bluuebunny/crossref_metadata_2025 huggingface dataset:
On Faraday's law in the presence of extended conductors
Authors: Bilbao Luis
Published: May 2018

The use of Faraday's Law of induction for calculating the induced currents in an extended conducting body is discussed. In a general case with arbitrary geometry, the solution to the problem of a moving metal object in the presence of a magnetic field is difficult and implies solving Maxwell's equations in a time-dependent situation. In many cases, including cases with good conductors (but not superconductors) Ampère's Law can be neglected and a simpler solution based solely in Faraday's law can be obtained. The integral form of Faraday's Law along any loop in the conducting body is equivalent to a Kirkhhoff's voltage law of a circuit. Therefore, a numerical solution can be obtained by solving a linear system of equations corresponding to a discrete number of loops in the body.
On the use of a stress–impedance model to describe sound propagation in a lined duct with grazing flow
Authors: Aurégan Yves
Published: May 2018

With flow, the acoustic effect of a locally reacting lined wall cannot be described by a single quantity independent of the incident wave, such as a wall impedance. At least two quantities, intrinsic to the liner and to the flow, are required to describe the effect of the lined wall regardless of the incident wave. In addition to the impedance, the unsteady tangential force exerted by the wall on the flow has to be taken into account. This force is due either to viscous effects or to the unsteady transfer of axial momentum from the flow into the lined wall. This paper describes a stress–impedance model, where the two variables used are the impedance and the friction factor that links the pressure to a tangential stress at the wall. The use of a wall stress helps to better understand the mechanisms of momentum transfer between the flow and the wall in the vicinity of an acoustic treatment.
Interplay of cation and anion redox in Li
4
Mn
2
O
5
cathode material and prediction of improved Li
4
(Mn,M)
2
O
5
electrodes for Li-ion batteries
Authors: Yao Zhenpeng , Kim Soo , He Jiangang , Hegde Vinay I. , Wolverton Chris
Published: May 2018

High–energy density cathode materials for Li-ion batteries leverage oxygen and transition metal redox activity with reduced cost.
Tumor immune evasion arises through loss of TNF sensitivity
Authors: Kearney Conor J. , Vervoort Stephin J. , Hogg Simon J. , Ramsbottom Kelly M. , Freeman Andrew J. , Lalaoui Najoua , Pijpers Lizzy , Michie Jessica , Brown Kristin K. , Knight Deborah A. , Sutton Vivien , Beavis Paul A. , Voskoboinik Ilia , Darcy Phil K. , Silke John , Trapani Joseph A. , Johnstone Ricky W. , Oliaro Jane
Published: May 2018

Whole-genome CRISPR screens identify resistance to TNF-mediated killing by T and NK cells as a tumor immune evasion mechanism.
Evaluation of Performance Characteristics of Panther Fusion Assays for Detection of Respiratory Viruses from Nasopharyngeal and Lower Respiratory Tract Specimens
Authors: Sam Soya S. , Caliendo Angela M. , Ingersoll Jessica , Abdul-Ali Deborah , Hill Charles E. , Kraft Colleen S.
Published: May 2018

Accurate and rapid diagnosis is needed for timely intervention and clinical management of acute respiratory infections. This study evaluated performance characteristics of the Panther Fusion assay for the detection of influenza A virus (Flu A), influenza B virus (Flu B), respiratory syncytial virus (RSV), parainfluenza viruses 1 to 3 (Para 1 to 3), human metapneumovirus (hMPV), rhinovirus (RV), and adenovirus (Adeno) targets in comparison to those of the eSensor and Lyra assays using 395 nasopharyngeal (NP) and 104 lower respiratory tract (LRT) specimens.
Similar Epitope Specificities of IgG and IgA Antibodies Elicited by Ad26 Vector Prime, Env Protein Boost Immunizations in Rhesus Monkeys
Authors: Kang Zi Han , Bricault Christine A. , Borducchi Erica N. , Stephenson Kathryn E. , Seaman Michael S. , Pau Maria , Schuitemaker Hanneke , van Manen Danielle , Wegmann Frank , Barouch Dan H.
Published: May 2018

Vaccine-elicited immunoglobulin G (IgG) has been shown to be important for protection against simian-human immunodeficiency virus (SHIV) infection in rhesus monkeys. However, it remains unclear whether vaccine-elicited IgA responses are beneficial or detrimental for protection. In this study, we evaluated the kinetics, magnitude, breadth, and linear epitope specificities of vaccine-elicited IgG and IgA responses in serum and mucosal secretions following intramuscular immunization with adenovirus 26 (Ad26) prime, Env protein boost vaccination regimens. The systemic and mucosal antibody responses exhibited kinetics similar to those of the serum antibody responses but lower titers than the serum antibody responses. Moreover, the IgG and IgA responses were correlated, both in terms of the magnitude of the responses and in terms of the antibody specificities against linear human immunodeficiency virus type 1 (HIV-1) Env, Gag, and Pol epitopes. These data suggest that IgG and IgA responses are highly coordinated in both peripheral blood and mucosal compartments following Ad26/Env vaccination in rhesus monkeys.

