bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of pain assessment by physicians, parents and children in an outpatient setting
Authors: Brudvik Christina , Moutte Svein-Denis , Baste Valborg , Morken Tone 
Published: October 2016

IntroductionOur objective was to compare pain assessments by patients, parents and physicians in children with different medical conditions, and analyse how this affected the physicians' administration of pain relief.Patients and methodsThis cross-sectional study involved 243 children aged 3–15 years treated at Bergen Accident and Emergency Department (ED) in 2011. The child patient's pain intensity was measured using age-adapted scales while parents and physicians did independent numeric rating scale (NRS) assessments.ResultsPhysicians assessed the child's mean pain to be NRS=3.2 (SD 2.0), parents: NRS=4.8 (SD 2.2) and children: NRS=5.5 (SD 2.4). The overall child–parent agreement was moderate (Cohen's weighted κ=0.55), but low between child–physician (κ=0.12) and parent–physician (κ=0.17). Physicians significantly underestimated pain in all paediatric patients ≥3 years old and in all categories of medical conditions. However, the difference in pain assessment between child and physician was significantly lower for fractures (NRS=1.2; 95% CI 0.5 to 2.0) compared to wounds (NRS=3.4; CI 2.2 to 4.5; p=0.001), infections (NRS=3.1; CI 2.2 to 4.0; p=0.002) and soft tissue injuries (NRS=2.4; CI 1.9 to 2.9; p=0.007). The physicians’ pain assessment improved with increasing levels of pain, but only 42.1% of children with severe pain (NRS≥7) received pain relief.ConclusionsPaediatric pain was significantly underestimated by ED physicians. In the absence of a self-report from the child, parents' evaluation should be listened to. Despite improved pain assessments in children with fractures and when pain was perceived to be severe, it is worrying that barely half of the children with severe pain received analgesics in the ED.
Skin and soft tissue infection management failure in the emergency department observation unit: a systematic review
Authors: Abetz Jeremy W , Adams Nicholas G , Mitra Biswadev 
Published: October 2016

IntroductionSkin and soft tissue infections (SSTIs) are commonly treated in ED observation units (EDOUs). The management failure rate in this setting is high, as evidenced by a large proportion of patients requiring inpatient admission. This systematic review sought to quantify the management failure rate and identify risk factors associated with management failure.MethodsSearches of six databases and grey literature were conducted with no limits on publication year or language. Manuscripts describing patients admitted to an EDOU setting (≤24 hours planned admission to EDOU) with a primary diagnosis of cellulitis or other SSTIs were included. Variables associated with failure of management, defined as inpatient admission, stay >28 hours (4 hours in ED, 24 hours in EDOU) or death, were extracted. A narrative description of variables associated with failure of EDOU admission was conducted.ResultsThere were 1119 unique articles identified through the literature search. Following assessment, 10 studies were included in the final systematic review, 9 of which reported the management failure rate (range 15%–38%). The presence of fever, a high total white blood cell count and known methicillin-resistantStaphylococcus aureusexposure were the most commonly reported variables associated with management failure.ConclusionA higher rate of EDOU management failure in SSTIs than the generally accepted rate of 15% was observed in most studies identified by this review. Risk factors identified were varied, but presence of a fever and elevated inflammatory markers were commonly associated with failure of EDOU admission by multiple studies. Recognition of risk factors and the increased application of clinical decision tools may help to improve disposition of patients at high risk for clinical deterioration or management failure.
Development of an index to define overall disease severity in IBD
Authors: Siegel Corey A , Whitman Cynthia B , Spiegel Brennan M R , Feagan Brian , Sands Bruce , Loftus Edward V , Panaccione Remo , D'Haens Geert , Bernstein Charles N , Gearry Richard , Ng Siew C , Mantzaris Gerassimos J , Sartor Balfour , Silverberg Mark S , Riddell Robert , Koutroubakis Ioannis E , O'Morain Colm , Lakatos Peter L , McGovern Dermot P B , Halfvarson Jonas , Reinisch Walter , Rogler Gerhard , Kruis Wolfgang , Tysk Curt , Schreiber Stefan , Danese Silvio , Sandborn William , Griffiths Anne , Moum Bjorn , Gasche Christoph , Pallone Francesco , Travis Simon , Panes Julian , Colombel Jean-Frederic , Hanauer Stephen , Peyrin-Biroulet Laurent 
Published: October 2016

