bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased tenofovir monoester concentrations in patients receiving tenofovir disoproxil fumarate with ledipasvir/sofosbuvir
Authors: Brooks Kristina M , Castillo-Mancilla Jose R , Blum Joshua , Huntley Ryan , MaWhinney Samantha , Alexander Keisha , Kerr Becky Jo , Ellison Lucas , Bushman Lane R , MacBrayne Christine E , Anderson Peter L , Kiser Jennifer J 
Published: April 2019

AbstractBackgroundIntracellular tenofovir diphosphate concentrations are markedly increased in HIV/HCV coinfected individuals receiving tenofovir disoproxil fumarate (TDF) with sofosbuvir-containing treatment. Sofosbuvir may inhibit the hydrolysis of TDF to tenofovir, resulting in increased concentrations of the disoproxil or monoester forms, which may augment cell loading. We sought to quantify tenofovir disoproxil and monoester concentrations in individuals receiving TDF with and without ledipasvir/sofosbuvir.MethodsHIV/HCV coinfected participants receiving TDF-based therapy were sampled pre-dose and 1 and 4 h post-dose prior to and 4 weeks after initiating ledipasvir/sofosbuvir. Tenofovir disoproxil was not detectable. Tenofovir monoester in plasma and tenofovir diphosphate in PBMC and dried blood spots (DBS) were quantified using LC-MS/MS. Geometric mean ratios (week 4 versus baseline) and 95% CIs were generated for the pharmacokinetic parameters. P values reflect paired t-tests.ResultsTen participants had complete data. At baseline, geometric mean (95% CI) tenofovir monoester plasma concentrations at 1 and 4 h post-dose were 97.4 ng/mL (33.0–287.5) and 0.74 ng/mL (0.27–2.06), respectively. With ledipasvir/sofosbuvir, tenofovir monoester concentrations at 4 h post-dose were 5.02-fold higher (95% CI 1.40–18.05; P = 0.019), but did not significantly differ at 1 h post-dose (1.72-fold higher, 95% CI 0.25–11.78; P = 0.54), possibly due to absorption variability. Tenofovir diphosphate in PBMC and DBS were increased 2.80-fold (95% CI 1.71–4.57; P = 0.001) and 7.31-fold (95% CI 4.47–11.95; P < 0.0001), respectively, after 4 weeks of ledipasvir/sofosbuvir.ConclusionsTenofovir monoester concentrations were increased in individuals receiving TDF with ledipasvir/sofosbuvir, consistent with inhibition of TDF hydrolysis. Additional studies are needed to determine the clinical relevance of this interaction.
Cost-Effectiveness of Colonoscopy-Based Colorectal Cancer Screening in Childhood Cancer Survivors
Authors: Gini Andrea , Meester Reinier G S , Keshavarz Homa , Oeffinger Kevin C , Ahmed Sameera , Hodgson David C , Lansdorp-Vogelaar Iris 
Published: April 2019

Abstract

Background
Childhood cancer survivors (CCS) are at increased risk of developing colorectal cancer (CRC) compared to the general population, especially those previously exposed to abdominal or pelvic radiation therapy (APRT). However, the benefits and costs of CRC screening in CCS are unclear. In this study, we evaluated the cost-effectiveness of early-initiated colonoscopy screening in CCS.

Methods
We adjusted a previously validated model of CRC screening in the US population (MISCAN-Colon) to reflect CRC and other-cause mortality risk in CCS. We evaluated 91 colonoscopy screening strategies varying in screening interval, age to start, and age to stop screening for all CCS combined and for those treated with or without APRT. Primary outcomes were CRC deaths averted (compared to no screening) and incremental cost-effectiveness ratios (ICERs). A willingness-to-pay threshold of $100 000 per life-years gained (LYG) was used to determine the optimal screening strategy.

Results
Compared to no screening, the US Preventive Services Task Force’s average risk screening schedule prevented up to 73.2% of CRC deaths in CCS. The optimal strategy of screening every 10 years from age 40 to 60 years averted 79.2% of deaths, with ICER of $67 000/LYG. Among CCS treated with APRT, colonoscopy every 10 years from age 35 to 65 years was optimal (CRC deaths averted: 82.3%; ICER: $92 000/LYG), whereas among those not previously treated with APRT, screening from age 45 to 55 years every 10 years was optimal (CRC deaths averted: 72.7%; ICER: $57 000/LYG).

