bluuebunny/crossref_metadata_2025 huggingface dataset:
Embracing and controlling risk dependency in cyber-insurance policy underwriting
Authors: Khalili Mohammad Mahdi , Liu Mingyan , Romanosky Sasha
Published: October 2019

This article highlights how cyber risk dependencies can be taken into consideration when underwriting cyber-insurance policies. This is done within the context of a base rate insurance policy framework, which is widely used in practice. Specifically, we show that there is an opportunity for an underwriter to better control the risk dependency and the risk spill-over, ultimately resulting in lower overall cyber risks across its portfolio. To do so, we consider a Service Provider (SP) and its customers as the interdependent insurer’s customers: a data breach suffered by the SP can cause business interruption to its customers. In underwriting both the SP and its customers, we show that the insurer can increase its profit by incentivizing the SP (through a discount on its premium) to invest more in security, thereby decreasing the chance of business interruption to the customers, and increasing social welfare. For comparison, we also consider a scenario where the insurer underwrites only the SP’s customers (but not the SP), and receives compensation from the SP’s insurance carrier when losses are attributed to the SP. We show how the insurer’s best strategy is to underwrite both the SP and its customers. We use an actual cyber-insurance policy and claims data to calibrate and substantiate our analytical findings.
Analysing group contract design using a threshold public goods experiment
Authors: Bouma Jetske A , Nguyen T T Binh , van der Heijden Eline , Dijk Justin J
Published: October 2019

This paper presents the results of a threshold public goods game experiment with heterogeneous players. The experiment is designed in close collaboration with the Dutch association of agri-environmental farmer collectives. Subjects are recruited at a university (study 1) and a farm management training centre (study 2), the subjects of the second study most resembling the subjects in the field. The experiment consists of several treatments and each treatment has two different distribution rules, which are varied in a within-subjects manner. After subjects have experienced both, they can vote for one of the two rules: either a differentiated bonus that results in equal payoff for all, or an undifferentiated, equal share of the group bonus. In a between-subjects manner, subjects can vote for a (minimum or average) threshold or are faced with an exogenous threshold. The results indicate that exogenous thresholds perform better, possibly because the focal point they provide facilitates coordination. With regard to the two distribution rules, the results are mixed: in study 1, average contributions and payoffs are higher under the ‘equal-payoff’ rule, but there is no significant difference between the two in study 2. Overall, our results suggest that environmental payment schemes should consider cost heterogeneity in the design of group contracts, and pay explicit attention to coordination problems too.
Cardiorespiratory fitness, muscular strength, and obesity in adolescence and later chronic disability due to cardiovascular disease: a cohort study of 1 million men
Authors: Henriksson Hanna , Henriksson Pontus , Tynelius Per , Ekstedt Mattias , Berglind Daniel , Labayen Idoia , Ruiz Jonatan R , Lavie Carl J , Ortega Francisco B
Published: October 2019

Aims

Cardiorespiratory fitness, muscular strength, and obesity in adulthood are risk factors for cardiovascular disease (CVD). However, little is known regarding the associations of these risk factors, already in adolescence, with later disability due to chronic CVD. Hence, we investigated associations of cardiorespiratory fitness, muscular strength, and body mass index (BMI) in adolescence with later chronic disability due to specific causes of CVD disability (i.e. cerebrovascular disease, ischaemic heart disease and heart failure).

Methods and results

This population-based cohort study included 1 078 685 male adolescents (16–19 years) from the Swedish military conscription register from 1972 to 1994. Cardiorespiratory fitness (bicycle ergometer test), muscular strength (knee extension strength), and BMI were measured during the conscription examination. Information about disability pension due to CVD was retrieved from the Social Insurance Agency during a mean follow-up of 28.4 years. Cardiorespiratory fitness was strongly and inversely associated with later risk of chronic CVD disability for all investigated causes. The association was particularly strong for ischaemic heart diseases (hazard ratio 0.11, 95% confidence interval 0.05–0.29 for highest vs. lowest fitness-quintiles). Furthermore, overweight/obesity were associated with CVD disability for all investigated causes. Conversely, associations of muscular strength with CVD disability were generally weak.

Conclusions

This study provides evidence for associations between low levels of cardiorespiratory fitness and obesity with later risk of chronic disability due to CVD. Preventive actions may begin at young ages and include promotion of cardiorespiratory fitness and healthy body weight.
Endophytic nitrogen fixation – a possible ‘hidden’ source of nitrogen for lodgepole pine trees growing at unreclaimed gravel mining sites
Authors: Padda Kiran Preet , Puri Akshit , Chanway Chris
Published: October 2019

