bluuebunny/crossref_metadata_2025 huggingface dataset:
Panda type elliptical core few-mode fiber
Authors: Yang Yi , Mo Qi , Fu Songnian , Liu Bo , Tang Ming , Liu Deming
Published: December 2018

Mode division multiplexing together with multiple-input multiple-output digital signal processing (MIMO-DSP) has the potential for fulfilling future ever-increasing transmission capacity demand. However, for the mitigation of severe mode coupling, the cost and computation complexity of MIMO-DSP become prohibitive with the growing numbers of guided modes arising in the traditional circular core few-mode fiber. We design, fabricate, and characterize panda type elliptical core few-mode fiber (PE-FMF) supporting six eigenmodes of LP01x, LP01y, LP11ax, LP11ay, LP11bx, and LP11by independent transmission. Such PE-FMF, with both low refractive index difference of 0.006 between the core and the cladding and low ellipticity of 1.449, can alleviate the trade-off between the eigenmode numbers and the desirable mode spacing occurring in traditional elliptical-core FMF design. The numerical results indicate that the minimal mode spacing among six eigenmodes is above 1.95 × 10−4 over the whole C + L band. The maintaining capability of both mode intensity profile and polarization is experimentally verified, when the PE-FMF is under a twisting rate range from 0 to 1.57 rad/m. During the fiber twisting, the mode intensity profile can be maintained and the polarization extinction ratio of individual eigenmode is above 20 dB over 50 m PE-FMF.
Black phosphorus frequency mixer for infrared optoelectronic signal processing
Authors: Suess Ryan J. , Hart Joseph D. , Leong Edward , Mittendorff Martin , Murphy Thomas E.
Published: December 2018

Black phosphorus possesses several attractive properties for optoelectronics, notably a direct and layer dependent bandgap that varies from the visible to mid-infrared and the ability to transfer the material to nearly arbitrary substrates. A less utilized property of black phosphorus for optoelectronics is the nonlinear photoresponse. The photocarrier lifetime in black phosphorus exhibits a strong nonlinear dependence on the excitation density that is utilized in the present work for optoelectronic mixing. In this scheme, two telecommunications-band lasers are intensity-modulated by a radio frequency (RF) and local oscillator (LO) frequency and focused onto a black phosphorus photoconductive detector. Above the saturation carrier density, the photocurrent is proportional to the square root of the optical power which produces photocurrents at the sum and difference frequencies of the input beams. The bandwidth of the mixing process increases from 10 to 100 MHz for incident powers of 0.01 to 1 mW, respectively. An excess carrier model accurately describes the power dependence of the cutoff frequency and mixing conversion, which are both limited by photocarrier recombination. Optimizing our device geometry to support larger bias fields and decreased carrier transit times could increase the maximum RF/LO frequency beyond a GHz by reducing the excess carrier lifetime. Frequency mixing based on the photocarrier nonlinearity in multilayer black phosphorus demonstrated here can be readily extended to mid-infrared wavelengths as long as 4 µm.
In Pursuit of Fluorinated Sigma Receptor Ligand Candidates Related to [
Authors: Jwad Rasha S. , Pang Alan H. C. , Hunter Luke , Read Roger W.
Published: December 2018

This paper describes the synthesis of N-arylmethyl(1-benzyl) and N-aroyl(1-benzoyl) 4-(4-fluoromethylphenoxymethyl)piperidines as potential sigma receptor ligands analogous to the potent and highly selective sigma-1 ligand [18F]-FPS, but with enhanced or alternative binding and transport profiles. The synthesis involves N-aroylation of 4-hydroxmethylpiperidine or ethyl nipecotate, functional group manipulation of the ester group or simple activation of the hydroxyl group to introduce the phenoxy component, and subsequent functional group manipulation to reduce the amide group and introduce the fluorine into the fluoromethyl substituent. In its development, the synthesis was found to require early N-aroylation of the piperidine precursor to avoid complications due to anchimeric assistance by its nitrogen in subsequent displacement reactions. New evidence is presented on the pathway followed in a literature report of direct displacement of a benzylic hydroxyl group by fluoride ion under Appel-like conditions. Relevant to the literature report, the halide ion in the fluoromethylphenoxy 1-benzylpiperidine derivatives was surprisingly labile to hydrolytic displacement on chromatography and this aspect is worthy of further study. Moreover, the NMR spectra of the amides were complicated by geometric isomerism about the amide C(O)–N bond, but detailed analysis of spectra from 2-anisoyl derivatives allowed the assignment of diastereomeric contributors to consistent, secondary atropisomerism about the aryl–C(O) bond.
Macroscopic dynamics and the collapse of urban traffic
Authors: Olmos Luis E. , Çolak Serdar , Shafiei Sajjad , Saberi Meead , González Marta C.
Published: December 2018

Stories of mega-jams that last tens of hours or even days appear not only in fiction but also in reality. In this context, it is important to characterize the collapse of the network, defined as the transition from a characteristic travel time to orders of magnitude longer for the same distance traveled. In this multicity study, we unravel this complex phenomenon under various conditions of demand and translate it to the travel time of the individual drivers. First, we start with the current conditions, showing that there is a characteristic time