IMPORTANCEVaccine-elicited IgG responses are important for protection against simian-human immunodeficiency virus (SHIV) infection in nonhuman primates. However, much less is known about the role and function of IgA, despite it being the predominant antibody in mucosal sites. There is debate as to whether HIV-1-specific IgA responses are beneficial or detrimental, since serum anti-Env IgA titers were shown to be inversely correlated with protection in the RV144 clinical trial. We thus assessed vaccine-elicited IgG and IgA antibody responses in peripheral blood and mucosal secretions following vaccination with the Ad26/Env vaccine.
Frequencies of Circulating Th1-Biased T Follicular Helper Cells in Acute HIV-1 Infection Correlate with the Development of HIV-Specific Antibody Responses and Lower Set Point Viral Load
Authors: Baiyegunhi Omolara , Ndlovu Bongiwe , Ogunshola Funsho , Ismail Nasreen , Walker Bruce D. , Ndung'u Thumbi , Ndhlovu Zaza M.
Published: May 2018

The HIV epidemic in southern Africa accounts for almost half of the global HIV burden, with HIV-1 clade C being the predominant strain. It is therefore important to define immune correlates of clade C HIV control that might have implications for vaccine design in this region. T follicular helper (Tfh) cells are critical for the development of HIV-specific antibody responses and could play a role in viral control. Here we showed that the early induction of circulating Tfh1 cells during acute infection correlated positively with the magnitude of p24-specific IgG and was associated with a lower set point viral load. This study highlights a key Tfh cell subset that could limit HIV replication by enhancing antibody generation. This study underscores the importance of circulating Tfh cells in promoting nonneutralizing antibodies during HIV-1 infection.
The impact of SIGN glaucoma guidelines on false-positive referrals from community optometrists in Central Scotland
Authors: Sii Samantha , Nasser Ahmad , Loo Cheng Yi , Croghan Catherine , Rotchford Alan , Agarwal Pankaj Kumar
Published: May 2018

Background

Since the introduction of National Institute for Health and Care Excellence glaucoma guidelines 2009, the number of referrals from community optometrists to hospital eye services has increased across the UK, resulting in increase in first visit discharge rates (FVDRs).

Aim

To assess the impact of Scottish Intercollegiate Guidelines Network (SIGN) 144 on quality of referrals from community optometrists.

Methodology

A retrospective study of patient records who attended as new adult glaucoma referrals to clinics in Princess Alexandra Eye Pavilion, Edinburgh, and in Greater Glasgow and Clyde, was carried out across October–November 2014 (group 1) and September–October 2016 (group 2), before and after the introduction of SIGN 144. The primary outcome of this study is FVDRs. A secondary outcome is the extent of compliance to referral recommendations by SIGN guidelines.

Results

Three hundred and twelve and 325 patients were included in groups 1 and 2, respectively. There was a significant decline in FVDRs between these two periods from 29.2% to 19.2%.
(
p=
0.004) (OR 0.58 (95%CI 0.40 to 0.84)). Post-SIGN guidelines, 87% of referrals were compliant to SIGN referral criteria while 13% remained non-compliant. The main reasons for non-compliance were no repeatable visual field defects (42.0%) and referrals due to high intraocular pressure were either not repeated or not interpreted in the context of age and central corneal thickness (36.8%).

Conclusion

Patients referred after the introduction of SIGN guidelines were 33.5% less likely to be discharged at the first visit. Although compliance to most recommendations in SIGN guidelines has improved, there is still a need to improve adherence to referral criteria
Variable effectiveness of stepwise implementation of nudge-type interventions to improve provider compliance with intraoperative low tidal volume ventilation
Authors: O’Reilly-Shah Vikas N , Easton George S , Jabaley Craig S , Lynde Grant C
Published: May 2018

Background

Identifying mechanisms to improve provider compliance with quality metrics is a common goal across medical disciplines. Nudge interventions are minimally invasive strategies that can influence behavioural changes and are increasingly used within healthcare settings. We hypothesised that nudge interventions may improve provider compliance with lung-protective ventilation (LPV) strategies during general anaesthesia.

Methods

We developed an audit and feedback dashboard that included information on both provider-level and department-level compliance with LPV strategies in two academic hospitals, two non-academic hospitals and two academic surgery centres affiliated with a single healthcare system. Dashboards were emailed to providers four times over the course of the 9-month study. Additionally, the default setting on anaesthesia machines for tidal volume was decreased from 700 mL to 400 mL. Data on surgical cases performed between 1 September 2016 and 31 May 2017 were examined for compliance with LPV. The impact of the interventions was assessed via pairwise logistic regression analysis corrected for multiple comparisons.

Results

A total of 14 793 anaesthesia records were analysed. Absolute compliance rates increased from 59.3% to 87.8%preintervention to postintervention. Introduction of attending physician dashboards resulted in a 41% increase in the odds of compliance (OR 1.41, 95% CI 1.17 to 1.69, p=0.002). Subsequently, the addition of advanced practice provider and resident dashboards lead to an additional 93% increase in the odds of compliance (OR 1.93, 95% CI 1.52 to 2.46, p<0.001). Lastly, modifying ventilator defaults led to a 376% increase in the odds of compliance (OR 3.76, 95% CI 3.1 to 4.57, p<0.001).

Conclusion

Audit and feedback tools in conjunction with default changes improve provider compliance.
Challenges in end-of-life dementia care
Authors: Fetherston Anne A , Rowley Grace , Allan Charlotte L
Published: May 2018

Dementia is a chronic, progressive disease that is now much more widely recognised and treated. Patients with dementia may require palliative care when they reach the end stage of their illness, or they may have mild–moderate cognitive symptoms comorbid with a life-limiting illness. The variety of presentations necessitates a highly individual approach to care planning, and patients should be encouraged to set their own goals and contribute to advanced care planning where possible. Assessment and management of distressing symptoms at the end of life can be greatly helped by a detailed knowledge of the individuals’ prior wishes, interdisciplinary communication and recognition of changes in presentation that may result from new symptoms, for example, onset of pain, nutritional deficits and infection. To navigate complexity at the end of life, open communication that involves patients and families in decisions, and is responsive to their needs is vital and can vastly improve subjective experiences. Complex ethical dilemmas may pervade both the illness of dementia and provision of palliative care; we consider how ethical issues (eg, providing care under restraint) influence complex decisions relating to resuscitation, artificial nutrition and treatment refusal in order to optimise quality of life.
Brock malignancy risk calculator for pulmonary nodules: validation outside a lung cancer screening population
Authors: Chung Kaman , Mets Onno M , Gerke Paul K , Jacobs Colin , den Harder Annemarie M , Scholten Ernst T , Prokop Mathias , de Jong Pim A , van Ginneken Bram , Schaefer-Prokop Cornelia M
Published: May 2018

Objective

To assess the performance of the Brock malignancy risk model for pulmonary nodules detected in routine clinical setting.