Lodgepole pine (Pinus contorta var. latifolia) trees have been thriving on unreclaimed gravel mining sites in British Columbia, Canada, with tissue nitrogen-content and growth-rate unaffected by extremely low soil nitrogen-levels. This indicates that pine trees could be accessing a hidden nitrogen source to fulfill their nitrogen requirements – possibly via endophytic nitrogen-fixation. Endophytic bacteria originally isolated from native pine trees growing at gravel sites were selected (n = 14) for in vitro nitrogen-fixation assays and a year long greenhouse study to test the overall hypothesis that naturally occurring endophytic nitrogen-fixing bacteria sustain pine tree growth under nitrogen-limited conditions. Each of the 14 bacteria colonized the internal tissues of pine trees in the greenhouse study and fixed significant amounts of nitrogen from atmosphere (23%–53%) after one year as estimated through 15N isotope dilution assay. Bacterial inoculation also significantly enhanced the length (31%–64%) and biomass (100%–311%) of pine seedlings as compared to the non-inoculated control treatment. In addition, presence of the nifH gene was confirmed in all 14 bacteria. Our results support the possibility that pine trees associate with nitrogen-fixing bacteria, capable of endophytic colonization, to survive at unreclaimed gravel mining pits and this association could potentially be utilized for effective reclamation of highly disturbed sites in a sustainable manner.
Association between matrix Gla protein and ulcerative colitis according to DNA microarray data
Authors: Dong Xu-Yang , Wu Mei-Xu , Zhang Hui-Min , Lyu Hong , Qian Jia-Ming , Yang Hong
Published: October 2019

Background

Matrix Gla protein (MGP) is a secreted protein contributed to the immunomodulatory functions of mesenchymal stromal cells. Microarray profiling found a significantly higher expression level of the extracellular matrix gene MGP in patients with ulcerative colitis (UC). However, little is known about the role of MGP in UC and its upstream signaling regulation. This study aimed to identify the expression of MGP in UC and its upstream regulator mechanism.

Methods

Colonic mucosa biopsies were obtained from patients with UC and healthy controls. DNA microarray profiling was used to explore underlying genes correlating with UC development. Mice were fed with water containing different concentrations of dextran sodium sulfate (DSS) to induce an experimental colitis model. Colonic tissues were collected and evaluated using immunohistochemistry, immunoblot, real-time polymerase chain reaction, and chromatin immunoprecipitation assay. Bioinformatics analysis was performed to identify candidate MGP gene-promoter sequence and transcription-initiation sites. Luciferase-reporter gene assay was conducted to examine the potential transcription factor of MGP gene expression.

Results

The expression of MGP was significantly increased in colonic tissues from UC patients and DSS-induced colitis models, and was positively correlated with disease severity. Bioinformatics analysis showed a conserved binding site for Egr-1 in the upstream region of human MGP gene. The significantly higher level of Egr-1 gene expression was found in UC patients than in healthy controls. The activity of luciferase was significantly enhanced in the Egr-1 expression plasmid co-transfected group than in the control group and was further inhibited when co-transfected with the Egr-1 binding-site mutated MGP promoter.

Conclusions

Up-regulated expression of MGP was found in UC patients and DSS-induced colitis. The expression of MGP can be regulated by Egr-1.
Epigenetic Age Acceleration and Cognitive Function in African American Adults in Midlife: The Atherosclerosis Risk in Communities Study
Authors: Bressler Jan , Marioni Riccardo E , Walker Rosie M , Xia Rui , Gottesman Rebecca F , Windham B Gwen , Grove Megan L , Guan Weihua , Pankow James S , Evans Kathryn L , Mcintosh Andrew M , Deary Ian J , Mosley Thomas H , Boerwinkle Eric , Fornage Myriam
Published: October 2019

Methylation levels measured at defined sites across the genome have recently been shown to be correlated with an individual’s chronological age. Age acceleration, or the difference between age estimated from DNA methylation status and chronological age, has been proposed as a novel biomarker of aging. In this study, the cross-sectional association between two different measures of age acceleration and cognitive function was investigated using whole blood samples from 2,157 African American participants 47–70 years of age in the population-based Atherosclerosis Risk in Communities (ARIC) Study. Cognition was evaluated using three domain-specific tests. A significant inverse association between a 1-year increase in age acceleration calculated using a blood-based age predictor and scores on the Word Fluency Test was found using a general linear model adjusted for chronological age, gender, and years of education (β = −0.140 words; p = .001) and after adding other potential confounding variables (β = −0.104 words, p = .023). The results were replicated in 1,670 European participants in the Generation Scotland: Scottish Family Health Study (fully adjusted model: β = −0.199 words; p = .034). A significant association was also identified in a trans-ethnic meta-analysis across cohorts that included an additional 708 European American ARIC study participants (fully adjusted model: β = −0.110 words, p = .003). There were no associations found using an estimate of age acceleration derived from multiple tissues. These findings provide evidence that age acceleration is a correlate of performance on a test of verbal fluency in middle-aged adults.
Electroacupuncture therapy ameliorates motor dysfunction via brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in a mouse model of Parkinson's disease
Authors: Pak Malk Eun , Ahn Sung Min , Jung Da Hee , Lee Hong Ju , Ha Ki Tae , Shin Hwa Kyoung , Choi Byung Tae
Published: October 2019