τ

that takes a representative group of commuters to arrive at their destinations once their maximum density has been reached. While this time differs from city to city, it can be explained by

Γ

, defined as the ratio of the vehicle miles traveled to the total vehicle distance the road network can support per hour. Modifying

Γ

can improve

τ

and directly inform planning and infrastructure interventions. In this study we focus on measuring the vulnerability of the system by increasing the volume of cars in the network, keeping the road capacity and the empirical spatial dynamics from origins to destinations unchanged. We identify three states of urban traffic, separated by two distinctive transitions. The first one describes the appearance of the first bottlenecks and the second one the collapse of the system. This collapse is marked by a given number of commuters in each city and it is formally characterized by a nonequilibrium phase transition.
The role of industry-specific, occupation-specific, and location-specific knowledge in the growth and survival of new firms
Authors: Jara-Figueroa C. , Jun Bogang , Glaeser Edward L. , Hidalgo Cesar A.
Published: December 2018

How do regions acquire the knowledge they need to diversify their economic activities? How does the migration of workers among firms and industries contribute to the diffusion of that knowledge? Here we measure the industry-, occupation-, and location-specific knowledge carried by workers from one establishment to the next, using a dataset summarizing the individual work history for an entire country. We study pioneer firms—firms operating in an industry that was not present in a region—because the success of pioneers is the basic unit of regional economic diversification. We find that the growth and survival of pioneers increase significantly when their first hires are workers with experience in a related industry and with work experience in the same location, but not with past experience in a related occupation. We compare these results with new firms that are not pioneers and find that industry-specific knowledge is significantly more important for pioneer than for nonpioneer firms. To address endogeneity we use Bartik instruments, which leverage national fluctuations in the demand for an activity as shocks for local labor supply. The instrumental variable estimates support the finding that industry-specific knowledge is a predictor of the survival and growth of pioneer firms. These findings expand our understanding of the micromechanisms underlying regional economic diversification.
How science and technology developments impact employment and education
Authors: Martinez Wendy
Published: December 2018

A better understanding of how developments in science and technology influence the creation of new occupations and subsequent changes in educational programs can help decision makers at all levels of our society. As a result of research and development efforts, innovations are achieved, resulting in the creation of new occupations and the demand for employees with expertise in these new areas. To fulfill the demand, universities and colleges often revise their programs to address these needs. Several data sources are described in this paper that might help us to explore the relationship between advancements in industry, emerging occupations, and educational changes over time.
Cryo-EM structure of the native butyrylcholinesterase tetramer reveals a dimer of dimers stabilized by a superhelical assembly
Authors: Leung Miguel Ricardo , van Bezouwen Laura S. , Schopfer Lawrence M. , Sussman Joel L. , Silman Israel , Lockridge Oksana , Zeev-Ben-Mordehai Tzviya
Published: December 2018

The quaternary structures of the cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), are essential for their localization and function. Of practical importance, BChE is a promising therapeutic candidate for intoxication by organophosphate nerve agents and insecticides, and for detoxification of addictive substances. Efficacy of the recombinant enzyme hinges on its having a long circulatory half-life; this, in turn, depends strongly on its ability to tetramerize. Here, we used cryoelectron microscopy (cryo-EM) to determine the structure of the highly glycosylated native BChE tetramer purified from human plasma at 5.7 Å. Our structure reveals that the BChE tetramer is organized as a staggered dimer of dimers. Tetramerization is mediated by assembly of the C-terminal tryptophan amphiphilic tetramerization (WAT) helices from each subunit as a superhelical assembly around a central lamellipodin-derived oligopeptide with a proline-rich attachment domain (PRAD) sequence that adopts a polyproline II helical conformation and runs antiparallel. The catalytic domains within a dimer are asymmetrically linked to the WAT/PRAD. In the resulting arrangement, the tetramerization domain is largely shielded by the catalytic domains, which may contribute to the stability of the human BChE (HuBChE) tetramer. Our cryo-EM structure reveals the basis for assembly of the native tetramers and has implications for the therapeutic applications of HuBChE. This mode of tetramerization is seen only in the cholinesterases but may provide a promising template for designing other proteins with improved circulatory residence times.
Bilateral comparison of luminous flux using lamps as transfer standards (EURAMET.PR-K4.2)
Authors: Dubard J , Obein G , Suryani D
Published: December 2018

The Laboratoire National de Métrologie et d'Essais, LNE-CNAM (France) and The National Institute of Metrology, RCM LIPI (Indonesia) agreed in December 2013 to conduct a bilateral comparison on luminous flux using a group of lamps as transfer standards.

The aims of the comparison were:

• To link the RCM LIPI realized lumen to the CCPR K4 reference value

• To demonstrate the RCM LIPI capability in calibrating tungsten standards lamps.

The comparison and its protocol were approved by the CCPR and registered with KCDB with the comparison number: EURAMET.PR-K4.2.