Methods

In two academic centres in the Netherlands, we established a list of patients aged ≥40 years who received a chest CT scan between 2004 and 2012, resulting in 16 850 and 23 454 eligible subjects. Subsequent diagnosis of lung cancer until the end of 2014 was established through linking with the National Cancer Registry. A nested case–control study was performed (ratio 1:3). Two observers used semiautomated software to annotate the nodules. The Brock model was separately validated on each data set using ROC analysis and compared with a solely size-based model.

Results

After the annotation process the final analysis included 177 malignant and 695 benign nodules for centre A, and 264 malignant and 710 benign nodules for centre B. The full Brock model resulted in areas under the curve (AUCs) of 0.90 and 0.91, while the size-only model yielded significantly lower AUCs of 0.88 and 0.87, respectively (p<0.001). At 10% malignancy risk, the threshold suggested by the British Thoracic Society, sensitivity of the full model was 75% and 81%, specificity was 85% and 84%, positive predictive values were 14% and 10% at negative predictive value (NPV) of 99%. The optimal threshold was 6% for centre A and 8% for centre B, with NPVs >99%.

Discussion

The Brock model shows high predictive discrimination of potentially malignant and benign nodules when validated in an unselected, heterogeneous clinical population. The high NPV may be used to decrease the number of nodule follow-up examinations.
Response of dry bean to Group 15 herbicides applied preplant incorporated
Authors: Soltani Nader , Shropshire Christy , Sikkema Peter H.
Published: May 2018

A study consisting of four field experiments was conducted over a 2-yr period (2016, 2017) near Exeter and Ridgetown, ON, to compare the tolerance of adzuki, kidney, small red, and white beans to four Group 15 herbicides including pethoxamid (1200 and 2400 g a.i. ha−1), S-metolachlor (1600 and 3200 g a.i. ha−1), dimethenamid-P (693 and 1386 g a.i. ha−1), and pyroxasulfone (100 and 200 g a.i. ha−1) applied preplant incorporated (PPI). At 1 wk after emergence (WAE), pethoxamid, S-metolachlor, dimethenamid-P, and pyroxasulfone caused as much as 22%, 17%, 38%, and 15% adzuki bean injury, respectively. The injury decreased with time; at 8 WAE, pethoxamid, S-metolachlor, dimethenamid-P, and pyroxasulfone applied PPI caused as much as 3%, 4%, 12%, and 7% adzuki bean injury, respectively. The injury was lower in other market classes of dry bean. At 1, 2, and 4 WAE, pethoxamid, S-metolachlor, dimethenamid-P, and pyroxasulfone caused as much as 4%, 2%, 4%, and 14% injury in kidney bean, 3%, 2%, 4%, and 12% injury in small red bean, and 5%, 3%, 6%, and 13% injury in white bean, respectively. However, the injury at 8 WAE was 5% or less in kidney, small red, and white beans with all Group 15 herbicides evaluated. Based on this research, pyroxasulfone was the most injurious to dry beans, it reduced plant height as much as 15% and seed yield as much as 17%. The Group 15 herbicides evaluated were more injurious to adzuki bean than kidney, small red, or white beans.
A label propagation approach based on local optimization
Authors: Zhang Xiaohong , Jiang Yulin , Ren Jianji , Tang Chaosheng
Published: May 2018

Community detection offers an important way to understand the structures and functions of social network. The label propagation algorithm has attracted vast attention since it is very suitable for discovering communities from large-scale networks. However, the algorithm suffers from the instability and inefficiency problem caused by the random policies it adopted. In this paper, we propose a novel label propagation approach based on local optimization to deal with the problem. The approach introduces a pre-propagation mechanism to optimize randomly initialized labels according to special factors, for example, node compactness. After that, it traverses and relabels nodes in the descending order of aggregate influence. The experiment results demonstrate the usefulness and effectiveness of our approach.
Symmetry-guided design of topologies for supercomputer networks
Authors: Sabino Alan U. , Vasconcelos Miguel F. S. , Deng Yuefan , Ramos Alexandre F.
Published: May 2018

A family of graphs optimized as the topologies for interconnection networks is proposed. The needs of such topologies with minimal diameters and minimal mean path lengths are met by special constructions of the weight vectors in a representation of the symplectic algebra. Such design of topologies can conveniently reconstruct the mesh and hypercube, widely used as network topologies, as well as many other classes of graphs potentially suitable for network topologies.
Evolution of algebraic terms 3: Term continuity and beam algorithms
Authors: Clark David M. , Spector Lee
Published: May 2018

The first paper in this series introduced the notion of term to term operation continuity for finite groupoids, and proved that two testable conditions on a finite groupoid imply that it is term continuous (TC). The second presented an evolution inspired algorithm for finding terms for operations, and gave experimental evidence that, in general, it was successful exactly when the groupoid was both idemprimal and TC. In this paper, we describe a new class of algorithms for finding terms which brings these results together. Theorems about idemprimality and term continuity show how each of these two properties impact our algorithms. They lead to a final explanation for the success of our algorithms when the groupoid is both idemprimal and TC.
On Jones’ subgroup of R. Thompson’s group T
Authors: Nikkel Jordan , Ren Yunxiang
Published: May 2018

