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Background Cancer cachexia causes significant morbidity and mortality in advanced lung cancer patients. Clinical benefit of β-hydroxy-β-methylbutyrate, arginine, and glutamine (HMB/Arg/Gln) was assessed in newly diagnosed patients. Methods NOURISH, a prospective, two-arm, open-label, multi-centre, randomised controlled phase II trial compared cachexia in patients who received HMB/Arg/Gln with those who did not. All patients received structured nutritional, exercise and symptom control via a Macmillan Durham Cachexia Pack. Conducted in five UK centres, patients aged > 18 years, with newly diagnosed advanced small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC), who were able to take oral nutrition, with a performance status of 0-to-2 and a life expectancy > 4 months were eligible for trial entry. Patients suitable for treatment with curative intent were ineligible. The trial was designed as a signal-seeking pilot study with target recruitment of 96 patients. One-to-one randomisation was stratified by diagnosis (SCLC or NSCLC), stage of disease (locally advanced or metastatic) and performance status. The primary outcome measure was treatment success defined as a patient being alive without significant loss of lean body mass (not > 5%) by 12 weeks. Secondary outcome measures included quality of life. Results Between February-2012 and February-2013, 38 patients were recruited, 19 to each arm. Baseline characteristics were balanced. The trial was halted due to slow accrual and partial adherence. Trial data demonstrated no evidence of treatment benefit. No serious adverse events were reported during the trial. Conclusions Further evaluation of HMB/Arg/Gln in this setting could not be recommended on the basis of this trial. Clinical trial registration ISRCTN registry: 39911673; 14-Apr-2011 10.1186/ISRCTN39911673.

No abstract available.

This conceptual paper suggests that the distinction between an autocratic and democratic leadership orientation may serve as an important moderator of the relationship between key organizational characteristics and workplace bullying. More specifically, we explore leader autocratic vs. democratic power orientations and leader agentic vs. communal orientations as the theoretical bases for developing a new model of perceived leadership orientation as a moderator of the relationships between certain key organizational characteristics and perceptions of workplace bullying behavior. Our model proposes differential moderating effects for both leader autocratic-democratic power orientation and leader agentic-communal orientation. Particularly, we contend that democratic and communal leadership orientations may lead to fewer perceptions of bullying in the workplace. We conclude with a discussion of our model’s practical implications and suggestions for future research on this subject.

This study integrates past research addressing decision‐making, employee selection, and influence processes in an attempt to provide both a theoretical and empirical foundation for future research addressing initial impressions throughout the interview process. Using data from a simulated hiring situation comprised of 28 recruiters and 229 applicants, the results suggest that initial impressions formed at the beginning of the interview make a substantive impact on final impressions. However, impressions formed at the career fair do not appear to impact final impressions without considering the interactive effects of decision confidence. Hypotheses proposing that decision confidence would moderate linkages between initial impressions formed at the beginning of the interview and both interview scores and final impressions were not supported. We discuss the theoretical and practical implications of these findings for selection.

Importance Perioperative chemotherapy and surgery are a standard of care for operable gastroesophageal adenocarcinoma. Anti-HER2 therapy improves survival in patients with advanced HER2-positive disease. The safety and feasibility of adding lapatinib to perioperative chemotherapy should be assessed. Objectives To assess the safety of adding lapatinib to epirubicin, cisplatin, and capecitabine (ECX) chemotherapy and to establish a recommended dose regimen for a phase 3 trial. Design, Setting, and Participants Phase 2 randomized, open-label trial comparing standard ECX (sECX: 3 preoperative and 3 postoperative cycles of ECX with modified ECX plus lapatinib (mECX+L). This multicenter national trial was conducted in 29 centers in the United Kingdom in patients with histologically proven, HER2-positive, operable gastroesophageal adenocarcinoma. Registration forERBB/HER2testing took place from February 25, 2013, to April 19, 2016, and randomization took place between May 24, 2013, and April 21, 2016. Data were analyzed May 10, 2017, to May 25, 2017. Interventions Patients were randomized 1:1 open-label to sECX (3 preoperative and 3 postoperative cycles of 50 mg/m2of intravenous epirubicin on day 1, 60 mg/m2intravenous cisplatin on day 1, 1250 mg/m2 of oral capecitabine on days 1 through 21) or mECX+L (ECX plus lapatinib days 1 through 21 in each cycle and as 6 maintenance doses). The first 10 patients in the mECX+L arm were treated with 1000 mg/m2of capecitabine and 1250 mg of lapatinib per day, after which preoperative toxic effects were reviewed according to predefined criteria to determine doses for subsequent patients. Main Outcomes and Measures Proportion of patients experiencing grade 3 or 4 diarrhea with mECX+L. A rate of 20% or less was considered acceptable. No formal comparison between arms was planned. Results Between February 2013, and April 2016, 441 patients underwent central HER2 testing and 63 (14%) were classified as HER2 positive. Forty-six patients were randomized; 44 (24 sECX, 20 mECX+L) are included in this analysis. Two of the first 10 patients in the mECX+L arm reported preoperative grade 3 diarrhea; thus, no dose increase was made. The primary endpoint of preoperative grade 3 or 4 diarrhea rates were 0 of 24 in the sECX arm (0%) and 4 of 20 in the mECX+L arm (21%). One of 24 in the sECX arm and 3 of 20 in the mECX+L arm stopped preoperative treatment early, and for 4 of 19 in the mECX+L arm, lapatinib dose was reduced. Postoperative complication rates were similar in each arm. Conclusions and Relevance Administration of 1250 mg of lapatinib per day in combination with ECX chemotherapy was feasible with some increase in toxic effects, which did not compromise operative management. Trial Registration ISRCTN.org identifier:46020948; clinicaltrialsregister.eu identifier:2006-000811-12

