bluuebunny/crossref_metadata_2025 huggingface dataset:
Option framing for upselling tourism services: Does cognitive availability prevent irrational choices?
Authors: Mayer Verônica Feder , Santos Glauber Eduardo de Oliveira , Marques Osiris Ricardo Bezerra
Published: August 2020

This article examines the effect of option framing and cognitive load on consumer choices of tourism services. Previous literature has shown that consumers tend to choose more options and spend more money when they begin the choice process from a complete set of options (downgrade/delete framing) than when they start choosing from a more basic set of options (upgrade/add framing). To exam this irrational behavior, we conducted two experimental studies with 561 consumers of leisure travel. The results of the two experiments provided robust evidence on the effect of the downgrade framing strategy on upselling tourism services and revealed that cognitive availability did not prevent consumers from making irrational choices. These findings indicate that decisions involving leisure trips may be even more susceptible than previously thought to cognitive biases and contextual influences due to their emotional and hedonic aspects, extending the existing literature on behavioral economics in tourism.
The psychological burden of a two-stage exchange of infected total hip and knee arthroplasties
Authors: Lueck Eva , Schlaepfer Thomas E , Schildberg Frank A , Randau Thomas M , Hischebeth Gunnar TR , Jaenisch Max , Ossendorff Robert , Wirtz Dieter C , Wimmer Matthias D
Published: August 2020

Infection is one of the most challenging complications after total joint arthroplasties affecting up to 30,000 patients in the US per year. This study investigates the psycho-social burden induced by the two-stage intervention in infected hip or knee replacements. All patients were treated with a two-stage exchange and were assessed at three different timepoints regarding their psychological conditions. Our findings suggest that psychological sequelae after treatment of periprosthetic joint infection are clearly underestimated in the literature and psychological correlates and side effects should be further highlighted during the training process of young surgeons.
Social workers’ construction of cultural competence in polarized cities
Authors: Abu-Rayya Hisham M , Strier Roni , Shwartz-Ziv Tamar
Published: August 2020

Mixed cities are defined as ethnically diverse cities located within turbulent contexts of intensive, ongoing intergroup political conflict. As such, they may pose serious challenges to social workers’ efforts to develop culturally competent practices, especially in the public service sector. This article examined social workers’ constructions of cultural competence in the social public services delivered to Arab and Jewish clients in Israeli mixed cities. Based on extensive qualitative data gathered from 80 public social workers in Haifa, Acre, and Jerusalem, this study discusses the strengths and limitations of the cultural competence approach, especially when applied in the context of varying degrees of political conflict.

Findings

Findings illustrated three approaches to the provision of social welfare services: (1) the “universal” construction, which corresponds to universal and egalitarian value-based approach, by which social work professionalism is claimed sufficient to ensure equal treatment for Israeli Arab and Jewish clients; (2) the “indispensable” cultural approach, which indicates that cultural competence is vital and unavoidable in addressing the ethno-diversity needs of Israeli Arab and Jewish clients in mixed cities; and (3) the “critical” construction, which critiques the cultural competence and universal approaches as lacking the complexity to address the problematic ethno-political nature of mixed city settings.

Applications

The study proposes to adopt an integrated cultural competence approach that combines vital elements of each discrete construction to guide social workers’ practices in mixed cities. Context-informed priorities may occasionally emphasize some elements and minimize others. Institutional support and training is necessary for the proposition to work.
Quantile foliation for modelling performance across body mass and age in Olympic weightlifting
Authors: Perperoglou Aris , Huebner Marianne
Published: August 2020

In this work, we develop ‘quantile foliation’ to predict outcomes for one explanatory variable based on two covariates and varying quantiles. This is an extension of quantile sheets.

Data from World Championships in Olympic weightlifting with athletes aged 13 to 90 are used to study performances across the life span. Weightlifters of all ages compete in body weight classes, and we study performance development for adolescents, age at peak performance and decline for Masters athletes who are 35 years or older.

In prior studies, weightlifting performances were compared with a body mass adjustment formula developed using world records. Although intended for elite athletes with highest performances, this formula was applied to weightlifters of all ages, and age factors for Masters were estimated based on these body mass adjustments. A comparison of youth athletes’ performances for different body mass has not been done.

With quantile foliation, it is possible to examine age-associated patterns of performance increase for youth and to study the decline after reaching the peak performance. This can be done for athletes with different body mass and different performance levels as measured by quantiles. R code and example data are available as supplementary materials.
Influence of the presence of open three-dimensional fiber structures on solid liquid cake filtration of limestone
Authors: Babin Markus , Liu Bo , Krammer Gernot
Published: August 2020