Background and aimDisease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC.MethodsUsing a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute.ResultsFor CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities.ConclusionsBased on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD.
Determination of the temperature dependence of the up- and down-quark masses in QCD
Authors: Dominguez C. A. , Hernandez L. A. 
Published: October 2016

The temperature dependence of the sum of the QCD up- and down-quark masses, (mu[Formula: see text]+[Formula: see text]md) and the pion decay constant, f[Formula: see text], are determined from two thermal finite energy QCD sum rules for the pseudoscalar-current correlator. This quark mass remains mostly constant for temperatures well below the critical temperature for deconfinement/chiral-symmetry restoration. As this critical temperature is approached, the quark mass increases sharply with increasing temperature. This increase is far more pronounced if the temperature dependence of the pion mass (determined independently from other methods) is taken into account. The behavior of f[Formula: see text](T) is consistent with the expectation from chiral symmetry, i.e. that it should follow the thermal dependence of the quark condensate, independently of the quark mass.
The Potent ALK Inhibitor Brigatinib (AP26113) Overcomes Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in Preclinical Models
Authors: Zhang Sen , Anjum Rana , Squillace Rachel , Nadworny Sara , Zhou Tianjun , Keats Jeff , Ning Yaoyu , Wardwell Scott D. , Miller David , Song Youngchul , Eichinger Lindsey , Moran Lauren , Huang Wei-Sheng , Liu Shuangying , Zou Dong , Wang Yihan , Mohemmad Qurish , Jang Hyun Gyung , Ye Emily , Narasimhan Narayana , Wang Frank , Miret Juan , Zhu Xiaotian , Clackson Tim , Dalgarno David , Shakespeare William C. , Rivera Victor M. 
Published: October 2016

AbstractPurpose: Non–small cell lung cancers (NSCLCs) harboring ALK gene rearrangements (ALK+) typically become resistant to the first-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) crizotinib through development of secondary resistance mutations in ALK or disease progression in the brain. Mutations that confer resistance to second-generation ALK TKIs ceritinib and alectinib have also been identified. Here, we report the structure and first comprehensive preclinical evaluation of the next-generation ALK TKI brigatinib.Experimental Design: A kinase screen was performed to evaluate the selectivity profile of brigatinib. The cellular and in vivo activities of ALK TKIs were compared using engineered and cancer-derived cell lines. The brigatinib–ALK co-structure was determined.Results: Brigatinib potently inhibits ALK and ROS1, with a high degree of selectivity over more than 250 kinases. Across a panel of ALK+ cell lines, brigatinib inhibited native ALK (IC50, 10 nmol/L) with 12-fold greater potency than crizotinib. Superior efficacy of brigatinib was also observed in mice with ALK+ tumors implanted subcutaneously or intracranially. Brigatinib maintained substantial activity against all 17 secondary ALK mutants tested in cellular assays and exhibited a superior inhibitory profile compared with crizotinib, ceritinib, and alectinib at clinically achievable concentrations. Brigatinib was the only TKI to maintain substantial activity against the most recalcitrant ALK resistance mutation, G1202R. The unique, potent, and pan-ALK mutant activity of brigatinib could be rationalized by structural analyses.Conclusions: Brigatinib is a highly potent and selective ALK inhibitor. These findings provide the molecular basis for the promising activity being observed in ALK+, crizotinib-resistant patients with NSCLC being treated with brigatinib in clinical trials. Clin Cancer Res; 22(22); 5527–38. ©2016 AACR.
Enrolling Adolescents in Disease/Target-Appropriate Adult Oncology Clinical Trials of Investigational Agents
Authors: Chuk Meredith K. , Mulugeta Yeruk , Roth-Cline Michelle , Mehrotra Nitin , Reaman Gregory H. 
Published: October 2016

