Design of Phase II cancer trials evaluating survival probabilities

BACKGROUND: Phase II cancer studies are undertaken to assess the activity of a new drug or a new treatment regimen. Activity is sometimes defined in terms of a survival probability, a binary outcome such as one-year survival that is derived from a time-to-event variable. Phase II studies are usually designed with an interim analysis so they can be stopped if early results are disappointing. Most designs that allow for an interim look are not appropriate for monitoring survival probabilities since many patients will not have enough follow-up by the time of the interim analysis, thus necessitating an inconvenient suspension of accrual while patients are being followed. METHODS: Two-stage phase II clinical trial designs are developed for evaluating survival probabilities. These designs are compared to fixed sample designs and to existing designs developed to monitor binomial probabilities to illustrate the expected reduction in sample size or study length possible with the use of the proposed designs. RESULTS: Savings can be realized in both the duration of accrual and the total study length, with the expected savings increasing as the accrual rate decreases. Misspecifying the underlying survival distribution and the accrual rate during the planning phase can adversely influence the operating characteristics of the designs. CONCLUSION: Two-stage phase II trials for assessing survival probabilities can be designed that do not require prolonged suspension of patient accrual. These designs are more efficient than single stage designs and more practical than existing two-stage designs developed for binomial outcomes, particularly in trials with slow accrual

Food Habits of the Red Fox in Nebraska

Food habits of red foxes (Vulpes vulpes) in Nebraska were deter· mined by analysis of 234 fox stomachs obtained from fur dealers during October 1978 through February 1979. Mammals were found most frequently (84%) and constituted the majority (77.4%) of the volume of food items. Cottontails (Sylvilagus floridanus) and jack· rabbits (Lepus sp.) were the most important items consumed based on frequency of occurrence (45.8%) and volume (49.2%). Remains of birds were difficult to identify, but ring-necked pheasants (Phasianus colchicus) occurred in 6.9% of the stomachs and comprised 8.4% of the volume of items consumed. Male foxes had a higher volume of rabbits (55.6%) in their stomachs than did females (39.3%), whereas females had a higher volume (24.6%) of mice and voles than did males (14.6%). Remains of livestock and poultry in fox stomachs rarely were found (2.6%) and constituted only about 1% of the volume of the foxes\u27 diet. Game animals comprised 62.5% of the volume of the foxes\u27 diet

TETRA Observation of Gamma Rays at Ground Level Associated with Nearby Thunderstorms

Terrestrial Gamma ray Flashes (TGFs) -- very short, intense bursts of electrons, positrons, and energetic photons originating from terrestrial thunderstorms -- have been detected with satellite instruments. TETRA, an array of NaI(Tl) scintillators at Louisiana State University, has now been used to detect similar bursts of 50 keV to over 2 MeV gamma rays at ground level. After 2.6 years of observation, twenty-four events with durations 0.02- 4.2 msec have been detected associated with nearby lightning, three of them coincident events observed by detectors separated by ~1000 m. Nine of the events occurred within 6 msec and 3 miles of negative polarity cloud-to-ground lightning strokes with measured currents in excess of 20 kA. The events reported here constitute the first catalog of TGFs observed at ground level in close proximity to the acceleration site.Comment: To be published in Journal of Geophysical Research: Space Phys. 118,

An Exploratory Study of the Experiences of Gay, Lesbian and Bisexual Fraternity and Sorority Members Revisited

The lead author questioned over 500 self-identified gay, lesbian, and bisexual (GLB) fraternity and sorority members to assess their reasons for joining; how their membership affected their sexual identity development and intimate relationships; the degree of homophobia and heterosexism encountered; how sexual orientation affected the quality of their fraternal experiences; and the level of acceptance or rejection they faced. Many respondents were in the early phases of sexual identity development at the time they joined, and most chose to conceal their sexual orientation from their fellow members. This study details the reactions from fellow members, assesses satisfaction with the fraternity or sorority experience, and reports the level of involvement of GLB students in their fraternities or sororities