KEY WORDS FOR SEARCH

Luminous flux, PR K4, Bilateral Comparison

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCPR, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Analytical and numerical modeling of the process for cluster emergence of objects in a random environment
Authors: Mostovoy Y A , Berdnikov V A
Published: December 2018

The task solution for probing a certain area by a swarm of objects randomly distributed is considered. This requires studying of statistical features for clusters emergence from swarm objects uniformly distributed in order to find such a concentration of the objects in the sensing area in which the number of random clusters will be maximal. Corresponding analytical dependencies have been obtained.
Uromodulin in a Pathway Between Decreased Renal Urate Excretion and Albuminuria
Authors: Krajcoviechova Alena , Marois-Blanchet Francois-Christophe , Troyanov Stephan , Harvey Francois , Dumas Pierre , Tremblay Johanne , Cifkova Renata , Awadalla Philip , Madore Francois , Hamet Pavel
Published: December 2018

BACKGROUND

The mechanism explaining the inverse association between renal urate and albumin excretion remains unclear. First, we evaluated the impact of candidate variants in the main urate transporter genes (i.e., SLC2A9, SLC22A12, ABCG2) on the association between fractional excretion of uric acid (FEUA) and urinary albumin/creatinine ratio (uACR). Second, we examined uromodulin and sodium excretion as mediators of the association between FEUA and uACR.

METHODS

We performed cross-sectional analysis of 737 French Canadians from the CARTaGENE cohort, a random sample of the Quebec population aged 40–69 years (a total of 20,004 individuals). Individuals with available genotyping and urinary data were obtained from a sub-study including gender-matched pairs with high and low Framingham Risk Score and vascular rigidity index. We further excluded individuals with an estimated glomerular filtration rate <60 ml/min/1.73 m2, glycosuria, and use of confounding medication. A spot urine sample was analyzed. Genotyping was performed using the Illumina Omni2.5–8 BeadChips. Genetic variants were analyzed using an additive model.

RESULTS

Final analyses included 593 individuals (45.5% of men; mean age 54.3 ± 8.6). We observed an antagonistic interaction between rs13129697 variant of the SLC2A9 gene and FEUA tertiles on uACR (P = 0.002). Using the mediation analysis, uromodulin explained 32%, fractional excretion of sodium (FENa) 44%, and uromodulin together with FENa explained 70% of the inverse relationship between FEUA and uACR. Bootstrapping process confirmed the role of both mediators.

CONCLUSIONS

Our data suggest that the association of albuminuria with decreased renal urate excretion may be modified by the transporter SLC2A9, and mediated by uromodulin and sodium handling.
ModL: exploring and restoring regularity when testing for positive selection
Authors: Mingrone Joseph , Susko Edward , Bielawski Joseph P
Published: December 2018

Motivation

Likelihood ratio tests are commonly used to test for positive selection acting on proteins. They are usually applied with thresholds for declaring a protein under positive selection determined from a chi-square or mixture of chi-square distributions. Although it is known that such distributions are not strictly justified due to the statistical irregularity of the problem, the hope has been that the resulting tests are conservative and do not lose much power in comparison with the same test using the unknown, correct threshold. We show that commonly used thresholds need not yield conservative tests, but instead give larger than expected Type I error rates. Statistical regularity can be restored by using a modified likelihood ratio test.

Results

We give theoretical results to prove that, if the number of sites is not too small, the modified likelihood ratio test gives approximately correct Type I error probabilities regardless of the parameter settings of the underlying null hypothesis. Simulations show that modification gives Type I error rates closer to those stated without a loss of power. The simulations also show that parameter estimation for mixture models of codon evolution can be challenging in certain data-generation settings with very different mixing distributions giving nearly identical site pattern distributions unless the number of taxa and tree length are large. Because mixture models are widely used for a variety of problems in molecular evolution, the challenges and general approaches to solving them presented here are applicable in a broader context.

Availability and implementation

https://github.com/jehops/codeml_modl

Supplementary information

Supplementary data are available at Bioinformatics online.
CNValidator: validating somatic copy-number inference
Authors: Smith Lucian P , Yamato Jon A , Kuhner Mary K
Published: December 2018

Motivation

CNValidator assesses the quality of somatic copy-number calls based on coherency of haplotypes across multiple samples from the same individual. It is applicable to any copy-number calling algorithm, which makes calls independently for each sample. This test is useful in assessing the accuracy of copy-number calls, as well as choosing among alternative copy-number algorithms or tuning parameter values.

Results

On a dataset of somatic samples from individuals with Barrett’s Esophagus, CNValidator provided feedback on the correctness of sample ploidy calls and also detected data quality issues.

Availability and implementation

CNValidator is available on GitHub at https://github.com/kuhnerlab/CNValidator.