Jones introduced unitary representations for the Thompson groups [Formula: see text] and [Formula: see text] from a given subfactor planar algebra. Some interesting subgroups arise as the stabilizer of certain vector, in particular the Jones subgroups [Formula: see text] and [Formula: see text]. Golan and Sapir studied [Formula: see text] and identified it as a copy of the Thompson group [Formula: see text]. In this paper, we completely describe [Formula: see text] and show that [Formula: see text] coincides with its commensurator in [Formula: see text], implying that the corresponding unitary representation is irreducible. We also generalize the notion of the Stallings 2-core for diagram groups to [Formula: see text], showing that [Formula: see text] and [Formula: see text] are not isomorphic, but as annular diagram groups they have very similar presentations.
Gravity’s universality: The physics underlying Tolman temperature gradients
Authors: Santiago Jessica , Visser Matt
Published: May 2018

We provide a simple and clear verification of the physical need for temperature gradients in equilibrium states when gravitational fields are present. Our argument will be built in a completely kinematic manner, in terms of the gravitational redshift/blueshift of light, together with a relativistic extension of Maxwell’s two column argument. We conclude by showing that it is the universality of the gravitational interaction (the uniqueness of free-fall) that ultimately permits Tolman’s equilibrium temperature gradients without any violation of the laws of thermodynamics.
Dynamic Analysis of a Coupled System of High-Speed Maglev Train and Curved Viaduct
Authors: Wang Z. L. , Xu Y. L. , Li G. Q. , Chen S. W. , Zhang X. L.
Published: May 2018

This study presents a framework for dynamic analysis of a coupled system of high-speed maglev train and curved viaduct. A series of trajectory coordinates are used to define the motion of maglev vehicles moving over a horizontally curved track, the stiffness and damping matrices of the equations can be thus reduced into those of the straight track. The curved viaduct system is modeled in the global coordinate system using the finite element method, in which the inner and outer rails in the different horizontal planes are duly included. The electromagnet force-air gap model is adopted for the maglev vehicle via its electromagnets and rails on the viaduct, by appropriate transformation of coordinates. By applying the proposed framework to the Shanghai maglev line, curved path-induced dynamic responses and characteristics of the vehicle are explored, which agree well with the measurement ones. The dynamic responses of the curved viaduct are also examined in the vertical, lateral and rotational directions by comparison with the straight viaduct. Moreover, the effect of various curve radii and cant deficiencies on the coupled system are investigated. The results show that for a maglev vehicle moving with an initial equilibrium state, its lateral and rotational response are mainly excited by track roughness. In addition to the track radius, cant deficiencies significantly affect the operational safety of the viaduct.
Few products, many h-fold sums
Authors: Bush Albert , Croot Ernie
Published: May 2018

Expanding upon a technique of Croot and Hart, we show that for every [Formula: see text], there exists an [Formula: see text] such that if [Formula: see text] is sufficiently large and [Formula: see text], then [Formula: see text].
Design and Evaluation of a Soft-Bodied Magnetic Anchored and Guided Endoscope
Authors: Cheng Truman , Zhang Xue , Ng Calvin Sze Hang , Chiu Philip Wai Yan , Li Zheng
Published: May 2018

A major challenge of minimally invasive surgery (MIS), particularly in laparoendoscopic single site (LESS) surgery, is trocar crowding. Trocar crowding causes instruments fencing, limited instrument access and limited endoscope views. It also increases the workload of surgeons. One strategy to alleviate the problem is to use magnetic anchored and guided system (MAGS). Existing MAGS endoscopes are assembled by multiple miniature components and actuated by onboard motors. This makes them complex, difficult to manufacture as well as requires additional power consumption. In this work, we present a novel soft-bodied magnetic anchored and guided endoscope, which comprises of a silicon structure, the magnets and a wireless camera module. The developed endoscope incorporates benefits of both MAGS (e.g. wireless steering and translation) and soft-bodied devices (e.g. compactness, lightweight, safety and simple fabrication). We model the moment loads experienced by the silicon structure to optimize the design of the endoscope. Performance and feasibility of the endoscope are validated using both benchtop setting and animal cadaver.
Transactivation domain of p53 regulates DNA repair and integrity in human iPS cells
Authors: Kannappan Ramaswamy , Mattapally Saidulu , Wagle Pooja A. , Zhang Jianyi
Published: May 2018

The role of p53 transactivation domain (p53-TAD), a multifunctional and dynamic domain, on DNA repair and retaining DNA integrity in human induced pluripotent stem cells (hiPSCs) has never been studied. p53-TAD was knocked out in iPSCs using CRISPR/Cas9 and was confirmed by DNA sequencing. p53-TAD knockout (KO) cells were characterized by accelerated proliferation, decreased population doubling time, and unaltered Bcl-2, Bcl-2-binding component 3, insulin-like growth factor 1 receptor, and Bax and altered Mdm2, p21, and p53-induced death domain transcript expression. In p53-TAD KO cells, the p53-regulated DNA repair proteins xeroderma pigmentosum group A, DNA polymerase H, and DNA-binding protein 2 expression were found to be reduced compared with p53 wild-type cells. Exposure to a low dose of doxorubicin (Doxo) induced similar DNA damage and DNA damage response (DDR) as measured by RAD50 and MRE11 expression, checkpoint kinase 2 activation, and γH2A.X recruitment at DNA strand breaks in both cell groups, indicating that silence of p53-TAD does not affect the DDR mechanism upstream of p53. After removal of Doxo, p53 wild-type hiPSCs underwent DNA repair, corrected their damaged DNA, and restored DNA integrity. Conversely, p53-TAD KO hiPSCs did not undergo complete DNA repair and failed to restore DNA integrity. More importantly, continuous culture of p53-TAD KO hiPSCs underwent G2/M cell cycle arrest and expressed the cellular senescent marker p16INK4a. Our data clearly show that silence of the TAD of p53 did not affect DDR but affected the DNA repair process, implying the crucial role of p53-TAD in maintaining DNA integrity. Therefore, activating p53-TAD domain using small molecules may promote DNA repair and integrity of cells and prevent cellular senescence.

