bluuebunny/crossref_metadata_2025 huggingface dataset:
On generalized diffusion and heat systems on an evolving surface with a boundary
Authors: Koba Hajime
Published: December 2019

We consider a diffusion process on an evolving surface with a piecewise Lipschitz-continuous boundary from an energetic point of view. We employ an energetic variational approach with both surface divergence and transport theorems to derive the generalized diffusion and heat systems on the evolving surface. Moreover, we investigate the boundary conditions for the two systems to study their conservation and energy laws. As an application, we make a mathematical model for a diffusion process on an evolving double bubble. Specifically, this paper is devoted to deriving the representation formula for the unit outer co-normal vector to the boundary of a surface.
6. Unknot or knot to be?
Authors: Earl Richard
Published: December 2019

‘Unknot or knot to be?’ explains that a knot is a smooth, simple, closed curve in 3D space. Being simple and closed means the curve does not cross itself except that its end returns to its start. All knots are topologically the same as a circle; what makes a circle knotted—or not—is how that circle has been placed into 3D space. The central problem of knot theory is a classification theorem: when is there an ambient isotopy between two knots or how do we show that no such isotopy exists? Key elements of knot theory are discussed, including the three Reidemeister moves, prime knots, adding knots, and the Alexander and Jones polynomials.
Extensive paraphyly in the typical owl family (Strigidae)
Authors: Salter Jessie F , Oliveros Carl H , Hosner Peter A , Manthey Joseph D , Robbins Mark B , Moyle Robert G , Brumfield Robb T , Faircloth Brant C
Published: December 2019

The typical owl family (Strigidae) comprises 194 species in 28 genera, 14 of which are monotypic. Relationships within and among genera in the typical owls have been challenging to discern because mitochondrial data have produced equivocal results and because many monotypic genera have been omitted from previous molecular analyses. Here, we collected and analyzed DNA sequences of ultraconserved elements (UCEs) from 43 species of typical owls to produce concatenated and multispecies coalescent-based phylogenetic hypotheses for all but one genus in the typical owl family. Our results reveal extensive paraphyly of taxonomic groups across phylogenies inferred using different analytical approaches and suggest the genera Athene, Otus, Asio, Megascops, Bubo, and Strix are paraphyletic, whereas Ninox and Glaucidium are polyphyletic. Secondary analyses of protein-coding mitochondrial genes harvested from off-target sequencing reads and mitochondrial genomes downloaded from GenBank generally support the extent of paraphyly we observe, although some disagreements exist at higher taxonomic levels between our nuclear and mitochondrial phylogenetic hypotheses. Overall, our results demonstrate the importance of taxon sampling for understanding and describing evolutionary relationships in this group, as well as the need for additional sampling, study, and taxonomic revision of typical owl species. Additionally, our findings highlight how both divergence and convergence in morphological characters have obscured our understanding of the evolutionary history of typical owls, particularly those with insular distributions.
Potential Impacts of Translocation of Neonicotinoid Insecticides to Cotton (Gossypium hirsutum (Malvales: Malvaceae)) Extrafloral Nectar on Parasitoids
Authors: Jones Asher G , Hoover Kelli , Pearsons Kirsten , Tooker John F , Felton Gary W
Published: December 2019

Neonicotinoid seed treatments are frequently used in cotton (Gossypium hirsutum L. [Malvales: Malvaceae]) production to provide protection against early-season herbivory. However, there is little known about how these applications affect extrafloral nectar (EFN), an important food resource for arthropod natural enemies. Using enzyme-linked immunosorbent assays, we found that neonicotinoids were translocated to the EFN of clothianidin- and imidacloprid-treated, greenhouse-grown cotton plants at concentrations of 77.3 ± 17.3 and 122.6 ± 11.5 ppb, respectively. We did not find differences in the quantity of EFN produced by neonicotinoid-treated cotton plants compared to untreated controls, either constitutively or after mechanical damage. Metabolomic analysis of sugars and amino acids from treated and untreated plants did not detect differences in overall composition of EFN. In bioassays, female Cotesia marginiventris (Cresson) (Hymenoptera: Braconidae) parasitoid wasps that fed on EFN from untreated, clothianidin-treated, or imidacloprid-treated plants demonstrated no difference in mortality or parasitization success. We also conducted acute toxicity assays for C. marginiventris fed on honey spiked with clothianidin and imidacloprid and established LC50 values for male and female wasps. Although LC50 values were substantially higher than neonicotinoid concentrations detected in EFN, caution should be used when translating these results to the field where other stressors could alter the effects of neonicotinoids. Moreover, there are a wide range of possible sublethal impacts of neonicotinoids, none of which were explored here. Our results suggest that EFN is a potential route of exposure of neonicotinoids to beneficial insects and that further field-based studies are warranted.
Early postoperative statin administration does not affect the rate of atrial fibrillation after cardiac surgery
Authors: Khan Jahangir A , Laurikka Jari O , Järvinen Otto H , Khan Niina K , Järvelä Kati M
Published: December 2019

OBJECTIVES

Postoperative atrial fibrillation is the most frequent complication after cardiac surgery, and the use of statins in preventing them is being extensively studied. The aim of this study was to investigate whether a pause in the administration of statins affects the occurrence of atrial fibrillation after cardiac surgery in a prospective randomized and controlled setting.

