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Family navigator programs are becoming increasingly common among families of children with autism. Yet, it is unclear how family navigators are developed; by exploring the input of families of children with autism, such programs can be responsive to family needs. In this study, 12 parents of autistic children from low-resourced communities were interviewed to inform the development of a family navigator program. Findings demonstrated that programs need to prepare navigators to address barriers such as limited knowledge and difficulty accepting an autism diagnosis. Programs should teach navigators to use strategies with families including educating families about services and connecting families with peer support. Program content should reflect direct services, government services, and advocacy strategies. Implications are discussed.

Supplementary Figure 1 - PDF files 2472K, Expression of cell surface markers throughout CLL PBMC

Purpose: Despite advances in the treatment of chronic lymphocytic leukemia (CLL), the disease remains incurable with standard therapies and relapse is inevitable. A growing body of evidence indicates that alterations in the adhesion properties of neoplastic cells play a pivotal role in the development and progression of CLL.Experimental Design: The expression of 71 cell surface molecules was examined on CLL peripheral blood mononuclear cells (PBMCs) over 3 weeks in culture. The most highly upregulated marker, CD62L, was examined further for expression on CD5+/CD19+ CLL cells in vitro and in lymph node and bone marrow biopsies. The prosurvival role of CD62L was examined using a functional blocking antibody and therapeutic potential evaluated by comparison with current chemotherapy agents.Results: Blocking CD62L resulted in apoptosis of CLL cells but not PBMCs from healthy donors suggesting a novel role for CD62L in CLL cell survival. The beneficial effect of coculturing CLL cells with bone marrow stromal cells or endothelial cells does not protect CLL cells from anti-CD62L–related toxicity. Moreover, combining fludarabine or mafosfamide with the anti-CD62L in vitro produced an additive effect both with and without stromal cells.Conclusion: This is the first reported data showing that blocking the activation and homing marker, CD62L, regulates CLL cell survival in vitro. These data also suggest that therapeutic antibodies against CD62L may provide additional clinical benefit to patients with CLL receiving current standard chemotherapy protocols. Clin Cancer Res; 19(20); 5675–85. ©2013 AACR.

Supplementary Figure Legends - PDF files 57K, Figure Legends

Supplementary Table 2 - PDF files 77K, CD markers used in phenotype screen

Supplementary Figure 3 - PDF files 1469K, Correlation of CD62L antibody toxicity and clinical parameters

Supplementary Table 1 - PDF files 69K, Patient Data

Supplementary Table 1 from Induction of Human Arylamine N-Acetyltransferase Type I by Androgens in Human Prostate Cancer Cells

International audience; Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD.

Rapid developments in sensor technology, data processing tools and data storage capability have helped fuel an increased appetite for equipment health monitoring in mechanical systems. As a result, the number of sensors and amount of data collected for health monitoring has grown tremendously. It is hoped that by collecting large quantities of operational data, predictive tools can be developed that will provide operational, maintenance and safety benefits. Data mining and machine learning techniques are important tools in addressing the ensuing challenge of extracting useful results from the data collected. In this work, the sensor data from a gas turbine system was analyzed with the objective of failure modeling and prediction. Previous efforts had used a two-class approach for this problem, to distinguish healthy and failed states of the system. In this work, a third class labelled as deteriorated data is added prior to each failure event to explore the ability of machine learning models to provide early warning of upcoming incidents. Several maintenance incidents were recorded by the sensor system in two separate vehicles. Three approaches to selecting training data were used. The first followed a traditional method of randomly selecting data points from all data according to a desired percentage of failed data to include in training, target ratios between failed and healthy data in each data set, as well as target ratios between training and testing data. The second data selection strategy was to consider data related to failure incidents as a whole and select certain incidents to include in training, and the remaining ones to be unseen in testing. The third approach was cross-validation which is typically used as a technique to evaluate how a classifier will perform on unseen data while still using the entirety of the data to train the final classifier. In addition to investigating training and data selection strategies, the effect of hyperparameter optimization was explored as well as the effect of varying the time period of the deteriorated class. Using the gas turbine data, which included 7 failure incidents and 76 predictor variables, a variety of classifier models of the system were developed in a three-class problem to differentiate healthy, deteriorated and failed system states. The classifier methods included support vector machines, Gaussian Naïve Bayes, random forest, adaboost, multilayer perceptron, k-nearest neighbor, and XG boost. Ensemble models were also created to leverage all the individual classifier models that were developed. This paper will describe the comprehensive results that were obtained using the various approaches and combinations, highlighting the respective benefits and limitations.

