bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender differences and individual, household, and workplace characteristics: Regional geographies of extended working lives
Authors: Shelton Nicola , Head Jenny , Carr Ewan , Zaninotto Paola , Hagger‐Johnson Gareth , Murray Emily
Published: November 2018

Increasing labour market participation among older workers is embedded in government policy in the United Kingdom and many other industrialised countries with rises in the state pension age in response to increasing life expectancy. Despite this, many workers stop working before state pension age with around a 20% reduction in the proportion of adults in work between ages 50 and 60 in 2011 in England and Wales. This paper considers the risk of remaining in work by region and gender between 2001 and 2011 for adults aged 40–49 in 2001. Men had significantly higher risk of extended working in the East Midlands (1.4×) East of England (1.5×), South East (1.6×), and South West (1.6×) compared with the North East. Women in all regions apart from London and Wales had significantly higher risk of extended working compared with the North East: ranging from 1.15 times in the North West and West Midlands to 1.6 times in the South West. Adjustment for nonemployment‐related socio‐economic status, housing tenure, qualifications, and car ownership, and employment status in 2001 attenuated all significant regional differences in extended working in men and in women in most regions. Workplace characteristics attenuated most of the remaining regional differences in women: women working in larger employers in 2001 or working at distances of 200 km or more, abroad or from home, had lower risk of remaining in work, whereas access to a car and higher working hours increased risk. Policies to increase qualifications and skills among older adults are recommended.
The timing of cumulus cell removal for intracytoplasmic sperm injection influences the capability of embryonic development
Authors: Mizuno Satoshi , Ishikawa Yuko , Matsumoto Hiroshi , Sato Manabu , Ida Mamoru , Fukuda Aisaku , Morimoto Yoshiharu
Published: November 2018

Purpose

To determine whether the presence of intact cumulus cells during the preincubation period for ICSI should be considered as a critical factor in fertilization and embryonic development.

Methods

The cohort of this prospective randomized study was limited to infertile women younger than 39 years of age who underwent controlled ovarian stimulation for ICSI between October 2013 and May 2015 and whose embryos were to be incubated until day 5. Women with estradiol levels of <2000 pmol/L on the day of HCG injection were excluded. Cumulus cells were removed immediately after OPU in Group A and at 120 minutes after OPU in Group B. ICSI was performed with all mature oocytes, and fertilized oocytes were cultured to the blastocyst stage. Maturation, fertilization, blastocyst, good quality blastocyst, pregnancy, live birth, and miscarriage rates were compared.

Results

There were no significant differences in maturation, fertilization, blastocyst, pregnancy, live birth, or miscarriage rates between Groups A and B. However, the percentage of good quality blastocysts was significantly higher in Group B than Group A (52.0% vs 33.1%).

Conclusions

Intact cumulus cells should be maintained during the preincubation period, as they are important to embryonic development after fertilization.
Applying facilely synthesized CuO/CeO2 photocatalyst to accelerate methylene blue degradation in hypersaline wastewater
Authors: Li Zhendong , Liu Dongfang , Huang Wenli , Sun Yanmei , Li Songrong , Wei Xiaocheng
Published: November 2018

Textile and dye effluents have strong color, unstable pH and COD, a lot of inorganic salt, and high biotoxicity. It is difficult and inefficient to remove dyes from high‐saline wastewater by traditional methods. In this study, a simple synthetic CuO/CeO2 photocatalyst is used to achieve high efficiency photodegradation of methylene blue in high salt wastewater. The p‐type CuO/n‐type CeO2 heterojunction photocatalyst is synthesized by a modified hydrothermal‐calcination method. The XRD and XPS reveal the successful synthesis of CuO/CeO2 composite. The SEM and TEM images show that the sample consists of large amounts of well‐dispersed CuO nanosphere loading on the CeO2 layers. DRS exhibits the absorption band (about 510 nm) and the band gap energy (2.43 eV) of the CuO/CeO2 composite. Compared with pure CuO, CeO2, and TiO2 (P25), the prepared CuO/CeO2 can increase the mineralization rate of MB by 18.19%~33.74%. More than 80% of MB can be effectively removed in the wastewater containing 5~80 g/L NaCl with a wide pH value range of 2.11~9.02, and the degradation processes follow the pseudofirst‐order reaction kinetics. Active species trapping experiments confirm that the degradation of methylene blue is mainly attributed to hydroxyl radical; besides, O2▪− and hole (h+) also play important roles. Chlorine ions have dual effects in photocatalytic reactions. This work could provide a new approach to construct new heterojunction photocatalysts and a deeper insight for the treatment of hypersaline dye wastewater.
Tribological properties of Ti‐doped diamond‐like carbon coatings under dry friction and PAO oil lubrication
Authors: Guo Youzhi , Guo Peng , Sun Lili , Li Xiaowei , Ke Peiling , Li Qiang , Wang Aiying
Published: November 2018

