bluuebunny/crossref_metadata_2025 huggingface dataset:
More than $1 billion needed annually to secure Africa’s protected areas with lions
Authors: Lindsey Peter A. , Miller Jennifer R. B. , Petracca Lisanne S. , Coad Lauren , Dickman Amy J. , Fitzgerald Kathleen H. , Flyman Michael V. , Funston Paul J. , Henschel Philipp , Kasiki Samuel , Knights Kathryn , Loveridge Andrew J. , Macdonald David W. , Mandisodza-Chikerema Roseline L. , Nazerali Sean , Plumptre Andrew J. , Stevens Riko , Van Zyl Hugo W. , Hunter Luke T. B.
Published: October 2018

Significance

Protected areas (PAs) are the cornerstone of conservation yet face funding inadequacies that undermine their effectiveness. Using the conservation needs of lions as a proxy for those of wildlife more generally, we compiled a dataset of funding in Africa’s PAs with lions and estimated a minimum target for conserving the species and managing PAs effectively. PAs with lions require $1.2 to $2.4 billion or $1,000 to $2,000/km
2
annually, yet receive just $381 million or $200/km
2
(median) annually. Nearly all PAs with lions are inadequately funded; deficits total $0.9 to $2.1 billion. Governments and donors must urgently and significantly invest in PAs to prevent further declines of lions and other wildlife and to capture the economic, social, and environmental benefits that healthy PAs can confer.
Coiled-coil structure-dependent interactions between polyQ proteins and Foxo lead to dendrite pathology and behavioral defects
Authors: Kwon Min Jee , Han Myeong Hoon , Bagley Joshua A. , Hyeon Do Young , Ko Byung Su , Lee Yun Mi , Cha In Jun , Kim Seung Yeol , Kim Dong Young , Kim Ho Min , Hwang Daehee , Lee Sung Bae , Jan Yuh Nung
Published: October 2018

Significance

It remains unclear how the structural properties of polyglutamine (polyQ) proteins, which underlie several neurodegenerative disorders, including Huntington’s disease and spinocerebellar ataxias (SCAs), translate into the toxicity of these proteins. Here, we demonstrate that coiled-coil structures in expanded polyQ regions of SCA type 3 (SCA3) proteins cause dendrite defects in
Drosophila
neurons, as well as behavioral abnormalities. Moreover, interactions of SCA3 with Foxo mediated by coiled-coil domains of these two proteins resulted in functional impairment of this transcription factor, whereas its overexpression significantly rescued the SCA3-induced defects. Our study expanded the current understanding of neuronal pathology mediated by polyQ proteins via the coiled-coil–mediated interactions. These results may have important implications in therapeutic strategies for polyQ protein-related diseases.
Completely top–down hierarchical structure in quantum mechanics
Authors: Aharonov Yakir , Cohen Eliahu , Tollaksen Jeff
Published: October 2018

Significance

We provide quantitative evidence for the strong emergence of correlations within pre- and postselected quantum systems. These correlations are robust and can be verified by either weak or strong (projective) measurements. They give rise to intriguing effects within many-body quantum systems. Our analysis supports a top–down structure in quantum mechanics according to which higher-order correlations can always determine lower-order ones, but not vice versa.
Arrhythmia mutations in calmodulin cause conformational changes that affect interactions with the cardiac voltage-gated calcium channel
Authors: Wang Kaiqian , Holt Christian , Lu Jocelyn , Brohus Malene , Larsen Kamilla Taunsig , Overgaard Michael Toft , Wimmer Reinhard , Van Petegem Filip
Published: October 2018

Calmodulin (CaM) represents one of the most conserved proteins among eukaryotes and is known to bind and modulate more than a 100 targets. Recently, several disease-associated mutations have been identified in the
CALM
genes that are causative of severe cardiac arrhythmia syndromes. Although several mutations have been shown to affect the function of various cardiac ion channels, direct structural insights into any CaM disease mutation have been lacking. Here we report a crystallographic and NMR investigation of several disease mutant CaMs, linked to long-QT syndrome, in complex with the IQ domain of the cardiac voltage-gated calcium channel (Ca
V
1.2). Surprisingly, two mutants (D95V, N97I) cause a major distortion of the C-terminal lobe, resulting in a pathological conformation not reported before. These structural changes result in altered interactions with the Ca
V
1.2 IQ domain. Another mutation (N97S) reduces the affinity for Ca
2+
by introducing strain in EF hand 3. A fourth mutant (F141L) shows structural changes in the Ca
2+
-free state that increase the affinity for the IQ domain. These results thus show that different mechanisms underlie the ability of CaM disease mutations to affect Ca
2+
-dependent inactivation of the voltage-gated calcium channel.
Forces drive basement membrane invasion in
Caenorhabditis elegans
Authors: Cáceres Rodrigo , Bojanala Nagagireesh , Kelley Laura C. , Dreier Jes , Manzi John , Di Federico Fahima , Chi Qiuyi , Risler Thomas , Testa Ilaria , Sherwood David R. , Plastino Julie
Published: October 2018

