bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Characterization of Tumor-Initiating Cells in Multiple Myeloma
Authors: Gao Minjie , Bai Hua , Jethava Yogesh , Wu Yujie , Zhu Yuqi , Yang Ye , Xia Jiliang , Cao Huojun , Franqui-Machin Reinaldo , Nadiminti Kalyan , Thomas Gregory S , Salama Mohamed E , Altevogt Peter , Bishop Gail , Tomasson Michael , Janz Siegfried , Shi Jumei , Chen Lijuan , Frech Ivana , Tricot Guido , Zhan Fenghuang
Published: August 2019

Background

Treatment failures in cancers, including multiple myeloma (MM), are most likely due to the persistence of a minor population of tumor-initiating cells (TICs), which are noncycling or slowly cycling and very drug resistant.

Methods

Gene expression profiling and real-time quantitative reverse transcription polymerase chain reaction were employed to define genes differentially expressed between the side-population cells, which contain the TICs, and the main population of MM cells derived from 11 MM patient samples. Self-renewal potential was analyzed by clonogenicity and drug resistance of CD24+ MM cells. Flow cytometry (n = 60) and immunofluorescence (n = 66) were applied on MM patient samples to determine CD24 expression. Therapeutic effects of CD24 antibodies were tested in xenograft MM mouse models containing three to six mice per group.

Results

CD24 was highly expressed in the side-population cells, and CD24+ MM cells exhibited high expression of induced pluripotent or embryonic stem cell genes. CD24+ MM cells showed increased clonogenicity, drug resistance, and tumorigenicity. Only 10 CD24+ MM cells were required to develop plasmacytomas in mice (n = three of five mice after 27 days). The frequency of CD24+ MM cells was highly variable in primary MM samples, but the average of CD24+ MM cells was 8.3% after chemotherapy and in complete-remission MM samples with persistent minimal residual disease compared with 1.0% CD24+ MM cells in newly diagnosed MM samples (n = 26). MM patients with a high initial percentage of CD24+ MM cells had inferior progression-free survival (hazard ratio [HR] = 3.81, 95% confidence interval [CI] = 5.66 to 18.34, P < .001) and overall survival (HR = 3.87, 95% CI = 16.61 to 34.39, P = .002). A CD24 antibody inhibited MM cell growth and prevented tumor progression in vivo.

Conclusion

Our studies demonstrate that CD24+ MM cells maintain the TIC features of self-renewal and drug resistance and provide a target for myeloma therapy.
Structural Inequality in Refugee Participation in Higher Education
Authors: Naylor Ryan , Terry Les , Rizzo Alberto , Nguyen Nga , Mifsud Nathan
Published: August 2019

Structural inequality is a framework that examines conditions in which groups of people experience unequal opportunities in terms of roles, rights and decision-making compared to others. This research sought to examine whether students from refugee backgrounds faced structural inequalities in their access to higher education. Data regarding the participation of refugee students in higher education between 2011 and 2014 was obtained from the Australian Department of Education and Training. This data was compared with sector averages and those of students from formal equity backgrounds to establish possible structural impediments to university study. Students from refugee backgrounds were found to face both horizontal and vertical inequalities in their access to higher education, as do other equity groups. The experience of refugee students appears to have unique features, however, including gender, age, type of institution accessed and potentially field of study. These barriers may be addressed to some extent by university outreach and support programmes, but more will be required to facilitate full participation in higher education by these students.
Factors affecting canine fecal and parasitic contamination of public green spaces of Buenos Aires city, Argentina, and visitors’ perception of such contamination
Authors: Rubel Diana , Nemirovsky Sergio I , Gorosito Irene , Servián Andrea , Garbossa Graciela
Published: August 2019

Canine fecal contamination in public green areas is difficult to control. Our objectives were to assess: (i) the relationship between fecal contamination in public green spaces of Buenos Aires (Argentina) and the type of green space (boulevard/square/park), considering their area, presence/absence of control measures, and human population density in the surroundings (high or low); (ii) the perception of people of such contamination and (iii) the frequency of parasites in dog feces. In each green space (n = 26), feces were counted in thirty 25-m2 plots randomly located. The opinion survey consisted of asking people (358) what their perception of fecal contamination was, whether it bothered them and whether they thought it was hazardous to the dogs’ or people’ health. Canine fecal samples randomly collected (n = 112) were concentrated and examined microscopically. Mixed-effect generalized linear models were fitted to evaluate the effect of selected variables on fecal contamination. People’s perception of human and canine health risks were assessed by logistic regression. Canine fecal contamination was lower in squares with control measures and in parks with control measures located in densely populated areas, and higher in boulevards located in densely populated areas. The visitor’s perception was that feces were associated with dirtiness (77%) and odor (30.8%). Parasites were detected in 51.8% of fecal samples. Our results confirm that environmental control measures decrease canine fecal contamination of public green spaces, and that more than 65% of the people interviewed do not relate fecal contamination to risks to human/dog health.
A young galaxy cluster in the old Universe
Authors: Hashimoto Tetsuya , Goto Tomotsugu , Momose Rieko , Ho Chien-Chang , Makiya Ryu , Chiang Chia-Ying , Kim Seong Jin
Published: August 2019

