Prospective evaluation of circulating VEGF in patients with advanced non-small cell lung cancer treated with bevacizumab, pemetrexed and cisplatin in the trial SAKK19/09.

Aim: Bevacizumab is a monoclonal antibody directed against the vascular endothelial growth factor (VEGF). The previous phase II trial ABIGAIL (Reck, 2010) suggested circulating VEGF as a prognostic, but not predictive, biomarker for patients (pts) with non-small cell lung cancer (NSCLC) treated with bevacizumab. We prospectively measured VEGF in the multicenter phase II trial SAKK19/09 (NCT01116219). Methods: SAKK19/09 enrolled 77 evaluable patients (pts) with previously untreated, advanced nonsquamous NSCLC and EGFR wild type. Pts received 4 cycles of cisplatin 75mg/m2 (or carboplatin AUC5), pemetrexed 500mg/m2 and bevacizumab 7.5mg/kg, followed by maintenance therapy with pemetrexed and bevacizumab until progression by RECIST1.1. Follow-up CT scans were performed every 6 weeks until week 54 and every 12 weeks thereafter. Baseline EDTA blood samples were sent by same-day courier to the central laboratory for centrifugation, aliquoting, and freezing. Upon completion of enrollment, aliquots were thawed, and VEGF quantification was performed centrally using Luminex® Performance Assay Human Base Kit A (R&D Systems, Abingdon, UK). The mean value was used to stratify pts into two groups (low versus high VEGF). Best response rate assessed by RECIST1.1 (CR + PR versus SD + PD). Results: Clinical results of the SAKK19/09 trial were reported previously (Gautschi, 2013). Baseline plasma VEGF was detectable in 71 of 77 (92%) evaluable patients treated with chemotherapy and bevacizumab. The mean value was 74.9 pg/ml, the median 47.5 pg/ml, and the range 3.55 to 310 pg/ml. Using the mean as a predefined cutoff value, 50 patients had low VEGF levels and 21 patients had high VEGF levels. High VEGF was significantly associated with shorter PFS (4.1 vs 8.3 months, HR = 2.56; 95%CI: 1.43- 4.57; p = 0.0015) and OS (8.7 vs 17.5 months, HR = 2.67; 95% CI: 1.37-5.20; p = 0.0041), but not with best response rate ( p = 0.2256). Conclusions: Consistent with the ABIGAIL trial, circulating VEGF was prognostic, but not predictive for response, in the current trial. Further work is ongoing to identify potentially predictive biomarkers for bevacizumab, using comprehensive proteomic analyses. Disclosure: S.I. Rothschild: I received honoraria for the participation in advisory boards from Eli Lilly and Roche and for presentations at scientific symposiums sponsored by Roche; O. Gautschi: Honoraria for advisory boards of Eli Lilly and Roche; R. Cathomas: Advisory board member: Eli Lilly. All other authors have declared no conflicts of interest.

Neoadjuvant chemotherapy and extrapleural pneumonectomy (EPP) of malignant pleural mesothelioma (MPM) with or without hemithoracic radiotherapy: final results of the randomized multicenter phase II trial SAKK17/04.

Aim: We have previously documented the feasibility of neoadjuvant chemotherapy and EPP in a multicenter trial of MPM (Weder, Ann Oncol 18: 1196, 2007). The objectives of the trimodality trial SAKK17/04 (NCT00334594) were to evaluate the time to loco-regional relapse with or without high dose hemithoracic radiotherapy in a prospective multicenter randomized phase II trial in patients with R0 and R1 resection after neoadjuvant chemotherapy and EPP. Methods: Eligible patients had pathologically confirmed MPM, surgically resectable TNM stage (T1-3 N0-2 M0), PS0-1, ages 18-70 years. Part 1 had a phase II design, and included neoadjuvant chemotherapy with 3 cycles of cisplatin and pemetrexed, followed by restaging and EPP. The primary endpoint of part 1 was complete macroscopic resection (R0-1). Part 2 randomized consenting patients with R0-1 resection into two parallel phase II arms (control arm A and radiotherapy arm B). The primary endpoint for part 2 was loco-regional relapse-free survival (RFS). To detect a 1 year increase with 80% power and 10% alpha, 37 patients were needed for arm B. Secondary endpoints included operability, tolerability of chemotherapy and radiotherapy, survival, and translational research Results: Because accrual of part 2 was slower than planned, the trial was stopped in 2013. Overall, 153 patients entered the trial, of whom 125 underwent surgery and 99 had a complete macroscopic resection (primary endpoint part 1). Of the later patients, 54 could be randomized 1:1 into each arm. Reasons for non-randomization included patient refusal in 24 and ineligibility or protocol deviations in 21. Of the 27 patients randomized to hemithoracic radiotherapy, 25 completed the treatment as planned. For part 1 the median RFS was 8.8 (95%CI: 7.3-10.7) and median OS was 15.0 (95% CI: 12.1-19.3) months. For part 2 the median local RFS for group A was 7.6 (95%CI: 5.5-10.7) and for group B 9.4 (95%CI: 6.5-11.9) months (primary endpoint part 2), while the overall RFS and OS for group A were 5.7 (95%CI: 3.5-8.8) and 16.9 (95%CI: 10.7-23.6) months and for group B 7.6 (95% CI:5.2-10.6) and 14.9 (95%CI: 7.0-17.6) months. Conclusions: This study did not reach the primary endpoint which was defined as one-year increase in loco-regional relapse-free survival and thus does not support the routine use of hemithoracic RT after neoadjuvant chemotherapy and EPP. Disclosure: All authors have declared no conflicts of interest.