Titanium‐doped diamond‐like carbon (Ti‐DLC) coatings with Ti concentration of 4 at.% (Ti4at.%‐DLC) and 27 at.% (Ti27at.%‐DLC) were prepared by a hybrid ion beam deposition system for comparison. The tribological behaviors of Ti‐DLC coatings under dry friction and boundary lubrication conditions were systematically investigated. Results showed that, under dry friction, the Ti4at.%‐DLC coating displayed lower friction coefficient (0.07) and wear rate due to the continuous transfer film formed in the sliding interface, while Ti27at.%‐DLC coating was worn out at initial stage due to severe abrasive wear. And under boundary lubrication, both the Ti4at.%‐DLC and Ti27at.%‐DLC coatings showed excellent tribological properties attributing to the formation of oil film between sliding interface. In particular, Ti27at.%‐DLC performed the lowest wear rate of 1.12 × 10−16 m3 N−1 m−1 in this friction case. In conclusion, compared with Ti27at.%‐DLC coating, Ti4at.%‐DLC coating exhibited better tribological performances both under dry friction and boundary lubrication. The present result provides guidance for the selection of DLC coatings according to the realistic environment of starved‐oil and rich‐oil conditions.
A powerful and data‐adaptive test for rare‐variant–based gene‐environment interaction analysis
Authors: Yang Tianzhong , Chen Han , Tang Hongwei , Li Donghui , Wei Peng
Published: November 2018

As whole‐exome/genome sequencing data become increasingly available in genetic epidemiology research consortia, there is emerging interest in testing the interactions between rare genetic variants and environmental exposures that modify the risk of complex diseases. However, testing rare‐variant–based gene‐by‐environment interactions (GxE) is more challenging than testing the genetic main effects due to the difficulty in correctly estimating the latter under the null hypothesis of no GxE effects and the presence of neutral variants. In response, we have developed a family of powerful and data‐adaptive GxE tests, called “aGE” tests, in the framework of the adaptive powered score test, originally proposed for testing the genetic main effects. Using extensive simulations, we show that aGE tests can control the type I error rate in the presence of a large number of neutral variants or a nonlinear environmental main effect, and the power is more resilient to the inclusion of neutral variants than that of existing methods. We demonstrate the performance of the proposed aGE tests using Pancreatic Cancer Case‐Control Consortium Exome Chip data. An R package “aGE” is available at http://github.com/ytzhong/projects/.
Efficient Conversion of Cellulose to 5‐Hydroxymethylfurfural in NaHSO4/ZrO2/H2O‐THF Biphasic System
Authors: Fang Xiaowei , Wang Ze , Yuan Bo , Song Wenli , Li Songgeng , Lin Weigang
Published: November 2018

5‐hydroxymethylfurfural (HMF) is an important bio‐based platform chemical for liquid fuel production. Herein, efficient conversion of cellulose to HMF in NaHSO4/ZrO2/H2O‐THF biphasic system was investigated with a high HMF yield up to 86.5%. In the co‐catalytic system, H+ ions given from NaHSO4 was promotive to all steps of the cellulose‐to‐HMF conversion; abundant alkaline sites of ZrO2 was particularly favorable to the glucose‐to‐fructose isomerization. The accelerated conversion of glucose as well as the fast extraction of HMF from aqueous phase to tetrahydrofuran (THF) phase, favored the inhibition of humins which was generated from condensation between glucose and HMF. Only a trace amount of humins over ZrO2 was detected after reaction, which guaranteed the reusability of ZrO2 in six running experiments without any post‐treatment. The good reusability of ZrO2, the low ‐cost of NaHSO4, and the biomass‐derived THF were advantageous for potential industrial application.
Cross‐Coupling Reactions of Aryltriethoxysilanes and Diaryldiselenides ‐ A New Route for the Synthesis of Diarylselenides
Authors: Sahani Amber J. , Burange Anand S. , Narasimhan Swetha , Jayaram Radha V.
Published: November 2018

The present work reports, the new route for the synthesis of diarylselenides by coupling of aryltriethoxysilanes with diaryldiselenides. Various ligands were screened for the said coupling in presence of a copper salt. Cu(II)/bpy in DMSO showed excellent activity for the coupling of aryltriethoxysilanes with various diaryldiselenides. In the present work, no fluoride source was used for the activation of aryltriethoxysilanes and also a possible mechanism was proposed for the said reaction. Moreover, diaryldisuphides and diarylditellurides were also effectively coupled with aryltriethoxysilanes using proposed catalytic system. Importantly, use of non‐precious metal based catalytic system, makes the protocol interesting.
Green Synthesis of the Ag/Bentonite Nanocomposite UsingEuphorbia larica Extract: A Reusable Catalyst for Efficient Reduction of Nitro Compounds and Organic Dyes
Authors: Sajadi S. Mohammad , Kolo Kamal , Hamad Samir M. , Mahmud Sarbast. A. , Barzinjy Azeez A. , Hussein Sarbast M.
Published: November 2018

During this study, a rapid and simple method is presented for the green synthesis of the Ag/bentonite nanocomposite using Euphorbia larica extract as a stabilizing and reducing agent. The average size of biosynthesized Ag nanoparticles (NPs) was estimated less than 32 nm. The catalytic activity of Ag/bentonite nanocomposite was investigated in the reduction of 4‐nitrophenol (4‐NP) and some organic dyes including Congo red (CR), Methylene blue (MB) and Rhodamine B (RhB). According to the catalytic results, the biosynthesized Ag/bentonite nanocomposite can be used as an appropriate catalyst for an efficient, simple and economic strategy to degrade various organic dyes from wastewaters. Recyclability tests demonstrated catalyst stability and its capability in practical applications.
Metal‐Free Synthesis of the Functionalized Quinoxalines via α‐Aminocarbonyl Compounds with o‐Phenylenediamine
Authors: Pu Jinghong , Liu Xingxing , Luo Xinliang , Zhan Zhenzhen , Zhang Yixin , Huang Guosheng
Published: November 2018

