bluuebunny/crossref_metadata_2025 huggingface dataset:
Stable multi‐player evolutionary game for two‐choice resource allocation problems
Authors: Naghavi Parnia , Kebriaei Hamed , Shah‐Mansouri Vahid
Published: March 2019

The authors consider the problem of multi‐player evolutionary game with two strategies and an arbitrary number of players. A randomised probabilistic access model is considered where the users randomly select the strategies. The strategies are a selection between two radio access technologies to receive service from. For a fair resource allocation between a number of users, the payoff function of each player is considered to be inversely proportional to the number of players choosing a strategy. It is valid for the radio access technology selection problem where resources are divided fairly between the users. The necessary and sufficient conditions for the existence and uniqueness of a mixed Nash equilibrium point of the game is provided. In addition, it is proved that the mixed Nash equilibrium point of the game is globally asymptotically stable and also evolutionarily stable strategy.
Life‐time characteristics of random wound compressed stator windings under thermal stress
Authors: Kulan Mehmet C. , Baker Nick J.
Published: March 2019

Compression of windings is known to give thermal and performance benefits. The aim here is to investigate how the health of stator winding insulation systems are influenced by on‐tooth coil pressing. A set of compressed coils have been aged by exposing them to high temperatures. Winding insulation resistance (IR) was monitored during this process to experimentally validate whether compressed coils remained healthy in terms of electrical insulation. In this case, a single stress (i.e. temperature) model is used to predict the reliability of the compressed coils. Accelerated life tests have been conducted to inspect the life expectancy and thermal endurance of the compressed stator coils. The employed statistical model (Arrhenius‐Weibull) demonstrates that on‐tooth coil pressing reduces the life expectancy dramatically due to reduced turn to ground wall insulation dielectric strength.
Channel‐based antenna synthesis for improved in‐vehicle UWB MB‐OFDM communications
Authors: Sharma Ashwani , Garcia Zuazola Ignacio J. , Martnez Ramón , Perallos Asier , Batchelor John C.
Published: March 2019

Ultra‐wide band (UWB) is an attractive technology for innovative in‐vehicle wireless communications requiring high data rates and multiband orthogonal frequency division multiplexing (MB‐OFDM) a suitable scheme for the accomplishment due to its high performance, low‐power and low‐cost characteristics. To contribute toward improved UWB MB‐OFDM communications inside vehicles, a channel‐based antenna synthesis technique to customise in‐vehicle UWB antennas that reduce ‘blind spots’ in the communication channel is proposed and presented. For the realisation, a comprehensive analysis was utilised and comprised an in‐car channel evaluation including bit‐error‐rate (BER) estimations and radiation pattern‐and‐source syntheses. The channel was measured using a standard antenna to set up the base of the experiments and the distribution of the impulse responses and signal‐to‐noise ratios in the vehicle's passenger plane shown. The currently available IEEE 802.15.3a channel models were perceived unrealistic for the in‐vehicle application and the reason for measuring the channel practically. Using these specific channel measurements, the synthesised pattern is unveiled and consequently the channel‐based antenna synthesis technique used to predict the antenna source. The antenna with optimised pattern‐and‐source showed an improved BER performance compared with the standard antenna in this application; that is, a figure of merit of 37.73% minimised ‘blind spots’.
Carrier sense multiple access with collision avoidance‐aware connectivity quality of downlink broadcast in vehicular relay networks
Authors: Ma Xiaoting , Zhao Junhui , Gong Yi , Sun Xiaoke
Published: March 2019

In vehicular relay networks, the quality of communication link has a significant impact on the stable and reliable communication requirements. Most earlier studies focused on the influence of relay probability on link connectivity while little attention has been paid to the impact of packet collision. In complex mobile scenarios, vehicle density is proportional to relay probability, while proportional to data packet collision probability. Meanwhile, vehicle density and packet collision affect the quality of communication link in the relay network. This condition inspires them to study the link connectivity in vehicular relay networks based on carrier sense multiple access with collision avoidance. First, the relationships among vehicle density, vehicle speed, packet collision probability and relay probability are studied in relay communication. Second, due to the high‐speed movement of vehicles, an analysis model, considering the mobility of vehicle nodes, is conducted to analyse the downlink performance in relay communication networks. Finally, a platoon scheme is proposed to reduce packet collision probability, considering the vehicle density and backoff window size on vehicle‐to‐roadside unit communication. Extensive numerical results indicate that the platoon model has a great advantage in terms of downlink performance, especially in the case of dense traffic flow.
Fully substrate‐integrated dense dielectric patch antenna and array
Authors: Tang Shi‐Chang , Wang Xue‐Ying , Lu Qing‐Yuan , Chen Jian‐Xin
Published: March 2019

Here, a fully substrate‐integrated dense dielectric patch (DDP) antenna and array is proposed. The DDP resonator based on high‐permittivity substrate on the top layer is reasonably constructed and implemented by making full use of the printed circuit board (PCB) technology, whose characteristics are theoretically analysed in detail. Accordingly, the DDP antenna element operating at the dominate TM101 mode (cavity mode) is designed, which is fed by the substrate‐integrated strip line (SISL) through a feeding slot. The slot resonant frequency is close to the TM101 mode of the DDP so that the antenna impedance bandwidth (BW) is extended. For further demonstration, a 1 × 4 array based on the DDP antenna element is designed and fabricated. The simulated and measured results are given, showing good agreement. The impedance BW for |S11| < −10 dB is about 8.4% and the peak gain reaches 11.77 dBi.
Multiple incipient fault classification approach for enhancing the accuracy of dissolved gas analysis (DGA)
Authors: Wani Shufali Ashraf , Gupta Dhawal , Farooque Md. Umar , Khan Shakeb A
Published: March 2019