Parkinson’s disease (PD) is characterized by dopaminergic neuron loss in the substantia nigra. However, specific sensory stimulation via electroacupuncture (EA) therapy may attenuate this loss by promoting the expression of endogenous neurotrophic factors in a manner similar to physical therapy. We investigated the potential protective effects of EA on dopaminergic neurons in a mouse model of PD and whether these effects are associated with the promotion of endogenous brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Mouse models of PD were generated using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine. Motor performance was assessed using behavioral tests, and Western blot experiments, enzyme-linked immunosorbent assays, and immunohistochemical assays were performed. In both mouse models, EA treatment ameliorated motor impairments and dopaminergic neuron loss; these changes were accompanied by increases in BDNF and GDNF. In the MPTP group, EA treatment improved motor dysfunction by attenuating dopaminergic neuron loss in the substantia nigra, similar to the effects of levodopa. EA treatment significantly upregulated BDNF and GDNF expression in both the substantia nigra and striatum. Moreover, EA treatment induced the expression of cAMP response element binding protein (CREB) as well as Akt and Pitx3 in dopaminergic neurons in the substantia nigra. However, levodopa treatment did not induce BDNF/GDNF activation or related signaling factors. Thus, EA therapy may exert protective effects on dopaminergic neurons by upregulating the expression of BDNF, GDNF, and related signaling factors, thereby improving motor function. Hence, EA may represent an effective adjuvant therapy for motor deficits in patients with PD.
Separating the scattered wavefield from teleseismic P using curvelets on the long beach array data set
Authors: Zhang Jia , Langston Charles A
Published: October 2019

A dense seismic array, composed of over 5000 stations with an average spacing close to 120 m was deployed in Long Beach, CA, by NodalSeismic and Signal Hill Petroleum as part of a survey associated with the Long Beach oilfield. Among many interesting wave propagation effects that have been reported by others, we observe that the coda of teleseismic P waves display waves caused by obvious local scattering from the Signal Hill popup structure between strands of the Newport-Inglewood fault. The density of the seismic array allows space-based methods, such as the Curvelet transform, to be investigated to separate the teleseismic and local scattered wavefields. We decompose a synthetic wavefield composed of a teleseismic plane wave and local scattered spherical wave in the curvelet domain to test the plausibility of our curvelet analysis and then apply the technique to the Long Beach array data set. Background noise is removed by a soft thresholding method and a declustering technique is applied to separate the teleseismic and local scattered wavefield in the curvelet domain. Decomposed results illustrate that the signal-to-noise ratio of the teleseismic P wave can be significantly improved by curvelet analysis. The scattered wavefield is composed of locally propagating Rayleigh waves from the pop-up structure and from the Newport Inglewood fault itself. Observing the wavefield both in space and time clearly improves understanding of wave propagation complexities due to structural heterogeneity.
Oxidized regenerated cellulose for a clear thoracoscopic view: a single-centre randomized trial
Authors: Shimizu Nahoko , Tanaka Yugo , Kuroda Sanae , Nakamura Hayate , Matsumoto Gaku , Mitsui Suguru , Sakai Shuto , Minami Kazuhiro , Doi Takefumi , Hokka Daisuke , Maniwa Yoshimasa
Published: October 2019

OBJECTIVES

During video-assisted thoracoscopic surgery (VATS), blood oozing from the surface of the access port wound can hamper the surgical view. Although this oozing is difficult to prevent, it can be decreased by placing a wound edge protector with oxidized regenerated cellulose (ORC) on the surface of the access port wound, thereby improving the surgical outcomes and safety of VATS.

METHODS

We conducted a prospective, single-centre, open-label, randomized clinical trial to evaluate the operative outcomes of VATS when using the ORC (ORC group) compared with operative outcomes without using the ORC (non-ORC group). The primary end point was interruption of the operation as a result of blood oozing from the surface of the access port wound. The secondary end points were the other intraoperative and postoperative outcomes.

RESULTS

A total of 108 patients were divided into the ORC group (n = 54) and the non-ORC group (n = 54). Compared with the non-ORC group, the ORC group had fewer patients with an interruption in the operation (11.1% vs 51.8%; P < 0.001), less need for wound haemostasis of the access ports during wound closure (44.4% vs 72.2%; P = 0.003), similar rates of postoperative deaths and complications and a tendency for shorter operation times (149.3 vs 168.8 min, respectively; P = 0.083).

CONCLUSION

The use of an ORC sheet around a wound edge protector for haemostasis can ensure a clear view during VATS.

Clinical trial registration number

UMIN000031112.
A weak maximum principle for optimal control problems with mixed constraints under a constant rank condition
Authors: Andreani Roberto , Antunes de Oliveira Valeriano , Tomaz Pereira Jamielli , Nunes Silva Geraldo
Published: October 2019

Necessary optimality conditions for optimal control problems with mixed state-control equality constraints are obtained. The necessary conditions are given in the form of a weak maximum principle and are obtained under (i) a new regularity condition for problems with mixed linear equality constraints and (ii) a constant rank type condition for the general non-linear case. Some instances of problems with equality and inequality constraints are also covered. Illustrative examples are presented.
A Tannakian Framework forG-displays and Rapoport–Zink Spaces
Authors: Daniels Patrick
Published: October 2019