Galaxies evolve from a blue star-forming phase into a red quiescent one by quenching their star formation activity. In high-density environments, this galaxy evolution proceeds earlier and more efficiently. Therefore, local galaxy clusters are dominated by well-evolved red elliptical galaxies. The fraction of blue galaxies in clusters monotonically declines with decreasing redshift, i.e. the Butcher–Oemler effect. In the local Universe, observed blue fractions of massive clusters are as small as ≲0.2. Here we report a discovery of a ‘blue cluster’ that is a local galaxy cluster with an unprecedentedly high fraction of blue star-forming galaxies yet hosted by a massive dark matter halo. The blue fraction is 0.57, which is 4.0σ higher than those of the other comparison clusters under the same selection and identification criteria. The velocity dispersion of the member galaxies is 510 km s−1, which corresponds to a dark matter halo mass of 2.0$^{+1.9}_{-1.0}\times 10^{14}$ M⊙. The blue fraction of the cluster is more than 4.7σ beyond the standard theoretical predictions including semi-analytic models of galaxy formation. The probability to find such a high blue fraction in an individual cluster is only 0.003 per cent, which challenges the current standard frameworks of the galaxy formation and evolution in the ΛCDM universe. The spatial distribution of galaxies around the blue cluster suggests that filamentary cold gas streams can exist in massive haloes even in the local Universe. However these cold streams have already disappeared in the theoretically simulated local universes.
Spatial and velocity offsets of Galactic masers from the centres of spiral arms
Authors: Vallée Jacques P
Published: August 2019

Some theories about the spiral arms of galaxies predict an offset between different tracers of star formation. Our goal in this paper is to find such an offset between the observed locations of radio masers and the locations of the arms, using a recent four-arm model fitted to the CO 1–0 gas. Our method is to compare a recent global four-arm spiral model (as fitted to the arms’ tangents in the observed broad CO 1–0 gas) with the recent results for the trigonometric distances of radio masers, for the main arms (Cygnus–Norma, Perseus, Sagittarius–Carina, Scutum and Norma). Our results indicate that most radio masers are near the inner edge of each spiral arm (towards the Galactic Centre). These masers are offset from the model arm (where the broad CO 1–0 molecular region resides), by 0.34 ± 0.06 kpc inward. In radial velocity space, the median offset between masers and the CO-fitted model is around 10 ± 1 km s–1. Based on the fact that the masers are observed here to be radially inward of the broad CO gas in the Cygnus arm at 15 kpc along the Galactic meridian, the corotation radius of the Milky Way disc is >15 kpc distant from the Galactic Centre and the density wave’s angular pattern speed is <15 km s–1 kpc–1. The pitch angle of the arm should be measured using many arm tracers, and located on both sides of the Galactic meridian, to ensure better precision and to avoid a bias pertinent to a single tracer.
Time-slicing spiral galaxies with SDSS-IV MaNGA
Authors: Peterken Thomas , Fraser-McKelvie Amelia , Aragón-Salamanca Alfonso , Merrifield Michael , Kraljic Katarina , Knapen Johan H , Riffel Rogério , Brownstein Joel , Drory Niv
Published: August 2019

Spectra of galaxies contain a wealth of information about the stellar populations from which they are made. With integral field unit (IFU) surveys, such data can be used to map out stellar population properties across the face of a galaxy, allowing one to go beyond simple radial profiles and study details of non-axisymmetric structure. To-date, however, such studies have been limited by the quality of available data and the power of spectral analysis tools. We now take the next step and study the barred spiral galaxy MCG + 07-28-064 from observations obtained as part of the SDSS-IV MaNGA project. We find that we can decompose this galaxy into ‘time slices,’ which reveal the varying contributions that stars of differing ages make to its bar and spiral structure, offering new insight into the evolution of these features. We find evidence for the ongoing growth of the bar, including the most recent star formation on its leading edge, and for the underlying density wave responsible for spiral structure. This pilot study indicates that there is a wealth of untapped information on the spatial distribution of star formation histories available in the current generation of IFU galaxy surveys.
Integral field spectroscopy of Green Peas – I. Disentangling disc-like turbulence and strong outflow kinematics in SDSS J083843.63+385350.5
Authors: Bosch G , Hägele G F , Amorín R , Firpo V , Cardaci M V , Vílchez J M , Pérez-Montero E , Papaderos P , Dors O L , Krabbe A C , Campuzano-Castro F
Published: August 2019

Integral field spectroscopy is well known for providing detailed insight of extended sources thanks to the possibility of handling space resolved spectroscopic information. Simple and straightforward analysis such as single line fitting yields interesting results, although it might miss a more complete picture in many cases. Violent star-forming regions, such as starburst galaxies, display very complex emission line profiles due to multiple kinematic components superposed in the line of sight. We perform a spatially resolved kinematical study of a single Green Pea (GP) galaxy, SDSS J083843.63+385350.5, using a new method for analysing integral field unit observations of emission line spectra. The method considers the presence of multiple components in the emission line profiles and makes use of a statistical indicator to determine the meaningful number of components to fit the observed profiles. We are able to identify three distinct kinematic features throughout the field and discuss their link with a rotating component, a strong outflow, and a turbulent mixing layer. We also derive an updated star formation rate for SDSS J0838 and discuss the link between the observed signatures of a large-scale outflow and of the Lyman continuum leakage detected in GP galaxies.
Dark-age reionization and galaxy formation simulation – XIX. Predictions of infrared excess and cosmic star formation rate density from UV observations
Authors: Qiu Yisheng , Mutch Simon J , da Cunha Elisabete , Poole Gregory B , Wyithe J Stuart B
Published: August 2019