Multiple incipient faults are practically known to exist in transformers. They tend to produce suddenly changing ratio limits in ratio‐based methods or oscillation of fault location in graphical methods. In consequence, the energy associated with them lies in‐between low and high severity single faults. Hence multiple fault detection needs to be addressed appropriately which may otherwise pose the serious constraints during transformer condition monitoring. In this study, novel and intelligent classification approach is proposed to upgrade the classical dissolved gas analysis (DGA) technique to cater the requirement of multiple fault diagnosis. This consists of Duval‐triangle‐based optimised fuzzy inference system and neural network models sensitive to both single and multiple incipient faults. Both models have been rigorously trained and tested using dataset credited to field and literatures to achieve high fault recognition and isolation rates, alternatively low false detection and no‐detection rates. Both parameters are combined into single index to determine the accuracy in terms of F1 score which is evaluated to be >97%. The diagnostic ability of the scheme is highly promising and can improve reliability of transformer fault forecasting by DGA.
New second-order radial epiderivatives and applications to optimality conditions
Authors: Zhang Xiaoyan , Wang Qilin
Published: March 2019

In this paper, we introduce the second-order weakly composed radial epiderivative of set-valued maps, discuss its relationship to the second-order weakly composed contingent epiderivative, and obtain some of its properties. Then we establish the necessary optimality conditions and sufficient optimality conditions of Benson proper efficient solutions of constrained set-valued optimization problems by means of the second-order epiderivative. Some of our results improve and imply the corresponding ones in recent literature.
Umsatzsteuer in der Physiotherapie – Wann die LeistungUmsatz ist
Authors: Päper Mirko
Published: March 2019

Heilbehandlungen sind in Deutschland grundsätzlich umsatzsteuerfrei – vorausgesetzt sie wurden vom Arzt oder einem Heilpraktiker verordnet. Anders sieht es mit Präventionsleistungen und Anschlussbehandlungen aus. Hier fallen Steuern an, die der Praxisinhaber auf seine Preise aufschlagen sollte. Steuerberater Mirko Päper erklärt, worauf Therapeuten beim Thema Umsatzsteuer achten müssen.
Impact of endoscopic ultrasound on diagnosis and management of presumed mucinous neoplasms when done for pancreatic cyst morphology change on non-invasive surveillance imaging
Authors: Madhani Kamraan , Yousaf Muhammad , Aamar Ali , Ooka Kohtaro , Muniraj Thiruvengadam , Aslanian Harry , Salem Ronald , Farrell James
Published: March 2019

Background and study aims Guidelines for management of presumed neoplastic pancreatic cysts have encouraged noninvasive imaging for low-risk surveillance, while reserving endoscopic ultrasound for worrisome features including morphologic change. We aim to study the impact of endoscopic ultrasound on diagnosis and management compared with non-invasive imaging.

Patients and methods A single-institution pancreatic cyst database was retrospectively queried for patients who underwent endoscopic ultrasound for the indication of change in cyst morphology. Diagnoses were classified as presumed mucinous neoplasm with or without worrisome features or high-risk stigmata and non-mucinous lesions. Management decisions were defined a priori as surgical evaluation for patients with high-risk stigmata, positive cytology or mural nodule, or continued surveillance for all others.

Results Between January 2013 and October 2016, 709 pancreas cyst endoscopic ultrasounds were performed of which 89 were for cyst morphology change seen on noninvasive imaging including 10 presumed pseudocysts, nine presumed serous cystadenomas, and 70 presumed mucinous cystic neoplasms. Cyst morphologic changes included increase in caliber of the main pancreatic duct (7 cases), increase in cyst size (68 cases), cyst ≥ 30 mm (10 cases), and presence of a solid nodule (1 case). Median cyst size increase was 5 mm with interquartile range of 4 mm over 2.1 ± 1.9 years. Endoscopic ultrasound done for morphologic change resulted in a change in diagnosis and management in 16 % and 13 % of cases, respectively.

Conclusion Endoscopic ultrasound has a modest but clinically significant role in impacting diagnosis and management for presumed mucinous cystic neoplasms when performed for the indication of cyst morphology change.
Rückblick: 10 Jahre neuroreha
Authors: Freivogel Susanna
Published: March 2019

Seit 10 Jahren bietet die Zeitschrift „neuroreha“ einen wahren Schatz
therapeutisch relevanter Informationen. Sie hilft Therapeuten, diejenigen
Maßnahmen in der Therapie einzusetzen, die sich in wissenschaftlichen Studien
als erfolgreich erwiesen haben. Gründungsherausgeberin Susanna Freivogel zeigt
auf, wie Zeitschriften helfen können, die Therapiewelt zu verändern.
Die Schlaganfallrehabilitation der Zukunft voranbringen:
Was sind die nächsten Schritte?
Authors: Kwakkel Gert
Published: March 2019

Gute Theorien sind die Grundlage für adäquate restaurative Therapien. Präzise
Antworten und fundierte Erkenntnisse über die Mechanismen, die wir mit unseren
Rehabilitationstherapien beeinflussen wollen, spielen eine Schlüsselrolle für
adäquate restaurative Therapien.
App-gestützte ambulante Therapie
Authors: Lotze Martin , Ladda Marie
Published: March 2019