Significance

Basement membrane is a particular kind of sheet-like extracellular matrix that separates tissue compartments. Invasion of cells through basement membrane barriers is a key aspect of many normal and pathological processes, including organ development and cancer cell metastasis. Invasive protrusions are rich in actin, a cytoskeletal biopolymer, the self-assembly of which can produce force and remodel extracellular matrix. However, in the invasive protrusion, actin has been attributed a function in scaffolding and trafficking, and its mechanical role has not been explored. Here we show that invading cells in
C. elegans
apply forces via actin assembly to break through basement membrane, and that force production is one of the key features of invasion.
Dopamine D2 receptor-mediated circuit from the central amygdala to the bed nucleus of the stria terminalis regulates impulsive behavior
Authors: Kim Bokyeong , Yoon Sehyoun , Nakajima Ryuichi , Lee Hyo Jin , Lim Hee Jeong , Lee Yeon-Kyung , Choi June-Seek , Yoon Bong-June , Augustine George J. , Baik Ja-Hyun
Published: October 2018

Significance

Impulsivity is a tendency to act with little or no forethought or consideration of the consequences and is a major component of various psychiatric disorders. However, little is known about the brain circuits that regulate reward-related impulsivity. Our genetic manipulations reveal that dopamine D2 receptors in the central nucleus of the amygdala have a crucial role in reward-related impulsive behavior. By using optogenetics to control the neurons that possess these receptors, we have identified elements of a neural circuit that contributes to regulating impulsivity. This information should enable approaches to managing impulsivity associated with neuropsychiatric disorders such as attention-deficit/hyperactivity disorder, bipolar disorder, and addiction-related disorders.
EHD2 is a mechanotransducer connecting caveolae dynamics with gene transcription
Authors: Torrino Stéphanie , Shen Wei-Wei , Blouin Cédric M. , Mani Satish Kailasam , Viaris de Lesegno Christine , Bost Pierre , Grassart Alexandre , Köster Darius , Valades-Cruz Cesar Augusto , Chambon Valérie , Johannes Ludger , Pierobon Paolo , Soumelis Vassili , Coirault Catherine , Vassilopoulos Stéphane , Lamaze Christophe
Published: October 2018

Caveolae are small invaginated pits that function as dynamic mechanosensors to buffer tension variations at the plasma membrane. Here we show that under mechanical stress, the EHD2 ATPase is rapidly released from caveolae, SUMOylated, and translocated to the nucleus, where it regulates the transcription of several genes including those coding for caveolae constituents. We also found that EHD2 is required to maintain the caveolae reservoir at the plasma membrane during the variations of membrane tension induced by mechanical stress. Metal-replica electron microscopy of breast cancer cells lacking EHD2 revealed a complete absence of caveolae and a lack of gene regulation under mechanical stress. Expressing EHD2 was sufficient to restore both functions in these cells. Our findings therefore define EHD2 as a central player in mechanotransduction connecting the disassembly of the caveolae reservoir with the regulation of gene transcription under mechanical stress.
Ribosome biogenesis factor Ltv1 chaperones the assembly of the small subunit head
Authors: Collins Jason C. , Ghalei Homa , Doherty Joanne R. , Huang Haina , Culver Rebecca N. , Karbstein Katrin
Published: October 2018

The correct assembly of ribosomes from ribosomal RNAs (rRNAs) and ribosomal proteins (RPs) is critical, as indicated by the diseases caused by RP haploinsufficiency and loss of RP stoichiometry in cancer cells. Nevertheless, how assembly of each RP is ensured remains poorly understood. We use yeast genetics, biochemistry, and structure probing to show that the assembly factor Ltv1 facilitates the incorporation of Rps3, Rps10, and Asc1/RACK1 into the small ribosomal subunit head. Ribosomes from Ltv1-deficient yeast have substoichiometric amounts of Rps10 and Asc1 and show defects in translational fidelity and ribosome-mediated RNA quality control. These defects provide a growth advantage under some conditions but sensitize the cells to oxidative stress. Intriguingly, relative to glioma cell lines, breast cancer cells have reduced levels of LTV1 and produce ribosomes lacking RPS3, RPS10, and RACK1. These data describe a mechanism to ensure RP assembly and demonstrate how cancer cells circumvent this mechanism to generate diverse ribosome populations that can promote survival under stress.
Part I Investment Treaties and the Settlement of Investment Disputes: The Framework, 2 The Energy Charter Treaty
Authors: Emmanuel Gaillard , Mark McNeill
Published: October 2018

The landscape of investment arbitration has shifted dramatically, with Europe — and the Energy Charter Treaty (ECT) — playing important roles in that transition. As the number of investment treaty arbitrations continues to mount, the ECT remains the most frequently invoked investment agreement with over 100 publicly known arbitrations filed to date. This chapter begins with some brief remarks on the genesis of the ECT. Each subsequent section focuses on a different aspect of the Treaty’s investment-related features, including the definitions of ‘Investor’ and ‘Investment’ in Article 1 of the ECT; the denial of benefits provision in Article 17(1), the Treaty’s substantive investment protections in Part III; and the dispute resolution mechanisms in Articles 26 and 27. Where useful, the chapter compares the Treaty’s text with analogous provisions in other investment agreements and addresses relevant arbitral decisions under the ECT.
Part II Guide to Key Preliminary and Procedural Issues, 8 Challenges of Arbitrators in Investment Arbitration: Still Work in Progress?
Authors: Loretta Malintoppi , Alvin Yap
Published: October 2018