We present a new analysis of high-redshift UV observations using a semi-analytic galaxy formation model, and provide self-consistent predictions of the infrared excess (IRX)–β relations and cosmic star formation rate density. We combine the Charlot & Fall dust attenuation model with the meraxes semi-analytic model, and explore three different parametrizations for the dust optical depths, linked to star formation rate, dust-to-gas ratio, and gas column density, respectively. A Bayesian approach is employed to statistically calibrate model-free parameters including star formation efficiency, mass loading factor, dust optical depths, and reddening slope directly against UV luminosity functions and colour–magnitude relations at $z$ ∼ 4–7. The best-fitting models show excellent agreement with the observations. We calculate IRX using energy balance arguments and find that the large intrinsic scatter in the IRX–β plane correlates with specific star formation rate. Additionally, the difference among the three dust models suggests at least a factor of 2 systematic uncertainty in the dust-corrected star formation rate when using the Meurer IRX–β relation at $z$ ≳ 4.
Slow and massive: low-spin SMBHs can grow more
Authors: Zubovas Kastytis , King Andrew
Published: August 2019

Active galactic nuclei (AGNs) probably control the growth of their host galaxies via feedback in the form of wide-angle wind-driven outflows. These establish the observed correlations between supermassive black hole (SMBH) masses and host galaxy properties, e.g. the spheroid velocity dispersion σ. In this paper we consider the growth of the SMBH once it starts driving a large-scale outflow through the galaxy. To clear the gas and ultimately terminate further growth of both the SMBH and the host galaxy, the black hole must continue to grow its mass significantly, by up to a factor of a few, after reaching this point. The mass increment ΔMBH depends sensitively on both galaxy size and SMBH spin. The galaxy size dependence leads to ΔMBH ∝ σ5 and a steepening of the M–σ relation beyond the analytically calculated M ∝ σ4, in agreement with observation. Slowly spinning black holes are much less efficient in producing feedback, so at any given σ the slowest spinning black holes should be the most massive. Current observational constraints are consistent with this picture, but insufficient to test it properly; however, this should change with upcoming surveys.
Star-forming, rotating spheroidal galaxies in the GAMA and SAMI surveys
Authors: Moffett Amanda J , Phillipps Steven , Robotham Aaron S G , Driver Simon P , Bremer Malcolm N , Cortese Luca , Wong O Ivy , Brough Sarah , Brown Michael J I , Bryant Julia J , Conselice Christopher J , Croom Scott M , George Koshy , Goldstein Greg , Goodwin Michael , Holwerda Benne W , Hopkins Andrew M , Konstantopoulos Iraklis S , Lawrence Jon S , Lorente Nuria P F , Medling Anne M , Owers Matt S , Pimbblet Kevin A , Richards Samuel N , Sweet Sarah M , van de Sande Jesse
Published: August 2019

The Galaxy And Mass Assembly (GAMA) survey has morphologically identified a class of ‘Little Blue Spheroid’ (LBS) galaxies whose relationship to other classes of galaxies we now examine in detail. Considering a sample of 868 LBSs, we find that such galaxies display similar but not identical colours, specific star formation rates, stellar population ages, mass-to-light ratios, and metallicities to Sd-Irr galaxies. We also find that LBSs typically occupy environments of even lower density than those of Sd-Irr galaxies, where ∼65 per cent of LBS galaxies live in isolation. Using deep, high-resolution imaging from VST KiDS and the new Bayesian, 2D galaxy profile modelling code profit, we further examine the detailed structure of LBSs and find that their Sérsic indices, sizes, and axial ratios are compatible with those of low-mass elliptical galaxies. We then examine SAMI Galaxy survey integral field emission line kinematics for a subset of 62 LBSs and find that the majority (42) of these galaxies display ordered rotation with the remainder displaying disturbed/non-ordered dynamics. Finally, we consider potential evolutionary scenarios for a population with this unusual combination of properties, concluding that LBSs are likely formed by a mixture of merger and accretion processes still recently active in low-redshift dwarf populations. We also infer that if LBS-like galaxies were subjected to quenching in a rich environment, they would plausibly resemble cluster dwarf ellipticals.
Emission from the circumgalactic medium: from cosmological zoom-in simulations to multiwavelength observables
Authors: Augustin R , Quiret S , Milliard B , Péroux C , Vibert D , Blaizot J , Rasera Y , Teyssier R , Frank S , Deharveng J-M , Picouet V , Martin D C , Hamden E T , Thatte N , Pereira Santaella M , Routledge L , Zieleniewski S
Published: August 2019