We develop a Tannakian framework for group-theoretic analogs of displays, originally introduced by Bültel and Pappas, and further studied by Lau. We use this framework to define Rapoport–Zink functors associated to triples $(G,\{\mu \},[b])$, where $G$ is a flat affine group scheme over ${\mathbb{Z}}_p$ and $\mu$ is a cocharacter of $G$ defined over a finite unramified extension of ${\mathbb{Z}}_p$. We prove these functors give a quotient stack presented by Witt vector loop groups, thereby showing our definition generalizes the group-theoretic definition of Rapoport–Zink spaces given by Bültel and Pappas. As an application, we prove a special case of a conjecture of Bültel and Pappas by showing their definition coincides with that of Rapoport and Zink in the case of unramified EL-type local Shimura data.
Ebola Patient Virus Cycle Threshold and Risk of Household Transmission of Ebola Virus
Authors: Reichler Mary R , Bruden Dana , Thomas Harold , Erickson Bobbie Rae , Knust Barbara , Duffy Nadia , Klena John , Hennessy Thomas ,   the Household Transmission Investigative Team, Bangura James , Keimbe Charles , Jambai Amara , Morgan Oliver , Farmar Ismail , Davies Francis , Mohamed Dumbuya Sima , Kamara Hannah , Mohamed Kallon Yayah , Kpukumu Joseph , Abu Sheku , Bangura Fatmata , Saidu Bangura Rahim , Bangura Tomeh , Benya Hassan , Blango Sandi , Conteh Imurana , Conteh Peter , Jabbie Bintu , Jabbie Sheku , Kamara Luseni , Lansana Francis , Rogers Maada , Sahr Sewa Brima , Yamba Matthew , Bessler P , Washburn Faith , Ervin E , Campbell S , Chung W , Nichols E , Hersey S
Published: October 2019

Background

Identifying risk factors for household transmission of Ebola virus (EBOV) is important to guide preventive measures during Ebola outbreaks.

Methods

We enrolled all confirmed persons with EBOV disease who were the first case patient in a household from December 2014 to April 2015 in Freetown, Sierra Leone, and their household contacts. Index patients and contacts were interviewed, and contacts were followed up for 21 days to identify secondary cases. Epidemiologic data were linked to EBOV real-time reverse-transcription polymerase chain reaction cycle threshold (Ct) data from initial diagnostic specimens obtained from enrolled index case patients.

Results

Ct data were available for 106 (71%) of 150 enrolled index patients. Of the Ct results, 85 (80%) were from blood specimens from live patients and 21 (20%) from oral swab specimens from deceased patients. The median Ct values for blood and swab specimens were 21.0 and 24.0, respectively (P = .007). In multivariable analysis, a Ct value from blood specimens in the lowest quintile was an independent predictor of both increased risk of household transmission (P = .009) and higher secondary attack rate among household contacts (P = .03), after adjustment for epidemiologic factors.

Conclusions

Our findings suggest the potential to use Ct values from acute EBOV diagnostic specimens for index patients as an early predictor of high-risk households and high-risk groups of contacts to help prioritize EBOV disease investigation and control efforts.
Assessment of in situ techniques to determine indigestible components in the feed and feces of cattle receiving supplemental condensed tannins1
Authors: Norris Aaron B , Tedeschi Luis O , Muir James P
Published: October 2019

Reliable assessments of indigestible dietary components are required when using internal markers to estimate diet digestibility and determine the potentially digestible portion of the fiber. The lack of a standardized methodology and understanding of how antinutritional factors influence indigestible residues can result in erroneous estimates with inconsistent variation across trials and among studies. Previous studies have detailed suitable bag porosity and sample size (SS) with incubation length (IL) varying from 96 to 504 h, with many assuming that 288-h IL yields truly indigestible components. Recent studies have primarily investigated the variation that exists among feedstuffs, but most have failed to account for possible effects of secondary compounds. Using 2 similar concentrate diets, one of which contained supplemental condensed tannins (CT), we investigated the effect of bag type (BT; 10 and 25 μm), SS (20 and 40 mg/cm2), and IL (288 and 576 h) on in situ indigestible DM (iDM) and neutral detergent fiber (iNDF) residues of feed and feces, and resultant DM and NDF digestibilities. There were no 3-way interactions (P > 0.05), but 2-way interactions were present for iDM and iNDF residues with BT × SS influencing the control (no CT) ration (P < 0.01), SS × IL impacting feed containing CT (P < 0.01), and BT × IL affecting both feedstuffs (P ≤ 0.01). For the control diet, only BT × SS affected DM and NDF digestibilities. Whereas the CT diet did not demonstrate any significant interactions for digestibilities. Values of iDM were largely influenced by contamination that varied greatly based on intrinsic factors associated with the bag and incubation duration. The presence of CT influenced iDM and iNDF to varying degrees due to possible trapping of CT–substrate complexes. For the control diet, the use of 25-μm bags resulted in lower fecal recoveries relative to the 10 μm (P < 0.01). However, there appears to be a dynamic relationship among BT, SS, and IL within respective diets and sample types that can affect indigestible components and resultant digestibility estimates. Based on simulations from these data, the sample size required to attain 90% power when utilizing 2 incubation animals exceeds the triplicate and quadruplicate replications commonly utilized. Further emphasizing the necessity for a more complete understanding of incubation dynamics to design biologically and statistically valid investigations.
Dietary tributyrin supplementation and submaximal exercise promote activation of equine satellite cells
Authors: Gonzalez Madison L , Jacobs Robert D , Ely Kristine M , Johnson Sally E
Published: October 2019