The COVID-19 pandemic has brought the most significant disruption to education in history (United Nations, 2020), not least in Tourism, Hospitality, and Events (THE). While growing evidence explores the reshaping of higher education in a COVID-19 era, limited discussion exists on the specific impacts for current and future students of THE and the challenges of rebuilding student and wider stakeholder confidence in THE education and careers. This paper advances this discussion by focusing on the impact of COVID-19 on the THE educational experience. A case example approach is adopted to illustrate the responses of four universities in the pre, during, and post phases of students’ educational journey. Common approaches are drawn using lesson drawing, broader implications and issues affecting institutions and students are explored and lessons for the future of THE education are extrapolated. Finally, the paper also suggests avenues for future research.

Pediatric obstructive sleep apnea has significant negative effects on health and behavior in childhood including depression, failure to thrive, neurocognitive impairment, and behavioral issues. It is strongly associated with an increased risk for chronic adult disease such as obesity and diabetes, accelerated atherosclerosis, and endothelial dysfunction. Accumulating evidence suggests that adult-onset non-communicable diseases may originate from early life through a process by which an insult applied at a critical developmental window causes long-term effects on the structure or function of an organism. In recent years, there has been increased interest in the role of epigenetic mechanisms in the pathogenesis of adult disease susceptibility. Epigenetic mechanisms that influence adaptive variability include histone modifications, non-coding RNAs, and DNA methylation. This review will highlight what is currently known about the phenotypic associations of epigenetic modifications in pediatric obstructive sleep apnea and will emphasize the importance of epigenetic changes as both modulators of chronic disease and potential therapeutic targets.

Background Patients receiving peritoneal dialysis (PD) endure an ongoing regimen of daily fluid exchanges and are at risk of potentially life-threatening complications and debilitating symptoms that can limit their ability to participate in life activities. The aim of the study was to identify the characteristics, content and psychometric properties of measures for life participation used in research in PD. Methods We searched MEDLINE, Embase, PsychInfo, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Central Register of Controlled Trials from inception to May 2020 for all studies that reported life participation in patients on PD. The characteristics, dimensions of life participation and psychometric properties of these measures were extracted and analyzed. Results Of the 301 studies included, 17 (6%) were randomized studies and 284 (94%) were nonrandomized studies. Forty-two different measures were used to assess life participation. Of these, 23 (55%) were used in only one study. Fifteen (36%) measures were specifically designed to assess life participation, while 27 (64%) measures assessed broader constructs, such as quality of life, but included questions on life participation. The 36-Item Short Form Health Survey and Kidney Disease Quality of Life Short Form were the most frequently used measures [122 (41%) and 86 (29%) studies, respectively]. Eight (19%) measures had validation data to support their use in patients on PD. Conclusions The many measures currently used to assess life participation in patients receiving PD vary in their characteristics, content and validation. Further work to pilot and validate potential measures is required to establish a core patient-reported outcome measure to assess life participation in patients receiving PD.

Within luxury hotels targeting multinational segments, frontline service staff are essential to creating unique, personalized experiences for high-value, discerning clientele. Performing emotional labor and utilizing cultural intelligence are key to ensuring exceptional cross-cultural service encounters, but which also create additional pressures for frontline staff. This study aims to assess the impacts of a comprehensive range of emotional labor and cultural intelligence (CQ) on employees’ job satisfaction. Cognitive CQ, motivational CQ, emotive dissonance, and expression of naturally felt emotions were shown to influence job satisfaction. Moreover, the study engaged senior executives from luxury hotels to further discuss the survey results. This approach helped the researchers and practitioners to (re)contextualize the study’s key findings, which were used to reflect on managers’ understanding of cultural intelligence, emotional labor and job satisfaction. The discussions highlighted how these issues were incorporated in luxury hotels’ human resource practices in general and especially during the COVID-19 crisis.

Workplace sexual harassment is an issue that has gained increasing prominence in recent years. Owing to factors such as long working hours, night shifts, the prevalence of alcohol and the intimacy of “hospitality service”, the hospitality/tourism industry is particularly susceptible to the problem of sexual harassment (Davis, 1998; Poulston, 2008b; Yagil, 2008). Sexual harassment can have numerous negative effects, including poor working relationships, monetary loss (Gutek, 1985; Schneider et al., 1997), employee dissatisfaction, loss of attachment to the organisation (Boyd, 2002; Gettman & Gelfand, 2007) and increased employee turnover intentions (Burke, 1995; Laband & Lentz, 1998). At an organisational level, high turnover and labour costs are recognised human resource management challenges in the hospitality/tourism industry and, therefore, it is critical for the industry to pay attention to the problem of sexual harassment. However, protecting associates from unwanted sexual attention, whether from colleagues, managers or customers, is also about an employer’s duty of care for their staff and touches on a range of associated equal opportunities and wider ethical concerns (Goldsmith et al., 1997).The purpose of the study is to investigate sexual harassment among tour leaders in Taiwan. The research objectives of this study are as follows:1.To investigate tour leaders’ experiences of sexual harassment behavior at work; 2.To investigate tour leaders’ awareness of the organisational policies/regulations relating to sexual harassment in the workplace.