We simulate the flux emitted from galaxy haloes in order to quantify the brightness of the circumgalactic medium (CGM). We use dedicated zoom-in cosmological simulations with the hydrodynamical adaptive mesh refinement code ramses, which are evolved down to z = 0 and reach a maximum spatial resolution of 380 h−1 pc and a gas mass resolution up to $1.8\times 10^{5} \, h^{-1}\, \rm {M}_{\odot }$ in the densest regions. We compute the expected emission from the gas in the CGM using cloudy emissivity models for different lines (e.g. Lyα, C iv, O vi, C vi, O viii) considering UV background fluorescence, gravitational cooling and continuum emission. In the case of Lyα, we additionally consider the scattering of continuum photons. We compare our predictions to current observations and find them to be in good agreement at any redshift after adjusting the Lyα escape fraction. We combine our mock observations with instrument models for Faint Intergalactic Redshifted Emission Balloon-2 (FIREBall-2; UV balloon spectrograph) and HARMONI (visible and NIR IFU on the ELT) to predict CGM observations with either instrument and optimize target selections and observing strategies. Our results show that Lyα emission from the CGM at a redshift of 0.7 will be observable with FIREBall-2 for bright galaxies (NUV∼18 mag), while metal lines like O vi and C iv will remain challenging to detect. HARMONI is found to be well suited to study the CGM at different redshifts with various tracers.
A CO-multilayer outer atmosphere for eight evolved stars revealed with VLTI/AMBER
Authors: Hadjara M , Cruzalèbes P , Nitschelm C , Chen X , Michael E A , Moreno E
Published: August 2019

We determine the physical parameters of the outer atmosphere of a sample of eight evolved stars, including the red supergiant α Scorpii, the red giant branch stars α Bootis and γ Crucis, the K giant λ Velorum, the normal M giants BK Virginis and SW Virginis, and the Mira star W Hydrae (in two different luminosity phases) by spatially resolving the stars in the individual carbon monoxide (CO) first overtone lines. We used the Astronomical Multi-BEam combineR (AMBER) instrument at the Very Large Telescope Interferometer (VLTI), in high-resolution mode (λ/Δλ ≈ 12 000) between 2.28 and 2.31 $\, \mu {\rm m}$ in the K band. The maximal angular resolution is 10 mas, obtained using a triplet telescope configuration, with baselines from 7 to 48 m. By using a numerical model of a molecular atmosphere in a spherical shells (MOLsphere), called pampero (an acronym for the ‘physical approach of molecular photospheric ejection at high angular resolution for evolved stars’), we add multiple extended CO layers above the photospheric marcs model at an adequate spatial resolution. We use the differential visibilities and the spectrum to estimate the size (R) of the CO molsphere, its column density (NCO) and temperature (Tmol) distributions along the stellar radius. The combining of the χ2 minimization and a fine grid approach for uncertainty analysis leads to reasonable NCO and Tmol distributions along the stellar radius of the MOLsphere.
Impact of In Vivo Protein Folding Probability on Local Fitness Landscapes
Authors: Faber Matthew S , Wrenbeck Emily E , Azouz Laura R , Steiner Paul J , Whitehead Timothy A
Published: August 2019

It is incompletely understood how biophysical properties like protein stability impact molecular evolution and epistasis. Epistasis is defined as specific when a mutation exclusively influences the phenotypic effect of another mutation, often at physically interacting residues. In contrast, nonspecific epistasis results when a mutation is influenced by a large number of nonlocal mutations. As most mutations are pleiotropic, the in vivo folding probability—governed by basal protein stability—is thought to determine activity-enhancing mutational tolerance, implying that nonspecific epistasis is dominant. However, evidence exists for both specific and nonspecific epistasis as the prevalent factor, with limited comprehensive data sets to support either claim. Here, we use deep mutational scanning to probe how in vivo enzyme folding probability impacts local fitness landscapes. We computationally designed two different variants of the amidase AmiE with statistically indistinguishable catalytic efficiencies but lower probabilities of folding in vivo compared with wild-type. Local fitness landscapes show slight alterations among variants, with essentially the same global distribution of fitness effects. However, specific epistasis was predominant for the subset of mutations exhibiting positive sign epistasis. These mutations mapped to spatially distinct locations on AmiE near the initial mutation or proximal to the active site. Intriguingly, the majority of specific epistatic mutations were codon dependent, with different synonymous codons resulting in fitness sign reversals. Together, these results offer a nuanced view of how protein folding probability impacts local fitness landscapes and suggest that transcriptional–translational effects are as important as stability in determining evolutionary outcomes.
Pulmonary Hypertension as a Primary Presentation for Schistosomiasis, a Case Report of Unusual Presentation
Authors: Hussein Mogahed Ismail Hassan
Published: August 2019

The combination of schistosomiasis and pulmonary hypertension (PH) was always recognized as a very rare one; in medical literature, PH is considered as a manifestation of hepatosplenic schistosomiasis but not a manifestation of schistosomal infection until recently. Only 18.5% of patients that have a documented hepatosplenic schistosomiasis were found with PH. Schistosomiasis rarely causes PH without evident hepatosplenic manifestations. Here, we are reporting a case of a patient whose first clinical presentation was features of PH. We use this case as an opportunity to outline pathological mechanisms, causes and classification of PH. A structured and thorough workup for PH is emphasized. It is important to exclude all other secondary causes to be able to diagnose primary PH especially in the absence of a positive family history and advanced diagnostic technology.
Fertilization-Coupled Sperm Nuclear Fusion Is Required for Normal Endosperm Nuclear Proliferation
Authors: Maruyama Daisuke , Higashiyama Tetsuya , Endo Toshiya , Nishikawa Shuh-ichi
Published: August 2019