NEW & NOTEWORTHY The p53 transactivation domain (TAD) in human induced pluripotent stem cells (iPSCs) was deleted using the CRISPR/Cas9 system. Deletion of p53-TAD resulted in increased cell proliferation but did not affect iPSC pluripotency. DNA repair machinery upstream of p53 was not affected in p53-TAD knockout, but p53-regulated DNA repair proteins xeroderma pigmentosum group A, DNA polymerase H, and DNA-binding protein 2 were affected. Finally, p53-TAD was found to be necessary for iPSCs to repair damaged DNA and retain DNA integrity.
The Landscape of Actionable Genomic Alterations in Cell-Free Circulating Tumor DNA from 21,807 Advanced Cancer Patients
Authors: Zill Oliver A. , Banks Kimberly C. , Fairclough Stephen R. , Mortimer Stefanie A. , Vowles James V. , Mokhtari Reza , Gandara David R. , Mack Philip C. , Odegaard Justin I. , Nagy Rebecca J. , Baca Arthur M. , Eltoukhy Helmy , Chudova Darya I. , Lanman Richard B. , Talasaz AmirAli
Published: May 2018

Purpose: Cell-free DNA (cfDNA) sequencing provides a noninvasive method for obtaining actionable genomic information to guide personalized cancer treatment, but the presence of multiple alterations in circulation related to treatment and tumor heterogeneity complicate the interpretation of the observed variants.

Experimental Design: We describe the somatic mutation landscape of 70 cancer genes from cfDNA deep-sequencing analysis of 21,807 patients with treated, late-stage cancers across >50 cancer types. To facilitate interpretation of the genomic complexity of circulating tumor DNA in advanced, treated cancer patients, we developed methods to identify cfDNA copy-number driver alterations and cfDNA clonality.

Results: Patterns and prevalence of cfDNA alterations in major driver genes for non–small cell lung, breast, and colorectal cancer largely recapitulated those from tumor tissue sequencing compendia (The Cancer Genome Atlas and COSMIC; r = 0.90–0.99), with the principal differences in alteration prevalence being due to patient treatment. This highly sensitive cfDNA sequencing assay revealed numerous subclonal tumor-derived alterations, expected as a result of clonal evolution, but leading to an apparent departure from mutual exclusivity in treatment-naïve tumors. Upon applying novel cfDNA clonality and copy-number driver identification methods, robust mutual exclusivity was observed among predicted truncal driver cfDNA alterations (FDR = 5 × 10−7 for EGFR and ERBB2), in effect distinguishing tumor-initiating alterations from secondary alterations. Treatment-associated resistance, including both novel alterations and parallel evolution, was common in the cfDNA cohort and was enriched in patients with targetable driver alterations (>18.6% patients).

Conclusions: Together, these retrospective analyses of a large cfDNA sequencing data set reveal subclonal structures and emerging resistance in advanced solid tumors. Clin Cancer Res; 24(15); 3528–38. ©2018 AACR.
High-Fat Diet-Induced Inflammation Accelerates Prostate Cancer Growth via IL6 Signaling
Authors: Hayashi Takuji , Fujita Kazutoshi , Nojima Satoshi , Hayashi Yujiro , Nakano Kosuke , Ishizuya Yu , Wang Cong , Yamamoto Yoshiyuki , Kinouchi Toshiro , Matsuzaki Kyosuke , Jingushi Kentaro , Kato Taigo , Kawashima Atsunari , Nagahara Akira , Ujike Takeshi , Uemura Motohide , Pena Maria Del Carmen Rodriguez , Gordetsky Jennifer B. , Morii Eiichi , Tsujikawa Kazutake , Netto George J. , Nonomura Norio
Published: May 2018

Purpose: High-fat diet (HFD) could induce prostate cancer progression. The aim of this study is to identify mechanisms of HFD-induced prostate cancer progression, focusing on inflammation.

Experimental Design: We administered HFD and celecoxib to autochthonous immunocompetent Pb-Cre+;Pten(fl/fl) model mice for prostate cancer. Tumor growth was evaluated by tumor weight and Ki67 stain, and local immune cells were assessed by flow cytometry at 22 weeks of age. Cytokines which correlated with tumor growth were identified, and the changes of tumor growth and local immune cells after inhibition of the cytokine signals were evaluated in the mice. IHC analyses using prostatectomy specimens of obese patients were performed.

Results: HFD accelerated tumor growth and increased the myeloid-derived suppressor cells (MDSCs) fraction and M2/M1 macrophage ratio in the model mice. Celecoxib-suppressed tumor growth, and decreased both local MDSCs and M2/M1 macrophage ratio in HFD-fed mice. HFD-induced tumor growth was associated with IL6 secreted by prostatic macrophages, as were phosphorylated STAT3 (pSTAT3)-positive tumor cells. Anti-IL6 receptor antibody administration suppressed tumor growth, and decreased local MDSCs and pSTAT3-positive cell fractions in HFD-fed mice. The tumor-infiltrating CD11b-positive cell count was significantly higher in prostatectomy specimens of obese than those of nonobese patients with prostate cancer.

