bluuebunny/crossref_metadata_2025 huggingface dataset:
Fusion product studies via fast ion D–D and D–3He fusion on JET
Authors: Sharapov S.E. , Hellsten T. , Kiptily V.G. , Craciunescu T. , Eriksson J. , Fitzgerald M. , Girardo J.-B. , Goloborod’ko V. , Hellesen C. , Hjalmarsson A. , Johnson T. , Kazakov Y. , Koskela T. , Mantsinen M. , Monakhov I. , Nabais F. , Nocente M. , Perez von Thun C. , Rimini F. , Santala M. , Schneider M. , Tardocchi M. , Tsalas M. , Yavorskij V. , Zoita V.
Published: August 2016

Dedicated fast ion D–D and D–3He fusion experiments were performed on JET with carbon wall (2008) and ITER-like wall (2014) for testing the upgraded neutron and energetic ion diagnostics of fusion products. Energy spectrum of D–D neutrons was the focus of the studies in pure deuterium plasmas. A significant broadening of the energy spectrum of neutrons born in D–D fast fusion was observed, and dependence of the maximum D and D–D neutron energies on plasma density was established. Diagnostics of charged products of aneutronic D–3He fusion reactions, 3.7 MeV alpha-particles similar to those in D–T fusion, and 14.6 MeV protons, were the focus of the studies in D–3He plasmas. Measurements of 16.4 MeV gamma-rays born in the weak secondary branch of D(3He, γ)5Li reaction were used for assessing D–3He fusion power. For achieving high yield of D–D and D–3He reactions at relatively low levels of input heating power, an acceleration of D beam up to the MeV energy range was used employing 3rd harmonic (

f
=
3

f

C
D

) ICRH technique. These results were compared to the techniques of D beam injection into D–3He mixture, and 3He-minority ICRH in D plasmas.
Evolution of the Boson gas at zero temperature: Mean-field limit and second-order correction
Authors: Grillakis Manoussos , Machedon Matei , Margetis Dionisios
Published: August 2016

A large system of

N
N

integer-spin atoms, called Bosons, manifests one of the most coherent macroscopic quantum states known to date, the “Bose-Einstein condensate”, at extremely low temperatures. As

N
→
∞

N\to \infty

, this system is usually described by a mean-field limit: a single-particle wave function, the condensate wave function, that satisfies a nonlinear Schrödinger-type equation. In this expository paper, we review kinetic aspects of the mean-field Boson evolution. Furthermore, we discuss recent advances in the rigorous study of second-order corrections to this mean-field limit. These corrections originate from the quantum-kinetic mechanism of pair excitation, which lies at the core of pioneering works in theoretical physics including ideas of Bogoliubov, Lee, Huang, Yang and Wu. In the course of our exposition, we revisit the formalism of Fock space, which is indispensable for the analysis of pair excitation.
Singular twisted sums generated by complex interpolation
Authors: Castillo Jesús , Ferenczi Valentin , González Manuel
Published: August 2016

We present new methods to obtain singular twisted sums

X

⊕
Ω

X

X\oplus _\Omega X

(i.e., exact sequences

0
→
X
→
X

⊕
Ω

X
→
X
→
0

0\to X\to X\oplus _\Omega X \to X\to 0

in which the quotient map is strictly singular) when

X
X

is an interpolation space arising from a complex interpolation scheme and

Ω
\Omega

is the induced centralizer.

Although our methods are quite general, we are mainly concerned with the choice of

X
X

as either a Hilbert space or Ferenczi’s uniformly convex Hereditarily Indecomposable space. In the first case, we construct new singular twisted Hilbert spaces (which includes the only known example so far: the Kalton-Peck space

Z
2

Z_2

). In the second case we obtain the first example of an H.I. twisted sum of an H.I. space.

During our study of singularity we introduce the notion of a disjointly singular twisted sum of Köthe function spaces and construct several examples involving reflexive

p
p

-convex Köthe function spaces (which includes the function space version of the Kalton-Peck space

Z
2

Z_2

).

We then use Rochberg’s description of iterated twisted sums to show that there is a sequence

F

n

\mathcal F_n

of H.I. spaces so that

F

m
+
n

\mathcal F_{m+n}

is a singular twisted sum of

F

m

\mathcal F_m

and

F

n

\mathcal F_n

, while for

l
>
n

l>n

the direct sum

F

n

⊕

F

l
+
m

\mathcal F_n \oplus \mathcal F_{l+m}

is a nontrivial twisted sum of

F

l

\mathcal F_l

and

F

m
+
n

\mathcal F_{m+n}

.
Xenopus TACC2 is a microtubule plus end–tracking protein that can promote microtubule polymerization during embryonic development
Authors: Rutherford Erin L. , Carandang Leslie , Ebbert Patrick T. , Mills Alexandra N. , Bowers Jackson T. , Lowery Laura Anne
Published: August 2016