Prognosis of CLL patients has historically been determined by categorization into Rai or Binet risk groups based on physical examination and blood counts, however given heterogeneity within Rai or ...

Social decision making is often challenging for autistic individuals. Twenty autistic adolescents made decisions in the socially interactive context of a one-shot ultimatum game, and performance was compared to a large matched typical reference sample. Theory of mind, executive functioning and emotion regulation were measured via direct assessments, self- and parent report. Relative to the reference sample, autistic adolescents proposed fewer fair offers, and this was associated with poorer theory of mind. Autistic adolescents responded similarly to the reference sample when making decisions about offers proposed to them, however they did not appear to down regulate their negative emotion in response to unfair treatment in the same way. Atypical processes may underpin even apparently typical decisions made by autistic adolescents.

Pressure ulcer interventions are commonly assessed with measures of seating interface pressure, such as peak pressure gradients (PPGs). Decreases in PPG magnitudes may reduce pressure ulcer risk by decreasing tissue deformation and increasing tissue perfusion of at-risk weight-bearing tissues. Changes in PPG directions, which have previously been overlooked in the seating pressure literature, may provide a transient increase in blood flow to at-risk tissues, even if the PPG magnitude and location remain the same. The purpose of this study was to assess both PPG components in response to combinations of wheelchair tilt and recline angles. Thirteen power wheelchair users were recruited into the study. Six combinations of wheelchair tilt (15°, 25°, and 35°) and recline (10° and 30°) were tested in random order. Each combination was tested with 5-min upright sitting, 5-min tilt and recline, and 5-min maximal pressure relief recovery. Changes in PPG magnitudes and PPG directions under the left ischial tuberosity were computed for the six angle combinations. The findings in this study suggested that when combining wheelchair tilt and recline, the recline function may be particularly useful in reducing PPG magnitudes, while the tilt function may be particularly useful in manipulating PPG directions.

Much of the literature on authenticity is Western-centric, while little work addresses the concept in the Asian environment. The literature relating to authenticity from Asian tourists’ point of view is even underdeveloped. This study therefore aims to fill the knowledge gap by investigating Chinese tourists’ perspective of authenticity. It also examines tourists’ perceived authenticity as a multi-dimensional construct in a consumer-based model, the relationship with heritage motivation and tourist satisfaction. Findings indicate that Chinese tourists’ perceptions of authenticity are closely related to objective and constructive authenticity. The study demonstrates that heritage motivation has a significant positive influence on perceived authenticity and that perceived authenticity has a strong ability to predict tourist satisfaction.

Advances in technology have enabled the installation of an increasing number of sensors in various mechanical systems allowing for more detailed equipment health monitoring capabilities. It is hoped the sensor data will enable development of predictive tools to prevent system failures. This work describes continued analysis of sensor data surrounding a seizure of a turbocharger within a propulsion system. The objective of the analysis was to characterize and distinguish healthy and failed states of the turbocharger. The analysis approach included mapping of multi-dimensional sensor data to a low-dimensional space using various linear and nonlinear techniques in order to highlight and visualize the underlying structure of the information. To provide some physical insight into the structure of the low-dimensional representation, the transformation plots were analyzed from the perspective of several engine signals. By overlaying operating ranges of individual sensor signals, certain regions of the mappings could be associated with distinct operational states of the engine, and several anomalies could be related to various points in the turbocharger seizure. Although the failed points did not map to an obvious outlier location in the transformations, incorporating expert domain knowledge with the data mining tools significantly enhanced the insight derived from the sensor data.

This study aims to explore the extent of gender differences among Chinese tour leaders’ roles and the relationship of such differences to emotional labour, perceived organisational support and perceived supervisor support. The findings revealed surface acting and deep acting to be the two major strategies of emotional labour. Gender difference is found in performing surface acting strategies. Further analysis of gender differences showed that women tour leaders perform better with more care from organisation and rewards. Men tour leaders perform better with more supervisors’ care, concern, recognition and appreciation; and job training and facilitation.