Angiosperms exhibit double fertilization, a process in which one of the sperm cells released from the pollen tube fertilizes the egg, while the other sperm cell fertilizes the central cell, giving rise to the embryo and endosperm, respectively. We have previously reported two polar nuclear fusion-defective double knockout mutants of Arabidopsis thaliana immunoglobulin binding protein (BiP), a molecular chaperone of the heat shock protein 70 (Hsp70) localized in the endoplasmic reticulum (ER), (bip1 bip2) and its partner ER-resident J-proteins, ERdj3A and P58IPK (erdj3a p58ipk). These mutants are defective in the fusion of outer nuclear membrane and exhibit characteristic seed developmental defects after fertilization with wild-type pollen, which are accompanied by aberrant endosperm nuclear proliferation. In this study, we used time-lapse live-cell imaging analysis to determine the cause of aberrant endosperm nuclear division in these mutant seeds. We found that the central cell of bip1 bip2 or erdj3a p58ipk double mutant female gametophytes was also defective in sperm nuclear fusion at fertilization. Sperm nuclear fusion was achieved after the onset of the first endosperm nuclear division. However, division of the condensed sperm nucleus resulted in aberrant endosperm nuclear divisions and delayed expression of paternally derived genes. By contrast, the other double knockout mutant, erdj3b p58ipk, which is defective in the fusion of inner membrane of polar nuclei but does not show aberrant endosperm nuclear proliferation, was not defective in sperm nuclear fusion at fertilization. We thus propose that premitotic sperm nuclear fusion in the central cell is critical for normal endosperm nuclear proliferation.
Negation, expressivism, and intentionality
Authors: Pérez Carballo Alejandro
Published: August 2019

Many think that expressivists have a special problem with negation. I disagree. For if there is a problem with negation, I argue, it is a problem shared by those who accept some plausible claims about the nature of intentionality. Whether there is any special problem for expressivists turns, I will argue, on whether facts about what truth-conditions beliefs have can explain facts about basic inferential relations among those beliefs. And I will suggest that the answer to this last question is, on most plausible attempts at solving the problem of intentionality, ‘no’.
Impact of adding tacrolimus to initial treatment of interstitial pneumonitis in polymyositis/dermatomyositis: a single-arm clinical trial
Authors: Takada Kazuki , Katada Yoshinori , Ito Satoshi , Hayashi Taichi , Kishi Jun , Itoh Kenji , Yamashita Hiroyuki , Hirakata Michito , Kawahata Kimito , Kawakami Atsushi , Watanabe Norihiko , Atsumi Tatsuya , Takasaki Yoshinari , Miyasaka Nobuyuki
Published: August 2019

Objective

Interstitial pneumonia is common and has high short-term mortality in patients with PM and DM despite glucocorticoid (GC) treatment. Retrospective studies suggested that the early use of immunosuppressive drugs with GCs might improve its short-term mortality.

Methods

A multicentre, single-arm, 52-week-long clinical trial was performed to test whether the initial combination treatment with tacrolimus (0.075 mg/kg/day, adjusted for the target whole-blood trough levels between 5 and 10 ng/ml) and GCs (0.6–1.0 mg/kg/day of prednisolone followed by a slow taper) improves short-term mortality of PM/DM-interstitial pneumonia patients. The primary outcome was overall survival. We originally intended to compare, by using propensity-score matching, the outcome data of clinical trial patients with that of historical control patients who were initially treated with GCs alone.

Results

The 52-week survival rate with the combination treatment (N = 26) was 88.0% (95% CI, 67.3, 96.0). Safety profiles of the combination treatment were consistent with those known for tacrolimus and high-dose GCs individually. Serious adverse events occurred in 11 patients (44.0%), which included four opportunistic infections. Only 16 patients, including only 1 deceased patient, were registered as historical controls, which precluded meaningful comparative analysis against the clinical trial patients.

Conclusion

Our study provided findings which suggest that initial treatment with tacrolimus and GCs may improve short-term mortality of PM/DM-interstitial pneumonia patients with manageable safety profiles. This was the first prospective clinical investigation conducted according to the Good Clinical Practice Guideline of the International Conference on Harmonization for the treatment of this potentially life-threatening disease.

Trial registration

ClinicalTrials.gov, http://clinicaltrials.gov, NCT00504348.
Development of a Novel AOP for Cyp2F2-Mediated Lung Cancer in Mice
Authors: Hill Thomas , Conolly Rory B
Published: August 2019

Traditional methods for carcinogenicity testing rely heavily on the rodent bioassay as the standard for identification of tumorigenic risk. As such, identification of species-specific outcomes and/or metabolism are a frequent argument for regulatory exemption. One example is the association of tumor formation in the mouse lung after exposure to Cyp2F2 ligands. The adverse outcome pathway (AOP) framework offers a theoretical platform to address issues of species specificity that is consistent, transparent, and capable of integrating data from new approach methodologies as well as traditional data streams. A central premise of the AOP concept is that pathway progression from the molecular initiating event (MIE) implies a definable “response-response” (R-R) relationship between each key event (KE) that drives the pathway towards a specific adverse outcome (AO). This article describes an AOP for lung cancer in the mouse from an MIE of Cyp2F2-specific reactive metabolite formation, advancing through KE that include protein and/or nucleic acid adducts, diminished Club Cell 10 kDa (CC10) protein expression, hyperplasia of CC10 deficient Club cells, and culminating in the AO of mixed-cell tumor formation in the distal airways. This tumor formation is independent of route of exposure and our AOP construct is based on overlapping mechanistic events for naphthalene, styrene, ethyl benzene, isoniazid, and fluensulfone in the mouse. This AOP is intended to accelerate the explication of an apparent mouse-specific outcome and serve as a starting point for a quantitative analysis of mouse-human differences in susceptibility to the tumorigenic effects of Cyp2F2 ligands.
Associations Between Parity, Breastfeeding, and Risk of Maternal Type 2 Diabetes Among Postmenopausal Women
Authors: Luo Juhua , Hendryx Michael , LeBlanc Erin S. , Shadyab Aladdin H. , Qi Lihong , Sealy-Jefferson Shawnita , Manson JoAnn E.
Published: August 2019

OBJECTIVE:

To examine associations among parity, breastfeeding history, and risk of developing type 2 diabetes among postmenopausal women.