Abstract
The enrollment of adolescents with cancer in clinical trials is much lower than that of younger pediatric patients. For adolescents with “adult-type” cancers, lack of access to relevant trials is cited as one of the reasons for this discrepancy. Adolescents are generally not eligible for enrollment in adult oncology trials, and initial pediatric trials for many drugs are conducted years later, often after the drug is approved. As a result, accrual of adolescents to these trials may be slow due to off-label use, prospectively collected safety and efficacy data are lacking at the time of initial approval, and, most importantly, these adolescents have delayed access to effective therapies. To facilitate earlier access to investigational and approved drugs for adolescent patients with cancer, and because drug exposure is most often similar in adolescents and adults, we recommend the inclusion of adolescents (ages 12–17) in disease- and target-appropriate adult oncology trials. This approach requires careful monitoring for any differential safety signals, appropriate pharmacokinetic evaluations, and ensuring that ethical requirements are met. Inclusion of adolescents in adult oncology trials will require the cooperation of investigators, cooperative groups, industry, institutional review boards, and regulatory agencies to overcome real and perceived barriers. Clin Cancer Res; 23(1); 9–12. ©2016 AACR.
Mechanisms of Resistance to Antibody–Drug Conjugates
Authors: Loganzo Frank , Sung Matthew , Gerber Hans-Peter 
Published: October 2016

AbstractDrug resistance limits the effectiveness of cancer therapies. Despite attempts to develop curative anticancer treatments, tumors evolve evasive mechanisms limiting durable responses. Hence, diverse therapies are used to attack cancer, including cytotoxic and targeted agents. Antibody–drug conjugates (ADC) are biotherapeutics designed to deliver potent cytotoxins to cancer cells via tumor-specific antigens. Little is known about the clinical manifestations of drug resistance to this class of therapy; however, recent preclinical studies reveal potential mechanisms of resistance. Because ADCs are a combination of antibody and small molecule cytotoxin, multifactorial modes of resistance are emerging that are inherent to the structure and function of the ADC. Decreased cell-surface antigen reduces antibody binding, whereas elevated drug transporters such as MDR1 and MRP1 reduce effectiveness of the payload. Inherent to the uniqueness of the ADC, other novel resistance mechanisms are emerging, including altered antibody trafficking, ADC processing, and intracellular drug release. Most importantly, the modular nature of the ADC allows components to be switched and replaced, enabling development of second-generation ADCs that overcome acquired resistance. This review is intended to highlight recent progress in our understanding of ADC resistance, including approaches to create preclinical ADC-refractory models and to characterize their emerging mechanisms of resistance. Mol Cancer Ther; 15(12); 2825–34. ©2016 AACR.
A Way Forward for Cancer Chemoprevention: Think Local
Authors: Al Rabadi Luai , Bergan Raymond 
Published: October 2016

Abstract
As cells progress through carcinogenesis, the associated exponential expansion of genetic and molecular aberrations and resultant heterogeneity make therapeutic success increasingly unattainable. Therapeutic intervention at early stages of carcinogenesis that occurs within the primary organ and in the face of a lower burden of molecular aberrations, constitutes a basic tenet of cancer chemoprevention, and provides a situation that favors a greater degree of therapeutic efficacy compared with that of advanced cancer. A longstanding barrier to chemoprevention relates to the requirement for essentially no systemic toxicity, and the fact that when large numbers of people are treated, the emergence of systemic toxicity is almost universal. A rational means to address this in fact relates to a second basic tenet of the chemopreventive strategy: the focus of therapeutic intervention is to disrupt a process that is in essence localized to a single organ. Based upon this consideration, a strategy which is based upon local delivery of therapeutics to an at-risk organ will achieve therapeutic efficacy while avoiding systemic delivery and its associated toxicity. This article will review the rationale for undertaking such an approach, describe successful clinical achievements based on this strategy, describe ongoing efforts to expand the impact of this approach, and together will highlight the high impact that this approach has already had on the field as well as its extremely high potential for future impact. Cancer Prev Res; 10(1); 14–35. ©2016 AACR.
Species diversity and spatial distribution of snakes in Jigme Dorji National Park and adjoining areas, western Bhutan
Authors: Koirala Bal Krishna , Gurung Dhan Bdr , Lhendup Phurba , Phuntsho Sonam 
Published: October 2016