The independence and impartiality of arbitrators continue to be an actively debated issue, partly due to the perceived opaqueness and inconsistency of challenge decisions and the standards to be applied to those challenges. This has in turn elicited responses on three fronts, each of which is addressed in this chapter. First, arbitral institutions have recently either revised their rules and practices or introduced more innovative approaches to challenges of arbitrators. This is mirrored by the adoption of dedicated guidelines by professional associations on issues relating to conflicts of interests of arbitrators. Second, some States have introduced their own codes of conduct for arbitrators in bilateral and multilateral investment treaties and in the investment chapters of free trade agreements, which are designed to take precedence over the institutional rules governing the arbitration. Third, changes in the way challenges are being decided by arbitrators and appointing authorities have also emerged.
Part II Guide to Key Preliminary and Procedural Issues, 9 Piercing the Veil of Confidentiality: The Recent Trend towards Greater Public Participation and Transparency in Investment Treaty Arbitration
Authors: Andrea J Menaker , Eckhard Hellbeck
Published: October 2018

Over the past few years, the US, Canada, and the EU have incorporated ‘transparency’ provisions into their investment treaties. Arbitration under those treaties thus will not be confidential, regardless of the arbitral rules governing them. By contrast, Russia’s 2016 regulation for the negotiation of investment treaties expressly provides for confidentiality of arbitration, including the award, unless both parties consent in writing to disclose information. This chapter traces the development of public disclosure and participation in investment arbitration. It is divided into three sections: public access to arbitral documents, third-party written submissions, and public access to arbitration hearings. Each section addresses developments under NAFTA Chapter 11, the evolution of the practice under the International Centre for Settlement of Investment Dispute (ICSID) Arbitration Rules, the approach taken by the new UNCITRAL Rules on Transparency, the status of other arbitration rules, and the practice of certain States as shown in their recent agreements.
Part III Guide to Key Jurisdictional Issues, 13 Burden and Standard of Proof at the Jurisdictional Stage
Authors: Baiju S Vasani , Timothy L Foden , Hafsa Zayyan
Published: October 2018

This chapter considers a situation where a respondent party argues that the tribunal is without jurisdiction to hear the claims or counterclaims in the first place. In this case, does the respondent party, as the ‘moving party’, have to prove the lack of jurisdiction? Or is it the claimant who is in fact claiming jurisdiction, who has to prove its existence? Or in light of the fact that jurisdiction is a matter for the tribunal to decide for itself, even sua sponte, does neither party hold the burden of proof on this issue? Recent decisions in international arbitration law demonstrate that the burden of proof at the jurisdictional phase is an issue in flux. Despite a long line of decisions holding, perhaps simplistically, that the burden lies with the claimant, many recent cases have suggested that it can lie with either party, depending on which party is asserting the particular fact.
Part III Guide to Key Jurisdictional Issues, 16 The Umbrella Clause: Is the Umbrella Closing?
Authors: Katia Yannaca-Small
Published: October 2018

‘Umbrella clauses’ are inserted in treaties to provide additional protection to investors and are directed at covering investment agreements that host countries frequently conclude with foreign investors. Inclusion of umbrella clauses in investment treaties provides a mechanism to make host States’ promises ‘enforceable’ and comes as an additional protection of investor-state contracts, which raises the controversial issue of whether the umbrella clause seeks to elevate contractual breaches to treaty breaches. For a better understanding of the clause, this chapter (i) gives an overview of its history; (ii) briefly discusses the significance of the language included in a number of bilateral investment treaties; and (iii) looks at the effect, scope and conditions of application of the umbrella clause as interpreted by arbitral tribunals.
Part III Guide to Key Jurisdictional Issues, 17 Counterclaims in Investment Treaty Arbitration
Authors: Mark A Clodfelter , Diana Tsutieva
Published: October 2018

The last decade has seen an increase in the efforts of respondent States to have their own claims against investor-claimants heard in investor-State proceedings commenced against them. The investment arbitration case law has revealed a host of legal and practical difficulties in admitting counterclaims. Most of these stem from the core requirement that parties must consent to submit their differences to investment arbitration. The applicable arbitration rules have also been cited as a bar to counterclaims. This chapter explores the functionality of applicable procedural rules as bases for an investment tribunal’s authority to hear counterclaims under the two main investment law regimes: the International Centre for Settlement of Investment Dispute (ICSID) Convention and Arbitration Rules and the United Nations Commission on International Trade Law Arbitration Rules. A review of the milestone cases under these two regimes reveals the major problems that have arisen.
Part IV Guide to Key Substantive Issues, 22 Indirect Expropriation and the Right to Regulate: Has the Line Been Drawn?
Authors: Katia Yannaca-Small
Published: October 2018

This chapter focuses on the way in which arbitral tribunals have dealt with indirect expropriation claims based on investment agreements. It also looks at the cross-fertilization with two other sources of jurisprudence which deal with similar issues, under different circumstances and different legal bases, i.e. the US–Iran Claims tribunal and the European Court of Human Rights. The chapter (i) describes the basic concepts of the obligation to compensate for indirect expropriation; (ii) reviews whether and how legal instruments and other texts articulate the difference between indirect expropriation and the right of the governments to regulate without compensation; and (iii) identifies a number of criteria which emerge from jurisprudence and state practice for determining whether an indirect expropriation has occurred, and compensation is due.
The Composition of Bank Capital
Authors: Gleeson Simon
Published: October 2018