An expeditious one‐pot, metal‐free multicomponent synthesis of quinoxalines has been developed, from easily available starting materials as α‐aminocarbonyl compounds and o‐phenylenediamine instead of complex catalyst systems. The reaction has a broad substrate scope and displays excellent functional‐group tolerance. This method could be easily applied to many fields.
A1‐A2 Type Wide Bandgap Polymers for High‐Performance Polymer Solar Cells: Energy Loss and Morphology
Authors: An Yongkang , Liao Xunfan , Chen Lie , Xie Qian , Zhang Ming , Huang Bin , Liao Zhihui , Guo Hui , Jazib Ali , Han Jihui , Liu Feng , Jen Alex K.‐Y. , Chen Yiwang
Published: November 2018

Introducing electron‐withdrawing groups onto donor‐acceptor (D‐A) type conjugated materials is a commonly used method for lowering their highest occupied molecular orbital (HOMO) energy level to achieve higher open circuit voltage (Voc) in polymer solar cells (PSCs). However, this method is rather costly due to the tedious synthesis and low yield involved in preparing the target monomers. Here, a novel design concept of using two different acceptor units to construct acceptor1‐acceptor2 (A1‐A2) type polymers with a deep HOMO level is proposed. Two A1‐A2 type wide bandgap (WBG) polymers, PB24‐3TDC and PB68‐3TDC, were designed for PSCs. The developed polymers possess proper energy levels and complementary absorption with an efficient electron acceptor ITIC‐Th. More importantly, by slightly regulating the alkyl side‐chains, molecular stacking and photoluminescence (PL) emission energy loss of polymers can be alternated significantly. As a result, tuned Voc from 0.9 to 1.0 V and short‐circuit current (Jsc) from 9.4 to 17.0 mA cm−2 can be achieved. The device based on PB24‐3TDC:ITIC‐Th exhibits a higher power conversion efficiency (PCE) of 10.3% compared to PB68‐3TDC:ITIC‐Th based device with a PCE of 7.88%. These results show that the design concept of A1‐A2 type polymer donors have great potential for blending with non‐fullerene acceptors for achieving high performance PSCs.
Constraint forces from imposed deformations
Authors: Berger Johannes , Feix Jürgen
Published: November 2018

In statically indeterminate systems, imposed deformation generally cannot set freely. In order to achieve the deformation compatibility, constraint forces are required. From this, it can be deduced that the constraint forces for a given deformation are dependent on the stiffness of the system. The greater the stiffness, the greater the internal constraint forces. For this reason, constraint forces in reinforced concrete structures are generally worth mentioning and must be taken into account in the design. The accurate development of a constraint force depends on numerous factors. These are mainly the stiffness distribution over the length, stiffness of the cross section, ductility of the reinforcement and creep ability of concrete. To gain more information about the real behavior, experiments were carried out on reinforced concrete beams and prestressed beams.
Development of Divide‐and‐Conquer Density‐Functional Tight‐Binding Method for Theoretical Research on Li‐Ion Battery
Authors: Chou Chien‐Pin , Sakti Aditya Wibawa , Nishimura Yoshifumi , Nakai Hiromi
Published: November 2018

The density‐functional tight‐binding (DFTB) method is one of the useful quantum chemical methods, which provides a good balance between accuracy and computational efficiency. In this account, we reviewed the basis of the DFTB method, the linear‐scaling divide‐and‐conquer (DC) technique, as well as the parameterization process. We also provide some refinement, modifications, and extension of the existing parameters that can be applicable for lithium‐ion battery systems. The diffusion constants of common electrolyte molecules and LiTFSA salt in solution have been estimated using DC‐DFTB molecular dynamics simulation with our new parameters. The resulting diffusion constants have good agreement to the experimental diffusion constants.
Environment and strain energy related micromechanics analysis for properties of carbon nanotubes
Authors: Gao Ming , Bian Lichun
Published: November 2018

In the present study, a theoretical prediction of the effect of thermal environment on elastic properties of single‐walled carbon nanotubes (SWCNTs) is reported, and a molecular structural mechanics model is proposed in which the covalent bonds are traded as a truss. The influences of the temperature and the coefficient of thermal expansion (CTE) on Young's modulus and shear modulus of both armchair and zigzag SWCNTs are investigated. When CTE is and remains constant, the surface Young's modulus and the normal Young's modulus are reduced, respectively, as compared with the normal temperature. With the change of CTE, its effect on the elastic constant is far greater than the temperature effect itself. According to the principle of elastic theory, a temperature‐dependent continuum shell model of strain energy is also established. The strain energy of single‐walled carbon nanotubes decreases with the increase of the temperature.
Lambda models from Chern-Simons theories
Authors: Schmidtt David M.
Published: November 2018

Abstract

In this paper we refine and extend the results of [1], where a connection between the AdS
5 × S
5 superstring lambda model on S
1 = ∂D and a double Chern-Simons (CS) theory on D based on the Lie superalgebra

$$ \mathfrak{p}\mathfrak{s}\mathfrak{u} $$

p
s
u

(2, 2|4) was suggested, after introduction of the spectral parameter z. The relation between both theories mimics the well-known CS/WZW symplectic reduction equivalence but is non-chiral in nature. All the statements are now valid in the strong sense, i.e. valid on the whole phase space, making the connection between both theories precise. By constructing a z-dependent gauge field in the 2+1 Hamiltonian CS theory it is shown that: i) by performing a symplectic reduction of the CS theory the Maillet algebra satisfied by the extended Lax connection of the lambda model emerges as a boundary current algebra and ii) the Poisson algebra of the supertraces of z-dependent Wilson loops in the CS theory obey some sort of spectral parameter generalization of the Goldman bracket. The latter algebra is interpreted as the precursor of the (ambiguous) lambda model monodromy matrix Poisson algebra prior to the symplectic reduction. As a consequence, the problematic non-ultralocality of lambda models is avoided (for any value of the deformation parameter λ ⊂ [0, 1]), showing how the lambda model classical integrable structure can be understood as a byproduct of the symplectic reduction process of the z-dependent CS theory.
A fusion for the periodic Temperley-Lieb algebra and its continuum limit
Authors: Gainutdinov Azat M. , Jacobsen Jesper Lykke , Saleur Hubert
Published: November 2018