Purpose The Cancer Esophagus Gefitinib trial demonstrated improved progression-free survival with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib relative to placebo in patients with advanced esophageal cancer who had disease progression after chemotherapy. Rapid and durable responses were observed in a minority of patients. We hypothesized that genetic aberration of the EGFR pathway would identify patients benefitting from gefitinib. Methods A prespecified, blinded molecular analysis of Cancer Esophagus Gefitinib trial tumors was conducted to compare efficacy of gefitinib with that of placebo according to EGFR copy number gain (CNG) and EGFR, KRAS, BRAF, and PIK3CA mutation status. EGFR CNG was determined by fluorescent in situ hybridization (FISH) using prespecified criteria and EGFR FISH-positive status was defined as high polysomy or amplification. Results Biomarker data were available for 340 patients. In EGFR FISH-positive tumors (20.2%), overall survival was improved with gefitinib compared with placebo (hazard ratio [HR] for death, 0.59; 95% CI, 0.35 to 1.00; P = .05). In EGFR FISH-negative tumors, there was no difference in overall survival with gefitinib compared with placebo (HR for death, 0.90; 95% CI, 0.69 to 1.18; P = .46). Patients with EGFR amplification (7.2%) gained greatest benefit from gefitinib (HR for death, 0.21; 95% CI, 0.07 to 0.64; P = .006). There was no difference in overall survival for gefitinib versus placebo for patients with EGFR, KRAS, BRAF, and PIK3CA mutations, or for any mutation versus none. Conclusion EGFR CNG assessed by FISH appears to identify a subgroup of patients with esophageal cancer who may benefit from gefitinib as a second-line treatment. Results of this study suggest that anti-EGFR therapies should be investigated in prospective clinical trials in different settings in EGFR FISH-positive and, in particular, EGFR-amplified esophageal cancer.

OBJECTIVES To evaluate the feasibility and adherence to home delivery (HD) of pemetrexed maintenance treatment in patients with advanced non-squamous non-small cell lung cancer (nsqNSCLC). MATERIALS AND METHODS Exploratory, prospective, single-arm, Phase II study in advanced nsqNSCLC patients, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1 that did not progress after 4 first-line induction cycles of a platinum doublet. The first cycle of pemetrexed (500mg/m(2)) was hospital administered, further cycles were HD until progressive disease or discontinuation. Feasibility was assessed by the adherence rate to HD (probability of reversion to hospital administration or treatment discontinuation due to HD) as primary endpoint, and by health-related quality-of-life (HRQoL: EQ-5D, lung cancer symptom scale [LCSS]), satisfaction with HD, overall survival (OS), and safety. RESULTS 52 patients (UK & Sweden) received a median of 4 (range 1-19) pemetrexed maintenance cycles. Adherence rate up to Cycle 6 was 98.0% (95% confidence interval [CI]: 86.4%, 99.7%). All but 2 patients remained on HD. 1 patient discontinued after Cycle 1 (patient decision), and 1 after Cycle 6 (non-compliance with oral dexamethasone). 87% (33/38) of the patients preferred home to hospital treatment and in 90% (28/31) of cases, physicians were satisfied with distant management of patients. During HD Cycles 2-4 mean change from baseline ranged from 3.0 to 7.7 for EQ-5D visual analog scale. The 6-month OS rate was 73% (95% CI: 58%, 83%). 1 patient had an HD-related adverse event (device-related infection, Grade 2) and 1 patient died after Cycle 1, before HD, due to a possibly drug-related atypical pneumonia. CONCLUSION HD of pemetrexed maintenance treatment in patients with advanced nsqNSCLC was feasible, safe, and preferred by patients, while maintaining HRQoL. Physicians were satisfied with distant patient management.

