bluuebunny/crossref_metadata_2025 huggingface dataset:
Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis
Authors: Cox Andrew G. , Tsomides Allison , Kim Andrew J. , Saunders Diane , Hwang Katie L. , Evason Kimberley J. , Heidel Jerry , Brown Kristin K. , Yuan Min , Lien Evan C. , Lee Byung Cheon , Nissim Sahar , Dickinson Bryan , Chhangawala Sagar , Chang Christopher J. , Asara John M. , Houvras Yariv , Gladyshev Vadim N. , Goessling Wolfram
Published: September 2016

Significance

Dietary selenium and selenoproteins play important roles in regulating redox processes that impact human health. The human genome includes 25 genes for selenoproteins, which have diverse roles in redox homeostasis, thyroid hormone metabolism, endoplasmic reticulum quality control, selenium transport, and other functions. Selenoprotein H (
seph
) is a recently identified nucleolar oxidoreductase with DNA-binding properties whose function is not well understood. In this work, we used a unique combination of unbiased metabolomic and transcriptomic approaches in zebrafish to discover that
seph
is an essential regulator of redox homeostasis that regulates p53. In addition, we demonstrate the
seph
-deficient adults are prone to chemically induced carcinogenesis. Our results suggest that
seph
suppresses oxidative stress and DNA damage in the nucleolus.
A novel orvinol analog, BU08028, as a safe opioid analgesic without abuse liability in primates
Authors: Ding Huiping , Czoty Paul W. , Kiguchi Norikazu , Cami-Kobeci Gerta , Sukhtankar Devki D. , Nader Michael A. , Husbands Stephen M. , Ko Mei-Chuan
Published: August 2016

Significance

A potent opioid analgesic without addictive and respiratory adverse effects has been a predominant goal for opioid medicinal chemistry since the isolation of morphine from opium in the 19th century. Here we report a functional profile of a unique analog, BU08028, targeting a combination of a classical and nonclassical opioid receptors in monkeys. By examining behavioral, physiological, and pharmacologic factors, the present study demonstrates that BU08028 exhibits full antinociception and antihypersensitivity without reinforcing effects (i.e., abuse liability), respiratory depression, pruritus, adverse cardiovascular events, or acute physical dependence. Because monkey models provide the most phylogenetically appropriate evaluation of opioid receptor functions and drug effects, these findings provide a translational bridge for such ligands as effective analgesics without safety and abuse liability concerns.
Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation
Authors: Lourenço Elaine V. , Liu Aijing , Matarese Giuseppe , La Cava Antonio
Published: September 2016

Significance

Leptin is an adipocytokine whose activity has been associated with the development and maintenance of proinflammatory immune responses. Here we show that genetic deficiency of leptin protected mice from systemic lupus erythematosus (SLE) and reduced production of autoantibodies and renal disease. In a spontaneous animal model of SLE, the administration of leptin promoted an acceleration of the disease, whereas leptin blockade protected from autoimmunity. We suggest that these effects of leptin on SLE could possibly be exploited therapeutically in the disease.
Anatomy of the β-branching enzyme of polyketide biosynthesis and its interaction with an acyl-ACP substrate
Authors: Maloney Finn P. , Gerwick Lena , Gerwick William H. , Sherman David H. , Smith Janet L.
Published: August 2016

Significance

Polyketides are a chemically diverse class of natural products with broad pharmaceutical applications. β-Branching in modular polyketide synthase pathways contributes to this diversity by introducing alkyl branches into polyketide intermediates, ranging from simple methyl groups to more unusual structures, including the curacin A cyclopropane ring. Branching replaces the β-carbonyl of a polyketide intermediate, which is more commonly reduced and/or methylated. Furthermore, β-branching is catalyzed by cassettes of standalone enzymes and is targeted to a specific point in a polyketide synthase PKS pathway by specialized acyl carrier proteins (ACPs). In these structural studies, we have begun to elucidate the mechanisms of ACP selectivity by the initiating enzyme of β-branching. This work may be essential for rational efforts to diversify polyketides using unnatural β-branching schemes.
Functional role of T-cell receptor nanoclusters in signal initiation and antigen discrimination
Authors: Pageon Sophie V. , Tabarin Thibault , Yamamoto Yui , Ma Yuanqing , Nicovich Philip R. , Bridgeman John S. , Cohnen André , Benzing Carola , Gao Yijun , Crowther Michael D. , Tungatt Katie , Dolton Garry , Sewell Andrew K. , Price David A. , Acuto Oreste , Parton Robert G. , Gooding J. Justin , Rossy Jérémie , Rossjohn Jamie , Gaus Katharina
Published: August 2016

Significance

T-cell activation requires the translation of antigen binding to the T-cell receptor (TCR) into intracellular signaling. However, how antigen recognition and signal transduction are mechanistically linked is poorly understood. Here, we used single-molecule localization microscopy to link TCR clustering to signaling. We found that the likelihood of a single receptor to initiate signaling upon ligand binding depended on receptor-to-receptor spacing, with TCRs in dense clusters having the highest signaling efficiency. This means that antigen recognition must first be translated into a spatial reorganization of receptors into dense, signaling-competent clusters before signaling can begin. Thus, the quality of an antigen in terms of signaling is given by its ability to densely cluster receptors.
Class II major histocompatibility complex mutant mice to study the germ-line bias of T-cell antigen receptors
Authors: Silberman Daniel , Krovi Sai Harsha , Tuttle Kathryn D. , Crooks James , Reisdorph Richard , White Janice , Gross James , Matsuda Jennifer L. , Gapin Laurent , Marrack Philippa , Kappler John W.
Published: September 2016