Abstract

The equivalent of fusion in boundary conformal field theory (CFT) can be realized quite simply in the context of lattice models by essentially glueing two open spin chains. This has led to many developments, in particular in the context of chiral logarithmic CFT.

We consider in this paper a possible generalization of the idea to the case of bulk conformal field theory. This is of course considerably more difficult, since there is no obvious way of merging two closed spin chains into a big one. In an earlier paper, two of us had proposed a “topological” way of performing this operation in the case of models based on the affine Temperley-Lieb (ATL) algebra, by exploiting the associated braid group representation and skein relations. In the present work, we establish — using, in particular, Frobenius reciprocity — the resulting fusion rules for standard modules of ATL in the generic as well as partially degenerate cases. These fusion rules have a simple interpretation in the continuum limit. However, unlike in the chiral case this interpretation does not match the usual fusion in non-chiral CFTs. Rather, it corresponds to the glueing of the right moving component of one conformal field with the left moving component of the other.
Outcomes and emergency medical services resource utilization among patients with syncope arriving to the emergency department by ambulance
Authors: Yau Lawrence , Mukarram Muhammad A. , Kim Soo-Min , Arcot Kirtana , Thavorn Kednapa , Stiell Ian G. , Taljaard Monica , Rowe Brian H. , Sivilotti Marco L. A. , Thiruganasambandamoorthy Venkatesh
Published: November 2018

Objective

Syncope accounts for 1% of emergency department (ED) visits, yet few experience a serious adverse event (SAE). Two-thirds of syncope patients are transported to the ED by ambulance, placing considerable burden on emergency medical services (EMS), and many of these transports may be unnecessary. We estimated the proportion of syncope patients who fell into a low-risk category based on an ED diagnosis of vasovagal syncope and the absence of EMS intervention, hospitalization, or SAE.

Methods

We conducted a multicentre prospective cohort study enrolling adult syncope patients transported to the ED by ambulance over 13 months. We collected demographics and EMS interventions, and followed patients for 30 days to identify all SAE, including death, dysrhythmia, myocardial infarction, aortic dissection, pulmonary embolism, subarachnoid hemorrhage, significant hemorrhage, and related procedural interventions.

Results

Of 990 (67.2%) patients transported to the ED by ambulance, 121 had EMS interventions, 137 suffered 30-day SAE, 393 (39.7%; 95%CI 36.6, 42.8) were deemed low risk, 41 patients with vasovagal syncope were lost to follow-up, and 298 patients were diagnosed with non-vasovagal syncope. During transport, 121 (12.2%; 95%CI 10.2, 14.3) patients underwent some EMS intervention, and 137 (14.6%; 95%CI 12.4, 16.9) suffered SAEs within 30 days.

Conclusion

About 40% of patients transported to the ED by ambulance are at low risk and may not benefit from paramedic care or transport to a hospital. A robust clinical decision tool would help identify patients safe for treat-and-release, diversion to alternative care, or rapid offload into low-acuity ED areas, potentially reducing EMS workload and cost.
Female Immigration to ISIS: Unlocking Motives to Turn the Tide
Authors: Zafar Aniq
Published: November 2018

This essay presents the analysis, approach and understanding of the underlying reasons why
females join the “Islamic State in Iraq and Syria” (ISIS), accept its rules and impositions,
play an active role in it, and often actively recruit other women to join ISIS as perceived
by an experienced and savvy communications expert and professional who also took active part
in anti-terrorism campaigns in Pakistan. Previously he was a journalist who gained a deep
understanding of the political and policy-making dynamics in his country. Especially
valuable is the section on the “Way Forward”; that is, how to effectively tackle the
recruitment campaign and methodology of ISIS.
Women’s Role in Recruitment for ISIS/Islamist Networks in
Pakistan
Authors: Gul Imtiaz
Published: November 2018

