bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrical properties of bulk semi-insulating β-Ga2O3 (Fe)
Authors: Polyakov A. Y. , Smirnov N. B. , Shchemerov I. V. , Pearton S. J. , Ren Fan , Chernykh A. V. , Kochkova A. I.
Published: October 2018

The Fermi level in bulk semi-insulating β-Ga2O3 doped with Fe (∼5 × 1018 cm−3) is found to be pinned near Ec − 0.85 eV. At temperatures ≥400 K, Ni Schottky diodes showed good rectification and measurable low frequency capacitance, allowing the measurement of capacitance-frequency (C-f), capacitance-voltage (C-V), and capacitance-temperature (C-T) characteristics. The activation energy and the electron capture cross section obtained were (0.75–0.82) eV and (2–5) × 10−15 cm2, in good agreement with the reported signature of the E2 electron trap assigned to Fe. The concentration of the filled centers determined from C-V was close to the concentration of residual shallow donors in undoped materials. Photoinduced current transient spectroscopy measurements showed that Fe doping does not promote the generation of high densities of deep traps other than those related to Fe.
Skin lesions suspicious for melanoma: New Zealand excision margin guidelines in practice
Authors: Brian Tess , Jameson Michael B.
Published: October 2018

ABSTRACT

INTRODUCTION
New Zealand guidelines for cutaneous melanoma management recommend excision biopsy specimens of suspected lesions have a 2 mm horizontal margin, and a deep margin into upper subcutis.

AIM
To assess guideline compliance of suspicious lesion biopsies taken in the community and in a hospital.

METHODS
Patients admitted to Waikato Hospital, Hamilton, for diagnostic or treatment melanoma surgery during the year ending February 2016 were retrospectively identified, and their demographic and biopsy characteristics examined.

RESULTS
In total, 140 patients had excision biopsies: 61.4% were performed outside the hospital. Biopsy data were available for 126 specimens. Mean horizontal margin was greater (P = 0.001) in hospital biopsies (4.8 mm, standard deviation (s.d.) 3.7 mm) than biopsies performed elsewhere (2.8 mm; s.d. 1.8 mm). Horizontal margins >2.0 mm occurred in 70.6% of specimens; 21.6% of ≤2.0 mm specimens had a tumour-positive margin. Subsequent wide local excision identified residual melanoma in 9.6% of specimens, which was not associated (P = 0.3) with primary horizontal margin ≤2.0 mm. Mean deep margin of hospital biopsies (6.5 mm; s.d. 2.7 mm) was greater (P < 0.001) than in other biopsies (4.1 mm; s.d. 2.7 mm). Horizontal margin >2.0 mm specimens had greater (P < 0.001) mean deep margin (5.9 mm; s.d. 2.7 mm) than specimens with horizontal margin ≤2.0 mm (mean deep margin 3.3 mm; s.d. 2.7 mm). Deep margin ≤2.0 mm (19.0%) was independently associated with the facility where biopsy was performed (P = 0.001) and horizontal margin (P < 0.001).

DISCUSSION
The New Zealand biopsy deep margin recommendation does not lend itself to meaningful audit. Compliance with the horizontal margin recommendation was low, but of uncertain clinical significance.
Patients’ perceptions of team-based care in family practice: access, benefits and team roles
Authors: Szafran Olga , Kennett Sandra L. , Bell Neil R. , Green Lee
Published: October 2018

ABSTRACT INTRODUCTION The increasing complexity of health care and escalating prevalence of multiple chronic conditions have driven interprofessional team-based care in family practice. Most published studies examine team-based care from the perspective of health professionals. The purpose of this study was to examine patients’ perceptions of team-based care in family practice. METHODS This was a waiting room survey conducted in five family medicine academic teaching clinics in Edmonton, Alberta, Canada. Patients aged ≥18 years were invited to participate in a survey addressing patient access to team-based care, perceived benefits, preferred health professional and team member roles. RESULTS Of the 44.3% (565/1274) of respondents, 41.8% (231/552) reported receiving care from a team of health professionals, primarily for chronic disease management or pharmacy consultations. While there was a consistent pattern of patient perception that many aspects of care did not worsen with team-based care, improvements in knowledge of their medical condition (67.4%); the care received (65.0%); access to care (51.1%); ability to self-care (48.9%) and maintain their independence (43.7%); and overall health (51.1%) were reported. Some patients felt that team-based care reduced emergency visits (34.6%) and hospitalisations (29.9%), and 44.1% of patients felt that they had an active role on the team and made decisions about their care together with health professionals. CONCLUSION Patients perceive that team-based care in family practice has improved their knowledge and access to care, overall health and avoided some emergency department visits and hospital admissions. The findings support the continued development of team-based care in family practice.
Potential of shells of three species of eastern Australian freshwater mussels (Bivalvia: Hyriidae) as environmental proxy archives
Authors: Herath D. , Jacob D. E. , Jones H. , Fallon S. J.
Published: October 2018