In this work, the sensor data related to a diesel engine system and specifically its turbocharger subsystem were analyzed. An incident where the turbocharger seized was recorded by dozens of standard turbocharger-related sensors. By training models to distinguish between normal healthy operating conditions and deteriorated conditions, there is an opportunity to develop prognostic and predictive tools to ideally help prevent a similar occurrence in the future. Analysis of this event provides an opportunity to identify changes in equipment indicators with a known outcome. A number of data analysis tools were used to characterize the healthy and deteriorated states of the turbocharger system, including various supervised classification as well as semi-supervised and unsupervised anomaly detection techniques. The leader clustering algorithm was also implemented to reduce the amount of data to train and develop the models. This paper describes the results of this modeling process, validated by testing on healthy data from the same propulsion system and a second distinct one. Although this problem posed challenges due to the severely imbalanced class distribution, the supervised classifiers, in particular Support Vector Machine (SVM) and Random Forest (RF), performed very well in all metrics while the unsupervised anomaly detection models achieved near-perfect accuracy for identifying healthy turbocharger states.

Heritage, especially with World Heritage status, is increasingly becoming the main attraction of many tourist destinations. Heritage tourism is also the major tourism product in Hue city, Vietnam. Hitherto, there are almost no official statistics and research pertaining to heritage tourism as well as heritage tourists in Hue. This study aims at providing a preliminary profile of heritage tourists to Hue city and identifying different categories of heritage tourists, with a special focus on package tourists. The international heritage tourists’ profile seems to be similar to official statistics of international arrivals, indicating almost no difference in socio-demographic profile between heritage tourists and general tourists in the context of Hue. Various significant differences were found between international and domestic tourists in terms of tourist characteristics, trip profile and the perception of Hue. Adopting McKercher’s [(2002) Towards a classification of cultural tourists. International Journal of Tourism Research, 4, 29–38] cultural tourist classification, five categories of heritage tourists were identified, including purposeful heritage tourists, sightseeing heritage tourists, casual heritage tourists, incidental heritage tourists and serendipitous heritage tourists. Among these, sightseeing heritage tourists and purposeful heritage tourists were dominant.

This paper is about the position of workforce and employment considerations within the sustainable tourism narrative. The paper aims to address the relative neglect of this area within the discourse of sustainable tourism and highlights references to the workforce within the United Nations’ 2030 Agenda for Sustainable Development. The discussion follows the emerging field of sustainable human resource management and the contribution that this can make to meeting both the UN Sustainable Development Goals and to enhancing the recognition of workforce and employment issues within the related debate in tourism. The body of the paper highlights examples of key dimensions of work and employment across varied tourism contexts, where sustainability is of increasing consequence and significance. The paper concludes by drawing together the implications of these “mini-cases” and locating them within key principles of the 2030 Agenda for Sustainable Development.

Background: Breast conserving surgery (BCS) is preferred for suitable candidates, while mastectomy (MTX) with reconstruction (MTX + R) is considered a better option for patients requiring MTX. In Hong Kong, the rates of BCS and breast reconstruction are relatively low. This paper aims to study the surgical options and their predictors among Hong Kong breast cancer patients. Methods: Data is retrieved from the Hong Kong Breast Cancer Registry (HKBCR) from 2007 to 2013. A total of 4519 Stage I–II breast cancer patients who had surgical treatments were included in this retrospective study. Results: Our multivariate logistic regression shows that people who were younger (age

Resistance to therapeutic antibodies in chronic lymphocytic leukaemia (CLL) is common. In this study, we show that therapeutic antibodies against CD62L (CD62L-Ab) or CD20 (obinutuzumab) were able to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis (ADP) in primary cultures of CLL cells. CLL cells derived from patients with active disease requiring treatment displayed resistance to these antibodies, whereas patients with stable disease were sensitive. Using enrichment strategies and transcriptomic analyses, we show that antibody-dependent tumour cell killing was FcγR-dependent and mediated by macrophages. Moreover, we show that resistance cannot be attributed to total numbers or established subtypes of monocytes/macrophages, or the efficiency with which they bind an immune complex. Rather, ADCC/ADP resistance was due to reduced signalling activity through the activating FcγRs resulting in the transfer of dominance to the inhibitory FcγRIIb within macrophages. Most significantly, we show that resistance is an actionable event that could be reversed using inhibitors of FcγRIIb signalling in primary cultures of CLL cells that were previously insensitive to obinutuzumab or CD62L-Ab.