Purpose Treating small-cell lung cancer (SCLC) remains a therapeutic challenge. Experimental studies show that statins exert additive effects with agents, such as cisplatin, to impair tumor growth, and observational studies suggest that statins combined with anticancer therapies delay relapse and prolong life in several cancer types. To our knowledge, we report the first large, randomized, placebo-controlled, double-blind trial of a statin with standard-of-care for patients with cancer, specifically SCLC. Patients and Methods Patients with confirmed SCLC (limited or extensive disease) and performance status 0 to 3 were randomly assigned to receive daily pravastatin 40 mg or placebo, combined with up to six cycles of etoposide plus cisplatin or carboplatin every 3 weeks, until disease progression or intolerable toxicity. Primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), response rate, and toxicity. Results Eight hundred forty-six patients from 91 United Kingdom hospitals were recruited. The median age of recruited patients was 64 years of age, 43% had limited disease, and 57% had extensive disease. There were 758 deaths and 787 PFS events. No benefit was found for pravastatin, either in all patients or in several subgroups. For pravastatin versus placebo, the 2-year OS rate was 13.2% (95% CI, 10.0 to 16.7) versus 14.1% (95% CI, 10.9 to 17.7), respectively, with a hazard ratio of 1.01 (95% CI, 0.88 to 1.16; P = .90. The median OS was 10.7 months v 10.6 months, respectively. The median PFS was 7.7 months v 7.3 months, respectively. The median OS (pravastatin v placebo) was 14.6 months in both groups for limited disease and 9.1 months versus 8.8 months, respectively, for extensive disease. Adverse events were similar between groups. Conclusion Pravastatin 40 mg combined with standard SCLC therapy, although safe, does not benefit patients. Our conclusions are the same as those found in all four much smaller, randomized, placebo-controlled trials specifically designed to evaluate statin therapy in patients with cancer.

4022 Background: No large scale randomised data exists evaluating the impact of age and sex in patients (pts) undergoing potentially curative surgery and CTx for OG cancer. However, differences in age and sex may be contributing factors to variability in CTx dose-response and toxicity which could also impact survival. Methods: Data from four prospective randomised controlled trials were pooled using a two-stage meta-analysis. For survival data, hazard ratios were calculated for pts

Background Midwifery education is the foundation for preparing competent midwives to provide a high standard of safe, evidence-based care for women and their newborns. Global competencies and standards for midwifery education have been defined as benchmarks for establishing quality midwifery education and practice worldwide. However, wide variations in type and nature of midwifery education programs exist. Aim To explore and discuss the opportunities and challenges of a global quality assurance process as a strategy to promote quality midwifery education. Discussion Accreditation and recognition as two examples of quality assurance processes in education are discussed. A global recognition process, with its opportunities and challenges, is explored from the perspective of four illustrative case studies from Ireland, Kosovo, Latin America and Bangladesh. The discussion highlights that the establishment of a global recognition process may assist in promoting quality of midwifery education programs world-wide, but cannot take the place of formal national accreditation. In addition, a recognition process will not be feasible for many institutions without additional resources, such as financial support or competent evaluators. In order to achieve quality midwifery education through a global recognition process the authors present 5 Essential Challenges for Quality Midwifery Education. Conclusion Quality midwifery education is vital for establishing a competent workforce, and improving maternal and newborn health. Defining a global recognition process could be instrumental in moving toward this goal, but dealing with the identified challenges will be essential.