METHODS

A total of 301 patients without chronic atrial fibrillation with prior statin medication scheduled for elective or urgent cardiac surgery involving the coronary arteries and/or heart valves were prospectively recruited and randomized for statin re-initiation on either the first (immediate statin group) or the fifth (late statin group) postoperative day, using the original medication and dosage. The immediate statin group comprised 146 patients and the late statin group 155 patients. Except for a somewhat higher rate of males (85% vs 73%, P = 0.016) in the immediate statin group, the baseline characteristics and the distribution of procedures performed within the groups were comparable. The occurrence of postoperative atrial fibrillation and the clinical course of the patients were compared between the groups.

RESULTS

The incidence of atrial fibrillation was 46% and the median delay after surgery before the onset of atrial fibrillation was 3 days in both groups (P = NS). No differences were observed in the frequency of the arrhythmia in any subgroup analyses or in other major complications or clinical parameters. No adverse effects related to early statin administration were detected.

CONCLUSIONS

Early re-initiation of statins does not appear to affect the occurrence of postoperative atrial fibrillation.

Clinical trial registration

European Union Drug Regulating Authorities Clinical Trials Database (EudraCT)—2016-001655-44.
High haemoglobin A1c level is a possible risk factor for ventricular fibrillation in sudden cardiac arrest among non-diabetic individuals in the general population
Authors: van Dongen Laura H , Blom Marieke T , Bardai Abdenasser , Homma Paulien C M , Beulens Joline W J , van der Heijden Amber A , Elders Petra , Tan Hanno L
Published: December 2019

Aims

This study aimed to establish whether higher levels of glycated haemoglobin (HbA1c) are associated with increased sudden cardiac arrest (SCA) risk in non-diabetic individuals.

Methods and results

Case–control study in non-diabetic individuals (HbA1c < 6.5%) in the Netherlands. Cases were SCA patients with electrocardiogram (ECG)-documented ventricular fibrillation (VF, the predominant cause of SCA) and HbA1c measurements immediately after VF, prospectively included in September 2009–December 2012. Controls (up to 10 per case) were age/sex-matched non-SCA individuals, included in July 2006–November 2007. We studied 306 cases (56.4 ± 6.8 years, 79.1% male) and 1722 controls (54.0 ± 6.8 years, 64.8% male). HbA1c levels were higher in cases than in controls (5.8 ± 0.3% vs. 5.4 ± 0.3%, P < 0.001). The proportion of increased HbA1c (≥5.7%) was 63.1% in cases and 19.3% in controls (P < 0.001). Multivariate regression models indicated that increased HbA1c was associated with a > six-fold increased VF risk [adjusted odds ratio (ORadj) 6.74 (5.00–9.09)] and that 0.1% increase in HbA1c level was associated with 1.4-fold increase in VF risk, independent of concomitant cardiovascular risk factors. Increased VF risk at higher HbA1c is associated with acute myocardial infarction (MI) as cause of VF [OR 1.14 (1.04–1.24)], but the association between HbA1c and VF was similar in non-MI patients [OR 1.32 (1.21–1.44)] and MI patients [OR 1.47 (1.37–1.58)].

Conclusion

Among non-diabetic individuals, risk of VF increased with rising HbA1c levels, independent of concomitant cardiovascular disease. Future studies should establish whether HbA1c level may be used as biomarker to recognize individuals at risk for VF.
Longitudinal Association Between Perceived Fatigability and Cognitive Function in Older Adults: Results from the Baltimore Longitudinal Study of Aging
Authors: Salerno Elizabeth A , Wanigatunga Amal A , An Yang , Urbanek Jacek K , Simonsick Eleanor M , Ferrucci Luigi , Resnick Susan M , Schrack Jennifer A
Published: December 2019

Background

Cognitive decline is consistently associated with diminished life satisfaction and inability to live independently. Identifying early, novel markers of cognitive decline is imperative for improving clinical detection and promoting long-term quality of life. Fatigability, one’s perceived exertion after a standardized walking task, has been associated with declines in physical function; however, it remains unclear as to whether these effects may also extend to cognitive function.

Methods

We examined whether perceived fatigability, assessed as the rating of perceived exertion (RPE) after a 5 min slow-paced treadmill walk (0.67 m/s, 0% grade), is longitudinally associated with cognitive performance in the domains of memory, executive functions, language, and attention among 934 cognitively intact individuals aged at least 50 years participating in the Baltimore Longitudinal Study of Aging (BLSA); Mage = 69.6 ± 10.1, 51.9% female participants. Continuous associations between RPE and each domain (individual test and composite scores) were assessed using linear mixed-effect models adjusted for demographics and comorbid conditions.

Results

In fully adjusted models, higher fatigability at baseline was associated with declines in all cognitive domains over an average 2.2 years of follow-up (p < .04 for all). Longitudinally, increased fatigability over time was associated with worsened executive functions (β= −0.01, p = .002).

Conclusions

These findings suggest that perceived fatigability after a standardized walking task may aid in identification of individuals at a higher risk of future cognitive decline. Future research should examine underlying biological mechanisms contributing to this relationship as well as whether future interventions may target fatigability in midlife to attenuate age-related cognitive decline.
Epidemiology of Perceived Physical Fatigability in Older Adults: The Long Life Family Study
Authors: LaSorda Kelsea R , Gmelin Theresa , Kuipers Allison L , Boudreau Robert M , Santanasto Adam J , Christensen Kaare , Renner Sharon W , Wojczynski Mary K , Andersen Stacy L , Cosentino Stephanie , Glynn Nancy W
Published: December 2019

Background

Fatigability is a construct that measures whole-body tiredness anchored to activities of a fixed intensity and duration; little is known about its epidemiology and heritability.