METHODS:

A prospective cohort study was conducted. One hundred thirty-six thousand six hundred fifty-two postmenopausal women aged 50–79 years participating in the Women's Health Initiative recruited from 40 clinical centers throughout the United States between 1993 and 1998, without baseline cancer or diabetes were followed for 14.2 years. Parity and breastfeeding data were collected by questionnaires administrated to all participants at baseline. Incident diabetes was assessed via validated self-report of physician-diagnosed diabetes treated with insulin or other hypoglycemic medications. Multivariable Cox proportional hazards regression models were used to assess associations between parity, breastfeeding and diabetes incidence, and racial–ethnic differences in the associations.

RESULTS:

During follow-up, 18,812 cases of incident diabetes were identified. Overall, a greater number of term pregnancies was associated with increased risk of diabetes (P for trend=.002), and longer duration of breastfeeding was associated with lower risk of diabetes (P for trend <.01). After further adjusting for adult weight gain among a subset of the cohort (n=75,558) with 9,110 cases, the association between parity and risk of diabetes were attenuated and became nonsignificant. Also, parous women with fewer than five term pregnancies did not have increased diabetes risk when breastfeeding for 3 months or more per child, which was associated with less weight gain.

CONCLUSION:

The results of this large, prospective study showed that the association between parity and risk of type 2 diabetes was most likely confounded by adult weight gain among postmenopausal women.
Strategies for Prescribing Aspirin to Prevent Preeclampsia
Authors: Mallampati Divya , Grobman William , Rouse Dwight J. , Werner Erika F.
Published: August 2019

OBJECTIVE:

To evaluate the cost effectiveness of various preeclampsia screening and aspirin prophylaxis strategies, including a strategy based on biomarker and ultrasound measures.

METHODS:

We designed a decision analysis to compare preeclampsia-related costs and effects of four strategies for aspirin use in pregnancy initiated before 16 weeks of gestation to prevent preeclampsia. The four strategies were: 1) no aspirin use, 2) biomarker and ultrasound measure–predicated use, 3) use based on the U.S. Preventive Services Task Force guidelines, and 4) universal aspirin use. Our outcomes were preeclampsia-related costs and number of cases per 100,000 pregnant women. Using a threshold of $90,843 per case of preeclampsia, one-way, two-way, and Monte-Carlo sensitivity analyses incorporating varying probabilities of risk reduction due to aspirin use, aspirin-related side effects, and costs were performed to identify ranges at which costs and risks of aspirin-related complications shifted the preferred strategy.

RESULTS:

Compared with universal aspirin administration, the use of U.S. Preventive Services Task Force guidelines is associated with $8,011,725 higher health care costs and 346 additional cases of preeclampsia per 100,000 pregnant women; biomarker and ultrasound screening is associated with an additional $19,216,551 and 308 additional cases. Similarly, no aspirin use is associated with an increased cost of $18,750,381 and 762 additional cases. Thus, universal aspirin use dominated all three other strategies. In a Monte Carlo simulation of 10,000 pregnant women, universal aspirin was the preferred strategy in 91% of simulations. The U.S. Preventive Task Force screen was preferred in 8.5% of simulations, and biomarker and ultrasound screening and no aspirin were preferred in 0% and 0.5% of simulations, respectively.

CONCLUSION:

Over a broad range of assumptions, universal aspirin administration is associated with fewer cases of preeclampsia and fewer costs relative to no aspirin administration and aspirin administration based on serum and ultrasound measures or clinical risk factors.
Small-Group, Community-Member Intervention for Urinary and Bowel Incontinence
Authors: Brown Heidi W. , Braun Emilie J. , Wise Meg E. , Myers Shannon , Li Zhanhai , Sampene Emmanuel , Jansen Sierra M. , Moberg D. Paul , Mahoney Jane E. , Rogers Rebecca G.
Published: August 2019

OBJECTIVE:

To evaluate the effects of Mind Over Matter: Healthy Bowels, Healthy Bladder, a small-group intervention, on urinary and bowel incontinence symptoms among older women with incontinence.

METHODS:

In this individually randomized group treatment trial, women aged 50 years and older with urinary, bowel incontinence, or both, were randomly allocated at baseline to participate in Mind Over Matter: Healthy Bowels, Healthy Bladder immediately (treatment group) or after final data collection (waitlist control group). The primary outcome was urinary incontinence (UI) improvement on the Patient Global Impression of Improvement at 4 months. Validated instruments assessed incontinence, self-efficacy, depression, and barriers to care-seeking. Intent-to-treat analyses compared differences between groups. Target sample size, based on an anticipated improvement rate of 45% in treated women vs 11% in the control group, 90% power, type I error of 0.05, with anticipated attrition of 25%, was 110.

