bluuebunny/crossref_metadata_2025 huggingface dataset:
Recruitment and retention in a 10-month social network-based intervention promoting diabetes self-management in socioeconomically deprived patients: a qualitative process evaluation
Authors: Vissenberg Charlotte , Nierkens Vera , Uitewaal Paul J M , Middelkoop Barend J C , Stronks Karien
Published: July 2017

Objectives

Socioeconomically deprived patients with type 2 diabetes often face challenges with self-management, resulting in more diabetes-related complications. However, these groups are often under-represented in self-management interventions. Evidence on effective recruitment and retention strategies is growing, but lacking for intensive self-management interventions. This study aims to explore recruitment, retention and effective intervention strategies in a 10-month group-based intervention among Dutch, Moroccan, Turkish and Surinamese patients from socioeconomically deprived neighbourhoods.

Methods

Participants were recruited through general practitioners (GPs) and participated in a 10-month social network-based intervention (10 groups, n=69):Powerful Together with Diabetes. This intervention also targeted the significant others of participants and aimed to increase social support for self-management and to decrease social influences hindering self-management. A qualitative process evaluation was conducted. Retention was measured using log books kept by group leaders. Further, we conducted 17 in-depth interviews with participants (multiethnic sample) and 18 with group leaders. Interviews were transcribed, coded and analysed using framework analyses.

Results

The GP's letter and reminder calls, an informational meeting and the intervention's informal nature facilitated recruitment. During the first months, positive group atmosphere, the intervention's perceived usefulness, opportunities to socialise and a reduction in practical barriers facilitated retention. After the first months, conflicting responsibilities and changes in the intervention's nature and planning hindered retention. Calls from group leaders and the prospect of a diploma helped participants overcome these barriers.

Conclusion

To promote retention in lengthy self-management interventions, it seems important that patients feel they are going on an outing to a social gathering that is enjoyable, recreational, useful and easy to attend. However, rewards and intensive personal recruitment and retention strategies remained necessary throughout the entire intervention period.

Trial registration number

Dutch Trial Register NTR1886; Results.
Coronary anatomy in children with bicuspid aortic valves and associated congenital heart disease
Authors: Koenraadt Wilke M C , Bartelings Margot M , Bökenkamp Regina , Gittenberger-de Groot Adriana C , DeRuiter Marco C , Schalij Martin J , Jongbloed Monique RM
Published: July 2017

Objective

In patients with bicuspid aortic valve (BAV), coronary anatomy is variable. High take-off coronary arteries have been described, but data are scarce, especially when associated with complex congenital heart disease (CHD). The purpose of this study was to describe coronary patterns in these patients.

Methods

In 84 postmortem heart specimens with BAV and associated CHD, position and height of the coronary ostia were studied and related to BAV morphology.

Results

High take-off right (RCA) and left coronary arteries (LCA) were observed in 23% and 37% of hearts, respectively, most frequently in hearts with hypoplastic left ventricle (HLV) and outflow tract anomalies. In HLV, high take-off was observed in 18/40 (45%) more frequently of LCA (n=14) than RCA (n=6). In hearts with aortic hypoplasia, 8/13 (62%) had high take-off LCA and 6/13 (46%) high take-off RCA. High take-off was seen 19 times in 22 specimens with perimembranous ventricular septal defect (RCA 8, LCA 11). High take-off was associated with type 1A BAV (raphe between right and left coronary leaflets), more outspoken for the RCA. Separate ostia of left anterior descending coronary artery and left circumflex coronary artery were seen in four hearts (5%), not related to specific BAV morphology.

Conclusion

High take-off coronary arteries, especially the LCA, occur more frequently in BAV with associated CHD than reported in normal hearts and isolated BAV. Outflow tract defects and HLV are associated with type 1A BAV and high take-off coronary arteries. Although it is unclear whether these findings in infants with detrimental outcome can be related to surviving adults, clinical awareness of variations in coronary anatomy is warranted.
A 10-year review of child injury hospitalisations, health outcomes and treatment costs in Australia
Authors: Mitchell Rebecca J , Curtis Kate , Foster Kim
Published: July 2017

Background

Childhood injury is a leading cause of hospitalisation, yet there has been no comprehensive examination of child injury and survival over time in Australia. To examine the characteristics, temporal trend and survival for children who were hospitalised as a result of injury in Australia.

Method

A retrospective examination of linked hospitalisation and mortality data for injured children aged 16 years or less during 1 July 2001 to 30 June 2012. Negative binomial regression examined change in injury hospitalisation trends. Cox proportional hazard regression examined the association of risk factors on 30-day survival.

Results

There were 6 86 409 injury hospitalisations, with an age-standardised rate of 1489 per 1 00 000 population (95% CI 1485.3 to 1492.4) in Australia. Child injury hospitalisation rates did not change over the 10-year period. For every severely injured child, there are at least 13 children hospitalised with minor or moderate injuries. The total cost of child injury hospitalisations was $A2.1 billion (annually $A212 million). Falls (38.4%) were the most common injury mechanism. Factors associated with a higher risk of 30-day mortality were: child was aged ≤10 years, higher injury severity, head injury, injured in a transport incident or following drowning and submersion or other threats to breathing, during self-harm and usual residence was regional/remote Australia.

