bluuebunny/crossref_metadata_2025 huggingface dataset:
Palladium-Catalyzed Selective Synthesis of 3-Hydroxy-2-oxindoles via Cascade C–H Cycloaddition and Oxidation of α-Aminoaceto­phenones
Authors: Tang Ri-Yuan , Zheng Wen-Xu , Liao Yan-Yan , Xu Li
Published: August 2018

A novel method for the synthesis of 3-hydroxy-2-oxindole (3-hydroxyindolin-2-one) derivatives by palladium-catalyzed tandem C–H cycloaddition and oxidation of α-aminoacetophenone has been developed. In the presence of Pd(OAc)2 and AgOAc, a variety of 3-hydroxy-2-oxindoles were synthesized in moderate yields. Control experiments show that the selective cycloaddition occurs prior to the oxidation is crucial for this successful chemical transformation.
Antibiotic Susceptibility Profile of ‘Vibrio Cholerae O1 Biotype El Tor Serotype Ogawa’ Outbreak in North Delhi, India
Authors: Jena Pragnya , Sharma Abha , Duggal Shalini , Bharara Tanisha , Gur Renu
Published: August 2018

Background Cholera remains a public health issue, especially in developing countries. We report a cholera outbreak in North Delhi.

Objective To report the causative agent of outbreak and to characterize, biotype, and analyze antimicrobial resistance pattern of V. cholerae isolated from cholera patients admitted to our hospital. The outbreak occurred from July 2016 to August 2016.

Materials and Methods A total of 179 stool samples from pediatrics department were received and processed according to the current Clinical and Laboratory Standards Institute (CLSI) guidelines.

Results Out of 179 stool samples received by the laboratory, 26 samples grew Vibrio cholerae O1 Biotype El Tor. Cefotaxime and ceftriaxone were the most sensitive drugs. All isolates were resistant to cotrimoxazole followed by tetracycline.

Conclusion According to the World Health Organization (WHO), cholera is becoming endemic in Delhi. Emergence of multiple antibiotic-resistant cholera isolates is a concern. Prompt identification and notification of cholera are the key measures to avert cholera outbreak. Clean water supply and improved sanitation measures should be taken for prevention of cholera.
A self-activated MgGa2O4 for persistent luminescence phosphor
Authors: Jiang Bin , Chi Fengfeng , Wei Xiantao , Chen Yonghu , Yin Min
Published: August 2018

The spinel compound MgGa2O4 synthesized by a high temperature solid state reaction method exhibits a long and bright blue persistent luminescence with UV source excitation. The blue afterglow can be observed by naked eyes in the dark for at least 10 min. The photoluminescence spectra of the MgGa2O4 host reveal a broad emission band in the range of 325–650 nm with the main peak at 424 nm and the secondary weaker peak at 480 nm under 265 nm excitation. The thermoluminescence curve disclosed a broad distribution of the traps existent in the MgGa2O4 host. In addition, a systematic investigation about the photoluminescence and the thermoluminescence of Mn2+ or Cr3+ single doped MgGa2O4 was also conducted to examine the doping effect. It is found that the distribution of traps responsible for thermoluminescence was disturbed significantly by different doping. A mechanism of the emission and the persistent luminescence is proposed in the light of the comparison of the results of the undoped host and the doped samples. The results indicate that the various vacancy defects in the MgGa2O4 host play an important role in its persistent luminescence.
Cherenkov radiation-based optical fibre diagnostics of fast electrons generated in intense laser-plasma interactions
Authors: Liu H. , Liao G.-Q. , Zhang Y.-H. , Zhu B.-J. , Zhang Z. , Li Y.-T. , Scott G. G. , Rusby D. R. , Armstrong C. , Zemaityte E. , Carroll D. C. , Astbury S. , Bradford P. , Woolsey N. C. , McKenna P. , Neely D.
Published: August 2018

Diagnosing fast electrons is important to understand the physics underpinning intense laser-produced plasmas. Here, we demonstrate experimentally that a Cherenkov radiation-based optical fibre can serve as a reliable diagnostic to characterize the fast electrons escaping from solid targets irradiated by ultra-intense laser pulses. Using optical fibre loops, the number and angular distributions of the escaping electrons are obtained. The data agree well with measurements made using image plate stacks. The optical fibre can be operated at high-repetition rates and is insensitive to x-rays and ion beams, which makes it advantageous over other routinely used fast electron diagnostics in some aspects.
The dynamics of knowledge acquisition via self-learning in complex networks
Authors: Lima Thales S. , de Arruda Henrique F. , Silva Filipi N. , Comin Cesar H. , Amancio Diego R. , Costa Luciano da F.
Published: August 2018

Studies regarding knowledge organization and acquisition are of great importance to understand areas related to science and technology. A common way to model the relationship between different concepts is through complex networks. In such representations, networks’ nodes store knowledge and edges represent their relationships. Several studies that considered this type of structure and knowledge acquisition dynamics employed one or more agents to discover node concepts by walking on the network. In this study, we investigate a different type of dynamics adopting a single node as the “network brain.” Such a brain represents a range of real systems such as the information about the environment that is acquired by a person and is stored in the brain. To store the discovered information in a specific node, the agents walk on the network and return to the brain. We propose three different dynamics and test them on several network models and on a real system, which is formed by journal articles and their respective citations. The results revealed that, according to the adopted walking models, the efficiency of self-knowledge acquisition has only a weak dependency on topology and search strategy.
Three-dimensional phase field modeling of inhomogeneous gas-liquid systems using the PeTS equation of state
Authors: Diewald Felix , Heier Michaela , Horsch Martin , Kuhn Charlotte , Langenbach Kai , Hasse Hans , Müller Ralf
Published: August 2018