Methods

Two generations of family members enriched for exceptional longevity and their spouses were enrolled (2006–2009) in the Long Life Family Study (LLFS). At Visit 2 (2014–2017, N = 2,355) perceived physical fatigability was measured using the 10-item self-administered Pittsburgh Fatigability Scale (PFS), along with demographic, medical, behavioral, physical, and cognitive risk factors.

Results

Residual genetic heritability of fatigability was 0.263 (p = 6.6 × 10–9) after adjustment for age, sex, and field center. PFS physical scores (mean ± SD) and higher physical fatigability prevalence (% PFS ≥ 15) were greater with each age strata: 60–69 (n = 1,009, 11.0 ± 7.6, 28%), 70–79 (n = 847, 12.5 ± 8.1, 37%), 80–89 (n = 253, 19.3 ± 9.9, 65.2%), and 90–108 (n = 266, 28.6 ± 9.8, 89.5%), p < .0001, adjusted for sex, field center, and family relatedness. Women had a higher prevalence of perceived physical fatigability compared to men, with the largest difference in the 80–89 age strata, 74.8% versus 53.5%, p < .0001. Those with greater body mass index, worse physical and cognitive function, and lower physical activity had significantly higher perceived physical fatigability.

Conclusions

Perceived physical fatigability is highly prevalent in older adults and strongly associated with age. The family design of LLFS allowed us to estimate the genetic heritability of perceived physical fatigability. Identifying risk factors associated with higher perceived physical fatigability can inform the development of targeted interventions for those most at risk, including older women, older adults with depression, and those who are less physically active.
Electromagnetic modelling with topography on regular grids with equivalent materials
Authors: Kamm Jochen , Becken Michael , Abreu Rafael
Published: December 2019

Maxwell’s equations are valid regardless of the choice of the coordinate system. By this property a change of coordinates can be equivalently expressed as a change of the material parameters. This idea opens a new approach to the problem of accurate electromagnetic modelling in the vicinity of steep topography or bathymetry. Via a change of coordinates, any earth model with complicated layer interfaces can be represented by an equivalent model where those interfaces are flat, but with its materials correspondingly altered. This new model could then be discretized on a regular mesh and fields could be computed by an appropriate finite difference or integral equation code. Unfortunately, this is not straightforward because both the new electric and magnetic materials are fully anisotropic. By instead applying a finite element secondary field approach to the equivalent model, we can completely account for the topography interface in the planar layered background model. The only modification required to existing finite element formulations is a slightly more complicated right-hand side of the linear system of equations, whereas the system matrix is unchanged in any coordinate system. In a numerical modelling experiment we confirm that our technique gives increased accuracy when compared with a recently published technique for dealing with topography in a secondary field formulation for the case of a magnetotelluric source field. In turn, in the vicinity of conductivity anomalies, accuracy can also be negatively affected.
The development of a new accountability measurement framework and tool for global health initiatives
Authors: Martin Hilber Adriane , Doherty Patricia , Nove Andrea , Cullen Rachel , Segun Tunde , Bandali Sarah
Published: December 2019

The Global Strategy for Women’s Children’s and Adolescents’ Health emphasizes accountability as essential to ensure that decision-makers have the information required to meet the health needs of their populations and stresses the importance of tracking resources, results, and rights to see ‘what works, what needs improvement and what requires increased attention’. However, results from accountability initiatives are mixed and there is a lack of broadly applicable, validated tools for planning, monitoring and evaluating accountability interventions. This article documents an effort to transform accountability markers—including political will, leadership and the monitor–review–act cycle—into a measurement tool that can be used prospectively or retrospectively to plan, monitor and evaluate accountability initiatives. It describes the development process behind the tool including the literature review, framework development and subsequent building of the measurement tool itself. It also examines feedback on the tool from a panel of global experts and the results of a pilot test conducted in Bauchi and Gombe states in Nigeria. The results demonstrate that the tool is an effective aid for accountability initiatives to reflect on their own progress and provides a useful structure for future planning, monitoring and evaluation. The tool can be applied and adapted to other accountability mechanisms working in global health.
The Legacies of the Stonewall Riots in Denmark and the Netherlands
Authors: Shield Andrew D J
Published: December 2019

The Netherlands and Denmark housed Europe’s first two postwar homophile organizations, and by the 1960s, activists were already debating anti-homosexual laws in national media (in the Netherlands) demonstrating publicly; thus Stonewall was not the origin of activism in either of these countries. Yet the events in New York City 1969 had two lasting influences in these countries: first, Stonewall catalyzed a transnational ‘consciousness’ (or solidarity) among gay and lesbian activists during a period of radicalization; and second, the Christopher Street Liberation Day 1970 inspired the visible demonstrations known today as ‘Pride’ celebrations. From 1971, Denmark’s national organization planned Christopher Street Day demonstrations every June; and that same year, a radical Gay Liberation Front split off from the association. From 1977, the Netherlands planned its own late-June demonstrations, often with transnational themes (e.g. Anita Bryant in 1977, the Iranian Revolution in 1979). In the following decades, these demonstrations of gay/lesbian visibility moved to August, and Denmark (and Belgium) dropped Christopher Street from event names. Yet scholars, activists, and the general public still evoke the memory of the first Liberation Day when referring to a ‘post-Stonewall’ era in the Netherlands and Denmark.
ILS-Aware Analysis of Low-Homoplasy Retroelement Insertions: Inference of Species Trees and Introgression Using Quartets
Authors: Springer Mark S , Molloy Erin K , Sloan Daniel B , Simmons Mark P , Gatesy John
Published: December 2019