Conclusions: HFD increased MDSCs and accelerated prostate cancer tumor growth via IL6/pSTAT3 signaling in the mice. This mechanism could exist in obese patients with prostate cancer. IL6-mediated inflammation could be a therapeutic target for prostate cancer. Clin Cancer Res; 24(17); 4309–18. ©2018 AACR.
Role of Elevated PHIP Copy Number as a Prognostic and Progression Marker for Cutaneous Melanoma
Authors: Bezrookove Vladimir , Nosrati Mehdi , Miller James R. , De Semir David , Dar Altaf A. , Vosoughi Elham , Vaquero Edith , Sucker Antje , Lazar Alexander J. , Gershenwald Jeffrey E. , Davies Michael A. , Schadendorf Dirk , Kashani-Sabet Mohammed
Published: May 2018

Purpose: Previous studies have indicated an important role for pleckstrin homology domain-interacting protein (PHIP) as a marker and mediator of melanoma metastasis. Here we aimed to confirm the role of PHIP copy number in successive stages of melanoma progression.

Experimental Design: PHIP copy number was examined using FISH in three independent cohorts by recording the percentage of cells harboring ≥3 copies of PHIP. The impact of PHIP copy number on survival was assessed using Cox regression analysis. The enrichment of PHIP was assessed in various molecular melanoma subtypes. PHIP expression was analyzed in The Cancer Genome Atlas (TCGA) melanoma cohort.

Results: Elevated PHIP copy number was significantly predictive of reduced distant metastasis-free survival (DMFS) and disease-specific survival (DSS), and increased prevalence of ulceration in primary melanoma (cohort No. 1). By multivariate analysis, PHIP FISH scores were independently predictive of DMFS and DSS. PHIP copy number was enriched in metastatic melanomas harboring mutant NRAS or expressing PTEN protein (cohort No. 2). PHIP copy number was significantly elevated in metastatic melanomas when compared with matched primary tumors from the same patient (cohort No. 3). Several of these associations were replicated using TCGA cohort analysis.

Conclusions: These results underscore the important role of PHIP copy-number elevation in melanoma progression, and identify molecular subtypes of melanoma in which PHIP is enriched. Finally, as elevated PHIP copy number appears to be selected for during the progression of primary to metastatic melanoma, these results confirm PHIP as a promising therapeutic target for melanoma. Clin Cancer Res; 24(17); 4119–25. ©2018 AACR.
Combining Variables for Cancer Risk Estimation: Is the Sum Better than the Parts?
Authors: Friedenreich Christine M. , McTiernan Anne
Published: May 2018

Examining joint exposures of modifiable breast cancer risk factors may provide advantages over individual exposure–disease association analyses. Using the Healthy Lifestyle Index, Arthur and colleagues analyzed the joint impacts of diet, alcohol, smoking, physical activity, and obesity on breast cancer risk, and subtypes, in postmenopausal women enrolled in the Women's Health Initiative. The analysis provides data for population-attributable risk estimations and future prevention trials to target multiple risk factors. The public health messages for the individual risk factors remain unchanged, however, and it is still not clear whether improving one risk factor can counteract the adverse effects of another. Cancer Prev Res; 11(6); 313–6. ©2018 AACR.

See related article by Arthur et al., p. 317
Cardiac Fibroma with Ventricular Tachycardia: An Unusual Clinical Presentation of Nevoid Basal Cell Carcinoma Syndrome
Authors: Ritter Alyssa L. , Granquist Eric J. , Iyer V. Ramesh , Izumi Kosuke
Published: May 2018

Pediatric cardiac tumors are rare and often benign with an incidence of approximately 0.03-0.32% and can be associated with genetic conditions. For example, approximately 3% of individuals with nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, have a cardiac fibroma. NBCCS is also characterized by lamellar or early calcification of the falx, jaw keratocysts, palmar and/or plantar pits, and a predisposition for basal cell carcinomas. Given the management implications of NBCCS, including appropriate cancer screenings and precautions, prompt identification of affected individuals is critical. We report a case of a 6-year-old female presenting with ventricular tachycardia secondary to cardiac fibroma. After diagnosis of recurrent jaw keratocysts, she was clinically and molecularly diagnosed with NBCCS. Identification of a cardiac fibroma should prompt careful assessment of past medical and family history with consideration of a diagnosis of NBCCS.
Symptom Burden of Atrial Fibrillation and Its Relation to Interventions and Outcome in Europe
Authors: Schnabel Renate B. , Pecen Ladislav , Rzayeva Nargiz , Lucerna Markus , Purmah Yanish , Ojeda Francisco M. , De Caterina Raffaele , Kirchhof Paulus
Published: May 2018

Background

Little is known about the association of atrial fibrillation symptom burden with quality of life and outcomes.