Significance

The evolutionary hypothesis for T-cell antigen receptor–peptide major histocompatibility complex (TCR–pMHC) interaction posits the existence of germ-line–encoded rules by which the TCR is biased toward recognition of the MHC. Understanding these rules is important for our knowledge of how to manipulate this important interaction at the center of adaptive immunity. In this study, we highlight the flexibility of thymic selection as well as the existence of these rules by generating knockin mutant MHC mice and extensively studying the TCR repertoires of T cells selected on the mutant MHC molecules. Identifying novel TCR subfamilies that are most evolutionarily conserved to recognize specific areas of the MHC is the first step in advancing our knowledge of this central interaction.
Pragmatic functions of formulaic speech in three different languages
Authors: Safont Jordà María-Pilar , Portolés Falomir Laura
Published: September 2016

The study examines early multilingual formulaic speech with a focus on the English classroom. We have followed a discourse-pragmatic approach in the analysis of our data, which comprises transcripts from eight 45-minute sessions. Transcripts from these sessions involved 184 participants from two different age ranges. In this analysis, we have considered formulas produced in three languages: Catalan, Spanish, and English. Our goal is to provide further evidence for the inherent dynamism and complexity of early multilingual pragmatic development, and in so doing, to acknowledge the role of the educational level and the language program adopted in the school. Findings are partly in line with (a) previous studies dealing with the identification of pragmatic functions in the EFL classroom (Llinares & Pastrana, 2013), and (b) the peculiarities of early third language learners (Portolés, 2015). Finally, we tackle the importance of adopting multilingual perspectives in the analyses of multilingual students.
Mecanismos interaccionales al servicio de la descortesía en el debate político
Authors: Fernández-García Francisco
Published: September 2016

Como parte de un proyecto investigador más amplio que encara un análisis global del funcionamiento de la descortesía en el debate electoral, este trabajo se propone dos objetivos. En primer lugar, revisar sucintamente los tres ejes en torno a los cuales se estructura dicha investigación (estrategias funcionales de descortesía, mecanismos lingüístico-discursivos mediante los que dichas estrategias se implementan y repercusiones sociales de los actos descorteses). En segundo lugar, como núcleo de la aportación, analizar un tipo específico de mecanismos, los de naturaleza interaccional, aislando cinco distintos subtipos y llevando a cabo una caracterización de su funcionamiento discursivo. Este análisis, realizado sin perder de vista los otros componentes de la investigación (estrategias y repercusiones sociales), pone de relieve el potencial de nuestro planteamiento triangular así como el relevante papel que, en el plano de los mecanismos, cumplen los vinculados al plano de la interacción conversacional.
Mortality Estimates for Red Snapper Based on Ultrasonic Telemetry in the Northern Gulf of Mexico
Authors: Williams-Grove Laura Jay , Szedlmayer Stephen T.
Published: August 2016

We used the Vemco Positioning System (VPS) to estimate mortalities from the fine-scale movements (~1-m accuracy) of Red Snapper Lutjanus campechanus on four artificial reef sites in the northern Gulf of Mexico in 2012, 2013, and 2014. Additional receivers on surrounding reef sites validated emigrations of tagged Red Snapper from the VPS-monitored sites. We tagged and released 86 Red Snapper and tracked 59 fish for extended periods (17 to 1,096 d). Telemetry tracking patterns identified fish status as active, emigrated, caught (F), or dead (M) at monthly intervals. At the end of the study, 17 fish had emigrated, 24 were caught by fishers, and 18 were active on VPS-monitored reef sites. For all years combined, annual fishing mortality was F = 0.44 (0.27–0.65, 95% confidence limit). In 2012, F = 0.72 (0.35–1.31) and was higher than other years, but the number of fish available for recapture at the start of the sportfishing season was low (n = 15). In 2013, F = 0.18 (0.07–0.42; n = 30), and in 2014, F = 0.42 (0.22–0.76; n = 28). One natural mortality (M) was detected in 2012, and M = 0.12 (0.02–0.69); no subsequent natural mortalities were detected in 2013 and 2014 (M = 0). Total instantaneous mortality (Z) for all years was Z = 0.48 (0.30–0.70). We attributed the low M to high fishing mortality but caution that sample sizes were small, which is typical of telemetry studies. The fates of 58 (98%) transmitter-tagged Red Snapper were successfully identified based on the VPS technology. Increases in F from 0.18 (2013) to 0.42 (2014) occurred when the length of the fishing season was decreased (42 to 9 d) and indicated that fishers increased effort during the shortened fishing season, and the management goal of reducing catch may not have been achieved.