Chronic lymphocytic leukemia (CLL) is predominantly a disease of accumulation rather than rapid proliferation. To date, no cell lines exist, as CLL cells undergo rapid apoptosis when cultured in vitro, suggesting that a favorable in vivo microenvironment is required. To identify survival signals we cultured primary CLL peripheral blood mononuclear cells (PBMCs) at high density, which has previously been shown to dramatically improve survival. Using antibody arrays we measured the level of 42 cytokines in culture supernatants and showed that inerleukin-6 (IL-6), IL-8, CXCL2 and CCL2 were highly up-regulated in culture. This is the first report to describe a role for CCL2 and CXCL2 in CLL cell survival. Importantly, CXCL2, IL-6 and IL-8 were significantly up-regulated in primary patient plasma. The addition of either CXCL2 or CCL2 enhanced CLL cell survival, while antibodies blocking these chemokines reduced survival. Co-culture of CLL cells and PBMC accessory cells separated by transwells provided a similar degree of survival protection compared to normal culture, whereas CLL cells cultured alone died rapidly. Interestingly, CCL2 and CXCL2 appeared to be produced by CLL cells but only when co-cultured with accessory cells. Thus, we speculate that accessory cells release soluble factors that promote the production of these pro-survival chemokines from CLL cells and physical interactions are not required. Our data support the concept that the CLL microenvironment is critical, and suggests that soluble factors are more important than physical interactions.

This study aims to explore the factors affecting the success of a popular tourist product, namely, theatrical performance, within the context of China's tourism industry and develop a model based on previously successful productions. Using qualitative software, 22 Chinese-language articles on theatrical performances are analyzed to generate a list of success factors, classified as internal and external. The internal factors are storyline and performing, market positioning and marketing strategy, investment and financial support, operation and management, performing team, outdoor venue, indoor/outdoor stage supporting facilities, continuous improvement, and production team. The external factors are collaboration between cultural industries and local tourism, government support, privatization, and social and cultural effect. This study also provides suggestions for the future development of theatrical performances in China.

BACKGROUND: Current measures for breast cancer prevention and options for treatment adopted in Hong Kong are mainly based on research data and clinical evidence from overseas. It is essential to establish a cancer-specific registry to monitor the status of breast cancer in Hong Kong. OBJECTIVES: We summarized the current status of breast cancer in Hong Kong based on the data collected from Hong Kong Breast Cancer Registry (HKBCR). METHODS: Prevalent and newly diagnosed breast cancers (including in situ and invasive breast cancers) were registered in the HKBCR. Information on patient demographics, risk factors, medical information, and survival were analyzed and reported in this study. RESULTS: Data of 2,330 breast cancer patients were analyzed. We observed an earlier median age at diagnosis in Hong Kong than those reported in other countries. Distribution of cancer stage was: stage 0 (11.4%), stage I (31.4%), stage II (41%), stage III (12.5%), stage IV (0.8%), and unclassified (2.9%). The percentages of patients who received surgery, chemotherapy, radiation therapy, and endocrine therapy were 98.7, 67.9, 64.8, and 64.1%, respectively. At a median follow-up of 1.2 years, locoregional recurrence was recorded at 2%, distant recurrence at 2.8%, and breast-cancer-related mortality at 0.3%. CONCLUSIONS: The HKBCR serves as a surveillance program to monitor disease and treatment patterns. It is pivotal to support research for more effective breast cancer prevention and treatment strategies in Hong Kong.

Management theories, especially those in the area of human resource management, are predominantly Western-centric in origin and in the empirical testing that underpins them. The purpose of this paper is to explore perceptions of one such theory, employee empowerment, in an Asian context. Information gathered from an open ended questionnaire and focus groups provide an in-depth examination of hotel managers' perceptions and practice of empowerment in the workplace. This study provides tentative indicators of significant culturally-driven differences in the understanding and application of employee empowerment (in terms of both research and practice) between Western and Asian contexts. The results of this study indicate that empowerment in Asian cultures relates much more to the individual and his/her merits, in contrast to organizationally-driven empowerment in Western countries. The findings also indicate that empowerment by hotel managers is related to the level of personal trust the manager has in an employee.

This article aims to develop a profile of the educational attainments, skills and attitudes, career needs, and plans of tour guides in China based on a study of both permanent and freelance guides. The findings indicate that tour guides are ill‐prepared for the booming tourism industry. The workforce in China's tour guide sector is currently dominated by young staff with an educational background in vocational and/or professional schools. Although a guide's work is challenging and demanding, tour guides in China do not appear to be highly respected either within society or among family circles. Tour guide work offers unstable career development prospects due to the relatively limited promotional prospects and poor training opportunities available. To attract and retain qualified guides, a focus on career management and training qualifications should be regarded as an urgent priority in human resources strategies. 本文以职业导游和兼职导游为调研对象，对中国导游的教育程度、技能、态度以及职业发展需要和计划的情况进行研究。研究结果显示导游没有做好充分准备以应付旅游业的急速发展。目前中国导游的主力主要是...