Final results of the SAKK 16/00 trial: a randomized phase III trial comparing neoadjuvant chemoradiation to chemotherapy alone in stage IIIA/N2 non-small cell lung cancer (NSCLC).

Aim: One standard option in the treatment of stage IIIA/N2 NSCLC is neoadjuvant chemotherapy followed by surgery. We investigated in a randomized trial whether the addition of neoadjuvant radiotherapy would improve the outcome. Here we present the final results of this study. Methods: Patients (pts.) with pathologically proven, resectable stage IIIA/N2 NSCLC, performance status 0-1, and adequate organ function were randomized 1:1 to chemoradiation (CRT) with 3 cycles of neoadjuvant chemotherapy (cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1, q3weeks) followed by accelerated concomitant boost radiotherapy (RT) with 44 Gy in 22 fractions in 3 weeks, or neoadjuvant chemotherapy alone (CT), with subsequent surgery for all pts. The primary endpoint was event-free survival (EFS). Results: 232 pts. were randomized in 23 centers, the median follow-up was 53 months. Two thirds were men, median age was 60 years (range 37-76). Histology was squamous cell in 33%, adenocarcinoma in 43%. Response rate to CRT was 61% vs. 44% with CT. 85% of all pts. underwent surgery, 30-day postoperative mortality was 1%. The rate of complete resection was 91% (CRT) vs. 81% (CT) and the pathological complete remission (pCR) rate was 16% vs. 12%. The median EFS was 13.1 months (95% CI 9.9 - 23.5) for the CRT group vs. 11.8 months (95% CI 8.4 - 15.2) in the CT arm (p 0.665). The median overall survival (OS) with CRT was 37.1 months (95% CI 22.6 -50), with CT 26.1 months ( 95% CI 26.1 - 52.1, p 0.938). The local failure rate was 23% in both arms. In the CT arm 12 pts. were given postoperative radiotherapy (PORT) for R1 resection, 6 pts. received PORT in violation of the protocol. Pts. with a pCR, mediastinal downstaging to ypN0/1 and complete resection had a better outcome. Toxicity of chemotherapy was substantial, especially febrile neutropenia was common, whereas RT was well tolerated. Conclusions: This is the first completed phase III trial to evaluate the role of induction chemoradiotherapy and surgery, in comparison to neoadjuvant CT alone followed by surgery. RT was active, it increased response, complete resection and pCR rates. However, this failed to translate into an improvement of local control, EFS or OS. Notably, surgery after induction treatment was safe, including pneumonectomy. The overall survival rates of our neoadjuvant regimen are very encouraging, especially for a multicenter setting. Disclosure: M. Pless: Advisory Board for Sanofi; R. Cathomas: Advisory Board Sanofi D.C. Betticher: Advisory Board Sanofi. All other authors have declared no conflicts of interest.

Under what conditions? Therapist and client characteristics moderate the role of change talk in brief motivational intervention.