Received July 20, 2015; accepted April 20, 2016 Published online August 30, 2016
Neighbourhood renewal, participation, and social capital in deprived areas: unintended consequences in a Nordic context
Authors: Hindhede Anette Lykke
Published: September 2016

This paper addresses the use of the concept of social capital in neighbourhood renewal programmes which aim to influence social and health-related processes. Based on a social network analysis of 17 groups comprising 133 members, qualitative interviews were conducted with 22 participants to consider the kinds of patterns and connections that build up in a neighbourhood renewal project in a small, deprived neighbourhood of a provincial town in Denmark. Results show that outcomes of community participation depend on the kind of social capital generated and on who is excluded from these resources or capital. Problems hindering inclusive participatory processes include self-exclusion and exclusionary dynamics in the neighbourhood. These dynamics centre on power struggles that lead the least powerful to opt out. Thus, the Danish ‘Ghetto Strategy’, which aims to increase local community participation and volunteering, could have the unintended consequence of increasing social and health inequalities rather than reducing them.
Observation of the loss of pre-disruptive runaway electrons in KSTAR ohmic plasma disruptions
Authors: Cheon MunSeong , Kim Junghee , An YoungHwa , Seo Dongcheol , Kim Hyunseok
Published: September 2016

A newly-developed fast neutron detector revealed a close relationship between the loss of pre-disruptive runaway electrons and the plasma disruption in KSTAR ohmic plasmas. It is observed that a burst of photoneutrons is generated exactly before the start of thermal quenches, indicating a bunch of runaway electrons which had existed before the disruption impacts the first wall at the time. The loss of runaway electrons could be identified also as a decrease in the measured electron temperature, forming a typical two-stage thermal quench trace. From the MHD pattern in the neutron signal during a low-q disruption, it could be identified that pre-disruptive runaway electrons are localized in the plasma, especially on the q  =  2 drift surface. These new findings suggest the pre-disruptive runaway electrons might play an important role in the plasma disruption mechanism.
The influence of temperature dynamics and dynamic finite ion Larmor radius effects on seeded high amplitude plasma blobs
Authors: Held M. , Wiesenberger M. , Madsen J. , Kendl A.
Published: September 2016

Thermal effects on the perpendicular convection of seeded pressure blobs in the scrape-off layer of magnetised fusion plasmas are investigated. Our numerical study is based on a four field full-F gyrofluid model, which entails the consistent description of high fluctuation amplitudes and dynamic finite Larmor radius effects. We find that the maximal radial blob velocity increases with the square root of the initial pressure perturbation and that a finite Larmor radius contributes to highly compact blob structures that propagate in the poloidal direction. An extensive parameter study reveals that a smooth transition to this compact blob regime occurs when the finite Larmor radius effect strength, defined by the ratio of the magnetic field aligned component of the ion diamagnetic to the

E

×

B

vorticity, exceeds unity. The maximal radial blob velocities agree excellently with the inertial velocity scaling law over more than an order of magnitude. We show that the finite Larmor radius effect strength affects the poloidal and total particle transport and present an empirical scaling law for the poloidal and total blob velocities. Distinctions to the blob behaviour in the isothermal limit with constant finite Larmor radius effects are highlighted.
Chronic Stress and Endothelial Dysfunction: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Kershaw Kiarri N. , Lane-Cordova Abbi D. , Carnethon Mercedes R. , Tindle Hilary A. , Liu Kiang
Published: September 2016

BACKGROUND

Endothelial dysfunction may represent an important link between chronic stress and cardiovascular disease (CVD) risk. However, few studies have examined the impact of chronic stress on endothelial dysfunction. The purpose of this study was to examine whether chronic stress was associated with flow-mediated dilation (FMD) and 2 biomarkers of endothelial dysfunction (intercellular adhesion molecule-1 (ICAM-1) and E-selectin) in a multiethnic sample of adults (ages 45–84 years).

METHODS

Data come from the baseline examination of Multi-Ethnic Study of Atherosclerosis participants. Chronic stress was assessed based on self-report of the presence and severity of ongoing problems in 5 domains. FMD was obtained using high-resolution ultrasound; biomarkers were assayed in different subsets of participants.

RESULTS

Higher chronic stress was associated with lower absolute FMD (mm FMD) in models adjusted for demographic and socioeconomic characteristics (0.169mm in high-stress participants vs. 0.178 and 0.179mm in medium and low-stress participants; P for trend = 0.04). This association remained unchanged with further adjustment for behavioral and biological CVD risk factors. Higher stress was related to higher ICAM-1 in models adjusted for sociodemographic characteristics and biological risk factors (P for trend = 0.005), but this association attenuated with adjustment for cigarette smoking (P for trend = 0.07). Chronic stress was not associated with E-selectin.