Postexercise skeletal muscle repair is dependent on the actions of satellite cells (SCs). The signal(s) responsible for activation of these normally quiescent cells in the horse remain unknown. The objective of the experiment was to determine whether submaximal exercise or tributyrin (TB) supplementation is sufficient to stimulate SC activation. Adult geldings were fed a control diet (n = 6) or a diet containing 0.45% TB (n = 6). After 30 d, the geldings performed a single bout of submaximal exercise. Middle gluteal muscle biopsies and blood were collected on days −1, 1, 3, and 5 relative to exercise. Diet had no effect on any parameter of physical performance. Total RNA isolated from the gluteal muscle of TB fed geldings contained greater (P < 0.05) amounts of myogenin mRNA than controls. Satellite cell isolates from TB supplemented horses had a greater (P = 0.02) percentage of proliferating cell nuclear antigen immunopositive (PCNA+) SC than controls after 48 h in culture. Submaximal exercise was sufficient to increase (P < 0.05) the percentage of PCNA(+) cells in all isolates obtained during recovery period. No change in the amount of gluteal muscle Pax7 mRNA, a lineage marker of SCs, occurred in response to either diet or exercise. Our results indicate that both submaximal exercise and TB prime SCs for activation and cell cycle reentry but are insufficient to cause an increase in Pax7 expression during the recovery period.
CBDR: An efficient storage repository for cultural big data
Authors: Sharma Seemu , Bawa Seema
Published: October 2019

Cultural data and information on the web are continuously increasing, evolving, and reshaping in the form of big data due to globalization, digitization, and its vast exploration, with common people realizing the importance of ancient values. Therefore, before it becomes unwieldy and too complex to manage, its integration in the form of big data repositories is essential. This article analyzes the complexity of the growing cultural data and presents a Cultural Big Data Repository as an efficient way to store and retrieve cultural big data. The repository is highly scalable and provides integrated high-performance methods for big data analytics in cultural heritage. Experimental results demonstrate that the proposed repository outperforms in terms of space as well as storage and retrieval time of Cultural Big Data.
The impact of inhomogeneous subgrid clumping on cosmic reionization
Authors: Mao Yi , Koda Jun , Shapiro Paul R , Iliev Ilian T , Mellema Garrelt , Park Hyunbae , Ahn Kyungjin , Bianco Michele
Published: October 2019

Cosmic reionization was driven by the imbalance between early sources and sinks of ionizing radiation, both of which were dominated by small-scale structure and are thus usually treated in cosmological reionization simulations by subgrid modelling. The recombination rate of intergalactic hydrogen is customarily boosted by a subgrid clumping factor, 〈n2〉/〈n〉2, which corrects for unresolved fluctuations in gas density n on scales below the grid-spacing of coarse-grained simulations. We investigate in detail the impact of this inhomogeneous subgrid clumping on reionization and its observables, as follows: (1) Previous attempts generally underestimated the clumping factor because of insufficient mass resolution. We perform a high-resolution N-body simulation that resolves haloes down to the pre-reionization Jeans mass to derive the time-dependent, spatially varying local clumping factor and a fitting formula for its correlation with local overdensity. (2) We then perform a large-scale N-body and radiative transfer simulation that accounts for this inhomogeneous subgrid clumping by applying this clumping factor-overdensity correlation. Boosting recombination significantly slows the expansion of ionized regions, which delays completion of reionization and suppresses 21 cm power spectra on large scales in the later stages of reionization. (3) We also consider a simplified prescription in which the globally averaged, time-evolving clumping factor from the same high-resolution N-body simulation is applied uniformly to all cells in the reionization simulation, instead. Observables computed with this model agree fairly well with those from the inhomogeneous clumping model, e.g. predicting 21 cm power spectra to within 20 per cent error, suggesting it may be a useful approximation.
Low-degree mixed modes in red giant stars with moderate core magnetic fields
Authors: Loi Shyeh Tjing , Papaloizou John C B
Published: October 2019

Observations of pressure-gravity mixed modes, combined with a theoretical framework for understanding mode formation, can yield a wealth of information about deep stellar interiors. In this paper, we seek to develop a formalism for treating the effects of deeply buried core magnetic fields on mixed modes in evolved stars, where the fields are moderate, i.e. not strong enough to disrupt wave propagation, but where they may be too strong for non-degenerate first-order perturbation theory to be applied. The magnetic field is incorporated in a way that avoids having to use this. Inclusion of the Lorentz force term is shown to yield a system of differential equations that allows for the magnetically-affected eigenfunctions to be computed from scratch, rather than following the approach of first-order perturbation theory. For sufficiently weak fields, coupling between different spherical harmonics can be neglected, allowing for reduction to a second-order system of ordinary differential equations akin to the usual oscillation equations that can be solved analogously. We derive expressions for (i) the mixed-mode quantisation condition in the presence of a field and (ii) the frequency shift associated with the magnetic field. In addition, for modes of low degree we uncover an extra offset term in the quantisation condition that is sensitive to properties of the evanescent zone. These expressions may be inverted to extract information about the stellar structure and magnetic field from observational data.
Star formation at the Galactic Centre: coevolution of multiple young stellar discs
Authors: Mastrobuono-Battisti Alessandra , Perets Hagai B , Gualandris Alessia , Neumayer Nadine , Sippel Anna C
Published: October 2019