Conclusions
Early initiation of colonoscopy screening for CCS is cost-effective, especially among those treated with APRT.
Citizens of Nowhere? Paradoxes of State Parental Responsibility for Unaccompanied Migrant Children in the United Kingdom
Authors: Meloni Francesca , Humphris Rachel 
Published: April 2019

AbstractSocial workers are confronted with a contradictory task: that of acting as state parents for unaccompanied asylum-seeking children, in an era of hostile migration policies and austerity. Mobilizing Young’s (2006) concept of ‘responsibility’, we ask: how is state parental responsibility towards unaccompanied minors given meaning, and with what consequences, for both frontline workers and unaccompanied minors alike? Drawing on interviews with frontline workers and unaccompanied minors in the United Kingdom (n = 107), we delineate three modes through which responsibility operates: namely outcomes, capacity and morality. We argue that the underlying logic of responsibility shifts the blame from sociopolitical structures to migrant children themselves, with crucial consequences for questions of social justice.
Dark molecular gas in Pegasus–Pisces
Authors: Donate Emmanuel , Blair Samantha , Chilton Zachary , Gladney Codie , Gordon Jeremy W , Goulart Micah C , Magnani Loris 
Published: April 2019

Abstract
We examine the molecular content of a large region (∼2200 square degrees) in Pegasus–Pisces with an estimated dark molecular gas fraction of 59 per cent. Using the extensive CO(1-0) Southern Galactic hemisphere, high-latitude survey by Magnani et al. (2000), we re-examined the CO-detectable mass estimates for the region. By averaging all the CO spectra in subsections ranging in size from 3° × 3° to 15° × 15°, we decreased the rms of the averaged CO spectra by factors of 3–10, effectively trading spatial resolution for sensitivity. With the new spectra, we are able to make estimates of the CO-detectable mass as a function of sensitivity. Using the optimal estimate, the CO-detectable mass increases from 2200 to 4000 M⊙, thereby decreasing the dark molecular gas fraction in the region to 0.24. CO(1–0) observations with rms values in the 20–30 mK range can nearly double the molecular mass in regions with diffuse and translucent molecular clouds.
Stellar encounters with giant molecular clouds
Authors: Kokaia Giorgi , Davies Melvyn B 
Published: April 2019

ABSTRACTGiant molecular clouds (GMCs) are believed to affect the biospheres of planets as their host star passes through them. We simulate the trajectories of stars and GMCs in the Galaxy and determine how often stars pass through GMCs. We find a strong decreasing dependence with Galactocentric radius, and with the velocity perpendicular to the Galactic plane, V$\mathrm{ z}$. The XY-component of the kinematic heating of stars was shown to not affect the GMC hit rate, unlike the Z-dependence (V$\mathrm{ z}$) implies that stars hit fewer GMCs as they age. GMCs are locations of star formation, therefore we also determine how often stars pass near supernovae. For the supernovae the decrease with V$\mathrm{ z}$ is steeper as how fast the star passes through the GMC determines the probability of a supernova encounter. We then integrate a set of Sun-like trajectories to see the implications for the Sun. We find that the Sun hits 1.6 ± 1.3 GMCs per Gyr which results in 1.5 ± 1.1 or (with correction for clustering) 0.8 ± 0.6 supernova closer than 10 pc per Gyr. The different the supernova frequencies are from whether one considers multiple supernovae per GMC crossing (few Myr) as separate events. We then discuss the effect of the GMC hits on the Oort cloud, and the Earth’s climate due to accretion, we also discuss the records of distant supernova. Finally, we determine Galactic Habitable Zone using our model. For the thin disc, we find it to lie between 5.8 and 8.7 kpc and for the thick disc to lie between 4.5 and 7.7 kpc.
Alignment of a circumbinary disc around an eccentric binary with application to KH 15D
Authors: Smallwood Jeremy L , Lubow Stephen H , Franchini Alessia , Martin Rebecca G 
Published: April 2019