A semi-structured, web-based questionnaire was developed to survey midwives (n = 241) employed by NHS Tayside, UK, to identify current practice and views on weight management of obese women during pregnancy and the puerperium. A total of 78 (32%) midwives submitted responses following email invitation. Most respondents (79%) reported always calculating women's body mass index (BMI) at booking, with 73% routinely explaining the BMI category. In terms of future practice for obese women, although few respondents (15%) currently offer personalised advice regarding weight management based on a woman's diet and physical activity levels, 77% of respondents thought such advice would be appropriate and 69% thought it could possibly be feasible to offer such advice. The respondents viewed weight management to be of importance and felt that universal advice is appropriate, but confidence in discussing weight management and knowledge of the subject was low. Strategies to improve midwife confidence and weight management services should include training, ongoing support and definition of the midwife's role within the multidisciplinary team to support practice in the future.

Given the stresses associated with today's demanding workplaces, work/life (w/l) initiatives continue to grow in importance as an organizational development (OD) intervention. In a period of increasing accountability, it is important for scholars and practitioners to demonstrate how OD interventions, like w/l initiatives, can be used as a strategic business tool to ameliorate the impact of stress in the workplace. To address this gap, the research questions for this study were based on the resource-based view of the firm (Barney, 1991), while using the Organization Development Human Capital Accounting System (ODHCAS) model (Morris, Storberg-Walker, & McMillan, 2009) as a basis for generating relevant metrics. This exploratory study used a survey instrument to compare senior human resource (HR) executives' perceptions of the strategic benefit of w/l initiatives in conjunction with their efforts to measure the impact of five types of w/l initiatives as they influence 16 measures representative of the elements of the ODHCAS. Findings from the study extend current research by revealing a relationship between HR executives' perceptions of the strategic impact of w/l initiatives and the decision to measure the impact of said initiatives.

The key issue facing forensic labs is “the classic economic problem—how to allocate limited resources with increasing demand for services, while maintaining high quality standards” (Speaker 2009). Employees are the biggest expense and most valuable resource that forensic labs possess, thus the question arises as to how to maximize human resource functions to best allocate resources through personnel. As the search is on to look for better practices to improve the operations as well as technical expertise of labs, human capital management is crucial to that objective. The purpose of this article is to process map some of the staffing issues facing forensic science labs, whether public or private, and to identify metrics from the FORESIGHT study (Houck et al. 2009) that might help lab directors create a working formula to better manage staffing (e.g., recruiting and selection) issues.

Purpose Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. This phase III study assessed the efficacy of vandetanib versus erlotinib in unselected patients with advanced non–small-cell lung cancer (NSCLC) after treatment failure with one to two prior cytotoxic chemotherapy regimens. Patients and Methods One thousand two hundred forty patients were randomly assigned to receive vandetanib 300 mg/d (n = 623) or erlotinib 150 mg/d (n = 617). The primary objective was to show superiority in progression-free survival (PFS) for vandetanib versus erlotinib. If the difference did not reach statistical significance for superiority, a noninferiority analysis was conducted. Results There was no significant improvement in PFS for patients treated with vandetanib versus erlotinib (hazard ratio [HR], 0.98; 95.22% CI, 0.87 to 1.10; P = .721); median PFS was 2.6 months for vandetanib and 2.0 months for erlotinib. There was also no significant difference for the secondary end points of overall survival (HR, 1.01; P = .830), objective response rate (both 12%), and time to deterioration of symptoms for pain (HR, 0.92; P = .289), dyspnea (HR, 1.07; P = .407), and cough (HR, 0.94; P = .455). Both agents showed equivalent PFS and overall survival in a preplanned noninferiority analysis. Adverse events (AEs; any grade) more frequent with vandetanib than erlotinib included diarrhea (50% v 38%, respectively) and hypertension (16% v 2%, respectively); rash was more frequent with erlotinib than vandetanib (38% v 28%, respectively). The overall incidence of grade ≥ 3 AEs was also higher with vandetanib than erlotinib (50% v 40%, respectively). Conclusion In patients with previously treated advanced NSCLC, vandetanib showed antitumor activity but did not demonstrate an efficacy advantage compared with erlotinib. There was a higher incidence of some AEs with vandetanib.

A stream of research exists that focuses on traditional mentoring (senior female managers mentoring junior members in a domestic organization). The literature further indicates that females are increasing in number but may receive less mentoring than males and expatriates may receive less mentoring than domestic employees. A new paradigm, reverse mentoring, has emerged (e.g., a junior person, knowledgeable of the rapid technological change and globalization of business, acts as the mentor for a senior person). This paper proposes a third type of mentoring, ‘reciprocal’, as essential for competition in global markets. It is argued that mentoring can become a strategic tool in the organizational knowledge creation and transfer process. Moreover, mentoring could serve as a competitive advantage in creating an effective support system for female global female managers.