Viele von uns trainieren bereits mit verschiedenen mobilen Techniken und Apps
unsere sportlichen Fähigkeiten in der Freizeit. Hier ist in den letzten Jahren
ein enormes Angebot entstanden, das jedoch nur begrenzt im professionellen
Training von Patienten mit Beeinträchtigungen genutzt werden kann.
Intensivbehandlung nach Quetschverletzung mit CRPS – Die Hand angst- und schmerzfrei einsetzen
Authors: Reinhold Ina
Published: March 2019

Ina Reinhold stellt ein stationäres Programm für Patienten vor, die nach einer Quetschverletzung ein CRPS entwickelt haben. Während ihres Klinikaufenthaltes erlernen diese, die betroffene Extremität wieder in ihr Körperbild zu integrieren und ihre Hand im Alltag einzusetzen.
Copper-Catalyzed Direct α-Nitration of Nitrostilbenes with Nitrogen Dioxide
Authors: Chen Kai , Gao Xi , Zou Hui , Xiao Guan , Peng Xin
Published: March 2019

A novel and efficient method for the direct α-nitration of nitrostilbenes was developed in which NO2 was used as the nitro source. This method provided (E)-α-nitrostilbenes derivatives in moderate to good yields. A broad substrate scope, mild and convenient conditions, and high stereoselectivity are important features of this method.
“Restricted Diffusion” within the Splenium of the Corpus Callosum: A Potential Pitfall in Young Infants on 3T Imaging and Marker of Normal Myelin Maturation
Authors: Tan Ai , Lim Yi
Published: March 2019

Purpose To determine the prevalence of “restricted diffusion” within the splenium of the corpus callosum (SOCC) on 3 Tesla (T) and 1.5T imaging systems and to establish the contribution of myelin maturation to the presence of “restricted diffusion” within the SOCC.

Materials and Methods The imaging database at our hospital was queried to build three cohorts of patients: (1) age < 4 months, with magnetic resonance imaging (MRI) scans done on a 3T system; (2) age < 4 months, with MRI scans done on a 1.5T system; and (3) age ≥ 4 months, with MRI scans done on a 3T system, for retrospective analysis. A total of 101 MRI scans were reviewed.

Results “Restricted diffusion” within the SOCC was present in 26 of 29 (90%) patients from cohort 1, in 1 of 37 (3%) patients from cohort 2, and in 1 of 35 (3%) patients from cohort 3. There is a significant difference in the prevalence of “restricted diffusion” in the SOCC between the three cohorts of patients.

Conclusions “Restricted diffusion” within the SOCC may be a normal finding in infants less than 4 months of age, imaged on a 3T system. The presence of “restricted diffusion” within the splenium may serve as a potential marker of normal brain maturation.
A Population-Level Analysis of Pituitary Carcinoma from the National Cancer Database
Authors: Carey Ryan M. , Kuan Edward C. , Workman Alan D. , Patel Neil N. , Kohanski Michael A. , Tong Charles C.L. , Chen Jinbo , Palmer James N. , Adappa Nithin D. , Brant Jason A.
Published: March 2019

Objectives Pituitary carcinoma is a rare entity with fewer than 200 total cases reported in the English literature. Analysis of the population-level data from the National Cancer Database (NCDB) affords the opportunity to study this poorly understood tumor type.

Methods The NCDB was queried for site, histology, and metastasis codes corresponding to pituitary carcinoma. Statistical analyses were performed to determine factors associated with overall survival (OS).

Results A total of 92 patients with pituitary carcinoma met inclusion criteria. The 1 and 5 years of OS for all patients was 93.3% (95% confidence interval [CI]: 88.2–98.6%) and 80.0% (95% CI: 71.6–89.4%), respectively. Patients with invasive primary tumor behavior had 1 and 5 years of OS of 69.2% (95% CI: 48.2–99.5%) and 52.7% (95% CI: 31.2–89.2%), respectively. Multivariate analysis demonstrated that compared with benign primary behavior, invasive behavior had increased all-cause mortality (hazard ratio [HR], 1,296, 95% CI: 15.1– > 2,000). Surgery without adjuvant radiation or chemotherapy was the most common therapy (48.9%), followed by no treatment (40.2%). Compared with surgery alone, no treatment had worse OS (HR, 11.83, 95% CI: 1.41–99.56). Increasing age and female sex were both associated with increased mortality.

Conclusions The most common treatment for pituitary carcinoma is surgery alone followed by no surgery. Surgery alone has significantly better OS compared with no treatment. The efficacy of radiation, chemotherapy, and neurohormonal treatments needs to be examined with prospective studies.
Higher offspring mortality with short interbirth intervals in free-ranging rhesus macaques
Authors: Lee D. Susie , Ruiz-Lambides Angelina V. , Higham James P.
Published: March 2019