Recently, an equation of state (EoS) for the Lennard-Jones truncated and shifted (LJTS) fluid has become available. As it describes metastable and unstable states well, it is suited for predicting density profiles in vapor-liquid interfaces in combination with density gradient theory (DGT). DGT is usually applied to describe interfaces in Cartesian one-dimensional scenarios. In the present work, the perturbed LJ truncated and shifted (PeTS) EoS is implemented into a three-dimensional phase field (PF) model which can be used for studying inhomogeneous gas-liquid systems in a more general way. The results are compared with the results from molecular dynamics simulations for the LJTS fluid that are carried out in the present work and good agreement is observed. The PF model can therefore be used to overcome the scale limit of molecular simulations. A finite element approach is applied for the implementation of the PF model. This requires the first and second derivatives of the PeTS EoS which are calculated using hyper-dual numbers. Several tests and examples of applications of the new PeTS PF model are discussed.
Gain-guided X-ray free-electron laser oscillator
Authors: Li Kai , Deng Haixiao
Published: August 2018

The X-ray free-electron laser oscillator (XFELO) has recently come to be reconsidered as a promising candidate for producing high-brightness, fully coherent pulses in the hard X-ray regime. This letter proposes a gain-guided XFELO scheme, without the need for the external focusing elements that are required in a conventional configuration. Self-consistent theoretical analysis and three-dimensional numerical simulation results verify that the X-ray transverse mode in such an “unstable” cavity is stable and robust owing to electron beam gain-guiding. The output pulse energy and the transverse and longitudinal coherence are comparable to those from conventional XFELOs. This promising scheme is expected to contribute significantly to the construction and operation of a real XFELO.
Imaging in-plane 90° magnetization switching in a (Ga,Mn)As epitaxial layer
Authors: Al-Qadi B. , Sakatoku Y. , Nishizawa N. , Munekata H.
Published: August 2018

The dynamics associated with in-plane, 90° magnetization switching in a (Ga,Mn)As epitaxial layer is studied on the basis of images obtained using a home-made magneto-optical microscope. A small contrast between two different 90° domains caused by magnetic birefringence (MB) is enhanced by digital image processing. Two consecutive 90° switchings are captured clearly in temperature regimes below and above the half-value of the Curie temperature. The dynamics is not the same for the first and the second switching, presumably reflecting the influence of the ⟨110⟩ uniaxial anisotropy and spin-dependent pinning sites. In particular, in the low-temperature regime, the first switching that passes via the relatively easy uniaxial (REU) axis (the [1–10] axis) is dominated by smooth 90° domain wall (DW) motion, whereas the second switching that passes via the relatively hard uniaxial (RHU) axis (the [110] axis) occurs through nucleation and coalescence of 90° domains together with the DW motion. In the high-temperature regime, the first switching via the REU axis is initiated by nucleations and their rapid expansion, whereas the second switching via the RHU axis is dominated by relatively slow DW motion. DW velocity is extracted from MB images and analyzed on the basis of thermally activated depinning and flow models. The values of two key parameters, namely, the activation volume and DW mobility, are deduced and compared with values from the literature. They are (28 nm)3 and 0.35 nm s−1 Oe at 10 K, respectively.
The aerodynamic stability of a new type of Multi-tower cable-stayed bridge with rhombic stiffening cables
Authors: Wang Xiaowei , Li Yingmin , Song Weiju
Published: August 2018

Aerodynamic stability is an important problem in the design and research of long-span multi-tower cable-stayed Bridges. The three-dimensional nonlinear aerodynamic stability analysis method is used to qualitatively analyze the aerodynamic stability of a new type of rhombic stiffened cable-stayed bridge in this paper, and compared with conventional cable-stayed bridges. The results show that the new rhombus stiffener can greatly increase the longitudinal stiffness of the structure and reduce the vibration period of the structure. The maximum lateral displacement, vertical displacement and torsion Angle of the structure under wind load are reduced, and the critical unstable wind speed of the structure is increased. It can be seen that the aerodynamic stability of the new type of rhombus cable-stayed bridge is better than conventional cable-stayed bridge.
An adaptive variational procedure for a two-phase model with variable density and viscosity
Authors: Yang Min
Published: August 2018

In this paper we present an adaptive variational procedure to solve a two-phase field model with variable density, viscosity. The model is a couple system that consists of incompressible Navier-Stokes equations and Allen-Cahn equation. In the scheme the projection method based on pressure is used to deal with the Navier-Stokes equations and stabilization approach is used for the Allen-Cahn equation. By some subtle explicit-implicit treatments, the proposed scheme is energy stable. In particular the adaptive refinement/coarsening is carried out by evaluating the residual error indicators on the error estimates of the Allen-Cahn equation. Some numerical examples are performed to show the accuracy and efficiency.
Four-variable expanders over the prime fields
Authors: Koh Doowon , Mojarrad Hossein , Pham Thang , Valculescu Claudiu
Published: August 2018

