bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urinary incontinence in women: treatment barriers and significance for Danish and German GPs
Authors: Elsner Susanne , Juergensen Martina , Faust Elke , Niesel Achim , Pedersen Louise Schreiber , Rudnicki Peter Martin , Waldmann Annika 
Published: October 2019

Abstract

Background
Female urinary incontinence (UI) is common. Only scant information exists on the significance of UI for GPs’ consultations.

Objectives
(i) To assess the significance of female UI for GPs and to look at barriers that could be detrimental to treatment by comparing GPs from Denmark and Germany, with different health systems and access to UI guidelines. (ii) To assess whether GPs’ gender and age were relevant to the discussion of UI.

Methods
We conducted a cross-sectional survey. In the Fehmarn belt-region, a Danish–German border region, a self-developed questionnaire was sent to all the GPs (n = 930).

Results
In total, 407 GPs returned the questionnaire (43%); 403 questionnaires were analysed. Using a scale from 0 (never) to 10 (always), addressing UI was reported with an average score of 3.8 (SD: 2.1) among Danish and 3.5 (SD: 2.1) among German GPs. The topic was discussed more frequently with female (4.2; SD 2.2) than with male GPs (3.2; SD 2.0). Danish GPs estimated the prevalence among their female patients at 10% (SD: 8.0) and German GPs at 14% (SD: 11.2). 61% of the Danish and 19% of the German GPs used UI guidelines. German GPs significantly more often reported the barrier ‘uncertainty of how to treat UI’ [OR = 5.39 (95% CI: 2.8; 10.4)].

Conclusions
In consultations with female GPs, UI was discussed significantly more frequently than with male GPs. Compared with the Danish GPs, German GPs stated significantly more uncertainties regarding UI treatment measures, and tended not to use UI guidelines.
FRAND licensing and implementation chains
Authors: Kühnen Thomas 
Published: October 2019

Abstract
It is conventional wisdom that the proprietors of standard-essential patents (“SEPs”) are free to choose the implementation stage at which they offer FRAND licenses for their inventions; ordinarily, these proprietors offer licenses to the actors at the end of the implementation chain, because the consumer goods incorporating patented technology, considering their high sales price, promise the putatively highest licensing fees. The patent users upstream from the licensee are denied their own FRAND license on the grounds that they are sufficiently protected against patent infringement actions by virtue of the licenses granted to their buyers. The present article will show that both assumptions are incorrect. First, every interested party has a claim to a license absent any special prerequisites; hence, the party at the beginning of the implementation chain, too, has such a claim, even if a FRAND license has already been granted at the distribution stage downstream from said party. Second, the amount of a FRAND royalty will not depend on the position of the license applicant within the implementation chain.
Pragmatic Health Assessment in Early Childhood: The PROMIS® of Developmentally Based Measurement for Pediatric Psychology
Authors: Blackwell Courtney K , Wakschlag Lauren , Krogh-Jespersen Sheila , Buss Kristin A , Luby Joan , Bevans Katherine , Lai Jin-Shei , Forrest Christopher B , Cella David 
Published: October 2019

Abstract

Objective
To illustrate the integration of developmental considerations into person-reported outcome (PRO) measurement development for application in early childhood pediatric psychology.

Methods
Combining the state-of-the-science Patient-Reported Outcome Measurement Information System (PROMIS®) mixed-methods instrument development approach with considerations from developmental measurement science, we developed 12 PROMIS early childhood (PROMIS EC) parent report measures to evaluate common mental, social, and physical health outcomes for ages 1–5. Through this interdisciplinary effort, we identified key considerations for early childhood PROs that enable reliable and valid assessment within the real-world constraints of clinical care settings.

Results
Four key considerations are highlighted as key to this process: (a) Engage diverse content experts to identify meaningful and relevant constructs; (b) Balance salient features for early childhood with lifespan coherence of constructs; (c) Emphasize observable features across the typical/atypical spectrum; and (d) Ensure feasibility and relevancy for clinical and research application. Each consideration is discussed using exemplars from the PROMIS EC measurement development process.