Microtubule dynamics is regulated by plus end–tracking proteins (+TIPs), which localize to the plus ends of microtubules (MTs). We previously showed that TACC1 and TACC3, members of the transforming acidic coiled-coil protein family, can act as +TIPs to regulate MT dynamics in Xenopus laevis. Here we characterize TACC2 as a +TIP that localizes to MT plus ends in front of EB1 and overlapping with TACC1 and TACC3 in multiple embryonic cell types. We also show that TACC2 can promote MT polymerization in mesenchymal cells but not neuronal growth cones, thus displaying cell-type specificity. Structure–function analysis demonstrates that the C-terminal region of TACC2 is both necessary and sufficient to localize to MT plus ends and promote increased rates of MT polymerization, whereas the N-terminal region cannot bind to MT plus ends but can act in a dominant-negative capacity to reduce polymerization rates. Finally, we analyze mRNA expression patterns in Xenopus embryos for each TACC protein and observe neural enrichment of TACC3 expression compared with TACC1 and TACC2, which are also expressed in mesodermal tissues, including somites. Overall these data provide a novel assessment of all three TACC proteins as a family of +TIPs by highlighting the unique attributes of each, as well as their collective characteristics.
Neonate Auditory Brainstem Responses to CE-Chirp and CE-Chirp Octave Band Stimuli II: Versus Adult Auditory Brainstem Responses
Authors: Cobb Kensi M. , Stuart Andrew
Published: August 2016

Objectives:

The purpose of the study was to examine the differences in auditory brainstem response (ABR) latency and amplitude indices to the CE-Chirp stimuli in neonates versus young adults as a function of stimulus level, rate, polarity, frequency and gender.

Design:

Participants were 168 healthy neonates and 20 normal-hearing young adults. ABRs were obtained to air- and bone-conducted CE-Chirps and air-conducted CE-Chirp octave band stimuli. The effects of stimulus level, rate, and polarity were examined with air-conducted CE-Chirps. The effect of stimulus level was also examined with bone-conducted CE-Chirps and CE-Chirp octave band stimuli. The effect of gender was examined across all stimulus manipulations.

Results:

In general, ABR wave V amplitudes were significantly larger (p < 0.0001) and latencies were significantly shorter (p < 0.0001) for adults versus neonates for all air-conducted CE-Chirp stimuli with all stimulus manipulations. For bone-conducted CE-Chirps, infants had significantly shorter wave V latencies than adults at 15 dB nHL and 45 dB nHL (p = 0.02). Adult wave V amplitude was significantly larger for bone-conducted CE-Chirps only at 30 dB nHL (p = 0.02). The effect of gender was not statistically significant across all measures (p > 0.05).

Conclusions:

Significant differences in ABR latencies and amplitudes exist between newborns and young adults using CE-Chirp stimuli. These differences are consistent with differences to traditional click and tone burst stimuli and reflect maturational differences as a function of age. These findings continue to emphasize the importance of interpreting ABR results using age-based normative data.
Neural Correlates of Selective Attention With Hearing Aid Use Followed by ReadMyQuips Auditory Training Program
Authors: Rao Aparna , Rishiq Dania , Yu Luodi , Zhang Yang , Abrams Harvey
Published: August 2016

Objectives:

The objectives of this study were to investigate the effects of hearing aid use and the effectiveness of ReadMyQuips (RMQ), an auditory training program, on speech perception performance and auditory selective attention using electrophysiological measures. RMQ is an audiovisual training program designed to improve speech perception in everyday noisy listening environments.

Design:

Participants were adults with mild to moderate hearing loss who were first-time hearing aid users. After 4 weeks of hearing aid use, the experimental group completed RMQ training in 4 weeks, and the control group received listening practice on audiobooks during the same period. Cortical late event-related potentials (ERPs) and the Hearing in Noise Test (HINT) were administered at prefitting, pretraining, and post-training to assess effects of hearing aid use and RMQ training. An oddball paradigm allowed tracking of changes in P3a and P3b ERPs to distractors and targets, respectively. Behavioral measures were also obtained while ERPs were recorded from participants.

Results:

After 4 weeks of hearing aid use but before auditory training, HINT results did not show a statistically significant change, but there was a significant P3a reduction. This reduction in P3a was correlated with improvement in d prime (d′) in the selective attention task. Increased P3b amplitudes were also correlated with improvement in d′ in the selective attention task. After training, this correlation between P3b and d′ remained in the experimental group, but not in the control group. Similarly, HINT testing showed improved speech perception post training only in the experimental group. The criterion calculated in the auditory selective attention task showed a reduction only in the experimental group after training. ERP measures in the auditory selective attention task did not show any changes related to training.

Conclusions:

Hearing aid use was associated with a decrement in involuntary attention switch to distractors in the auditory selective attention task. RMQ training led to gains in speech perception in noise and improved listener confidence in the auditory selective attention task.
Validation of Using Claims Data to Measure Safety of Lumbar Fusion Surgery
Authors: Patel Neel K. , Moses Rachel A. , Martin Brook I. , Lurie Jon D. , Mirza Sohail K.
Published: August 2016

Study Design.

Retrospective analysis of patients undergoing elective lumbar fusion operations, comparing rates of repeat spine surgery based on method of ascertainment.

Objective.

We report the accuracy of a claims-based approach for reporting repeat surgery compared with medical records abstraction as the “gold standard.”

Summary of Background Data.

Previous studies have reported the validity of a claims-based algorithm for grouping patients by surgical indication and classifying operative features, but their accuracy in measuring surgical quality indicators has not been widely examined.

Methods.