This paper presents the results of a study conducted on the diversity and spatial distribution of snakes along the elevation gradients of Mochu River valley in Jigme Dorji National Park and its adjoining areas. The survey was conducted from July–September 2014 and May–July 2015. The study aimed to assess the diversity and distribution of snakes using opportunistic the visual encounter survey technique. A total of 17 species of snakes belonging to 15 genera and three families were documented during the study period. More than 53% of species were recorded in the lower sampling sites (between 1,200–500 m) indicating more favourable climatic conditions and habitat types for snakes assemblages at lower elevations indicating the importance of protecting low land forest areas for the conservation of snakes in the Bhutanese mountain ecosystem.
On the occurrence of Common Baron (Lepidoptera: Nymphalidae: Limenitidinae: Euthalia aconthea Cramer, 1777) in the Delhi area and analysis of abiotic factors affecting its distribution in India
Authors: Bais Rajv K. Singh 
Published: October 2016

This paper gives details of the occurrence of Euthalia aconthea from Delhi area situated in the Indo-Gangetic plains. Occurrence records of this species suggest that it is most frequent in five zones of India, despite the fact that its main larval food plant Mango Mangifera indica is abundantly available almost throughout India. Possible abiotic factors are hypothesized for this distribution.
Long-Term Follow-Up After Catheter Ablation of Atrioventricular Nodal Reentrant Tachycardia in Children
Authors: Backhoff David , Klehs Sophia , Müller Matthias J. , Schneider Heike E. , Kriebel Thomas , Paul Thomas , Krause Ulrich 
Published: October 2016

Background—
Catheter ablation of the slow conducting pathway (SP) is treatment of choice for atrioventricular nodal reentrant tachycardia (AVNRT). Although there are abundant data on AVNRT ablation in adult patients, little is known about the long-term results ≥3 years after AVNRT ablation in pediatric patients.

Methods and Results—
Follow-up data from 241 patients aged ≤18 years who had undergone successful AVNRT ablation were analyzed. Median age at ablation had been 12.5 years, and median follow-up was 5.9 years. Radiofrequency current had been used in 168 patients (70%), whereas cryoenergy had been used in 73 patients (30%). Procedural end point of AVNRT ablation had been either SP ablation (no residual dual atrioventricular nodal physiology) or SP modulation (residual SP conduction allowing for a maximum of one atrial echo beat). After the initial AVNRT ablation, calculated freedom from AVNRT was 96% at 1 year, 94% at 3 years, 93% at 5 years, and 89% at 8 years. Age, sex, body weight, the choice of ablation energy, and the procedural end point of AVNRT ablation did not impact freedom from AVNRT. Six of 22 AVNRT recurrences (27%) occurred ≥5 years after ablation. No late complications including atrioventricular block were noted.

