in dictating platelet-collagen interactions. By integrative proteomic and glycoproteomic analysis of collagen-platelet interactive proteins with N-glycan manipulation, we demonstrate that the interaction of platelet adhesive receptors with collagen are highly N-glycan regulated, with glycans on many receptors playing positive roles on collagen binding, with glycans on other platelet glycoproteins exhibiting inhibitory roles on the binding to collagen. Our results significantly enhance our understanding of the details of glycans influencing the platelet-collagen interaction.
Nitrogen utilisation by the metabolic generalist pathogen Mycobacterium tuberculosis
Authors: Agapova Aleksandra , Hunt Debbie M. , Petridis Michael , Garza-Garcia Acely , Sohaskey Charles D. , Carvalho Luiz Pedro S. de
Published: August 2018

Bacterial metabolism is fundamental to pathogenesis and has a dominant effect on bacterial killing by antibiotics. Here we explore how Mycobacterium tuberculosis utilises amino acids as nitrogen sources, using a combination of bacterial physiology and stable isotope tracing coupled to liquid chromatography mass spectrometry metabolomics methods. Our results define core properties of the nitrogen metabolic network from M. tuberculosis, such as: (i) the lack of homeostatic control of amino acid pool sizes; (ii) similar rates of utilisation of different amino acids as sole nitrogen sources; (iii) improved nitrogen utilisation from amino acids compared to ammonium; and (iv) co-metabolism of nitrogen sources. Finally, we discover that alanine dehydrogenase, is involved in ammonium assimilation in M. tuberculosis, in addition to its essential role in alanine utilisation. This study represents the first in-depth analysis of nitrogen source utilisation by metabolic generatlist M. tuberculosis and reveals a flexible metabolic network with characteristics that are likely product of evolution in the human host.
Palantir characterizes cell fate continuities in human hematopoiesis
Authors: Setty Manu , Kiseliovas Vaidotas , Levine Jacob , Gayoso Adam , Mazutis Linas , Pe’er Dana
Published: August 2018

Recent studies using single cell RNA-seq (scRNA-seq) data derived from differentiating systems have raised fundamental questions regarding the discrete vs continuous nature of both differentiation and cell fate. Here we present Palantir, an algorithm that models trajectories of differentiating cells, which treats cell-fate as a probabilistic process, and leverages entropy to measure the changing nature of cell plasticity along the differentiation trajectory. Palantir generates a high resolution pseudotime ordering of cells, and assigns each cell state with its probability to differentiate into each terminal state. We apply Palantir to human bone marrow scRNA-seq data and detect key landmarks of hematopoietic differentiation. Palantir’s resolution enables identification of key transcription factors driving lineage fate choices, as these TFs closely track when cells lose plasticity. We demonstrate that Palantir is generalizable to diverse tissue types and well-suited to resolve less studied differentiating systems.
Active information maintenance in working memory by a sensory cortex
Authors: Zhang Xiaoxing , Yan Wenjun , Wang Wenliang , Fan Hongmei , Hou Ruiqing , Chen Yulei , Chen Zhaoqin , Duan Shumin , Compte Albert , Li Chengyu T.
Published: August 2018

Working memory is a critical function of the brain to maintain and manipulate information over delay periods of seconds. Sensory areas have been implicated in working memory; however, it is debated whether the delay-period activity of sensory regions is actively maintaining information or passively reflecting top-down inputs. We hereby examined the anterior piriform cortex, an olfactory cortex, in head-fixed mice performing a series of olfactory working memory tasks. Information maintenance is necessary in these tasks, especially in a dual-task paradigm in which mice are required to perform another distracting task while actively maintaining information during the delay period. Optogenetic suppression of the piriform cortex activity during the delay period impaired performance in all the tasks.Furthermore, electrophysiological recordings revealed that the delay-period activity of the anterior piriform cortex encoded odor information with or without the distracting task.Thus, this sensory cortex is critical for active information maintenance in working memory.
Parameter tuning is a key part of dimensionality reduction via deep variational autoencoders for single cell RNA transcriptomics
Authors: Hu Qiwen , Greene Casey S.
Published: August 2018

Single-cell RNA sequencing (scRNA-seq) is a powerful tool to profile the transcriptomes of a large number of individual cells at a high resolution. These data usually contain measurements of gene expression for many genes in thousands or tens of thousands of cells, though some datasets now reach the million-cell mark. Projecting high-dimensional scRNA-seq data into a low dimensional space aids downstream analysis and data visualization. Many recent preprints accomplish this using variational autoencoders (VAE), generative models that learn underlying structure of data by compress it into a constrained, low dimensional space. The low dimensional spaces generated by VAEs have revealed complex patterns and novel biological signals from large-scale gene expression data and drug response predictions. Here, we evaluate a simple VAE approach for gene expression data, Tybalt, by training and measuring its performance on sets of simulated scRNA-seq data. We find a number of counter-intuitive performance features: i.e., deeper neural networks can struggle when datasets contain more observations under some parameter configurations. We show that these methods are highly sensitive to parameter tuning: when tuned, the performance of the Tybalt model, which was not optimized for scRNA-seq data, outperforms other popular dimension reduction approaches – PCA, ZIFA, UMAP and t-SNE. On the other hand, without tuning performance can also be remarkably poor on the same data. Our results should discourage authors and reviewers from relying on self-reported performance comparisons to evaluate the relative value of contributions in this area at this time. Instead, we recommend that attempts to compare or benchmark autoencoder methods for scRNA-seq data be performed by disinterested third parties or by methods developers only on unseen benchmark data that are provided to all participants simultaneously because the potential for performance differences due to unequal parameter tuning is so high.
Deep-learning-based flexible pipeline for segmenting and tracking cells in 3D image time series for whole brain imaging
Authors: Wen Chentao , Miura Takuya , Fujie Yukako , Teramoto Takayuki , Ishihara Takeshi , Kimura Koutarou D.
Published: August 2018

The brain is a complex system that operates based on coordinated neuronal activities. Brain-wide cellular calcium imaging techniques have quickly advanced in recent years and become powerful tools for understanding the neuronal activities of small animal models. The whole brain imaging generally requires to extract the neuronal activities from three-dimensional (3D) image series. Unfortunately, the 3D image series are obtained under imaging conditions different among laboratories and extracting neuronal activities from the data requires multiple processes. Therefore researchers need to develop their own software, which has prevented the application of whole-brain imaging experiments in more laboratories. Here, we combined traditional image processing techniques with the powerful deep-learning method which can be flexibly modified to fit 3D image data in the nematodeCaenorhabditis elegansobtained under different conditions. We first trained the 3D U-net deep network to classify each pixel into cell and non-cell categories. Cells merged as a whole region were further separated into individual cells by watershed segmentation. The cells were then tracked in 3D space over time with the combination of a feedforward network and a point set registration method to use local and global relative positions of the cells, respectively. Remarkably, one manually annotated 3D image combined with data augmentation was sufficient for training the deep networks to obtain satisfactory tracking results. Our method correctly tracked more than 98% of neurons in three different image datasets and successfully extracted brain-wide neuronal activities. Our method worked well even when the sampling rate was reduced: 86% correct in case 4/5 frames were removed, and when artificial noise was added into the raw images: 91% correct in case 35 times of background-level noise was added. Our results proved that deep learning is widely applicable to different datasets and can help us in establishing a flexible pipeline for extracting whole brain activities.