Conclusions
PROMIS EC provides an illustration of how well-established PRO measures for youth can be adapted for younger children by incorporating developmental considerations. This process and resulting key considerations provide clinicians and researchers in the field of pediatric psychology with guidance for adapting PROs to early childhood, enabling critical continuity in domains of high salience to pediatric psychologists.
Evisceration Versus Enucleation Following Ocular Trauma, a Retrospective Analysis at a Level One Trauma Center
Authors: Reed Donovan , Papp Alexandra , Brundridge Wesley , Mehta Aditya , Santamaria Joseph , Valentin Frank , Davies Brett 
Published: October 2019

Abstract

Introduction
Penetrating and perforating ocular trauma is often devastating and may lead to complete visual loss in the traumatized eye and subsequent compromise of the fellow eye. Enucleation is commonly utilized for management of a non-salvageable eye following penetrating and perforating ocular injuries. Recently, the use of evisceration for non-salvageable traumatized eyes has increased. As a technically easier alternative, evisceration offers several advantages to the ocular trauma surgeon to include faster surgical times, better cosmesis and motility, and improved patient outcomes. Debate still persists concerning whether or not evisceration is a viable option in the surgical management of a non-salvageable eye following ocular trauma given the theoretical increased risk of sympathetic ophthalmia and technical difficulty in construction of the scleral shell with extensive and complex corneoscleral lacerations. A retrospective analysis at a level 1 trauma center was performed to evaluate the practicality of evisceration in ocular trauma.

Materials and Methods
Eyes that underwent evisceration or enucleation following ocular trauma at San Antonio Military Medical Center, a level 1 trauma center, between 01 January 2014 and 30 December 2016 were examined. Factors evaluated include mechanism of injury, defect complexity, ocular trauma score, and time from injury to surgical intervention. Surgical outcomes were assessed.

Results
In total, 29 eyes were examined, 15 having undergone evisceration and 14 enucleation. The average size of the scleral defect before evisceration was 20 mm in length, and 23 mm before enucleation. The mechanism of injury and characterization of the defects among the two groups were relatively similar and described. Overall comparison of the two study groups in terms of surgical outcomes and complications was also relatively similar, as demonstrated. No cases of postoperative persistent pain, sympathetic ophthalmia, infection, or hematoma were identified for either group.

Conclusions
The postoperative outcomes demonstrated for the evisceration group are comparable to enucleation, which is consistent with the recent literature. Defect size and complexity did not affect surgical construction of the scleral shell during evisceration. If consistently proven to be a safe and viable alternative to enucleation, evisceration can offer shorter surgical times and better cosmesis for patients. More research into the long-term complication rates and more cases of evisceration for use following ocular trauma should be assessed. Still, this analysis demonstrates that evisceration is a viable surgical alternative and perhaps superior to enucleation for the management of a non-salvageable eye following extensive ocular trauma in many cases.
How AGN feedback drives the size growth of the first quasars
Authors: van der Vlugt Dieuwertje , Costa Tiago 
Published: October 2019

ABSTRACT
Quasars at $z = 6$ are powered by accretion on to supermassive black holes with masses $M_{\rm BH} \sim 10^9 \rm \, M_{\odot}$. Their rapid assembly requires efficient gas inflow into the galactic nucleus, sustaining black hole accretion at a rate close to the Eddington limit, but also high central star formation rates. Using a set of cosmological ‘zoom-in’ hydrodynamic simulations performed with the moving mesh code Arepo, we show that $z = 6$ quasar host galaxies develop extremely tightly bound stellar bulges with peak circular velocities $300\!-\!500 \, \rm km \, s^{-1}$ and half-mass radii ${\approx}0.5 \, \rm kpc$. Despite their high binding energy, we find that these compact bulges expand at $z \, \lt \, 6$, with their half-mass radii reaching ${\approx}5 \, \rm kpc$ by $z = 3$. The circular velocity drops by factors of ≈2 from their initial values to $200\!-\!300 \, \rm km \, s^{-1}$ at $z \, \approx \, 3$ and the stellar profile undergoes a cusp-core transformation. By tracking individual stellar populations, we find that the gradual expansion of the stellar component is mainly driven by fluctuations in the gravitational potential induced by bursty AGN feedback. We also find that galaxy size growth and the development of a cored stellar profile does not occur if AGN feedback is ineffective. Our findings suggest that AGN-driven outflows may have profound implications for the internal structure of massive galaxies, possibly accounting for their size growth, the formation of cored ellipticals as well as for the saturation of the MBH–σ⋆ seen at high-velocity dispersions σ⋆.
Exploring suppressed long-distance correlations as the cause of suppressed large-angle correlations
Authors: Copi Craig J , Gurian James , Kosowsky Arthur , Starkman Glenn D , Zhang Hezi 
Published: October 2019