With more than 5.5 million fractures and 1 million bone repair surgeries annually, bone graft plays a significant role in aiding fracture repair. In the United States alone, surgeons perform an estimated 500,000 to 600,000 bone grafting procedures annually. With the advent of possibilities from bone substitutes, growth factors, and stem cell research, the potential for enhancing bone healing is vast. This article attempts to survey current trends and to highlight upcoming techniques in the future of bone healing.

The roles of IGF-I and IGFBP-3 in the regulation of proximal tubule, and renal cell carcinoma cell proliferation.BackgroundInsulin-like growth factor I (IGF-I), a potent proximal tubule cell (PTC) mitogen, has been implicated in the progression of many human cancers. Our previous work on human renal tissues has suggested that IGF-I and several of its binding proteins (IGFBP-3 and -6) are up-regulated in clear cell renal cell carcinoma (RCC).MethodsTo further elucidate the role of IGF-I and IGFBPs in RCC growth, immunohistochemistry, thymidine incorporation, and Western analysis were performed in primary cultures of normal PTC (priPTC) and clear-cell RCC (priRCC), as well as in SN12K1 cells (a cell line derived from metastatic RCC).ResultsBy immunohistochemistry, IGFBP-3 and IGF-I were prominently expressed in SN12K1 cells, and weakly expressed in priPTC and priRCC. Incubation with 100ng/mL IGF-I significantly augmented DNA synthesis by priPTC (mean ± SD 120.7%± 19.7% of controls, P < 0.05), priRCC (238.7%± 279.9% of controls, P < 0.01), and SN12K1(120.0%± 22.9% of controls, P < 0.05). Neutralizing antibodies to IGF-I and IGF-I receptor significantly suppressed SN12K1 growth (81.9%± 13.5% of control, P < 0.01 and 87.4%± 16.2% of control, P < 0.05, respectively). Removal of endogenous IGFBP-3 by an anti-IGFBP-3 increased SN12K1 DNA synthesis (243.9%± 35.3% of control, P < 0.001), which was partially abrogated by coincubation with exogenous IGFBP-3 (135.97%± 5.9% of controls, P < 0.001). Using Western analysis, IGFBP-3 expression was enhanced in IGF-I–stimulated SN12K1 cells exposed to exogenous IGF-I. Coincubation with anti-IGFBP-3 further enhanced IGF-I–induced DNA synthesis.ConclusionRCC cells express IGF-I and IGFBP-3, and are responsive to exogenous IGF-I stimulation. Moreover, in SN12K1 cells (derived from metastatic RCC), autocrine IGF-I and IGFBP-3 actions, respectively, stimulated and inhibited growth. These results suggest that IGF-I and IGFBP-3 may be potential candidates for therapeutic manipulation in patients with advanced RCC.

Erythropoietin (EPO) has recently been shown to exert important cytoprotective and anti-apoptotic effects in experimental brain injury and cisplatin-induced nephrotoxicity. The aim of the present study was to determine whether EPO administration is also renoprotective in both in vitro and in vivo models of ischaemic acute renal failure.Primary cultures of human proximal tubule cells (PTCs) were exposed to either vehicle or EPO (6.25-400 IU/ml) in the presence of hypoxia (1% O(2)), normoxia (21% O(2)) or hypoxia followed by normoxia for up to 24 h. The end-points evaluated included cell apoptosis (morphology and in situ end labelling [ISEL], viability [lactate dehydrogenase (LDH release)], cell proliferation [proliferating cell nuclear antigen (PCNA)] and DNA synthesis (thymidine incorporation). The effects of EPO pre-treatment (5000 U/kg) on renal morphology and function were also studied in rat models of unilateral and bilateral ischaemia-reperfusion (IR) injury.In the in vitro model, hypoxia (1% O(2)) induced a significant degree of PTC apoptosis, which was substantially reduced by co-incubation with EPO at 24 h (vehicle 2.5+/-0.5% vs 25 IU/ml EPO 1.8+/-0.4% vs 200 IU/ml EPO 0.9+/-0.2%, n = 9, P0.05). At high concentrations (400 IU/ml), EPO also stimulated thymidine incorporation in cells exposed to hypoxia with or without subsequent normoxia. LDH release was not significantly affected. In the unilateral IR model, EPO pre-treatment significantly attenuated outer medullary thick ascending limb (TAL) apoptosis (EPO 2.2+/-1.0% of cells vs vehicle 6.5+/-2.2%, P0.05, n = 5) and potentiated mitosis (EPO 1.1+/-0.3% vs vehicle 0.5+/-0.3%, respectively, P0.05) within 24 h. EPO-treated rats exhibited enhanced PCNA staining within the proximal straight tubule (6.9+/-0.7% vs vehicle 2.4+/-0.5% vs sham 0.3+/-0.2%, P0.05), proximal convoluted tubule (2.3+/-0.6% vs vehicle 1.1+/-0.3% vs sham 1.2+/-0.3%, P0.05) and TAL (4.7+/-0.9% vs vehicle 0.6+/-0.3% vs sham 0.3+/-0.2%, P0.05). The frequency of tubular profiles with luminal cast material was also reduced (32.0+/-1.6 vs vehicle 37.0+/-1.3%, P = 0.05). EPO-treated rats subjected to bilateral IR injury exhibited similar histological improvements to the unilateral IR injury model, as well as significantly lower peak plasma creatinine concentrations than their vehicle-treated controls (0.04+/-0.01 vs 0.21+/-0.08 mmol/l, respectively, P0.05). EPO had no effect on renal function in sham-operated controls.The results suggest that, in addition to its well-known erythropoietic effects, EPO inhibits apoptotic cell death, enhances tubular epithelial regeneration and promotes renal functional recovery in hypoxic or ischaemic acute renal injury.