Freshwater mussels in Australia are rarely studied for their life history and potential as palaeoclimate proxy archives. Therefore, we studied three freshwater mussel species from the Williams River, Hunter Valley, Australia, namely Alathyria profuga, Cucumerunio novaehollandiae and Hyridella drapeta, to identify their potential as new environmental proxy archives from Australian freshwater bodies. Growth analysis revealed that A. profuga and C. novaehollandiae produce distinctive growth lines, which allow the first identification of age and growth structure of these species. The oxygen isotope ratio in A. profuga shells and high-resolution element concentrations in all three species show cyclic, annual variations. A high correlation between growth rates and the combined winter air temperature and annual rainfall, as well as accurate temperature reconstruction using oxygen isotope values in the shells suggest that A. profuga has good potential as an environmental proxy archive. However, the low correlation observed between the Sr:Ca ratio and temperature limited the usefulness of the Sr:Ca ratio in A. profuga shells as a water temperate proxy. In contrast, growth rates and element ratios of C. novaehollandiae do not indicate a significant relationship with environmental variables, suggesting that this species, together with H. drapeta, is probably not suitable for palaeoclimatic studies.
Native-state imaging of calcifying and noncalcifying microalgae reveals similarities in their calcium storage organelles
Authors: Gal Assaf , Sorrentino Andrea , Kahil Keren , Pereiro Eva , Faivre Damien , Scheffel André
Published: October 2018

Significance

Coccolithophores are abundant unicellular marine algae that produce calcified scales via a controlled intracellular process. Understanding the cellular controls over the calcification process is a pressing need to predict the influence of changing oceanic conditions on these major contributors to global marine calcification and carbon fluxes. Using several microalgae, and a combination of state-of-the-art cryoelectron and cryo soft X-ray microscopy, we demonstrate that the recently discovered calcium stores of coccolithophores are similar to the common calcium storage organelles of noncalcifying organisms. These results relate questions of environmental and evolutionary significance to a large body of physiological and molecular genetic findings of better-characterized organisms, and therefore provide fresh entry points for understanding calcification in coccolithophores.
Cbln2 and Cbln4 are expressed in distinct medial habenula-interpeduncular projections and contribute to different behavioral outputs
Authors: Seigneur Erica , Polepalli Jai S. , Südhof Thomas C.
Published: October 2018

Significance

Cerebellins are important neurexin ligands that remain poorly understood. Two critical questions in particular remain unanswered: do different cerebellins perform distinct functions, and do these functions act in the initial establishment of synapses or in rendering nascent synapses capable of normal synaptic transmission? Here we report that in mice, two homologous cerebellins, Cbln2 and Cbln4, are expressed in different types of neurons of the medial habenula (MHb), and that these neurons project to distinct target neurons in the interpeduncular nucleus. Ablation of Cbln2 or Cbln4 from the MHb impairs distinct behaviors, but only ablation of Cbln2 affects synapse numbers. Our data show that different cerebellins perform distinct functions that involve synaptic information processing but not initial synapse formation.
A New Look at the Living Arrangements of Older Americans Using Multistate Life Tables
Authors: Raymo James M , Pike Isabel , Liang Jersey
Published: October 2018

Objectives

We extend existing research on the living arrangements of older Americans by focusing on geographic proximity to children, examining transitions in living arrangements across older ages, and describing differences by both race/ethnicity and educational attainment.

Method

We use data from the Health and Retirement Study (HRS) over a period of 10 years (2000–2010) to construct multistate life tables. These analyses allow us to describe the lives of older Americans between ages 65 and 90 in terms of the number of expected years of life in different living arrangements, reflecting both mortality and living arrangement transitions.

Results

Americans spend a substantial proportion of later life living near, but not with, adult children. There is a good deal of change in living arrangements at older ages and living arrangement-specific life expectancy differs markedly by race/ethnicity and educational attainment. However, overall life expectancy is not strongly related to living arrangements at age 65.

Discussion

Multistate life tables, constructed separately by sex, race/ethnicity, and educational attainment, provide a comprehensive description of sociodemographic differences in living arrangements across older ages in the United States. We discuss the potential implications of these differences for access to support and the exacerbation or mitigation of inequalities at older ages.
Volunteers’ Felt Respect and Its Associations With Volunteering Retention, Daily Affect, Well-being, and Mortality
Authors: Tse Dwight C K
Published: October 2018

Objectives

Volunteering is associated with improved physical and psychological well-being; volunteers feeling more respect for their work may have better well-being than their counterparts.

Methods

This study investigated the effects of felt respect for volunteer work on volunteering retention, daily affect, well-being (subjective, psychological, and social), and mortality. The study analyzed survey and mortality data from a national sample of 2,677 volunteers from the Midlife in the United States Study over a 20-year span. Daily affect data were obtained from a subsample of 1,032 volunteers.

Results

Compared to volunteers feeling less respect from others, those feeling more respect (a) were more likely to continue volunteering 10 and 20 years later, (b) had higher levels of daily positive affect and lower levels of daily negative affect, and (c) had higher levels of well-being over a 20-year period. The effect of felt respect on mortality was not statistically significant.