ABSTRACT
The absence of large-angle correlations in the map of cosmic microwave background temperature fluctuations is among the well-established anomalies identified in full-sky and cut-sky maps over the past three decades. Suppressed large-angle correlations are rare statistical flukes in standard inflationary cosmological models. One natural explanation could be that the underlying primordial density perturbations lack correlations on large distance scales. To test this idea, we replace Fourier modes by a wavelet basis with compact spatial support. While the angular correlation function of perturbations can readily be suppressed, the observed monopole- and dipole-subtracted correlation function is not generally suppressed. This suggests that suppression of large-angle temperature correlations requires a mechanism that has both real-space and harmonic-space effects.
Joint radio and X-ray modelling of PSR J1136+1551
Authors: Pétri J , Mitra D 
Published: October 2019

ABSTRACT
Multiwavelength observations of pulsar emission properties are powerful means to constrain their magnetospheric activity and magnetic topology. Usually a star centred magnetic dipole model is invoked to explain the main characteristics of this radiation. However, in some particular pulsars where observational constraints exist, such simplified models are unable to predict salient features of their multiwavelength emission. This paper aims to carefully model the radio and X-ray emission of PSR J1136+1551 with an off-centred magnetic dipole to reconcile both wavelength measurements. We simultaneously fit the radio pulse profile with its polarization and the thermal X-ray emission from the polar cap hotspots of PSR J1136+1551. We are able to pin down the parameters of the non-dipolar geometry (which we have assumed to be an offset dipole) and the viewing angle, meanwhile accounting for the time lag between X-ray and radio emission. Our model fits the data if the off-centred magnetic dipole lies about 20 per cent below the neutron star surface. We also expect very asymmetric polar cap shapes and sizes, implying non-antipodal and non-identical thermal emission from the hotspots. We conclude that a non-dipolar surface magnetic field is an essential feature to explain the multiwavelength aspects of PSR J1136+1551 and other similar pulsars.
Coupling 1D stellar evolution with 3D-hydrodynamical simulations on-the-fly II: stellar evolution and asteroseismic applications
Authors: Mosumgaard Jakob Rørsted , Jørgensen Andreas Christ Sølvsten , Weiss Achim , Silva Aguirre Víctor , Christensen-Dalsgaard Jørgen 
Published: October 2019

ABSTRACT
Models of stellar structure and evolution are an indispensable tool in astrophysics, yet they are known to incorrectly reproduce the outer convective layers of stars. In the first paper of this series, we presented a novel procedure to include the mean structure of 3D hydrodynamical simulations on-the-fly in stellar models, and found it to significantly improve the outer stratification and oscillation frequencies of a standard solar model. In this work, we extend the analysis of the method; specifically how the transition point between envelope and interior affects the models. We confirm the versatility of our method by successfully repeating the entire procedure for a different grid of 3D hydrosimulations. Furthermore, the applicability of the procedure was investigated across the HR diagram and an accuracy comparable to the solar case was found. Moreover, we explored the implications on stellar evolution and find that the red-giant branch is shifted about $40\, \mathrm{K}$ to higher effective temperatures. Finally, we present for the first time an asteroseismic analysis based on stellar models fully utilizing the stratification of 3D simulations on-the-fly. These new models significantly reduce the asteroseismic surface term for the two selected stars in the Kepler field. We extend the analysis to red giants and characterize the shape of the surface effect in this regime. Lastly, we stress that the interpolation required by our method would benefit from new 3D simulations, resulting in a finer sampling of the grid.
Binary outflows from young stars: interaction of co-orbital jet and wind
Authors: Lynch Chris J R , Smith Michael D , Glover Simon C O 
Published: October 2019