Supplementary information

Supplementary data are available at Bioinformatics online.
HIV activism in modern Russia: from NGOs to community development
Authors: Nartova Nadya , Krupets Yana , Shilova Anastasiia
Published: December 2018

In the context of the spreading HIV epidemic in Russia and the lack of government's effectiveness in addressing this problem, the role and the importance of HIV activism in protecting the rights and improving the quality of life of HIV positive people have been increasing. This article focuses on the development of the HIV community in St. Petersburg, one of the largest and the most problematic, in terms of the HIV epidemic, cities in Russia. The research was conducted within the qualitative methodology, using ethnographic case-study methods and biographical interviews. The authors use the analysis of field observations and nineteen interviews with men and women involved in HIV activism in St. Petersburg to show how collective actions of NGOs and action groups form the city HIV community through working with different groups and the development of participants' agency.
Hypothermia and cardiac electrophysiology: a systematic review of clinical and experimental data
Authors: Dietrichs Erik Sveberg , Tveita Torkjel , Smith Godfrey
Published: December 2018

Moderate therapeutic hypothermia procedures are used in post-cardiac arrest care, while in surgical procedures, lower core temperatures are often utilized to provide cerebral protection. Involuntary reduction of core body temperature takes place in accidental hypothermia and ventricular arrhythmias are recognized as a principal cause for a high mortality rate in these patients. We assessed both clinical and experimental literature through a systematic literature search in the PubMed database, to review the effect of hypothermia on cardiac electrophysiology. From included studies, there is common experimental and clinical evidence that progressive cooling will induce changes in cardiac electrophysiology. The QT interval is prolonged and appears more sensitive to decreases in temperature than the QRS interval. Severe hypothermia is associated with more pronounced changes, some of which are proarrhythmic. This is supported clinically where severe accidental hypothermia is commonly associated with ventricular fibrillation or asystole. J-waves in human electrocardiogram recordings are regularly but not always observed in hypothermia. Its relation to ventricular repolarization and arrhythmias is not obvious. Little clinical data exist on efficacy of anti-arrhythmic drugs in hypothermia, while experimental data show the potential of some agents, such as the class III antiarrhythmic bretylium. It is apparent that QT-prolonging drugs should be avoided.
BLINK: a package for the next level of genome-wide association studies with both individuals and markers in the millions
Authors: Huang Meng , Liu Xiaolei , Zhou Yao , Summers Ryan M , Zhang Zhiwu
Published: December 2018

Big datasets, accumulated from biomedical and agronomic studies, provide the potential to identify genes that control complex human diseases and agriculturally important traits through genome-wide association studies (GWAS). However, big datasets also lead to extreme computational challenges, especially when sophisticated statistical models are employed to simultaneously reduce false positives and false negatives. The newly developed fixed and random model circulating probability unification (FarmCPU) method uses a bin method under the assumption that quantitative trait nucleotides (QTNs) are evenly distributed throughout the genome. The estimated QTNs are used to separate a mixed linear model into a computationally efficient fixed effect model (FEM) and a computationally expensive random effect model (REM), which are then used iteratively. To completely eliminate the computationally expensive REM, we replaced REM with FEM by using Bayesian information criteria. To eliminate the requirement that QTNs be evenly distributed throughout the genome, we replaced the bin method with linkage disequilibrium information. The new method is called Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK). Both real and simulated data analyses demonstrated that BLINK improves statistical power compared to FarmCPU, in addition to remarkably reducing computing time. Now, a dataset with one million individuals and one-half million markers can be analyzed within three hours, instead of one week using FarmCPU.
Path Dependency in Jury Decision Making
Authors: Bindler Anna , Hjalmarsson Randi
Published: December 2018

A large behavioral economics literature is concerned with cognitive biases in individual and group decisions, including sequential decisions. These studies often find a negative path-dependency consistent with mechanisms such as the gambler's fallacy or contrast effects. We provide the first test for such biases in group decision making using observational data. Specifically, we study more than 27,000 verdicts adjudicated sequentially by over 900 juries for high-stake criminal cases at London's Old Bailey Criminal Court in the 18th and 19th centuries. Using jury fixed effects to account for heterogeneity in their baseline propensity to convict, we find that a previous guilty verdict significantly increases the chance of a subsequent guilty verdict by 6.7%–14.1%. This positive autocorrelation is robust to alternative estimation strategies, independent of jury experience and driven by the most recent lag and pairs of similar cases. Such positive path dependency may be explained by sequential assimilation effects, which may reflect a jury's desire to be internally consistent, and short-term “emotional” impacts of the characteristics and/or outcome of one case on another. As in modern-day jury studies, our results highlight that factors independent of the facts and evidence of the current case might affect jury behavior.
Safety and Efficacy of Lofexidine for Medically Managed Opioid Withdrawal: A Randomized Controlled Clinical Trial
Authors: Fishman Marc , Tirado Carlos , Alam Danesh , Gullo Kristen , Clinch Thomas , Gorodetzky Charles W.
Published: December 2018

Objectives:

To investigate the safety and efficacy of lofexidine for treating opioid withdrawal syndrome (OWS) and facilitating completion of opioid withdrawal.

Methods:

A multicenter, double-blind, placebo-controlled study was conducted at 18 US centers from June 2013 to December 2014. Participants (n = 603) aged ≥18 years, dependent on short-acting opioids, and seeking withdrawal treatment, randomized 3:3:2 to receive lofexidine 2.88 mg/d (n = 222), lofexidine 2.16 mg/d (n = 230), or placebo (n = 151) for 7 days. Primary outcome was the Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) scores rating withdrawal symptoms over days 1 to 7.