This chapter discusses the concept of bank capital. The essence of regulatory capital requirements as originally conceived was to procure that banks had sufficient capital to absorb both expected and unexpected losses. However, recent market developments have indicated two different but important functions of capital. Going Concern Capital is that capital which can absorb losses, both when the firm is in a state of financial health and during periods of financial stress, thus maintaining market confidence in the financial system and avoiding disruption to depositors. Gone Concern Capital is that capital which absorbs losses on the failure of a firm, protecting depositors in a winding up or resolution. The remainder of the chapter covers Tier 1 and Tier 2 capital; deductions; bank holdings in banking, financial, and insurance entities; provisioning, expected loss and revaluation; and capital monitoring.
Trading Book—Standardized Approaches
Authors: Gleeson Simon
Published: October 2018

This chapter discusses trading book models. Risk models come in a variety of types. However, for market risk purposes there have been a number of types which may be used within the framework. The simplest is the ‘CAD 1’ model — named after the first Capital Adequacy Directive, which permitted such models to be used in the calculation of regulatory capital. VaR models, permitted by Basel 2, were more complex, and this complexity was increased by Basel 2.5, which required the use of ‘stressed VAR’. In due course all of this will be replaced by the Basel 3 FRTB calculation, which rejects VAR and is based on the calculation of an expected shortfall (ES) market risk charge, a VaR based default risk charge (DRC) (for those exposures where the bank is exposed to the default of a third party), and a stressed ES-based capital add-on.
Group Supervision
Authors: Gleeson Simon
Published: October 2018

This chapter discusses banking group supervision. At first glance the necessity for the supervision of banking groups is not obvious. However, banks are now known to be subject to contagion risk. In theory the failure of a company which is a member of a bank group has no effect on the regulated bank. In practice, the failure of a company in a bank group will send a strong signal to the outside world that the group is in difficulty. It would in theory be possible to operate a group bank with such a degree of separation that the market as a whole believed that the bank would genuinely be unaffected by the failure of one of its subsidiaries. However, in practice the market believes that banks are closely connected with the groups of which they are members, and that failures elsewhere in a group will have important knock-on consequences for a group bank.
Potassium iodide and miltefosine inhibit biofilms of Sporothrix schenckii species complex in yeast and filamentous forms
Authors: Brilhante Raimunda Sâmia Nogueira , Silva Maria Lucilene Queiroz da , Pereira Vandbergue Santos , de Oliveira Jonathas Sales , Maciel Juliana Maria , Silva Isaac Neto Goes da , Garcia Lana Glerieide Silva , Guedes Glaucia Morgana de Melo , Cordeiro Rossana de Aguiar , Pereira-Neto Waldemiro de Aquino , de Camargo Zoilo Pires , Rodrigues Anderson Messias , Sidrim José Júlio Costa , Castelo-Branco Débora de Souza Collares Maia , Rocha Marcos Fábio Gadelha
Published: October 2018

This study aimed to evaluate the yeast biofilm growth kinetics and ultrastructure of Sporothrix schenckii complex and assess their mature biofilm susceptibility in filamentous and yeast forms to potassium iodide (KI) and miltefosine (MIL). Yeast biofilms were evaluated by crystal violet staining, XTT reduction assay and microscopic techniques. Susceptibility of planktonic and sessile cells was analyzed by broth microdilution. S. schenckii complex in yeast form produced biofilms, with an optimum maturation at 96 h, showing multilayered blastoconidia embedded in extracellular matrix. KI and MIL minimum inhibitory concentration (MIC) ranges against planktonic cells were 62,500–250,000 μg/ml and 0.125–4 μg/ml, respectively. KI and MIL reduced biofilm metabolic activity by 75.4% and 67.7% for filamentous form and 55.1% and 51.6% for yeast form, respectively. This study demonstrated that S. schenckii complex forms biofilms in vitro, and potassium iodide and miltefosine inhibit Sporothrix spp. biofilms in both filamentous and yeast forms.
Depression Increases the Rates of Neurological Complications and Failed Back Surgery Syndrome in Patients Undergoing Lumbar Spine Surgery
Authors: Schoell Kyle , Wang Christopher , D’Oro Anthony , Heindel Patrick , Lee Larry , Wang Jeffrey C. , Buser Zorica
Published: October 2018

Study Design:

This was a retrospective database study.

Objective:

The aim of this study was to use a large sample to accurately determine risk factors and rates of neurological complications in patients undergoing commonly performed lumbar spine surgeries.

Summary of Background Data:

Damage to neurological structures and failed back surgery syndrome (FBSS) are among the most feared complications of lumbar spine surgery. Despite the large impact on quality of life these complications have, reported rates of neurological complications vary immensely, ranging from 0.46% to 24%.

Materials and Methods:

Data were obtained for patients undergoing initial posterior lumbar interbody fusion, transforaminal lumbar interbody fusion, anterior lumbar interbody fusion, posterolateral fusion, discectomy, and laminectomy procedures from January 2007 to June 2015 covered by the nationwide insurance carrier Humana. Patient records were analyzed to determine rates of dural tear, damage to nervous tissue, cauda equina syndrome, neurogenic bowel/bladder, and FBSS following each procedure. Rates were determined for patients undergoing single/multilevel procedures, by age, and for patients with a previous diagnosis of depression to determine the influence these factors had on the risk of neurologic complications.