Historically, women in Pakistan’s northwestern territories bordering Afghanistan have
played a critical role in providing money and men to jihadist organizations such as the
Taliban, Al-Qaeda, and “Islamic State in Iraq and Syria” (ISIS). Lack of education, too
little exposure and a male-dominated conservative milieu constitute some of the ingredients
of support for these outfits. This was true for over three decades and the phenomenon
remained restricted to the rural, backward northwestern regions. But since the early 1990s,
outfits such as the Al-Hudda Foundation – an exclusively women-focused organization – began
serving as the initial hooks for middle- and upper-class women whom the Foundation targets.
It brainwashes women into using hijab, and also into believing that they
need to forge an alliance against the West and work for an Islamic, Sharia-based state. This
advocacy turns many affluent women into religious radicals who can potentially work as the
first line of recruits for extremist outfits like Daesh/IS. However small their numbers,
these women represent a big threat to the global liberal values of society.
2523 Noninvasive biomarkers for inflammatory bowel disease: Drawbacks and potential
Authors: Patel Vihang , Seif Sherif , Barrett Terrence
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Approximately 1.6 million Americans suffer from inflammatory bowel diseases (IBD), ulcerative colitis, and Crohn’s disease. It is a challenge for both physicians and patients alike to manage the disease, primarily due to lack of disease specific biomarkers. Endoscopy remains the gold standard to diagnose and evaluate IBD activity. Current biomarkers or their combinations cannot adequately predict IBD progression or relapse, and response to therapy. METHODS/STUDY POPULATION: In total, 97 IBD patients recruited at University of Kentucky undergoing endoscopy. Patients medical information was collected from electronic database including C-reactive protein (CRP), fecal calprotectin (FC), endoscopy/pathology report. RESULTS/ANTICIPATED RESULTS: The mean CRP and FC levels were 1.3 (normal <1) and 679 (normal <162), respectively. FC (sensitivity 74%) was more reliable to predict mucosal inflammation compare to CRP (sensitivity 36%). However, 52% of patients did not have FC performed (vs. CRP only 4%), and 45% of these patients failed to submit stool sample for analysis. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggests FC is the most promising noninvasive marker for disease monitoring in IBD. It correlates well with endoscopic activity and mucosal inflammation. However, further analysis must be done to evaluate barriers to testing and issues with compliance from patients. We feel strongly that a blood biomarker for disease activity is vital for disease monitoring and response to therapy in IBD.
2064 Regulation of retinal protein O-GlcNAcylation by angiotensin-(1-7) and cAMP
Authors: Dierschke Sadie , Arnold Amy , Dennis Michael M.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Increased retinal protein O-GlcNAcylation occurs in response to hyperglycemia and contributes to diabetic retinopathy. Renin-angiotensin system (RAS) blockers reduce the incidence of diabetic retinopathy. Beneficial effects of RAS blockers are often attributed to production of angiotensin-(1-7) (Ang1-7). The objective here is to determine the impact of Ang1-7 on retinal protein O-GlcNAcylation. METHODS/STUDY POPULATION: C57/BL6 mice were fed a high-fat diet for 8 weeks and then treated for 3 weeks with either a vehicle control, the RAS blocker captopril, or captopril and the Ang1-7 receptor antagonist A779. R28 cells were used to assess levels of O-GlcNAcylated proteins in response to Ang1-7, and the role of cAMP was investigated with addition of forskolin, 6-Bnz-cAMP-AM, and 8-pCPT-2-O-Me-cAMP-AM to cell culture medium. RESULTS/ANTICIPATED RESULTS: Captopril attenuated retinal protein O-GlcNAcylation in mice fed a high-fat diet. This effect was reversed by A779. Ang1-7 attenuated protein O-GlcNAcylation and increased cAMP levels. Forskolin and the EPAC selective cAMP analog 8-pCPT-2-O-Me-cAMP-AM, but not the PKA selective cAMP analog 6-Bnz-cAMP-AM, attenuated O-GlcNAcylation. Inhibiting EPAC blocked the effect of forskolin, whereas inhibiting PKA did not. DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates a novel role for Ang1-7 in the retina and identifies a potential EPAC-dependent mechanism that regulates protein O-GlcNAcylation. Thus, future therapeutics targeted at an Ang1-7/EPAC axis in retina may be used to address DR.
2464 Sexual dimorphism in a mouse model of syndromic thoracic aortic aneurysm
Authors: Chen Zheying , Daugherty Alan , Sheppard Mary
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Pre-clinical and clinical observations have noted that increased aortic dilation is associated with male sex. Using an experimental model of severe, syndromic thoracic aortic aneurysms, we quantify aortic dilation and elastin stability in male Versus female mice. METHODS/STUDY POPULATION: Ascending aortas from male and female FBN1mgR/mgR mice and their wild type littermates were assessed every 4 weeks from 6 to 18 weeks of age by ultrasound. Measurements were taken luminal edge to luminal edge in diastole. At termination, aortas were harvested for RT-PCR analysis of extracellular matrix genes. Aortas were serially sectioned and elastin fragmentation was imaged by auto-fluorescence. RESULTS/ANTICIPATED RESULTS: At 12 weeks of age, differences of aortic diameters between male and female FBN1mgR/mgR mice were significantly different (2.24±0.43 vs. 1.57±0.22 mm; p=0.002), while there were no significant differences between sexes of wild type littermates (1.29±0.13 vs. 1.23±0.08 mm; p=0.71). Male sex was associated with increased elastin but not fibrillin-1 mRNA expression. Ascending aortas from male and female FBN1mgR/mgR mice significantly differed in the degree of elastin fragmentation (2.76 vs. 1.85 breaks/ 100 µm aorta; p=0.03). DISCUSSION/SIGNIFICANCE OF IMPACT: Sexual dimorphism of thoracic aortic dilation observed in human TAA patients was recapitulated in the fibirllin-1 hypomorphic mouse model of syndromic thoracic aortic aneurysms. Differences in this mouse model could be explained by the differential expression of extracellular matrix genes.