Results:

Participants were of mean age, 35 years; 71% male. Pairwise differences in overall SOWS-Gossop log-transformed least squares means were statistically significant for lofexidine 2.16 mg (difference, −0.21; 95% CI, −0.37 to −0.04;P = 0.02) and 2.88 mg (−0.26; 95% CI, −0.44 to −0.09;P = 0.003) compared with placebo. Fewer than half of participants in both groups completed the study. Completion rates for lofexidine 2.16 mg (41.5%; odds ratio [OR], 1.85;P = 0.007) and 2.88 mg (39.6%; OR, 1.71;P = 0.02) were significantly better compared with placebo (27.8%). Overall adverse event (AE) rates were similar across groups. Common AEs for lofexidine included orthostatic hypotension, hypotension, and bradycardia, but resulted in few study discontinuations.

Conclusions:

Lofexidine 2.16 mg and 2.88 mg significantly reduced symptoms of OWS versus placebo, and increased absolute rates of completing the 7-day study by 14% and 12%, respectively (a relative increase of 85% and 71%). Data suggest that lofexidine is a generally safe and effective nonopioid treatment for opioid withdrawal. Lofexidine could serve as a withdrawal treatment option when a nonopioid agent is preferred or required, when agonist-assisted withdrawal is unavailable, when agonist discontinuation caused OWS, and during induction into maintenance treatment with opioid agonists or antagonists.

Trial Registration:

ClinicalTrials.gov identifier: NCT01863186.
Gene-function studies in systemic lupus erythematosus
Authors: Rosetti Florencia , de la Cruz Abigail , Crispín José C.
Published: December 2018

Purpose of review

The aim of this review is to discuss recent developments in our understanding of how systemic lupus erythematosus (SLE)-associated genes contribute to autoimmunity.

Recent findings

Gene-function studies have revealed mechanisms through which SLE-associated alleles of IFIH1, TNFAIP3, IRF5, and PRDM1 likely contribute to the development of autoimmunity. Novel research has identified Mac-1 (encoded by ITGAM), CaMK4, and iRhom2 as plausible therapeutic targets in lupus nephritis.

The work discussed in this review has broad implications for our understanding of the pathogenesis of SLE and for the development of novel therapeutic strategies.
The microbiome in systemic autoimmune disease: mechanistic insights from recent studies
Authors: Dehner Carina , Fine Rebecca , Kriegel Martin A.
Published: December 2018

Purpose of review

The resident bacterial communities and the host immune system have coevolved for millennia. However, recent changes in modern societies have disrupted this coevolutionary homeostasis and contributed to a rise in immune-mediated conditions. The purpose of this review is to provide an overview of recently elucidated mechanisms of how certain taxa within the bacterial microbiome propagate autoimmunity.

Recent findings

Interactions between the bacterial microbiome with innate and adaptive immune cells propagate autoreactivity, chronic inflammation, and tissue damage in susceptible hosts. These interactions contribute to autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus, which are the focus of this review. Recent findings suggest that autoimmune manifestations in genetically susceptible individuals can arise through cross-reactivity with commensal orthologs of autoantigens or commensal-mediated posttranslational modification of autoantigens. Physiologic responses to gut, oral, or skin commensal bacteria can thus be misdirected toward such autoantigens in susceptible hosts. In addition, recent studies highlight that a breach of the gut barrier and translocation of commensal bacteria to non-gut organs can trigger several autoimmune pathways that can be prevented by commensal vaccination or dietary interventions.

Complex host–microbiota interactions contribute to systemic autoimmunity outside the gut. On a molecular level, posttranslational modification of, and cross-reactivity with, autoantigens represent mechanisms of how the microbiota mediates autoimmunity. On a cellular level, translocation of live gut bacteria across a dysfunctional gut barrier allows for direct interactions with immune and tissue cells, instigating autoimmunity systemically.
No difference in outcomes in a matched cohort of operative versus nonoperatively treated displaced medial epicondyle fractures
Authors: Axibal Derek P. , Ketterman Brian , Skelton Anne , Carry Patrick , Georgopoulos Gaia , Miller Nancy , Mayer Stephanie W.
Published: December 2018

The purpose of our study was to compare the treatment outcomes and complications between operatively and nonoperatively treated displaced medial epicondyle fractures. Pediatric patients treated for an acute, displaced medial epicondyle fracture between 2005 and 2015 were retrospectively reviewed. A total of 22 operative participants were matched to 22 nonoperative participants, with an average displacement of 9.7 mm in both groups. There was no statistical difference in average length of immobilization, median time to full pronation/supination and flexion/extension, proportion of patients needing physical therapy, and complications. There were no statistical differences in outcomes between operative and nonoperatively treated, moderately displaced, pediatric medial epicondyle fractures. This suggests that operative and nonoperative interventions show equivalent outcomes for these injuries.
Sacubitril/Valsartan in Daily Clinical Practice: Data From a Prospective Registry
Authors: Vicent Lourdes , Esteban-Fernández Alberto , Gómez-Bueno Manuel , De-Juan Javier , Díez-Villanueva Pablo , Iniesta Ángel Manuel , Ayesta Ana , González-Saldívar Hugo , Rojas-González Antonio , Bover-Freire Ramón , Iglesias Diego , García-Aguado Marcos , Perea-Egido Jesús A. , Martínez-Sellés Manuel
Published: December 2018