Abstract
Jets from young stellar objects provide insight into the workings of the beating heart at the centre of star forming cores. In some cases, multiple pulsed outflows are detected such as the atomic and molecular jets from a proposed binary system in the T Tauri star HH 30. We investigate here the development and propagation of duelling atomic and molecular outflows stemming from the two stars in co-orbit. We perform a series of numerical experiments with the ZEUS-MP code with enhanced cooling and chemistry modules. The aim of this work is to identify signatures on scales of order 100 AU. The jet sources are off the grid domain and so it is the propagation and interaction from ∼ 20 AU out to 100 AU simulated here. We find that the molecular flow from the orbiting source significantly disturbs the atomic jet, deflecting and twisting the jet and disrupting the jet knots. Regions of high ionisation are generated as the atomic jet rams through the dense molecular outflow. Synthetic images in atomic and molecular lines are presented which demonstrate identifying signatures. In particular, the structure within the atomic jet is lost and Hα may trace the walls of the present CO cavity or where the walls have been recently. These results provide a framework for the interpretation of upcoming high resolution observations.
‘Drc’, a structurally novel ssDNA-binding transcription regulator of N4-related bacterial viruses
Authors: Boon Maarten , De Zitter Elke , De Smet Jeroen , Wagemans Jeroen , Voet Marleen , Pennemann Friederike L , Schalck Thomas , Kuznedelov Konstantin , Severinov Konstantin , Van Meervelt Luc , De Maeyer Marc , Lavigne Rob 
Published: October 2019

Abstract
Bacterial viruses encode a vast number of ORFan genes that lack similarity to any other known proteins. Here, we present a 2.20 Å crystal structure of N4-related Pseudomonas virus LUZ7 ORFan gp14, and elucidate its function. We demonstrate that gp14, termed here as Drc (ssDNA-binding RNA Polymerase Cofactor), preferentially binds single-stranded DNA, yet contains a structural fold distinct from other ssDNA-binding proteins (SSBs). By comparison with other SSB folds and creation of truncation and amino acid substitution mutants, we provide the first evidence for the binding mechanism of this unique fold. From a biological perspective, Drc interacts with the phage-encoded RNA Polymerase complex (RNAPII), implying a functional role as an SSB required for the transition from early to middle gene transcription during phage infection. Similar to the coliphage N4 gp2 protein, Drc likely binds locally unwound middle promoters and recruits the phage RNA polymerase. However, unlike gp2, Drc does not seem to need an additional cofactor for promoter melting. A comparison among N4-related phage genera highlights the evolutionary diversity of SSB proteins in an otherwise conserved transcription regulation mechanism.
Ring-shaped replicative helicase encircles double-stranded DNA during unwinding
Authors: Joo Sihwa , Chung Bong H , Lee Mina , Ha Tai H 
Published: October 2019

AbstractRing-shaped replicative helicases are hexameric and play a key role in cellular DNA replication. Despite their importance, our understanding of the unwinding mechanism of replicative helicases is far from perfect. Bovine papillomavirus E1 is one of the best-known model systems for replicative helicases. E1 is a multifunctional initiator that senses and melts the viral origin and unwinds DNA. Here, we study the unwinding mechanism of E1 at the single-molecule level using magnetic tweezers. The result reveals that E1 as a single hexamer is a poorly processive helicase with a low unwinding rate. Tension on the DNA strands impedes unwinding, indicating that the helicase interacts strongly with both DNA strands at the junction. While investigating the interaction at a high force (26–30 pN), we discovered that E1 encircles dsDNA. By comparing with the E1 construct without a DNA binding domain, we propose two possible encircling modes of E1 during active unwinding.
76. Validation of Systemic Inflammatory Mediators as Biomarkers for Severity and Adverse Outcomes in Clostridium difficile Infection
Authors: Dieterle Michael G , Putler Rosemary K B , Perry Donald A , Menon Anitha , Abernathy-Close Lisa , Perlman Naomi , Penkevich Aline , Standke Alexandra , Keidan Micah , Vendrov Kimberly , Bergin Ingrid L , Young Vincent B , Rao Krishna 
Published: October 2019

Abstract

Background
Clostridium difficile infection (CDI) can result in severe disease and death. We are currently unable to identify patients at risk for developing adverse outcomes. We previously showed multiple inflammatory mediators were associated with severity and adverse outcomes. Here, we set out to validate these findings in patients and a murine model of CDI.