2282 Targeted eccentric motor control to improve locomotion after incomplete spinal cord injury
Authors: O’Brien Kevin , Basso D. Michele , Schmiedeler James
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Incomplete spinal cord injury typically results in life-long disability, often in the form of profound loss of locomotion capability. Individuals who have experienced incomplete spinal cord injury exhibit persistent eccentric motor deficits, which are particularly prevalent in the weight acceptance phase of gait and emphasized in sagittal plane knee motion and frontal plane hip motion. METHODS/STUDY POPULATION: Motion analysis can capture the kinematic and joint-level deficits of these individuals, but it is impossible to directly calculate the contributions of individual muscles to weight acceptance due to the complexity of the musculoskeletal system. Instead, those muscle contributions must be simulated in order to approximate muscle power during locomotion. RESULTS/ANTICIPATED RESULTS: The traditional method for driving these simulations with electromyography readings is unavailable for individuals who have neuromuscular deficits (e.g., spasticity or paralysis), due to the need to generate reliable maximum voluntary isometric contractions for baseline purposes. Instead, this research develops a novel method for using resting electromyography data to drive musculoskeletal simulations using a muscle activation threshold paradigm. DISCUSSION/SIGNIFICANCE OF IMPACT: The simulation results of this method more closely resemble experimental results, but further simulation refinement is needed to fully capture the true muscle activity.
2027 The role of lysyl oxidase in systemic sclerosis-associated lung fibrosis
Authors: Nguyen Xinh-Xinh , Nishimoto Tetsuya , Takihara Takahisa , Mlakar Logan , Riemer Ellen , Heywood Jonathan , Bradshaw Amy , Feghali-Bostwick Carol
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology characterized by progressive fibrosis of the skin and multiple visceral organs. Effective therapies for SSc are needed. Lysyl oxidase (LOX) is a copper-dependent amide oxidase that plays a critical role in the crosslinking of the extracellular matrix (ECM). In this study, we investigated the role of LOX in the pathophysiology of SSc. METHODS/STUDY POPULATION: LOX expression and protein levels were measured in lung tissues and primary fibroblasts from patients with SSc and healthy controls. The effects of recombinant LOX (rLOX) were measured in vitro in primary fibroblasts, ex vivo in human lung tissues and in vivo in mice given bleomycin in combination with rLOX. LOX levels and activity were evaluated in lung fibroblasts treated with an endostatin-derived peptide that ameliorates fibrosis and in mice treated with bleomycin in combination with the peptide. Further, to differentiate the crosslinking activity of LOX from other potential effects, primary human fibroblasts were cultured with rLOX in the presence of the inhibitor, beta-aminopropionitrile. The expression levels of ECM (collagen and fibronectin), pro-fibrotic factors (IL-6 and TGF-beta), and transcription factor (c-Fos) were examined by real-time PCR, ELISA, immunoblotting, or hydroxyproline assay. RESULTS/ANTICIPATED RESULTS: LOX mRNA was increased in lung tissues and matching fibroblasts of SSc patients. rLOX-induced ECM production in vitro and ex vivo in lung fibroblasts and in human lung tissues maintained in organ culture, respectively. Additionally, TGF-beta and bleomycin induced ECM production, LOX mRNA expression and activity. Endostatin peptide abrogated these effects. In vivo, rLOX synergistically exacerbated pulmonary fibrosis in bleomycin-treated mice. The inhibition of LOX catalytic activity by beta-aminopropionitrile failed to abrogate LOX-induced ECM production. LOX increased the production of IL-6. IL-6 neutralization blocked the effects of LOX. Further, LOX induced c-Fos expression and its nuclear localization. DISCUSSION/SIGNIFICANCE OF IMPACT: LOX expression and activity were increased with fibrosis in vitro, ex vivo, and in vivo. LOX induced fibrosis via increasing ECM, IL-6 and c-Fos translocation to the nucleus. These effects were independent of the crosslinking activity of LOX and mediated by IL-6. Our findings suggest that inhibition of LOX may be a viable option for the treatment of lung fibrosis. Further, the use of human lung in organ culture establishes the relevance of our findings to human disease.
2045 The role of TGFβ in driving early cystic fibrosis lung disease
Authors: Kramer Elizabeth L. , Hardie William , Hudock Kristin , Davidson Cynthia , Ostmann Alicia , Clancy John P.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Transforming growth factor-beta (TGFβ) is a genetic modifier of cystic fibrosis (CF) lung disease. TGFβ’s pulmonary levels in young CF patients and its mechanism of action in CF are unknown. We examined TGFβ levels in children with CF and investigated responses of human airway epithelial cells (AECs) and mice to TGFβ. METHODS/STUDY POPULATION: TGFβ levels in bronchoalveolar lavage fluid from CF patients (n=15) and non-CF control patients (n=21)<6 years old were determined by ELISA. CF mice and non-CF mice were intratracheally treated with an adenoviral TGFβ1 vector or PBS; lungs were collected for analysis at day 7. Human CF and non-CF AECs were treated with TGFβ or PBS for 24 hours then collected for analysis. RESULTS/ANTICIPATED RESULTS: Young CF patients had higher bronchoalveolar lavage fluid TGFβ than non-CF controls (p=0.03). Mouse lungs exposed to TGFβ demonstrated inflammation, goblet cell hyperplasia, and decreased CFTR expression. CF mice had greater TGFβ-induced lung mechanics abnormalities than controls; both CF human AECs and CF mice showed higher TGFβ induced MAPK and PI3K signaling compared with controls. DISCUSSION/SIGNIFICANCE OF IMPACT: For the first time, we show increased TGFβ levels very early in CF. TGFβ drives CF lung abnormalities in mouse and human models; CF models are more sensitive to TGFβ’s effects. Understanding the role of TGFβ in promoting CF lung disease is critical to developing patient specific treatments.
2366 Urinary tract infections in children with kidney allografts: Risk factors and clinical consequences
Authors: Farrell Annie , Greenbaum Larry , Leong Traci