Short birth intervals have long been linked to adverse child outcomes in humans. However, it remains unclear the extent to which the birth interval has a direct influence on offspring mortality, independent of the confounding effects of modern environments and human sociocultural practices on reproductive behavior. Outside of humans, the relationship between birth intervals and offspring mortality has been rarely tested, leaving an open question of how much the findings from humans imply evolutionarily conserved mechanisms. Here, using ∼9,000 birth records from ∼1,400 free-ranging rhesus macaque mothers, we show that short birth intervals preceding or succeeding the birth of an offspring are both associated with higher offspring mortality, after controlling for heterogeneity across mothers and birth cohorts. We clarify that the mortality risk of a short birth interval to an offspring is contingent on the survival of its older or younger sibling, the condition that reduces maternal resources for investment in the offspring. This finding suggests that life-history tradeoffs between offspring quantity (a short birth interval) and quality (offspring survival) form an evolutionary force shaping variation in birth intervals. Consistent with the well-known observation made in humans, we also found a nonlinear relationship between the preceding interbirth interval and infant mortality. The overall congruence with the findings from the human literature indicates a robust relationship between birth intervals and offspring mortality.
p27 transcriptionally coregulates cJun to drive programs of tumor progression
Authors: Yoon Hyunho , Kim Minsoon , Jang Kibeom , Shin Miyoung , Besser Alexandra , Xiao Xue , Zhao Dekuang , Wander Seth A. , Briegel Karoline , Morey Lluis , Minn Andy , Slingerland Joyce M.
Published: March 2019

p27 shifts from CDK inhibitor to oncogene when phosphorylated by PI3K effector kinases. Here, we show that p27 is a cJun coregulator, whose assembly and chromatin association is governed by p27 phosphorylation. In breast and bladder cancer cells with high p27pT157pT198 or expressing a CDK-binding defective p27pT157pT198 phosphomimetic (p27CK−DD), cJun is activated and interacts with p27, and p27/cJun complexes localize to the nucleus. p27/cJun up-regulates
TGFB2
to drive metastasis in vivo. Global analysis of p27 and cJun chromatin binding and gene expression shows that cJun recruitment to many target genes is p27 dependent, increased by p27 phosphorylation, and activates programs of epithelial–mesenchymal transformation and metastasis. Finally, human breast cancers with high p27pT157 differentially express p27/cJun-regulated genes of prognostic relevance, supporting the biological significance of the work.
Development and Evaluation of a Standardized Research Definition for Opioid Overdose Outcomes
Authors: Binswanger Ingrid A. , Narwaney Komal J. , Gardner Edward M. , Gabella Barbara A. , Calcaterra Susan L. , Glanz Jason M.
Published: March 2019

Background: Increasing epidemiologic and intervention research is being conducted on opioid overdose, a serious and potentially fatal outcome. However, there is little consensus on how to verify opioid overdose outcomes for research purposes. To ensure reproducibility, minimize misclassification, and permit data harmonization across studies, standardized and consistent overdose definitions are needed. The aims were to develop a case criteria classification scheme based on information commonly available in medical records and to compare it with reviewing physician clinical impression and simple encounter documentation. Methods: In 2 large health systems, we developed a case criteria classification scheme for opioid overdose based on prior literature, expert opinion, and pilot testing with sample medical records. We then identified emergency department and hospital encounters ( n = 259) with at least 1 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code representing a broad range of opioid and non-opioid related poisonings. Physicians conducted structured medical record reviews to identify the proposed case criteria and generate a clinical impression, and trained abstractors verified documentation. We then compared the case criteria classification scheme with clinical impression and encounter documentation. Results: We developed a quantitative opioid overdose case criteria classification scheme that included 3 sets of major criteria and 9 minor criteria (supporting documentation). For the encounters identified using poisoning codes, the proportion verified as opioid overdoses using the case criteria classification scheme, clinical impression, and encounter documentation ranged from 50.4% to 52.7% at one site and 55.5% to 67.2% at the second site. Discrepancies across approaches and sites related to differences in available records and documentation of clinical signs of overdose. Conclusions: We propose a novel case criteria classification scheme for opioid overdose that could be used to rigorously and consistently define overdose across multiple research settings. However, prior to widespread use, further refinement and validation are needed.
Shrub tundra ecohydrology: rainfall interception is a major component of the water balance
Authors: Zwieback Simon , Chang Qianyu , Marsh Philip , Berg Aaron
Published: March 2019

As shrubs expand across the Arctic, they alter all cycles in the Earth system, including the water cycle. However, the coupling of shrubs with the water cycle during summer remains poorly understood. Rainfall interception, a major cause of divergent hydrological responses between vegetated and non-vegetated environments, is particularly poorly constrained. We quantified shrub rainfall interception and redistribution in birch and alder in the Western Canadian Arctic using networks of throughfall and stemflow gauges. We find that rainfall interception losses are a major component of the water budget, as effective rainfall was reduced by 15%–30% in the birches. Underneath alders, effective rainfall was almost as large or larger than gross rainfall, but they also left a rain shadow. The spatial variability in throughfall was substantial underneath both shrub species. Stemflow was a small but non-negligible component, as the alders concentrated ∼15% of rainfall to their few vertical stems, compared to the ∼8% the birches funnelled along their numerous, predominantly skewed stems. The substantial small-scale variability in effective rainfall may create islands in which conditions for certain biogeochemical processes are particularly favourable. On larger scales, rainfall interception reduces the water yield and thus the runoff received by downstream ecosystems such as lakes. The interception losses are predicted to increase with shrub density in a way that also depends on climatic conditions, with large losses in many coastal environments. The extent to which shrub expansion leads to drier Arctic ecosystems is, however, unclear because of the complex interplay between many ecohydrological processes. Shrub rainfall interception is one major, previously overlooked piece of this puzzle.
Freedom Summer “Homos”: An Archive Story
Authors: Francis Charles
Published: March 2019