Solid particles in a suspension can be separated effectively through cake filtration where the filter medium is decisive particularly during the initial stage when particle breakthrough can be high. To improve the filtrate quality and throughput, filtration aid additives are used, which are known to alter filter cake structure and thus reduce flow resistance but, in forming clusters, also stabilize fine particles that would otherwise pass through the filter (cake) easily. However, filter aids are costly, increase the complexity of the system and may have adverse effects for subsequent mechanical drying and washing. Instead of supplying additives, four alternative filter media were tested exhibiting an open, three-dimensional structure that reached deeply into the depth of the forming filter cake. An aqueous limestone suspension was investigated in a conventional laboratory test unit. Composite filter medium set-up delivered up to 15% faster filtration. The results indicate that the fiber structures give better performance that reach far into the cake and are oriented not only axially but also radially. In contrary to the initial hypothesis that an axial fiber structure would produce additional drainage channels along the surface of these fibers and thus support but deliquoring, the actual deliquoring performance with air blowing appeared to be slightly less efficient. Although not investigated yet, cake discharge with a 3-D filter layer present poses an additional challenge, rendering the concept of composite filters unpractical.
Dynamics with Cattaneo–Christov heat and mass flux theory of bioconvection Oldroyd-B nanofluid
Authors: Saeed Khan Noor , Shah Qayyum , Sohail Arif
Published: August 2020

Entropy generation in bioconvection two-dimensional steady incompressible non-Newtonian Oldroyd-B nanofluid with Cattaneo–Christov heat and mass flux theory is investigated. The Darcy–Forchheimer law is used to study heat and mass transfer flow and microorganisms motion in porous media. Using appropriate similarity variables, the partial differential equations are transformed into ordinary differential equations which are then solved by homotopy analysis method. For an insight into the problem, the effects of various parameters on different profiles are shown in different graphs.
Influence of market orientation, learning orientation, and innovativeness on operational performance of real estate business
Authors: Phorncharoen Irada
Published: August 2020

Small and medium-sized enterprises (SMEs) play important roles in driving domestic economy. The purpose of this research was to examine the causal relationship model among factors that influence on operational performance (OP) in real estate business (REB), Thailand. The 555 samples of REB entrepreneurs were randomly selected by the multi-stage sampling method. A questionnaire was employed as a research tool for collecting data and analyzed with the structural equation model (SEM). The generated model is fit (χ2/df = .835, p = .993, GFI = .960, AGFI = .945, CFI = 1.000, RMSEA = .000). Findings revealed statistically significant that market orientation (MO) has positively influenced on operational performance, innovativeness (IN) and learning orientation (LO) ( p < 0.001). Learning orientation has positively affected to innovativeness ( p < 0.05) but non-significant affected to operational performance ( p > 0.05). Lastly, innovativeness has positively influenced on operational performance ( p < 0.001). Additionally, learning orientation has mediated between market orientation and innovativeness. The antecedent factors (MO, IN and LO) have cooperatively explained the causal relationship model that influenced on operational performance at 62.80%. Therefore, entrepreneurs in REB are able to achieve strategically their operational performance by consideration and implementation in mainly of the activities related with market orientation and innovativeness.
Morbidity After Metal Allergy to a Total Ankle Implant
Authors: Gaston Tara E. , Kwan Stephanie , Skibicki Hope E. , Cheesman Quincy T. , Daniel Joseph N.
Published: August 2020

Metal allergy to total ankle arthroplasty is rare but can be both an unpredictable and devastating complication. Current literature describing metal allergy in orthopaedics is limited with there being no report to date on metal allergy after total ankle arthroplasty. Our patient underwent a total ankle arthroplasty and developed a diffuse rash 7 weeks postoperatively. The patient then tested positive for a metal allergy and ultimately was converted to an arthrodesis. In the setting of postoperative pain, swelling, erythema, or rash, it is important that metal allergy be on the differential diagnosis. Interestingly, when the patient here underwent allergy testing, only the articulating sides of the implant caused a positive reaction. Thus, allergy testing of both the articular and nonarticular sides of the component is of the utmost importance, as evidenced by the discrepancy found in this case.

Levels of Evidence: Level IV: Case report
Pondering the Potential of Hyaline Cartilage–Derived Chondroprogenitors for Tissue Regeneration: A Systematic Review
Authors: Vinod Elizabeth , Parameswaran Roshni , Ramasamy Boopalan , Kachroo Upasana
Published: August 2020

Objective

Chondroprogenitors have recently gained prominence due to promising results seen in in vitro and animal studies as a potential contender in cell-based therapy for cartilage repair. Lack of consensus regarding nomenclature, isolation techniques, and expansion protocols create substantial limitations for translational research, especially given the absence of distinct markers of identification. The objective of this systematic review was to identify and collate information pertaining to hyaline cartilage–derived chondroprogenitors, with regard to their isolation, culture, and outcome measures.

Design

As per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a web-based search of Scopus and PubMed databases was performed from January 2000 to May 2020, which yielded 509 studies. A total of 65 studies were identified that met the standardized inclusion criteria which comprised of, but was not limited to, progenitors derived from fibronectin adhesion, migrated subpopulation from explant cultures, and single-cell sorting.

Result

Literature search revealed that progenitors demonstrated inherent chondrogenesis and minimal tendency for hypertrophy. Multiple sources also demonstrated significantly better outcomes that bone marrow–derived mesenchymal stem cells and comparable results to chondrocytes. With regard to progenitor subgroups, collated evidence points to better and consistent outcomes with the use of migratory progenitors when compared to fibronectin adhesion assay–derived progenitors, although a direct comparison between the two cell populations is warranted.