Conclusions

Childhood injury hospitalisation rates have not reduced in 10 years. Children’s patterns of injury change with age, and priorities for injury prevention alter according to developmental stages. The development of a national multisectorial childhood injury monitoring and prevention strategy in Australia is long overdue.
The preventive effect of a soccer-specific ankle brace on acute lateral ankle sprains in girls amateur soccer players: study protocol of a cluster-randomised controlled trial
Authors: Thijs Karin , Huisstede Bionka , Goedhart Edwin , Backx Frank
Published: July 2017

Background

Acute lateral ankle sprains are the single most often diagnosed injury in female soccer players and often result in an inability to play. This highlights the need for effective prevention strategies. Proprioceptive training and/or the use of an external support to decrease inversion of the ankle joint can prevent or reduce the number of acute lateral ankle sprains. The effectiveness of a soccer-specific ankle brace in reducing first-time and recurrent acute lateral ankle sprains has never been investigated in girl soccer players. If effective, ankle braces could be introduced into soccer.

Study design

Cluster-randomised controlled trial.

Methods

Girl amateur soccer players (aged 14–18 years) will be allocated to an intervention or control group. The intervention group will be instructed to wear soccer-specific ankle braces on both ankles during soccer training and matches; the control group will continue playing soccer as usual. Primary outcomes are the incidence and severity of acute lateral ankle sprains. Secondary outcomes are the prognostic value of generalised joint hypermobility and functional stability on the risk of acute lateral ankle sprains and compliance with the intervention.

Discussion

The findings from this study may provide evidence to support the use of a soccer-specific ankle brace to prevent lateral ankle sprains during soccer. We hypothesise that this brace will reduce the incidence of ankle sprains among young amateur girl soccer players by 50%. The prevention of such injuries will be beneficial to players, clubs and society.

Trial registration number

The Netherlands Trial Register (NTR): NTR6045; Pre-results.
The third pathway of colorectal carcinogenesis
Authors: Rubio Carlos A , Puppa Giacomo , de Petris Giovanni , Kis Lorand , Schmidt Peter T
Published: July 2017

Aims

The majority of the colorectal carcinomas (CRC) arise in a vast mucosal area built with columnar cells and mucus-producing goblet cells. These carcinomas evolve via the conventional (tubular/villous) adenoma–carcinoma pathway, or the serrated adenoma–carcinoma pathway. Much less frequently CRC arise in the gut-associated lymphoid tissue (GALT) mucosal domain via the third pathway of colorectal carcinogenesis.

Methods

All publications on human colorectal GALT carcinomas in the literature were reviewed.

Results

Only 23 GALT-carcinomas found in 20 patients are in record. The GALT carcinomas were detected at surveillance colonoscopic biopsy in 11 patients (four had ulcerative colitis, two were members of a Lynch syndrome family, two of a CRC family, one had familial adenomatous polyposis (FAP), one prior colon adenomas and one a submucosal tumour), or at diagnostic colonoscopic biopsy in the remaining nine patients (three had rectal bleedings, two abdominal pains, one diverticular disease and one protracted constipation. In three, no ground disease or symptoms were provided). In six of the 23 GALT carcinomas, the luminal surface showed tumour cells, ulcerations or no descriptions were given. Ten (66.7%) of the remaining 15 GALT carcinomas showed on top, adenomas (n=8) or high-grade dysplasia (n=2).

Conclusions

The low frequency of GALT carcinomas might be explained by the fact that the colorectal mucosal areas occupied by GALT domains are minute. The finding that two-thirds of the 15 remaining GALT carcinomas (vide supra) were covered by high-grade dysplasia or by conventional adenomas strongly suggest that conventional non-invasive neoplasias might have preceded the majority of the GALT carcinomas in record.
Diagnosis of equine influenza
Authors: Rash Adam
Published: July 2017

During the summer months, there will be increased movement and, therefore, increased mixing of the horse population, leading to a higher risk of disease transmission and subsequent clinical cases. It is important that both vets and owners remain vigilant for equine influenza infection. Here, Adam Rash, of the Animal Health Trust, discusses the diagnosis of this disease
PCR cycles above routine numbers do not compromise high-throughput DNA barcoding results
Authors: Vierna J. , Doña J. , Vizcaíno A. , Serrano D. , Jovani R.
Published: July 2017

High-throughput DNA barcoding has become essential in ecology and evolution, but some technical questions still remain. Increasing the number of PCR cycles above the routine 20–30 cycles is a common practice when working with old-type specimens, which provide little amounts of DNA, or when facing annealing issues with the primers. However, increasing the number of cycles can raise the number of artificial mutations due to polymerase errors. In this work, we sequenced 20 COI libraries in the Illumina MiSeq platform. Libraries were prepared with 40, 45, 50, 55, and 60 PCR cycles from four individuals belonging to four species of four genera of cephalopods. We found no relationship between the number of PCR cycles and the number of mutations despite using a nonproofreading polymerase. Moreover, even when using a high number of PCR cycles, the resulting number of mutations was low enough not to be an issue in the context of high-throughput DNA barcoding (but may still remain an issue in DNA metabarcoding due to chimera formation). We conclude that the common practice of increasing the number of PCR cycles should not negatively impact the outcome of a high-throughput DNA barcoding study in terms of the occurrence of point mutations.
Bratteli–Vershik models for partial actions of ℤ
Authors: Giordano Thierry , Gonçalves Daniel , Starling Charles
Published: July 2017