We identified a subset of patients undergoing elective lumbar fusion operations at a single institution from 1996 to 2011, excluding those with spinal fracture, spinal cord injury, or cancer. From the medical record we abstracted the incidence of repeat spine operation or rehospitalization at 1 year. We cross-classified each event record with its corresponding value derived from claims. The sensitivity and specificity of the claims-based approach were calculated for reoperation within 30, 90, and 365 days, and all-cause hospital readmission within 30 days.

Results.

Medical records linked to claims data were obtained for 520 patients undergoing elective lumbar fusion. Reoperation rates based on chart review were 1.0%, 1.3%, 3.6%, compared with 0.8%, 1.7%, and 3.8% based on the final claims methods at 30, 90, and 365 days, respectively. The claims-based algorithm had sensitivities of 80.0%, 100%, and 94.1% and specificities of 100%, 99.6%, 99.2% for repeat surgery within 30, 90, and 365 days, respectively. The sensitivity for all-cause readmission was 50%.

Conclusion.

Health care quality improvement efforts often rely on administrative data to report surgical safety. We found that claims-based ascertainment of safety at a single institution was very accurate. However, accuracy depended on careful attention to the timing of outcomes, as well as the definitions and coding of repeat surgery, including how orthopedic device removal codes are classified.

Level of Evidence: 3
Diagnostic Accuracy of Somatosensory Evoked Potentials in Evaluating New Neurological Deficits After Posterior Cervical Fusions
Authors: Thirumala Parthasarathy D. , Melachuri Samyuktha R. , Kaur Jaspreet , Ninaci David , Melachuri Manasa K. , Habeych Miguel E. , Crammond Donald J. , Balzer Jeffrey R.
Published: August 2016

Study Design.

This study examined the diagnostic accuracy of significant changes of somatosensory evoked potentials (SSEPs) to evaluate and predict postoperative neurological deficits after posterior cervical fusions (PCF). Eight hundred forty six eligible patients underwent PCF at the University of Pittsburgh Medical Center (UPMC), from 2010 to 2012.

Objective.

To assess the specificity and sensitivity of intraoperative monitoring in predicting postoperative neurological deficits during PCF.

Summary of Background Data.

We calculated the predictive value, including sensitivity and specificity, of changes in SSEPs to identify neurological deficits postoperatively. We used a receiver operating characteristic (ROC) curve with SSEP categories as cutoff values to further evaluate the diagnostic accuracy of change in SSEPs and postoperative neurological deficit.

Methods.

All patients had preposition baselines and continuous SSEP monitoring throughout the surgery. Statistical analysis was completed using SPSS version 22 (IBM Corp., Armonk, NY).

Results.

Age and sex did not influence outcomes. Obesity affected patient outcome. The SSEP categories of significant changes and loss of responses resulted in a sensitivity/specificity of 0.30/0.96 and 0.16/0.98, respectively. The receiver operating characteristic curve has an area under the curve for significant change in/loss of SSEPs of 0.62/0.65 with a 95% confidence interval of 0.525 to 0.714/0.509 to 0.797.

Conclusion.

Significant SSEP changes during PCF are a very specific but poorly sensitive indicator of postoperative neurological deficits. The odds ratio for significant changes in SSEPs and loss of waveforms was 9.80 and 11.82, respectively, with a 95% confidence interval of 4.695 to 20.46 and 4.45 to 31.41, respectively.

Level of Evidence: 1
Decreased Risk of Radiation Pneumonitis With Coincident Concurrent Use of Angiotensin-converting Enzyme Inhibitors in Patients Receiving Lung Stereotactic Body Radiation Therapy
Authors: Alite Fiori , Balasubramanian Neelam , Adams William , Surucu Murat , Mescioglu Ibrahim , Harkenrider Matthew M.
Published: August 2016

Objectives:

Angiotensin-converting enzyme inhibitors (ACEi) have demonstrated decreased rates of radiation-induced lung injury in animal models and clinical reports have demonstrated decreased pneumonitis in the setting of conventionally fractionated radiation to the lung. We tested the role of ACEi in diminishing rates of symptomatic (grade ≥2) pneumonitis in the setting of lung stereotactic body radiation therapy (SBRT).

Methods:

We analyzed patients treated with thoracic SBRT to 48 to 60 Gy in 4 to 5 fractions from 2006 to 2014. We reviewed pretreatment and posttreatment medication profiles to document use of ACEi, angiotensin receptor blockers, bronchodilators, aspirin, PDE-5 inhibitors, nitrates, and endothelin receptor antagonists. Pneumonitis was graded posttreatment based on Common Terminology Criteria for Adverse Events Version 4.0. Univariate and multivariate analysis was performed and time to development of pneumonitis was evaluated by the Kaplan-Meier method.

Results:

A total of 189 patients were evaluated with a median follow-up of 24.8 months. The overall 1-year rate of symptomatic pneumonitis was 13.2%. The 1-year rate of symptomatic pneumonitis was 4.2% for ACEi users versus 16.3% in nonusers (P=0.03). On univariate analysis, the odds of developing grade 2 or greater pneumonitis were significantly lower for patients on ACEi (P=0.03). On multivariate analysis, after controlling for clinicopathologic characteristics and dosimetric endpoints, there was a significant association between ACEi use and decreased risk of clinical pneumonitis (P=0.04). Angiotensin receptor blockers or other bronchoactive medications did not show significant associations with development of pneumonitis.