RESULTS:

Among 121 women randomized (62 treatment group; 59 control group), 116 (95%) completed the 4-month assessment. Most participants were non-Hispanic white (97%), with a mean age of 75 years (SD 9.2, range 51–98); 66% had attended some college. There were no significant between-group differences at baseline. At 4 months, 71% of treated women vs 23% of women in the control group reported improved UI on Patient Global Impression of Improvement (P<.001); 39% vs 5% were much improved (P<.001). Regarding bowel incontinence, 55% of treated women vs 27% of women in the control group improved on Patient Global Impression of Improvement (P<.005), with 35% vs 11% reporting much improvement (P<.005). Treated women improved significantly more than women in the control group on all validated instruments of incontinence severity, quality of life, and self-efficacy. Care-seeking rates were similar between groups.

CONCLUSION:

Participation in a small-group intervention improves symptoms of both urinary and bowel incontinence in older women. Mind Over Matter is a feasible model with potential to bring effective behavioral solutions to the community.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT03140852.
What Is New in Uterine Conservation in the Clinical Setting of Uterovaginal Prolapse?
Authors: Richter Holly E.
Published: August 2019

This month we focus on current research in uterine conservation at the time of uterovaginal prolapse repair. Dr. Richter discusses four recent publications, which are concluded with a “bottom line” that is the take-home message. A complete reference for each can be found on Box 1 on this page along with direct links to the abstracts.
Influence of Social Media on the Decision to Undergo a Cosmetic Procedure
Authors: Arab Khalid , Barasain Omar , Altaweel Abdullah , Alkhayyal Jawaher , Alshiha Lulwah , Barasain Rana , Alessa Rania , Alshaalan Hayfaa
Published: August 2019

Background:

There is a rise of cosmetic procedures in Saudi Arabia. Social media have become a popular means of advertisements for cosmetic professional providers. There are currently no studies that determine the relationship between viewing cosmetic surgery advertisements and considering undergoing cosmetic procedures in female university students in Saudi Arabia.

Methods:

A cross-sectional study was conducted using an online survey. This survey determined the use of social media, cosmetic-related accounts followed by the respondent, and attitudes toward advertising for cosmetic treatments on social media. It also determines the influence of these accounts on female university students to consider undergoing cosmetic treatments in the future. The survey was distributed on multiple social media platforms and by Email.

Results:

Out of 816 completed questionnaires, 48.5% reported being influenced by social media to consider undergoing cosmetic procedures. Respondents (51.4%) follow plastic surgeons on social media (P < 0.001). The most common reported number of hours of social media use per day was >5 hours per day (53.2%; P < 0.026). Statistical significance was considered in relation to reporting being influenced by social media to consider undergoing cosmetic procedures in the future.

Conclusions:

Our findings revealed that viewing cosmetic surgery–related material on social media, spending longer hours on social media platforms, and having negative self-views when viewing social media are associated with an increased likelihood of considering undergoing cosmetic procedures in the future. Future studies using a validated questionnaire that assesses the likelihood of being influenced by social media to undergo cosmetic treatments are encouraged.
Rhinoplasty and External Nasal Splinting: Is It Really a Must?
Authors: Challita Raymond , Shouman Mohamad , Ghanime George
Published: August 2019

Background:

Rhinoplasty is a common and challenging procedure. Lateral osteotomy is routinely performed in most cases. Most of the surgeons have the habit of applying external nasal splints to stabilize the nasal tissues and bone in their new position postrhinoplasty. These splints are widely used despite the absence of any evidence supporting this practice. Moreover, these splints have a lot of disadvantages, so we conducted this study to evaluate the cosmetic result in their absence.

Patients and Methods:

A retrospective cross-sectional study was performed. Medical records of 211 patients operated on for rhinoplasty by the same surgeon from 2015 to 2017 were reviewed. All patients were operated using open technique. After surgery, a Steri-Strips dressing with an overlying layer of surgical tape was applied to the nose without the use of an external nasal splint. Most of the patients were followed up for 18 months. Complication rates, revision rates, and nasal bone widths were recorded.

Results:

Complication rates and revision rates were as follows: skin infection 0.99%, skin necrosis 0.99%, and secondary revision 3.48%. Finally 79.60% of patients had a decrease in their nasal bone width postsurgery.

Conclusion:

Based on the present study, external nasal splinting postrhinoplasty should not be routinely used. Satisfactory cosmetic results can be obtained while avoiding the complications, cost, and bulky dressings associated with external splints.
Creating a Defined Process to Improve the Timeliness of Serious Safety Event Determination and Root Cause Analysis
Authors: Donnelly Lane F. , Palangyo Tua , Bargmann-Losche Jessey , Rogers Kiley , Wood Mathew , Shin Andrew Y.
Published: August 2019

Introduction:

Serious Safety Events (SSEs) are defined as events in which there is a deviation from clinically accepted performance standards, causation, and significant patient harm or death. Given the nature of SSEs, it is important that the processes for declaration of SSEs, the performance of a root cause analysis (RCA), and action plan formation occur quickly, such that the window for potential recurrence of similar events is as small as possible. This manuscript describes a process put in place to improve the timeliness of SSE determination and RCA conduction and evaluates the effect of the process change on these parameters.