Results:

Analysis of 70,581 patient records revealed a dural tear rate of 2.87%, damage to the nervous tissue of 1.47%, cauda equina syndrome of 0.75%, neurogenic bowel or bladder of 0.45%, and FBSS of 15.05% following lumbar spine surgery. The incidence of complications was highest for patients undergoing multilevel procedures and posterior fusion. Depression was a significant risk factor for FBSS (risk ratio, 1.74; P<0.0001), damage to nervous tissue (1.41; P<0.0001), and dural tear (1.15; P<0.0001), but had no impact on risk of cauda equina syndrome or neurogenic bowel or bladder. Increased age was associated with higher rates of dural tear and damage to nervous tissue.

Conclusions:

Patients with a history of depression are at significantly increased risk for neurologic complications following lumbar spine surgery and should be managed accordingly.
The Role of Atomoxetine for Parkinson Disease–Related Executive Dysfunction
Authors: Warner Carly B. , Ottman Andreina A. , Brown Jamie N.
Published: October 2018

Background

Atomoxetine selectively inhibits the reuptake of norepinephrine. Given the noradrenergic system's role in executive function, pharmacotherapy options that affect norepinephrine are of particular clinical interest in Parkinson disease–related executive dysfunction.

Objective

The aim of this study was to assess the efficacy and safety of atomoxetine for Parkinson disease–related executive dysfunction.

Methods

MEDLINE (1946 to May 2018) and EMBASE (1947 to May 2018) were queried using the search term combination: Parkinson's disease, Parkinson disease, inhibition, impulse behavior, impulse control disorder, executive function, executive dysfunction, cognition, cognitive dysfunction, cognitive defect, response inhibition, strategic planning, strategy, or verbal fluency and atomoxetine hydrochloride or atomoxetine. Studies analyzed for relevance evaluated clinical outcomes of patients treated with atomoxetine for Parkinson disease–related executive dysfunction. Studies appropriate to the objective were evaluated, including 1 open-label flexible dose trial, 2 placebo-controlled longitudinal trials, and 4 placebo-controlled crossover single-dose trials.

Results

In patients with Parkinson disease, treatment with atomoxetine resulted in improvements in several markers of executive dysfunction including impulsivity, risk taking, and global cognition. Study durations ranged from single-dose trials to 10 weeks and used varying doses of atomoxetine. Atomoxetine was well tolerated in most studies with some reports of gastrointestinal adverse effects and insomnia.

Conclusions

Based on the reviewed literature, atomoxetine continues to be a therapy of interest for the treatment of executive dysfunction in patients with Parkinson disease. Larger long-term trials are necessary to further define the role of atomoxetine for patients with Parkinson disease–related executive dysfunction.
Isometric Cervical Muscular Strength in Pediatric Athletes With Multiple Concussions
Authors: Engelman Glenn , Carry Patrick , Sochanska Ada , Daoud Ariel Kiyomi , Wilson Julie , Provance Aaron
Published: October 2018

Objective:

To compare maximal cervical muscle strength among athletes with a history of 2 or more concussions relative to athletes with no history of a previous concussion.

Design:

Athletes in the 2 groups were frequency-matched. Linear mixed models were used to test for differences in peak isometric flexion, extension, left lateral flexion, and right lateral flexion cervical muscle torque between groups.

Setting:

Pediatric sports medicine clinic.

Participants:

Athletes with a history of multiple concussions (n = 16) and athletes with no previous concussion history (n = 17).

Interventions (or Assessment of Risk Factors or Independent Variables):

Concussion history (group), age, sex, neck girth, and height.

Main Outcome Measures:

Peak isometric torque measured with a stationary isokinetic dynamometer during a 3-second isometric hold.

Results:

There was no significant difference in peak flexion [mean difference: 21.2%, 95% confidence interval (CI): −6.6% to 57.4%, P = 0.1413], extension (mean difference: 17%, 95% CI, −6.8% to 47.1%, P = 0.1667), left lateral (mean difference: 4.4%, 95% CI, −16.9% to 31.1%, P = 0.7011), or right lateral (mean difference: 9.3%, 95% CI, −14.5% to 39.8%, P = 0.4627) isometric torque in the concussion group relative to the control group. Across all muscle actions, neck torque was significantly (P < 0.05) higher in male compared with female athletes. Increasing neck girth was also associated with a significant (P < 0.05) increase in neck torque.

Conclusions:

There was no evidence of a consistent cervical muscle strength deficit among athletes with a history of 2 or more concussions relative to athletes with no previous history of a concussion. Age, neck girth, and sex were significantly associated with cervical muscle strength.

Clinical Relevance:

Isometric cervical muscle strength testing may not be a reliable test for differentiating athletes with a history of multiple concussions relative to athletes with no history of concussions in the pediatric and adolescent population. Our study presents a reliable methodology for testing cervical muscle strength among young athletes.
Implementation of a Defecation Posture Modification Device
Authors: Modi Rohan M. , Hinton Alice , Pinkhas Daniel , Groce Royce , Meyer Marty M. , Balasubramanian Gokulakrishnan , Levine Edward , Stanich Peter P.
Published: October 2018

Goals:

The goal of this study was to evaluate the influence of defecation postural modification devices (DPMDs) on normal bowel patterns.