ABSTRACT
We analyse the evolution of a mildly inclined circumbinary disc that orbits an eccentric orbit binary by means of smoothed particle hydrodynamics (SPH) simulations and linear theory. We show that the alignment process of an initially misaligned circumbinary disc around an eccentric orbit binary is significantly different than around a circular orbit binary and involves tilt oscillations. The more eccentric the binary, the larger the tilt oscillations and the longer it takes to damp these oscillations. A circumbinary disc that is only mildly inclined may increase its inclination by a factor of a few before it moves towards alignment. The results of the SPH simulations agree well with those of linear theory. We investigate the properties of the circumbinary disc/ring around KH 15D. We determine disc properties based on the observational constraints imposed by the changing binary brightness. We find that the inclination is currently at a local minimum and will increase substantially before settling to coplanarity. In addition, the nodal precession is currently near its most rapid rate. The recent observations that show a reappearance of star B impose constraints on the thickness of the layer of obscuring material. Our results suggest that disc solids have undergone substantial inward drift and settling towards to disc mid-plane. For disc masses ∼0.001 M⊙, our model indicates that the level of disc turbulence is low (α ≪ 0.001). Another possibility is that the disc/ring contains little gas.
Opacities for photon splitting and pair creation in neutron star magnetospheres
Authors: Hu Kun , Baring Matthew G , Wadiasingh Zorawar , Harding Alice K 
Published: April 2019

ABSTRACT
Over the last four decades, persistent and flaring emission of magnetars observed by various telescopes has provided us with a suite of light curves and spectra in soft and hard X-rays, with no emission yet detected above around 1 MeV. Attenuation of such high-energy photons by magnetic pair creation and photon splitting is expected to be active in the magnetospheres of magnetars, possibly accounting for the paucity of gamma-rays in their signals. This paper explores polarization-dependent opacities for these two QED processes in static vacuum dipole magnetospheres of highly magnetized neutron stars, calculating attenuation lengths and determining escape energies, which are the maximum photon energies for transparency out to infinity. The numerical trajectory integral analysis in flat and curved space–times provides upper bounds of a few MeV or less to the visible energies for magnetars for locales proximate to the stellar surface. Photon splitting opacity alone puts constraints on the possible emission locales in their magnetospheres: regions within field loops of maximum altitudes $\, r_{{\rm max}}\sim 2\!-\!4\,$ stellar radii are not commensurate with maximum detected energies of around 250 keV. These constraints apply not only to magnetar flares but also to their quiescent hard X-ray tail emission. An exploration of photon splitting attenuation in the context of a resonant inverse Compton scattering model for the hard X-ray tails derives distinctive phase-resolved spectroscopic and polarimetric signatures, of significant interest for future MeV-band missions such as AMEGO and e-ASTROGAM.
Enrichment of Phosphatidylinositol 4,5-Bisphosphate in the Extra-Invasive Hyphal Membrane Promotes Colletotrichum Infection of Arabidopsis thaliana
Authors: Shimada Takashi L , Betsuyaku Shigeyuki , Inada Noriko , Ebine Kazuo , Fujimoto Masaru , Uemura Tomohiro , Takano Yoshitaka , Fukuda Hiroo , Nakano Akihiko , Ueda Takashi 
Published: April 2019

Abstract
Pathogenic fungi from the genus Colletotrichum form invasive hyphae; the hyphae are surrounded by an extra-invasive hyphal membrane (EIHM), which is continuous with the plant plasma membrane. Although the EIHM plays a crucial role as the interface between plant and fungal cells, its precise function during Colletotrichum infection remains elusive. Here, we show that enrichment of phosphoinositides (PIs) has a crucial role in Colletotrichum infection. We observed the localization of PIs in Arabidopsis thaliana cells infected by A. thaliana-adapted Colletotrichum higginsianum (Ch), and found that phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] was extremely enriched in the EIHM during Ch infection. We also found that phosphatidylinositol 4-phosphate-5 kinase (PIP5K), which catalyzes production of PI(4,5)P2, also accumulated at the EIHM. The overexpression of PIP5K3 in A. thaliana increased hyphal invasion by Ch. An exocytic factor, EXO84b, was targeted to the EIHM during Ch infection, although endocytic factors such as CLATHRIN LIGHT CHAIN 2 and FLOTILLIN 1 did not. Intriguingly, the interfacial membranes between A. thaliana and powdery mildew- or downy mildew-causing pathogens did not accumulate PI(4,5)P2. These results suggest that Ch could modify the PI(4,5)P2 levels in the EIHM to increase the exocytic membrane/protein supply of the EIHM for successful infection. Our results also suggest that PI(4,5)P2 biosynthesis is a promising target for improved defense against Colletotrichum infection.
Deposit Insurance, Bank Risk-Taking, and Failures: Evidence from Early Twentieth-Century State Deposit Insurance Systems
Authors: Aldunate Felipe 
Published: April 2019