Discussion

Greater level of felt respect for volunteer work is positively related to volunteers’ retention rates, daily affective experience, and well-being.
Higher Brackets on Cyclic and Negative Cyclic (Co)Homology
Authors: Fiorenza Domenico , Kowalzig Niels
Published: October 2018

The purpose of this article is to embed the string topology bracket developed by Chas–Sullivan and Menichi on negative cyclic cohomology groups as well as the dual bracket found by de Thanhoffer de Völcsey–Van den Bergh on negative cyclic homology groups into the global picture of a noncommutative differential (or Cartan) calculus up to homotopy on the (co)cyclic bicomplex in general, in case a certain Poincaré duality is given. For negative cyclic cohomology, this in particular leads to a Batalin–Vilkoviskiĭ (BV) algebra structure on the underlying Hochschild cohomology. In the special case in which this BV bracket vanishes, one obtains an $e_3$-algebra structure on Hochschild cohomology. The results are given in the general and unifying setting of (opposite) cyclic modules over (cyclic) operads.
Fear of catastrophic health expenditures and unrealistic expectations from supplementary health insurance: ethnic differences
Authors: HaGani Neta , Hayek Samah , Tarabeia Jalal , Yehia Mohammad , Green Manfred S
Published: October 2018

Background

In Israel, the whole population is covered by comprehensive universal health insurance. Despite that, most of the population purchases supplementary health insurance (SHI). It has been shown that individuals purchase more health insurance and preventive medicine when they are uncertain of their state of health, while a majority may not fully understand basic concepts in their health insurance coverage. The purpose of this study was to examine the role of fear of catastrophic health expenditures and unrealistic expectations in purchasing SHI, which does not cover expenses for life-threatening illnesses.

Methods

A cross-sectional survey was conducted among random samples of 814 Jews and 800 Arabs in Israel. A structured questionnaire was administered by telephone using random digit dialling. Log-linear regression was used to identify factors associated with reasons for purchasing SHI and expectations from SHI.

Results

The most common reason for purchasing SHI was fear of catastrophic health-related expenditures (41%). The most important service expected from SHI was ‘cancer medications’ (mean 4.68 [standard deviation 0.87]). Differences in the reasons for purchasing SHI and in expectations from SHI were found according to population group, age, gender and education.

Conclusions

Consumers’ misconceptions and fear of catastrophic health expenditures are major factors leading to the purchase of SHI, despite universal health coverage. Improved and accessible information should help consumers make informed decisions as to whether or not to purchase SHI.
Population Frequency of Serous Tubal Intraepithelial Carcinoma (STIC) in Clinical Practice Using SEE-Fim Protocol
Authors: Samimi Goli , Trabert Britton , Geczik Ashley M , Duggan Máire A , Sherman Mark E
Published: October 2018

Frequent detection of serous tubal intraepithelial carcinoma (STIC) among BRCA1/2 mutation carriers undergoing risk-reducing surgery prompted the hypothesis that many adnexal high-grade serous carcinomas (HGSCs) arise from the fallopian tube, rather than the ovary, as supposed. The changing paradigm has important implications for HGSC prevention. Most data related to the frequency of STIC are derived from case series and estimates vary widely. Therefore, we analyzed population-based data from 10 523 surgeries including salpingectomy (Jan 2014–Dec 2016) that were examined using the “Sectioning and Extensively Examining the Fimbria” protocol, which optimizes STIC detection. Overall, STIC was detected in 40 (0.38%) specimens, including 32 diagnosed with concurrent gynecologic cancer. STIC was detected in 8 (<0.01%) of 9392 cases with benign diagnoses. We conclude that the relative rarity of STIC diagnoses in routine pathology practice has critical implications for research aiming to elucidate the pathogenesis of HGSC and developing prevention strategies.
Patterns of Failure After Stereotactic Radiosurgery for Recurrent High-Grade Glioma: A Single Institution Experience of 10 Years
Authors: Ene Chibawanye I , Macomber Meghan W , Barber Jason K , Ferreira Manuel J , Ellenbogen Richard G , Holland Eric C , Rockhill Jason K , Silbergeld Daniel L , Halasz Lia M
Published: October 2018

BACKGROUND

Stereotactic radiosurgery (SRS) is a treatment modality that is frequently used as salvage therapy for small nodular recurrent high-grade gliomas (HGG). Due to the infiltrative nature of HGG, it is unclear if this highly focused technique provides a durable local control benefit.

OBJECTIVE

To determine how demographic or clinical factors influence the pattern of failure following SRS for recurrent high-grade gliomas.

METHODS

We retrospectively reviewed clinical, radiographic, and follow-up information for 47 consecutive patients receiving SRS for recurrent HGG at our institution between June 2006 and July 2016. All patients initially presented with an HGG (WHO grade III and IV). Following SRS for recurrence, all patients experienced treatment failure, and we evaluated patterns of local, regional, and distant failure in relation to the SRS 50% isodose line.

RESULTS

Most patients with recurrent HGG developed “in-field” treatment failure following SRS (n = 40; 85%). Higher SRS doses were associated with longer time to failure (hazards ratio = 0.80 per 1 Gy increase; 95% confidence interval 0.67-0.96; P = .016). There was a statistically significant increase in distant versus in-field failure among older patients (P = .035). This effect was independent of bevacizumab use (odds ratio = 0.54, P = 1.0).