Conclusion

Since chondroprogenitors exhibit favorable properties for cartilage repair, efficient characterization of progenitors is imperative, to complete their phenotypic profile, so as to optimize their use in translational research for neocartilage formation.
Investigation of the priority among the roentgenogram measurements in acetabular dysplasia
Authors: Sonekatsu Mayumi , Sonohata Motoki , Inoue Takao , Honke Hidefumi , Kitajima Masaru , Kawano Shunsuke , Taniguchi Wataru , Fukui Daisuke , Mawatari Masaaki
Published: August 2020

Purpose:

There are many radiographic parameters to evaluate developmental dysplasia of the hip joint (DDH); however, the priority between the parameters is unclear. We evaluated the priority of radiographic parameters in DDH.

Methods:

We retrospectively reviewed the radiographs of 82 consecutive patients aged above 85 years without hip osteoarthritis (OA; no osteoarthritis (NO) group), and 28 patients with early stage hip OA were set as the control group (OA group). We used the linear discriminant analysis (LDA) to consider the priority of the following parameters: acetabular roof obliquity (ARO), center-edge (CE) angle, Sharp angle, acetabular head index (AHI), and acetabular depth ratio (ADR).

Results:

The LDA of five different parameters revealed that the NO and OA groups could be almost distinguished with 83.6% accuracy ( p < 0.0001, Wilks’ lambda test). The standardized scoring coefficients were as follows: ARO, −0.23; CE, −0.43; Sharp, −0.29; AHI, 0.97; and ADR, 0.11. The AHI was particularly noticeable in the NO group.

Conclusion:

Dissociation of the AHI in the OA group was significantly higher than that of the other parameters in the OA group compared to the parameters in the NO group. A small AHI may be a risk parameter for hip OA due to DDH.
Effects of Psychological Interventions on the Prevention of Sports Injuries: A Meta-analysis
Authors: Li Shanshan , Wu Qianjin , Chen Zichao
Published: August 2020

Background:

Studies have shown that preventive psychological interventions can reduce the occurrence of sports injuries.

Purpose:

To systematically evaluate the published literature on the effects of psychological interventions on rates of sports injuries and propose a set of psychological interventions to reduce such injuries.

Study Design:

Systematic review; Level of evidence, 1.

Methods:

A total of 11 randomized controlled trials and intervention control trials involving 1287 participants were included. A random-effects model was used to analyze the data. Pooled results were expressed as effect sizes and 95% CIs. Bias and heterogeneity among the studies were assessed, and sensitivity and subgroup analyses were performed.

Results:

Meta-analysis suggested that preventive psychological interventions effectively prevented the occurrence of sports injuries (effect size = –0.55; P < .001), although the studies showed substantial heterogeneity ( I 2 = 94.2%; P < .001), which could not be attributed to specific variables. Nevertheless, sensitivity analysis suggested that overall results were reliable. No significant risk of publication bias was found.

Conclusion:

Preventive psychological interventions moderately reduced the risk of sports injuries. Risk screening also significantly reduced the risk of sports injuries. These interventions should focus on cognitive behavior and be administered in 1 to 6 sessions over 7 to 12 weeks for 60 minutes per session.
Assessing Knowledge-Based and Perceived Health Literacy Among Japanese Adolescents: A Cross-Sectional Study
Authors: Tsubakita Takashi , Kawazoe Nobuo , Ichikawa Mahoko , Matsumoto Satoko , Sugawara Masumi
Published: August 2020

Health literacy assessment is a major aspect of planning health education for adolescents. We evaluated the health literacy of Japanese adolescents using both perceived and knowledge-based health literacy scales. Study questionnaires were administered to 773 junior and senior high school students aged 12 to 18 years. We tested a model describing the hierarchical relations between functional, communicative, critical, and knowledge-based health literacy using path analysis. Critical health literacy was found to be influenced by functional, communicative, and knowledge-based health literacy, while functional and knowledge-based health literacy were correlated. The model, with slight modification, was supported. The result indicates that perceived functional health literacy scores did not directly correlate with higher perceived critical health literacy; rather, they only informed critical health literacy when participants had high knowledge-based health literacy.
Views of Canadian Patients on or Nearing Dialysis and Their Caregivers: A Thematic Analysis
Authors: Barnieh Lianne , King-Shier Kathryn , Hemmelgarn Brenda , Laupacis Andreas , Manns Liam , Manns Braden
Published: August 2020

Background:

Quality of life of patients receiving dialysis has been rated as poor.

Objective:

To synthesize the views of Canadian patients on or nearing dialysis, and those who care for them.

Design:

Secondary analysis of a survey, distributed through dialysis centres, social media and the Kidney Foundation of Canada.

Setting:

Pan-Canadian convenience sample.

Participants:

Patients, their caregivers and health-care providers.

Measurements:

Text responses to open-ended questions on topics relevant to end-stage renal disease.

Methods:

Statements related to needs, beliefs or feelings were identified, and were analysed by thematic content analysis.

Results:

A total of 544 relevant statements from 189 respondents were included for the thematic content analysis. Four descriptive themes were identified through the content analysis: gaining knowledge, maintaining quality of life, sustaining psychosocial wellbeing and ensuring appropriate care. Respondents primarily identified a need for more information, better communication, increased psychosocial and financial support for patients and their families and a strong desire to maintain their previous lifestyle.