DNA sequence alignments have provided the majority of data for inferring phylogenetic relationships with both concatenation and coalescent methods. However, DNA sequences are susceptible to extensive homoplasy, especially for deep divergences in the Tree of Life. Retroelement insertions have emerged as a powerful alternative to sequences for deciphering evolutionary relationships because these data are nearly homoplasy-free. In addition, retroelement insertions satisfy the “no intralocus-recombination” assumption of summary coalescent methods because they are singular events and better approximate neutrality relative to DNA loci commonly sampled in phylogenomic studies. Retroelements have traditionally been analyzed with parsimony, distance, and network methods. Here, we analyze retroelement data sets for vertebrate clades (Placentalia, Laurasiatheria, Balaenopteroidea, Palaeognathae) with 2 ILS-aware methods that operate by extracting, weighting, and then assembling unrooted quartets into a species tree. The first approach constructs a species tree from retroelement bipartitions with ASTRAL, and the second method is based on split-decomposition with parsimony. We also develop a Quartet-Asymmetry test to detect hybridization using retroelements. Both ILS-aware methods recovered the same species-tree topology for each data set. The ASTRAL species trees for Laurasiatheria have consecutive short branch lengths in the anomaly zone whereas Palaeognathae is outside of this zone. For the Balaenopteroidea data set, which includes rorquals (Balaenopteridae) and gray whale (Eschrichtiidae), both ILS-aware methods resolved balaeonopterids as paraphyletic. Application of the Quartet-Asymmetry test to this data set detected 19 different quartets of species for which historical introgression may be inferred. Evidence for introgression was not detected in the other data sets.
Reliability of hip range of motion measurement among experienced arthroscopic hip preservation surgeons
Authors: Harris Joshua D , Mather Richard C , Nho Shane J , Salvo John P , Stubbs Allston J , Van Thiel Geoffrey S , Wolff Andrew B , Christoforetti John J , Ellis Thomas J , Matsuda Dean K , Kivlan Benjamin R , Carreira Dominic S
Published: December 2019

The aim of this study was to determine (i) the reliability of hip range of motion measurement among experienced arthroscopic hip preservation surgeons and (ii) the magnitude of hip flexion change with posterior pelvic tilt. Five experienced arthroscopic hip preservation surgeons (5–18 years of hip surgery experience) performed passive hip range of motion (internal and external rotation), flexion (contralateral hip extended) and flexion with posterior pelvic tilt (contralateral hip maximally flexed) on five young healthy asymptomatic volunteers (three males, two females; 34.4 ± 10.7 years of age). Motion was measured via digital photography and goniometry. Inter-observer reliability was calculated via two-way mixed, single measures, intra-class correlation coefficient. Paired t-test was utilized to compare hip flexion (with contralateral hip extended) to hip flexion with posterior pelvic tilt (with contralateral hip in forced flexion). The reliabilities of measurements of hip flexion with posterior pelvic tilt and external rotation were excellent, that of hip flexion was fair, and that of hip internal rotation was poor. The magnitude of hip flexion increase with posterior pelvic tilt was 17.0° ± 3.0° (P < 0.001). The reliability of hip range of motion measurement by five experienced arthroscopic hip preservation surgeons was excellent for measures of hip flexion with posterior pelvic tilt and external rotation. Contralateral maximal hip flexion significantly increased ipsilateral hip flexion (approximately 17°).

Level of Evidence: Diagnostic, level III (without consistently applied reference standard)
Effects of chaos on the detectability of stellar streams
Authors: Mestre Martín , Llinares Claudio , Carpintero Daniel D
Published: December 2019

Observations show that stellar streams originating in satellite dwarf galaxies are frequent in the Universe. While such events are predicted by theory, it is not clear how many of the streams that are generated are washed out afterwards to the point in which it is impossible to detect them. Here, we study how these diffusion times are affected by the fact that typical gravitational potentials of the host galaxies can sustain chaotic orbits. We do this by comparing the behaviour of simulated stellar streams that reside in chaotic or non-chaotic regions of the phase space. We find that chaos does reduce the time interval in which streams can be detected. By analysing detectability criteria in configuration and velocity space, we find that the impact of these results on the observations depends on the quality of both the data and the underlying stellar halo model. For all the stellar streams, we obtain a similar upper limit to the detectable mass.
Cell-line specific RNA editing patterns in Trypanosoma brucei suggest a unique mechanism to generate protein variation in a system intolerant to genetic mutations
Authors: Kirby Laura E , Koslowsky Donna
Published: December 2019