Let

F

p

\mathbb {F}_p

be a prime field of order

p
>
2

p>2

, and let

A
A

be a set in

F

p

\mathbb {F}_p

with very small size in terms of

p
p

. In this note, we show that the number of distinct cubic distances determined by points in

A
×
A

A\times A

satisfies
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartAbsoluteValue left-parenthesis upper A minus upper A right-parenthesis cubed plus left-parenthesis upper A minus upper A right-parenthesis cubed EndAbsoluteValue much-greater-than StartAbsoluteValue upper A EndAbsoluteValue Superscript 8 slash 7 Baseline comma">

|

(
A
−
A

)
3

+
(
A
−
A

)
3

|

≫

|

A

|

8

/

7

,

|(A-A)^3+(A-A)^3|\gg |A|^{8/7},

\]
which improves a result due to Yazici, Murphy, Rudnev, and Shkredov. In addition, we investigate some new families of expanders in four and five variables. We also give an explicit exponent of a problem of Bukh and Tsimerman, namely, we prove that
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="max left-brace right-brace comma vertical-bar vertical-bar plus plus AA comma vertical-bar vertical-bar of ff left-parenthesis right-parenthesis comma upper A comma upper A much-greater-than StartAbsoluteValue upper A EndAbsoluteValue Superscript 6 slash 5 Baseline comma">

max

{

|

A
+
A

|

,

|

f
(
A
,
A
)

|

}

≫

|

A

|

6

/

5

,

\max \left \lbrace |A+A|, |f(A, A)|\right \rbrace \gg |A|^{6/5},

\]
where

f
(
x
,
y
)

f(x, y)

is a quadratic polynomial in

F

p

[
x
,
y
]

\mathbb {F}_p[x, y]

that is not of the form

g
(
α
x
+
β
y
)

g(\alpha x+\beta y)

for some univariate polynomial

g
g

.
Mechanoimmunology: molecular-scale forces govern immune cell functions
Authors: Pageon Sophie V. , Govendir Matt A. , Kempe Daryan , Biro Maté
Published: August 2018

Immune cell recognition of antigens is a pivotal process in initiating immune responses against injury, pathogens, and cancers. Breakthroughs over the past decade support a major role for mechanical forces in immune responses, laying the foundation for the emerging field of mechanoimmunology. In this Perspective, we discuss the mechanical forces acting at the level of ligand–receptor interactions and how they underpin receptor triggering, signal initiation, and immune cell activation. We also highlight the novel biophysical tools and advanced imaging techniques that have afforded us the recent progress in our understanding of the role of forces in immune cell functions.
Dietary Phosphorus and Ambulatory Blood Pressure in African Americans: The Jackson Heart Study
Authors: Olivo Robert E , Hale Sarah L , Diamantidis Clarissa J , Bhavsar Nrupen A , Tyson Crystal C , Tucker Katherine L , Carithers Teresa C , Kestenbaum Bryan , Muntner Paul , Tanner Rikki M , Booth John N , Mwasongwe Stanford E , Pendergast Jane , Boulware L Ebony , Scialla Julia J
Published: August 2018

BACKGROUND

Higher dietary phosphorus is associated with left ventricular hypertrophy and mortality, which are blood pressure (BP)-related outcomes. For this reason, we hypothesized that dietary phosphorus may be associated with adverse clinic and ambulatory BP patterns.

METHODS

Our study included 973 African American adults enrolled in the Jackson Heart Study (2000–2004) with 24-hour ambulatory BP monitoring (ABPM) data at baseline. We quantified dietary phosphorus from a validated Food Frequency Questionnaire as follows: (i) absolute daily intake, (ii) ratio of phosphorus-to-protein intake, (iii) phosphorus density, and (iv) energy-adjusted phosphorus intake. Using multivariable linear regression, we determined associations between dietary phosphorus intake and systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure in clinic and over daytime, nighttime, and 24-hour periods from ABPM. Extent of nocturnal BP dipping was also assessed. Using logistic regression, we modeled relationships between dietary phosphorus intake and clinically relevant qualitative BP phenotypes, such as masked, sustained, or white-coat hypertension and normotension.

RESULTS

There were no statistically significant associations between phosphorus intake and SBP or pulse pressure in adjusted models. Most metrics of higher phosphorus intake were associated with lower daytime, nighttime, and clinic DBP. Higher phosphorus intake was not associated with clinic or ABPM-defined hypertension overall, but most metrics of higher phosphorus intake were associated with lower odds of sustained hypertension compared to sustained normotension, white-coat hypertension, and masked hypertension. There were no associations between dietary phosphorus and nocturnal BP dipping.

CONCLUSIONS

These data do not support a role for higher phosphorus intake and higher BP in African Americans.
On entropy and information in gene interaction networks
Authors: Wallace Z S , Rosenthal S B , Fisch K M , Ideker T , Sasik R
Published: August 2018

Motivation

Modern biological experiments often produce candidate lists of genes presumably related to the studied phenotype. One can ask if the gene list as a whole makes sense in the context of existing knowledge: Are the genes in the list reasonably related to each other or do they look like a random assembly? There are also situations when one wants to know if two or more gene sets are closely related. Gene enrichment tests based on counting the number of genes two sets have in common are adequate if we presume that two genes are related only when they are in fact identical. If by related we mean well connected in the interaction network space, we need a new measure of relatedness for gene sets.