This “archive story” documents how the infamous Mississippi State Sovereignty Commission harnessed homophobia to crush gay civil rights activists at historically black Rust College in Holly Springs, Mississippi, during “Freedom Summer” in 1964. New information uncovered by the author, a self-described “archive activist” from the Mattachine Society of Washington, D.C., reveals how the Sovereignty Commission, working directly with the governor of Mississippi, accused and exposed students and faculty at Rust as “homos” and “queers” in pursuit of a single objective: convincing the Rust Methodist Board of Trustees to fire its activist president, Dr. Earnest Smith. The piece further explores how the reason for Dr. Smith’s departure from Rust remained enshrouded in silence for so many years. It ends by connecting the political use of homophobia in 1964 to the words of Judge Carlton Reeves on the challenges facing LGBTQ Mississippians today.
Anatomic Implants in Breast Reconstruction: A Comparison of Outcomes and Aesthetic Results Compared to Smooth Round Silicone Implants
Authors: Agochukwu-Nwubah Nneamaka , Boustany Ashley , Wetzel Margaret , Maus Jacob , Rinker Brian
Published: March 2019

Background

Direct comparison studies of outcomes and aesthetic satisfaction of anatomic implants compared to other implants are scarce in the literature.

Objectives

The objective of this study was to compare outcomes and aesthetic satisfaction of patients who underwent breast reconstruction with anatomic implants vs other implants (smooth round silicone).

Methods

A retrospective chart review was performed of patients who underwent implant-based breast reconstruction over 3 years. Outcomes including complications, number of surgeries, need for revisions, and aesthetic satisfaction of patients were tracked and compared.

Results

A total of 156 patients met inclusion criteria for this study. A total of 123 underwent reconstruction with a round implant, and 33 underwent reconstruction with an anatomic implant. Of the 156 patients, 38 underwent a 1-stage direct-to-implant reconstruction and the remainder underwent a 2-stage implant reconstruction. The round and anatomic implant groups did not differ with regards to number of surgeries, revisions, utilization of contralateral symmetry procedures, implant-related reoperations, complications, implant loss, infection, capsular contracture, and seroma. The Breast Q survey had a response rate of 27%. On all parameters, the round and anatomic implant groups did not significantly differ.

Conclusions

There were no significant differences among round and shaped implants in regards to complications, revision surgeries, and overall outcomes. Furthermore, patients showed no differences regarding satisfaction and well-being when surveyed on the Breast Q survey. The decision of implant choice in breast reconstruction should be based on surgeon comfort and the patient’s needs/body type.

Level of Evidence: 4
Rehabilitation of the Dysmorphic Lower Eyelid From Hyaluronic Acid Filler: What to Do After a Good Periocular Treatment Goes Bad
Authors: Skippen Brent , Baldelli Ilaria , Hartstein Morris , Casabona Gabriela , Montes Jose Raul , Bernardini Francesco
Published: March 2019

Background

Chronic, long-lasting edema accompanied by the Tyndall effect as a delayed reaction to hyaluronic acid (HA) filler injection seems to occur exclusively in the eyelids.

Objectives

The authors sought to present a treatment algorithm for management of patients with chronic lower eyelid edema as a delayed complication of HA filler injection.

Methods

Retrospective study including 61 patients with delayed-onset chronic periocular edema following uneventful HA filler injection in the lower eyelids or cheeks. All patients underwent hyaluronidase enzyme dissolution followed by secondary treatment. Three retreatment options were presented: (1) observation, (2) secondary treatment with HA filler, and (3) lower eyelid blepharoplasty.

Results

All patients underwent filler dissolution using hyaluronidase. The mean age was 48 years and 97% of the patients were female. Single treatment was effective in 92% of patients with 8% requiring another hyaluronidase injection to completely eradicate residual edema. Six patients (10%) were satisfied after hyaluronidase only and 6 patients (10%) underwent lower eyelid blepharoplasty. Secondary treatment with HA filler was performed in 48 patients (80%). All were satisfied with final results without further edema in the follow-up period.

Conclusions

Delayed-onset chronic lower eyelid edema is a frequent HA-related complication and cause of concern when considering periocular HA treatment. Previous treatment has been limited to either hyaluronidase only or blepharoplasty as a secondary solution after hyaluronidase, with only a minority of patients satisfied. Hyaluronidase, shortly followed by HA filler retreatment, is a safe and effective solution.

Level of Evidence: 4
On marginal and conditional parameters in logistic regression models
Authors: Stanghellini Elena , Doretti Marco
Published: March 2019

We derive the exact formula linking the parameters of marginal and conditional logistic regression models with binary mediators when no conditional independence assumptions can be made. The formula has the appealing property of being the sum of terms that vanish whenever parameters of the conditional models vanish, thereby recovering well-known results as particular cases. It also permits the disentangling of direct and indirect effects as well as quantifying the distortion induced by the omission of relevant covariates, opening the way to sensitivity analysis. As the parameters of the conditional models are multiplied by terms that are always bounded, the derivations may also be used to construct reasonable bounds on the parameters of interest when relevant intermediate variables are unobserved. We assume that, conditionally on a set of covariates, the data-generating process can be represented by a directed acyclic graph. We also show how the results presented here lead to the extension of path analysis to a system of binary random variables.
Immunogenicity of the Currently Recommended Pneumococcal Vaccination Schedule in Patients With Inflammatory Bowel Disease
Authors: van Aalst Mariëlle , Garcia Garrido Hannah M , van der Leun Josephine , Meek Bob , van Leeuwen Ester M M , Löwenberg Mark , D’Haens Geert R , Ponsioen Cyriel Y I , Grobusch Martin P , Goorhuis Abraham
Published: March 2019

Background

Patients with inflammatory bowel disease (IBD) are at increased risk of invasive pneumococcal infections. Therefore, vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) 2 months later is recommended. However, the level of immunogenicity induced by this vaccination schedule in IBD patients with and without immunosuppressive medication remains unclear.