Trypanosoma brucei possesses a highly complex RNA editing system that uses guide RNAs to direct the insertion and deletion of uridines in mitochondrial mRNAs. These changes extensively alter the target mRNAs and can more than double them in length. Recently, analyses showed that several of the edited genes possess the capacity to encode two different protein products. The overlapped reading frames can be accessed through alternative RNA editing that shifts the translated reading frame. In this study, we analyzed the editing patterns of three putative dual-coding genes, ribosomal protein S12 (RPS12), the 5′ editing domain of NADH dehydrogenase subunit 7 (ND7 5′), and C-rich region 3 (CR3). We found evidence that alternatively 5′-edited ND7 5′ and CR3 transcripts are present in the transcriptome, providing evidence for the use of dual ORFs in these transcripts. Moreover, we found that CR3 has a complex set of editing pathways that vary substantially between cell lines. These findings suggest that alternative editing can work to introduce genetic variation in a system that selects against nucleotide mutations.
Whole-exome sequencing reveals the impact of UVA light mutagenesis in xeroderma pigmentosum variant human cells
Authors: Moreno Natália Cestari , de Souza Tiago Antonio , Garcia Camila Carrião Machado , Ruiz Nathalia Quintero , Corradi Camila , Castro Ligia Pereira , Munford Veridiana , Ienne Susan , Alexandrov Ludmil B , Menck Carlos Frederico Martins
Published: December 2019

UVA-induced mutagenesis was investigated in human pol eta-deficient (XP-V) cells through whole-exome sequencing. In UVA-irradiated cells, the increase in the mutation frequency in deficient cells included a remarkable contribution of C>T transitions, mainly at potential pyrimidine dimer sites. A strong contribution of C>A transversions, potentially due to oxidized bases, was also observed in non-irradiated XP-V cells, indicating that basal mutagenesis caused by oxidative stress may be related to internal tumours in XP-V patients. The low levels of mutations involving T induced by UVA indicate that pol eta is not responsible for correctly replicating T-containing pyrimidine dimers, a phenomenon known as the ‘A-rule’. Moreover, the mutation signature profile of UVA-irradiated XP-V cells is highly similar to the human skin cancer profile, revealing how studies involving cells deficient in DNA damage processing may be useful to understand the mechanisms of environmentally induced carcinogenesis.
The Transpalpebral Versus the Transciliary Variant of the Supraorbital Keyhole Approach: Anatomic Concepts for Aneurysm Surgery
Authors: Rychen Jonathan , Zumofen Daniel W , Riina Howard A , Mariani Luigi , Guzman Raphael
Published: December 2019

BACKGROUND

The supraorbital craniotomy (SOC) is classically performed through a skin incision in the patient's eyebrow. A variant with a skin incision in the patient's eyelid has become increasingly popular in recent years.

OBJECTIVE

To compare the transpalpebral and the transciliary variants of the SOC with regard to their potential role in aneurysm surgery.

METHODS

We carried out cadaveric dissections and virtual craniotomies on computerized tomography datasets. The skin incision, the craniotomy location and size, the working angles, and the achievable exposure of neurovascular structures were assessed and compared for both variants of the SOC.

RESULTS

The skin incision measured 4 cm for the transpalpebral and 3 cm for the transciliary variant. The skin could be retracted 1.5 cm upward from the lower edge of the orbital rim with the transpalpebral and 2.5 cm upward with the transciliary variant. The craniotomy size was 2.5 × 1.5 cm for both variants, given that the transpalpebral variant included an orbital osteotomy. The bony opening in the transpalpebral variant was 1 cm more caudal; this restricted the craniocaudal working angles and, thereby, limited the achievable exposure of neurovascular structures in the paraclinoid area and along the sphenoid ridge.

CONCLUSION

If the orbital rim and the anterior aspect of the orbital roof are removed, then the transpalpebral variant of the SOC enables a bony opening that is just as large as that of the transciliary variant. Nonetheless, the more caudal location of the bony opening alters the available working angles and may impede exposure of key structures during aneurysm surgery.
Implementation of a Cost-Effective Physical Therapy Approach (Coach2Move) to Improve Physical Activity in Community-Dwelling Older Adults With Mobility Problems: Protocol for a Cluster-Randomized, Stepped Wedge Trial
Authors: Heij Ward , Teerenstra Steven , Sweerts Lieke , Staal J Bart , Nijhuis-van der Sanden Maria W G , Hoogeboom Thomas J
Published: December 2019

Background

Coach2Move is a personalized treatment strategy by physical therapists to elicit physical activity in community-dwelling older adults with mobility problems.

Objective

The primary objective of this study is to assess the effectiveness and cost-effectiveness of the implementation of Coach2Move compared with regular care physical therapy in daily clinical practice.

Design, Setting, Participants, and Intervention

A multicenter cluster-randomized stepped wedge trial is being implemented in 16 physical therapist practices (4 clusters of 4 practices in 4 steps) in the Netherlands. The study aims to include 400 older adults (≥70 years) living independently with mobility problems and/or physically inactive lifestyles. The intervention group receives physical therapy conforming to the Coach2Move strategy; the usual care group receives typical physical therapist care.