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Background: Renal transplantation (tx) is the optimal treatment for end-stage renal disease (ESRD) in children, but post-tx urinary tract infections (UTIs) may cause morbidity and reduce allograft survival. Objectives: To quantify the number and risk factors for UTIs in pediatric kidney tx recipients in preparation for an analysis of the morbidity and impact of UTIs on allograft survival. METHODS/STUDY POPULATION: Methods: We identified all patients who underwent kidney tx between 2001 and 2016 (n=390) at Children’s Healthcare of Atlanta (CHOA). Patients were included if they had >1 year of follow-up at CHOA. We conducted an IRB-approved, retrospective review of patient demographics, medical history, and tx outcomes in the 5 years following tx. RESULTS/ANTICIPATED RESULTS: Results: Of the 205 records reviewed to date, we identified 176 eligible patients (61.9% male). Mean age at tx was 11.7±5.5 years. In total, 58.5% had a deceased and 41.5% had a living kidney donor. Obstructive uropathy was the etiology of ESRD in 21.0%. Mean UTIs in all patients was 1.1/patient±2.7. On preliminary analysis, patients with a history of obstructive uropathy were more likely to develop a UTI than patients without (45.9% vs. 25.2%, p=0.014). There is a trend to more UTIs in patients with a history of obstructive uropathy compared with patients without (2.1±3.5 vs. 0.9±2.4, p=0.055). In males, there were more UTIs in patients with a history of obstructive uropathy compared to patients without (1.7±2.9 vs. 0.5±1.5, p=0.024). In all, 23.2% of all patients were on UTI prophylaxis post-tx; trimethoprim-sulfamethoxazole was the prophylactic antibiotic in 54.5%. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: UTIs are common post kidney tx in children, especially in those with a history of obstructive uropathy. The associated morbidity and impact on graft survival are unknown.
2266 Big data approaches in translational science: The influence of psychiatric and trauma history in predicting smoking during pregnancy in a cohort of female like-sex twin pairs
Authors: Houston-Ludlam Alexandra N. , Grant Julia D. , Bucholz Kathleen K. , Madden Pamela A. F. , Heath Andrew C.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Smoking during pregnancy (SDP) is associated with negative health outcomes, both proximal (e.g., preterm labor, cardiovascular changes, low birth weight) and distal (e.g., increased child externalizing behaviors and attention deficit/hyperactivity disorder (ADHD) symptoms, increased risk of child smoking). As pregnancy provides a unique, strong incentive to quit smoking, investigating SDP allows analysis of individual predictive factors of recalcitrant smoking behaviors. Utilizing a female twin-pair cohort provides a model system for characterizing genotype×environment interactions using statistical approaches. METHODS/STUDY POPULATION: Using women from the Missouri Adolescent Female Twin Study, parental report of twin ADHD inattentive and hyperactive symptoms at twin median age 15, and twin report of DSM-IV lifetime diagnosis of major depressive disorder, trauma exposure (physical assault and childhood sexual abuse), collected at median age 22, were merged with Missouri birth record data for enrolled twins, leading to 1553 individuals of European ancestry and 163 individuals of African-American ancestry included in final analyses. A SDP propensity score was calculated from sociodemographic variables (maternal age, marital status, educational attainment, first born child) and used as a 6-level ordinal covariate in subsequent logistic regressions. RESULTS/ANTICIPATED RESULTS: For European ancestry individuals, parental report of hyperactive ADHD symptoms and exposure to childhood sexual abuse were predictive of SDP, while a lifetime diagnosis of major depressive disorder, parental report of inattentive ADHD symptoms, and exposure to assaultive trauma were all not significantly predictive of future SDP. For African-American individuals, none of these variables were significant in predicting future SDP. DISCUSSION/SIGNIFICANCE OF IMPACT: Understanding this relationship of risk-mechanisms is important for clinical understanding of early predictors of SDP and tailoring interventions to at risk individuals. Ultimately, the focus of this research is to mitigate risk to pregnant smokers and their children. Additionally, the cohort-ecological approach informs how well research and administrative (vital record) data agree. This allows for evaluation of whether administrative data improve prediction in research cohorts, and conversely if research data improve prediction over standard sociodemographic variables available in administrative data.
2216 Characterizing physician trust and healthcare-based discrimination among long-term HIV viral trajectory groups in Washington, DC
Authors: Michel Katherine G. , Wang Cuiwei , Doyle Allison , Robinson Camille , Ocampo Joanne M. F. , Goparaju Lakshmi , Kassaye Seble
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Discrimination within the healthcare system and physician distrust have been associated with adverse clinical outcomes for people living with HIV; however, many studies do not link these variables to biological data. We hypothesize that perceived healthcare discrimination and physician distrust associates with higher longitudinal viremia among HIV-positive women. METHODS/STUDY POPULATION: A 2006 cross-sectional survey assessed healthcare-based discrimination and physician trust in 92 HIV-positive and 46 high-risk HIV-negative women from the Washington DC Women’s Interagency HIV Study (DC-WIHS). In addition, we identified HIV viral load trajectories and demographics from the HIV-positive women who contributed≥4 semi-annual visits from 1994 to 2015. Viral suppression was defined by assay detection limits (<80 to <20 copies/mL). Group-based probability trajectory analyses grouped women based on longitudinal viral load patterns, and identified 3 groups: sustained viremia (n=32) with low-viral suppression over time, intermittent viremia (n=27) with varying suppression over time, and non-viremia (n=33) with high-longitudinal viral suppression. Ordinal logistic regression models assessed trajectory group and discrimination variables, controlling for demographics, using