Methods

We prospectively assessed the immunogenicity of PCV13 followed by PPSV23 in IBD patients by measuring serotype-specific pneumococcal immunoglobulin G antibody concentrations at baseline and 4–8 weeks postvaccination. Response to vaccination was defined as a postvaccination antibody concentration ≥1.3 μg/mL for 70% of the measured serotypes. We analyzed the immunogenic effect of 4 different medication regimens: (1) conventional immunomodulators (ie, oral prednisolone >10 mg/day, thiopurines, methotrexate); (2) anti–tumor necrosis factor agents; (3) combination therapy; and (4) no treatment with immunosuppressive agents (control group).

Results

One hundred forty-one IBD patients were included, of whom 37 were controls. Adequate response to vaccination was 59% (61/104) in patients using immunosuppressive agents (groups 1–3) vs 81% (30/37) in controls (odds ratio, 0.33 [95% confidence interval, .13–.82]). A combination of different immunosuppressive drugs most severely impaired the immune response to pneumococcal vaccination (response, 52% [15/29]).

Conclusions

Although the sequential vaccination schedule of PCV13 followed by PPSV23 is safe, immunogenic, and thus beneficial in the majority of IBD patients, those receiving immunosuppressive agents, and especially those receiving combination therapy, have an impaired immune response compared to controls. Therefore, preferably, vaccinations should be administered before the initiation of immunosuppressive therapy.

Clinical Trials Registration

Dutch trial register #6315.
Isolation of novel quorum-sensing active bacteria from microbial mats in Shark Bay Australia
Authors: Charlesworth James C , Watters Cara , Wong Hon Lun , Visscher Pieter T , Burns Brendan P
Published: March 2019

Quorum sensing is a potent system of genetic control allowing phenotypes to be coordinated across localized communities. In this study, quorum sensing systems in Shark Bay microbial mats were delineated using a targeted approach analyzing whole mat extractions as well as the creation of an isolate library. A library of 165 isolates from different mat types were screened using the AHL biosensor E. coli MT102. Based on sequence identity 30 unique isolates belonging to Proteobacteria, Actinobacteria and Firmicutes were found to activate the AHL biosensor, suggesting AHLs or analogous compounds were potentially present. Several of the isolates have not been shown previously to produce signal molecules, particularly the members of the Actinobacteria and Firmicutes phyla including Virgibacillus, Halobacillius, Microbacterium and Brevibacterium. These active isolates were further screened using thin-layer chromatography (TLC) providing putative identities of AHL molecules present within the mat communities. Nine isolates were capable of producing several spots of varying sizes after TLC separation, suggesting the presence of multiple signalling molecules. This study is the first to delineate AHL-based signalling in the microbial mats of Shark Bay, and suggests quorum sensing may play a role in the ecosphysiological coordination of complex phenotypes across microbial mat communities.
The seagrass holobiont: understanding seagrass-bacteria interactions and their role in seagrass ecosystem functioning
Authors: Tarquinio Flavia , Hyndes Glenn A , Laverock Bonnie , Koenders Annette , Säwström Christin
Published: March 2019

This review shows that the presence of seagrass microbial community is critical for the development of seagrasses; from seed germination, through to phytohormone production and enhanced nutrient availability, and defence against pathogens and saprophytes. The tight seagrass-bacterial relationship highlighted in this review supports the existence of a seagrass holobiont and adds to the growing evidence for the importance of marine eukaryotic microorganisms in sustaining vital ecosystems. Incorporating a micro-scale view on seagrass ecosystems substantially expands our understanding of ecosystem functioning and may have significant implications for future seagrass management and mitigation against human disturbance.
Like a Castor Seed: Jaina Philosophers on the Nature of Liberation
Authors: Bajželj Ana
Published: March 2019

This article examines the nature of the spatial transition of liberated jīvas, a special episode in the life of jīvas that according to Jaina philosophy takes place between the destruction of all karman that binds them to saṃsāra on the one hand and their dwelling in the space of liberated beings on the other. As the place of karmically bound jīvas that are capable of attaining liberation is located far below the space of liberated beings, the disembodied liberated jīvas must travel upwards to reach it. Focused on Umāsvāti’s Tattvārtha-sūtra with four commentaries, the article describes and analyses the discussions and issues that developed around the doctrine of the jīva’s final journey.
BIG TECH BANKING
Authors: de la Mano Miguel , Padilla Jorge
Published: March 2019

In this paper we explore the likely implications of the entry of Big Tech platforms into retail banking and the appropriate response of regulators and policy makers to this new industry development. We find that the entry of Big Tech platforms may transform the banking industry in radical ways: although it may possibly increase competition to the benefit of consumers in the short term, within a few years Big Tech companies may succeed in monopolizing the origination and distribution of loans to consumers and Small and Medium Enterprises (SMEs), forcing traditional banks to become “low cost manufacturers,” which merely fund the loans intermediated by the Big Techs. This situation may harm competition, reduce consumer welfare, and bring about an increase in financial instability in the medium or long term. We analyze alternative policy responses aimed at maximizing the positive impact on consumer welfare of Big Tech entry while limiting the risk of monopolization as well as the potential adverse implications of such entry on market integrity and financial stability.
Material patterning on substrates by manipulation of fluidic behavior
Authors: Li Yitan , Wang Hao , Xu Henglu , Wu Shiting , Li Xuemei , Yu Jiapeng , Huang Chaoyu , Zhang Zeyao , Sun Hao , Han Lu , Li Meihui , Cao Anyuan , Pan Zhenhai , Li Yan
Published: March 2019