Purpose To compare gefitinib with placebo in chemotherapy naïve patients with advanced non–small-cell lung cancer (NSCLC) and poor performance status. Patients and Methods NSCLC patients (chemotherapy naïve, WHO performance status 2 or 3; unfit for chemotherapy; stage IIIB/IV) were randomly assigned to gefitinib (250 mg/d) plus best supportive care (BSC; n = 100) or placebo plus BSC (n = 101). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), quality of life (QOL), pulmonary symptom improvement (PSI), and safety. Correlation of gefitinib efficacy with EGFR gene copy number (fluorescent in situ hybridization [FISH]) was explored. Results Hazard ratios (HRs; gefitinib:placebo) were 0.82 (95% CI, 0.60 to 1.12; P = .217) for PFS and 0.84 (95% CI, 0.62 to 1.15; P = .272) for OS. As expected for this patient population, OS for both arms was poor, at about 3 months. ORRs were 6.0% (gefitinib) and 1.0% (placebo). QOL and PSI rates were 21.1% and 28.3% (gefitinib) and 20.0% and 28.3% (placebo), respectively. In EGFR FISH-positive patients (n = 32), HRs were 0.29 (95% CI, 0.11 to 0.73) for PFS and 0.44 (95% CI, 0.17 to 1.12) for OS. No unexpected adverse events occurred. Conclusion There was no statistically significant difference in PFS, OS, and ORRs after treatment with gefitinib or placebo, in the overall population; improvements in QOL and symptoms were similar in both groups. Tolerability profile of gefitinib was consistent with previous studies. PFS was statistically significantly improved for gefitinib-treated patients with EGFR FISH-positive tumors.

PurposeThe purpose of this paper is to conceptually demonstrate that the relationship between turnover and innovation is not direct as some research suggests, but rather indirect, with organizational learning as the prerequisite social mechanism that ties the two phenomena together.Design/methodology/approachThis paper integrates research across a number of related areas to develop a model of the immediate and indirect organizational consequences of different rates of knowledge worker turnover.FindingsThe paper finds that certain conditions and mechanisms must first be in place to pave the way to innovation. Grounded in social capital theory, this paper describes how turnover rates and organizational learning can be curvilinearly related with respect to ambidextrous learning; how betweenness centrality and learning culture can moderate this relationship; and why organizational learning should mediate the turnover‐innovation relationship.Research limitations/implicationsFaulty decisions based on simplified beliefs place organizational performance in a precarious position. Studies must consider how changes in personnel affect activities where interpersonal relationships are critical. Turnover that beneficially breathes diversity, critical evaluation, and creativity should result in benefits that more than offset its costs.Originality/valueBy taking an in‐depth look at previously disconnected research, the paper offers a unified model that more accurately depicts the processes and outcomes that intercede and explain how knowledge worker turnover rates come to influence innovation.

Acquisitions continue to be an important topic for management scholars and practitioners alike. Managers are actively involved in both sides of the acquisition equation (target and acquirer) from valuation (preacquisition) all the way through to integration (postacquisition). During this tumultuous period, it now appears that the top management team of a successful target firm is integral to postacquisition success. The authors examine the role that "imposed" changes placed on the newly acquired firm has on the retention of the top management team. The compulsory changes appear to be a key factor in the turnover of top management team members and thus diminish the value of the acquired firm. Furthermore, this study suggests that top management team turnover detrimentally affects postacquisition firm performance.

The complex global business environment has created a host of problems for managers, none of which is more difficult to address than bullying in the workplace. The rapid rate of change and the ever-increasing complexity of organizational environments of business throughout the world have increased the opportunity for bullying to occur more frequently. This article addresses the foundations of bullying by examining the ‘nature’ (i.e., bullying behavior influenced by the innate genetic make-up of an individual) and the ‘nurture’ (i.e., individuals learn to be bullies and environments allow the behavior to perpetuate) arguments for the occurrence of bullying behavior. In addition, guidelines are presented for managers in global organizations to use in assessing and monitoring bullying activities in global organizations.

Workplace bullying in global organizations occurs for several reasons, including growing diversity, increased dispersion of employees in geographic locations, lack of experience of managers with new environments, and varying requirements. To gain insight into the bullying phenomenon, one must examine the characteristics of the bully, the target of bullying activities (e.g., the victim or the bullied), observers of the bullying (e.g., bystanders), and resulting changes in the organizational culture because of the bullying. One additional element to be assessed is the means by which bullying activities are embodied in an organization's culture (i.e., social/emotional contagion). This paper proposes a model of bullying in global organizations and examines the potential of social/emotional contagion developing in global organizations’ cultures.