Methods
CDI was diagnosed by the clinical microbiology laboratory. Sera were collected ≤48 hours after diagnosis from pilot (October 2010–November 2012) and validation (January–September 2016) cohorts. Inflammatory mediators were measured with a custom multiplex assay. IDSA severity was defined as serum creatinine >1.5-fold above baseline or white blood cell count >15,000 cells/mL. The 30-day outcomes were all-cause mortality and disease-related complications (DRCs): ICU admission, colectomy, or death attributed to CDI. We sought to validate our patient findings in a murine model of CDI: 67 antibiotic-treated mice were infected with 630 g (37 mice), a low virulence strain, or VPI 10463 (30 mice), a highly virulent strain. Host responses were assessed with a murine version of the multiplex panel. Unadjusted and adjusted models were built using logistic and L1 regression, respectively.

Results
The pilot cohort had 156 CDI cases; 63 (40%) with IDSA severity. The inflammatory response in IDSA severe cases was distinct based on redundancy analysis of all measured analytes (P = 0.01). In unadjusted analysis, IL-2R, IL-6, and procalcitonin associated with severity (P < 0.001, P = 0.003, and P = 0.003, respectively). The same findings were seen in the validation cohort of 272 cases (Figure 1). Unadjusted analyses revealed several predictors of severity and outcomes (Table 1). Adjusted models performed well (Figure 2) with AUCs of 0.74 [0.67–0.81] (IDSA severity), 0.89 [0.83–0.95] (death), and 0.84 [0.74–0.95] (DRCs). Application of each model to the mouse cohort for high vs. low virulence infections revealed AUCs of 0.59 [0.44–0.74], 0.96 [0.90–1.0], and 0.89 [0.81–0.97] (Figure 3).

Conclusion
In both humans and a murine CDI model, a panel of biomarkers from sera associated with severe CDI and predicted adverse outcomes. Our results support the possibility of a serum-based biomarker panel to inform medical decision-making for patients with CDI.

Disclosures
All Authors: No reported Disclosures.
87. Heart and Lung Transplants From HCV-Viremic Donors to Uninfected Patients: Longer-Term Follow-Up
Authors: Woolley Ann E , Goldberg Hilary J , Singh Steve K , Mehra Mandeep R , Givertz Michael M , Coppolino Antonio , Cheng Vivien , Fanikos John , Harrington David P , Mallidi Hari R , Baden Lindsey R 
Published: October 2019

Abstract

Background
The DONATE HCV Trial demonstrated that hearts and lungs can be safely transplanted from HCV-infected donors using a shortened, 4-week, pre-emptive course of direct-acting antivirals (DAA). The 6-month results from that study of 35 patients are encouraging, but longer-term data from a larger cohort are needed to better define the risk–benefit profile.

Methods
We conducted a single-center trial to transplant thoracic organs from HCV viremic donors, irrespective of HCV genotype, to HCV-uninfected adults. Sofosbuvir/velpatasvir, a pan-genotypic DAA, was pre-emptively administered for 4 weeks, beginning within hours of transplant. The primary outcome was a composite of HCV clearance and graft survival at 6 months post-transplant. Secondary outcomes included graft survival and mortality at 12 months and the occurrence of grade 3 or higher adverse events (AEs). This protocol is IRB approved and all participants provided written informed consent (NCT03086044).

Results
Between March 2017 and March 2019, 57 participants were enrolled: 46 received lung and 11 received heart transplants. The median donor HCV viral load (VL) was 889,817 IU/mL (IQR 212,062–4,641,078). Of the 57 recipients, 53 (93%) had detectable HCV VL immediately after transplant, with median VL of 1,460 IU/mL (IQR 463–6,618). HCV VL became negative by about 2 weeks and subsequently remained undetectable in all participants. Forty-nine of 49 (100%) and 34 of 35 (97%) participants were alive with excellent graft function and an undetectable HCV VL at 6 months and 1-year post-transplant, respectively. No treatment-related serious AEs were identified. Outcomes between transplant recipients from HCV donors vs. non-HCV donors were similar, including the occurrence of renal failure, respiratory failure, and non-HCV infections.

Conclusion
In patients who received thoracic organs from HCV viremic donors, a 4-week antiviral treatment course initiated within hours of transplant prevented the establishment of HCV infection. These data demonstrate that thoracic organs from HCV viremic donors can be transplanted safely with excellent graft and recipient survival at 12 months with a similar AE profile compared with transplant recipients who received thoracic organs from non-HCV donors. Two-year outcomes will be available in October 2019.

Disclosures
All Authors: No reported Disclosures.