Results

We derive entropy, interaction information and mutual information for gene sets on interaction networks, starting from a simple phenomenological model of a living cell. Formally, the model describes a set of interacting linear harmonic oscillators in thermal equilibrium. Because the energy function is a quadratic form of the degrees of freedom, entropy and all other derived information quantities can be calculated exactly. We apply these concepts to estimate the probability that genes from several independent genome-wide association studies are not mutually informative; to estimate the probability that two disjoint canonical metabolic pathways are not mutually informative; and to infer relationships among human diseases based on their gene signatures. We show that the present approach is able to predict observationally validated relationships not detectable by gene enrichment methods. The converse is also true; the two methods are therefore complementary.

Availability and implementation

The functions defined in this paper are available in an R package, gsia, available for download at https://github.com/ucsd-ccbb/gsia.
isiKnock: in silico knockouts in signaling pathways
Authors: Hannig Jennifer , Giese Heiko , Schweizer Börje , Amstein Leonie , Ackermann Jörg , Koch Ina
Published: August 2018

isiKnock is a new software that automatically conducts in silico knockouts for mathematical models of signaling pathways. The software allows for the prediction of the behavior of biological systems after single or multiple knockout. The implemented algorithm applies transition invariants and the novel concept of Manatee invariants. A knockout matrix visualizes the results. The tool enables the analysis of dependencies, for example, in signal flows from the receptor activation to the cell response at steady state.

Availability and implementation

isiKnock is an open-source tool, freely available at http://www.bioinformatik.uni-frankfurt.de/tools/isiKnock/. It requires at least Java 8 and runs under Microsoft Windows, Linux, and Mac OS.
The effect of monoamines reuptake inhibitors on aerobic exercise performance in bank voles from a selection experiment
Authors: Jaromin Ewa , Sadowska Edyta T , Koteja Paweł
Published: August 2018

Exercise performance depends on both physiological abilities (e.g., muscle strength) and behavioral characteristics (e.g., motivation). We tested the hypothesis that evolution of increased aerobic exercise performance can be facilitated by evolution of neuropsychological mechanisms responsible for motivation to undertake physical activity. We used a unique model system: lines of bank voles Myodes glareolus selected for high swim-induced aerobic metabolism (“aerobic” A lines). In generation 21, voles from the 4 A lines achieved a 57% higher “voluntary maximum” swim-induced aerobic metabolism (VO2swim) than voles from 4 unselected, “control” C lines. In C lines, VO2swim was 9% lower than the maximum forced-exercise aerobic metabolism (VO2run; P = 0.007), while in A lines it was even higher than VO2run, although not significantly (4%, P = 0.15). Thus, we hypothesized that selection changed both the aerobic capacity and the neuronal mechanisms behind motivation to undertake activity. We investigated the influence of reuptake inhibitors of dopamine (DARI), serotonin (SSRI), and norepinephrine (NERI) on VO2swim. The drugs decreased VO2swim both in C and A lines (% decrease compared with saline: DARI 8%, P < 0.001; SSRI 6%, P < 0.001; NERI 8%, P < 0.001), but the proportional response differed between selection directions only for NERI (stronger effect in C lines: P = 0.008) and the difference was marginally non-significant for SSRI (P = 0.07) and DARI (P = 0.06). Thus, the results suggest that all the 3 monoamines are involved in signaling pathways controlling the motivation to be active and that norepinephrine could have played a role in the evolution of increased aerobic exercise performance in our animal model.
Implementation of the Stopping Elderly Accidents, Deaths, and Injuries Initiative in Primary Care: An Outcome Evaluation
Authors: Johnston Yvonne A , Bergen Gwen , Bauer Michael , Parker Erin M , Wentworth Leah , McFadden Mary , Reome Chelsea , Garnett Matthew
Published: August 2018

Background and Objectives

Older adult falls pose a growing burden on the U.S. health care system. The Centers for Disease Control and Prevention’s Stopping Elderly Accidents, Deaths, and Injuries (STEADI) initiative was developed as a multifactorial approach to fall prevention that includes screening for fall risk, assessing for modifiable risk factors, and prescribing evidence-based interventions to reduce fall risk. The purpose of this study was to determine the impact of a STEADI initiative on medically treated falls within a large health care system in Upstate New York.

Research Design and Methods

This cohort study classified older adults who were screened for fall risk into 3 groups: (a) At-risk and no Fall Plan of Care (FPOC), (b) At-risk with a FPOC, and (c) Not-at-risk. Poisson regression examined the group’s effect on medically treated falls when controlling for other variables. The sample consisted of 12,346 adults age 65 or older who had a primary care visit at one of 14 outpatient clinics between September 11, 2012, and October 30, 2015. A medically treated fall was defined as a fall-related treat-and-release emergency department visit or hospitalization.

Results

Older adults at risk for fall with a FPOC were 0.6 times less likely to have a fall-related hospitalization than those without a FPOC (p = .041), and their postintervention odds were similar to those who were not at risk.