Let [Formula: see text] and [Formula: see text] be open subsets of the Cantor set with nonempty disjoint complements, and let [Formula: see text] be a homeomorphism with dense orbits. Building on the ideas of Herman, Putnam and Skau, we show that the partial action induced by [Formula: see text] can be realized as the Vershik map on an ordered Bratteli diagram, and that any two such diagrams are equivalent.
Black hole thermodynamics in Snyder phase space
Authors: Saghafi Sara , Nozari Kourosh
Published: July 2017

By defining a noncommutative symplectic structure, we study thermodynamics of Schwarzschild black hole in a Snyder noncommutative phase space for the first time. Since natural cutoffs are the results of compactness of symplectic manifolds in phase space, the physics of black holes in such a space would be affected mainly by these cutoffs. In this respect, this study provides a basis for more deeper understanding of the black hole thermodynamics in a pure mathematical viewpoint.
Applications of fluorescence lifetime imaging in clinical medicine
Authors: Wang Zhanwen , Zheng Yanping , Zhao Deqiang , Zhao Ziwei , Liu Lixin , Pliss Artem , Zhu Feiqi , Liu Jun , Qu Junle , Luan Ping
Published: July 2017

Fluorescence lifetime is not only associated with the molecular structure of fluorophores, but also strongly depends on the environment around them, which allows fluorescence lifetime imaging microscopy (FLIM) to be used as a tool for precise measurement of the cell or tissue microenvironment. This review introduces the basic principle of fluorescence lifetime imaging technology and its application in clinical medicine, including research and diagnosis of diseases in skin, brain, eyes, mouth, bone, blood vessels and cavity organs, and drug evaluation. As a noninvasive, nontoxic and nonionizing radiation technique, FLIM demonstrates excellent performance with high sensitivity and specificity, which allows to determine precise position of the lesion and, thus, has good potential for application in biomedical research and clinical diagnosis.
comeNgo
Authors: Zhang Tianyang , Cui Peng , Faloutsos Christos , Lu Yunfei , Ye Hao , Zhu Wenwu , Yang Shiqiang
Published: July 2017

How do social groups, such as Facebook groups and Wechat groups, dynamically evolve over time? How do people join the social groups, uniformly or with burst? What is the pattern of people quitting from groups? Is there a simple universal model to depict the come-and-go patterns of various groups?

In this article, we examine temporal evolution patterns of more than 100 thousands social groups with more than 10 million users. We surprisingly find that the evolution patterns of real social groups goes far beyond the classic dynamic models like SI and SIR. For example, we observe both diffusion and non-diffusion mechanism in the group joining process, and power-law decay in group quitting process, rather than exponential decay as expected in SIR model. Therefore, we propose a new modelcomeNgo, a concise yet flexible dynamic model for group evolution. Our model has the following advantages: (a) Unification power: it generalizes earlier theoretical models and different joining and quitting mechanisms we find from observation. (b) Succinctness and interpretability: it contains only six parameters with clear physical meanings. (c) Accuracy: it can capture various kinds of group evolution patterns preciously, and the goodness of fit increases by 58% over baseline. (d) Usefulness: it can be used in multiple application scenarios, such as forecasting and pattern discovery. Furthermore, our model can provide insights about different evolution patterns of social groups, and we also find that group structure and its evolution has notable relations with temporal patterns of group evolution.
Perceptual Lightness Modeling for High-Dynamic-Range Imaging
Authors: Abebe Mekides Assefa , Pouli Tania , Larabi Mohamed-Chaker , Reinhard Erik
Published: July 2017

The human visual system (HVS) non-linearly processes light from the real world, allowing us to perceive detail over a wide range of illumination. Although models that describe this non-linearity are constructed based on psycho-visual experiments, they generally apply to a limited range of illumination and therefore may not fully explain the behavior of the HVS under more extreme illumination conditions. We propose a modified experimental protocol for measuring visual responses to emissive stimuli that do not require participant training, nor requiring the exclusion of non-expert participants. Furthermore, the protocol can be applied to stimuli covering an extended luminance range. Based on the outcome of our experiment, we propose a new model describing lightness response over an extended luminance range. The model can be integrated with existing color appearance models or perceptual color spaces. To demonstrate the effectiveness of our model in high dynamic range applications, we evaluate its suitability for dynamic range expansion relative to existing solutions.
Saliency Detection on Light Field
Authors: Zhang Jun , Wang Meng , Lin Liang , Yang Xun , Gao Jun , Rui Yong
Published: July 2017

Saliency detection has recently received increasing research interest on using high-dimensional datasets beyond two-dimensional images. Despite the many available capturing devices and algorithms, there still exists a wide spectrum of challenges that need to be addressed to achieve accurate saliency detection. Inspired by the success of the light-field technique, in this article, we propose a new computational scheme to detect salient regions by integrating multiple visual cues from light-field images. First, saliency prior maps are generated from several light-field features based on superpixel-level intra-cue distinctiveness, such as color, depth, and flow inherited from different focal planes and multiple viewpoints. Then, we introduce the location prior to enhance the saliency maps. These maps will finally be merged into a single map using a random-search-based weighting strategy. Besides, we refine the object details by employing a two-stage saliency refinement to obtain the final saliency map.

