Multiple testing to establish superiority/equivalence of a new treatment compared with kappa standard treatments

In this paper we develop multiple hypotheses testing procedures to compare a new treatment with a set of standard treatments in a clinical trial. The aim is to classify the new treatment with respect to each of the standards, by specifying those to which the new treatment is superior, those to which the new treatment is equivalent and those to which one can establish neither superiority nor equivalence. We propose several stepwise procedures and compare them with respect to their familywise error rates and power. The step-down methods SD1 and SD2 test for superiority first, followed by tests for equivalence for those comparisons where we cannot establish superiority. The step-up methods SU1 and SU2 test for equivalence first, followed by tests for superiority for those comparisons where we can establish at least equivalence. The methods SD3 and SU3 apply the tests for superiority and equivalence in pairs. All the methods require that we specify a threshold value delta > 0 in advance for defining equivalence. In applications where it is not possible to specify a value delta, we can use the method SD1 by testing for superiority first, followed by one-sided confidence limits on the efficacy differences for those comparisons where we cannot establish superiority.     

L-(-)-desmethylselegiline, a metabolite of selegiline [L-(-)-deprenyl], protects mesencephalic dopamine neurons from excitotoxicity in vitro

Selegiline [L-(-)-deprenyl], a monoamine oxidase B inhibitor, has been used in the treatment of Parkinson's disease as a putative neuroprotective agent. Selegiline is metabolized rapidly in the gastrointestinal tract and liver to desmethylselegiline (DMS) and methamphetamine. We have previously shown that selegiline protects dopamine neurons in mesencephalic cultures from toxicity resulting from activation of glutamate receptors. In the present study we examined whether DMS has similar neuroprotective effects. Our data show that DMS protects dopamine neurons from N-methyl-D-aspartate receptor-mediated excitotoxic damage. The efficacy of DMS is greater than that of selegiline, as it can cause protection at lower concentrations and provide significantly greater levels of protection at the same concentrations. Our results suggest that DMS might be the active compound responsible for the neuroprotective properties of selegiline.     

Alterations in adhesion, transport, and membrane characteristics in an adhesion-deficient pseudomonad

A stable adhesion-deficient mutant of Burkholderia cepacia G4, a soil pseudomonad, was selected in a sand column assay. This mutant (ENV435) was compared to the wild-type strain by examining the adhesion of the organisms to silica sand and their transport through two aquifer sediments that differed in their sand, silt, and clay contents. We compared the longitudinal transport of the wild type and the adhesion mutant to the transport of a conservative chloride tracer in 25-cm-long glass columns. The transport of the wild-type strain was severely retarded compared to the transport of the conservative tracer in a variety of aquifer sediments, while the adhesion mutant and the conservative tracer traveled at similar rates. An intact sediment core study produced similar results; ENV435 was transported at a faster rate and in much greater numbers than G4. The results of hydrophobic interaction chromatography revealed that G4 was significantly more hydrophobic than ENV435, and polyacrylamide gel electrophoresis revealed significant differences in the lipopolysaccharide O-antigens of the adhesion mutant and the wild type. Differences in this cell surface polymer may explain the decreased adhesion of strain ENV435.     