Limitations:

Convenience sample; questions were originally asked with a different intent (to identify patient-important research issues).

Conclusions:

Patients on or nearing dialysis and their caregivers identified four major themes, gaining knowledge, maintaining quality of life, sustaining psychosocial wellbeing and ensuring appropriate care, several of which could be addressed by the health care system without requiring significant resources. These include the development of patient materials and resources, or sharing of existing resources across Canadian renal programs, along with adopting better communication strategies. Other concerns, such as the need for increased psychosocial and financial support, require consideration by health care funders.
Normal modes analysis and surface electrostatics of haemagglutinin proteins as fingerprints for high pathogenic type A influenza viruses
Authors: Righetto Irene , Filippini Francesco
Published: August 2020

Background

Type A influenza viruses circulate and spread among wild birds and mostly consist of low pathogenic strains. However, fast genome variation timely results in the insurgence of high pathogenic strains, which when infecting poultry birds may cause a million deaths and strong commercial damage. More importantly, the host shift may concern these viruses and sustained human-to-human transmission may result in a dangerous pandemic outbreak. Therefore, fingerprints specific to either low or high pathogenic strains may represent a very important tool for global surveillance.

Results

We combined Normal Modes Analysis and surface electrostatic analysis of a mixed strain dataset of influenza A virus haemagglutinins from high and low pathogenic strains in order to infer specific fingerprints. Normal Modes Analysis sorted the strains in two different, homogeneous clusters; sorting was independent of clades and specific instead to high vs low pathogenicity. A deeper analysis of fluctuations and flexibility regions unveiled a special role for the 110-helix region. Specific sorting was confirmed by surface electrostatics analysis, which further allowed to focus on regions and mechanisms possibly crucial to the low-to-high transition.

Conclusions

Evidence from previous work demonstrated that changes in surface electrostatics are associated with the evolution and spreading of avian influenza A virus clades, and seemingly involved also in the avian to mammalian host shift. This work shows that a combination of electrostatics and Normal Modes Analysis can also identify fingerprints specific to high and low pathogenicity. The possibility to predict which specific mutations may result in a shift to high pathogenicity may help in surveillance and vaccine development.
Correction to: Statistical methods for predicting tuberculosis incidence based on data from Guangxi, China
Authors: Zheng Yanling , Zhang Liping , Wang Lei , Rifhat Ramziya
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Quantitative analyses of essential fatty acids in cereals and green vegetables by isotope dilution-gas chromatography/mass spectrometry
Authors: Lee Sunyoung , Lim Dong Kyu , Baek Song-Yee , Seo Dongwon , Park Jong-Su , Kwak Byung-Man , Won Jongeun , Lee Joonhee , Kim Byungjoo
Published: August 2020

Abstract

An analytical method for the accurate determination of essential fatty acids in cereals and green vegetables is established based on isotope dilution-gas chromatography/mass spectrometry (ID-GC/MS). In this approach, 13C-labeled fatty acids were added as internal standards to the samples prior to the sample preparation. Repeatability and reproducibility for the analyses of the essential fatty acids extracted from homogenized cereals and green vegetables were examined to validate the ID-GC/MS method. The repeatability and reproducibility were within 2% relative standard deviation. The developed method provides higher-order measurement results with the relative expanded uncertainties of 1–2% and 2–4% for cereals and green vegetables, respectively. Based on the fatty acid measurements, the developed ID-GC/MS method can be used as a candidate reference method for the quantitation of essential fatty acids in cereals and green vegetables. The developed method was also applied to analyze several commercially available products including cereal and vegetable powders.
Correction to: The color of risk protection orders: gun violence, gun laws, and racial justice
Authors: Swanson Jeffrey W.
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Vendor effects on murine gut microbiota and its influence on lipopolysaccharide-induced lung inflammation and Gram-negative pneumonia
Authors: Wolff Nora S. , Jacobs Max C. , Haak Bastiaan W. , Roelofs Joris J. T. H. , de Vos Alex F. , Hugenholtz Floor , Wiersinga W. Joost
Published: August 2020

Background

The microbiome has emerged as an important player in the pathophysiology of a whole spectrum of diseases that affect the critically ill. We hypothesized that differences in microbiota composition across vendors can influence murine models of pulmonary lipopolysaccharide (LPS) inflammation and Gram-negative pneumonia.

Methods

A multi-vendor approach was used with genetically similar mice derived from three different vendors (Janvier, Envigo, Charles River). This model was employed to study the effect on the host response to a pulmonary LPS challenge (1 μgKlebsiella pneumoniaeLPS, intranasal), as well as experimentalK. pneumoniaeinfection (ATCC43816,1 × 104CFU, intranasal).

Results

Gut microbiota analysis revealed profound intervendor differences in bacterial composition as shown by beta diversity and at various taxonomic levels. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 release in lung and bronchoalveolar lavage fluid (BALF) were determined 6 and 24 h after intranasal treatment with LPS. No differences were found between the groups, with the exception for Envigo, showing a higher level of TNFα in lung and BALF at 6 h compared to Janvier and Charles River. In another set of experiments, mice from different vendors were subjected to a clinically relevant model of Gram-negative pneumonia (K. pneumoniae). At 12 and 36 h post-infection, no intervendor differences were found in bacterial dissemination, or TNFα and IL-6 levels in the lungs. In line, markers for organ failure did not differ between groups.