In addition, we present a more challenging benchmark dataset for light-field saliency analysis, named
HFUT-Lytro
, which consists of 255 light fields with a range from 53 to 64 images generated from each light-field image, therein spanning multiple occurrences of saliency detection challenges such as occlusions, cluttered background, and appearance changes. Experimental results show that our approach can achieve 0.6--6.7% relative improvements over state-of-the-art methods in terms of the
F-measure
and
Precision
metrics, which demonstrates the effectiveness of the proposed approach.
Open source social media intelligence for enabling government applications
Authors: Agarwal Swati
Published: July 2017

Open-source social media intelligence (OSSMInt) is a field comprising of techniques and applications to analyze and mine open-source social media data for extracting actionable information and useful insights. The focus of the work presented in this paper is on novel applications and techniques of OSSMInt in the government sector. I propose and develop several novel use-cases and applications around OSSMInt for government and broadly divide them into three categories: identification, prediction, and response applications. In particular, I present solutions, tools and techniques for analyzing data from micro-blogging website to analyze citizen complaints and grievances in the public sector [response]. The research presented in this paper also describes my work on analyzing data from Twitter micro-blogging website to early forecast a civil unrest and protest [prediction]. Furthermore, I build various applications around identification and detection that are useful for the government and security analysts. I demonstrate the application of OSSMInt for identifying religious conflicts within society by mining public opinions on Tumblr website and fill the gaps of offline surveys. The study presented in this paper propose solutions for enabling law enforcement agencies to detect, prevent and combat online radicalization and extremism (content, users, and communities) by mining data from Tumblr, Twitter and YouTube websites [identification]. Furthermore, I also propose and build an application for detecting secret message exchanged in an adversarial communication and capture the obfuscated terms in messages. The central component of my proposed solution approach is the application of information retrieval and machine learning based techniques and algorithms. The study consists of experimenting with a diverse range of machine learning algorithms such as unsupervised, semi-supervised and supervised learning (k-NN, SVM, naive Bayes, random forest and decision tree) based algorithms. Based on the experimental results, I observe that there are several untapped opportunities as well as technical challenges in exploiting open-source social media data by the government for intelligence gathering. Furthermore, social media is a rich source of information for building security informatics based applications by mining the content, users, links and relationships on social media platforms.
Upcoming SIGWEB supported conferences
Authors: Samuel Hamman
Published: July 2017

The Special Interest Group on Hypertext and the Web, SIGWEB was created in 1989 to support the community participating in the annual ACM Hypertext Conference. Now in its third decade, SIGWEB has grown considerably and now sponsors seven annual conferences of different sizes and covering a wide range of topics. SIGWEB supports several specialized conferences, short courses, and workshops, as well as the Annual Hypertext Conference. SIGWEB sponsored conferences focus on timely topics in applied and computational hypertext and Web disciplines and provide a place for members and the entire applied Hypermedia and Web community to exchange ideas and to meet with and expand their network of colleagues. In this article, we provide a brief overview of SIGWEB sponsored conferences, in addition to events that are in cooperation with SIGWEB.
Learning to search for images without annotations
Authors: Kordumova Svetlana
Published: July 2017

This thesis contributes to learning machines what is in an image by avoiding direct manual annotation as training data. We either rely on tagged data from social media platforms to recognize concepts, or on objects semantics and layout to recognize scenes. We focus our effort on image search.
Report from EVOSTAR 2017
Authors: Paechter Ben
Published: July 2017

The 20th Edition of the EvoStar series of conferences took place in Amsterdam between 19th and 21st April 2017.
The Monkeying of the Americas: Primate Biogeography in the Neotropics
Authors: Lynch Alfaro Jessica
Published: July 2017

Monkeys first arrived in the Neotropics about 36 Ma, and the ancestry of all living Neotropical primates (Platyrrhini) traces to a single common ancestral population from 24 to 19 Ma. The availability of lush Amazonian habitat, the rise of the Andes, the transition from the lacustrine to riverine system in the Amazon Basin, and the intermittent connection between the Amazon and the Atlantic tropical forests have all shaped how primates spread and diversified. Primates outcompeted native South American mammals but faced an influx of North American fauna with the closing of the Isthmus of Panama. Humans, extreme newcomers in the Neotropics, have influenced primate habitat and ecology over the last 13,000 years, with radical transformations in the last 500 years as a result of European colonization and land use change. Neotropical primate biogeography informs taxonomic work and conservation efforts, with a mind toward mitigating effects of direct human impact and human-mediated climate change.
Electroweak Measurements at the LHC
Authors: Hamel de Monchenault Gautier
Published: July 2017

To our present knowledge, all of the physics at the LHC can be described in the framework of the Standard Model of particle physics. Indeed, the newly discovered Higgs boson with a mass close to 125 GeV seems to confirm the predictions of the theory. Thus, in addition to looking for direct manifestations of the physics beyond the Standard Model, the LHC aims to perform ever more stringent tests of the Standard Model, in particular in the sectors of electroweak symmetry breaking and gauge interactions at high energies. In this article, I review recent experimental results in the field of electroweak interactions at the LHC.
Wearable knee health system employing novel physiological biomarkers
Authors: Inan Omer T. , Whittingslow Daniel C. , Teague Caitlin N. , Hersek Sinan , Pouyan Maziyar Baran , Millard-Stafford Mindy , Kogler Geza F. , Sawka Michael N.
Published: July 2017