Discussion and Implications

This study demonstrated that implementation of STEADI fall risk screening and prevention strategies among older adults in the primary care setting can reduce fall-related hospitalizations and may lower associated health care expenditures.
A Framework of Minority Stress: From Physiological Manifestations to Cognitive Outcomes
Authors: Forrester Sarah N , Gallo Joseph J , Whitfield Keith E , Thorpe Roland J
Published: August 2018

Cognitive impairment and dementia continue to threaten the aging population. Although no one is immune, certain groups, namely black older persons, are more likely to have a diagnosis of certain dementias. Because researchers have not found a purely biological reason for this disparity, they have turned to a biopsychosocial model. Specifically, black persons in the United States are more likely to live with social conditions that affect their stress levels which in turn affect physiological regulation leading to conditions that result in higher levels of cognitive impairment or dementia. Here we discuss some of these social conditions such as discrimination, education, and socioeconomic status, and how physiological dysregulation, namely allostatic load that can lead to cognitive impairment and dementia in black persons especially.
Impacts of a multi-trap line on benthic habitat containing emergent epifauna within the Mid-Atlantic Bight
Authors: Schweitzer Cara C , Lipcius Romuald N , Stevens Bradley G
Published: August 2018

Alteration and degradation of benthic structure by fishing gear can impede efforts to manage fish stock sustainably. Although the impacts of mobile gear are well known, effects of passive gear (e.g. fish traps) upon structure have been little studied. We modified commercial traps for American lobster Homarus americanus and black sea bass Centropristis striata by attaching GoPro® cameras to ascertain the degree and nature of impacts to seafloor habitats. Customized traps were included within a line of 20 traps, deployed and retrieved according to standard commercial fishing practice. Less than 5% of traps landed directly on bedforms when deployed. However, during retrieval traps dragged along the ocean floor, increasing trap–habitat contact rate to 50%, and causing traps to collide with corals, bryozoans, and other epifauna. Drag time of traps depended on the position in the trap line. Experimentally extending the trap line reduced drag time during retrieval for traps near the distal end of the line. Our results show that impacts of commercial trap fishing can be substantial during trap retrieval, and that the impact depends on their location on a trap line. Fishing practices should be developed that minimize effects of trap retrieval on structural benthic habitat.
Exponential Sums Over Finite Fields and the Large Sieve
Authors: Perret-Gentil Corentin
Published: August 2018

By using a variant of the large sieve for Frobenius in compatible systems developed in [24] and [27], we obtain zero-density estimates for arguments of $\ell $-adic trace functions over finite fields with values in some algebraic subsets of the cyclotomic integers, when the monodromy groups are known. This applies in particular to hyper-Kloosterman sums and general exponential sums considered by Katz.
Towards Evidence-Based Guidelines in Neurological Surgery
Authors: Shank Christopher D , Lepard Jacob R , Walters Beverly C , Hadley Mark N
Published: August 2018

Neurological surgery practice is based on the science of balancing probabilities. A variety of clinical guidance documents have influenced how we collectively practice our art since the early 20th century. The quality of the science within these guidelines varies widely, as does their utility in positively shaping our practice.

The guidelines development process in neurological surgery has evolved significantly over the last 30 yr. Historically based in expert opinion, as a specialty we have increasingly relied on objective medical evidence to guide our clinical practice. We assessed the changing practice guidelines development process and the impact of scientifically robust guidelines on patient care.

The evolution of the guidelines development process in neurological surgery was chronicled. Several subspecialty guidelines were extracted and reviewed in detail. Their impact on practice patterns was evaluated. The importance of evidence-based research and practice guidelines development was discussed.

Evidence-based practice guidelines serve to chronicle multiple acceptable treatment options and help us move towards more standardized care for specific disease processes. They help refute false “standards of care.” Guidelines-based care supported by solid medical evidence has the potential to streamline patient care and improve patient outcomes. The guidelines development process identifies areas, issues, and strategies for which little medical evidence exists, as well as topics that need focused scientific investigation and future study.

The production of evidence-based practice recommendations is a vital part of furthering our specialty. Guidelines development advances our science, augments the resident education process, and protects our practice from undue external influence.
Quitting Failure and Success With and Without Using Medication: Latent Classes of Abstinence and Adherence to Nicotine Monotherapy, Combination Therapy, and Varenicline
Authors: McCarthy Danielle E , Versella Mark V
Published: August 2018

Introduction

Nonadherence to pharmacotherapies complicates studies of comparative pharmacotherapy effectiveness. Modeling adherence and abstinence simultaneously may facilitate analysis of both treatment acceptability and effectiveness.

Methods

Secondary analyses of a three-arm randomized comparative trial of nicotine patch, varenicline, and combination nicotine patch and lozenge among adult daily smokers (N = 1086) were conducted. Adherence rates collected via interactive voice response systems during the first 27 days of quitting were compared across treatment conditions. Repeated measures latent class analyses of adherence and abstinence in 3-day parcels through 27 days of a quit attempt were conducted with treatment, demographic, and smoking history covariates.

Results

Adherence varied across treatments and was lowest for nicotine lozenge use in combination nicotine replacement therapy (NRT). Five latent classes that differed significantly in 6-month abstinence rates were retained, including three subgroups of adherent participants varying in treatment response and two nonadherent groups varying in abstinence probabilities. Nonadherence was more likely among those receiving varenicline and combination NRT, relative to patch monotherapy. Varenicline and combination NRT did not promote abstinence among adherent latent classes but did promote abstinence among those partially adherent, relative to patch alone. Combination therapy attenuated increased risk of treatment disengagement with more years smoking. Minority smokers, those high in dependence, and those with shorter past abstinence were at increased risk for low-adherence and low-abstinence latent classes.

