Surgical outcomes of deep sclerectomy versus Baerveldt aqueous shunt implantation following initial failed deep sclerectomy

Purpose: To examine the efficacy and safety of repeat deep sclerectomy (DS) versus Baerveldt shunt (BS) implantation as second line surgery following failed primary DS. Methods: Fifty one patients were prospectively recruited to undergo BS implantation following failed DS and 51 patients underwent repeat DS, for which data was collected retrospectively. All eyes had at least one failed DS. Surgical success was defined as IOP≤21mmHg and 20% reduction in IOP from baseline. Success rates, number of glaucoma medications (GMs), IOP, and complication rates were compared between the two groups at year 1, post-operatively. Results: Mean age, sex and the proportion of glaucoma subtypes were similar between groups. Preoperatively IOP was significantly lower in DS group vs BS group (18.8mmHg vs 23.8mmHg, p<0.01, two sample t-test). Postoperatively IOP was significantly higher in DS group than BS group (14.6mmHg vs 12.0mmHg, p<0.01, two-sample t-test). In the DS group, 47% of eyes did not achieve 20% reduction in IOP from baseline, as a result the success rates were significantly lower in eyes with DS (51%) than in eyes with BS (88%) (p=0.02, log-rank test). Preoperatively the number of GMs used in DS and BS groups were similar (2.2 vs 2.7 p=0.02, two sample t-test). Postoperatively there remained no significant difference in GMs between groups (0.9 vs 1.1, p= 0.58, two sample t-test). Complication rates were similar between the two groups (12% vs 10%). Conclusions: Baerveldt tube implantation was more effective in lowering IOP than repeat deep sclerectomy in eyes with failed primary DS, at year one. Complications were minor and infrequent in both groups

Perceptions of twelve-step mutual-help groups and their associations with motivation, treatment attendance and alcohol outcomes among chronically homeless individuals with alcohol problems.

BACKGROUND: Twelve-step mutual-help groups (TMGs) are among the most available forms of support for homeless individuals with alcohol problems. Qualitative research, however, has suggested that this population often has negative perceptions of these groups, which has been shown to be associated with low TMG attendance. It is important to understand this population's perceptions of TMGs and their association with alcohol outcomes to provide more appropriate and better tailored programming for this multiply affected population. The aims of this cross-sectional study were to (a) qualitatively examine perception of TMGs in this population and (b) quantitatively evaluate its association with motivation, treatment attendance and alcohol outcomes. METHODS: Participants (N=62) were chronically homeless individuals with alcohol problems who received single-site Housing First within a larger evaluation study. Perceptions of TMGs were captured using an open-ended item. Quantitative outcome variables were created from assessments of motivation, treatment attendance and alcohol outcomes. RESULTS: Findings indicated that perceptions of TMGs were primarily negative followed by positive and neutral perceptions, respectively. There were significant, positive associations between perceptions of TMGs and motivation and treatment attendance, whereas no association was found for alcohol outcomes. CONCLUSIONS: Although some individuals view TMGs positively, alternative forms of help are needed to engage the majority of chronically homeless individuals with alcohol problems.

Sepsis: a roadmap for future research.

Sepsis is a common and lethal syndrome: although outcomes have improved, mortality remains high. No specific anti-sepsis treatments exist; as such, management of patients relies mainly on early recognition allowing correct therapeutic measures to be started rapidly, including administration of appropriate antibiotics, source control measures when necessary, and resuscitation with intravenous fluids and vasoactive drugs when needed. Although substantial developments have been made in the understanding of the basic pathogenesis of sepsis and the complex interplay of host, pathogen, and environment that affect the incidence and course of the disease, sepsis has stubbornly resisted all efforts to successfully develop and then deploy new and improved treatments. Existing models of clinical research seem increasingly unlikely to produce new therapies that will result in a step change in clinical outcomes. In this Commission, we set out our understanding of the clinical epidemiology and management of sepsis and then ask how the present approaches might be challenged to develop a new roadmap for future research.