OBJECTIVE: Client change talk has been proposed as a mechanism of change in motivational interviewing (MI) by mediating the link between therapist MI-consistent behaviors (MICO) and client behavioral outcomes. We tested under what circumstances this mechanism was supported in the context of a clinical trial of brief MI for heavy drinking among nontreatment seeking young men. METHOD: We conducted psycholinguistic coding of 174 sessions using the MI Skill Code 2.1 and derived the frequency of MICO and the strength of change talk (CTS) averaged over the session. CTS was examined as a mediator of the relationship between MICO and a drinking composite score measured at 3-month follow-up, controlling for the composite measure at baseline. Finally, we tested therapist gender and MI experience as well as client readiness to change and alcohol problem severity as moderators of this mediation model. RESULTS: CTS significantly predicted outcome (higher strength related to less drinking), but MICO did not predict CTS. However, CTS mediated the relationship between MICO and drinking outcomes when therapists had more experience in MI and when clients had more severe alcohol problems (i.e., significant conditional indirect effects). CONCLUSIONS: The mechanism hypothesized by MI theory was operative in our brief MI with heavy drinking young men, but only under particular conditions. Our results suggest that attention should be paid to therapist selection, training, and/or supervision until they reach a certain level of competence, and that MI might not be appropriate for nontreatment seeking clients drinking at a lower level of risk. (PsycINFO Database Record

Assessment of research competences using e-portfolio

The challenges posed by the assessment of distance learning is a topic that requires, on the one hand, evolution with new trends and, on the other improving evaluative processes, to promote good practices. This demand becomes more imperative when we are dealing with a formativescenario based on distance assessment of competence-based learning.The Open University of Catalonia has begun to work with these formative tools, promoting new practices for online education. A very clear example of these educational practices is the assessment of research competences using the e-portfolio system. To meet this aim a profound and solid process has been developed over recent years, with the intention of making this tool an assessment alternative, and providing the opportunity to use it in a formative context. The objective is to study its strengths and limitations keeping in mind the final goal of offering the higher education community a validated assessment system.

Quality of Abdominal Surgical Nursing Care

The study evaluates the quality of abdominal surgical nursing care. The data were collected from patients (n=1208) having undergone abdominal surgical operations on their last day of hospitalization and nurses (n=218) working in the same wards. Three instruments originally created in Finland and adapted to the Lithuanian context were used: (1) Good Nursing Care Scale for patients and nurses (GNCS-P, GNCS-N), (2) Nurse Competence Scale (NCS), and (3) Nurse Empowerment Scale (NES). Patient and nurses’ perceptions of the quality of nursing care were evaluated. In addition, nurses’ perceptions of their competence and empowerment were evaluated. The patient and nurses' perceptions of the quality of abdominal surgical nursing care were positive, with more criticism in the nurses’ perceptions. Both patients and nurses gave the lowest evaluation to the quality in the progress of nursing care and the co-operation with significant others. The nurses gave the highest evaluation to the self-assessed level of their competence and the frequency of using competences in practice, with the highest assessment given to situation management and their role at work and the lowest to teaching-coaching and ensuring quality. The nurse perceptions of their empowerment were positive in the qualities and performance of an empowered nurse and empowerment promoting factors, with the highest evaluation in moral principles and sociability and the lowest evaluation in the future-orientedness and expertise. The empowerment-impeding factors were evaluated as negative. The perceptions of the quality of nursing care of both patients and nurses had significant correlations with patient and nurse satisfaction and nurse job independence. The nurse perceptions of their competence and empowerment correlated with their education, the type of the nurse license, completed courses of development of their knowledge and skills, nurse job independence, and nurse satisfaction. The nurse perceptions of the quality of nursing care had a positive correlation with their perceptions of competence and empowerment. Generally, the quality of nursing care was evaluated as high and had correlations with the patients' demographic and satisfaction factors and with the nurse demographic, work-related, and satisfaction factors. The study produced the knowledge that the quality in co-operation with significant others and the progress of nursing process, surgical nurse competence in teaching-coaching, and future-orientedness of surgical nurse empowerment need to be improved in order to develop the quality of abdominal surgical nursing care. The knowledge may be used to offer better services for abdominal surgical patients and increase their satisfaction with nursing care, as well as to increase nurses' satisfaction with work and independence at work. The study suggests implications for clinical practice and management, nursing education, and nursing research.

Hybrid warfare – just a twist of compound warfare? : views on warfare from the United States Armed Forces perspective

The wars the Western armies are involved with today are different from those that were fought in the end of 20th century. To explain this change, the Western military thinkers have come up with various different types of definitions of warfare over the last 30 years, each describing the tendencies involved in the conflicts of the time. The changing nature of conflicts surfaced a new term – hybrid warfare. The term was to describe and explain the multi-modality and complexity of modern day conflict. This thesis seeks the answer for the question: what is the development of thought behind hybrid warfare? In this thesis the Vietnam War (1965-1975) is used as an example of compound warfare focusing on the American involvement in the war. The Second Lebanon War (2006) serves as an example of hybrid warfare. Both case studies include an irregular opposing force, namely National Liberation Front in Vietnam War and Hezbollah in the Second Lebanon War. These two case studies are compared with the term full spectrum operations introduced in the current U.S. Department of Army Field Manual No. 3-0 Operations to see the differences and similarities of each term. The perspective of this thesis is the American point of view. This thesis concludes that hybrid warfare, compound warfare and full spectrum operations are very similar. The first two terms are included in the last one. Although hybrid warfare is not officially defined, it will most likely remain to be used in the discussion in the future, since hybrid wars and hybrid threats are officially accepted terms.