Conclusions

Varenicline and combination nicotine patch and lozenge are less likely to be used as directed and may not increase first-month abstinence better than patch alone when taken adherently.

Implications

This secondary analysis of adherence and abstinence in a comparative effectiveness trial shows that adherence is highest for the nicotine patch, next highest for varenicline, and lowest for combination nicotine patch and lozenge therapy due to low lozenge use. Distinct latent classes were found that varied in both first-month abstinence and adherence. Varenicline and combination NRT may not enhance abstinence over patch alone among smokers who take medication adherently. Adherent use of medication especially benefits those who are low in dependence and have positive quitting histories; it is less beneficial to at-risk smokers and members of racial minorities.
Multiple Aneurysms Clipping Through the Eyebrow Approach: 2-Dimensional Operative Video
Authors: Aldea Sorin , Gaillard Stephan
Published: August 2018

The eyebrow approach is a versatile technique that may apply to various vascular and tumoral pathologies of the anterior skull base. We present a case of multiple aneurysms clipping through the eyebrow approach and we discuss the nuances of this technique. A 44-yr-old patient presented with incidentally found aneurysms. Angiography showed 2 4.5-mm aneurysms on the left middle cerebral artery (MCA) and internal carotid artery (ICA) bifurcations. At surgery, the patient is positioned supine with the head elevated, slightly rotated, and extended in order to obtain good access and gravity retraction of the brain. A 3-cm incision is placed in the eyebrow and a small supraorbital bone flap is raised. The floor of the orbit and the edges of the craniotomy are thoroughly drilled in order to maximize the working space. After dural opening, the sylvian fissure was widely dissected and the MCA aneurysm was identified. A large opening of the sylvian and carotid cistern allows retractor free surgery. The ICA bifurcation aneurysm is then dissected and clipped. The MCA aneurysm is treated last in order to avoid a conflict between instruments especially during clipping. Aneurysms occlusion and vessel permeability is verified by Doppler ultrasonography and indocyanine green (ICG) angiography. After achieving hemostasis, the dura is closed and a subcuticular continuous suture is used at the skin. The postoperative course was uneventful. The eyebrow approach allows simultaneous treatment of multiple aneurysms of the anterior circle of Willis in selected cases. Proper positioning, drilling of the orbital floor and extensive arachnoid dissection are the key steps of this procedure.
Expanding the toolbox for Synechocystis sp. PCC 6803: validation of replicative vectors and characterization of a novel set of promoters
Authors: Ferreira Eunice A , Pacheco Catarina C , Pinto Filipe , Pereira José , Lamosa Pedro , Oliveira Paulo , Kirov Boris , Jaramillo Alfonso , Tamagnini Paula
Published: August 2018

Cyanobacteria are promising ‘low-cost’ cell factories since they have minimal nutritional requirements, high metabolic plasticity and can use sunlight and CO2 as energy and carbon sources. The unicellular Synechocystis sp. PCC 6803, already considered the ‘green’ Escherichia coli, is the best studied cyanobacterium but to be used as an efficient and robust photoautotrophic chassis it requires a customized and well-characterized toolbox. In this context, we evaluated the possibility of using three self-replicative vectors from the Standard European Vector Architecture (SEVA) repository to transform Synechocystis. Our results demonstrated that the presence of the plasmid does not lead to an evident phenotype or hindered Synechocystis growth, being the vast majority of the cells able to retain the replicative plasmid even in the absence of selective pressure. In addition, a set of heterologous and redesigned promoters were characterized exhibiting a wide range of activities compared to the reference PrnpB, three of which could be efficiently repressed. As a proof-of-concept, from the expanded toolbox, one promoter was selected and assembled with the ggpS gene [encoding one of the proteins involved in the synthesis of the native compatible solute glucosylglycerol (GG)] and the synthetic device was introduced into Synechocystis using one of the SEVA plasmids. The presence of this device restored the production of the GG in a ggpS deficient mutant validating the functionality of the tools/device developed in this study.
Differentiation of diabetic foot ulcer–derived induced pluripotent stem cells reveals distinct cellular and tissue phenotypes
Authors: Kashpur Olga , Smith Avi , Gerami-Naini Behzad , Maione Anna G. , Calabrese Rossella , Tellechea Ana , Theocharidis Georgios , Liang Liang , Pastar Irena , Tomic-Canic Marjana , Mooney David , Veves Aristidis , Garlick Jonathan A.
Published: August 2018