CONCLUSIONS

Our findings suggest chronic stress is related to endothelial dysfunction, possibly in part through other stress-associated CVD risk factors such as cigarette smoking.
Highly enriched 7Be in the ejecta of Nova Sagittarii 2015 No. 2 (V5668 Sgr) and the Galactic 7Li origin
Authors: Molaro P. , Izzo L. , Mason E. , Bonifacio P. , Della Valle M.
Published: September 2016

We report on the evidence of highly blueshifted resonance lines of the singly ionized isotope of 7Be ii in high resolution UVES spectra of Nova Sagittarii 2015 No. 2 (V5668 Sgr). The resonance doublet lines 7Be ii at λλ313.0583, 313.1228 nm are clearly detected in several non-saturated and partially resolved high velocity components during the evolution of the outburst. The total absorption identified with Be ii has an equivalent width much larger than all other elements and comparable to hydrogen. We estimate an atomic fraction N(7Be)/N(Ca) ≈ 53–69 from unsaturated and resolved absorption components. The detection of 7Be in several high velocity components shows that 7Be has been freshly created in a thermonuclear runaway via the reaction 3He(α, γ)7Be during the Nova explosion, as postulated by Arnould & Norgaar, however in much larger amounts than predicted by current models. 7Be ii decays to 7Li ii with a half-life of 53.22 d, comparable to the temporal span covered by the observations. The non-detection of 7Li i requires that 7Li remains ionized throughout our observations. The massive Be ii ejecta result into a 7Li production that is ≈ 4.7–4.9 dex above the meteoritic abundance. If such a high production is common even in a small fraction (≈5 per cent) of Novae, they can make all the stellar7Li of the Milky Way.
Kant and the Laws of Nature
Authors: Massimi Michela
Published: August 2016

Immanuel Kant’s complex and nuanced view on the laws of nature has been at the center of renewed attention among Kant scholars since the late 20th century. Kant’s view is one of the best examples in the Early Modern period of the philosophical view of nature as “ordered” and “lawful” that emerged with the scientific advancements of the 17th and 18th centuries. Building on the extraordinary success of Isaac Newton’s mechanics and optics, but also on the burgeoning chemistry of Stephen Hales in England and Herman Boerhaave and Pieter van Musschenbroek in the Netherlands, among many others, Kant’s lifelong engagement with the natural sciences (broadly construed) influenced and fed into his mature Critical-period philosophy. Explaining why laws of nature seemingly govern the natural world (as much as the moral law regulates the realm of human freedom and choice) is key to Kant’s transcendental philosophy. Kant seems to embrace a coherent account of what it is to be a law, in moral philosophy and in theoretical philosophy. When it comes to theoretical philosophy (and in particular, to Kant’s philosophy of nature, which is our topic), the main question is how it is possible for us to come to know nature as ordered and lawful. Where does the lawfulness of nature come from? In the Critique of Pure Reason and in the Prolegomena, Kant held the view that our faculty of understanding is the primary source of nature’s lawfulness because the a priori categories of the understanding “prescribe laws to nature”—that is, they play the role of constitutive a priori principles for our experience of nature. Yet, already in the first Critique, and even more so in Critique of the Power of Judgment, Kant stressed the importance of the faculty of reason, first, and the faculty of reflective judgment, second—with their regulative principles—in offering a system of laws necessary for our knowledge of nature. The crucial distinction between constitutive principles of the understanding versus regulative principles of reason and reflective judgment leads, in turn, to a series of further distinctions in Kant’s philosophy. For example, it leads to the different status of laws in the physical sciences and in the life sciences, which in turn became the battleground for the debate concerning mechanical explanations versus teleological explanations.
Wide Variation of Surgical Cost in the Treatment of Periarticular Lower Extremity Injuries Between 6 Fellowship-Trained Trauma Surgeons
Authors: Wetzel Robert J. , Kempton Laurence B. , Lee Edwin S. , Zlowodzki Michael , McKinley Todd O. , Virkus Walter W.
Published: August 2016

Objectives:

We hypothesized that negligible surgical material cost variation exists between traumatolgists for treatment of bimalleolar ankle and bicondylar tibial plateau fractures.

Design:

Retrospective medical record review.

Setting:

Academic level 1 Trauma Center; 2-year period.

Patients/Participants:

Current Procedure Terminology codes for open treatment of bimalleolar ankle and bicondylar tibial plateau fractures identified patients. Patients who had operative treatment of other injuries under the same anesthetic session were excluded. Only definitive treatment procedures were analyzed.

Intervention:

We analyzed the intraoperative material costs of these procedures and compared them between surgeons. This analysis was done with a newly developed proprietary program designed for inventory and cost analysis.

Main Outcome Measurements:

Mean and median total case material costs were compared using one-way analysis of variance. Individual items that significantly increased costs were identified.

Results:

We identified 88 bimalleolar ankle and 46 bicondylar tibial plateau fractures treated by 6 surgeons. The mean intraoperative material cost per bimalleolar ankle fracture was $1099. The least expensive surgeon's mean case cost was $613, which was significantly less than the most expensive surgeon's $2243 (P = 0.009). The median cost range was $598–$784. The top quartile of cases resulted in 57% of overall material cost for ankle fractures. The mean intraoperative material cost per bicondylar tibial plateau fracture was $3219 (range $1839–$4088, P = 0.064). The range of median costs ($1826–$3989) was significantly wider than for ankle fractures. Bone void fillers, locking plates, adjunctive external fixators, mini-fragment locking plates, cannulated screws, single-use taps, guidewires, and drill bits all substantially increased costs.