Positive Outcomes Influence the Rate and Time to Publication, but Not the Impact Factor of Publications of Clinical Trial Results

Objectives: Publication bias may affect the validity of evidence based medical decisions. The aim of this study is to assess whether research outcomes affect the dissemination of clinical trial findings, in terms of rate, time to publication, and impact factor of journal publications. Methods and Findings: All drug-evaluating clinical trials submitted to and approved by a general hospital ethics committee between 1997 and 2004 were prospectively followed to analyze their fate and publication. Published articles were identified by searching Pubmed and other electronic databases. Clinical study final reports submitted to the ethics committee, final reports synopses available online and meeting abstracts were also considered as sources of study results. Study outcomes were classified as positive (when statistical significance favoring experimental drug was achieved), negative (when no statistical significance was achieved or it favored control drug) and descriptive (for non-controlled studies). Time to publication was defined as time from study closure to publication. A survival analysis was performed using a Cox regression model to analyze time to publication. Journal impact factors of identified publications were recorded. Publication rate was 48·4% (380/785). Study results were identified for 68·9% of all completed clinical trials (541/785). Publication rate was 84·9% (180/212) for studies with results classified as positive and 68·9% (128/186) for studies with results classified as negative (p<0·001). Median time to publication was 2·09 years (IC95 1·61-2·56) for studies with results classified as positive and 3·21 years (IC95 2·69-3·70) for studies with results classified as negative (hazard ratio 1·99 (IC95 1·55-2·55). No differences were found in publication impact factor between positive (median 6·308, interquartile range: 3·141-28·409) and negative result studies (median 8·266, interquartile range: 4·135-17·157). Conclusions: Clinical trials with positive outcomes have significantly higher rates and shorter times to publication than those with negative results. However, no differences have been found in terms of impact factor.

Vulnerability as a heuristic for interdisciplinary research: Assessing the thematic and methodological structure of empirical life-course studies

Changes in human lives are studied in psychology, sociology, and adjacent fields as outcomes of developmental processes, institutional regulations and policies, culturally and normatively structured life courses, or empirical accounts. However, such studies have used a wide range of complementary, but often divergent, concepts. This review has two aims. First, we report on the structure that has emerged from scientific life course research by focusing on abstracts from longitudinal and life course studies beginning with the year 2000. Second, we provide a sense of the disciplinary diversity of the field and assess the value of the concept of 'vulnerability' as a heuristic tool for studying human lives. Applying correspondence analysis to 10,632 scientific abstracts, we find a disciplinary divide between psychology and sociology, and observe indications of both similarities of-and differences between-studies, driven at least partly by the data and methods employed. We also find that vulnerability takes a central position in this scientific field, which leads us to suggest several reasons to see value in pursuing theory development for longitudinal and life course studies in this direction.

Planning and reporting of quality-of-life outcomes in cancer trials.

BACKGROUND: Information about the impact of cancer treatments on patients' quality of life (QoL) is of paramount importance to patients and treating oncologists. Cancer trials that do not specify QoL as an outcome or fail to report collected QoL data, omit crucial information for decision making. To estimate the magnitude of these problems, we investigated how frequently QoL outcomes were specified in protocols of cancer trials and subsequently reported. DESIGN: Retrospective cohort study of RCT protocols approved by six research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We compared protocols to corresponding publications, which were identified through literature searches and investigator surveys. RESULTS: Of the 173 cancer trials, 90 (52%) specified QoL outcomes in their protocol, 2 (1%) as primary and 88 (51%) as secondary outcome. Of the 173 trials, 35 (20%) reported QoL outcomes in a corresponding publication (4 modified from the protocol), 18 (10%) were published but failed to report QoL outcomes in the primary or a secondary publication, and 37 (21%) were not published at all. Of the 83 (48%) trials that did not specify QoL outcomes in their protocol, none subsequently reported QoL outcomes. Failure to report pre-specified QoL outcomes was not associated with industry sponsorship (versus non-industry), sample size, and multicentre (versus single centre) status but possibly with trial discontinuation. CONCLUSIONS: About half of cancer trials specified QoL outcomes in their protocols. However, only 20% reported any QoL data in associated publications. Highly relevant information for decision making is often unavailable to patients, oncologists, and health policymakers.