Diabetic foot ulcers (DFUs) are a major complication of diabetes, and there is a critical need to develop novel cell‐ and tissue‐based therapies to treat these chronic wounds. Induced pluripotent stem cells (iPSCs) offer a replenishing source of allogeneic and autologous cell types that may be beneficial to improve DFU wound‐healing outcomes. However, the biologic potential of iPSC‐derived cells to treat DFUs has not, to our knowledge, been investigated. Toward that goal, we have performed detailed characterization of iPSC‐derived fibroblasts from both diabetic and nondiabetic patients. Significantly, gene array and functional analyses reveal that iPSC‐derived fibroblasts from both patients with and those without diabetes are more similar to each other than were the primary cells from which they were derived. iPSC‐derived fibroblasts showed improved migratory properties in 2‐dimensional culture. iPSC‐derived fibroblasts from DFUs displayed a unique biochemical composition and morphology when grown as 3‐dimensional (3D), self‐assembled extracellular matrix tissues, which were distinct from tissues fabricated using the parental DFU fibroblasts from which they were reprogrammed. In vivo transplantation of 3D tissues with iPSC‐derived fibroblasts showed they persisted in the wound and facilitated diabetic wound closure compared with primary DFU fibroblasts. Taken together, our findings support the potential application of these iPSC‐derived fibroblasts and 3D tissues to improve wound healing.—Kashpur, O., Smith, A., Gerami‐Naini, B., Maione, A. G., Calabrese, R., Tellechea, A., Theocharidis, G., Liang, L., Pastar, I., Tomic‐Canic, M., Mooney, D., Veves, A., Garlick, J. A. Differentiation of diabetic foot ulcer–derived induced pluripotent stem cells reveals distinct cellular and tissue phenotypes. FASEB J. 33, 1262–1277 (2019). www.fasebj.org
Health Information Counselors: A New Profession for the Age of Big Data
Authors: Fiske Amelia , Buyx Alena , Prainsack Barbara
Published: August 2018

Health care is increasingly data driven. Concurrently, there are concerns that health professionals lack the time and training to guide patients through the growing medical “data jungle.” In the age of big data, ever wider domains of people’s lives are “datafied,” which renders ever more information—at least in principle—usable for health care purposes. Turning data into meaningful information for clinical practice—and deciding what data or information should not be used for this purpose—requires a significant amount of time, resources, and skill. The authors argue that academic medicine should lead the way in navigating the use of complex, highly personal data in clinical practice. To make data actionable for both clinicians and patients, the authors propose that the best way to navigate the interface between patients and providers in the era of data-rich medicine would be the creation of a new profession entirely: health information counselors (HICs). HICs would have broad knowledge of various kinds of health data and data quality evaluation techniques, as well as analytic skills in statistics and data interpretation. Trained also in interpersonal communication, health management, insurance systems, and medico-legal aspects of data privacy, HICs would know enough about clinical medicine to advise on the relevance of any kind of data for prevention, diagnosis, and treatment. The creation of this new specialty would help patients and health care professionals to make more informed choices about how increasing amounts of health data and information can or should inform health care.
The Incidence, Clinical Features, and a Comparison Between Early and Delayed Onset of Postoperative Spinal Epidural Hematoma
Authors: Anno Masato , Yamazaki Takashi , Hara Nobuhiro , Ito Yusuke
Published: August 2018

Study Design.

A retrospective observational study.

Objective.

To investigate the incidence and clinical features of symptomatic postoperative spinal epidural hematoma (PSEH) with regard to spinal level and to compare early and delayed onset cases.

Summary of Background Data.

PSEH is a serious complication of spinal surgeries. The difference in clinical manifestations between early and delayed PSEH remains unclear.

Methods.

Patients who underwent spinal surgeries between 1999 and 2013 at our institution, were reviewed through their medical records. For patients with PSEH, the incidence, duration to onset, duration from onset to evacuation, symptoms, recovery rate (American Spinal Injury Association grade), neurological outcomes, comorbidities, and preoperative use of anticoagulant drugs were examined. We next compared patients with early onset PSEH (onset until day 3) versus delayed onset (onset day 4 or later) regarding these clinical factors.

Results.

Fourteen patients (0.42%, 14/3371) developed symptomatic PSEH. Initial symptoms were observed between 0 and 7 days (mean 2.6 ± 2.4 d) and almost half (43%, 6/14) occurred during the delayed phase (mean 5.0 ± 1.1 d postsurgery). Paralysis was the predominant symptom in patients with cervical and thoracic surgeries (100%, 6/6), whereas severe pain was most frequent in patients with lumbar procedures (63%, 5/8) (P = 0.019). No significant differences were identified between early and delayed groups. Neurological outcome was good in 10 cases, partial in two cases, and poor in two cases.

Conclusion.

The frequency was consistent in every spinal region, and the symptoms due to PSEH were correlated with spinal level. Almost half the cases were diagnosed after a delay (day 4 or later), which supports the necessity to follow up patients with spinal surgeries more carefully for a week or so and to educate patients and comedical staff about the possibility of delayed hematoma disorders in order not to defer timely intervention.

Level of Evidence: 4
Incidence and Prevalence of Pressure Injuries in Adult Intensive Care Patients: A Systematic Review and Meta-Analysis
Authors: Chaboyer Wendy P. , Thalib Lukman , Harbeck Emma L. , Coyer Fiona M. , Blot Stijn , Bull Claudia F. , Nogueira Paula C. , Lin Frances F.
Published: August 2018

Objectives:

To systematically assess the incidence and prevalence of pressure injuries in adult ICU patients and the most frequently occurring pressure injury sites.

Data Sources:

MEDLINE, Embase, the Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature.

Study Selection:

Observational studies reporting incidence rates, cumulative incidence, and prevalence of pressure injuries.

Data Extraction:

Two reviewers independently screened studies, extracted data, and assessed the risk of bias. Meta-analyses of pooled weighted estimates were calculated using random effect models with 95% CIs reported due to high heterogeneity. Sensitivity analyses included studies that used skin inspection to identify a pressure injury, studies at low risk of bias, studies that excluded stage 1 and each stage of pressure injury.