Conclusions:

Incidental concurrent use of ACEi demonstrated efficacy in diminishing rates of symptomatic pneumonitis in the setting of lung SBRT.
Effects of Miconazole Oral Gel on Blood Concentrations of Tacrolimus and Cyclosporine: A Retrospective Observational Study
Authors: Ishiwata Yasuyoshi , Nagata Masashi , Arai Takafumi , Makiishi Misato , Yoshikawa Maho , Takahashi Hiromitsu , Kohsaka Hitoshi , Yasuhara Masato
Published: August 2016

Background:

Although azole antifungal agents have been shown to affect the pharmacokinetics of calcineurin inhibitors such as tacrolimus (TAC) and cyclosporine (CyA) by inhibiting drug metabolism, there are few clinical reports on drug interactions between miconazole (MCZ) oral gel and calcineurin inhibitors. In this study, the effects of MCZ oral gel on the blood concentrations of TAC and CyA were investigated.

Methods:

In this retrospective study, 18 patients concomitantly administered MCZ oral gel and TAC (9 for dermatomyositis, 3 for myasthenia gravis, 2 for systemic lupus erythematosus, 2 for rheumatoid arthritis, 1 for polymyositis, 1 for prevention of graft-versus-host disease after bone marrow transplantation), and 15 patients concomitantly administered MCZ oral gel and CyA (11 for interstitial pneumonia, 2 for pemphigus, 1 for eosinophilic granulomatosis with polyangiitis, 1 for systemic lupus erythematosus) were evaluated. The dose-adjusted blood concentrations of TAC or CyA were compared before and after the initiation of MCZ oral gel.

Results:

The trough blood concentration/dose (C/D) ratios of TAC and CyA increased significantly with the administration of MCZ oral gel. The median C/D ratios of TAC and CyA increased by 108% (range: –44% to 216%) and 44% (range: −34% to 195%), respectively.

Conclusions:

These results suggest that MCZ oral gel affects the pharmacokinetics of TAC and CyA. Detailed monitoring of the blood concentrations of these drugs, followed by dose adjustments, is needed for each patient because of the difficulties associated with accurately predicting the degree of the effects of MCZ oral gel.
Reductions in Retrobulbar and Retinal Capillary Blood Flow Strongly Correlate With Changes in Optic Nerve Head and Retinal Morphology Over 4 Years in Open-angle Glaucoma Patients of African Descent Compared With Patients of European Descent
Authors: Siesky Brent , Harris Alon , Carr Joseph , Verticchio Vercellin Alice , Hussain Rehan M. , Parekh Hembree Priyanka , Wentz Scott , Isaacs Michael , Eckert George , Moore Nicholas A.
Published: August 2016

Purpose:

To investigate the relationship of changes in ocular blood flow with optic nerve head (ONH) and retinal morphology in open-angle glaucoma (OAG) patients of African versus European descent (ED) over 4 years.

Materials and Methods:

In this study, 112 patients with OAG were examined at baseline, 79 [59 ED, 20 African descent (AD)] of which were followed for 4 years. Retinal capillary blood flow was assessed with Heidelberg retinal flowmetry. Retrobulbar blood flow was measured by color Doppler imaging. Retinal structural changes were examined with optical coherence tomography and Heidelberg retinal tomography-III. Mixed-model analysis of covariance was used to test for the significance of change from baseline to 4-year follow-up, and Pearson correlation coefficients were calculated to evaluate linear associations.

Results:

In OAG patients of AD, structural changes of the ONH demonstrated a strong association with the end diastolic velocities and resistive indices of the short posterior ciliary arteries over 4 years. In addition, there was a significantly larger increase in the avascular area of the inferior retina in patients of AD, and this reduction in retinal capillaries strongly correlated with a reduction in macular thickness.

Conclusions:

Reductions in retinal capillary and retrobulbar blood flow strongly correlated with changes in the ONH and macular thickness over 4 years in OAG patients of AD compared with ED. These data suggest that ocular vascular health may be a more influential contributing factor in the pathophysiology of OAG in patients of AD compared with ED.
Comparison of Endoscopic Robotic versus Sternotomy Approach for the Resection of Left Atrial Tumors
Authors: Moss Emmanuel , Halkos Michael E. , Miller Jeffrey S. , Murphy Douglas A.
Published: August 2016

Objective

Primary cardiac tumors most commonly occur in the left atrium. The aim of this study was to compare outcomes among patients undergoing isolated left atrial tumor resection via sternotomy or robotic approach.

Methods

From 2003 to 2013, 69 patients underwent isolated left atrial tumor resection at 3 affiliated hospitals with either a sternotomy (n = 39) or robotic approach (n = 30). A retrospective review of prospectively collected data was performed, and outcomes were compared between the sternotomy and robotic groups. Univariate and multivariate analyses controlling for pertinent preoperative characteristics were performed.