Clinical Development Strategies and Outcomes in First-in-Human Trials of Monoclonal Antibodies.

PURPOSE: We conducted a comprehensive review of the design, implementation, and outcome of first-in-human (FIH) trials of monoclonal antibodies (mAbs) to clearly determine early clinical development strategies for this class of compounds. METHODS: We performed a PubMed search using appropriate terms to identify reports of FIH trials of mAbs published in peer-reviewed journals between January 2000 and April 2013. RESULTS: A total of 82 publications describing FIH trials were selected for analysis. Only 27 articles (33%) reported the criteria used for selecting the starting dose (SD). Dose escalation was performed using rule-based methods in 66 trials (80%). The median number of planned dose levels was five (range, two to 13). The median of the ratio between the highest planned dose and the SD was 27 (range, two to 3,333). Although in 56 studies (68%) at least one grade 3 or 4 toxicity event was reported, no dose-limiting toxicity was observed in 47 trials (57%). The highest planned dose was reached in all trials, but the maximum-tolerated dose (MTD) was defined in only 13 studies (16%). The median of the ratio between MTD and SD was eight (range, four to 1,000). The recommended phase II dose was indicated in 34 studies (41%), but in 25 (73%) of these trials, this dose was chosen without considering toxicity as the main selection criterion. CONCLUSION: This literature review highlights the broad design heterogeneity of FIH trials testing mAbs. Because of the limited observed toxicity, the MTD was infrequently reached, and therefore, the recommended phase II dose for subsequent clinical trials was only tentatively defined.

Research networks and inventors’ mobility as drivers of innovation evidence from Europe

We investigate the importance of the labour mobility of inventors, as well as the scale, extent and density of their collaborative research networks, for regional innovation outcomes. To do so, we apply a knowledge production function framework at the regional level and include inventors’ networks and their labour mobility as regressors. Our empirical approach takes full account of spatial interactions by estimating a spatial lag model together, where necessary, with a spatial error model. In addition, standard errors are calculated using spatial heteroskedasticity and autocorrelation consistent estimators to ensure their robustness in the presence of spatial error autocorrelation and heteroskedasticity of unknown form. Our results point to the existence of a robust positive correlation between intraregional labour mobility and regional innovation, whilst the relationship with networks is less clear. However, networking across regions positively correlates with a region’s innovation intensity.

Prevalence and clinical outcomes for patients with MET protein expression in patients with non-small cell lung cancer in Europe: Results from the European Thoracic Oncology Platform Lungscape Project.

Aim The reported prevalence of MET overexpression varies from 25-55% in non-small cell lung cancer (NSCLC) and clinical correlations are emerging slowly. In a well-defined NSCLC cohort of the Lungscape program, we explore the epidemiology, the natural history of IHC MET positivity and its association to OS, RFS and TTR. Methods Resected stage I-III NSCLC identified based on the quality of clinical data and FFPE tissue availability were assessed for MET expression using immunohistochemistry (IHC) on TMAs (CONFIRM anti total c-MET assay, clone SP44, Ventana BenchMark platform). All cases were analysed at participating pathology laboratories using the same protocol, after passing an external quality assurance program. MET positive status is defined as ≥ 50% of tumor cells staining with 2+ or 3+ intensity. Results A total of 2709 cases are included in the iBiobank and will be analysed. IHC MET expression is currently available for 1552 patients, with positive MET IHC staining in 380 cases [24.5%; IHC 3+ in 157 cases (41.3%) and 2+ in 223 cases (58.7%)]. The cohort of 1552 patients includes 48.2%, 44.7% and 4.4% cases of adenocarcinoma, squamous and large cell histologies, respectively. IHC MET status was independent of stage, age and smoking history. Significant differences in MET positivity were associated with gender (32% vs. 21% for female vs. male, p < 0.001), with performance status (25% vs. 18% for 0 vs. 1-3, p = 0.006), and histology (34%, 14% and 24% for adenocarcinoma, squamous and large cell carcinoma, p < 0.001). IHC MET positivity was independent of the IHC ALK status (p = 0.08). At last FU, 52% of patients were still alive, with a median FU of 4.8 yrs. No association of IHC MET was found with OS, RFS or TTR. Conclusions The preliminary results for this large multicentre European cohort describe a prevalence of MET overexpression that seems lower than previous observations in NSCLC, such as reported for the OAM4971g trial, suggesting potential biological differences between surgically resected and metastatic disease. Analysis for the full cohort is ongoing and results will be presented. Disclosure L. Bubendorf: Disclosures: Stock ownership: Roche Advisory boards: Roche, Pfizer Research support: Roche; K. Schulze: Full time employee of Roche; A. Das-Gupta: I am a full time employee of Roche. All other authors have declared no conflicts of interest.