Conclusion:

This study demonstrated variation in intraoperative material cost between 6 traumatologists resulting from practice variations despite similar specialty training. The cost differences resulting from practice variation reveal potential savings through increased standardization of surgical care for similar injuries. We identified high-cost items, which could lead to cost savings if used only when they will have clinical benefit.
Limb Salvage With Intrepid Dynamic Exoskeletal Orthosis Versus Transtibial Amputation: A Comparison of Functional Gait Outcomes
Authors: Mangan Katharine I. , Kingsbury Trevor D. , Mazzone Brittney N. , Wyatt Marilynn P. , Kuhn Kevin M.
Published: August 2016

Objectives:

To determine if there is a difference in functional gait outcomes between patients with limb injuries treated with either transtibial amputation or limb preservation with the Intrepid Dynamic Exoskeletal Orthosis.

Design:

Retrospective prognostic study.

Setting:

Tertiary referral military hospital.

Patients:

This study included 10 transtibial amputees and 10 limb preservation patients using the Intrepid Dynamic Exoskeletal Orthosis who were matched by body mass index after excluding for nontraumatic, proximal ipsilateral, contralateral, spine, or traumatic brain injuries. Transtibial amputation patients were also excluded if they did not have a gait study between 6 and 12 months after independent ambulation. Limb preservation were excluded if they did not complete the “Return to Run” program.

Interventions:

An observational study of functional outcomes using instrumented gait analysis.

Outcome Measures:

Spatiotemporal, kinetic (vertical ground reaction force), unified deformable power, work, and efficiency.

Results:

Limb preservation patients walked with a significantly slower cadence (P = 0.036) and spent less time on their affected limb in stance (P = 0.045), and longer in swing (P = 0.019). Amputees had significantly increased maximum positive power in both limbs (P = 0.004 and P = 0.029) and increased maximum negative power on the unaffected limb (P = 0.035). Amputees had significantly increased positive and negative work in the affected limb (P = 0.0009 and P = 0.014) and positive work in the unaffected limb (P = 0.042). There was no significant difference in the kinetic data or efficiency.

Conclusions:

Limb preservation patients spend less time on their affected limb as a percentage of the gait cycle. The unified deformable power demonstrated more dynamic gait in amputees, with peak values closer to normative data.

Level of Evidence:

Therapeutic level III. See Instructions for Authors for a complete description of levels of evidence.
Improving Heart Failure Outcomes
Authors: Coen Jennifer , Curry Kimberly
Published: August 2016

This article identifies and explains barriers to optimal outcomes of heart failure and the role of the clinical nurse specialist in overcoming these obstacles, improving patient outcomes and quality of life. In recent years, advances in heart failure management have increased survival rates, and as a result, the number of patients requiring services to manage disease progression and the complex array of symptoms associated with end-stage heart disease. Management of the heart failure patient is dependent on the severity of the disease and wide range of available treatment regimens. Disease progression can be unpredictable and treatment regimens increasingly complex. The authors present a typical case of a patient with heart failure, identify the barriers to optimal outcomes in managing heart failure, as well as describe the roles of the clinical nurse specialist in overcoming these barriers within 3 spheres of clinical nurse specialist influence: patient, health care provider, and health care systems. The clinical nurse specialist role is ideally suited to positively affect heart failure outcomes. These positive effects are drawn from the dynamic and unique nature of the clinical nurse specialist role and are perpetrated through the 3 spheres of clinical nurse specialist practice: patient, health care provider, and heath care system.
Real-time assessment of alcohol drinking and drug use in opioid-dependent polydrug users
Authors: Preston Kenzie L. , Jobes Michelle L. , Phillips Karran A. , Epstein David H.
Published: August 2016

We investigated relationships between drinking, other drug use, and drug craving, using ecological momentary assessment (EMA), in a sample of polydrug users who were not heavy drinkers. In a prospective longitudinal cohort study, 114 heroin and cocaine users on methadone-maintenance treatment carried handheld electronic diaries during waking hours and were screened for drug and alcohol use for up to 25 weeks. Individuals who fulfilled the Diagnostic and Statistical Manual of Mental Disorders criteria for alcohol abuse or dependence were excluded. Participants responded to 2–5 random prompts per day to report on their moods, cravings, and activities and initiated entries when they used or acutely craved heroin or cocaine. Drinking alcohol was assessed in both types of entries. Breath alcohol was measured three times weekly. Participants reported drinking alcohol in 1.6% of random-prompt entries, 3.7% of event-contingent entries when craving cocaine and/or heroin, and 11.6% of event-contingent entries when using cocaine and/or heroin. Alcohol drinking was also associated with higher craving ratings and prestudy alcohol use. More drinking was detected by ambulatory self-report than by in-clinic breath testing. Even though we had screened out heavy drinkers from our sample of polydrug users, drinking was associated with heroin and cocaine craving and actual use.
High-Grade Cervical Dysplasia After Negative Loop Electrosurgical Excision Procedure
Authors: Kuroki Lindsay M. , James-Nywening Laura , Wu Ningying , Liu Jingxia , Powell Matthew A. , Thaker Premal H. , Massad L. Stewart
Published: August 2016

Objectives

To describe the prevalence and correlates of high-grade cervical intraepithelial neoplasia (CIN2+) after a negative loop electrosurgical excision procedure (LEEP), performed for high-grade squamous intraepithelial lesion (HSIL) cervical cytology.