Patterned materials on substrates are of great importance for a wide variety of applications. In solution-based approaches to material patterning, fluidic flow is inevitable. Here we demonstrate not only the importance of fluidic behavior but also the methodology of engineering the flow pattern to guide the material crystallization and assembly. We show by both experiment and simulation that substrate heating, which is generally used to accelerate evaporation, produces irregular complex vortexes. Instead, a top-heating–bottom-cooling (THBC) set-up offers an inverse temperature gradient and results in a single Marangoni vortex, which is desired for ordered nanomaterial patterning near the contact line. We then realize the fabrication of large-scale patterns of iodide perovskite crystals on different substrates under THBC conditions. We further demonstrate that harnessing the flow behavior is a general strategy with great feasibility to pattern various functional materials ranging from inorganic, organic, hybrid to biological categories on different substrates, presenting great potential for practical applications.
Variants in the CHRNA5–CHRNA3–CHRNB4 Region of Chromosome 15 Predict Gastrointestinal Adverse Events in the Transdisciplinary Tobacco Use Research Center Smoking Cessation Trial
Authors: Culverhouse Robert C , Chen Li-Shiun , Saccone Nancy L , Ma Yinjiao , Piper Megan E , Baker Timothy B , Bierut Laura J
Published: March 2019

Introduction

Reducing adverse events from pharmacologic treatment is an important goal of precision medicine and identifying genetic predictors of adverse events is a step toward this goal. In 2012, King et al. reported associations between genetic variants and adverse events in a placebo-controlled smoking cessation trial of varenicline and bupropion. Strong associations were found between gastrointestinal adverse events and 11 variants in the CHRNA5–CHRNA3–CHRNB4 region of chromosome 15, a region repeatedly associated with smoking-related phenotypes. Our goal was to replicate, in an independent sample, the impact of variants in the CHRNA5–CHRNA3–CHRNB4 region on gastrointestinal adverse events and to extend the analyses to adherence and smoking cessation.

Methods

The University of Wisconsin Transdisciplinary Tobacco Use Research Center (TTURC) conducted a multiarmed, placebo-controlled smoking cessation trial of bupropion and nicotine replacement therapy that included 985 genotyped European-ancestry participants. We evaluated relationships between our key variables using logistic regression.

Results

Gastrointestinal adverse events were experienced by 31.6% TTURC participants. Each of the CHRNA5–CHRNA3–CHRNB4 associations from the King et al. study was found in TTURC, with the same direction of effect. Neither these variants nor the gastrointestinal adverse events themselves were associated with adherence to medication or successful smoking cessation.

Conclusions

Variants in the CHRNA5–CHRNA3–CHRNB4 region of chromosome 15 are associated with gastrointestinal adverse events in smoking cessation. Additional independent variants in this region strengthen the association. The consistency between the results of these two independent studies supports the conclusion that these findings reflect biological response to the use of smoking cessation medication.

Implications

The fact that our findings from the TTURC smoking cessation trial support the independent findings of King et al. suggest that associations of variants in the CHRNA5–CHRNA3–CHRNB4 region of chromosome 15 with gastrointestinal adverse events while taking medications for smoking cessation reflect biology. However, although adherence to medication was a strong predictor of successful smoking cessation in TTURC, neither adverse events nor the genetic variants associated with them predicted either adherence or successful cessation in this study. Thus, although we should strive to minimize adverse events during treatment, we should not expect that to increase successful smoking cessation substantially.
Antimicrobial Susceptibility of Acinetobacter calcoaceticus–Acinetobacter baumannii Complex and Stenotrophomonas maltophilia Clinical Isolates: Results From the SENTRY Antimicrobial Surveillance Program (1997–2016)
Authors: Gales Ana C , Seifert Harald , Gur Deniz , Castanheira Mariana , Jones Ronald N , Sader Helio S
Published: March 2019

Background

Acinetobacter calcoaceticus–A. baumannii (Acb) complex and Stenotrophomonas maltophilia represent frequent causes of hospital-acquired infections. We evaluated the frequency and resistance rates of Acb complex and S. maltophilia isolates from medical centers enrolled in the SENTRY Program.

Methods

A total of 13 752 Acb complex and 6467 S. maltophilia isolates were forwarded to a monitoring laboratory by 259 participating sites from the Asia-Pacific region, Latin America, Europe, and North America between 1997 and 2016. Confirmation of species identification and antimicrobial susceptibility testing were performed using conventional methods and/or matrix-assisted laser desorption ionization–time of flight mass spectrometry and the broth microdilution method, respectively. Antimicrobial susceptibility results were interpreted by CLSI and EUCAST 2018 criteria.