stepwise selection with significance level of α=0.05. RESULTS/ANTICIPATED RESULTS: Most women were African American (60%), insured at the time of visit (89%) and nonsmokers (56%). While physician trust did not differ by HIV viral trajectory group, trust was lower among HIV-negative women compared with HIV-positive women (p=0.03). Over 1 in 5 HIV-positive women reported discrimination in the healthcare system based on HIV status (21.3%). Report of discrimination based on drug/alcohol use was higher among HIV-negative participants (19.2% vs. 6.5%, p=0.01). Among women with longitudinal sustained viremia, report of discrimination based on race ethnicity (29%, p=0.004) and sexual orientation (15.6%, p=0.008) were higher than within the nonviremic and intermittent trajectory groups. DISCUSSION/SIGNIFICANCE OF IMPACT: Physician trust did not associate with increased longitudinal viral suppression among HIV-positive women in Washington, DC. Lack of physician trust among high-risk HIV-negative women could have implications for uptake of prevention methods. Reports of discrimination vary between HIV-positive and HIV-negative women in the Washington, DC area. The findings of healthcare system distrust among HIV-negative women has implications outside the realm of HIV, as this lack of trust may impact risk for other disease states among similar populations of women.
2198 Cognitive and behavioral side effects in patients treated with droxidopa for neurogenic orthostatic hypotension
Authors: McDonell Katherine , Shibao Cyndya , Biaggioni Italo , Robertson David , Claassen Daniel
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: To describe adverse behavioral symptoms attributed to droxidopa therapy for neurogenic orthostatic hypotension (nOH). METHODS/STUDY POPULATION: BACKGROUND: Droxidopa, a norepinephrine (NE) precursor, improves symptoms of nOH by replenishing NE levels. Central NE effects are poorly described but may offer potential benefits given the pathophysiologic progression of α-synuclein-related disorders. Here we report a series of cognitive and behavioral side effects linked to droxidopa therapy. METHODS: We identified 5 patients treated at Vanderbilt University who developed behavioral symptoms including mania, irritability, and disorientation shortly after the initiation of droxidopa for nOH. Comprehensive chart reviews were performed for all patients, including analysis of droxidopa titration schedule and dosing, medical comorbidities, clinical course, and outcome. All patients had symptoms of synucleinopathy, manifesting with autonomic failure, REM behavior disorder, and parkinsonism. Four met criteria for idiopathic PD, and one was diagnosed with pure autonomic failure but had concomitant symptoms of parkinsonism and REM sleep behavior disorder. RESULTS/ANTICIPATED RESULTS: Our patients had no significant cognitive or behavioral symptoms before the initiation of droxidopa. The average decrease in blood pressure upon standing was 27 mmHg systolic and 17 mmHg diastolic. Behavioral disturbances were observed early in the titration period and at relatively low doses of droxidopa (total daily doses ranging from 300 to 800 mg/day; droxidopa therapeutic dose range 900–1800 mg/d). The most common symptoms reported were mania, irritability, and confusion. Symptoms resolved with dose reduction in 4 patients, and droxidopa was discontinued in 1 patient due to persistent irritability. No other medical comorbidities or alternative etiologies were identified to explain these effects. DISCUSSION/SIGNIFICANCE OF IMPACT: Droxidopa is a prodrug designed to act peripherally, but may also have important, yet poorly described, central effects. We hypothesize that these behavioral manifestations result from an “overdose” of key NE networks linking orbitofrontal and mesolimbic regions. Further studies are warranted to better characterize central NE effects in patients treated with droxidopa.
2547 Long-term response to treatment and disease recurrence in a prospective cohort of morphea patients
Authors: Florez-Pollack Stephanie , O’Brien Jack C. , Jacobe Heidi T.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Morphea (localized scleroderma) is an autoimmune disease characterized that is widely thought to have a monophasic course, in which an initial period of inflammation (activity) ultimately results in scarring, atrophy, and functional impairment (damage). Understanding the long-term clinical course of morphea is important for the planning of future interventional studies, and as a tool for clinicians in determining risk for poor disease outcomes. METHODS/STUDY POPULATION: We conducted a prospective cohort study of 130 participants enrolled in the Morphea in Children and Adults Cohort over a median follow-up time of 4.3 years, to determine the rates of response to treatment and disease recurrence as measured by the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT). To determine risk factors for recurrence of disease activity, survival analysis using the log-rank test was used to compare subgroups by morphea type, therapy, and age at disease onset. RESULTS/ANTICIPATED RESULTS: Within a 1-year follow-up period, 66% of patients treated with methotrexate and 46% of patients with UVA1 phototherapy had achieved complete response to treatment. In patients who had achieved response to treatment, 29% experienced disease recurrence at an average of 1.7 years after documented disease inactivity. Patients with generalized morphea experienced higher recurrence rates than those with linear morphea (HR: 3.03, 95% CI: 1.48–6.22), and those treated with UVA1 phototherapy had higher recurrence over those treated with methotrexate (HR: 2.33, 95% CI: 1.03–5.31). In patients with follow-up periods longer than 5 years (n=50), disease recurrence was observed in 44% of patients and the majority of recurrence represented new activity in an area of pre-existing morphea (82%). DISCUSSION/SIGNIFICANCE OF IMPACT: This study highlights the previously under-studied dynamic long-term course of morphea, and identifies the clinical characteristics that predispose patients to having a relapsing-remitting course. We conclude that patients with morphea should be followed closely over time even in the absence of disease activity due to the potential for disease recurrence.