Results

Patients’ characteristics in the 2 groups were similar, with the exception of a history of chronic obstructive pulmonary disease (sternotomy, 12.8% vs robotic, 0%; P < 0.04) and elective surgical status (sternotomy, 64.1% vs robotic, 93.3%; P < 0.02). On univariate analysis, robotic-assisted surgery was associated with significantly shorter postoperative mechanical ventilation, intensive care unit (ICU) length of stay (LOS), hospital LOS, and a lower rate of perioperative blood transfusion. After controlling for patient comorbidity in a multiple logistic regression model, there remained a trend toward decreased blood transfusions (adjusted odds ratio, 0.33; CI, 0.09–1.20; P = 0.09), shorter ICU (16.3 fewer hours; P = 0.11), and hospital LOS (1.1 fewer days; P = 0.17) in the robotic group. There was one postoperative stroke in the sternotomy group and none in the robotic group (P = 0.21).

Conclusions

Robotic-assisted left atrial tumor resection is feasible and may be associated with a lower incidence of perioperative blood transfusion as well as shorter ventilation time, and shorter ICU and hospital LOS.
Extracorporeal Left Ventricular Circulatory Support as a Bridge to Implantable LVAD for a Patient With Pan-Left Ventricular Thrombosis
Authors: Ogawa Mitsugu , Balsara Keki R. , Masood Muhammad Faraz , Itoh Akinobu
Published: August 2016

We present the case of a 57 year old woman who developed pan-left ventricular thrombus while being supported with central extracorporeal membrane oxygenation support for cardiogenic shock. The left heart thrombus was evacuated emergently through the aortic valve, left atriotomy, and left ventriculotomy. The cannulation was then revised with the addition of a 36 French angled cannula in the apex of the left ventricle to decompress the ventricle, minimize stasis, and allow for any residual microthrombus to be trapped in the oxygenator membrane, not causing embolization. Once her neurological status was confirmed intact, a durable device was implanted. She recovered well without any neurological injury.
Sertraline as an Additional Treatment for Cholestatic Pruritus in Children
Authors: Thébaut Alice , Habes Dalila , Gottrand Frédéric , Rivet Christine , Cohen Joseph , Debray Dominique , Jacquemin Emmanuel , Gonzales Emmanuel
Published: August 2016

Objectives:

Pruritus is a severe symptom accompanying chronic cholestasis. It can be debilitating and difficult to control. In children, first‐line treatments are ursodeoxycholic acid and rifampicin. Refractory pruritus may require invasive therapies including liver transplantation. Clinical trials based on small samples of adult patients suggest that serotonin reuptake inhibitors can improve pruritus in cholestatic or uremic disease. We performed a prospective, multicenter study to assess efficiency and safety of the serotonin reuptake inhibitor sertraline in treating children with refractory cholestatic pruritus.

Methods:

Twenty children experiencing refractory cholestatic pruritus related to Alagille syndrome or progressive familial intrahepatic cholestasis were included from 4 centers between 2007 and 2014, and treated with sertraline at a starting dose of 1 mg · kg−1 · day−1 and thereafter individually adapted up to 4 mg · kg−1 · day−1. Before and after 3 months with therapy, pruritus was assessed using a visual itching scale graded on 10 points, a skin scratch marks score and a sleeping impairment score.

Results:

Sertraline was prescribed at a median daily dose of 2.2 mg · kg−1 · day−1. After 3 months, pruritus improved in 14 out of 20 treated patients, and the median itching score decreased significantly from 8/10 (5–10) to 5/10 (2–10). Likewise, skin scratch marks and sleep quality improved in 9 of these 14 patients. Nonsevere adverse events were reported in 6 children, leading to treatment discontinuation in 3.

Conclusion:

Our data suggest that sertraline may constitute a useful drug in the management of refractory cholestatic pruritus in children.
Brief Report: High HIV Incidence in a South African Community of Men Who Have Sex With Men: Results From the Mpumalanga Men's Study, 2012–2015
Authors: Lane Tim , Osmand Thomas , Marr Alexander , Struthers Helen , McIntyre James A. , Shade Starley B.
Published: August 2016

Cross-sectional studies among African men who have sex with men (MSM) populations demonstrate high HIV prevalence, but few incidence estimates exist. The Mpumalanga Men's Study in Gert Sibande, Mpumalanga province, South Africa, involved 3 serial cross-sectional surveys of MSM recruited through respondent-driven sampling between 2012 and 2015. Successive surveys recaptured a nested cohort of 179, contributing 144.3 person-years (PY) of observation. We observed 18 seroconversions, or incidence of 12.5/100 (PY) (95% confidence interval CI: 8.1 to 19.2/100 PY). Presumptions of high incidence among MSM were confirmed and demonstrate an urgent need for biomedical prevention and treatment programming for MSM in South Africa.
Asymptomatic Atherosclerosis in Primary Sjögren Syndrome
Authors: Garcia Ana Beatriz Andrêo , Dardin Luciana Paula , Minali Paulo Alexandre , Czapkowsky Adriano , Ajzen Sergio Aron , Trevisani Virginia Fernandes Moça
Published: August 2016

Background

Primary Sjögren syndrome is a chronic inflammatory autoimmune disease. The delay in diagnosis allows the establishment of a chronic inflammatory state, which makes primary Sjögren syndrome an interesting model for the study of atherosclerosis.

Objectives

The aim of this study was to evaluate subclinical atherosclerosis in 49 patients with Sjögren syndrome using noninvasive methods.