Knee injuries and chronic disorders, such as arthritis, affect millions of Americans, leading to missed workdays and reduced quality of life. Currently, after an initial diagnosis, there are few quantitative technologies available to provide sensitive subclinical feedback to patients regarding improvements or setbacks to their knee health status; instead, most assessments are qualitative, relying on patient-reported symptoms, performance during functional tests, and physical examinations. Recent advances have been made with wearable technologies for assessing the health status of the knee (and potentially other joints) with the goal of facilitating personalized rehabilitation of injuries and care for chronic conditions. This review describes our progress in developing wearable sensing technologies that enable quantitative physiological measurements and interpretation of knee health status. Our sensing system enables longitudinal quantitative measurements of knee sounds, swelling, and activity context during clinical and field situations. Importantly, we leverage machine-learning algorithms to fuse the low-level signal and feature data of the measured time series waveforms into higher level metrics of joint health. This paper summarizes the engineering validation, baseline physiological experiments, and human subject studies—both cross-sectional and longitudinal—that demonstrate the efficacy of using such systems for robust knee joint health assessment. We envision our sensor system complementing and advancing present-day practices to reduce joint reinjury risk, to optimize rehabilitation recovery time for a quicker return to activity, and to reduce health care costs.
Novel Gene and Network Associations Found for Acute Lymphoblastic Leukemia Using Case–Control and Family-Based Studies in Multiethnic Populations
Authors: Nakka Priyanka , Archer Natalie P. , Xu Heng , Lupo Philip J. , Raphael Benjamin J. , Yang Jun J. , Ramachandran Sohini
Published: July 2017

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, suggesting that germline variants influence ALL risk. Although multiple genome-wide association (GWA) studies have identified variants predisposing children to ALL, it remains unclear whether genetic heterogeneity affects ALL susceptibility and how interactions within and among genes containing ALL-associated variants influence ALL risk.

Methods: Here, we jointly analyzed two published datasets of case–control GWA summary statistics along with germline data from ALL case–parent trios. We used the gene-level association method PEGASUS to identify genes with multiple variants associated with ALL. We then used PEGASUS gene scores as input to the network analysis algorithm HotNet2 to characterize the genomic architecture of ALL.

Results: Using PEGASUS, we confirmed associations previously observed at genes such as ARID5B, IKZF1, CDKN2A/2B, and PIP4K2A, and we identified novel candidate gene associations. Using HotNet2, we uncovered significant gene subnetworks that may underlie inherited ALL risk: a subnetwork involved in B-cell differentiation containing the ALL-associated gene CEBPE, and a subnetwork of homeobox genes, including MEIS1.

Conclusions: Gene and network analysis uncovered loci associated with ALL that are missed by GWA studies, such as MEIS1. Furthermore, ALL-associated loci do not appear to interact directly with each other to influence ALL risk, and instead appear to influence leukemogenesis through multiple, complex pathways.

Impact: We present a new pipeline for post hoc analysis of association studies that yields new insight into the etiology of ALL and can be applied in future studies to shed light on the genomic underpinnings of cancer. Cancer Epidemiol Biomarkers Prev; 26(10); 1531–9. ©2017 AACR.
Rural–Urban Differences in Cancer Incidence and Trends in the United States
Authors: Zahnd Whitney E. , James Aimee S. , Jenkins Wiley D. , Izadi Sonya R. , Fogleman Amanda J. , Steward David E. , Colditz Graham A. , Brard Laurent
Published: July 2017

Background: Cancer incidence and mortality rates in the United States are declining, but this decrease may not be observed in rural areas where residents are more likely to live in poverty, smoke, and forego cancer screening. However, there is limited research exploring national rural–urban differences in cancer incidence and trends.

Methods: We analyzed data from the North American Association of Central Cancer Registries' public use dataset, which includes population-based cancer incidence data from 46 states. We calculated age-adjusted incidence rates, rate ratios, and annual percentage change (APC) for: all cancers combined, selected individual cancers, and cancers associated with tobacco use and human papillomavirus (HPV). Rural–urban comparisons were made by demographic, geographic, and socioeconomic characteristics for 2009 to 2013. Trends were analyzed for 1995 to 2013.

Results: Combined cancers incidence rates were generally higher in urban populations, except for the South, although the urban decline in incidence rate was greater than in rural populations (10.2% vs. 4.8%, respectively). Rural cancer disparities included higher rates of tobacco-associated, HPV-associated, lung and bronchus, cervical, and colorectal cancers across most population groups. Furthermore, HPV-associated cancer incidence rates increased in rural areas (APC = 0.724, P < 0.05), while temporal trends remained stable in urban areas.

Conclusions: Cancer rates associated with modifiable risks—tobacco, HPV, and some preventive screening modalities (e.g., colorectal and cervical cancers)—were higher in rural compared with urban populations.

Impact: Population-based, clinical, and/or policy strategies and interventions that address these modifiable risk factors could help reduce cancer disparities experienced in rural populations. Cancer Epidemiol Biomarkers Prev; 27(11); 1265–74. ©2017 AACR.
Pediatric Phase I Trial and Pharmacokinetic Study of Trebananib in Relapsed Solid Tumors, Including Primary Tumors of the Central Nervous System ADVL1115: A Children's Oncology Group Phase I Consortium Report
Authors: Leary Sarah E.S. , Park Julie R. , Reid Joel M. , Ralya Andrew T. , Baruchel Sylvain , Wu Bing , Roberts Timothy P.L. , Liu Xiaowei , Minard Charles G. , Fox Elizabeth , Weigel Brenda , Blaney Susan
Published: July 2017

Purpose: Trebananib is a first-in-class antiangiogenic peptibody (peptide–Fc fusion protein) that inhibits Angiopoietin 1 and 2. A pediatric phase 1 trial was performed to define trebananib dose-limiting toxicities (DLT), recommended phase 2 dose (RP2D), and pharmacokinetics (PK).