Studies of the Galactic Centre suggest that in situ star formation may have given rise to the observed stellar population near the central supermassive black hole (SMBH). Direct evidence for a recent starburst is provided by the currently observed young stellar disc (2–7 Myr) in the central 0.5 pc of the Galaxy. This result suggests that star formation in galactic nuclei may occur close to the SMBH and produce initially flattened stellar discs. Here, we explore the possible build-up and evolution of nuclear stellar clusters near SMBHs through in situ star formation producing stellar discs similar to those observed in the Galactic Centre and other nuclei. We use N-body simulations to model the evolution of multiple young stellar discs and explore the potential observable signatures imprinted by such processes. Each of the five simulated discs is evolved for 100 Myr before the next one is introduced in the system. We find that populations born at different epochs show different morphologies and kinematics. Older and presumably more metal-poor populations are more relaxed and extended, while younger populations show a larger amount of rotation and flattening. We conclude that star formation in central discs can reproduce the observed properties of multiple stellar populations in galactic nuclei differing in age, metallicity, and kinematic properties.
899. Influenza Vaccine Effectiveness Against Laboratory-Confirmed Influenza in Children Hospitalized with Respiratory Illness in the United States, 2016–2017 and 2017–2018 Seasons
Authors: Campbell Angela P , Ogokeh Constance E , McGowan Craig , Rha Brian , Selvarangan Rangaraj , Staat Mary A , Weinberg Geoffrey A , Boom Julie A , Englund Janet A , Williams John V , Halasa Natasha B , Szilagyi Peter G , Harrison Christopher J , Klein Eileen J , McNeal Monica , Michaels Marian G , Sahni Leila C , Stewart Laura S , Lively Joana Y , Beacham Lauren , Payne Daniel C , Fry Alicia M , Patel Manish
Published: October 2019

Background

Annual national estimates of influenza vaccine effectiveness (VE) typically measure protection against outpatient medically attended influenza illness. We assessed influenza VE in preventing laboratory-confirmed influenza hospitalization in children across two influenza A(H3N2)-predominant seasons.

Methods

Children < 18 years hospitalized with acute respiratory illness were enrolled at 7 pediatric hospitals in the New Vaccine Surveillance Network. We included subjects ≥6 months with ≤10 days of symptoms enrolled during the 2016–2017 and 2017–2018 seasons (date of first through last influenza-positive case for each site). Combined mid-turbinate and throat swabs were tested using molecular assays. We estimated age-stratified VE from a test-negative design using logistic regression to compare the odds of vaccination among cases positive for influenza with controls testing negative, adjusting for age, enrollment month, site, underlying comorbidities, and race/ethnicity. Full/partial vaccination was defined using ACIP criteria. We verified vaccine receipt from state immunization registries and/or provider records.

Results

Among 3441 children with complete preliminary data, in 2016–2017, 156/1,710 (9%) tested positive for influenza: 91 (58%) with influenza A(H3N2), 5 (3%) with A(H1N1), and 60 (38%) with B viruses. In 2017–2018, 193/1,731 (11%) tested positive: 87 (45%) with influenza A(H3N2), 47 (24%) with A(H1N1), and 58 (30%) with B. VE for all vaccinated children (full and partial) against any influenza was 48% (95% confidence interval, 26%–63%) in 2016–2017 and 45% (24%–60%) in 2017–2018. Combining seasons, VE for fully and partially vaccinated children against any influenza type was 46% (32%–58%); by virus, VE was 30% (4%–49%) for influenza A(H3N2), 71% (46%–85%) for A(H1N1), and 57% (36%–70%) for B viruses. There was no statistically significant difference in VE by age or full/partial vaccination status for any virus (table).

Conclusion

Vaccination in the 2016–2017 and 2017–2018 seasons nearly halved the risk of children being hospitalized with influenza. These findings support the use of vaccination to prevent severe illness in children. Our study highlights the need for a better understanding of the lower VE against influenza A(H3N2) viruses.

Disclosures

All Authors: No reported Disclosures.
962. Trends in Cervical Pre-cancers by Race and Ethnicity During the Human Papillomavirus Vaccine Era, HPV Vaccine Impact Monitoring Project (HPV-IMPACT), United States, 2008–2016
Authors: Gargano Julia , Lewis Rayleen , Hunt Hillary , McClung Nancy , Bennett Nancy M , Griffin Marie , Niccolai Linda , Park Ina , Powell Melissa , Brackney Monica , Scahill Mary , Pemmaraju Manideepthi , Fink Deanna , Ehlers Sara , Cleveland Angela , Unger Elizabeth R , Markowitz Lauri
Published: October 2019

Background

Since human papillomavirus (HPV) vaccine introduction in the United States in 2006, cervical pre-cancer incidence has declined in young women, but pre-cancer trends have not been reported by race/ethnicity. We evaluated trends in cervical pre-cancers from 2008 to 2016 in non-Hispanic (NH) white, NH black, NH Asian, and Hispanic women identified through active population-based surveillance in the 5-site Human Papillomavirus Vaccine Impact Monitoring Project (HPV-IMPACT).

Methods

We analyzed data on cervical intraepithelial neoplasia (CIN) grades 2–3 and adenocarcinoma in situ (CIN2+) cases aged 20–39 years. Annual CIN2+ rates per 100,000 women were calculated stratified by race/ethnicity in 5-year age groups, using multiple imputation to account for 10% missing race/ethnicity data. Rates were also calculated using estimated numbers screened for cervical cancer to control for known declines in screening. Trends, evaluated using JoinPoint software, are presented as average annual percentage changes (AAPC) with 95% confidence intervals (CI).