Abstract
I use the introduction of deposit insurance in eight U.S. states in the early twentieth-century to study the effects of deposit insurance on the banking system. Using a triple difference approach exploiting regulatory differences between national and state banks and between states, I find that insured banks experienced higher deposit growth and decreased funding costs. I also observe a replacement of demand deposits by riskier time deposits. However, I find no aggregate effects on failure rates or risk-taking. Using hand-collected micro-level data, I show that small and large banks reacted differently and that banks facing funding problems especially benefited.
Received July 20, 2017; editorial decision November 12, 2018 by Editor Efraim Benmelech.
Health-Related Quality of Life With Ulipristal Acetate for Treatment of Uterine Leiomyomas
Authors: Lukes Andrea S. , Soper David , Harrington Amanda , Sniukiene Vilma , Mo Yifan , Gillard Patrick , Shulman Lee 
Published: April 2019

OBJECTIVE:
To investigate effects of ulipristal acetate on health-related quality of life (QOL) and symptom severity in women with symptomatic uterine leiomyomas and abnormal uterine bleeding.

METHODS:
Women were randomized to ulipristal (5 mg, 10 mg) or placebo in two phase 3, multicenter, double-blind, placebo-controlled trials (VENUS I and II). Health-related QOL and symptom severity were assessed at baseline, and over one (VENUS I and II) and two (VENUS II) 12-week treatment courses using the Uterine Fibroid Symptom Health-Related Quality of Life questionnaire. In pooled VENUS I and II data, change from baseline to the end of the first course for each Uterine Fibroid Symptom Health-Related Quality of Life scale was analyzed, including a Revised Activities subscale that measured physical and social activities. The proportion of women achieving meaningful change in the Symptom Severity (20 or more points), Health-Related QOL Total (20 or more points), and Revised Activities (30 or more points) scales was calculated. In VENUS II data, change from baseline to the end of each course in each scale was analyzed for each treatment arm.

RESULTS:
In pooled analyses, the intent-to-treat population included 589 patients (placebo, n=169; ulipristal 5 mg, n=215; ulipristal 10 mg, n=205). Significantly greater improvements from baseline in all Uterine Fibroid Symptom Health-Related Quality of Life scales were observed with both ulipristal doses compared with placebo (P<.001). A meaningful change in Revised Activities was achieved by 51 patients receiving placebo (34.9%), compared with 144 (73.5%; OR 5.0 [97.5% CI 2.9–8.6]) and 141 (80.6%; OR 7.9 [97.5% CI 4.3–14.6]) patients receiving ulipristal 5 mg, and 10 mg, respectively. In VENUS II, at end of courses 1 and 2, both ulipristal doses demonstrated significant improvements from baseline compared with placebo for all Uterine Fibroid Symptom Health-Related Quality of Life scales (P<.01). Mean Revised Activities scores showed that beneficial ulipristal effects were maintained in course 2, and improvements occurred on switching to ulipristal; results for other scales were similar.

CONCLUSION:
Ulipristal was associated with significant improvements in health-related QOL and symptom severity compared with placebo for women with symptomatic uterine leiomyomas.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02147197 and NCT02147158.

FUNDING SOURCE:
Allergan plc, Dublin, Ireland.
Raynaud Phenomenon of the Nipple
Authors: Jansen Sierra , Sampene Katherine 
Published: April 2019

BACKGROUND:
Obstetricians often feel ill-equipped to address the symptom of breast pain in pregnant and postpartum patients.

Cases:
In the first case, a 40-year-old woman in the second trimester of pregnancy reported nipple discoloration and severe pain. She was treated with nifedipine, and her symptoms decreased quickly and markedly. In the second case, a 32-year-old woman presented for a routine postpartum visit. She described breast pain and sporadic purple discoloration of the nipples, a finding confirmed on examination. Conservative measures of maintaining warmth were recommended.