An Exploratory Study of the Experiences of Gay, Lesbian and Bisexual Fraternity and Sorority Members Revisited

The lead author questioned over 500 self identified gay, lesbian, and bisexual (GLB) fraternity and sorority members to assess their reasons for joining; how their membership affected their sexual identity development and intimate relationships; the degree of homophobia and heterosexism encountered; how sexual orientation affected the quality of their fraternal experiences; and the level of acceptance or rejection they faced. Many respondents were in the early phases of sexual identity development at the time they joined, and most chose to conceal their sexual orientation from their fellow members. This study details the reactions from fellow members, assesses satisfaction with the fraternity or sorority experience, and reports the level of involvement of GLB students in their fraternities or sororities

Fusion of secretory vesicles isolated from rat liver

Secretory vesicles isolated from rat liver were found to fuse after exposure to Ca2+. Vescle fusion is characterized by the occurrence of twinned vesicles with a continuous cleavage plane between two vesicles in freeze-fracture electron microscopy. The number of fused vesicles increases with increasing Ca2+-concentrations and is half maximal around 10–6 m. Other divalent cations (Ba2+, Sr2+, and Mg2+) were ineffective. Mg2+ inhibits Ca2+-induced fusion. Therefore, the fusion of secretory vesiclesin vitro is Ca2+ specific and exhibits properties similar to the exocytotic process of various secretory cells. Various substances affecting secretionin vivo (microtubular inhibitors, local anethetics, ionophores) were tested for their effect on membrane fusion in our system. The fusion of isolated secretory vesicles from liver was found to differ from that of pure phospholipid membranes in its temperature dependence, in its much lower requirement for Ca2+, and in its Ca2+-specificity. Chemical and enzymatic modifications of the vesicle membrane indicate that glycoproteins may account for these differences

Immediate early protein of equid herpesvirus type 1 as a target for cytotoxic T-lymphocytes in the thoroughbred horse

Cytotoxic T-lymphocytes (CTLs) are associated with protective immunity against disease caused by equid herpesvirus type 1 (EHV-1). However, the EHV-1 target proteins for CTLs are poorly defined. This limits the development of vaccine candidates designed to stimulate strong CTL immunity. Here, classical CTL assays using lymphocytes from horses of three defined MHC class I types that experienced natural infection with EHV-1 and a modified vaccinia virus construct containing an EHV-1 gene encoding the immediate-early (IE) protein are reported. Horses homozygous for the equine leukocyte antigen (ELA)-A2 haplotype, but not the ELA-A5 haplotype, produced MHC-restricted CTL responses against the IE protein. Previously, horses homozygous for the ELA-A3 haplotype also mounted CTL responses against the IE protein. Both haplotypes are common in major horse breeds, including the Thoroughbred. Thus, the IE protein is an attractive candidate molecule for future studies of T-cell immunity to EHV-1 in the horse

Health Literacy and Computer-Assisted Instruction: Usability and Patient Preference

The authors investigated the feasibility of using computer-assisted instruction in patients of varying literacy levels by examining patients’ preferences for learning and their ability to use 2 computer-based educational programs. A total of 263 participants 50–74 years of age with varying health literacy levels interacted with 1 of 2 educational computer programs as part of a randomized trial of a colorectal cancer screening decision aid. A baseline and postprogram evaluation survey were completed. More than half (56%) of the participants had limited health literacy. Regardless of literacy level, doctors were the most commonly used source of medical information—used frequently by 85% of limited and adequate literacy patients. In multivariate logistic regression, only those with health insurance (OR = 2.35, p = .06) and computer use experience (OR = 0.39, p .03) predicted the ability to complete the programs without assistance compared with those without health insurance or prior computer use, respectively. Although patients with limited health literacy had less computer experience, the majority completed the programs without any assistance and stated that they learned more than they would have from a brochure. Future research should investigate ways that computer-assisted instruction can be incorporated in medical care to enhance patient understanding