Results

A total of 18,222 CIN2+ cases (62% NH white, 16% NH black, 16% Hispanic, 6% Asian) were reported from 2008 to 2016. CIN2+ rates among 20–24 year-olds declined significantly in all groups: NH white, AAPC: −14.2 (95% CI: −16.3, −12.1); NH black, AAPC: −15.5 (−19.5, −11.4); Asian, AAPC: −14.8 (−20.5, −8.8); Hispanic, AAPC: −14.3 (−17.9, −10.5). In 25–29 year olds, a significant decline was observed for NH whites only (AAPC: −2.4, [−4.0, −0.8]). No declines were seen in 30–34 or 35–39 year olds. Among screened 20–24 year-olds, significant but smaller declines were observed (AAPC: −9.8 to −8.4); no declines were observed in screened 25–29 year olds or older groups.

Conclusion

In this evaluation of CIN2+ trends by race/ethnicity during the HPV vaccine era, the significant declines in 20–24 year olds across all groups, including among screened women, is consistent with equitable vaccine impact on CIN2+.

Disclosures

All Authors: No reported Disclosures.
971. The Role of Inflammation and Innate Effectors in Passive Immunization for Acinetobacter baumannii Infections
Authors: Nielsen Travis B , Yan Jun , Luna Brian M , Talyansky Yuli , Bonomo Robert A , Spellberg Brad
Published: October 2019

Background

We have previously demonstrated that A. baumannii virulence is driven by avoidance of innate effector clearance, resulting in LPS-TLR4 triggering of excess inflammation in the host. We also raised a monoclonal antibody (MAb) that improved survival of mice lethally infected with A. baumannii.

Methods

Mice were selectively depleted of innate effectors (macrophages with liposomal clodronate, neutrophils with cyclophosphamide, and/or complement with cobra venom factor), infected with an XDR clinical blood isolate of A. baumannii, and treated with placebo or anti-A. baumannii MAb.

Results

Single disruption of macrophages or neutrophils did not enhance lethality but complement deficiency did. In contrast, singly disrupting complement or neutrophils did not impact bacterial density but macrophage disruption markedly increased it. Thus, a dissociation of bacterial density and survival was observed. MAb therapy was completely protective in mice depleted of a single effector. While dual depletion resulted in diminished MAb efficacy in terms of survival, mice retaining neutrophils had marked improvements in survival with MAb therapy compared with other dual-depletion groups. The dissociation of bacterial density and survival suggested that inflammation was a primary driver of host outcome. Levels of IL-10 and TNFα had a reciprocal relationship in mice across effector depletion groups and were lower in mouse groups with higher survival when adjusted for bacterial density. IL-10 disruption completely abrogated the survival benefit of MAb therapy without altering bacterial clearance mediated by MAb. In contrast, TNFα disruption enhanced MAb efficacy for survival, and the presence of TNFα was antagonistic to MAb efficacy.

Conclusion

These results confirm that host outcomes from A. baumannii infection are driven by host inflammatory response rather than bacterial density alone. Furthermore, novel therapeutic approaches seeking to improve outcomes from such infections must seek to shift the balance of pro-/anti-inflammatory cytokines to favor a down-modulated inflammatory response.

Disclosures

All Authors: No reported Disclosures.
972. A Mycobacterium tuberculosis Secreted Lipid Triggers Cough Through a Neuronal Cough Receptor
Authors: Cruz Paxton , Ruhl Cody , Shiloh Michael
Published: October 2019

Background

A hallmark symptom of active pulmonary tuberculosis vital for disease transmission is cough. The current paradigm for tuberculosis-related cough is that it results from airway damage or irritation. However, there is limited experimental data to support this theory, and whether Mycobacterium tuberculosis (Mtb) induces cough to facilitate its own transmission has not been explored. The cough reflex is a complex and coordinated event involving both the nervous and musculoskeletal systems initiated by particulate or chemical molecules activating nociceptive neurons, which sense pain or irritation. This activation induces a signaling cascade ultimately resulting in a cough. Respiratory nociceptive neurons innervate the airway of humans and most mammals and thus are poised to respond to noxious molecules to help protect the lung from damage. Because Mtb is a lung pathogen, cough is a primary mechanism of Mtb transmission, and respiratory nociceptive neurons activate cough, we hypothesized that Mtb produces molecules that stimulate cough thereby facilitating its spread from infected to uninfected individuals. We previously identified a cough molecule produced by Mtb, and in this work characterize its neuronal receptor using genetics, biochemistry, and pharmacology.

Methods

We used an in vitro neuronal activation bioassay to study Mtb cough-inducing molecules. We also used a biochemical assay to identify the cough receptor. Finally, we used gene silencing, biochemistry, and pharmacologic inhibition to validate and characterize the activity of the newly discovered cough receptor.

Results

We isolated a complex lipid produced by Mtb that activates nociceptive neurons. Both an organic Mtb extract and the purified molecule alone were sufficient to induce cough in a conscious guinea pig cough model and guinea pigs infected with wild-type Mtb cough much more frequently than guinea pigs infected with Mtb strains unable to produce nociceptive molecules. Using genetics, biochemistry, and pharmacology techniques, we identified and validated a cough receptor for the Mtb lipid expressed on nociceptive neurons.

Conclusion

We conclude that Mtb produces a molecule that activates nociceptive neurons and induces cough through a specific neuronal receptor. These findings have significant implications for our understanding of Mtb transmission.