Methods and Results

In the Prevention of Thromboembolic Events–European Registry in Atrial Fibrillation (n=6196 patients with atrial fibrillation; mean±SD age, 71.8±10.4 years; 39.7% women), we assessed European Heart Rhythm Association score symptoms and calculated correlations with the standardized health status questionnaire (
EQ
‐5D‐5L). Patients were followed up for atrial fibrillation therapies and outcomes (stroke/transient ischemic attack/arterial thromboembolism, coronary events, heart failure, and major bleeding) over 1 year. Most individuals (92%) experienced symptoms. Correlations with health status and quality of life were modest. In multivariable‐adjusted regression models, the dichotomized European Heart Rhythm Association score (intermediate/frequent versus never/occasional symptoms) was associated with cardioversions (odds ratio [
OR
], 1.21; 95% confidence interval [
CI
], 1.01–1.45) and catheter ablation (
OR,
1.97; 95%
CI,
1.44–2.69), and inversely related with heart rate control (
OR,
0.80; 95%
CI,
0.70–0.92) and heart failure incidence (
OR,
1.65; 95%
CI,
1.16–2.34). Anxiety was inversely related with stroke/transient ischemic attack/arterial thromboembolism (
OR,
0.55; 95%
CI,
0.32–0.93), whereas chest pain related positively with coronary events (
OR,
2.45; 95%
CI,
1.42–4.22). Fatigue (
OR,
1.84; 95%
CI,
1.30–2.60), dyspnea (
OR,
2.33; 95%
CI,
1.63–3.33), and anxiety (
OR,
1.72; 95%
CI,
1.16–2.55) were associated with heart failure incidence. Palpitations were positively associated with cardioversion (
OR,
1.32; 95%
CI,
1.08–1.61) and ablation therapy (
OR,
2.02; 95%
CI,
1.48–2.76).

Conclusions

A higher symptom burden, in particular palpitations, predicted interventions to restore sinus rhythm. The score itself had limited predictive value, but its individual components were related to different and specific clinical events, and may thus be helpful to target patient management.
MR‐proADM as a Prognostic Marker in Patients With ST‐Segment–Elevation Myocardial Infarction—DANAMI‐3 (a Danish Study of Optimal Acute Treatment of Patients With STEMI) Substudy
Authors: Falkentoft Alexander C. , Rørth Rasmus , Iversen Kasper , Høfsten Dan E. , Kelbæk Henning , Holmvang Lene , Frydland Martin , Schoos Mikkel M. , Helqvist Steffen , Axelsson Anna , Clemmensen Peter , Jørgensen Erik , Saunamäki Kari , Tilsted Hans‐Henrik , Pedersen Frants , Torp‐Pedersen Christian , Kofoed Klaus F. , Goetze Jens P. , Engstrøm Thomas , Køber Lars
Published: May 2018

Background

Midregional proadrenomedullin (
MR
‐pro
ADM
) has demonstrated prognostic potential after myocardial infarction (
MI
). Yet, the prognostic value of
MR
‐pro
ADM
at admission has not been examined in patients with ST‐segment–elevation
MI
(
STEMI
).

Methods and Results

The aim of this substudy, DANAMI‐3 (The Danish Study of Optimal Acute Treatment of Patients with
ST
‐segment–elevation myocardial infarction), was to examine the associations of admission concentrations of
MR
‐pro
ADM
with short‐ and long‐term mortality and hospital admission for heart failure in patients with
ST
‐segment–elevation myocardial infarction. Outcomes were assessed using Cox proportional hazard models and area under the curve using receiver operating characteristics. In total, 1122 patients were included. The median concentration of
MR
‐pro
ADM
was 0.64 nmol/L (25th–75th percentiles, 0.53–0.79). Within 30 days 23 patients (2.0%) died and during a 3‐year follow‐up 80 (7.1%) died and 38 (3.4%) were admitted for heart failure. A doubling of
MR
‐pro
ADM
was, in adjusted models, associated with an increased risk of 30‐day mortality (hazard ratio, 2.67; 95% confidence interval, 1.01–7.11;
P
=0.049), long‐term mortality (hazard ratio, 3.23; 95% confidence interval, 1.97–5.29;
P
<0.0001), and heart failure (hazard ratio, 2.71; 95% confidence interval, 1.32–5.58;
P
=0.007). For 30‐day and 3‐year mortality, the area under the curve for
MR
‐pro
ADM
was 0.77 and 0.78, respectively. For 3‐year mortality, area under the curve (0.84) of the adjusted model marginally changed (0.85;
P
=0.02) after addition of
MR
‐pro
ADM
.

Conclusions

Elevation of admission
MR
‐pro
ADM
was associated with long‐term mortality and heart failure, whereas the association with short‐term mortality was borderline significant.
MR
‐pro
ADM
may be a marker of prognosis after ST‐segment–elevation myocardial infarction but does not seem to add substantial prognostic information to established clinical models.

Clinical Trial Registration

URL
:
http:/www.ClinicalTrials.gov
/. Unique identifiers:
NCT
01435408 and
NCT
01960933.
The genus Ctenomelynthus (Hemiptera: Heteroptera: Coreidae: Acanthocephalini), with the description of three new species and key to the known species
Authors: BRAILOVSKY HARRY
Published: May 2018

The genus Ctenomelynthus Breddin (1903) is redescribed, and three new species: C. sanchezi from French Guiana, and Venezuela, C. urbinus from Brazil, and C. venustulus from Suriname are described. Ctenomelynthus willineri (Kormilev, 1952), is synonymized under C. coxalis Breddin, 1903. One species, C. bridarollii (Kormilev) is designated as a nomen dubium. New distributional records for C. brunneiventris Breddin, C. coxalis Breddin, and C. inermibus (Distant) are included. Dorsal and ventral photographs and parameres of some species are included. A key to the six known species is given.
Radar-Observed Characteristics of Precipitation in the Tropical High Andes of Southern Peru and Bolivia
Authors: Endries Jason L. , Perry L. Baker , Yuter Sandra E. , Seimon Anton , Andrade-Flores Marcos , Winkelmann Ronald , Quispe Nelson , Rado Maxwell , Montoya Nilton , Velarde Fernando , Arias Sandro
Published: May 2018