CONCLUSION

Based on our experience, the majority of treatment failures after SRS for recurrent HGG were “in-field.” Older patients, however, presented with more distant failures. Our results indicate that higher SRS doses delivered to a larger area as fractioned or unfractioned regimen may prolong time to failure, especially in the older population.
‘One Stroak of His Razour’: Tales of Self-Gelding in Early Modern England
Authors: Skuse Alanna
Published: October 2018

This article examines stories of men who gelded themselves in early modern England. These events, it argues, were shaped and partly motivated by a culture in which castration was seen as both degrading and potentially empowering. Religious precedents such as that of Origen of Alexandria framed self-gelding as a foolhardy activity, but one which nevertheless indicated an impressive degree of mastery over the body and its urges. Meanwhile, judicial and popular contexts framed castration as a humiliating and emasculating ordeal. Instances of self-gelding in this period are rare but nonetheless illuminating. Relayed in medical texts and popular ballads, such actions typically occurred as a response to emotional distress. In particular, men gelded themselves as a means to express feelings of emasculation within heterosexual relationships, and to dramatically renounce their role in the libidinal economy.
Diagnosing acute compartment syndrome: are current textbooks misleading?
Authors: Oron Amir , Netzer Niv , Rosinsky Philip , Elmaliache Danielle , Ben-Galim Peleg
Published: October 2018

Background:

Prompt diagnosis of acute compartment syndrome (ACS) is critical when trying to prevent irreversible limb damage. Pain out of proportion and pain on passive tendon stretching are sufficient clinical indicators of ACS. Primary care physicians may delay in making the diagnosis of ACS because they may rely on the classic “5 P” signs. However, paralysis and pulselessness will not appear until the later stages of ACS, at a time when irreversible damage has occurred. The aim of this study was to evaluate the guidelines for diagnosis of ACS as perceived by graduating medical students and primary care physicians and as published in textbooks.

Methods:

One hundred and seventeen medical students and primary care physicians were questioned as to the diagnostic criteria of ACS. Eleven medical textbooks were reviewed to evaluate the diagnostic approach to ACS.

Results:

Of the 117 participants, only 29 (24.8%) answered correctly. Of eleven textbooks, three specifically mentioned the classic “5 P” signs but still provided the correct diagnostic steps, including the essential elements of pain beyond proportion and pain upon passive tendon stretching. Disappointingly, seven textbooks made no mention of the potentially life and limb-threatening diagnosis of ACS, and only one textbook outlined the path to diagnosis of ACS with no mention of the “5 P” signs.

Conclusions:

The misguided diagnosis according to the “5 P” signs in nonorthopaedic medical textbooks that clinicians in multiple disciplines depend on may result in devastating consequences. Pulselessness, paresthesia, and paralysis are signs that appear too late in the course of the disease to serve as diagnostic signs and are not signs to be waited for, a point to be emphasized in teaching.
Readmissions With Dehydration After Ileostomy Creation: Rethinking Risk Factors
Authors: Justiniano Carla F. , Temple Larissa K. , Swanger Alex A. , Xu Zhaomin , Speranza Jenny R. , Cellini Christina , Salloum Rabih M. , Fleming Fergal J.
Published: October 2018

BACKGROUND:

Twenty-nine percent of postileostomy discharges are readmitted, most commonly because of dehydration. However, there is a lack of detailed data specifically evaluating factors associated with readmission with dehydration. In addition, patients with a history of an ileostomy have often been excluded from previous studies and therefore represent a group of understudied ileostomates.

OBJECTIVE:

This study aimed to evaluate factors available at discharge associated with 30-day readmission for dehydration, rather than all-cause readmissions.

DESIGN:

This was a retrospective cohort study.

SETTING:

Study patients received ileostomies at a tertiary academic medical center from 2014 to 2016.

PATIENTS:

Patients with a preexisting ileostomy that was not recreated per the operative note were excluded, whereas those who received a new ileostomy were included.

MAIN OUTCOME MEASURE:

The primary outcome measured was 30-day readmission for dehydration as defined by objective clinical criteria.

RESULTS:

A total of 262 patients underwent ileostomy creation and were discharged alive. Twenty-five percent were ≥65 years of age, 53% were men, 14% had a history of ileostomy, 18% had a creatinine >1.0 on discharge, and 26% had high ileostomy output at any time during the index admission. Among all ileostomates, the all-cause readmission rate was 30%. Mean days to readmission for any cause was 8.5, whereas for dehydration it was 11.6 days. Of the readmissions, 37% were readmitted with a diagnosis of dehydration, and dehydration was the sole reason in 26%. Among those with dehydration, the most common length of stay was 2 days. In multivariable logistic regression, 30-day readmission with dehydration was associated with older age, male sex, history of an ileostomy, high ileostomy output during index admission, and a discharge creatinine >1.0.

LIMITATIONS:

This study was limited by its retrospective design.

CONCLUSIONS:

Ileostomy dehydration efforts have focused on new ileostomy patients; however, our data suggest that patients with a history of an ileostomy are actually at risk for readmission with dehydration. Further studies aimed at the reduction of readmission with dehydration after ileostomy are warranted and should include patients with a history of an ileostomy. See Video Abstract at http://links.lww.com/DCR/A643.
Prognostic Impact of Hypochloremia in Patients With Stage I to III Colorectal Cancer After Radical Resection
Authors: Li Qingguo , Dai Weixing , Jia Huixun , Li Yaqi , Xu Ye , Li Xinxiang , Cai Guoxiang , Cai Sanjun
Published: October 2018

BACKGROUND:

Recent studies have suggested that electrolyte disorders might be a negative prognostic factor for some diseases.