Conclusions—
Cumulatively, catheter ablation of AVNRT continued to be effective in >90% of our pediatric patients during the long-term course. A significant part of recurrences occurred >5 years post ablation. Body weight, energy source, and the end point of ablation had no impact on long-term results. No adverse sequelae were noted.
A new subspecies of Nacaduba cyanea Cramer, 1775, from Buru, Maluku, Indonesia (Lepidoptera, Lycaenidae)
Authors: Tennent W. John , Gassó Miracle M. Eulàlia 
Published: October 2016

“Across the world, natural-history collections hold thousands of species awaiting identification. In fact, researchers today find many more novel animals and plants by sifting through decades-old specimens than they do by surveying tropical forests and remote landscapes. An estimated three-quarters of newly named mammal species are already part of a natural-history collection at the time they are identified. They sometimes sit unrecognised for a century or longer, hidden in drawers, half-forgotten in jars, misidentified, unlabelled.” Museums: The endangered dead (C. Kemp, Nature 518 (7539): 292–294, London, 19th February 2015)
A new subspecies of Nacaduba cyanea (Cramer, 1775), N. c. sanane ssp. n., from the Indonesian island of Buru is described and illustrated. It is compared with nominotypical cyanea (TL: “West-Indiën” [= West Indies]; recte: “Oost-Indiën” [= East Indies]) and N. c. obiana (Fruhstorfer, 1915) (TL: Obi). All eight currently recognised Moluccan subspecies of N. cyanea, including N. c. sanane ssp. n., are illustrated and a map depicting their distribution in the Moluccas is presented.
An Expendable Microstructure Profiler for Deep Ocean Measurements
Authors: Shang Xiaodong , Qi Yongfeng , Chen Guiying , Liang Changrong , Lueck Rolf G. , Prairie Brett , Li Hua 
Published: October 2016

AbstractMeasurements of turbulence in the deep ocean, particularly close to the bottom, are extremely sparse because of the difficulty and operational risk of obtaining deep profiles near the seafloor. A newly developed expendable instrument—the VMP-X (Vertical Microstructure Profiler–Expendable)—carries two microstructure shear probes to measure the fluctuations of vertical shear into the dissipation range and can profile down to a depth of 6000 m. Data from nine VMP-X profiles in the western Pacific Ocean near 11.6°N over rough topography display bottom-intensified turbulence with dissipation rates increasing by two factors of 10 to 4 W kg−1 within 200 m above the bottom. In contrast, over smooth topography in the southern South China Sea near 11°N, three profiles show that turbulence in the bottom boundary layer increases only slightly, with dissipation rates reaching 1 W kg−1. The eddy diffusivity over rough topography reached to 5 m2 s−1. The average diffusivity over all depths was 0.3 and 0.9 m2 s−1 for the tests in the southern South China Sea and in the western Pacific Ocean, respectively, and these values are much larger than previous estimates of less than ≈0.1 m2 s−1 for the main thermocline.
The Role of Convectively Generated Gravity Waves on Convective Initiation: A Case Study
Authors: Su Tao , Zhai Guoqing 
Published: October 2016

Abstract
A case study of a convection initiation (CI) event involving a mesoscale gravity wave is presented. This severe convection event occurred in east China on 5 June 2009. High-frequency automatic weather station (AWS) data, visible satellite data, and Doppler radar data were combined to depict the features of the gravity wave and the development of several convection centers. The gravity wave was manifested by a surface pressure dip and surface wind shift propagating westward away from the early convection. The pressure dip propagated at a speed of &gt;30 m s−1, which is comparable with that in previous observational studies of convectively generated gravity waves. A special focus is on the initiation of a deep convection cell in Anhui Province, which resulted in 25 deaths. Surface observations showed two precursors before CI, including a convergence line and wind shift at the eastern end of the convergence line. High-resolution numerical simulations with the Weather Research and Forecasting (WRF) Model were used to examine the structure of the gravity waves and forecast CI processes. The model reproduced the observed features of the gravity wave and the precursors before CI. Three-dimensional model results showed that CI occurred at the intersection between a convergence line and the gravity wave. The relationships between the wind shift and the pressure drop are consistent with polarization relation in ducted gravity waves. As the updraft of the gravity wave intersected with the convergence line, the low-level updraft strengthened and led to CI. The gravity wave, which had stronger updraft than downdraft, suggested a positive contribution to CI.