Leaders do not necessarily have the best interests of the organization in mind when they make decisions. Many times, leaders treat their own personal goals as more important in relation to the goals of the organization and frequently adopt a short-term decision horizon. Thus, leaders become destructive and make decisions for their own good at the expense of the organization. This article examines the bully as a leader and how the bully creates a dysfunctional environment where the bullied, the observer, and the organization suffer negative impact due to the decisions made by the bully. The externalities of bullying (i.e., unintended explicit and/or implicit consequences of bullying activities on the members of the organization) are discussed to highlight the importance of examining the spillover impact of bullying activities in organizations. In addition, the authors propose a method to address the negative impact of those who engage in bullying on the organizational as a whole.

Published information on the effectiveness of bronchial thermoplasty (BT) for severe asthma in ‘real life’ patients is limited. We compared safety and efficacy outcomes 12 months post procedure in 10 clinic patients and 15 patients recruited to clinical trials of BT at the same centre. Baseline asthma severity was greater in the clinic group. Adverse events were similar. Clinical improvements occurred in 50% of the clinic patients compared with 73% of the research patients.

Malignant mesothelioma (MM) is an aggressive cancer of mesothelial cells of pleural and peritoneal cavities. In 85% of cases both pleural and peritoneal MM is caused by asbestos exposure. Although both are asbestos-induced cancers, the incidence of pleural MM is significantly higher (85%) than peritoneal MM (15%). It has been proposed that carcinogenesis is a result of asbestos-induced inflammation but it is not clear what contributes to the differences observed between incidences of these two cancers. We hypothesize that the observed differences in incidences of pleural and peritoneal MM are the result of differences in the direct response of these cell types to asbestos rather than to differences mediated by the in vivo microenvironment. To test this hypothesis we characterized cellular responses to asbestos in a controlled environment. We found significantly greater changes in genome-wide expression in response to asbestos exposure in pleural mesothelial cells as compared to peritoneal mesothelial cells. In particular, a greater response in many common genes (IL-8, ATF3, CXCL2, CXCL3, IL-6, GOS2) was seen in pleural mesothelial cells as compared to peritoneal mesothelial cells. Unique genes expressed in pleural mesothelial cells were mainly pro-inflammatory (G-CSF, IL-1β, IL-1α, GREM1) and have previously been shown to be involved in development of MM. Our results are consistent with the hypothesis that differences in incidences of pleural and peritoneal MM upon exposure to asbestos are the result of differences in mesothelial cell physiology that lead to differences in the inflammatory response, which leads to cancer.

Purpose – The purpose of this paper is to examine and develop a cross‐level model of the phenomenon of bullying at three levels (e.g. individual, group, and organizational).Design/methodology/approach – This is a theory‐based paper operationalizing transactional coping theory across three levels of an organization relative to bullying activities.Findings – There can be spillover from bullying from the dyadic level to other levels in the organization. While bullying is frequently discussed as an individual‐to‐individual phenomenon, the conflict can reverberate up to the group and organizational level. The interaction between the three levels needs to be taken into consideration when developing effective managerial plans to address the negative consequences of bullying.Research limitations/implications – Additional research is needed to address the interaction effect between all three levels that can be impacted by bullying acts. Without addressing the spillover from one level to another, remediation progra...

Why does bullying occur in an organization? How will the globalization of an organization facilitate the process and encourage bullying to occur in that organization? What can be done to reduce the level/impact of bullying in an organization that is in transition? These are the focal questions addressed in this paper. Reference Point Theory (RPT) is applied to the bullying phenomena in an effort to illustrate the various reference points that can be used by the bully, the bullied, ‘others’ in the global organizations, as well as the management of the organization. The divergent reference points used by individuals in the organization can encourage bullying to occur and make attempts to reduce the resulting conflict much more difficult to implement. The paper develops a process to reduce the level of bullying during the transition to global organization and to limit the impact of bullying events that do occur in the organization.