Conclusions

Although there was a marked variation in the gut microbiota composition of mice from different vendors, the hypothesized impact on our models of pulmonary inflammation and severe pneumonia was limited. This is of significance for experimental settings, showing that differences in gut microbiota do not have to lead to differences in outcome.
Application of persimmon (Diospyros kaki L.) peel extract in indigo dyeing as an eco-friendly alternative reductant
Authors: Yoo Dong Il , Shin Younsook
Published: August 2020

The aim of this study is to investigate the efficacy of persimmon (Diospyros kaki L.) peel extract as a reductant for indigo dyeing. Dried persimmon peel was water extracted and its sugar contents and functionalities were determined. Its reducing power was studied in terms of redox potential of the indigo bath and color strength (K/S value) of the ramie fabrics dyed in the indigo reduction bath. Total sugar content of the extract was 74.3%. Antioxidant capacity reached up to 86.0% at 3.5 μg/mL of the extract concentration. The persimmon peel extract had an effect on indigo reduction and the maximum color strength was obtained within one or two day. At 2–3% of the extract concentration, the redox potential of the indigo bath was maintained in the range of − 550 ~ − 600 mV for 10 days. With increase in the extract concentration, reduction state lasted for longer time and higher color strength was obtained. The persimmon peel extract can be used for indigo reduction dyeing as a sustainable, nontoxic, biodegradable alternative to sodium dithionite.
Multiple corticosteroids allergy in a patient with asthma: a case report
Authors: Mahadi Mahrunissa , Wan Ahmad Kammal Wan Syazween Lyana , Md Nor Norazirah , Jamil Adawiyah
Published: August 2020

Background

Allergy towards systemic corticosteroid is rare. This case report discusses the investigations to confirm diagnosis and alternative treatments.

Case presentation

A 51-year-old asthmatic woman developed severe anaphylactic reaction following administration of systemic hydrocortisone. Skin prick, intradermal, and intravenous provocation tests confirmed allergy to triamcinolone, hydrocortisone, and dexamethasone. Skin prick tests (SPTs) were negative to all the aforementioned drugs. Intradermal test (IDT) with triamcinolone 1:10 concentration resulted in a 2-mm wheal associated with rhonchi. IDT with hydrocortisone 1:10 concentration showed an 8-mm wheal with rhonchi. IDTs to dexamethasone and carboxymethylcellulose were negative. Generalized rhonchi were observed with intravenous dexamethasone full concentration challenge.

Conclusions

Corticosteroid allergy should be suspected in asthma patients with worsening bronchospasm after its administration. Due to its rarity, such diagnosis can easily be missed, resulting in increased morbidity and mortality in patients.
The sacred versus the secular in UK psychiatry
Authors: Poole Rob
Published: August 2020

I comment on two papers by Koenig and colleagues that advocate the integration of religion into routine psychiatric practice. In my opinion, their selective overview of research, although useful, lacks balance. It omits any mention of the literature on worldwide scandals over child sex abuse (and other abuses of power) perpetrated and facilitated by religious authority within several faith groups. There is no mention of damaging ‘religiously informed’ treatments such as sexual orientation conversion therapy, which is still practised in the UK despite widespread condemnation. Their recommendations for clinical practice conflate association with causation. They do not offer practice guidance on managing the impact of power imbalances associated with religion in multicultural societies. In summary, despite more than a decade of research and debate, there are still no generally accepted ways of avoiding boundary violations where psychiatrists introduce religion into their clinical practice.
Development and psychometric evaluation of the Transdiagnostic Decision Tool: matched care for patients with a mental disorder in need of highly specialised care
Authors: van Krugten Frédérique C. W. , van der Feltz-Cornelis Christina M. , Boeschoten Manon A. , van Broeckhuysen-Kloth Saskia A. M. , van Eck van der Sluijs Jonna F. , van Ee Elisa , van Es Saskia M. , Schoorl Maartje , Tak Lineke M. , Brouwer Werner B. F. , Hakkaart-van Roijen Leona
Published: August 2020

Background

Early identification of patients with mental health problems in need of highly specialised care could enhance the timely provision of appropriate care and improve the clinical and cost-effectiveness of treatment strategies. Recent research on the development and psychometric evaluation of diagnosis-specific decision-support algorithms suggested that the treatment allocation of patients to highly specialised mental healthcare settings may be guided by a core set of transdiagnostic patient factors.

Aims

To develop and psychometrically evaluate a transdiagnostic decision tool to facilitate the uniform assessment of highly specialised mental healthcare need in heterogeneous patient groups.

Method

The Transdiagnostic Decision Tool was developed based on an analysis of transdiagnostic items of earlier developed diagnosis-specific decision tools. The Transdiagnostic Decision Tool was psychometrically evaluated in 505 patients with a somatic symptom disorder or post-traumatic stress disorder. Feasibility, interrater reliability, convergent validity and criterion validity were assessed. In order to evaluate convergent validity, the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) and the ICEpop CAPability measure for Adults (ICECAP-A) were administered.