Bias in dissemination of clinical research findings: structured OPEN framework of what, who and why, based on literature review and expert consensus.

OBJECTIVE: The aim of this study is to review highly cited articles that focus on non-publication of studies, and to develop a consistent and comprehensive approach to defining (non-) dissemination of research findings. SETTING: We performed a scoping review of definitions of the term 'publication bias' in highly cited publications. PARTICIPANTS: Ideas and experiences of a core group of authors were collected in a draft document, which was complemented by the findings from our literature search. INTERVENTIONS: The draft document including findings from the literature search was circulated to an international group of experts and revised until no additional ideas emerged and consensus was reached. PRIMARY OUTCOMES: We propose a new approach to the comprehensive conceptualisation of (non-) dissemination of research. SECONDARY OUTCOMES: Our 'What, Who and Why?' approach includes issues that need to be considered when disseminating research findings (What?), the different players who should assume responsibility during the various stages of conducting a clinical trial and disseminating clinical trial documents (Who?), and motivations that might lead the various players to disseminate findings selectively, thereby introducing bias in the dissemination process (Why?). CONCLUSIONS: Our comprehensive framework of (non-) dissemination of research findings, based on the results of a scoping literature search and expert consensus will facilitate the development of future policies and guidelines regarding the multifaceted issue of selective publication, historically referred to as 'publication bias'.

Setting priorities in clinical and health services research: Properties of an adapted and updated method

Objectives: The objectives of this study is to review the set of criteria of the Institute of Medicine (IOM) for priority-setting in research with addition of new criteria if necessary, and to develop and evaluate the reliability and validity of the final priority score. Methods: Based on the evaluation of 199 research topics, forty-five experts identified additional criteria for priority-setting, rated their relevance, and ranked and weighted them in a three-round modified Delphi technique. A final priority score was developed and evaluated. Internal consistency, test–retest and inter-rater reliability were assessed. Correlation with experts’ overall qualitative topic ratings were assessed as an approximation to validity. Results: All seven original IOM criteria were considered relevant and two new criteria were added (“potential for translation into practice”, and “need for knowledge”). Final ranks and relative weights differed from those of the original IOM criteria: “research impact on health outcomes” was considered the most important criterion (4.23), as opposed to “burden of disease” (3.92). Cronbach’s alpha (0.75) and test–retest stability (interclass correlation coefficient = 0.66) for the final set of criteria were acceptable. The area under the receiver operating characteristic curve for overall assessment of priority was 0.66. Conclusions: A reliable instrument for prioritizing topics in clinical and health services research has been developed. Further evaluation of its validity and impact on selecting research topics is required

Choice of Business Process Modeling Methodology - Case Northern Dimension Research Centre (NORDI) in Lappeenranta University of Technology

The main outcome of the master thesis is innovative solution, which can support a choice of business process modeling methodology. Potential users of this tool are people with background in business process modeling and possibilities to collect required information about organization’s business processes. Master thesis states the importance of business process modeling in implementation of strategic goals of organization. It is made by revealing the place of the concept in Business Process Management (BPM) and its particular case Business Process Reengineering (BPR). In order to support the theoretical outcomes of the thesis a case study of Northern Dimension Research Centre (NORDI) in Lappeenranta University of Technology was conducted. On its example several solutions are shown: how to apply business process modeling methodologies in practice; in which way business process models can be useful for BPM and BPR initiatives; how to apply proposed innovative solution for a choice of business process modeling methodology.