Sacubitril/valsartan (SV) is a new therapy in heart failure with reduced ejection fraction. Our aim was to determine the efficacy and safety of this drug daily clinical practice. We performed a multicenter registry in 10 hospitals. All patients who started SV from October 2016 to March 2017 on an outpatient basis were included. A total of 427 patients started treatment with SV. Mean follow-up was 7.0 ± 0.1 months. Forty-nine patients (11.5%) discontinued SV, and 12 (2.8%) died. SV discontinuation was associated with higher cardiovascular (hazard ratio 13.22, 95% confidence interval, 6.71–15.73, P < 0.001) and all-cause mortality (hazard ratio 13.51, 95% confidence interval 3.22–56.13, P < 0.001). Symptomatic hypotension occurred in 71 patients (16.6%). Baseline N-terminal pro–B-type natriuretic peptide levels, functional class, and left ventricular ejection fraction improved at the end of follow-up in patients who continued with SV (all P values ≤0.001). This improvement was not significant in patients with SV discontinuation. SV has a good tolerability in patients from daily clinical practice. SV withdrawal in patients with heart failure and reduced ejection fraction was independently associated with increased all-cause mortality. Patients who continued with SV presented an improvement in functional class left ventricular ejection fraction and N-terminal pro–B-type natriuretic peptide levels.
Atorvastatin Improves Doxorubicin-Induced Cardiac Dysfunction by Modulating Hsp70, Akt, and MAPK Signaling Pathways
Authors: Gao Ge , Jiang Shiliang , Ge Lili , Zhang Shanshan , Zhai Chungang , Chen Wenqiang , Sui Shujian
Published: December 2018

Atorvastatin is a lipid-regulating drug that is commonly used in clinical practice and can stabilize plaques. Increasing evidence shows that statins have anti–heart failure (HF) effects, but their specific mechanism is not clear. The purpose of this study was to investigate the cardioprotective effects of atorvastatin on HF in rats and its mechanism. Continuous intraperitoneal injection of 2.5 mg/kg/w doxorubicin for 6 weeks, with a cumulative dose of 15 mg/kg, was used to induce a rat model of HF. Then, the rats were treated with low-dose atorvastatin, high-dose atorvastatin, or saline for 4 weeks. In the DOX-treated groups, echocardiography showed decreases in left ventricular ejection fraction and fractional shortening and increases in left ventricular end-diastolic diameter and left ventricular posterior wall thickness compared with those in the control group, and increased levels of brain natriuretic peptide and Hsp70 were also found in the doxorubicin-treated groups. Compared with saline intervention, atorvastatin ameliorated left ventricular ejection fraction, fractional shortening, left ventricular end-diastolic diameter, and left ventricular posterior wall thickness (a significant difference was observed only in the high-dose group) and reduced serum brain natriuretic peptide. Hematoxylin and eosin staining showed that atorvastatin ameliorated myocardial injury. The improvement in cardiac function induced by atorvastatin was accompanied by increased Hsp70 expression, decreased p-ERK and p-JNK expression, and a reduction in myocardial fibrosis shown by Masson staining. In addition, atorvastatin had a protective effect on the myocardial apoptosis signaling pathway, with increased p-Akt expression and downregulated cleaved caspase-3 expression, and the reduction in myocardial apoptosis was confirmed by a TUNEL assay. Therefore, our experiments demonstrated that atorvastatin may protect cardiac function by modulating Hsp70, p-Akt, p-ERK, and p-JNK signaling to reduce myocardial fibrosis and myocardial apoptosis.
Factors related to age at menopause among Korean women: the Korean Longitudinal Survey of Women and Families
Authors: Kim Young-taek , Cha Chiyoung , Lee Mi-ran
Published: December 2018

Objective:

The purpose of this study was to explore factors influencing age of menopause among Korean women.

Methods:

For this secondary analysis study, panel data for Waves 4 through 6 of the Korean Longitudinal Survey of Women were used. Women aged 40 to 60 who were menstruating at Wave 4 were included in the analysis (N = 5,437). Sociodemographic, health status, and health behavioral factors were examined to explore their influence on menopause using Kaplan–Meier analysis and Cox regression analysis.

Results:

Korean women who perceived themselves to be overweight or obese, who had depressive symptoms, or who smoked or were current smokers had higher probabilities of experiencing the onset of menopause, whereas those who had educational achievement lower than high school had a lower probability of experiencing the onset menopause.

Conclusions:

Various factors influenced menopause, including sociodemographic, health status, and health behaviors. Specific tailored interventions for the management of depressive symptoms and smoking cessation could be developed to target modifying variables for Korean women, in preparation for menopause. Also, the role of perceived body weight on menopause could be further explored to identify sociocultural factors for age at menopause.
The effect of a midwife-based counseling education program on sexual function in postmenopausal women: a randomized controlled clinical trial
Authors: Naeij Ehtram , Khani Soghra , Firouzi Armin , Moosazadeh Mahmood , Mohammadzadeh Farnaz
Published: December 2018

Objective:

The present study was conducted to investigate the effect of a midwife-based counseling education program on sexual function in postmenopausal women.