Results

The six-item clinician-administered Transdiagnostic Decision Tool demonstrated excellent feasibility and acceptable interrater reliability. Spearman's rank correlations between the Transdiagnostic Decision Tool and ICECAP-A (−0.335), EQ-5D-5L index (−0.386) and EQ-5D-visual analogue scale (−0.348) supported convergent validity. The area under the curve was 0.81 and a cut-off value of ≥3 was found to represent the optimal cut-off value.

Conclusions

The Transdiagnostic Decision Tool demonstrated solid psychometric properties and showed promise as a measure for the early detection of patients in need of highly specialised mental healthcare.
Second malignant neoplasms among survivors of pediatric Hodgkin disease treated with low-dose radiation (15–25.5 Gy) and chemotherapy
Authors: O'Brien M. M. , Donaldson S. S. , Whittemore A. S. , Link M. P.
Published: August 2020

10003

Background: Second malignant neoplasms (SMN) are a known complication of Hodgkin disease (HD) treatment. While it is theorized that lower radiation doses may be associated with lower SMN risk, long-term follow-up of children treated with low-dose radiation is lacking. We report the occurrence of SMN among pediatric HD survivors treated at Stanford with chemotherapy and low-dose radiation from 1970 to 1990. Methods: Patients received 6 cycles of MOPP (mechlorethamine, vincristine, prednisone, procarbazine) with 15–25.5 Gy radiation ± 10 Gy boost or 3 MOPP and 3 ABVD cycles (doxorubicin, bleomycin, vinblastine, dacarbazine) with 15 Gy radiation ± 10 Gy boost. Follow-up was obtained through 9/1/2007. Standardized incidence ratios (SIRs) and absolute excess risk (AER) for SMN were calculated using the SEER9 database (1973–2004). Cumulative SMN incidence was determined by the Kaplan-Meier method. Univariate associations were evaluated with the chi-square test or t-test. Multivariate analysis was performed with Cox proportional hazards regression using chronological age as the time scale. Results: One hundred ten of 112 patients achieved remission; median follow-up is 20.6 years. Four patients developed secondary leukemia. Fifteen patients developed 17 secondary solid tumors (5 thyroid carcinomas, 6 breast carcinomas, 4 sarcomas, 1 bladder paraganglioma, 1 melanoma) at a median of 15.4 years. All solid tumors except the melanoma occurred within or at the margin of radiation fields, ranging in dose from 15–26.5 Gy. There were no cases of lung, gastric, or colorectal carcinoma. Cumulative incidence of any SMN is 17% (95%CI 10.5–26.7) at 20 years following HD diagnosis. The SIR for any SMN is 22.9 (95%CI 14.2–35) with an AER of 93.7 cases per 10,000 person-years. In univariate analysis, older age at HD diagnosis (>11 years) and female gender were associated with SMN (p<0.05). In multivariate analysis, there were no statistically significant associations. Conclusions: The incidence of SMN in pediatric HD survivors is elevated following treatment with chemotherapy and low-dose radiation. Sarcomas, breast, and thyroid carcinomas occurred with similar frequency and latency as found in studies of HD survivors who received high-dose radiation.

No significant financial relationships to disclose.
Temporal trends in cause-specific late mortality among five-year survivors of childhood cancer
Authors: Armstrong G. T. , Pan Z. , Ness K. , Srivastava D. , Robison L. L.
Published: August 2020

10004

Background: Five-year survival rates for childhood cancer have increased over the past 4 decades, increasing the number of long-term survivors. Among 5-yr survivors, the impact of changes in therapy on cause-specific late mortality has not been thoroughly assessed. Methods: Late mortality was evaluated over 3 eras (1974–81, 1982–90, 1991–2000) in 26,643 5-year survivors diagnosed <21 years of age from the SEER population-based registry. Cause-specific mortality was categorized as death from recurrence/progression of primary disease, external causes, and non-recurrence/non-external causes (Non-Recur/Ext) (i.e., deaths from health conditions including sequelae of cancer therapy). Results: All-cause and Recurrence mortality was significantly lower in more recent eras ( Table ). No significant improvement in late mortality attributable to Non-Recur/Ext causes was seen. Additionally, all-cause mortality was significantly lower in more recent eras for 5-year survivors of ALL, AML, Hodgkin, NHL, and CNS tumors, but not neuroblastoma and Ewing's Sarcoma where an increase in cumulative incidence of late mortality was seen in more recent eras. Significant improvement in late mortality from Recurrence by era was seen in most diagnostic groups. Conclusions: All-cause late mortality has improved with more recent eras, attributable to reduced rates of mortality from progression of primary disease (i.e., durable remission). Importantly, however, efforts to reduce the toxicity of more recent therapies have not produced detectable reduction in mortality attributable to other health conditions including sequelae of cancer therapy (non-Recur/Ext causes of death), which would include death from second malignancy, cardiac and pulmonary conditions. Worsening late mortality for 5-year survivors of neuroblastoma and Ewing's sarcoma may be due to improved use of salvage therapies that delay, but do not ultimately prevent death. [Table: see text]