Increased cancer mortality following a history of nonmelanoma skin cancer

CONTEXT: Cancer registries have reported an increased incidence of melanoma and certain noncutaneous cancers following nonmelanoma skin cancer (NMSC). Whether these findings were attributable to intensified surveillance, shared risk factors, or increased cancer susceptibility remains unclear. OBJECTIVE: To determine whether a history of NMSC predicts cancer mortality. DESIGN: Prospective cohort with 12-year mortality follow-up adjusted for multiple risk factors. SETTING: Cancer Prevention Study II, United States and Puerto Rico. PARTICIPANTS: Nearly 1.1 million adult volunteers who completed a baseline questionnaire in 1982. MAIN OUTCOME MEASURE: Deaths due to all cancers and common cancers. RESULTS: After adjusting for age, race, education, smoking, obesity, alcohol use, and other conventional risk factors, a baseline history of NMSC was associated with increased total cancer mortality (men's relative risk [RR], 1.30; 95% confidence interval [CI], 1.23-1.36; women's RR, 1.26; 95% CI, 1.17-1.35). Exclusion of deaths due to melanoma reduced these RRs only slightly. Mortality was increased for the following cancers: melanoma (RR, 3.36 in men, 3.52 in women); pharynx (RR, 2.77 in men, 2.81 in women); lung (RR, 1.37 in men, 1.46 in women); non-Hodgkin lymphoma (RR, 1.32 in men, 1.50 in women); in men only, salivary glands (RR, 2.96), prostate (RR, 1.28), testis (RR, 12.7), urinary bladder (RR, 1.41), and leukemia (RR, 1.37); and in women only, breast (RR, 1.34). All-cause mortality was slightly increased (adjusted men's RR, 1.03 [95% CI, 1.00-1.06]; women's RR, 1.04 [95% CI, 1.00-1.09]). CONCLUSIONS: Persons with a history of NMSC are at increased risk of cancer mortality. Although the biological mechanisms are unknown, a history of NMSC should increase the clinician's alertness for certain noncutaneous cancers as well as melanoma.     

Bone response to implant surface morphology

This study was designed to measure implant osseointegration using different surface treatments. Bilateral distal intramedullary implantation of titanium cylinders 25 mm x 5 mm was performed in 60 rabbits. The 3 surfaces tested were fiber mesh, mean pore size 400 microns; grit-blasted, mean surface roughness 6 microns; and acid-etched, mean surface roughness 18 microns. Scanning electron microscopy was used to measure the percentage of the surface of each implant in contact with bone at 2, 6, and 12 weeks postimplantation. Mechanical pull-out testing of the bone-implant interface was performed at 12 weeks. Overall, acid-etched surfaces demonstrated greater mean osseointegration than fiber mesh surfaces. All 3 surfaces demonstrated similar interface strengths. Acid etching has potential as a means of enhancing bony apposition in cementless fixation.     

Prevalence and Predictors of Transitions in Smoking Behavior Among College Students.

The prevalence of smoking among college students is surprisingly high and represents a significant public health issue. However, there are few longitudinal studies of smoking in this population. This study examined the prevalence and predictors of transitions in smoking behavior among a cohort of 548 college students. Over the course of 4 years, 87% of daily smokers and almost 50% of occasional smokers continued to smoke. Among nonsmokers, 11.5% began smoking occasionally and none became daily smokers. In general, predictors of smoking behavior change were significant only among baseline occasional smokers and included gender, smoking outcome expectancies, and affect regulation expectations. Peer and parental smoking, demographics, affect, stress, and alcohol use were generally not predictive of change. Tobacco control interventions targeted at college students are clearly warranted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age of initiating selected health-risk behaviors among high school students in the United States

The XYL1 and XYL2 genes from Pichia stipitis encoding xylose reductase (XR) and xylilitol dehydrogenase (XDH), respectively, were transformed into Saccharomyces cerevisiae. These two genes were placed in different directions under the control of the alcohol dehydrogenase I (ADHI) and phosphoglycerate kinase (PGK) promoters and inserted into the E. coli-yeast shuttle plasmid YEp24. Different recombinant S. cerevisiae strains were constructed with different specific activities of XR and XDH. The highest XR or XDH activities were obtained when the expressed gene was controlled by the PGK promoter and located downstream after the ADHI promoter-gene-terminator sequence. The XR/XDH ratio (ratio of specific enzyme activities of XR and XDH) in these recombinant S. cerevisiae strains varied from 17.5 to 0.06. In order to enhance xylose utilization, in the XYL1, XYL2 containing S. cerevisiae strains, the native TKL1 gene encoding transketolase and the TALI gene encoding transaldolase were also overexpressed, which showed considerably good growth on the xylose plate. Fermentation of the recombinant S. cerevisiae strains containing XYL1, XYL2, TKL1, and TAL1 were studied with mixtures of glucose and xylose. The strain with XR/XDH ratio of 0.06 consumed 3.25 g/L xylose and formed no xylitol and less glycerol and acetic acid, but more ethanol compared with the strains with a higher XR/XDH ratio.     