Methods:

A randomized clinical trial was conducted on 52 eligible postmenopausal women. Participants’ sexual function was assessed using the Female Sexual Function Index (FSFI). The women were randomly allocated into two groups: (1) the intervention group, in which the participants received a midwife-based counseling education program in 4 sessions held at 10-day intervals, with each session lasting for 70 minutes; (2) the control group, in which the participants only received routine care. Data were collected 1 week before the start of the sessions, 2 weeks after the end of the sessions, and 2 months after the last follow-up.

Results:

No statistically significant differences were reported between the groups in terms of personal and sociodemographic characteristics and sexual function before the intervention; the total FSFI score was 17.05 (±4.54) in the intervention group and 16.66 (±3.62) in the control group. After the program, in the first and second follow-ups, the scores reached 27.18 (±4.61) and 28.20 (±4.43) in the intervention group and 16.06 (±3.94) and 16.32 (±2.98) in the control group. Significant improvements were observed in the total score of sexual function and all the FSFI domains in the intervention group, but not in the control group (P < 0.001).

Conclusion:

Midwife-based counseling education can be an appropriate approach to improving sexual function in postmenopausal women.
Glaucoma Workup in Congenital Zika Syndrome
Authors: de Oliveira Daniela R. , Ventura Camila V. , Esporcatte Bruno L.B. , Gracitelli Carolina P.B. , Dias Natalia de Carvalho , Ventura Liana O. , Belfort Rubens , Rolim-de-Moura Christiane
Published: December 2018

Purpose:

The main aim of this study was to perform a glaucoma workup in infants with congenital Zika syndrome (CZS).

Patient and Methods:

This cross-sectional study included 188 eyes of 107 children (1.1±0.3 y; range, 0.3 to 1.8 y) with CZS. The confirmation of the syndrome was possible in 77 of 107 (72.0%) of the enrolled infants based on positive immunoglobulin M antibody capture enzyme-linked immunosorbent assay for Zika virus in the cerebrospinal fluid. All infants underwent a complete ophthalmic examination and bilateral fundus imaging was captured using a wide-angle digital fundus camera (RetCam).

Results:

Five eyes (2.6%) presented 2 criteria for glaucoma diagnosis: 1 eye (0.5%) presented increased intraocular pressure and increased vertical cup-to-disc ratio (CDR); 3 eyes (1.6%) presented increased horizontal corneal diameter and increased vertical, and 1 eye (0.5%) presented myopia related to increased axial length and increased vertical CDR. When excluding the CDR criterion, there was no case of glaucoma in this sample. A significant correlation was observed between high vertical CDR and small cephalic perimeter at birth (P=0.002) and the presence of clinical macular lesions (P=0.031).

Conclusion and Relevance:

Although childhood glaucoma was not detected in this sample, increased vertical CDR is present in children with CZS, associated with microcephaly and clinical macular lesions at birth. This finding may lead to a misdiagnosis of glaucoma.
Identification of Gardnerella vaginalis and Atopobium vaginae in Women With Bacterial Vaginosis in Northern Iran
Authors: Roohbakhsh Esmaeil , Mojtahedi Ali , Roohbakhsh Zahra , Khavari-Nejad Ramezan Ali , Amirmozafari Nour
Published: December 2018

Background

Bacterial vaginosis is the most common lower genital tract infection among women of reproductive age. Its causative agent is often the bacterium Gardnerella vaginalis, which exists in synergism with other mostly anaerobic bacteria such as Atopobium vaginae, Mobiluncus curtisii, and Megasphaera type I.

Methods

A total of 211 women, who referred to obstetrics and gynecology clinics in Rasht City for suspected vaginal infections, were tested for possible bacterial vaginosis. The presence of G. vaginalis and A. vaginae was verified by 5 different laboratory methods based on the Amsel criteria. These methods included determination of pH, whiff test, and observation of clue cells in a direct smear. Polymerase chain reaction using specific primers was performed on the extracted DNA from the vaginal specimens.

Results

Sixty cases of bacterial vaginosis, of the 211 women tested for suspected vaginal infections, were confirmed using Amsel criteria. In 44% (29/66) and 29% (19/66) of these bacterial vaginosis cases, the presence of G. vaginalis and A. vaginae was confirmed by polymerase chain reaction, respectively.

Conclusions

Gardnerella vaginalis had a very high prevalence in the 18- to 35-year-old women suffering from bacterial vaginosis in this region of Iran. Presumably, these cases were recommended for appropriate treatment, but the wider issue is about prevention in this age group and appropriate public health messages to raise awareness.
Translating peripheral bladder afferent mechanosensitivity to neuronal activation within the lumbosacral spinal cord of mice
Authors: Grundy Luke , Harrington Andrea M. , Caldwell Ashlee , Castro Joel , Staikopoulos Vasiliki , Zagorodnyuk Vladimir P. , Brookes Simon J.H. , Spencer Nick J. , Brierley Stuart M.
Published: December 2018