This study used the first detailed radar measurements of the vertical structure of precipitation obtained in the central Andes of southern Peru and Bolivia to investigate the diurnal cycle and vertical structure of precipitation and melting-layer heights in the tropical Andes. Vertically pointing 24.1-GHz Micro Rain Radars in Cusco, Peru (3350 m MSL, August 2014–February 2015), and La Paz, Bolivia (3440 m MSL, October 2015–February 2017), provided continuous 1-min profiles of reflectivity and Doppler velocity. The time–height data enabled the determination of precipitation timing, melting-layer heights, and the identification of convective and stratiform precipitation features. Rawinsonde data, hourly observations of meteorological variables, and satellite and reanalysis data provided additional insight into the characteristics of these precipitation events. The radar data revealed a diurnal cycle with frequent precipitation and higher rain rates in the afternoon and overnight. Short periods with strong convective cells occurred in several storms. Longer-duration events with stratiform precipitation structures were more common at night than in the afternoon. Backward air trajectories confirmed previous work indicating an Amazon basin origin of storm moisture. For the entire dataset, median melting-layer heights were above the altitude of nearby glacier termini approximately 17% of the time in Cusco and 30% of the time in La Paz, indicating that some precipitation was falling as rain rather than snow on nearby glacier surfaces. During the 2015–16 El Niño, almost half of storms in La Paz had melting layers above 5000 m MSL.
The Implications of an Idealized Large-Scale Circulation for Mechanical Work Done by Tropical Convection
Authors: Kamieniecki Jan A. , Ambaum Maarten H. P. , Plant Robert S. , Woolnough Steven J.
Published: May 2018

A thermodynamic analysis is presented of an overturning circulation simulated by two cloud-resolving models, coupled by a weak temperature gradient parameterization. Taken together, they represent two separated regions over different sea surface temperatures, and the coupling represents an idealized large-scale circulation such as the Walker circulation. It is demonstrated that a thermodynamic budget linking net heat input to the generation of mechanical energy can be partitioned into contributions from the large-scale interaction between the two regions, as represented by the weak temperature gradient approximation, and from convective motions in the active warm region and the suppressed cool region. Model results imply that such thermodynamic diagnostics for the aggregate system are barely affected by the strength of the coupling, even its introduction, or by the SST contrast between the regions. This indicates that the weak temperature gradient parameterization does not introduce anomalous thermodynamic behavior. We find that the vertical kinetic energy associated with the large-scale circulation is more than three orders of magnitude smaller than the typical vertical kinetic energy in each region. However, even with very weak coupling circulations, the contrast between the thermodynamic budget terms for the suppressed and active regions is strong and is relatively insensitive to the degree of the coupling. Additionally, scaling arguments are developed for the relative values of the terms in the mechanical energy budget.
The NCAR–NOAA Global Hawk Dropsonde System
Authors: Wick Gary A. , Hock Terrence F. , Neiman Paul J. , Vömel Holger , Black Michael L. , Spackman J. Ryan
Published: May 2018

A new remotely controlled Airborne Vertical Atmospheric Profiling System (AVAPS) dropsonde system has been developed for and deployed on the NASA Global Hawk (GH) unmanned aircraft. Design, fabrication, and operation of the system was led by the National Center for Atmospheric Research (NCAR) with support from the National Oceanic and Atmospheric Administration (NOAA) Unmanned Aircraft Systems (UAS) Program. The system has employed the NCAR Research Dropsonde 94 (NRD94) dropsonde, a smaller and lighter version of the standard RD94 dropsonde deployed from manned aircraft but with virtually identical sensors. The dropsondes provide in situ atmospheric profiles of temperature, pressure, and humidity at a 2-Hz data rate, and wind speed and direction at 4 Hz. The system is capable of carrying up to 90 dropsondes and can support eight simultaneous soundings. Operation from the GH means that the dropsondes can be deployed from altitudes up to 19.8 km during flights in excess of 24-h duration. The dropsonde launch is commanded directly by an operator on the ground in coordination with the aircraft commander. Over 2700 total dropsondes have been deployed from the GH during four major campaigns since 2011. Data are processed in near–real time and have been employed by forecasters, for assimilation in numerical weather prediction models, and in diverse research studies. Intercomparison studies suggest the performance of the GH NRD94 dropsondes is similar to those deployed from manned aircraft. This paper describes the components and operation of the system and illustrates its unique capabilities through highlights of data application to research on the Arctic atmosphere, atmospheric rivers, and tropical cyclones.
The Interaction between Deep Convection and Easterly Wave Activity over Africa: Convective Transitions and Mechanisms
Authors: Mekonnen Ademe , Rossow William B.
Published: May 2018

Recent work using observational data from the International Satellite Cloud Climatology Project (ISCCP) and reanalysis products suggests that African easterly waves (AEWs) form in association with a “transition” process from smaller and scattered convection into larger and organized mesoscale convective activity. However, the transition process is unclear and how mesoscale convection initiates AEWs is not well understood. Analysis based on 25 years of ISCCP and reanalysis datasets show that increasing intradiurnal activity, atmospheric instability, and specific humidity precede the development of well-organized convection over the Ethiopian highlands. Atmospheric instability favors a high frequency of scattered, isolated convection to the east of the Ethiopian highlands, first, followed by a continuing and large increase in instability and increasing humidity, which supports well-organized larger-scale convection. The timing of the changes of thermodynamic variables shows that the dominant transition process is scattered, with weakly organized convection transitioning into the well-organized mesoscale convection, and this initiates the AEWs. Slightly before the mesoscale convection peaks over the Ethiopian highlands, low-level moist westerlies, low- to midlevel wind shear, and positive relative vorticity increase over the region. Evidence shows that the large-scale and local environment enables the scattered and less well-organized convection to merge and form larger and well-organized convection. The dynamic processes suggest that the dominant pathway for AEW initiation is scattered convection transitioning to large and well-organized convection over the Ethiopian highlands and this initiates AEWs westward of the Ethiopian highlands.