Value Creation in Crowd-Business: Developing a Framework for Successful Implementation of Crowdsourcing Initiatives

By recent years the phenomenon called crowdsourcing has been acknowledged as an innovative form of value creation that must be taken seriously. Crowdsourcing can be defined as an act of outsourcing tasks originally performed inside an organization, or assigned externally in form of a business relationship, to an undefinably large, heterogeneous mass of potential actors. This thesis constructs a framework for successful implementation of crowdsourcing initiatives. Firms that rely entirely on their own research and ideas cannot compete with the innovative capacity that crowd-powered firms have. Nowadays, crowdsourcing has become one of the key capabilities of businesses due to its innovative capabilities, in addition to the existing internal resources of the firm. By utilizing crowdsourcing the business gains access to an enormous pool of competence and knowledge. However, various risks remain such as uncertainty of crowd structure and loss of internal know-how. Crowdsourcing Success Framework introduces a step by step model for implementing crowdsourcing into the everyday operations of the business. It starts from the decision to utilize crowdsourcing and continues further into planning, organizing and execution. Finally, this thesis presents the success factors of crowdsourcing initiative.

The oral motor capacity and feeding performance of preterm newborns at the time of transition to oral feeding

The objective of the present study was to determine the oral motor capacity and the feeding performance of preterm newborn infants when they were permitted to start oral feeding. This was an observational and prospective study conducted on 43 preterm newborns admitted to the Neonatal Intensive Care Unit of UFSM, RS, Brazil. Exclusion criteria were the presence of head and neck malformations, genetic disease, neonatal asphyxia, intracranial hemorrhage, and kernicterus. When the infants were permitted to start oral feeding, non-nutritive sucking was evaluated by a speech therapist regarding force (strong vs weak), rhythm (rapid vs slow), presence of adaptive oral reflexes (searching, sucking and swallowing) and coordination between sucking, swallowing and respiration. Feeding performance was evaluated on the basis of competence (defined by rate of milk intake, mL/min) and overall transfer (percent ingested volume/total volume ordered). The speech therapist's evaluation showed that 33% of the newborns presented weak sucking, 23% slow rhythm, 30% absence of at least one adaptive oral reflex, and 14% with no coordination between sucking, swallowing and respiration. Mean feeding competence was greater in infants with strong sucking fast rhythm. The presence of sucking-swallowing-respiration coordination decreased the days for an overall transfer of 100%. Evaluation by a speech therapist proved to be a useful tool for the safe indication of the beginning of oral feeding for premature infants.

Early detection and intervention for infants at risk of autism spectrum disorders

Autism is a developmental disorder that is characterized by abnonnal social interactions and communications as well as repetitive and restricted activities and interests. There is evidence of a genetic component, as 5% of younger siblings are diagnosed if their older sibling has been diagnosed. Autism is generally not diagnosed until age 3 at the earliest, yet it has been shown that early intervention for children with autism can greatly increase their functioning. Because of this, it is important that symptoms of autism are identified as early as possible so that diagnosis can occur as soon as possible to allow these children the earliest intervention. This thesis was divided into two parts. The first looked at the psychometrics of two proposed measures, the Parent Observation Checklist (POC), administered monthly, and the Infant Behavior Summary Evaluation (mSE), administered bimonthly, to see if they can be used with the infant population to identify autistic symptoms in infants who are at high risk for autism or related problems because they have an older sibling with autism. Study 1 reported acceptable psychometric properties of both the POC and IBSE in terms of test-retest reliability, internal consistency, construct validity and predictive validity. These results provide preliminary evidence that parent report measures can help to detect early symptoms of ASD in infants. The POC was shown to differentiate infants who were diagnosed from a matched group that was not diagnosed by 3 years of age. The second part of this thesis involved a telephone interview of parents who reported developmental and/or behavior problems in their high-risk infants that may be early signs of Autism Spectrum Disorder (ASD). During the interview, a service questionnaire was administered to see what interventions (including strategies recommended by the researchers) their at risk infants and affected older siblings were receiving, how satisfied the parents were with them and how effective they felt the interventions were. 3 Study 2 also yielded promising results. Parents utilized a variety of services for at risk infants and children with ASD. The interventions included empirically validated early intervention (e.g., ABA) to non-empirically validated treatments (e.g., diet therapy). The large number of nonempirically validated treatments parents used was surprising, yet parents reported being involved and satisfied, and thought that the services were effective. Parents' perceptions of their stress levels went down slightly and feelings of competence rose when they accessed services for their infants. Overall, the results of this thesis provide new evidence that parent-report methods hold promise as early detection instruments for ASD in at-risk infants. More research is needed to further validate these instruments as well as to understand the variables related to the parents' choice of early intervention for their at risk and affected children.