No significant financial relationships to disclose.
Gender differences in long-term dexrazoxane cardioprotection in doxorubicin-treated children with acute lymphoblastic leukemia
Authors: Lipshultz S. E. , Scully R. E. , Lipsitz S. R. , Sallan S. E. , Silverman L. B. , Miller T. L. , Orav E. J. , Colan S. D.
Published: August 2020

10005

Background: Doxorubicin (DOX) causes progressive cardiac dysfunction, particularly in females. Adding dexrazoxane (DZR) to DOX treatment resulted in reduced myocardial injury in children with acute lymphoblastic leukemia (ALL) during Dana-Farber Cancer Institute Protocol 95–01. Methods: We centrally remeasured echocardiograms from childhood high-risk ALL survivors in their first continuous remission who were randomly assigned to treatment with DOX only (n = 66; 30 mg/m2/dose for 10 doses) or DOX plus DZR 30 minutes prior (n = 68; 300 mg/m2/dose). Results: Demographics and median follow-up (DOX 5.3 vs. DZR/DOX 5.5 y) were similar in both arms. Mean left ventricle (LV) end systolic dimension (ESD) z-score was significantly larger than predicted for body-surface area for DOX (mean = 0.46, P-value [deviation of mean from normal] = 0.01) but not so for DZR/DOX (mean = 0.06, P = 0.74); DOX LV fractional shortening (FS; -0.78, P = .001; DZR/DOX = -0.38, P = 0.11) and thickness to dimension ratio (-0.96, P < .001; DZR/DOX = -0.32, P = 0.08) were also abnormal. LV end diastolic posterior wall thickness (EDPWT) was reduced in both groups, though more so for DOX (-1.19, P < .001) than DZR/DOX (-0.74, P < .001). By gender, 5 years post treatment LVESD z-score was significantly larger than normal for DOX males (mean = 0.48, P = 0.04) but not DZR/DOX males (0.19, P = 0.41) or females (DOX female = 0.38, P = 0.22; DZR/DOX female = -0.17, P = 0.56). LVFS z-score was significantly different from normal in DOX females (mean = -1.29, P < .001), but not DZR/DOX females (-0.22, P = 0.54) or males (DOX = -0.45, P = 0.15; DZR/DOX = -0.52, P = 0.09), as was LV thickness to dimension ratio (DOX female = -1.03, P < .001; DZR/DOX female = 0.02, P = 0.93). DZR/DOX females were the only group with normal LVEDPWT z-score (mean = -0.43, P = 0.07; DOX/female = -1.43, P < .001; DOX male = -1.05, P < .001; DZR/DOX male = -0.94, P < .001). Conclusions: While its impact is seen in all groups, primarily females drive the long-term DZR cardioprotective effect. DZR/DOX females exhibit more normal LV dimensions and more appropriate wall thickness for LV dimension, both of which are consistent with less LV remodeling. DZR/DOX females also have more normal LV function than females who received DOX only or males of either group.

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Role of ALK activation in the development and maintenance of the neoplastic phenotype in neuroblastoma
Authors: Regairaz M. , Munier F. , Sartelet H. , Marty V. , Castaing M. , Michiels S. , Fabre M. , Roesel J. , Vassal G.
Published: August 2020

10008

Background: Activating mutations of the Anaplastic Lymphoma Kinase (ALK) receptor could be responsible for most familial neuroblastoma cases and for up to 15% of somatic cases. The objective of the present study was to further investigate the role of ALK activation in neuroblastoma. Methods: Tissue microarrays were constructed containing 101 primary tumors and 56 paired normal tissues. Sections were immunostained with anti-ALK or anti-P-ALK antibodies, and with antibodies directed against the ALK ligands: PTN (Pleiotrophin) or MDK (Midkine). The Wilcoxon signed rank test was applied for comparison of paired data. Associations with prognostic factors were analyzed using t-tests. Effects of the ALK inhibitor TAE684 (Novartis) on cell proliferation and signaling was evaluated in wild-type or mutated ALK neuroblastoma cell lines and xenografts. Results: ALK was expressed in about 100% of tumors and normal tissues, while phospho-ALK was detected in 5% of normal tissues and 50% of tumors. Sequencing of the kinase domain of ALK showed that its phosphorylation was largely independent of mutations and we found that MDK and PTN ligands were expressed in 66% and 50% of tumors, respectively. Interestingly, ALK, P-ALK, and MDK were expressed at higher levels in tumors as compared with paired normal tissues (p < 0.0001), while PTN showed an inverse tendency, being more expressed in normal tissues (p = 0.07). In tumors, P-ALK was associated with good-prognosis factors, including favorable stages (p = 0.01), absence of MYCN amplification (p = 0.05) and a younger age at diagnosis (p = 0.03). Inhibition of cell proliferation by TAE684 was detectible in all neuroblastoma cell lines, regardless of ALK status. However, TAE684 failed to demonstrate antitumor activity in advanced stage neuroblastoma xenografts expressing either a wild-type or a mutated ALK. Interestingly, ALK pathway activation (P-STAT3, P-AKT) was weak or barely detectible in these xenografts. Conclusions: ALK activation occurs during neuroblastoma oncogenesis, along with a concomitant switch between the expressions of PTN and MDK. However, ALK may not be a relevant therapeutic target since in vivo inhibition showed no antitumor activity.