Disclosures

All Authors: No reported Disclosures.
1828. Bedaquiline Resistance in Mycobacterium intracellulare Is Mediated by the Transcriptional Repressor MmpT5
Authors: Alexander David , Yoneda Joshua , Bhat Supriya , Oleksyn Teagan , Chen Jeffrey , Andrew Cameron
Published: October 2019

Background

Bedaquiline (BDQ) is an FDA approved antibiotic with antimycobacterial activity. BDQ resistance has been observed in several Mycobacterium species. High-level resistance is due to mutations in ATP synthase. Low -level resistance is attributed to drug efflux. Previously, we suggested that the MmpSL5 efflux system mediates BDQ resistance in M. intracellulare. Here, we examine the role of MmpT5 in transcriptional regulation of mmpSL5 and BDQ resistance.

Methods

In this study, mmpSL5-mmpT5 genes were cloned from 2 pre-treatment (wild-type mmpT5) and 2 relapse (mutant mmpT5) isolates of M. intracellulare and transformed into M. smegmatis. BDQ MICs were determined as well as cell survival after 24 hours exposure to an inhibitory concentration (0.07 µg/mL) of BDQ. Transcription of the M. intracellulare mmpT5 and mmpSL5 promoters was monitored with luciferase reporter gene fusions in the presence of wild-type and mutant alleles of mmpT5. Single and multigene constructs were created using the MoClo system, and transformed into E. coli DH5α. Constructs containing the M. tuberculosis rv0678 gene, which mediates low-level BDQ resistance in M. tuberculosis, were also examined.

Results

The BDQ MIC for the M. smegmatis control strain, and all strains containing mmpSL5-mmpT5 constructs, was 0.007 µg/mL. Even so, strains containing mutant mmpT5 alleles showed enhanced survival after 24 hours exposure to 0.007 µg/mL BDQ. Bacterial colonies associated with mutant mmpT5 alleles exhibited altered morphology relative to wild-type strains. Transcription of mmpSL5 was repressed by wild-type mmpT5, but neither mutant mmpT5 nor rv0678 repressed transcription. The mmpT5 luciferase reporter was not active.

Conclusion

MmpT5 represses transcription of mmpSL5 whereas the operon is dysregulated by mmpT5 mutations. Although Rv0678 regulates mmpSL expression in M. tuberculosis, it cannot repress the M. intracellulare mmpSL5 genes. The mmpSL5-mmpT5 genes have no impact on the BDQ MIC for M. smegmatis, but constructs containing mutant mmpT5 alleles do enhance bacterial survival. The altered morphology of these colonies suggests that BDQ resistance is mediated by cell wall changes in combination with drug efflux.

Disclosures

All Authors: No reported Disclosures.
1879. A 20/20 Vision: Successful Integration of a Prescribing Dashboard for Outpatient Antimicrobial Stewardship to Target 20% Reduction by the Year 2020
Authors: Gentry Erin , Kowalkowski Marc , Burns Ryan , Sweeney Chloe , Collins Cliff , Ann Medaris Leigh , Spencer Melanie , Handy Elizabeth , Davidson Lisa
Published: October 2019

Background

At least 30% of antibiotics prescribed in the ambulatory setting are unnecessary, including high rates of overuse for acute respiratory infections (ARI). We designed and evaluated whether a multifaceted outpatient stewardship program leveraging multidisciplinary stakeholder engagement, education tools, and an innovative prescribing dashboard decreased antibiotic prescribing in ARI.

Methods

In November 2017, the Carolinas HealthCare Outpatient Antimicrobial Stewardship Empowerment Network (CHOSEN) launched an antibiotic awareness campaign in over 150 ambulatory practices in the Charlotte metropolitan area, reaching over one million patients. The campaign included online and in-person tools for patients and providers, targeted education at meetings, and social and mass media exposure. In March 2018, a provider level prescribing dashboard was introduced to target inappropriate antibiotic prescribing in ARI (acute sinusitis, nonsuppurative otitis media, nonbacterial pharyngitis, URI, cough, allergy, and influenza). Data were collected for family medicine (FM), internal medicine (IM), urgent care (UC) and pediatric medicine (PM); 10% and 20% relative reduction targets (years 2019 and 2020, respectively) were set for each service line. We compared pre (April 2016–March 2018) vs. post (April 2018–March 2019) intervention prescribing rates (calculated as the number of encounters with antibiotics vs. total) as rate ratios and used segmented regression models to assess change over time.

Results

There were 1,001,335 pre and 448,390 post-intervention encounters. Postintervention prescribing rates (antibiotics per 100 encounters) decreased for all service lines, FM (49.4 to 39.3), IM (49.7 to 41.2), UC (49.8 to 44.4), and PM (40.6 to 36.1) vs. pre-intervention (all rate ratios, P ≤ 0.01). All service lines met the target 2019 10% reduction goals. Post-implementation, FM and IM showed immediate decreases in prescribing (figure). After an initial increase, UC showed a significant month-to-month decrease (figure).

Conclusion

Integration of a prescribing dashboard within a multifaceted antibiotic awareness campaign reduced inappropriate outpatient antibiotic prescribing for ARI and achieved interim targets consistent with 2020 reduction goals.

Disclosures

All Authors: No reported Disclosures.