Examining the influence of the coach athlete relationship on motivation and performance in female rugby players

The purpose of the study was two-fold; first, the association between interpersonal coaching styles and self-determined motivation was examined, followed by the investigation of the motivation-performance relationship. Participants included 221 female Canadian Interuniversity Sport (CIS) rugby players, aged sixteen to thirty-three (M= 20.1: SD = 2.26), who reported the number of years they played CIS rugby (M= 2.3: SD = 1.37) and organized rugby (M= 5.9: SD = 2.31). Multiple and bivariate regressions were employed with autonomy-support, structure, and involvement accounting for 17%, 41 % and 22% of the variance of competence, autonomy and relatedness. The three basic needs accounted for 40% of the variance of motivation, and motivation accounted for 2% of the variance of athletes' perceptions of performance. Findings indicated that autonomy-support emerged as a predictor of all three basic needs, involvement predicted relatedness and competence, autonomy predicted motivation, and motivation predicted athletes' perception of performance.

Legalistic or Inspirational? Comparing University Conflict of Interest Policies

In response to growing public and policy concern about conflicts of interest (COI) in university research, academic institutions in North America and Europe have introduced policies to manage COI. However, depending on their form and content, COI policies can be more or less helpful in the effective management of COI. In this paper, we examine and compare the design and content of COI policies at two Canadian research universities (the Université de Montréal and the University of Waterloo), which we suggest, exemplify two general categories or poles on a spectrum of policy approaches. We describe 1) a legalistic approach that promotes a concise but rigid structure, and 2) an inspirational approach that encourages principle-based deliberation and wider interpretation. Each of these approaches has its particular strengths and weaknesses. We conclude with some recommendations to help administrators and policy makers improve the quality, utility and effectiveness of university COI policies.

Rapport des parents aux devoirs à la maison : milieux favorisés et milieux défavorisés

Cette recherche vise à voir s’il existe une différence entre les familles favorisées et celles défavorisées en ce qui concerne le rapport qu’elles entretiennent avec les devoirs à la maison. D’après quelques écrits, la réalisation des devoirs peut être plus difficile en milieu défavorisé (Carvalho, 2009; Cooper, Lindsay et Nye, 2000; Dolle, 2007; Grolnick, Benjet, Kurowski, et Apostoleris, 1997 ; Hoover-Dempsey, Bassler et Brissie, 1992; Kronholz, 1997; Odum, 1994; Scott-Jones, 1984 ; Symeou, 2009), et c’est cette problématique qui est concernée dans ce travail. Les participants sont quatorze parents d’élèves du deuxième cycle du primaire de deux écoles, une dans la région montréalaise (milieu défavorisé) et une dans la région des Laurentides (milieu favorisé). Pour réaliser la comparaison, sept parents de chacun des milieux ont été interviewés à l’aide d’un questionnaire portant sur le processus des devoirs, sur la participation parentale et sur leur sentiment de compétence à aider leur enfant durant les devoirs. Les résultats ont montré que la réalisation des devoirs est plus longue en milieu défavorisé et que les conflits sont plus présents dans ce type de milieu. Aussi, la motivation des enfants à l’égard des devoirs en milieu défavorisé est plus faible, ce qui pourrait expliquer le fait que les parents de ce milieu semblent offrir plus de soutien lors des devoirs. Par ailleurs, le soutien des pères lors des devoirs semble être plus fréquent en milieu favorisé et cette situation pourrait s’expliquer par les conditions de travail plus favorables comparativement à celles des pères en milieu défavorisé.

University Textbooks: An Acceptable Conflict of Interest?

Étude de cas / Case study

Reference Letters and Conflict of Interest: A Professor’s Dilemma

Étude de cas / Case study