Enhancement of outcome from intracytoplasmic sperm injection: does co-culture or assisted hatching improve implantation rates?

In two separate prospectively randomized trials, intracytoplasmic sperm injection (ICSI) cycles were studied in a controlled manner to monitor the effects of either bovine oviductal epithelial cell co-culture (n = 119) or assisted hatching by zona drilling (n = 100). In the first study, immediately following ICSI, all eggs were placed directly either onto partial monolayers of bovine oviductal cells or into regular culture medium. Although the embryo developmental rate was apparently compromised in part by the presence of the co-culture cells, ultimately there were no significant differences in either the viable pregnancy rate (31.6% co-culture versus 29.0% control) or the embryonic implantation rate (11.4% co-culture versus 13.6% control). Assisted hatching also had no significant impact on ICSI cycle outcome in terms of either the viable pregnancy rate (30.0% assisted hatching versus 32.0% control) or the embryonic implantation rate (8.5% assisted hatching versus 13.5% control). However, in female patients aged > or = 35 years, assisted hatching appeared to convey a marginally significant benefit in terms of both the viable pregnancy rate (35.5% assisted hatching versus 11.1% control) and the embryonic implantation rate (10.3% assisted hatching versus 3.1% control). It seems that the overall improvement of ICSI cycle outcome cannot be achieved by the general application of either co-culture or assisted hatching. Nevertheless, it is possible that there remain specific patient groups that might benefit from selected use of either of these modalities.     

Loss of physical functioning among geriatric cancer patients: relationships to cancer site, treatment, comorbidity and age

This study investigated differences in physical functioning and physical role limitations according to cancer site and treatment modality in a sample of 590 patients 65 years and older diagnosed with breast, colon, lung or prostate cancer. Analysis of covariance procedures were utilised to test for differences in levels of physical functioning and physical role limitations according to cancer site and treatment modality, adjusting for differences in age, comorbid conditions and retrospective physical functioning. Physical functioning and physical role limitations were measured using two subscales of the Medical Outcomes Studies MOS 36-item Short Form Health Survey (SF-36). Physical functioning prior to diagnosis, and to a lesser degree comorbidity, contributed significantly to current levels of physical functioning and physical role limitations. Patients with lung cancer reported lower physical functioning and physical role limitation scores than patients with prostate cancer, and patients treated with surgery only reported lower physical functioning and physical role limitation scores than patients treated with neither surgery nor radiation. No gender differences were observed among the reduced sample consisting of patients with colon or lung cancer. It is important not only that physicians and oncologists are cognizant of the fact that some cancers (particularly lung cancer) may be more physically debilitating than others, but that the patient's history of comorbid conditions and pre-existing physical limitations may be important factors in predicting current physical functioning.     

Allergy to Ficus benjamina: at the workplace and at home

In four patients, two women aged 40 and 42 years and two men aged 49 and 37 years, type I allergy to Ficus benjamina was established. Two patients had been sensitized by contact with these pot plants at their homes. The other two patients were plant growers. F. benjamina is a non-flowering, currently very popular pot plant to be found in both private houses and public buildings. The symptoms comprise itching and swelling of the eyelids, tears, running nose, wheezing and dyspnoea. In one plant grower contact urticaria progressing to dermatitis of the hand was the main symptom. Only one patient had a clear-cut atopy. Both plant growers showed a cross-allergy to other Ficus species. Two patients had a cross-allergy to latex and the associated cluster of tropical fruit (banana, kiwi, avocado, and chestnut). Removal of the ficus plants from the homes and change to another crop or to another occupation completely resolved the complaints of these patients.