Professional development among educators pursuing a B.Ed. program in special education in Tanzania : a study of motives and perceived outcomes

Implementation of different policies and plans aiming at providing education for all is a challenge in Tanzania. The need for educators and professionals with relevant knowledge and qualifications in special education is substantial. Teacher education does not equip educators with sufficient knowledge and skills in special education and professional development programs in special education are few in number. Up to 2005 no degree programs in special education at university level were available in Tanzania. The B.Ed. Special Education program offered by the Open University of Tanzania in collaboration with Åbo Akademi University in Finland was one of the efforts aimed at addressing the big national need for teachers and other professionals with degree qualifications in special education. This pilot program offered unique possibilities to study professional development in Tanzania. The research group in this study consisted of the group of students who participated in the degree program 2005-2007. The study is guided by three theoretical perspectives: individual, social and societal. The individual perspective emphasizes psychological factors as motives, motivation, achievement, self-directed behavior and personal growth. Within social perspective, professional development is viewed as situated within the social and cultural context. The third perspective, the societal, focuses on change, reforms, innovations and transformation of school systems and societies. Accordingly, professional development is viewed as an individual, social and societal phenomenon. The overall aim of the study is to explore the participants’ motives for participating in a B.Ed. Special Education program and the perceived outcomes of the program in terms of professional development. In order to achieve the objectives of the study, a case study approach was adopted. Questionnaires and semi-structured interviews were administered in three waves between January 2007 and February 2009 to the 35 educators participating in the B.Ed. Special Education program. The findings of the study reveal that the participants expressed motives which were related to job performance, knowledge, skills, academic degree and career. Also altruistic motives were expressed by the participants in terms of helping and supporting students with special needs and their communities. The perceived outcomes of the program were in line with the expressed motives. However, the results indicate that the participants also learned new skills, as interaction skills and guidance and counseling skills. Increased self-confidence was also mentioned as an outcome. The participants also got deepened understanding of disability issues. In addition, they learned strategies for creating awareness of persons with disability in the communities. Thus the findings of the study indicate positive outcomes of the program in terms of professional development. The conclusion of the study is that individual, social and societal factors interact when it comes to explaining why Tanzanian educators in special education choose to pursue a degree program in special education. The individual motives, as increased knowledge and better prospects of career development interact with the social and societal motives to help and support vulnerable student groups. The study contributes to increased understanding of the complexity of professional development and of the realities educators meet when educational reforms are implemented in a developing country.

Antecedents and Performance Outcomes of Entrepreneurial Orientation: a Comparative Cross-Country Study

Development of entrepreneurial orientation (EO) within a company is considered to be significant for firm performance in a contemporary market society with constantly changing environment. Considered as entrepreneurial, the firm is able to innovate, make risky investments and be proactive. The purpose of the thesis is to investigate factors which influence EO, the impact of EO on firm performance, and a mediating role of EO in developed and emerging market contexts. The empirical research is conducted quantitatively in a form of a survey in Russia and Finland. The results of the thesis have shown that the relationship between antecedents, EO and firm performance outcomes is different in developed and emerging contexts and can be explained by cultural differences and institutional development. The empirical research has both theoretical and practical novelty. It contributes to the existing literature on EO by the usage of comparative cross-country approach and a broader three-way interaction model between the variables. A general practical implication of the research is that managers may benefit from developing entrepreneurial strategic posture in particular contexts.

Control of CD4 gene expression: connecting signals to outcomes in T cell development

The control of CD4 gene expression is essential for proper T lymphocyte development. Signals transmitted from the T-cell antigen receptor (TCR) during the thymic selection processes are believed to be linked to the regulation of CD4 gene expression during specific stages of T cell development. Thus, a study of the factors that control CD4 gene expression may lead to further insight into the molecular mechanisms that drive thymic selection. In this review, we discuss the work conducted to date to identify and characterize the cis-acting transcriptional control elements in the CD4 locus and the DNA-binding factors that mediate their function. From these studies, it is becoming clear that the molecular mechanisms controlling CD4 gene expression are very complex and differ at each stage of development. Thus, the control of CD4 expression is subject to many different influences as the thymocyte develops.