Background:

The introduction of DPMDs has brought increased awareness to bowel habits in western populations.

Materials and Methods:

A prospective crossover study of volunteers was performed that included real-time collection of data regarding bowel movements (BMs) for 4 weeks (first 2 wk without DPMD and subsequent 2 wk with DPMD). Primary outcomes of interest included BM duration, straining, and bowel emptiness with and without DPMD use.

Results:

In total, 52 participants (mean age, 29 y and 40.1% female) were recruited for this study. At baseline 15 subjects (28.8%) reported incomplete emptying, 23 subjects (44.2%) had increased straining, and 29 subjects (55.8%) noticed blood on their toilet paper in the past year. A total of 1119 BMs were recorded (735 without DPMD and 384 with DPMD). Utilizing the DPMD resulted in increased bowel emptiness (odds ratio, 3.64; 95% confidence interval (CI), 2.78-4.77) and reduced straining patterns (odds ratio, 0.23; 95% CI, 0.18-0.30). Moreover, without the DPMD, participants had an increase in BM duration (fold increase, 1.25; 95% CI, 1.17-1.33).

Conclusions:

DPMDs positively influenced BM duration, straining patterns, and complete evacuation of bowels in this study.
Do Parents of Discharged Pediatric Emergency Department Patients Read Discharge Instructions?
Authors: Wallin Dina , Vezzetti Robert , Young Andrew , Wilkinson Matthew
Published: October 2018

Objectives

The percentage of discharged emergency department (ED) patients who read discharge instructions (DCIs) is unknown. In this study of parents of pediatric ED patients, we attempt to quantify the DCI readership rate and identify variables associated with readership. We hypothesized that few families would read their child's DCIs.

Methods

We conducted a prospective, randomized study of parents of pediatric patients who were discharged home from the ED. We randomized participants to receive a study invitation as either the second or the second to last page of their DCIs. We incentivized study participation with a $10 gift card and then used the invitation response rate as a proxy for DCI readership. We utilized logistic regression to identify predictor variables showing significant association with readership.

Results

One thousand patients were randomized; 963 were included in the final analysis. Eighty-four subjects, 8.8% (95% confidence interval, 7.0%–10.7%), responded to investigators. In the final regression model, private insurance (adjusted odds ratio, 1.76; P = 0.036), placement of the study invitation early within DCIs (adjusted odds ratio, 1.93; P = 0.011), and laceration diagnosis (adjusted odds ratio, 2.97; P = 0.012) predicted readership, whereas parents of Hispanic children were less likely to respond, even after adjustment for language spoken (adjusted odds ratio, 0.57; P = 0.028).

Conclusions

A minority of parents of patients discharged from the pediatric ED appear to read through their child's DCIs, with Hispanic families and those without private insurance least likely to read. Future research can explore how best to reach these particularly vulnerable families.
Governing with nature: a European perspective on putting rewilding principles into practice
Authors: Jepson P. , Schepers F. , Helmer W.
Published: October 2018

Academic interest in rewilding is moving from commentary to discussion on future research agendas. The quality of rewilding research design will be enhanced if it is informed by knowledge of the rewilding practice. Here, we describe the conceptual origins and six case study examples of a mode of rewilding that emerged in the Dutch Delta and is being promoted and supported by Rewilding Europe, an umbrella organization established in 2011. The case experiences presented help position this version of rewilding in relation to the US 3C's version and point towards a rewilding action philosophy characterized by pragmatic realism and pioneer projects around which multiactor networks interested in policy innovation and change form. We argue that scaling-up the models of rewilding presented is constrained by institutional cultures and will require innovations in conservation finance and business models. Nonetheless, we suggest that the expanding European Rewilding Network and associated facilities, such as the European Wildlife Bank, represent a valuable asset for natural science research, aimed at exploring the ecological impacts of grazing and the relationship between role of restored herbivore guilds and biotical expansion, and for social science research investigating concepts such as non-human agency and autonomy. Lastly, we ask applied scientists to view rewilding as an uncertain and unfolding conservation approach and to refrain from seeking to specify it as a management approach supporting the delivery of pre-determined targets and/or ideals. This is because such actions may constrain the transformative potential of rewilding practice.

This article is part of the theme issue ‘Trophic rewilding: consequences for ecosystems under global change’.
Effects of large herbivores on tundra vegetation in a changing climate, and implications for rewilding
Authors: Olofsson Johan , Post Eric
Published: October 2018

In contrast to that of the Pleistocene epoch, between approximately 2.6 million and 10 000 years before present, the extant community of large herbivores in Arctic tundra is species-poor predominantly due to human extinctions. We here discuss how this species-poor herbivore guild influences tundra ecosystems, especially in relation to the rapidly changing climate. We show that present herbivore assemblages have large effects on tundra ecosystem composition and function and suggest that the effect on thermophilic species expected to invade the tundra in a warmer climate is especially strong, and that herbivores slow ecosystem responses to climate change. We focus on the ability of herbivores to drive transitions between different vegetation states. One such transition is between tundra and forest. A second vegetation transition discussed is between grasslands and moss- and shrub-dominated tundra. Contemporary studies show that herbivores can drive such state shifts and that a more diverse herbivore assemblage would have even higher potential to do so. We conclude that even though many large herbivores, and especially the megaherbivores, are extinct, there is a potential to reintroduce large herbivores in many arctic locations, and that doing so would potentially reduce some of the unwanted effects of a warmer climate.