Experimental Design: Trebananib was administered by weekly infusion. Three dose levels (10, 15, or 30 mg/kg/dose) were evaluated using a rolling-six design. Part 2 evaluated a cohort of subjects with primary central nervous system (CNS) tumors. Pharmacokinetic sampling and analysis of peripheral blood biomarkers was performed during the first 4 weeks. Response was evaluated after 8 weeks. Correlative studies included angiogenic protein expression and DCE-MRI.

Results: Thirty-seven subjects were enrolled (31 evaluable for toxicity) with median age 12 years (range, 2 to 21). Two of 19 evaluable non-CNS subjects developed DLT at the 30 mg/kg dose level, including venous thrombosis and pleural effusion. In the CNS cohort, 3/12 subjects developed DLT, including decreased platelet count, transient ischemic attack, and cerebral edema with headache and hydrocephalus. Other grade 3 or 4 toxicities included lymphopenia (n = 4), anemia, thrombocytopenia, neutropenia, vomiting, and hypertension (n = 1 each). Response included stable disease in 7 subjects, no partial or complete responses. Two subjects continued study treatment with prolonged stable disease for 18 cycles (neuroblastoma) and 26 cycles (anaplastic astrocytoma). Pharmacokinetics appeared linear over 3 dose levels. Correlative studies demonstrated increased PlGF and sVCAM-1, but no change in endoglin or perfusion by DCE-MRI.

Conclusions: Trebananib was well tolerated in pediatric patients with recurrent or refractory solid or CNS tumors. RP2D is 30 mg/kg. Clin Cancer Res; 23(20); 6062–9. ©2017 AACR.
Numb−/low Enriches a Castration-Resistant Prostate Cancer Cell Subpopulation Associated with Enhanced Notch and Hedgehog Signaling
Authors: Guo Yanjing , Zhang Kai , Cheng Chaping , Ji Zhongzhong , Wang Xue , Wang Minglei , Chu Mingliang , Tang Dean G. , Zhu Helen He , Gao Wei-Qiang
Published: July 2017

Purpose: To elucidate the role and molecular mechanism of Numb in prostate cancer and the functional contribution of Numb−/low prostate cancer cells in castration resistance.

Experimental Design: The expression of Numb was assessed using multiple Oncomine datasets and prostate cancer tissues from both humans and mice. The biological effects of the overexpression and knockdown of Numb in human prostate cancer cell lines were investigated in vitro and in vivo. In addition, we developed a reliable approach to distinguish between prostate cancer cell populations with a high or low endogenous expression of Numb protein using a Numb promoter–based lentiviral reporter system. The difference between Numb−/low and Numbhigh prostate cancer cells in the response to androgen-deprivation therapy (ADT) was then tested. The likely downstream factors of Numb were analyzed using luciferase reporter assays, immunoblotting, and quantitative real-time PCR.

Results: We show here that Numb was downregulated and negatively correlated with prostate cancer advancement. Functionally, Numb played an inhibitory role in xenograft prostate tumor growth and castration-resistant prostate cancer development by suppressing Notch and Hedgehog signaling. Using a Numb promoter–based lentiviral reporter system, we were able to distinguish Numb−/low prostate cancer cells from Numbhigh cells. Numb−/low prostate cancer cells were smaller and quiescent, preferentially expressed Notch and Hedgehog downstream and stem-cell–associated genes, and associated with a greater resistance to ADT. The inhibition of the Notch and Hedgehog signaling pathways significantly increased apoptosis in Numb−/low cells in response to ADT.

Conclusions: Numb−/low enriches a castration-resistant prostate cancer cell subpopulation that is associated with unregulated Notch and Hedgehog signaling. Clin Cancer Res; 23(21); 6744–56. ©2017 AACR.
Head and Neck Carcinoma Immunotherapy: Facts and Hopes
Authors: Whiteside Theresa L.
Published: July 2017

Cancer of the head and neck (HNC) is a heterogeneous disease of the upper aerodigestive tract, encompassing distinct histologic types, different anatomic sites, and human papillomavirus (HPV)–positive as well as HPV-negative cancers. Advanced/recurrent HNCs have poor prognosis with low survival rates. Tumor-mediated inhibition of antitumor immune responses and a high mutational burden are common features of HNCs. Both are responsible for the successful escape of these tumors from the host immune system. HNCs evolve numerous mechanisms of evasion from immune destruction. These mechanisms are linked to genetic aberrations, so that HNCs with a high mutational load are also highly immunosuppressive. The tumor microenvironment of these cancers is populated by immune cells that are dysfunctional, inhibitory cytokines, and exosomes carrying suppressive ligands. Dysfunctional immune cells in patients with recurrent/metastatic HNC can be made effective by the delivery of immunotherapies in combination with conventional treatments. With many promising immune-based strategies available, the future of immune therapies in HNC is encouraging, especially as methods for genetic profiling and mapping the immune landscape of the tumor are being integrated into a personalized approach. Efficiency of immune therapies is expected to rapidly improve with the possibility for patients' selection based on personal immunogenomic profiles. Noninvasive biomarkers of response to therapy will be emerging as a better understanding of the various molecular signals co-opted by the tumors is gained. The emerging role of immunotherapy as a potentially beneficial addition to standard treatments for recurrent/metastatic HNC offers hope to the patients for whom no other therapeutic options exist. Clin Cancer Res; 24(1); 6–13. ©2017 AACR.
FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious BRCA Mutation–Associated Advanced Ovarian Cancer
Authors: Balasubramaniam Sanjeeve , Beaver Julia A. , Horton Sara , Fernandes Laura L. , Tang Shenghui , Horne Hisani N. , Liu Jinzhong , Liu Chao , Schrieber Sarah J. , Yu Jingyu , Song Pengfei , Pierce William , Robertson Kim J. , Palmby Todd R. , Chiu Haw-Jyh , Lee Eunice Y. , Philip Reena , Schuck Robert , Charlab Rosane , Banerjee Anamitro , Chen Xiao Hong , Wang Xing , Goldberg Kirsten B. , Sridhara Rajeshwari , Kim Geoffrey , Pazdur Richard
Published: July 2017