Measurements

Measurements are taken at baseline and 3, 6, and 12 months after the start of treatment. The primary outcomes for effectiveness are the amount of physical activity (LASA Physical Activity Questionnaire) and functional mobility (Timed Up and Go test). Trial success can be declared if at least 1 parameter improves while another does not deteriorate. Secondary outcomes are level of frailty (Evaluative Frailty Index for Physical Activity), perceived effect (Global Perceived Effect and Patient Specific Complaints questionnaire), quality of life (EQ-5D-5 L), and health care expenditures. Multilevel linear regression analyses are used to compare the outcomes between treatment groups according to an intention-to-treat approach. Alongside the trial, a mixed-methods process evaluation is performed to understand the outcomes, evaluate therapist fidelity to the strategy, and detect barriers and facilitators in implementation.

Limitations

An important limitation of the study design is the inability to blind treating therapists to study allocation.

Discussion

The trial provides insight into the effectiveness and cost-effectiveness of the Coach2Move strategy compared with usual care. The process evaluation provides insight into influencing factors related to outcomes and implementation.
Cognitive Brain Signatures of Youth With Early Onset and Relatives With Schizophrenia: Evidence From fMRI Meta-analyses
Authors: Arsalidou Marie , Yaple Zachary , Jurcik Tomas , Ushakov Vadim
Published: December 2019

Deficits in cognitive function are a major characteristic of schizophrenia. Many functional magnetic resonance imaging (fMRI) studies examine brain correlates of cognitive function in adults with schizophrenia, showing altered implication of associative areas such as the prefrontal cortex and temporal cortex. fMRI studies also examine brain representation of cognitive function in adolescents with early onset schizophrenia and those at risk of the disorder, yet results are often inconsistent. We compile and analyze data from eligible fMRI studies using quantitative meta-analyses to reveal concordant brain activity associated with adolescent relatives of patients with schizophrenia and those with early onset schizophrenia. Results show similar functional hubs of brain activity (eg, precuneus) yet in opposite hemispheres and clusters in ventrolateral rather than dorsolateral prefrontal cortices. Other areas of altered implication include the middle temporal gyrus, insula, and cerebellum. We discuss the findings in reference to the protracted maturation of the prefrontal cortex and possible effects due to the medication status of the two groups.
Epidemiology and Outcomes of Early Morning Neuroparalytic Syndrome Following Snake Bite—A Retrospective Study
Authors: Samprathi Madhusudan , Gupta Vipul , Jayashree Muralidharan , Bansal Arun , Baranwal Arun , Nallasamy Karthi
Published: December 2019

Objective

Snake envenomation has been poorly studied in developing countries. ‘Early morning neuroparalytic syndrome’ (EMNS), the classical clinical constellation caused by krait bites, refers to nighttime, indoor bites where nonspecific symptoms progress to neuroparalysis. Literature regarding EMNS in children is scarce. This study was planned to describe the clinical profile, intensive care needs and predictors of outcome in children with EMNS.

Methods

It is a retrospective study of children below 12 years admitted with a clinical diagnosis of snake envenomation to the pediatric intensive care unit (PICU) of a tertiary care hospital in North India. Patient records were reviewed from the electronic patient database manager. Comparison was made between the EMNS group and the non-EMNS group and between survivors and nonsurvivors within the EMNS group.

Results

Of the 111 children with snake envenomation, 76 had neuroparalysis (68%) and 51 had EMNS. In the EMNS cohort, 37 (72.5%) belonged to rural areas, 46 (90.2%) had indoor bites and 39 (76.5%) were witnessed. Patients with EMNS were more likely to have absent fang marks, hypoxemia at admission, bulbar palsy and need for PICU admission. Mortality rate was 13.7% in EMNS; predictors included younger age, presence of ptosis, cardiac arrest at admission and nonavailability of PICU bed (univariable analysis) but none of them independently predicted mortality.

Conclusion

Younger age, presence of ptosis, cardiac arrest at admission and nonavailability of intensive care beds increase the risk of mortality in children with EMNS. Timely recognition and respiratory support may reduce mortality in these children.
Putting Global Governance in Its Place
Authors: Rodrik Dani
Published: December 2019

Greater interdependence is often taken to require more global governance, but the logic requires scrutiny. Cross-border spillovers do not always call for international rules. The canonical cases for global governance are based on two sets of circumstances: global commons and “beggar-thy-neighbor” (BTN) policies. The world economy is not a global commons (outside of climate change), and much of our current discussions deal with policies that are not true BTNs. Some of these are beggar-thyself policies; others may produce domestic benefits, addressing real market distortions or legitimate social objectives. The case for global governance in such policies, I will argue, is very weak, and possibly outweighed by the risk that global oversight or regulation would backfire. While these policy domains are certainly rife with failures, such failures arise not from weaknesses of global governance, but from failures of national governance and cannot be fixed through international agreements or multilateral cooperation. I advocate a mode of global governance that I call “democracy-enhancing global governance,” to be distinguished from “globalization-enhancing global governance.”
Geographic variation in the laryngeal morphology of a widely distributed South-American anuran: behavioural and evolutionary implications
Authors: López Carlos , Quispe Maricel , Villalón Aldo , Concha Miguel L , Penna Mario , Velásquez Nelson A
Published: December 2019