Data Synthesis:

Twenty-two studies, 10 reporting cumulative incidence of pressure injury irrespective of stage, one reporting incidence rate (198/1,000 hospital-days), and 12 reporting prevalence were included. The 95% CI of cumulative incidence and prevalence were 10.0–25.9% and 16.9–23.8%. In studies that used skin inspection to identify pressure injuries, the 95% CI of cumulative incidence was 9.4–27.5%; all prevalence studies used skin inspection therefore the results were unchanged. In studies assessed as low risk of bias, the 95% CI of cumulative incidence and prevalence were 6.6–36.8% and 12.2–24.5%. Excluding stage 1, the 95% CI of cumulative incidence and prevalence were 0.0–23.8% and 12.4–15.5%. Five studies totalling 406 patients reported usable data on location; 95% CI of frequencies of PIs were as follows: sacrum 26.9–48.0%, buttocks 4.1–46.4%, heel 18.5–38.9%, hips 10.9–15.7%, ears 4.3–19.7%, and shoulders 0.0–40.2%.

Conclusions:

Although well-designed studies are needed to ensure the scope of the problem of pressure injuries is better understood, it is clear prevention strategies are also required.
Epidemiology of Cause of Death in Pediatric Acute Respiratory Distress Syndrome
Authors: Dowell Jasmine C. , Parvathaneni Kaushik , Thomas Neal J. , Khemani Robinder G. , Yehya Nadir
Published: August 2018

Objectives:

Investigations of acute respiratory distress syndrome in adults suggest hypoxemia is an uncommon cause of death. However, the epidemiology of death in pediatric acute respiratory distress syndrome is not well characterized. We aimed to describe the cause, mode, and timing of death in pediatric acute respiratory distress syndrome nonsurvivors. We hypothesized that most deaths would be due to nonpulmonary factors, rather than hypoxemia.

Design:

Retrospective, decedent-only analysis.

Setting:

Two large, academic PICUs.

Patients:

Nonsurvivors with pediatric acute respiratory distress syndrome.

Interventions:

None.

Measurements and Main Results:

Of 798 subjects with pediatric acute respiratory distress syndrome, there were 153 nonsurvivors (19% mortality). Median time to death was 6 days (interquartile range, 3–13 d) after pediatric acute respiratory distress syndrome onset. Patients dying less than 7 days after pediatric acute respiratory distress syndrome onset had greater illness severity and worse oxygenation. Patients dying less than 7 days were more likely to die of a neurologic cause, including brain death. Patients dying greater than or equal to 7 days after pediatric acute respiratory distress syndrome onset were more commonly immunocompromised. Multisystem organ failure predominated in deaths greater than or equal to 7 days. Withdrawal of therapy was the most common mode of death at all timepoints, accounting for 66% of all deaths. Organ dysfunction was common at time of death, irrespective of cause of death. Refractory hypoxemia accounted for only a minority of pediatric acute respiratory distress syndrome deaths (20%).

Conclusions:

In pediatric acute respiratory distress syndrome, early deaths were due primarily to neurologic failure, whereas later deaths were more commonly due to multisystem organ failure. Deaths from neurologic causes accounted for a substantial portion of nonsurvivors. Refractory hypoxemia accounted for only a minority of deaths. Our study highlights limitations associated with using death as an endpoint in therapeutic pediatric acute respiratory distress syndrome trials.
Analysis of Observational Self-matched Data to Examine Acute Triggers of Outcome Events with Abrupt Onset
Authors: Mostofsky Elizabeth , Coull Brent A. , Mittleman Murray A.
Published: August 2018

Several self-matched approaches have been proposed, including case-crossover, case-time control, fixed-effects case-time control, and self-controlled case series. Rather than comparing treatment effects between different individuals, studies use these approaches to evaluate the acute effects of transient exposures, often called “triggers,” by comparing outcome risk among the same individual at different times. This eliminates confounding by between-person characteristics that remain stable over time, allowing for valid analyses even in situations where information on some health behaviors is not available, such as long-term smoking history. However, to attain valid results, differences in the probability of exposure and outcome that change over time must be addressed in the design and analysis of the study. In this article, we describe the setting, assumptions and analytic options for conducting studies using self-matched data. Approaches that involve matching or a group of noncases to address time-varying confounding may have less statistical flexibility but they are powerful tools that overcome the need to assume a particular form of any time trends in potential confounders. If data are available for all of the person–time under study, there is a gain in statistical efficiency and the ability to address time-varying confounding using flexible regression models, under the strong assumption of no mis-specification of the model.
The role of ultrasound in the evaluation of acute pelvic pain in pregnancy and postpartum period: a review
Authors: Park Sung Bin
Published: August 2018

Purpose of review

Acute pelvic pain in pregnant and postpartum patients presents diagnostic and therapeutic challenges. Ultrasound remains the primary imaging modality of choice for assessing pregnant and postpartum women. The purpose of this review is to help practitioners ensure a correct diagnosis of acute pelvic pain in pregnancy and the postpartum period.

Recent findings

This review describes the various causes and highlights the sonographic features and characteristics of acute pelvic pain in pregnancy and the postpartum period.

Evaluation of acute pelvic pain in pregnancy and the postpartum period is challenging. Knowledge of the clinical settings and sonographic features of acute pelvic pain in pregnancy and the postpartum period can lead to accurate diagnosis and appropriate management of the condition.