Methods:

A causal analysis was performed of the baseline process to determine factors contributing to long process times. A new process was created and implemented both for the SSE determination process and the RCA completion process. We calculated the mean time for the pre-implementation phase (April 2016–December 2017) and the post-implementation phase (March 2018–January 2019) for both SSE determination and RCA completion. We evaluated differences with a two-sided t test assuming unequal variances.

Results:

Comparing pre- versus post- implementation phases, the mean time for SSE determination for events that met the SSE criteria decreased from 38.4 to 4.8 days (P < 0.0001), determination for events that did not meet the SSE criteria decreased from 38.4 to 3.8 days (P < 0.0001), and RCA completion time dropped from 118.0 to 26.2 days (P < 0.0001).

Conclusions:

A targeted intervention can significantly reduce SSE determination and RCA conduction times.
Diagnosis and Treatment of Scalp Arteriovenous Malformations With Intracranial Extension
Authors: Kanth Aditi M. , Ricci Joseph A. , Adetayo Oluwaseun A.
Published: August 2019

Scalp arteriovenous malformations (AVMs) are rare entities that may present as large, tortuous vascular lesions with resultant craniofacial deformity. Radiologic findings include feeding arteries and veins associated with dilated tortuous vessels. Intracranial extension is rare. A 5-year-old African American male presented with an occipital mass presumed to be a dermoid cyst on referral. Further workup revealed the presence of a scalp AVM that demonstrated extension into the left sigmoid sinus. Radiologic and intraoperative images are presented. Literature search revealed only 4 patients with scalp AVM extending intracranially into the sagittal sinus, 2 of which were managed with coagulation and division of the feeding vessels and the other 2 underwent preoperative embolization. Our patient is the 1st to be reported to have sigmoid sinus extension. Scalp AVMs with intracranial extension are rare, and require further preoperative workup. Following ultrasound evaluation, computed tomography angiography, magnetic resonance angiography, magnetic resonance imaging, or cerebral angiography can be considered. Treatment entails resection, but preoperative embolization is increasingly used, mirroring patients without intracranial extension. Further studies are needed to evaluate the efficacy and risk profile of these treatments.
Sclerotherapy for Extensive Vascular Malformation in the Tongue
Authors: Couto Douglas Augusto Fernandes , Ito Fabio Augusto , Lima Heliton Gustavo de , Novais Josuel Divino , Novais Jaqueline Benedita , Dallazen Eduardo , Takahama Ademar
Published: August 2019

Vascular malformations (VMs) are benign lesions of blood vessels originated from an error in vascular morphogenesis during the embryologic phase. Generally, when located in the head and neck region VMs occurs in lips, tongue, buccal mucosa, gums, or palate. The VMs are usually asymptomatic, varies in size and may cause facial asymmetries. Different therapeutic modalities are available to treat VMs, which include surgical excision, cautery, cryotherapy, laser therapy, and sclerosing agents. The authors report 2 patients with extensive VM in the tongue treated with intralesional injection of a low-dose solution of monoethanolamine oleate (MO) and lidocaine. The first patient was a 69-year-old male patient and the 2nd a 65-year-old woman. In both patients, it were performed weekly application of 1:1 MO (Ethamolin) with Lidocaine (lidocaine 3% 1:50,000) in the amount of 0.1 mL of the solution per cm3 of lesion, with a total of 12 applications for each patient at the end of the treatment, with good results and without complications. It is important to be alert in which situation sclerotherapy should be used and that small doses of the sclerotherapeutic agent is essential for the prevention of complications after the procedure. Therefore, these patients showed that the sclerotherapy with MO may be an effective and simple treatment for extensive oral benign vascular lesions. In both patients, there was a great improvement in the clinical aspect of the lesions and patient's satisfaction.
The Effect of Warfarin on the Fibrin Architecture of Platelet-Rich Fibrin
Authors: Bootkrajang Methakorn , Chinkrua Chonatee , Aschaitrakool Yuthakran
Published: August 2019

Aim:

The aim of the study was to compare the macroscopic and microscopic factors, using scanning electron microscopy (SEM), of platelet-rich fibrin (PRF) between patients taking warfarin and healthy volunteers.

Materials and methods:

Twenty participants were selected (55 years old or older). Ten patients undertaking warfarin therapy with an International Normalized Ratio (INR) range from 2.50 to 4.00 acted as an experimental group and 10 healthy volunteers acted as a control group. Twenty-five-milliliter blood samples were collected from the 20 patients for PRF production and laboratory screening (INR and hematocrit). Then, PRF clots were compressed to a 1-millimeter membrane. All PRF sample macroscopic features (color, length, and width) were recorded and prepared for SEM evaluation. Images were obtained with SEM with 8000 times magnification. The percentage of the fibrin density was measured using ImageJ software (NIH, Bethesda, MD). Descriptive analysis was used to describe the macroscopic features. An independentttest and 1-way analysis of variance were used to compare both groups and each segment of PRF.

Results:

All macroscopic features were totally identical. The fibrin density average from the upper to lower end was 89.09% ± 1.99%, 88.11% ± 3.25%, and 88.61% ± 2.65% (control group) and 88.62% ± 1.53%, 88.62% ± 1.20%, and 89.54% ± 2.17% (experimental group), respectively. There were no significant differences in the macroscopic features between the 2 groups and no differences in the microscopic features between the 2 groups and within each group.

Conclusions:

Warfarin did not have an effect on PRF when the macroscopic and microscopic features were compared between healthy volunteers and warfarin therapy volunteers.