Bullying in organizations has become one the prime social phenomena which can have a direct as well as indirect impact on the productivity of employees and managers. While bullying is a part of the fabric of society, the rate of occurrence as well as the severity of bullying acts in the workplace is alarming. This paper puts forth a model that illustrates the triangular relationship and interaction between the three components in the bullying event: 1) the organizational environment and its impact on the occurrence of bullying activities; 2) the characteristics of those that bully; and 3) the characteristics of those being bullied (e.g., victims of bullying). These three interrelated issues form the triangle of bullying that is examined in this paper. This paper posits that a major source of many of the personnel relational problems faced in the workplace between coworker and coworker or manager and employees comes from bullies, just like the ones experienced on the childhood playground. Research shows that child bullies and those bullied as children have the potential to become adult bullies. Combine that with the complex, diverse, global business arena that creates high levels of stress, it is easy to understand why there is the possibility of boardroom/workplace bullies. "Bullying at work is claimed to be more crippling and devastating problem for employees than all other work related stress put together... " (Einarsen, 1999).

Bullying is a common and constantly reoccurring phenomenon in organizations. The increasing diversity of the workplace is an accepted fact, which has the potential to increase the occurrence of status inconsistency. The purpose of this paper is to examine the theory of status inconsistency and its usefulness as a predictor to identifying when bullying might occur in a work group setting. In addition, the possible impact of bullying on group dynamics and ultimately group performance is explored. The central tenet of this paper is that bullying is a possible behaviour given a group member's intense emotional feelings of stress related to status inconsistency. The paper concludes by highlighting a few managerial implications relative to effectively addressing bullying behaviour in groups and identifying future directions to better understanding and researching bullying in a group context. In a recent study, it was found that: (1) 78% of the respondents felt incivility [bullying] in the workplace has worsened...

Summary Background Evidence is scarce for the effectiveness of therapies for oesophageal cancer progressing after chemotherapy, and no randomised trials have been reported. We aimed to compare gefitinib with placebo in previously treated advanced oesophageal cancer. Methods For this phase 3, parallel, randomised, placebo-controlled trial, eligible patients were adults with advanced oesophageal cancer or type I/II Siewert junctional tumours, histologically confirmed squamous-cell carcinoma or adenocarcinoma, who had progressed after chemotherapy, with WHO performance status 0–2, and with measurable or evaluable disease on CT scan. Participants were recruited from 48 UK centres and randomly assigned (1:1) to gefitinib (500 mg) or matching placebo by simple randomisation with no stratification factors. Patients, clinicians, and trial office staff were masked to treatment allocation. Treatment continued until disease progression, unacceptable toxicity, or patient choice. The primary outcome was overall survival, analysed by intention to treat. This trial is registered, number ISRCTN29580179. Findings Between March 30, 2009, and Nov 18, 2011, 450 patients were randomly assigned to treatment groups (one patient withdrew consent; 224 patients allocated gefitinib and 225 allocated placebo included in analyses). Overall survival did not differ between groups (median 3·73 months, 95% CI 3·23–4·50, for gefitinib vs 3·67 months, 95% CI 2·97–4·37, for placebo; hazard ratio [HR] 0·90, 95% CI 0·74–1·09, p=0·29). Among the prespecified patient-reported outcomes (110 patients on gefitinib and 121 on placebo completed both baseline and 4 week questionnaires and were included in analyses), odynophagia was significantly better in the gefitinib group (adjusted mean difference −8·61, 95% CI −14·49 to −2·73; n=227; p=0·004), whereas the other outcomes were not significantly improved compared with placebo: global quality of life (2·69, 95% CI −2·33 to 7·72, n=231, p=0·293), dysphagia (−3·18, 95% CI −8·36 to 2·00, n=231, p=0·228), and eating (−4·11, 95% CI −9·96 to 1·75, n=229, p=0·168). Median progression-free survival was marginally longer with gefitinib than it was with placebo (1·57 months, 95% CI 1·23–1·90 in the gefitinib group vs 1·17 months, 95% CI 1·07–1·37 in the placebo group; HR 0·80, 95% CI 0·66–0·96, p=0·020). The most common toxicities were diarrhoea (36 [16%] of 224 patients on gefitinib vs six [3%] of 225 on placebo) and skin toxicity (46 [21%] vs two [1%]), both mostly grade 2. The commonest grade 3–4 toxicities were fatigue (24 [11%] vs 13 [6%] patients) and diarrhoea (13 [6%] vs two [1%]). Serious adverse events were reported in 109 (49%) of 224 patients assigned to gefitinib and 101 (45%) of 225 on placebo. 54 (24%) of patients in the gefitinib group achieved disease control at 8 weeks, as did 35 (16%) of patients on placebo (p=0·023). Interpretation The use of gefitinib as a second-line treatment in oesophageal cancer in unselected patients does not improve overall survival, but has palliative benefits in a subgroup of these difficult-to-treat patients with short life expectancy. Future research should focus on identification of predictive biomarkers to identify this subgroup of benefiting patients. Funding Cancer Research UK.