Methods

One hundred six women from our university-based colposcopy clinic underwent LEEP between 2007 and 2014. Negative LEEP was defined as CIN1 or less. Persistence/recurrence estimates were calculated by treatment (see-and-treat vs 3-step conventional strategy—cervical cytology, colposcopic biopsy, LEEP) and LEEP results (negative vs positive) using the Kaplan-Meier method. Predictors of CIN2+ after a negative LEEP were examined by multivariate Cox proportional hazards model.

Results

Overall, the prevalence of CIN2+ after a negative LEEP for HSIL was 14%. Persistence/recurrence of CIN2+ was similar between women with a negative and positive see-and-treat LEEP (25% vs 15%) and those with a negative or positive 3-step conventional LEEP (7% vs 22%) (log-rank, P = 0.58). Positive LEEP margin was more common among women with a positive LEEP (53.7% see-and-treat vs 42.6% conventional) compared with a negative result (0% see-and-treat vs 3.7% conventional, P < 0.0001). The risk of CIN2+ after a negative LEEP did not differ by management strategy (log-rank, P = 0.85) or LEEP result (log-rank, P = 0.58). In multivariate analysis, correlates of persistent/recurrent CIN2+ included older age (adjusted odds ratio [aOR], 1.09; P = 0.0003), history of previous LEEP (aOR, 8.99; P < 0.0001), and positive LEEP margin (aOR, 13.56; P = 0.0005).

Conclusions

A negative LEEP does not allow less stringent surveillance, as CIN2+ risk is similar to that after CIN2+ is found in the LEEP specimen, whether the specimen was obtained by see-and-treat or conventional 3-step approach.
Convenient Access to Professional Interpreters in the Hospital Decreases Readmission Rates and Estimated Hospital Expenditures for Patients With Limited English Proficiency
Authors: Karliner Leah S. , Pérez-Stable Eliseo J. , Gregorich Steven E.
Published: August 2016

Background:

Twenty-five million people in the United States have limited English proficiency (LEP); this growing and aging population experiences worse outcomes when hospitalized. Federal requirements that hospitals provide language access services are very challenging to implement in the fast-paced, 24-hour hospital environment.

Objective:

To determine if increasing access to professional interpreters improves hospital outcomes for older patients with LEP.

Design:

Natural experiment on a medicine floor of an academic hospital.

Participants:

Patients age 50 years or above discharged between January 15, 2007 and January 15, 2010.

Exposure:

Dual-handset interpreter telephone at every bedside July 15, 2008 to Mar 14, 2009.

Outcome Measures:

Thirty-day readmission, length of stay, estimated hospital expenditures.

Results:

Of 8077 discharges, 1963 were for LEP, and 6114 for English proficient patients. There was a significant decrease in observed 30-day readmission rates for the LEP group during the 8-month intervention period compared with 18 months preintervention (17.8% vs. 13.4%); at the same time English proficient readmission rates increased (16.7% vs. 19.7%); results remained significant in adjusted analyses. This improved readmission outcome for the LEP group was not maintained during the subsequent postintervention period when the telephones became less accessible. There was no significant intervention impact on length of stay in either unadjusted or adjusted analyses. After accounting for interpreter services costs, the estimated 119 readmissions averted during the intervention period were associated with estimated monthly hospital expenditure savings of $161,404.

Conclusions:

Comprehensive language access represents an important, high value service that all medical centers should provide to achieve equitable, quality healthcare for vulnerable LEP populations.
Barriers to Care and Health Care Utilization Among the Publicly Insured
Authors: Allen Elizabeth M. , Call Kathleen T. , Beebe Timothy J. , McAlpine Donna D. , Johnson Pamela Jo
Published: August 2016

Background:

Although the Affordable Care Act has been successful in expanding Medicaid to >17 million people, insurance alone may not translate into access to health care. Even among the insured, substantial barriers to accessing services inhibit health care utilization.

Objectives:

We examined the effect of selected barriers to health care access and the magnitude of those barriers on health care utilization.

Research Design:

Data come from a 2008 survey of adult enrollees in Minnesota’s public health care programs. We used multivariate logistic regression to estimate the effects of perceived patient, provider, and system-level barriers on past year delayed, foregone, and lack of preventive care.

Subjects:

A total of 2194 adults enrolled in Minnesota Health Care Programs who were mostly female (66%), high school graduates (76%), unemployed (62%), and living in metro areas (67%) were included in the analysis.

Results:

Reporting problems across all barriers increased the odds of delayed care from 2 times for provider-related barriers (OR=2.0; 95% CI, 1.2–3.3) to >6 times for access barriers (OR=6.2; 95% CI, 3.8–10.2) and foregone care from 2.6 times for family/work barriers (OR=2.6; 95% CI, 1.3–5.1) to >7 times for access barriers (OR=7.1; 95% CI, 3.9–13.1). Perceived discrimination was the only barrier consistently associated with all 3 utilization outcomes.

Conclusions:

Multiple types of barriers are associated with delayed and foregone care. System-level barriers and discrimination have the greatest effect on health care seeking behavior.
Depressive Symptoms and Salivary Telomere Length in a Probability Sample of Middle-Aged and Older Adults
Authors: Whisman Mark A. , Richardson Emily D.
Published: August 2016

Objective

To examine the association between depressive symptoms and salivary telomere length in a probability sample of middle-aged and older adults, and to evaluate age and sex as potential moderators of this association and test whether this association was incremental to potential confounds.