The recent literature has addressed many financial and managerial aspects of downsizing, end-user computing, outsourcing, re-engineering, and CASE-based applications development. In contrast, little is known about how the IS community perceives and is affected by these emerging practices. A recent study examined the perceptions and attitudes of IS specialists in Hong Kong, London and New York City. This article reports on the survey results from Hong Kong, where staff members of IS departments expressed serious concerns about emerging IT management practices as well as their changing roles and responsibilities. Few IS specialists foresaw the rise of systems integrators/coordinators or favoured changes away from the traditional IS career path. These attitudes were related to perceptions of skill set inadequacy, limited training and self-development opportunities, and reluctance to serve as change agents. Both gender and work experience significantly affected perceptions as well as attitudes. The implications for both IS and human resource management are considered while specific areas for further research are identified.

Purpose: Despite advances in the treatment of chronic lymphocytic leukemia (CLL), the disease remains incurable with standard therapies and relapse is inevitable. A growing body of evidence indicates that alterations in the adhesion properties of neoplastic cells play a pivotal role in the development and progression of CLL. Experimental Design: The expression of 71 cell surface molecules was examined on CLL peripheral blood mononuclear cells (PBMCs) over 3 weeks in culture. The most highly upregulated marker, CD62L, was examined further for expression on CD5+/CD19+ CLL cells in vitro and in lymph node and bone marrow biopsies. The prosurvival role of CD62L was examined using a functional blocking antibody and therapeutic potential evaluated by comparison with current chemotherapy agents. Results: Blocking CD62L resulted in apoptosis of CLL cells but not PBMCs from healthy donors suggesting a novel role for CD62L in CLL cell survival. The beneficial effect of coculturing CLL cells with bone marrow stromal cells or endothelial cells does not protect CLL cells from anti-CD62L–related toxicity. Moreover, combining fludarabine or mafosfamide with the anti-CD62L in vitro produced an additive effect both with and without stromal cells. Conclusion: This is the first reported data showing that blocking the activation and homing marker, CD62L, regulates CLL cell survival in vitro. These data also suggest that therapeutic antibodies against CD62L may provide additional clinical benefit to patients with CLL receiving current standard chemotherapy protocols. Clin Cancer Res; 19(20); 5675–85. ©2013 AACR.

The development of accurate load spectra for helicopters is necessary for life cycle management and life extension efforts. This paper explores continued efforts to utilize evolutionary computation (EC) methods and machine learning techniques to estimate several helicopter dynamic loads. Estimates for the main rotor normal bending (MRNBX) on the Australian Black Hawk helicopter were generated from an input set that included thirty standard flight state and control system parameters under several flight conditions (full speed forward level flight, rolling left pullout at 1:5g, and steady 45◦ left turn at full speed). Multiobjective genetic algorithms (MOGA) used in combination with the Gamma test found reduced subsets of predictor variables with modeling potential. These subsets were used to estimate MRNBX using Cartesian genetic programming and neural network models trained by deterministic and evolutionary computation techniques, including particle swarm optimization (PSO), differential evolution (DE), and MOGA. PSO and DE were used alone or in combination with deterministic methods. Different error measures were explored including a fuzzy-based asymmetric error function. EC techniques played an important role in both the exploratory and modeling phase of the investigation. The results of this work show that the addition of EC techniques in the modeling stage generated more accurate and correlated models than could be obtained using only deterministic optimization., IEEE 2012 Congress on Evolutionary Computation CEC 2012, June 10-15, 2012, Brisbane, Australia