This article is part of the theme issue ‘Trophic rewilding: consequences for ecosystems under global change’.
Can trophic rewilding reduce the impact of fire in a more flammable world?
Authors: Johnson Christopher N. , Prior Lynda D. , Archibald Sally , Poulos Helen M. , Barton Andrew M. , Williamson Grant J. , Bowman David M. J. S.
Published: October 2018

Large vertebrates affect fire regimes in several ways: by consuming plant matter that would otherwise accumulate as fuel; by controlling and varying the density of vegetation; and by engineering the soil and litter layer. These processes can regulate the frequency, intensity and extent of fire. The evidence for these effects is strongest in environments with intermediate rainfall, warm temperatures and graminoid-dominated ground vegetation. Probably, extinction of Quaternary megafauna triggered increased biomass burning in many such environments. Recent and continuing declines of large vertebrates are likely to be significant contributors to changes in fire regimes and vegetation that are currently being experienced in many parts of the world. To date, rewilding projects that aim to restore large herbivores have paid little attention to the value of large animals in moderating fire regimes. Rewilding potentially offers a powerful tool for managing the risks of wildfire and its impacts on natural and human values.

This article is part of the theme issue ‘Trophic rewilding: consequences for ecosystems under global change’.
Hope and caution: rewilding to mitigate the impacts of biological invasions
Authors: Derham Tristan T. , Duncan Richard P. , Johnson Christopher N. , Jones Menna E.
Published: October 2018

Rewilding is a novel approach to ecological restoration. Trophic rewilding in particular aims to reinstate ecological functions, especially trophic interactions, through the introduction of animals. We consider the potential for trophic rewilding to address biological invasions. In this broad review, we note some of the important conceptual and ethical foundations of rewilding, including a focus on ecosystem function rather than composition, reliance on animal agency, and an appeal to an ethic of coexistence. Second, we use theory from invasion biology to highlight pathways by which rewilding might prevent or mitigate the impacts of an invasion, including increasing biotic resistance. Third, we use a series of case studies to illustrate how reintroductions can mitigate the impacts of invasions. These include reintroductions and positive management of carnivores and herbivores including European pine martens (Martes martes), Eurasian otters (Lutra lutra), dingoes (Canis dingo), Tasmanian devils (Sarcophilus harrisii) and tule elk (Cervus canadensis nannodes). Fourth, we consider the risk that rewilding may enable a biological invasion or aggravate its impacts. Lastly, we highlight lessons that rewilding science might take from invasion biology.

This article is part of the theme issue ‘Trophic rewilding: consequences for ecosystems under global change’.
Rapid statistical methods for inferring intra- and inter-hospital transmission of nosocomial pathogens from whole genome sequence data
Authors: Aspbury Marianne , Sciberras James , Corander Jukka , Bayliss Sion C. , Donker Tjibbe , Feil Edward J. , James Richard
Published: October 2018

Whole genome sequence (WGS) data for bacterial pathogens can provide evidence as to the source of nosocomial infection, and more specifically the ability to distinguish between intra- and inter-hospital transmission. This is currently achieved either through using SNP thresholds, which can lack statistical robustness, or by constructing phylogenetic trees, which can be computationally expensive and difficult to interpret. Here we compare two alternative statistical approaches using 1022 genomes of methicillin resistantStaphylococcus aureus(MRSA) clone ST22. In 71% of cases both methods predict the same hospital origin, which is also supported by the ML tree. Robust assignments are divided approximately equally between intra-hospital transmission and inter-hospital transmission. Our approaches are rapid and produce intuitive output that could inform on immediate infection control priorities, as well as providing long-term data on inter-hospital transmission networks. We discuss the strengths and weakness of our methods, and the generalisability of this approach.

One Sentence Summary

We present rapid statistical methods for distinguishing intra- versus inter-hospital transmission of bacterial pathogens using whole genome sequence data; these methods do not require the use of SNP thresholds or the generation and interpretation of phylogenetic trees.
Child Growth Predicts Brain Functional Connectivity and Future Cognitive Outcomes in Urban Bangladeshi Children Exposed to Early Adversities
Authors: Xie Wanze , Jensen Sarah K.G. , Wade Mark , Kumar Swapna , Westerlund Alissa , Kakon Shahria H. , Haque Rashidul , Petri William A. , Nelson Charles A.
Published: October 2018

Background

Faltered growth has been shown to affect 161 million children worldwide and derail cognitive development from early childhood. The neural pathways by which growth faltering in early childhood affects future cognitive outcomes remain unclear, which is partially due to the scarcity of research using both neuroimaging and sensitive behavioral techniques in low-income settings. We employed EEG to examine the association between growth faltering and brain functional connectivity and whether brain functional connectivity mediates the effect of early adversity on cognitive development.

Methods

We recruited participants from an urban impoverished neighborhood in Dhaka, Bangladesh. One sample consisted of 85 children whose EEG and growth measures (height for age, weight for age, and weight to height) were collected at 6 months and cognitive outcomes were assessed at 27 months. Another sample consisted of 115 children whose EEG and growth measures were collected at 36 months and IQ scores were assessed at 48 months. Path analysis was used to test the effect of growth measures on cognitive outcomes through brain functional connectivity.