Results

Acb complex and S. maltophilia were most frequently isolated from patients hospitalized with pneumonia (42.9% and 55.8%, respectively) and bloodstream infections (37.3% and 33.8%, respectively). Colistin and minocycline were the most active agents against Acb complex (colistin MIC50/90, ≤0.5/2 mg/L; 95.9% susceptible) and S. maltophilia (minocycline MIC50/90, ≤1/2 mg/L; 99.5% susceptible) isolates, respectively. Important temporal decreases in susceptibility rates among Acb complex isolates were observed for all antimicrobial agents in all regions. Rates of extensively drug-resistant Acb complex rates were highest in Europe (66.4%), followed by Latin America (61.5%), Asia-Pacific (56.9%), and North America (38.8%). Among S. maltophilia isolates, overall trimethoprim-sulfamethoxazole (TMP-SMX) susceptibility rates decreased from 97.2% in 2001–2004 to 95.7% in 2013–2016, but varied according to the geographic region.

Conclusions

We observed important reductions of susceptibility rates to all antimicrobial agents among Acb complex isolates obtained from all geographic regions. In contrast, resistance rates to TMP-SMX among S. maltophilia isolates remained low and relatively stable during the study period.
Geographic and Temporal Patterns of Antimicrobial Resistance in Pseudomonas aeruginosa Over 20 Years From the SENTRY Antimicrobial Surveillance Program, 1997–2016
Authors: Shortridge Dee , Gales Ana C , Streit Jennifer M , Huband Michael D , Tsakris Athanasios , Jones Ronald N
Published: March 2019

Background

The SENTRY Antimicrobial Surveillance Program was established in 1997 and encompasses over 750 000 bacterial isolates from ≥400 medical centers worldwide. Among the pathogens tested, Pseudomonas aeruginosa remains a common cause of multidrug-resistant (MDR) bloodstream infections and pneumonia in hospitalized patients. In the present study, we reviewed geographic and temporal trends in resistant phenotypes of P. aeruginosa over 20 years of the SENTRY Program.

Methods

From 1997 to 2016, 52 022 clinically significant consecutive isolates were submitted from ≥200 medical centers representing the Asia-Pacific region, Europe, Latin America, and North America. Only 1 isolate per patient per infection episode was submitted. Isolates were identified by standard algorithms and/or matrix-assisted laser desorption ionization-time of flight mass spectrometry. Susceptibility testing was performed by Clinical and Laboratory Standards Institute (CLSI) methods and interpreted using CLSI and European Committee on Antimicrobial Susceptibility Testing 2018 criteria at JMI Laboratories.

Results

The most common infection from which P. aeruginosa was isolated was pneumonia in hospitalized patients (44.6%) followed by bloodstream infection (27.9%), with pneumonia having a slightly higher rate of MDR (27.7%) than bloodstream infections (23.7%). The region with the highest percentage of MDR phenotypes was Latin America (41.1%), followed by Europe (28.4%). The MDR rates were highest in 2005–2008 and have decreased in the most recent period. Colistin was the most active drug tested (99.4% susceptible), followed by amikacin (90.5% susceptible).

Conclusions

Over the 20 years of SENTRY Program surveillance, the rate of MDR P. aeruginosa infections has decreased, particularly in Latin America. Whether the trend of decreasing resistance in P. aeruginosa is maintained will be documented in future SENTRY Program and other surveillance reports.
Temporal and Geographic Variation in Antimicrobial Susceptibility and Resistance Patterns of Enterococci: Results From the SENTRY Antimicrobial Surveillance Program, 1997–2016
Authors: Pfaller Michael A , Cormican Martin , Flamm Robert K , Mendes Rodrigo E , Jones Ronald N
Published: March 2019

Background

The SENTRY Antimicrobial Surveillance Program was established in 1997 and presently encompasses more than 750 000 bacterial isolates from over 400 medical centers worldwide. Among these pathogens, enterococci represents a prominent cause of bloodstream (BSIs), intra-abdominal (IAIs), skin and skin structure, and urinary tract infections (UTIs). In the present study, we reviewed geographic and temporal trends in Enterococcus species and resistant phenotypes identified throughout the SENTRY Program.

Methods

From 1997 to 2016, a total of 49 491 clinically significant enterococci isolates (15 species) were submitted from 298 medical centers representing the Asia-Pacific (APAC), European, Latin American (LATAM), and North American (NA) regions. Bacteria were identified by standard algorithms and matrix-assisted laser desorption ionization–time of flight mass spectrometry. Susceptibility (S) testing was performed by reference broth microdilution methods and interpreted using Clinical and Laboratory Standards Institute/US Food and Drug Administration and European Committee on Antimicrobial Susceptibility Testing criteria.

Results

The most common Enterococcus species in all 4 regions were Enterococcus faecalis (64.7%) and E. faecium (EFM; 29.0%). Enterococci accounted for 10.7% of BSIs in NA and was most prominent as a cause of IAIs (24.0%) in APAC and of UTIs (19.8%) in LATAM. A steady decrease in the susceptibility to ampicillin and vancomycin was observed in all regions over the 20-year interval. Vancomycin-resistant enterococci (VRE) accounted for more than 8% of enterococcal isolates in all regions and was most common in NA (21.6%). Among the 7615 VRE isolates detected, 89.1% were the VanA phenotype (91.0% EFM) and 10.9% were VanB. Several newer antimicrobial agents demonstrated promising activity against VRE, including daptomycin (99.6–100.0% S), linezolid (98.0%–99.6% S), oritavancin (92.2%–98.3% S), tedizolid (99.5%–100.0% S), and tigecycline (99.4%–100.0% S).

Conclusions

Enterococci remained a prominent gram-positive pathogen in the SENTRY Program from 1997 through 2016. The overall frequency of VRE was 15.4% and increased over time in all monitored regions. Newly released agents with novel mechanisms of action show promising activity against VRE.