Airframe structural integrity assessment is a major activity for all helicopter operators. The accurate estimation of component loads is an important element in life cycle management and life extension efforts. This paper explores continued efforts to utilize a wide variety of computational intelligence techniques to estimate some of these helicopter dynamic loads. Estimates for two main rotor sensors (main rotor normal bending and pushrod axial load) on the Australian Black Hawk helicopter were generated from an input set that consisted of thirty standard flight state and control system parameters. These estimates were produced for two flight conditions: full speed forward level flight and left rolling pullout at 1.5g. Two sampling schemes were attempted, specifically k-leaders sampling and a biased sampling scheme. Ensembles were constructed from the top performing models that used conjugate gradient, Levenberg-Marquardt (LM), extreme learning machines, and particle swarm optimization (PSO) as the learning method. Hybrid and memetic approaches combining the deterministic optimization and evolutionary computation techniques were also explored. The results of this work show that using a biased sampling scheme significantly improved the predictions, particularly at the peak values of the target signal. Hybrid models using PSO and LM learning provided accurate and correlated predictions for the main rotor loads in both flight conditions., IEEE 2012 International Joint Conference on Neural Networks (IJCNN 2012), June 10-15, 2012, Brisbane, Australia

Accurately determining component loads on a helicopter is an important goal in the helicopter structural integrity field. While measuring dynamic component loads directly is possible, these measurement methods are not reliable and are difficult to maintain. This paper explores the potential of using computational intelligence methods to estimate some of these helicopter dynamic loads. Thirty standard timedependent flight state and control system parameters were used to construct a set of 180 input variables to estimate the main rotor blade normal bending during forward level flight at full speed. Unsupervised nonlinear mapping was used to study the structure of the multidimensional time series from the predictor and target variables. Based on these criteria, black and white box modeling techniques (including ensemble models) for main rotor blade normal bending prediction were applied. They include neural networks, local linear regression and model trees, in combination with genetic algorithms based on residual variance (gamma test) for predictor variables selection. The results from this initial work demonstrate that accurate models for predicting component loads can be obtained using the entire set of predictor variables, as well as with smaller subsets found by computational intelligence based approaches., The 2011 International Joint Conference on Neural Networks (IJCNN), July 31 - August 5, 2011, San Jose, California, USA

This study seeks to explore attributes affecting the level of tourist satisfaction with and loyalty towards theatrical performance in China. Based on four focus group discussions with 31 participants, the study identifies 34 attributes that affect the level of tourist satisfaction with theatrical performance, and groups them into five categories: stage, performance, venue, service, and tourist-related attributes. The findings on tourist loyalty reveal that most of the respondents would not watch the same theatrical performance alone in the future; however, they would recommend it to others. The study concludes with a discussion of the rich and insightful findings and their implications for tourism industry practitioners.

Human arylamine N-acetyltransferases (NAT) bioactivate arylamine and heterocyclic amine carcinogens present in red meat and tobacco products. As a result, factors that regulate expression of NATs have the potential to modulate cancer risk in individuals exposed to these classes of carcinogens. Because epidemiologic studies have implicated well-done meat consumption as a risk factor for prostate cancer, we have investigated the effects of androgens on the expression of arylamine N-acetyltransferase type I (NAT1). We show that NAT1 activity is induced by R1881 in androgen receptor (AR)–positive prostate lines 22Rv1 and LNCaP, but not in the AR-negative PC-3, HK-293, or HeLa cells. The effect of R1881 was dose dependent, with an EC50 for R1881 of 1.6 nmol/L. Androgen up-regulation of NAT1 was prevented by the AR antagonist flutamide. Real-time PCR showed a significant increase in NAT1 mRNA levels for R1881-treated cells (6.60 ± 0.80) compared with vehicle-treated controls (1.53 ± 0.17), which was not due to a change in mRNA stability. The increase in NAT1 mRNA was attenuated by concurrent cycloheximide treatment, suggesting that the effect of R1881 may not be by direct transcriptional activation of NAT1. The dominant NAT1 transcript present following androgen treatment was type IIA, indicating transcriptional activation from the major NAT1 promoter P1. A series of luciferase reporter deletions mapped the androgen responsive motifs to a 157-bp region of P1 located 745 bases upstream of the first exon. These results show that human NAT1 is induced by androgens, which may have implications for cancer risk in individuals. [Cancer Res 2007;67(1):85–92]