Primary afferent neurons transduce distension of the bladder wall into action potentials that are relayed into the spinal cord and brain, where autonomic reflexes necessary for maintaining continence are coordinated with pathways involved in sensation. However, the relationship between spinal circuits involved with physiological and nociceptive signalling from the bladder has only been partially characterised. We used ex vivo bladder afferent recordings to characterise mechanosensitive afferent responses to graded distension (0-60 mm Hg) and retrograde tracing from the bladder wall to identify central axon projections within the dorsal horn of the lumbosacral (LS) spinal cord. Labelling of dorsal horn neurons with phosphorylated-MAP-kinase (pERK), combined with labelling for neurochemical markers (calbindin, calretinin, gamma aminobutyric acid, and parvalbumin) after in vivo bladder distension (20-60 mm Hg), was used to identify spinal cord circuits processing bladder afferent input. Ex vivo bladder distension evoked an increase in primary afferent output, and the recruitment of both low- and high-threshold mechanosensitive afferents. Retrograde tracing revealed bladder afferent projections that localised with pERK-immunoreactive dorsal horn neurons within the superficial laminae (superficial dorsal horn), dorsal gray commissure, and lateral collateral tracts of the LS spinal cord. Populations of pERK-immunoreactive neurons colabelled with calbindin, calretinin, or gamma aminobutyric acid, but not parvalbumin. Noxious bladder distension increased the percentage of pERK-immunoreactive neurons colabelled with calretinin. We identified LS spinal circuits supporting autonomic and nociceptive reflexes responsible for maintaining continence and bladder sensations. Our findings show for the first time that low- and high-threshold bladder afferents relay into similar dorsal horn circuits, with nociceptive signalling recruiting a larger number of neurons.
The Value of Diffusion-Weighted MRI in the Long-term follow-up After Subtotal Petrosectomy for Extensive Cholesteatoma and Chronic Suppurative Otitis Media
Authors: Delrue Stefan , De Foer Bert , van Dinther Joost , Zarowski Andrzej , Bernaerts Anja , Vanspauwen Robby , Casselman Jan W. , Offeciers Erwin , Somers Thomas
Published: December 2018

Objective:

To report the long-term follow-up with diffusion-weighted magnetic resonance imaging (DW MRI) after subtotal petrosectomy (SP) with blind sac closure of the external auditory canal for extensive cholesteatoma and chronic suppurative otitis media.

Study Design:

Retrospective clinical record study.

Setting:

Tertiary referral center.

Patients:

Thirty-one patients (31 ears) with extensive cholesteatoma and 17 patients (19 ears) with chronic suppurative otitis media without cholesteatoma who underwent SP between July 1995 and December 2015.

Interventions:

All 48 patients were followed clinically and with DW MRI to rule out residual cholesteatoma.

Main Outcome Measure:

Residual cholesteatoma, indicated by a marked hyperintensity on non-echoplanar (non-EP) DW MRI.

Results:

In the cholesteatoma group the mean interval between surgery and the latest DW MRI was 3.9 years. Seven patients presented with a residual cholesteatoma pearl. The mean interval between surgery and detection of residual disease was 3.7 years. In the chronic suppurative otitis media group the mean interval between surgery and the latest DW MRI was 5.3 years. Residual cholesteatoma was found in three patients. Mean interval between surgery and the detection of disease was 4.5 years.

Conclusions:

This study shows the importance of DW MRI in the follow-up after SP for cholesteatoma and chronic suppurative otitis media. A little higher residual cholesteatoma rate was found compared with earlier studies, where patients were followed only clinically. One may wonder whether reintervention is always needed or whether in selected cases with small pearls, one may still observe these by a watchful waiting policy with DW MRI.
Otopathology of Unilateral Cochlear Implantation in Patients With Bilateral Temporal Bone Fracture
Authors: Trakimas Danielle R. , Knoll Renata M. , Ishai Reuven , Lee Daniel J. , Jung David H. , Nadol Joseph B. , Remenschneider Aaron K. , Kozin Elliott D.
Published: December 2018

Objective:

Audiometric outcomes following cochlear implantation (CI) in patients with temporal bone fracture (TBF) are variable and the pathophysiology is not well understood. Herein, we describe otopathologic findings in two such cases to provide insight into pathophysiology and outcomes.

Patients:

Two patients had a history of head trauma resulting in bilateral TBF and sudden, profound, sensorineural hearing loss.

Intervention:

Both cases underwent unilateral CI following head trauma.

Main Outcome Measures:

Both TBs from each patient were harvested postmortem and histologically analyzed to determine fracture lines, intralabyrinthine fibroosseous changes, and spiral ganglion neuron (SGN) counts. Clinical histories and audiometric outcomes were also reviewed.

Results:

In both cases, the implanted TB showed extensive intracochlear ossification, which was greater when fracture involved the cochlea. In contrast, the nonimplanted cochleae were patent with small osseous deposits at the round window membrane. Interaural SGN counts were lower on the implanted side and hearing results were moderate to poor.

Conclusions:

Otopathologic analyses of patients with a CI after bilateral TBF are rare. Based on otopathology of two patients with bilateral TBF and subsequent CI, implanted TBs show extensive intracochlear fibroosseous changes greater than the nonimplanted side. Findings have implications for auditory rehabilitation after TBF.