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Phase I study of sorafenib in children with refractory solid tumors: A Children's Oncology Group Phase I Consortium trial
Authors: Widemann B. C. , Fox E. , Adamson P. C. , Baruchel S. , Kim A. , Ingle A. M. , Bender J. Glade , Stempak D. , Balis F. M. , Blaney S. M.
Published: August 2020

10012

Background: Sorafenib, an oral multitargeted kinase inhibitor, is indicated for treatment of adults with refractory renal cell or hepatocelluar carcinoma. We performed a phase I trial to determine the toxicities, maximum tolerated dose (MTD), pharmacokinetics (PK), and pharmacodynamics (PD) of sorafenib in children with refractory solid tumors. Methods: Sorafenib was administered q12h for 28 consecutive day cycles. Cohorts of 3–12 patients were enrolled at 105, 130, 150, 200, and 250 mg/m2/dose dose levels. Results: 34 eligible pts [16M, median age 14.6 yrs, (range, 5–21)] with osteosarcoma (n = 8), rhabdomyosarcoma (n = 3), other sarcomas (n = 13), hepatoblastoma (n = 3), or other solid tumors (n = 7) received 1–22 cycles (median 2). Grade 3 dose-limiting toxicity (DLT) occurred in 4/6 pts at the starting dose (150 mg/m2) and included hypertension (n = 1), rash/urticaria (n = 1), back pain (n = 1), thrombocytopenia (n = 1) and ALT/AST (n = 1). No DLTs were observed at 105 (n = 6) or 130 (n = 3) mg/m2, and the dose was re-escalated to 150 mg/m2 with modified eligibility criteria (normal ALT) and revised guidelines for grading and management of hypertension. Gr 3 DLTs occurred in 1/6 pts (lipase) at 150 mg/m2 and 2/2 pts (hyponatremia, hand-foot syndrome) at 250 mg/m2. At 200 mg/m2 only 1/6 pts experienced DLT (gr 3 ALT). No objective responses were observed, but 2 pts had tumor shrinkage. Sorafenib AUC did not increase proportionally with dose - the mean AUC0–24h was similar at 150 mg/m2 (28±24 μg · h/mL, n = 9) and 200 mg/m2 (28±17 μg · h/mL, n = 4). Tmax was prolonged and variable (10±11 h, n = 19). Plasma VEGFR (n = 13) decreased from 9.9±1.6 ng/mL at baseline to 8.3±1.7 ng/mL by d 28 (p < 0.001). Conclusions: The MTD of sorafenib in children with solid tumors is 200 mg/m2, similar to the adult recommended dose (400 mg).

No significant financial relationships to disclose.
Elevated expression of VEGFR-2 and VEGFA in desmoplastic small round cell tumor (DSRCT) and activity of bevacizumab and irinotecan in a xenograft model of DSRCT
Authors: Magnan H. D. , Chou T. , LaQuaglia M. P. , Gerald W. , Ladanyi M. , Merchant M. S.
Published: August 2020

10016

Background: Desmoplastic small round cell tumor (DSRCT) is an aggressive tumor with poor response to multimodality therapies. Given the vascular nature of many DSRCT, we sought to determine if VEGF targeting could be effective in a preclinical model of DSRCT. Methods: RNA was extracted from frozen tumor samples (DSRCT, alveolar soft part sarcoma, alveolar rhabdomyosarcoma, synovial sarcoma, and Ewing sarcoma) and a human DSRCT cell line, JN-DSRCT. Microarray profiling utilized Affymetrix U133A/B or Affymetrix U133 Plus 2.0 chips. DSRCT xenografts were established by intramuscular injection of 20 million JN-DSRCT cells into the lower extremity of SCID/bg mice. A primary tumor developed within 8 - 12 weeks with concomitant development of abdominal metastases. Mice were treated during primary tumor growth with bevacizumab (5ug/kg IP weekly), irinotecan (2.5mg/kg IP ×10 days q3 weeks), or a combination of both. Results: Microarray data demonstrated an average of 4.5 times higher RNA expression of VEGFR-2 (KDR) in DSRCT tumor samples as compared to the other translocation-associated sarcomas (p = 3.6 E-12). VEGFR-2 was highly expressed in the JN-DSRCT line as compared to other sarcoma lines. VEGFA was also highly overexpressed in the DSRCT line and tumor samples when compared to the other translocation-associated sarcomas (2.5 times, p = 1.1E-10). Xenografts treated with bevacizumab had slowed growth over 100 days compared to control groups (volume of 0.52 mm3 vs 1.52, p = 0.002). Marked long term regressions were evident following treatment with the combination of irinotecan plus bevacizumab compared with irinotecan alone (0.12mm3 vs 0.44 at 100 days, p < 0.0001). Conclusions: VEGFR-2 and VEGFA are overexpressed in DSRCT. DSRCT xenografts were highly responsive to bevacizumab or bevacizumab plus irinotecan. Taken together, the expression data and the sustained response of DSRCT xenografts to bevacizumab suggest that VEGF-dependent angiogenesis is important for DSRCT tumor biology and represents an attractive target for therapy. These studies suggest that irinotecan and bevacizumab should be considered for inclusion in clinical trials for the treatment of DSRCT.

No significant financial relationships to disclose.