Methods

Participants were 3,609 individuals from the 2008 wave of the Health and Retirement Study. Telomere length assays were performed using quantitative real-time polymerase chain reaction on DNA extracted from saliva samples. Depressive symptoms were assessed via interview, and health and lifestyle factors, traumatic life events, and neuroticism were assessed via self-report. Regression analyses were conducted to examine the associations between predictor variables and salivary telomere length.

Results

After adjusting for demographics, depressive symptoms were negatively associated with salivary telomere length (b = −.003; p = .014). Furthermore, this association was moderated by sex (b = .005; p = .011), such that depressive symptoms were significantly and negatively associated with salivary telomere length for men (b = − .006; p < .001) but not for women (b = − .001; p = .644). The negative association between depressive symptoms and salivary telomere length in men remained statistically significant after additionally adjusting for cigarette smoking, body mass index, chronic health conditions, childhood and lifetime exposure to traumatic life events, and neuroticism.

Conclusions

Higher levels of depressive symptoms were associated with shorter salivary telomeres in men, and this association was incremental to several potential confounds. Shortened telomeres may help account for the association between depression and poor physical health and mortality.
Physical modelling of tsunamis generated by three-dimensional deformable granular landslides on planar and conical island slopes
Authors: McFall Brian C. , Fritz Hermann M.
Published: September 2016

Tsunamis generated by landslides and volcanic island collapses account for some of the most catastrophic events recorded, yet critically important field data related to the landslide motion and tsunami evolution remain lacking. Landslide-generated tsunami source and propagation scenarios are physically modelled in a three-dimensional tsunami wave basin. A unique pneumatic landslide tsunami generator was deployed to simulate landslides with varying geometry and kinematics. The landslides were generated on a planar hill slope and divergent convex conical hill slope to study lateral hill slope effects on the wave characteristics. The leading wave crest amplitude generated on a planar hill slope is larger on average than the leading wave crest generated on a convex conical hill slope, whereas the leading wave trough and second wave crest amplitudes are smaller. Between 1% and 24% of the landslide kinetic energy is transferred into the wave train. Cobble landslides transfer on average 43% more kinetic energy into the wave train than corresponding gravel landslides. Predictive equations for the offshore propagating wave amplitudes, periods, celerities and lengths generated by landslides on planar and divergent convex conical hill slopes are derived, which allow an initial rapid tsunami hazard assessment.
Metacoder: An R Package for Visualization and Manipulation of Community Taxonomic Diversity Data
Authors: Foster Zachary S. L. , Sharpton Thomas J. , Grünwald Niklaus J.
Published: September 2016

Community-level data, the type generated by an increasing number of metabarcoding studies, is often graphed as stacked bar charts or pie graphs that use color to represent taxa. These graph types do not convey the hierarchical structure of taxonomic classifications and are limited by the use of color for categories. As an alternative, we developedmetacoder, an R package for easily parsing, manipulating, and graphing publication-ready plots of hierarchical data.Metacoderincludes a dynamic and flexible function that can parse most text-based formats that contain taxonomic classifications, taxon names, taxon identifiers, or sequence identifiers.Metacodercan then subset, sample, and order this parsed data using a set of intuitive functions that take into account the hierarchical nature of the data. Finally, an extremely flexible plotting function enables quantitative representation of up to 4 arbitrary statistics simultaneously in a tree format by mapping statistics to the color and size of tree nodes and edges.Metacoderalso allows exploration of barcode primer bias by integrating functions to run digital PCR. Although it has been designed for data from metabarcoding research,metacodercan easily be applied to any data that has a hierarchical component such as gene ontology or geographic location data. Our package complements currently available tools for community analysis and is provided open source with an extensive online user manual.

Note: This article was previously submitted as a pre-print: Zachary S. L. Foster, Thomas J. Sharpton, Niklaus J. Grünwald. 2016.Metacoder: An R package for manipulation and heat tree visualization of community taxonomic data from metabar-coding. BioRxiv 071019; doi:http://dx.doi.org/10.1101/071019.
The Effects of Pitch Shifts on Delay-induced Changes in Vocal Sequencing in a Songbird
Authors: Wyatt MacKenzie , Berthiaume Emily A. , Kelly Conor W. , Sober Samuel J.
Published: August 2016

Like human speech, vocal behavior in songbirds depends critically on auditory feedback. In both humans and songbirds, vocal skills are acquired by a process of imitation whereby current vocal production is compared to an acoustic target. Similarly, performance in adulthood relies strongly on auditory feedback, and online manipulations of auditory signals can dramatically alter acoustic production even after vocalizations have been well learned. Artificially delaying auditory feedback can disrupt both speech and birdsong, and internal delays in auditory feedback have been hypothesized as a cause of vocal dysfluency in persons who stutter. Furthermore, in both song and speech online shifts of the pitch (fundamental frequency) of auditory feedback lead to compensatory changes in vocal pitch for small perturbations, but larger pitch shifts produce smaller changes in vocal output. Intriguingly, large pitch shifts can partially restore normal speech in some dysfluent speakers, suggesting that the effects of auditory feedback delays might be ameliorated by online pitch manipulations. While birdsong provides a promising model system for understanding speech production, the interaction between sensory feedback delays and pitch shifts have not yet been assessed in songbirds. To investigate this, we asked whether the addition of a pitch shift modulates delay-induced changes in Bengalese finch song, hypothesizing that pitch shifts would reduce the effects of feedback delays. Compared the effects of delays alone, combined delays and pitch shifts resulted in a significant reduction in behavioral changes in one type of sequencing (branch points) but not another (distribution of repeated syllables).