Methods

We assessed traditional risk factors such as hypertension, diabetes, dyslipidemia, smoking, and family history of atherosclerosis. Patients with prior cardiovascular events and a history of atherosclerosis were excluded. Clinical and laboratory features were recorded, as well as the European League Against Rheumatism Sjögren’s Syndrome Activity Index calculation. The atherosclerosis evaluation was done by carotid intima-media thickness, measured by ultrasonography, and ankle-brachial index (ABI).

Results

Fifteen patients (31%) had at least 1 traditional risk factor, and 65.3% had a European League Against Rheumatism Sjögren’s Syndrome Activity Index score from mild to moderate. Only 2 patients had increased carotid intima-media thickness. However, 59% presented ABI alterations. Multiple correspondence analysis showed a clear correlation between low ABI and the positivity of autoantibodies (antinuclear antibodies, anti-SSA, rheumatoid factor).

Conclusions

The subgroup of patients with positive autoantibodies showed low ABI, which may represent a higher risk of early atherosclerosis and indicate the need for more careful monitoring in this group.
Rheumatologists and Ophthalmologists Differ in Treatment Decisions for Ocular Behçet Disease
Authors: Palestine Alan Gary , Kolfenbach Jason Roy , Ozzello Daniel J.
Published: August 2016

Background

Ocular involvement in patients with Behçet disease represents a significant clinical morbidity in this disease, and the prevention of visual impairment is an important treatment goal. There are no randomized controlled trials for the treatment of ocular Behçet disease; however, clinicians must still make treatment decisions.

Objectives

The goals of this study were to describe the treatment preferences of rheumatologists and ophthalmologists for the treatment of ocular Behçet disease and to identify factors that influence these decisions.

Methods

Eight hundred fifty-two rheumatologists and 934 ophthalmologists were surveyed via e-mail regarding their choice of therapy for a hypothetical patient with ocular Behçet disease. Respondents were asked to select first- and second-choice therapies and then reselect first and second choices assuming there would be no issues with cost or insurance prior authorization.

Results

One hundred thirty two physicians (7.4%) who were willing to recommend treatment completed the survey: 68 rheumatologists and 64 ophthalmologists. The most common first-choice therapy for both specialties was a biologic agent. Significantly more rheumatologists than ophthalmologists chose methotrexate (P < 0.025) and azathioprine (P < 0.005) as their first-choice therapy. After assuming there were no concerns with cost or prior authorization, rheumatologists were still more likely to choose azathioprine compared with ophthalmologists (P < 0.02), and ophthalmologists were more likely to choose local steroid implants (P < 0.02). Both rheumatologists and ophthalmologists increased their choice of an anti–tumor necrosis factor agent when cost and prior authorization issues were removed (P < 0.0001 and 0.008, respectively).

Conclusions

Physician decision making is influenced by medical specialty and concerns regarding cost and prior authorization.
Multi-alternative decision-making with non-stationary inputs
Authors: Nunes Luana F. , Gurney Kevin
Published: August 2016

One of the most widely implemented models for multi-alternative decision-making is the multihypothesis sequential probability ratio test (MSPRT). It is asymptotically optimal, straightforward to implement, and has found application in modelling biological decision-making. However, the MSPRT is limited in application to discrete (‘trial-based’), non-time-varying scenarios. By contrast, real world situations will be continuous and entail stimulus non-stationarity. In these circumstances, decision-making mechanisms (like the MSPRT) which work by accumulating evidence, must be able to discard outdated evidence which becomes progressively irrelevant. To address this issue, we introduce a new decision mechanism by augmenting the MSPRT with a rectangular integration window and a transparent decision boundary. This allows selection and de-selection of options as their evidence changes dynamically. Performance was enhanced by adapting the window size to problem difficulty. Further, we present an alternative windowing method which exponentially decays evidence and does not significantly degrade performance, while greatly reducing the memory resources necessary. The methods presented have proven successful at allowing for the MSPRT algorithm to function in a non-stationary environment.
Geophysical fluid dynamics: whence, whither and why?
Authors: Vallis Geoffrey K.
Published: August 2016

This article discusses the role of geophysical fluid dynamics (GFD) in understanding the natural environment, and in particular the dynamics of atmospheres and oceans on Earth and elsewhere. GFD, as usually understood, is a branch of the geosciences that deals with fluid dynamics and that, by tradition, seeks to extract the bare essence of a phenomenon, omitting detail where possible. The geosciences in general deal with complex interacting systems and in some ways resemble condensed matter physics or aspects of biology, where we seek explanations of phenomena at a higher level than simply directly calculating the interactions of all the constituent parts. That is, we try to develop theories or make simple models of the behaviour of the system as a whole. However, these days in many geophysical systems of interest, we can also obtain information for how the system behaves by almost direct numerical simulation from the governing equations. The numerical model itself then explicitly predicts the emergent phenomena—the Gulf Stream, for example—something that is still usually impossible in biology or condensed matter physics. Such simulations, as manifested, for example, in complicated general circulation models, have in some ways been extremely successful and one may reasonably now ask whether understanding a complex geophysical system is necessary for predicting it. In what follows we discuss such issues and the roles that GFD has played in the past and will play in the future.
Lagrangian transport for two-dimensional deep-water surface gravity wave groups
Authors: van den Bremer T. S. , Taylor P. H.
Published: August 2016