OBJECTIVE:

The purpose of this study was to systematically evaluate the prognostic role of electrolyte disorders in patients with stage I to III colorectal cancer who received radical surgical resection.

DESIGN:

This study was retrospectively performed.

SETTINGS:

The study was conducted at a single tertiary care center.

PATIENTS:

Patients with colorectal cancer who underwent radical resection in between April 2007 and April 2014 were included.

MAIN OUTCOME MEASURES:

The Kaplan–Meier method was adopted to estimate the overall and disease-free survival with and without propensity score matching.

RESULTS:

In total, our study recruited 5089 eligible patients. In prematching analysis, patients with hypochloremia showed both shorter overall survival (HR = 0.943 (95% CI, 0.908–0.980); p = 0.003) and disease-free survival (HR = 0.957 (95% CI, 0.933–0.981); p < 0.001) than those with normal serum chloride levels. In postmatching analysis, 770 patients from each group were compared, and the results further confirmed that hypochloremia was significantly associated with worse overall survival (HR = 0.646 (95% CI, 0.489–0.855); p = 0.002) and disease-free survival (HR = 0.782 (95% CI, 0.647–0.944); p = 0.01), with the hypochloremia group as a reference.

LIMITATIONS:

The study was limited by its retrospective nature.

CONCLUSIONS:

Hypochloremia diagnosed before treatment can independently prognosticate the overall and disease-free survival for patients with stage I to Ш colorectal cancer after radical resection. Intensive surveillance and management might improve the survival outcome for patients with hypochloremia. See Video Abstract at http://links.lww.com/DCR/A727.
Metabolism: The road to inflammation and atherosclerosis
Authors: Ali Lubna , Schnitzler Johan G. , Kroon Jeffrey
Published: October 2018

Purpose of review

Evidence accumulates suggesting that cellular metabolic alterations fuel and dictate the inflammatory state of cells. In this review, we provide an overview of the observed metabolic reprogramming in endothelial cells and innate immune cells upon interaction with modified lipoproteins, thereby contributing to the progression of atherosclerosis.

Recent findings

Inflammatory endothelial cells at sites exposed to disturbed flow patterns show increased glycolytic activity. Atherogenic factors further enhance these metabolic changes by upregulating the mitochondrial energy production and thereby facilitating increased energy expenditure. Metabolic alterations are pivotal for monocyte and macrophage function as well. Exposure to atherogenic particles such as oxidized phospholipids lead to a regulatory metabolic pro-inflammatory phenotype, mediated via Toll-like receptor (TLR) 2 and the transcription factor erythroid 2-related factor (Nrf) 2. Translational studies highlighted the importance of metabolic alterations, as atherosclerotic plaques in the carotid arteries showed an increased glycolytic signature.

Alterations in cellular metabolism play an important role in controlling and steering the inflammatory state of both endothelial cells and immune cells. Targeting glycolysis may therefore provide an interesting route to attenuate the progression of atherosclerosis.
Limited-Stage Hodgkin Lymphoma
Authors: Straus David J.
Published: October 2018

Early-stage classic Hodgkin lymphoma has been highly curable using extended-field radiation therapy (RT) alone, combined-modality therapy consisting of chemotherapy and RT, and more recently chemotherapy alone. Radiation therapy either to an extended field (extended-field RT) or to various iterations of an involved field (involved-field RT) is potentially associated with late morbidity and mortality, particularly second primary cancers and cardiovascular complications. Treatment with chemotherapy alone, when possible, can achieve a high cure rate while avoiding these risks. This review describes the evolution of treatment for early-stage classic Hodgkin lymphoma.
Subjective Cognitive Impairment and the Broad Autism Phenotype
Authors: Caselli Richard J. , Langlais Blake T. , Dueck Amylou C. , Locke Dona E.C. , Woodruff Bryan K.
Published: October 2018

Introduction:

Roughly 4% to 23% of the population embody stress prone personality and other traits characterizing a subclinical “broad autism phenotype” (BAP). Subjective cognitive impairment (SCI) among healthy elderly is associated with psychological distress leading us to predict BAP would be associated with SCI.

Methods:

The Autism Spectrum Quotient, a self-administered 50 item questionnaire, was completed by 419 consecutive members of the Arizona APOE Cohort who underwent neuropsychological testing every 2 years. SCI was assessed with self and informant versions of the Multidimensional Assessment of Neurodegenerative Symptoms (MANS) Questionnaire.

Results:

A total of 45 individuals scored in the BAP range, designated BAP+, and the rest were BAP−. At entry, both Multidimensional Assessment of Neurodegenerative Symptoms Questionnaire Self and Informant scores were higher in the BAP+ group (P<0.0001). After age 60, the BAP+ group had greater annual increases in Multidimensional Assessment of Neurodegenerative Symptoms Questionnaire Self scores (0.05 vs. 0.02; difference=0.03; 95% confidence interval, 0.004-0.05; P=0.02) yet there was no difference between groups in memory decline. Over ~10 years 33 individuals developed mild cognitive impairment: 4 in the BAP+ group (8.9%) and 29 in the BAP− group (7.8%), P=0.77.