On December 19, 2016, the FDA granted accelerated approval to rucaparib (RUBRACA; Clovis Oncology, Inc.) for the treatment of patients with deleterious BRCA mutation (germline and/or somatic)–associated advanced ovarian cancer who have been treated with two or more chemotherapies. The FDA also approved the FoundationFocus CDxBRCA test (Foundation Medicine, Inc.), the first next-generation sequencing-based companion diagnostic, for identifying patients with advanced ovarian cancer eligible for treatment with rucaparib based on detection of deleterious BRCA1 and/or BRCA2 mutations in tumor tissue. Rucaparib's approval was based primarily on efficacy data from 106 patients with BRCA mutation–associated ovarian cancer who had prior treatment with two or more chemotherapies and safety data from 377 patients with ovarian cancer treated with rucaparib 600 mg orally twice daily on two open-label, single-arm trials. Investigator-assessed objective response rate was 54% [57/106; 95% confidence interval (CI), 44–64], and median duration of response was 9.2 months (95% CI, 6.6–11.7). The approved companion diagnostic verified tumor BRCA mutation status retrospectively in 96% (64/67) of patients. Common adverse reactions (≥20%) to rucaparib were nausea, fatigue, vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea. This article summarizes the FDA review and data supporting rucaparib's accelerated approval. Clin Cancer Res; 23(23); 7165–70. ©2017 AACR.

See related commentary by Kohn et al., p. 7155
Sox10
+
Cells Contribute to Vascular Development in Multiple Organs—Brief Report
Authors: Wang Dong , Wu Fan , Yuan Haoyong , Wang Aijun , Kang Gyeong Jin , Truong Tan , Chen Lu , McCallion Andrew S. , Gong Xiaohua , Li Song
Published: July 2017

Objective—

Previous genetic lineage tracing studies showed that Sox10
+
cells differentiate into vascular mural cells, limited to neural crest–derived blood vessels in craniofacial tissues, aortic arch, pulmonary arch arteries, brachiocephalic, carotid arteries, and thymus. The purpose of this study was to investigate the contribution of Sox10
+
cells to the vascular development in other tissues and organs and their relationship with neural crest.

Approach and Results—

Using genetic lineage tracing technique based on Cre/LoxP system, we examined blood vessels in the adult organs of the mice expressing Sox10-Cre/Rosa-LoxP-red fluorescent protein or Wnt1-Cre/Rosa-LoxP-red fluorescent protein by immunohistological analysis. In addition to previously reported tissues and organs derived from neural crest, we showed that Sox10
+
cells also contributed to vascular mural cells in the lung, spleen, and kidney, which are derived from non-neural crest origin as evidenced by red fluorescent protein-negative blood vessels in these 3 organs of Wnt1-Cre/Rosa-LoxP-red fluorescent protein mice.

Conclusions—

This study demonstrates that Sox10
+
cells contribute to pericytes and smooth muscle cells in most parts of the body, including those from neural crest and non-neural crest, which has significant implications in vascular remodeling under physiological and pathological conditions.
Angiotensin II Type 1 Receptor‐Associated Protein Regulates Kidney Aging and Lifespan Independent of Angiotensin
Authors: Uneda Kazushi , Wakui Hiromichi , Maeda Akinobu , Azushima Kengo , Kobayashi Ryu , Haku Sona , Ohki Kohji , Haruhara Kotaro , Kinguchi Sho , Matsuda Miyuki , Ohsawa Masato , Minegishi Shintaro , Ishigami Tomoaki , Toya Yoshiyuki , Atobe Yoshitoshi , Yamashita Akio , Umemura Satoshi , Tamura Kouichi
Published: July 2017

Background

The kidney is easily affected by aging‐associated changes, including glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Particularly, renal tubulointerstitial fibrosis is a final common pathway in most forms of progressive renal disease. Angiotensin
II
type 1 receptor (
AT
1R)‐associated protein (
ATRAP
), which was originally identified as a molecule that binds to
AT
1R, is highly expressed in the kidney. Previously, we have shown that
ATRAP
suppresses hyperactivation of
AT
1R signaling, but does not affect physiological
AT
1R signaling.