The Lagrangian trajectories of neutrally buoyant particles underneath surface gravity wave groups are dictated by two physical phenomena: the Stokes drift results in a net displacement of particles in the direction of propagation of the group, whereas the Eulerian return flow, as described by the multi-chromatic wave theory of Longuet-Higgins & Stewart (1962
J. Fluid Mech.
13
, 481–504. (
doi:10.1017/S0022112062000877
)), transports such particles in the opposite direction. By pursuing a separation of scales expansion, we develop simple closed-form expressions for the net Lagrangian displacement of particles. By comparing the results from the separation of scales expansion at different orders in bandwidth, we study the effect of frequency dispersion on the local Lagrangian transport, which we show can be ignored for realistic sea states.
Maximal liquid bridges between horizontal cylinders
Authors: Cooray Himantha , Huppert Herbert E. , Neufeld Jerome A.
Published: August 2016

We investigate two-dimensional liquid bridges trapped between pairs of identical horizontal cylinders. The cylinders support forces owing to surface tension and hydrostatic pressure that balance the weight of the liquid. The shape of the liquid bridge is determined by analytically solving the nonlinear Laplace–Young equation. Parameters that maximize the trapping capacity (defined as the cross-sectional area of the liquid bridge) are then determined. The results show that these parameters can be approximated with simple relationships when the radius of the cylinders is small compared with the capillary length. For such small cylinders, liquid bridges with the largest cross-sectional area occur when the centre-to-centre distance between the cylinders is approximately twice the capillary length. The maximum trapping capacity for a pair of cylinders at a given separation is linearly related to the separation when it is small compared with the capillary length. The meniscus slope angle of the largest liquid bridge produced in this regime is also a linear function of the separation. We additionally derive approximate solutions for the profile of a liquid bridge, using the linearized Laplace–Young equation. These solutions analytically verify the above-mentioned relationships obtained for the maximization of the trapping capacity.
Social connectedness is associated with fibrinogen level in a human social network
Authors: Kim David A. , Benjamin Emelia J. , Fowler James H. , Christakis Nicholas A.
Published: August 2016

Socially isolated individuals face elevated rates of illness and death. Conventional measures of social connectedness reflect an individual's perceived network and can be subject to bias and variation in reporting. In this study of a large human social network, we find that greater indegree, a sociocentric measure of friendship and familial ties identified by a subject's social connections rather than by the subject, predicts significantly lower concentrations of fibrinogen (a biomarker of inflammation and cardiac risk), after adjusting for demographics, education, medical history and known predictors of cardiac risk. The association between fibrinogen and social isolation, as measured by low indegree, is comparable to the effect of smoking, and greater than that of low education, a conventional measure of socioeconomic disadvantage. By contrast, outdegree, which reflects an individual's perceived connectedness, displays a significantly weaker association with fibrinogen concentrations.
Soil management shapes ecosystem service provision and trade-offs in agricultural landscapes
Authors: Tamburini Giovanni , De Simone Serena , Sigura Maurizia , Boscutti Francesco , Marini Lorenzo
Published: August 2016

Agroecosystems are principally managed to maximize food provisioning even if they receive a large array of supporting and regulating ecosystem services (ESs). Hence, comprehensive studies investigating the effects of local management and landscape composition on the provision of and trade-offs between multiple ESs are urgently needed. We explored the effects of conservation tillage, nitrogen fertilization and landscape composition on six ESs (crop production, disease control, soil fertility, water quality regulation, weed and pest control) in winter cereals. Conservation tillage enhanced soil fertility and pest control, decreased water quality regulation and weed control, without affecting crop production and disease control. Fertilization only influenced crop production by increasing grain yield. Landscape intensification reduced the provision of disease and pest control. We also found tillage and landscape composition to interactively affect water quality regulation and weed control. Under N fertilization, conventional tillage resulted in more trade-offs between ESs than conservation tillage. Our results demonstrate that soil management and landscape composition affect the provision of several ESs and that soil management potentially shapes the trade-offs between them.
Diminishing-returns epistasis among random beneficial mutations in a multicellular fungus
Authors: Schoustra Sijmen , Hwang Sungmin , Krug Joachim , de Visser J. Arjan G. M.
Published: August 2016

Adaptive evolution ultimately is fuelled by mutations generating novel genetic variation. Non-additivity of fitness effects of mutations (called epistasis) may affect the dynamics and repeatability of adaptation. However, understanding the importance and implications of epistasis is hampered by the observation of substantial variation in patterns of epistasis across empirical studies. Interestingly, some recent studies report increasingly smaller benefits of beneficial mutations once genotypes become better adapted (called diminishing-returns epistasis) in unicellular microbes and single genes. Here, we use Fisher's geometric model (FGM) to generate analytical predictions about the relationship between the effect size of mutations and the extent of epistasis. We then test these predictions using the multicellular fungusAspergillus nidulansby generating a collection of 108 strains in either a poor or a rich nutrient environment that each carry a beneficial mutation and constructing pairwise combinations using sexual crosses. Our results support the predictions from FGM and indicate negative epistasis among beneficial mutations in both environments, which scale with mutational effect size. Hence, our findings show the importance of diminishing-returns epistasis among beneficial mutations also for a multicellular organism, and suggest that this pattern reflects a generic constraint operating at diverse levels of biological organization.
Sea urchins in a high-CO
2
world: the influence of acclimation on the immune response to ocean warming and acidification
Authors: Brothers C. J. , Harianto J. , McClintock J. B. , Byrne M.
Published: August 2016