Discussion:

Individuals who meet criteria for the BAP have escalating SCI with age, but no greater rate of memory decline or clinical progression to mild cognitive impairment.
Active recovery from concussion
Authors: Leddy John J. , Wilber Charles G. , Willer Barry S.
Published: October 2018

Purpose of review

Recent studies are challenging the utility of prolonged rest as treatment for concussion and postconcussion syndrome (PCS). The purpose of this paper is to review the evidence for active recovery from concussion and PCS.

Recent findings

Emerging data identify the central role of autonomic nervous system (ANS) dysfunction in concussion pathophysiology. The exercise intolerance demonstrated by athletes after sport-related concussion may be related to abnormal ANS regulation of cerebral blood flow. As aerobic exercise training improves ANS function, sub-symptom threshold exercise treatment is potentially therapeutic for concussion. A systematic assessment of exercise tolerance using the Buffalo Concussion Treadmill Test has been safely employed to prescribe a progressive, individualized subthreshold aerobic exercise treatment program that can return patients to sport and work. Multiple studies are demonstrating the efficacy of an active approach to concussion management.

Sustained rest from all activities after concussion, so-called ‘cocoon therapy’, is not beneficial to recovery. Evidence supports the safety, tolerability, and efficacy of controlled sub-symptom threshold aerobic exercise treatment for PCS patients. Further study should determine the efficacy and optimal timing, dose, and duration of subthreshold aerobic exercise treatment acutely after concussion because early intervention has potential to prevent PCS.
Fluctuating selection strength and intense male competition underlie variation and exaggeration of a water strider’s male weapon
Authors: Toubiana William , Khila Abderrahman
Published: October 2018

Sexually selected traits can reach high degrees of expression and variation under directional selection. A growing number of studies suggest that such selection can vary in space, time and form within and between populations. However, the impact of these fluctuations on sexual trait expression is poorly understood. The water striderMicrovelia longipesdisplays a striking case of exaggeration and phenotypic variation where males display extreme differences in the size of their rear legs. To study the origin and maintenance of this exaggerated trait, we conducted comparative behavioral and morphometric experiments in a sample ofMicroveliaspecies. We uncovered differences both in the mating behavior and the degree of sexual dimorphism across these species. Interestingly,M. longipesevolved a specific mating behavior where males compete for egg-laying sites, consisting of small floating objects, to intercept and copulate with gravid females. Field observations revealed rapid fluctuation inM. longipeshabitat stability and the abundance of egg-laying sites. Through male-male competition assays, we demonstrated that male rear legs are used as weapons to dominate egg-laying sites and that intense competition is associated with the evolution of rear leg length exaggeration. Paternity tests using genetic markers demonstrated that small males could only fertilize about 5% of the eggs when egg-laying sites are limiting, whereas this proportion increased to about 20% when egg-laying sites become abundant. Furthermore, diet manipulation and artificial selection experiments also showed that the exaggerated leg length inM. longipesmales is influenced by both genetic and nutritional factors. Collectively, our results highlight how fluctuation in the strength of directional sexual selection, through changes in the intensity of male competition, can drive the exaggeration and phenotypic variation in this weapon trait.
Regimes of Complex Lipid Bilayer Phases Induced by Cholesterol Concentration in MD Simulation
Authors: Pantelopulos George A. , Straub John E.
Published: October 2018

Cholesterol is essential to the formation of phase separated lipid domains in membranes. Lipid domains can exist in different thermodynamic phases depending on the molecular composition, and play significant roles in determining structure and function of membrane proteins. We investigate the role of cholesterol in the structure and dynamics of ternary lipid mixtures displaying phase separation using Molecular Dynamics simulations, employing a physiologically-relevant span of cholesterol concentration. We find that cholesterol can induce formation of three regimes of phase behavior, I) miscible liquid disordered bulk, II) phase separated, domain registered coexistence of liquid disordered and liquid ordered and domains, and III) phase separated, domain-anti-registered coexistence of liquid-disordered and newly-identified nanoscopic gel domains composed of cholesterol threads we name “cholesterolic gel” domains. These findings are validated and discussed in the context of current experimental knowledge, models of cholesterol spatial distributions, and models of ternary lipid mixture phase separation.
Tissue Fluidity Promotes Epithelial Wound Healing
Authors: Tetley Robert J. , Staddon Michael F. , Banerjee Shiladitya , Mao Yanlan
Published: October 2018

Epithelial tissues are inevitably damaged from time to time and must therefore have robust repair mechanisms. The behaviour of tissues depends on their mechanical properties and those of the surrounding environment1. However, it remains poorly understood how tissue mechanics regulates wound healing, particularly inin vivoanimal tissues. Here we show that by tuning epithelial cell junctional tension, we can alter the rate of wound healing. We observe cells moving past each other at the wound edge by intercalating, like molecules in a fluid, resulting in seamless wound closure. Using a computational model, we counterintuitively predict that an increase in tissue fluidity, via a reduction in junctional tension, can accelerate the rate of wound healing. This is contrary to previous evidence that actomyosin tensile structures are important for wound closure2–6. When we experimentally reduce tissue tension, cells intercalate faster and wounds close in less time. The role we describe for tissue fluidity in wound healing, in addition to its known roles in developing7,8and mature tissues9, reinforces the importance of the fluid state of a tissue.
TCR-pMHC bond length controls TCR ligand discrimination
Authors: Sasmal Dibyendu K. , Feng Wei , Roy Sobhan , Leung Peter , He Yanran , Cai Chufan , Cao Guoshuai , Lian Huada , Qin Jian , Hui Enfu , Schreiber Hans , Adams Erin , Huang Jun
Published: October 2018