Objective To evaluate the impact of a diet and physical activity intervention (BeWEL) on weight change in people with a body mass index >25 weight (kg)/height (m)2 at increased risk of colorectal cancer and other obesity related comorbidities. Design Multicentre, parallel group, randomised controlled trial. Setting Four Scottish National Health Service health boards. Participants 329 overweight or obese adults (aged 50 to 74 years) who had undergone colonoscopy after a positive faecal occult blood test result, as part of the national bowel screening programme, and had a diagnosis of adenoma confirmed by histopathology. 163 were randomised to intervention and 166 to control. Intervention Participants were randomised to a control group (weight loss booklet only) or 12 month intervention group (three face to face visits with a lifestyle counsellor plus monthly 15 minute telephone calls). A goal of 7% reduction in body weight was set and participants received a personalised energy prescription (2508 kJ (600 kcal) below that required for weight maintenance) and bodyweight scales. Motivational interviewing techniques explored self assessed confidence, ambivalence, and personal values concerning weight. Behavioural strategies included goal setting, identifying intentions of implementation, self monitoring of body weight, and counsellor feedback about reported diet, physical activity, and weight change. Main outcome measures The primary outcome was weight change over 12 months. Secondary outcomes included changes in waist circumference, blood pressure, fasting cardiovascular biomarkers, and glucose metabolism variables, physical activity, diet, and alcohol consumption. Results At 12 months, data on the primary outcome were available for 148 (91%) participants in the intervention group and 157 (95%) in the control group. Mean weight loss was 3.50 kg (SD 4.91) (95% confidence interval 2.70 to 4.30) in the intervention group compared with 0.78 kg (SD 3.77) (0.19 to 1.38) in the control group. The group difference was 2.69 kg (95% confidence interval 1.70 to 3.67). Differences between groups were significant for waist circumference, body mass index, blood pressure, blood glucose level, diet, and physical activity. No reported adverse events were considered to be related to trial participation. Conclusions Significant weight loss can be achieved by a diet and physical activity intervention initiated within a national colorectal cancer screening programme, offering considerable potential for risk reduction of disease in older adults. Trial registration Current Controlled Trials ISRCTN53033856.

Purpose: To develop a highly reproducible model of disseminated childhood neuroblastoma in mice to allow secondary evaluation of therapeutics against microscopic disseminated disease. Methods: CB17/Icr SCID were injected i.v. with 103 to 5×106 human NB-1691 neuroblastoma cells. NB-1691 cells were detected by PCR for synaptophysin and tyrosine hydroxylase in peripheral blood, and bone marrow. Therapeutic studies evaluated topotecan and vincristine as single agents or in combination. Topotecan was administered i.v. daily for 5 days on two consecutive weeks. Courses were repeated every 21 days for three cycles. Vincristine (1 mg/kg) was administered i.v. every 7 days for nine consecutive weeks. Treatment started 11–21 days after tumor cell inoculation. Results: Following injection of ≥1×105 cells 100% of mice developed disease. Mice inoculated with 107 cells survived a median of 42 days. Survival time was a linear function of the cell inoculum. At autopsy, gross tumor was routinely detected in many organs in particular liver, ovaries, kidneys and adrenals. NB-1691 cells were detected by PCR in peripheral blood, and bone marrow. Immunohistochemical staining showed that lesions were strongly positive for synaptophysin, chromogranin A and negative for leukocyte common antigen. Topotecan (0.6 mg/kg) alone extended median survival from 44 days (controls) to 95 days. When treatment was started 21 days after inoculation of NB-1691 cells, topotecan extended median survival from 39 days (controls) to 91 and 99 days at dose levels of 0.3 and 0.6 mg/kg, respectively. Vincristine (1 mg/kg) extended survival by a median of 9.5 days. In combination with vincristine (1 mg/kg), median survival was increased to 141 days (topotecan 0.6 mg/kg) and 159 days (topotecan 1.0 mg/kg). Conclusion: This model of disseminated neuroblastoma is highly reproducible. As this model may more closely simulate childhood disease it may be a valuable adjunct in developing new approaches to advanced stage, poor prognosis neuroblastoma.