Climate-induced ocean warming and acidification may render marine organisms more vulnerable to infectious diseases. We investigated the effects of warming and acidification on the immune response of the sea urchin
Heliocidaris erythrogramma
. Sea urchins were gradually introduced to four combinations of temperature and pH
NIST
(17°C/pH 8.15, 17°C/pH 7.6, 23°C/pH 8.15 and 23°C/pH 7.6) and then held in temperature–pH treatments for 1, 15 or 30 days to determine if the immune response would adjust to stressors over time. Coelomocyte concentration and type, phagocytic capacity and bactericidal activity were measured on day 1, 15 and 30 with different sea urchins used each time. At each time point, the coelomic fluid of individuals exposed to increased temperature and acidification had the lowest coelomocyte concentrations, exhibited lower phagocytic capacities and was least effective at inhibiting bacterial growth of the pathogen
Vibrio anguillarum
. Over time, increased temperature alleviated the negative effects of acidification on phagocytic activity. Our results demonstrate the importance of incorporating acclimation time to multiple stressors when assessing potential responses to future ocean conditions and indicate that the immune response of
H. erythrogramma
may be compromised under near-future ocean warming and acidification.
hdnom: Building Nomograms for Penalized Cox Models with High-Dimensional Survival Data
Authors: Xiao Nan , Xu Qing-Song , Li Miao-Zhu
Published: August 2016

We developed hdnom, an R package for survival modeling with high-dimensional data. The package is the first free and open-source software package that streamlines the workflow of penalized Cox model building, validation, calibration, comparison, and nomogram visualization, with nine types of penalized Cox regression methods fully supported. A web application and an online prediction tool maker are offered to enhance interac-tivity and flexibility in high-dimensional survival analysis.

Availability

The hdnom R package is available from CRAN:https://cran.r-project.org/package=hdnomunder GPL. The hdnom web application can be accessed athttp://hdnom.io. The web application maker is available fromhttp://hdnom.org/appmaker. The hdnom project website:http://hdnom.org.

Contact

qsxu@csu.edu.cnormiaozhu.li@duke.edu
Using null models to infer microbial co-occurrence networks
Authors: Connor Nora , Barberán Albert , Clauset Aaron
Published: August 2016

Although microbial communities are ubiquitous in nature, relatively little is known about the structural and functional roles of their constituent organisms’ underlying interactions. A common approach to study such questions begins with extracting a network of statistically significant pairwise co-occurrences from a matrix of observed operational taxonomic unit (OTU) abundances across sites. The structure of this network is assumed to encode information about ecological interactions and processes, resistance to perturbation, and the identity of keystone species. However, common methods for identifying these pairwise interactions can contaminate the network with spurious patterns that obscure true ecological signals. Here, we describe this problem in detail and develop a solution that incorporates null models to distinguish ecological signals from statistical noise. We apply these methods to the initial OTU abundance matrix and to the extracted network. We demonstrate this approach by applying it to a large soil microbiome data set and show that many previously reported patterns for these data are statistical artifacts. In contrast, we find the frequency of three-way interactions among microbial OTUs to be highly statistically significant. These results demonstrate the importance of using appropriate null models when studying observational microbiome data, and suggest that extracting and characterizing three-way interactions among OTUs is a promising direction for unraveling the structure and function of microbial ecosystems.

Author Summary

Microbes are ubiquitous in the environment. We know that microbial communities – the groups of microbes that live together, interact, and depend on one another – vary across environments. Multiple processes, ranging from competition between microbes to environmental stress, are believed to alter microbial community composition. Here, we describe a set of statistical techniques that can more accurately identify the underlying taxa relationships that structure the observed abundances of microbes across habitats. Using a large data set of soil samples collected across North and South America, we both illustrate the statistical artifacts that incorrect methods can introduce and describe proper techniques based on appropriate null models for studying how the abundances of taxa vary across soil samples. These tools improve our ability to distinguish ecologically meaningful interactions from simple statistical noise in such observational data. Our application of these tools suggests some previous claims about the network structure of microbial communities may be statistical artifacts. Furthermore, we find that three-way interactions among microbial taxa are significantly more common than we would expect at random, and thus may provide a novel means for identifying ecologically meaningful interactions.
Simulations of biomass dynamics in community food webs
Authors: Delmas Eva , Brose Ulrich , Gravel Dominique , Stouffer Daniel B. , Poisot Timothée
Published: August 2016

Food webs are the backbone upon which biomass flows through ecosystems. Dynamical models of biomass can reveal how the structure of food webs is involved in many key ecosystem properties, such as persistence, stability, etc.

In this contribution, we present BioEnergeticFoodWebs, an implementation of Yodzis & Innes (1992) bio-energetic model, in the high-performance computing language Julia.

We illustrate how this package can be used to conduct numerical experiments in a reproducible and standard way.

A reference implementation of this widely used model will ease reproducibility and comparison of results across studies.