T-cell receptors (TCRs) detect specifically and sensitively a small number of agonist peptide-major histocompatibility complexes (pMHCs) from an ocean of structurally similar self-pMHCs to trigger antigen-specific adaptive immune responses1–4. Despite intense efforts, the mechanism underlying TCR ligand discrimination remains a major unanswered question in immunology. Here we show that a TCR discriminates between closely related peptides by forming TCR-pMHC bonds with different lengths, which precisely control the accessibility of CD3ζ immunoreceptor tyrosine-based activation motifs (ITAMs) for phosphorylation. Using in situ fluorescence resonance energy transfer (FRET)3,5, we measured the intermolecular length of single TCR-pMHC bonds and the intramolecular distance of individual TCR-CD3ζ complexes at the membrane of live primary T cells. We found that an agonist forms a short TCR-pMHC bond to pull the otherwise sequestered CD3ζ off the inner leaflet of the plasma membrane, leading to full exposure of its ITAMs for strong phosphorylation. By contrast, a structurally similar weaker peptide forms a longer bond with the TCR, resulting in partial dissociation of CD3ζ from the membrane and weak phosphorylation. Furthermore, we found that TCR-pMHC bond length determines 2D TCR binding kinetics and affinity, T-cell calcium signaling and T-cell proliferation, governing the entire process of signal reception, transduction and regulation. Thus, our data reveal the fundamental mechanism by which a TCR deciphers the structural differences between foreign antigens and self-peptides via TCR-pMHC bond length to initiate different TCR signaling for ligand discrimination.
Forest quality, forest area and the importance of beta-diversity for protecting Borneo’s beetle biodiversity
Authors: Sharp Adam C. , Barclay Maxwell V. L. , Chung Arthur Y. C. , Rougemont Guillaume de , Turner Edgar C. , Ewers Robert M.
Published: October 2018

The lowland forest of Borneo is threatened by rapid logging for timber export and clearing for the expansion of timber and oil palm plantations. This combination of processes leaves behind landscapes dotted with small, often heavily-degraded forest fragments. The biodiversity value of such fragments, which are easily dismissed as worthless, is uncertain. We collected 187 taxa of rove beetles across a land-use gradient in Sabah, Malaysia, spanning pristine tropical lowland forest to heavily-degraded forest. Using these data, we identified shifts in alpha-, beta-, and gamma-diversity in response to forest quality and distance, then applied our findings from continuous expanses of forest to make predictions on hypothetical forest areas. We found that maintaining high forest quality is more important than forest area for conserving rare taxa (those important for conserving biodiversity per se), and that very small areas (10 ha) are likely to harbour the same richness of rove beetles as larger areas (100 ha) of equal forest quality. We estimate a decline in richness of 36% following heavy logging (removal of 95% of the vegetation biomass) from a forest area of 100 ha or less. Maintaining large forest area as well as high forest quality is important for conserving community composition, likely to be more important for conserving ecosystem functioning. We predict a decline of 35% in community diversity in conversion of a 100 ha area of unlogged forest to a 10 ha area of heavily-logged forest. Despite significant declines in alpha-diversity, beta-diversity within small rainforest areas may partially mitigate the loss of gamma-diversity, reinforcing the concept that beta-diversity is a dominant force determining the conservation of species in fragmented landscapes. In contrast to previous findings on larger animals, our results suggest that even small fragments of degraded forest might be important reservoirs of invertebrate biodiversity in tropical agriculture landscapes. These fragments, especially of lightly-logged forest, should be conserved where they occur and form an integral part of management for more sustainable agriculture in tropical landscapes.
Microscopy-based chromosome conformation capture enables simultaneous visualization of genome organization and transcription in intact organisms
Authors: Cardozo Gizzi Andres M , Cattoni Diego I. , Fiche Jean-Bernard , Espinola Sergio , Gurgo Julian , Messina Olivier , Houbron Christophe , Ogiyama Yuki , Papadopoulos Giorgio-Lucio , Cavalli Giacomo , Lagha Mounia , Nollmann Marcelo
Published: October 2018

Eukaryotic chromosomes are organized in multiple scales, from nucleosomes to chromosome territories. Recently, genome-wide methods identified an intermediate level of chromosome organization, topologically associating domains (TADs), that play key roles in transcriptional regulation. However, these methods cannot directly examine the interplay between transcriptional activation and chromosome architecture while maintaining spatial information. Here, we present a multiplexed, sequential imaging approach (Hi-M) that permits the simultaneous detection of chromosome organization and transcription in single nuclei. This allowed us to unveil the changes in 3D chromatin organization occurring upon transcriptional activation and homologous chromosome un-pairing during the awakening of the zygotic genome in intact Drosophila embryos. Excitingly, the ability of Hi-M to explore the multi-scale chromosome architecture with spatial resolution at different stages of development or during the cell cycle will be key to understand the mechanisms and consequences of the 4D organization of the genome.
Crystallographic and kinetic analyses of human IPMK reveal disordered domains modulate ATP binding and kinase activity
Authors: Seacrist Corey D. , Blind Raymond D.
Published: October 2018