Methods and Results

We hypothesized that
ATRAP
has a novel functional role in the physiological age‐degenerative process, independent of modulation of
AT
1R signaling.
ATRAP
‐knockout mice were used to study the functional involvement of
ATRAP
in the aging.
ATRAP
‐knockout mice exhibit a normal age‐associated appearance without any evident alterations in physiological parameters, including blood pressure and cardiovascular and metabolic phenotypes. However, in
ATRAP
‐knockout mice compared with wild‐type mice, the following takes place: (1) age‐associated renal function decline and tubulointerstitial fibrosis are more enhanced; (2) renal tubular mitochondrial abnormalities and subsequent increases in the production of reactive oxygen species are more advanced; and (3) life span is 18.4% shorter (median life span, 100.4 versus 123.1 weeks). As a key mechanism, age‐related pathological changes in the kidney of
ATRAP
‐knockout mice correlated with decreased expression of the prosurvival gene,
Sirtuin1
. On the other hand, chronic angiotensin
II
infusion did not affect renal sirtuin1 expression in wild‐type mice.

Conclusions

These results indicate that
ATRAP
plays an important role in inhibiting kidney aging, possibly through sirtuin1‐mediated mechanism independent of blocking
AT
1R signaling, and further protecting normal life span.
Mediation as Politics: How Nations Leverage Peace Engagements?
Authors: Beriker Nimet
Published: July 2017

This study proposes a conceptual model that depicts middle power mediation as a foreign policy strategy in the context of asymmetric alliance dynamics. It expands on Touval’s (2003) mediation-as-foreign policy perspective and argues that once mediation is conceived of as a viable political option in the conduct of foreign policy, engaging in mediation activity enables middle powers to create an extra space of political power not otherwise available. The article introduces an analytical model that explains the dynamics of mediation-as-foreign policy approach and the mechanisms that translate mediation engagement into political leverage. The analysis focuses on aspects of Turkish mediation efforts between 2002 and 2009 in the context of Turkish-us/eurelations.
World’s northenmost and rarely observed Nudibranchs: three new Onchidoridid species (Gastropoda: Doridida) from Russian seas
Authors: MARTYNOV ALEXANDER , KORSHUNOVA TATIANA
Published: July 2017

The world’s most northern species of the nudibranch genus Adalaria rossica sp. nov. from Franz Josef Land and a new species of Onchidoris expectata sp. nov. from the north-west Pacific Matua Island (Kurile Islands) are described. Prior to this study the nudibranch fauna from Franz Josef Land was represented only by two common North Atlantic species. Molecular taxonomic data were not applied for the Franz Josef Land nudibranchs previously. Nudibranchs of Matua Island have never been investigated. Furthermore, a new North Pacific taxon, Adalaria ultima sp. nov., is described here. The taxonomy of the onchidoridid genera Adalaria and Onchidoris is discussed.
Diurnal Cycle of Rainfall Associated with Landfalling Tropical Cyclones in China from Rain Gauge Observations
Authors: Hu Hao , Duan Yihong , Wang Yuqing , Zhang Xinghai
Published: July 2017

The diurnal variation of rainfall over China associated with landfalling tropical cyclones (TCs) is investigated using hourly rain gauge observations obtained from 2425 conventional meteorological stations in China. Records between 12 h prior to landfall and 12 h after landfall of 450 landfalling TCs in China from 1957 to 2014 are selected as samples. The harmonic analysis shows an obvious diurnal signal in TC rainfall with a rain-rate peak in the early morning and a minimum in the afternoon. The diurnal cycle in the outer region (between 400- and 900-km radii from the storm center) is found to be larger than in the core region (within 400 km of the storm center). This could be attributed to the effect of land on the inner core of the storms as the diurnal cycle is distinct in the core region well before landfall. As the result of this diurnal cycle, TCs making landfall at night tend to have cumulative precipitation, defined as the precipitation cumulated from the time at landfall to 12 h after landfall, about 30% larger than those making landfall around noon or afternoon. Moreover, the radial propagation of the diurnal cycle in TC rain rate, which has been a controversial phenomenon in some previous studies with remote sensing observations, was not present in this study that is based on rain gauge observations. Results also show that the diurnal signal has little dependence on the storm intensity 12 h prior to landfall.
The Impact of a Low Bias in Snow Water Equivalent Initialization on CFS Seasonal Forecasts
Authors: Broxton Patrick D. , Zeng Xubin , Dawson Nicholas
Published: July 2017

Across much of the Northern Hemisphere, Climate Forecast System forecasts made earlier in the winter (e.g., on 1 January) are found to have more snow water equivalent (SWE) in April–June than forecasts made later (e.g., on 1 April); furthermore, later forecasts tend to predict earlier snowmelt than earlier forecasts. As a result, other forecasted model quantities (e.g., soil moisture in April–June) show systematic differences dependent on the forecast lead time. Notably, earlier forecasts predict much colder near-surface air temperatures in April–June than later forecasts. Although the later forecasts of temperature are more accurate, earlier forecasts of SWE are more realistic, suggesting that the improvement in temperature forecasts occurs for the wrong reasons. Thus, this study highlights the need to improve atmospheric processes in the model (e.g., radiative transfer, turbulence) that would cause cold biases when a more realistic amount of snow is on the ground. Furthermore, SWE differences in earlier versus later forecasts are found to much more strongly affect April–June temperature forecasts than the sea surface temperature differences over different regions, suggesting the major role of snowpack in seasonal prediction during the spring–summer transition over snowy regions.