Significance Statement

Vocal behavior depends critically on an organism’s ability to monitor the sound of its own voice (“auditory feedback”). Studies of both humans and songbirds have demonstrated that successful vocal performance depends critically on the quality and timing of such feedback, however the interaction between vocal acoustics and the timing of auditory feedback is unclear. Here we used songbirds to examine this interaction by measuring vocal performance during delays and distortions (pitch shifts) of auditory feedback.
On the inconsistency of pollinator species traits for predicting either response to agricultural intensification or functional contribution
Authors: Bartomeus Ignasi , Cariveau Daniel P. , Harrison Tina , Winfree Rachael
Published: August 2016

The response and effect trait framework, if supported empirically, would provide for powerful and general predictions about how biodiversity loss will lead to loss in ecosystem function. This framework proposes that species traits will explain how different species respond to disturbance (i.e. response traits) as well as their contribution to ecosystem function (i.e. effect traits). However, predictive response and effect traits remain elusive for most systems. Here, we present detailed data on crop pollination services provided by native, wild bees to explore the role of six commonly used species traits in determining how crop pollination is affected by increasing agricultural intensification. Analyses were conducted in parallel for three crop systems (watermelon, cranberry, and blueberry) located within the same geographical region (mid-Atlantic USA). Bee species traits did not strongly predict species’ response to agricultural intensification, and the few traits that were weakly predictive were not consistent across crops. Similarly, no trait predicted species’ overall functional contribution in any of the three crop systems, although body size was a good predictor of per capita efficiency in two systems. So far, most studies looking for response or effect traits in pollination systems have found weak and often contradicting links. Overall we were unable to make generalizable predictions regarding species responses to land-use change and its effect on the delivery of ecosystem services. Pollinator traits may be useful for understanding ecological processes in some systems, but thus far the promise of traits-based ecology has yet to be fulfilled for pollination ecology.
A Repetitive Modular Oscillation Underlies Human Brain Electric Activity
Authors: Tozzi Arturo , Peters James F. , Jaušovec Norbert
Published: September 2016

The modular function j, central in the assessment of abstract mathematical problems, describes elliptic, intertwined trajectories that move in the planes of both real and complex numbers. Recent clues suggest that the j-function might display a physical counterpart, equipped with a quantifiable real component and a hidden imaginary one, currently undetectable by our senses and instruments. Here we evaluate whether the real part of the modular function can be spotted in the electric activity of the human brain. We assessed EEGs from five healthy males, eyes-closed and resting state, and superimposed the electric traces with the bidimensional curves predicted by the j-function. We found that the two trajectories matched in more than 85% of cases, independent from the subtending electric rhythm and the electrode location. Therefore, the real part of the j-function’s peculiar wave is ubiquitously endowed all over normal EEGs paths. We discuss the implications of such correlation in neuroscience and neurology, highlighting how the j-function might stand for the one of the basic oscillations of the brain, and how the still unexplored imaginary part might underlie several physiological and pathological nervous features.

SIGNIFICANCE STATEMENT

Our results point towards the brain as ubiquitously equipped with j-function’s oscillations, which movements take place on the plane of the complex numbers. It means that there must be, in brain electric activity, also a veiled complex part, which can be assessed with the help of imaginary numbers. The modular j-function provides further dimensions to the real numbers, in order to enlarge their predictive powers: it suggests the possible presence of hidden (functional or spatial) brain extra-dimensions. Furthermore, j-oscillations could be disrupted during pathologies, paving the way to novel approaches to central nervous system’s diseases.
An effect size distribution analysis of heart rate variability studies: Recommendations for reporting the magnitude of group differences
Authors: Quintana Daniel S.
Published: September 2016

The calculation of heart rate variability (HRV) is a popular tool used to investigate differences in cardiac autonomic control between population samples. When interpreting effect sizes to quantify the magnitude of group differences, researchers typically use Cohen's guidelines of small (0.2), medium (0.5), and large (0.8) effects. However, these guidelines were only proposed for use when the effect size distribution (ESD) was unknown. Despite the availability of effect sizes from hundreds of HRV studies, researchers still largely rely on Cohen's guidelines to interpret effect sizes. This article describes an ESD analysis of 297 HRV effect sizes from case-control studies, revealing that the 25th, 50th, and 75th effect size percentiles correspond with effect sizes of 0.25, 0.5, and 0.84, respectively. The ESD for separate clinical groups are also presented. The data suggests that Cohen's guidelines underestimate the magnitude of small and large effect sizes for the body of HRV case-control research. Therefore, to better reflect observed HRV effect sizes, the data suggest that effect sizes of 0.25, 0.5, and 0.85 should be interpreted as small, medium, and large effects. Researchers are encouraged to use the ESD dataset or their own collected datasets in tandem with the provided analysis script to perform bespoke ESD analyses relevant to their specific research area.