Sound-producing organs generate acoustic signals that have a fundamental role in communication systems. In species exhibiting different biogeographic patterns, variations of these structures can explain a large part of interpopulation differences of their signals. Pleurodema thaul is an anuran with an extensive geographic distribution in Chile and presents an evident divergence in its acoustic signals among three genetic/bioacoustic groups (i.e. northern, central and southern). By means of classic histology and 3D-reconstructions, we study the geographic variation in the larynx of P. thaul males from these three groups. In addition, volumes of six laryngeal structures are used as predictors of acoustic characteristics of advertisement calls recorded in previous studies for the same subjects used in the current study. After removing the effect of body size, the arytenoid cartilage, dilator muscle and vocal cords show significant differences between the three bioacoustic groups. Furthermore, arytenoid cartilage and dilator muscle volumes predict some temporal parameters and also the dominant frequency of advertisement calls. Our results show important geographic variation in laryngeal morphology, which is in correspondence with acoustic, behavioural and genetic variation in this species.
Construction of High-Density Linkage Maps and Identification of Quantitative Trait Loci Associated with Verticillium Wilt Resistance in Autotetraploid Alfalfa (Medicago sativaL.)
Authors: Yu Long-Xi , Zhang Fan , Culma Cesar Medina , Lin Sen , Niu Yi , Zhang Tiejun , Yang Qingchuan , Smith Mark , Hu Jinguo
Published: December 2019

Verticillium wilt (VW) of alfalfa is a devastating disease that causes forage yield reductions of up to 50% in the northern United States and Canada. The most effective method for controlling the disease is through the development and use of resistant varieties. To identify quantitative trait loci (QTL) for VW resistance in alfalfa, we used a full-sib population segregating for VW resistance. High-density linkage maps for both resistant and susceptible parents were constructed using single-dose alleles of single-nucleotide polymorphism markers generated by genotyping-by-sequencing. Five QTL associated with VW resistance were identified and they were in four linkage groups (4D, 6B, 6D, and 8C). Of those, three QTL (qVW-6D-1, qVW-6D-2, and qVW-8C) had higher logarithm of odds. Two putative candidates of nucleotide-binding site leucine-rich repeat disease resistance genes were identified in the QTL intervals of qVW-6D-2 and qVW-8C, respectively. The result agreed with our previous studies, in which similar resistance loci were identified in an association panel using genome-wide association. The results provide insight into the quantitative resistance to VW in alfalfa. The resistance loci and closely linked markers identified in the present study can be used in developing new alfalfa varieties with enhanced resistance to VW.
Genome-Wide Association Study Identifies Single Nucleotide Polymorphism Markers Associated with Mycelial Growth (at 15, 20, and 25°C), Mefenoxam Resistance, and Mating Type in Phytophthora infestans
Authors: Ayala-Usma D. A. , Danies G. , Myers K. , Bond M. O. , Romero-Navarro J. A. , Judelson H. S. , Restrepo S. , Fry W. E.
Published: December 2019

Phenotypic diversity among individuals defines the potential for evolutionary selection in a species. Phytophthora infestans epidemics are generally thought to be favored by moderate to low temperatures, but temperatures in many locations worldwide are expected to rise as a result of global climate change. Thus, we investigated variation among individuals of P. infestans for relative growth at different temperatures. Isolates of P. infestans came from three collections: (i) individual genotypes recently dominant in the United States, (ii) recently collected individuals from Central Mexico, and (iii) progeny of a recent sexual recombination event in the northeastern United States. In general, these isolates had optimal mycelial growth rates at 15 or 20°C. However, two individuals from Central Mexico grew better at higher temperatures than did most others and two individuals grew relatively less at higher temperatures than did most others. The isolates were also assessed for mefenoxam sensitivity and mating type. Each collection contained individuals of diverse sensitivities to mefenoxam and individuals of the A1 and A2 mating type. We then searched for genomic regions associated with phenotypic diversity using genotyping-by-sequencing. We found one single nucleotide polymorphism (SNP) associated with variability in mycelial growth at 20°C, two associated with variability in mycelial growth at 25°C, two associated with sensitivity to mefenoxam, and one associated with mating type. Interestingly, the SNPs associated with mefenoxam sensitivity were found in a gene-sparse region, whereas the SNPs associated with growth at the two temperatures and mating type were found both at more gene-dense regions.
Peripheral neuropathy
Authors: Nold Carrie Smith , Nozaki Kenkichi
Published: December 2019

Peripheral neuropathy is a common condition that can be encountered in a multitude of clinical settings. Treatment must be tailored to the underlying cause. This article reviews various causes of peripheral neuropathy and offers recommendations for evaluating patients to determine the cause of peripheral neuropathy.
The Power of Contribution and Attribution in Assessing Educational Outcomes for Individuals, Teams, and Programs
Authors: Schumacher Daniel J. , Dornoff Eric , Carraccio Carol , Busari Jamiu , van der Vleuten Cees , Kinnear Benjamin , Kelleher Matthew , Sall Dana R. , Warm Eric , Martini Abigail , Holmboe Eric
Published: December 2019