Findings

Faltered growth was found to be accompanied by overall increased functional connectivity in the theta and low-beta frequency bands for the 36-month-old cohort. For both cohorts, brain functional connectivity was negatively predictive of later cognitive outcomes at 27 and 48 months, respectively. Faltered growth was found to have a negative impact on children’s IQ scores in the older cohort, and this effect was found to be mediated by brain functional connectivity in the low-beta band.

Interpretation

The association found between growth measures and brain functional connectivity may reflect a broad deleterious effect of malnutrition on children’s brain development. The mediation effect of functional connectivity on the relation between physical growth and later IQ scores provides the first experimental evidence that brain functional connectivity may mediate the effect of biological adversity on cognitive development.

Funding

Bill and Melinda Gates Foundation (OPP1111625)
Cholinergic interneurons as a novel target of CRF in the striatum that is spared by repeated stress
Authors: Lemos Julia C. , Shin Jung Hoon , Ingebretson Anna E. , Dobbs Lauren K. , Alvarez Veronica A.
Published: October 2018

Acute stressors can stimulate appetitive and exploratory behaviors, not just produce negative affect that impair performance. Corticotropin releasing factor (CRF), which is released in the brain in response to stress, acts on different targets and circuits to mediate both the negative and positive effects of stress. In the nucleus accumbens, CRF facilitates appetitive behavior through mechanisms not fully understood. Here we report that cholinergic interneurons (CINs) are a novel target for CRF actions in the striatum. CRF enhances the spontaneous firing via activation of CRF-type 1 receptors expressed on CINs. This causes the activation muscarinic acetylcholine receptors type 5, which mediate CRF potentiation of dopamine transmission in the striatum. Repeated stress selectively dampens some CRF functions but spare effect on CINs and changes CRF-R1 expression in a cell-specific manner. These data highlight the existence of diverse CRF targets within the striatum, which vary in their resilience to stress.
Bile canaliculi contract autonomously by releasing calcium into hepatocytes via mechanosensitive calcium channel
Authors: Gupta Kapish , Chuan Ng Inn , Nguyen Binh P. , Tucker-Kellogg Lisa , Low Boon Chuan , Yu Hanry
Published: October 2018

Bile canaliculi (BC) are the smallest vessels of the biliary tree. They are formed from the apical surfaces of adjoining hepatocytes, resulting in lumenal conduits for bile flow. Bile is propelled along the BC by hepatocyte contractions that arise from cyclic waves of apico-basal Ca2+, but the source and regulation of Ca2+has been unclear. We report that BC contraction correlates with cyclic transfer of Ca2+from BC lumen to apico-basal Ca2+waves in adjacent hepatocytes, and does not correlate with endoplasmic reticulum Ca2+. BC contractility was triggered by ionophore A23187 and unaffected by Thapsigargin. The cycles of Ca2+transfer could be blocked by the mechanosensitive calcium channel inhibitor GsMTx-4, resulting in cholestatic generation of BC-derived vesicles. The mechanosensitive calcium channel Piezo-1 is preferentially localized at BC membranes, and its hyper-activation by Yoda1 causes increased Ca2+transfer and increased BC contractility. We propose that canaliculi achieve biomechanical homeostasis through the following feedback system: the pressure of accumulated bile is sensed by mechanosensitive channel, which transmit biliary calcium into adjacent hepatocytes for contraction of the BC lumen and propulsion of the bile.
Calculating the Effects of Autism Risk Gene Variants on Dysfunction of Biological Processes Identifies Clinically-Useful Information
Authors: Veatch Olivia J. , Mazzotti Diego R. , Sutcliffe James S. , Schultz Robert T. , Abel Ted , Tunc Birkan , Assouline Susan G. , Brodkin Edward S. , Michaelson Jacob J. , Nickl-Jockschat Thomas , Warren Zachary E. , Malow Beth A. , Pack Allan I.
Published: October 2018

Autism spectrum disorders (ASD) are neurodevelopmental conditions that are influenced by genetic factors and encompass a wide-range and severity of symptoms. The details of how genetic variation contributes to variable symptomatology are unclear, creating a major challenge for translating vast amounts of data into clinically-useful information. To determine if variation in ASD risk genes correlates with symptomatology differences among individuals with ASD, thus informing treatment, we developed an approach to calculate the likelihood of genetic dysfunction in Gene Ontology-defined biological processes that have significant overrepresentation of known risk genes. Using whole-exome sequence data from 2,381 individuals with ASD included in the Simons Simplex Collection, we identified likely damaging variants and conducted a clustering analysis to define subgroups based on scores reflecting genetic dysfunction in each process of interest to ASD etiology. Dysfunction in cognition-related genes distinguished a distinct subset of individuals with increased social deficits, lower IQs, and reduced adaptive behaviors when compared to individuals with no evidence of cognition-related gene dysfunction. In particular, a stop-gain variant in the pharmacogene encoding cycloxygenase-2 was associated with having an IQ<70 (i.e. intellectual disability), a key comorbidity in ASD. We expect that screening genes involved in cognition for deleterious variants in ASD cases may be useful for identifying clinically-informative factors that should be prioritized for functional follow-up. This has implications in designing more comprehensive genetic testing panels and may help provide the basis for more informed treatment in ASD.