CONCLUSION:
Raynaud phenomenon of the nipple is an underdiagnosed condition affecting women in both the prenatal and postpartum periods. A careful history and physical must be obtained in women presenting with breast pain, because diagnosis and treatment allows breastfeeding continuation and mitigation of symptoms.
Medication-Assisted Treatment Use Among Pregnant Women With Opioid Use Disorder
Authors: Krans Elizabeth E. , Kim Joo Yeon , James Alton Everette , Kelley David , Jarlenski Marian P. 
Published: April 2019

OBJECTIVE:
To evaluate temporal trends in medication-assisted treatment use among pregnant women with opioid use disorder.

METHODS:
We conducted a retrospective cohort study using Pennsylvania Medicaid administrative data. Trends in medication-assisted treatment use, opioid pharmacotherapy (methadone and buprenorphine) and behavioral health counselling, were calculated using pharmacy records and procedure codes. Cochrane-Armitage tests evaluated linear trends in characteristics of pregnant women using methadone compared with buprenorphine.

RESULTS:
In total, we evaluated 12,587 pregnancies among 10,741 women with opioid use disorder who had a live birth between 2009 and 2015. Across all years, 44.1% of pregnant women received no opioid pharmacotherapy, 27.1% used buprenorphine, and 28.8% methadone. Fewer than half of women had any behavioral health counseling during pregnancy. The adjusted prevalence of methadone use declined from 31.6% (95% CI 29.3–33.9%) in 2009 to 25.2% (95% CI 23.3–27.1%) in 2015, whereas the adjusted prevalence of buprenorphine use increased from 15.8% (95% CI 13.9–17.8%) to 30.9% (95% CI 28.8–33.0%). Greater increases in buprenorphine use were found in geographic regions with large metropolitan centers, such as the Southwest (plus 24.9%) and the Southeast (plus 12.0%), compared with largely rural regions, such as the New West (plus 5.2%). In 2015, the adjusted number of behavioral health counseling visits during pregnancy was 3.4 (95% CI 2.6–4.1) among women using buprenorphine, 4.0 (95% CI 3.3–4.7) among women who did not use pharmacotherapy, and 6.4 (95% CI 4.9–7.9) among women using methadone.

CONCLUSION:
Buprenorphine use among Medicaid-enrolled pregnant women with opioid use disorder increased significantly over time, with a small concurrent decline in methadone use. Behavioral health counseling use was low, but highest among women using methadone.
Industry Payments to Pediatric Orthopaedic Surgeons Reported by the Open Payments Database: 2014 to 2017
Authors: Pathak Neil , Mets Elbert J. , Mercier Michael R. , Galivanche Anoop R. , Bovonratwet Patawut , Smith Brian G. , Grauer Jonathan N. 
Published: April 2019

Background:
The Open Payments Database (OPD), mandated by the Sunshine Act, is a national registry of physician-industry transactions. Payments are reported as either General, Research, or Ownership payments. The current study aims to investigate trends in OPD General payments reported to pediatric orthopaedic surgeons from 2014 to 2017.

Methods:
General industry payments made to pediatric orthopaedic surgeons (as identified by OPD) were characterized by median payment, payment subtype, and census region. As fewer Research and Ownership payments were made, only payment totals for these categories were determined. General payment data were analyzed for trends using the nonparametric Mann-Whitney U test.

Results:
For General payments, there was an increase in the number of compensated pediatric orthopaedists from 2014 to 2017 (324 vs. 429). Of those compensated, there was no significant change in median payment per compensated surgeon ($201 vs. $197; P=0.82). However, a large percentage of total General payment dollars in pediatric orthopaedics were made to the top 5% of compensated pediatric orthopaedists each year (average 71% of total General industry compensation). For this top 5% group, median General payment per compensated surgeon increased from 2014 ($14,624) to 2017 ($32,752) (P=0.006). A significant increase in median subtype aggregate payment per surgeon was observed in the education (P<0.001) and royalty/license (P=0.031) subtypes; a significant decrease was observed for travel/lodging payments (P=0.01). Midwest pediatric orthopaedists received the highest median payment across all years studied. Few payments for research and ownership were made to pediatric orthopaedists. Four-year aggregate payment totals were $18,151 and $3,223,554 for Research and Ownership payments, respectively.

Conclusions:
Many expected payments to surgeons to decrease when put under the public scrutiny of the OPD. Not only was this decrease not observed for General payments to pediatric orthopaedic surgeons during the 2014 to 2017 period, but also the median General payment to the top 5% increased. These findings are important to note in the current era of increased transparency.

Level of Evidence:
Level III.