Recent discussions have brought attention to the utility of contribution analysis for evaluating the effectiveness and outcomes of medical education programs, especially for complex initiatives such as competency-based medical education. Contribution analysis focuses on the extent to which different entities contribute to an outcome. Given that health care is provided by teams, contribution analysis is well suited to evaluating the outcomes of care delivery. Furthermore, contribution analysis plays an important role in analyzing program- and system-level outcomes that inform program evaluation and program-level improvements for the future. Equally important in health care, however, is the role of the individual. In the overall contribution of a team to an outcome, some aspects of this outcome can be attributed to individual team members. For example, a recently discharged patient with an unplanned return to the emergency department to seek care may not have understood the discharge instructions given by the nurse or may not have received any discharge guidance from the resident physician. In this example, if it is the nurse’s responsibility to provide discharge instructions, that activity is attributed to him or her. This and other activities attributed to different individuals (e.g., nurse, resident) combine to contribute to the outcome for the patient. Determining how to tease out such attributions is important for several reasons. First, it is physicians, not teams, that graduate and are granted certification and credentials for medical practice. Second, incentive-based payment models focus on the quality of care provided by an individual. Third, an individual can use data about his or her performance on the team to help drive personal improvement. In this article, the authors explored how attribution and contribution analyses can be used in a complimentary fashion to discern which outcomes can and should be attributed to individuals, which to teams, and which to programs.
Effects of Tonic Spinal Cord Stimulation on External Mechanical and Thermal Stimuli Perception Using Quantitative Sensory Testing
Authors: Bordeleau Martine , Carrondo Cottin Sylvine , Cantin Léo , Gaudin Daniel , Alnemari Ahmed , Canuel Jean-François , Fugère François , Fournier-Gosselin Marie-Pierre , Vollert Jan , Prud’Homme Michel
Published: December 2019

Objectives:

Tonic spinal cord stimulation (SCS) is currently used to treat neuropathic pain. With this type of stimulation, an implantable pulse generator generates electrical paresthesias in the affected area through 1 or more epidural leads. The goal of this study was to evaluate the impact of tonic SCS on the sensory perception of chronic pain patients using quantitative sensory testing (QST).

Materials and Methods:

Forty-eight patients (mean age: 57 y) with chronic leg pain due to failed back surgery syndrome or complex regional pain syndrome treated with SCS were recruited from 3 research centers. Test procedures included 2 sessions (stimulation On or Off), with measures of detection thresholds for heat, touch, vibration, and of pain thresholds for cold, heat, pressure, the assessment of dynamic mechanical allodynia, and temporal pain summation. Three different areas were examined: the most painful area of the most painful limb covered with SCS-induced paresthesias (target area), the contralateral limb, and the ipsilateral upper limb. Wilcoxon signed-rank tests were used to compare the mean difference between On and Off for each QST parameter at each area tested. P-values <0.05 were considered significant.

Results:

Regarding the mean difference between On and Off, patients felt less touch sensation at the ipsilateral area (−0.4±0.9 g, P=0.0125) and were less sensitive at the contralateral area for temporal pain summation (−4.9±18.1 on Visual Analog Scale 0 to 100, P=0.0056) with SCS.

Discussion:

It is not clear that the slight changes observed were clinically significant and induced any changes in patients’ daily life. Globally, our results suggest that SCS does not have a significant effect on sensory perception.
Endoplasmic Reticulum Stress Contributes to Nociception via Neuroinflammation in a Murine Bone Cancer Pain Model
Authors: Mao Yanting , Wang Chenchen , Tian Xinyu , Huang Yulin , Zhang Ying , Wu Hao , Yang Shuai , Xu Ke , Liu Yue , Zhang Wei , Gu Xiaoping , Ma Zhengliang
Published: December 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Prolonged endoplasmic reticulum stress has been identified in various diseases. Inflammatory mediators, which have been shown to induce endoplasmic reticulum stress in several studies, have been suggested to serve as the important modulators in pain development. In this study, the authors hypothesized that the endoplasmic reticulum stress triggered by inflammatory mediators contributed to pain development.

Methods

The authors used a male mouse model of bone cancer pain. The control mice were intrathecally injected with tumor necrosis factor-α (TNF-α) and lipopolysaccharide, the bone cancer pain mice were intrathecally injected with the endoplasmic reticulum stress inhibitors 4-PBA and GSK2606414. The nociceptive behaviors, endoplasmic reticulum stress markers, and inflammatory mediators were assessed.

Results

Increased expression of the p-RNA-dependent protein kinase-like endoplasmic reticulum kinase and p-eukaryotic initiation factor 2α were found in the spinal neurons during bone cancer pain, along with upregulation of inflammatory mediators (TNF-α, interleukin 1β, and interleukin 6). Intrathecal administration of TNF-α or lipopolysaccharide increased the expression of endoplasmic reticulum stress markers in control mice. Inhibition of endoplasmic reticulum stress by intrathecal administration of 4-PBA (baseline vs. 3 h: 0.34 ± 0.16 g vs. 1.65 ± 0.40 g in paw withdrawal mechanical threshold, 8.00 ± 1.20 times per 2 min vs. 0.88 ± 0.64 times per 2 min in number of spontaneous flinches, P < 0.001, n = 8) or GSK2606414 (baseline vs. 3 h: 0.37 ± 0.08 g vs. 1.38 ± 0.11 g in paw withdrawal mechanical threshold, 8.00 ± 0.93 times per 2 min vs. 3.25 ± 1.04 times per 2 min in number of spontaneous flinches, P < 0.001, n = 8) showed time- and dose-dependent antinociception. Meanwhile, decreased expression of inflammatory mediators (TNF-α, interleukin 1β, and interleukin 6), as well as decreased activation of astrocytes in the spinal cord, were found after 4-PBA or GSK2606414 treatment.

Conclusions

Inhibition of inflammatory mediator–triggered endoplasmic reticulum stress in spinal neurons attenuates bone cancer pain via modulation of neuroinflammation, which suggests new approaches to pain relief.