Inositol polyphosphate multikinase (IPMK) is a member of the IPK-superfamily of kinases, catalyzing phosphorylation of several soluble inositols and the signaling phospholipid PI(4,5)P2(PIP2). IPMK also has critical non-catalytic roles in p53, mTOR/Raptor, TRAF6 and AMPK signaling mediated partly by two disordered domains. Although IPMK non-catalytic functions are well established, it is less clear if the disordered domains are important for IPMK kinase activity or ATP binding. Here, kinetic and structural analyses of an engineered human IPMK lacking all disordered domains (ΔIPMK) are presented. Although theKMfor PIP2is identical between ΔIPMK and wild type, ΔIPMK has a 1.8-fold increase inkcatfor PIP2, indicating the native IPMK disordered domains decrease IPMK activityin vitro. The 2.5 Å crystal structure of ΔIPMK is reported, confirming the conserved ATP-grasp fold. A comparison with other IPK-superfamily structures revealed a putative “ATP-clamp” in the disordered N-terminus, we predicted would stabilize ATP binding. Consistent with this observation, removal of the ATP clamp sequence increases theKMfor ATP 4.9-fold, indicating the N-terminus enhances ATP binding to IPMK. Together, these structural and kinetic studies suggest in addition to mediating protein-protein interactions, the disordered domains of IPMK impart modulatory capacity to IPMK kinase activity through multiple kinetic mechanisms.
Striatal-frontal network activation during voluntary task selection under conditions of monetary reward
Authors: Orr Joseph M. , Imburgio Michael J. , Bernard Jessica A. , Banich Marie T.
Published: October 2018

During voluntary task selection there are a number of internal and external biases that may guide such a choice. However, it is not well understood how reward influences task selection when multiple options are possible. To address this issue, we examined brain activation in a voluntary task-switching paradigm while participants underwent fMRI (n=19). To reinforce the overall goal to choose the tasks randomly, participants were told of a large bonus they would receive at the end of the experiment for making random task choices. We also examined how occasional, random rewards influenced both task performance and brain activation. We hypothesized that these transient rewards would increase the value of the just-performed task and therefore bias participants to choose to repeat the same task on the subsequent trial. Contrary to expectations, transient reward had no consistent behavioral effect on subsequent task choice. Nevertheless, the receipt of such rewards did influence activation in brain regions associated with reward processing as well as those associated with goal-directed control. In addition, reward on a prior trial was found to influence activation during task choice on a subsequent trial, with greater activation in a number of executive function regions as compared to no-reward trials. We posit that both the random presentation of transient rewards and the overall task bonus for random task choices together reinforced the goal to choose the tasks randomly, which in turn influenced activation in both reward-related regions and those regions involved in abstract goal processing.
Comparing faster evolving rplB and rpsC versus SSU rRNA for improved microbial community resolution
Authors: Guo Jiarong , Cole James R. , Brown C. Titus , Tiedje James M.
Published: October 2018

Many conserved protein-coding core genes are single copy and evolve faster, and thus are more resolving phylogenetic markers than the standard SSU rRNA gene but their use has been precluded by the lack of universal primers. Recent advances in gene targeted assembly methods for large shotgun metagenomes make their use feasible. To evaluate this approach, we compared the variation of two single copy ribosomal protein genes, rplB and rpsC, with the SSU rRNA gene for all completed bacterial genomes in NCBI RefSeq. As expected, among pairwise comparisons of all species that belong to the same genus, 94.9% and 91.0% of the pairs of rplB and rpsC, respectively, showed more variation than did their SSU rRNA gene sequences. We used a gene-targeted assembler, Xander, to assemble rplB and rpsC from shotgun metagenomic data from rhizosphere samples of three crops: corn (annual), and Miscanthus and switchgrass (both perennials). Both protein-coding genes separated all three communities whereas the SSU rRNA gene could only separate the annual from the two perennial communities in ordination analyses. Furthermore, assembled rplB and rpsC yielded significantly higher numbers of OTUs (alpha diversity) than the SSU rRNA gene. These results confirm these faster evolving marker genes offer increased resolution of for comparative microbiome studies.
A tenfold twin of the CrB structure type
Authors: Hornfeck Wolfgang
Published: October 2018

NiZr crystallized from an amorphous matrix or solidified from an undercooled melt exhibits a tenfold twinned microstructure, which is explained by an ideal twin model utilizing special geometric properties of the CrB structure type. The model is unique in several ways: (i) it contains no adjustable parameters other than a scaling factor accounting for the smallest interatomic distance; (ii) it features an irrational shift in the translational part of the twin operation; and (iii) it has many traits commonly observed for quasicrystals, connected to the occurrence of decagonal long-range orientational order, making NiZr the first experimental example of the recently introduced concept of {\bb Z}-module twinning. It is shown how these remarkable properties of the tenfold twin's structure model are related to one another and founded in number theory as well as in the mathematical theory of aperiodic order.