Optimal designs for dose finding studies

Identifying the "right" dose is one of the most critical and difficult steps in the clinical development process of any medicinal drug. Its importance cannot be understated: selecting too high a dose can result in unacceptable toxicity and associated safety problems, while choosing too low a dose leads to smaller chances of showing sufficient efficacy in confirmatory trials, thus reducing the chance of approval for the drug. In this paper we investigate the problem of deriving e?cient designs for the estimation of the minimum effective dose (MED) by determining the appropriate number and actual levels of the doses to be administered to patients, as well as their relative sample size allocations. More specifically, we derive local optimal designs that minimize the asymptotic variance of the MED estimate under a particular dose response model. The small sample properties of these designs are investigated via simulation, together with their sensitivity to misspeciffication of the true parameter values and of the underlying dose response model. Finally, robust optimal designs are constructed, which take into account a set of potential dose response profiles within classes of models commonly used in practice. --minimum effective dose,c-optimal design,dose response,Elfving's theorem

High zenith angle observations of PKS 2155-304 with the MAGIC telescope

The high frequency peaked BL Lac PKS 2155-304 with a redshift z=0.116 was discovered 1997 in the VHE range by the University of Durham Mark 6 gamma-ray telescope in Australia with a flux corresponding to approx. 0.2 times the Crab Nebula flux. It was later observed and detected with high significance by the Southern observatories CANGAROO and H.E.S.S. establishing this source as the best studied Southern TeV blazar. Detection from the Northern hemisphere was very difficult due to challenging observation conditions under large zenith angles. In July 2006, the H.E.S.S. collaboration reported an extraordinary outburst of VHE gamma-emission. During the outburst, the VHE gamma-ray emission was found to be variable on the time scales of minutes and at a mean flux of approx. 7 times the flux observed from the Crab Nebula. The MAGIC collaboration operates a 17m imaging air Cherenkov Telescope at La Palma (Northern Hemisphere). Follow up observations of the extraordinary outburst have been triggered in a Target of Opportunity program by an alert from the H.E.S.S. collaboration. The measured spectrum and light curve are presented.Comment: Contribution to the 31st ICRC, Lodz, Poland, July 200

Research and Applications of the Processes of Performance Appraisal: A Bibliography of Recent Literature, 1981-1989

[Excerpt] There have been several recent reviews of different subtopics within the general performance appraisal literature. The reader of these reviews will find, however, that the accompanying citations may be of limited utility for one or more reasons. For example, the reference sections of these reviews are usually composed of citations which support a specific theory or practical approach to the evaluation of human performance. Consequently, the citation lists for these reviews are, as they must be, highly selective and do not include works that may have only a peripheral relationship to a given reviewer\u27s target concerns. Another problem is that the citations are out of date. That is, review articles frequently contain many citations that are fifteen or more years old. The generation of new studies and knowledge in this field occurs very rapidly. This creates a need for additional reference information solely devoted to identifying the wealth of new research, ideas, and writing that is changing the field

FORTRAN 90 and SAS-IML Programs for Computation of Critical Values for Multiple Testing and Simultaneous Confidence Intervals

See paper for mathematical introduction.

Cognitive Ability and Career Attainment: The Moderating Effects of Early Career Success

Three explanations regarding the prediction that early career success will moderate the relationship between cognitive ability and career attainment are presented along with an empirical examination of this issue. Using longitudinal data provided for 156 managerial, professional, and technical employees, significant moderating effects for an age-graded index of early career success were observed. The relationships between two measures of cognitive ability and later career job level were stronger for individuals identified as below average with respect to early career success than for their above average counterparts. These results agree with the proposition that the acquisition of knowledge, skills, and information is particularly dependent upon cognitive ability for inhviduals competing without the advantages associated with early career signals of high potential

Political Influence Behavior and Career Success

In a recent review of the literature on politics and influence behavior in personnel/human resource management, Ferris and Judge (1991) noted that no studies had directly investigated the relationship between influence behavior and overall career success. In the present study the effect of political influence behavior on career success was investigated. Drawing from past research on influence behavior and relevant theory from social psychology, the effect of political influence behavior on career success was hypothesized to depend on the type of influence tactic employed. Support was found for the effect of political influence behavior in predicting career success, and for the differential effectiveness of influence behaviors. Implications of the results for the study of careers and career management processes are discussed

Reframing Turnover/Personality Research in the Context of the Attraction-Selection-Attrition Hypothesis

This paper re-examines data originally reported by Cowan & Dreher (1983) in their examination of personality correlates of turnover among managerial, professional, and technical employees. It is intended to reframe the relationship between personality and turnover in light of recent attention on the attraction-selection-attrition hypothesis and to make the results of the original study more accessable to those studying these issues. Results show no relationship between homogeneity based on personality dimensions measured by the Guilford-Zimmerman Temperament Survey (GZTS) and attrition from the organization. Therefore, no support can be offered for the homogeneity hypothesis. Based on these and other failures to find significant relationships between personality dimensions and homogeneity, we suggest that future research about the causes and effects of homogeneity should be based on research that delineates the domain of organizational fit

Reports on an Alternative Measure of Affective Disposition

Researchers investigating the dispositional source of job satisfaction have often used negative or positive affectivity as the measure of affective disposition. The present study tested the validity of an alternative measure of affective disposition which consists of an assessment of affective reactions to neutral stimuli common to everyday life. Results indicated that the measure, termed the Neutral Objects Satisfaction Questionnaire (NOSQ), displayed favorable psychometric properties. Furthermore, the NOSQ may be a better assessment of affective disposition than positive or negative affectivity because it had greater stability over time than one of the most common measures of positive and negative affectivity