Estimation and testing in targeted goup sequential covariate-adjusted randomized clinical trials.

This article is devoted to the construction and asymptotic study of adaptive group sequential covariate-adjusted randomized clinical trials analyzed through the prism of the semipara-metric methodology of targeted maximum likelihood estimation (TMLE). We show how to build, as the data accrue group-sequentially, a sampling design which targets a user-supplied optimal design. We also show how to carry out a sound TMLE statistical inference based on such an adaptive sampling scheme (therefore extending some results known in the i.i.d setting only so far), and how group-sequential testing applies on top of it. The procedure is robust (i.e., consistent even if the working model is misspecified). A simulation study confirms the theoretical results, and validates the conjecture that the procedure may also be efficient.

Meat quality of Angus, Simmental, Charolais and Limousin steers compared at the same intramuscular fat content.

Meat quality and marbling properties of Angus, Simmental, Charolais and Limousin steers (4×16) were compared at an average intramuscular fat content (IMF) of 3.25% in the M. longissimus dorsi. The steers were fattened on a forage-based diet until the desired, ultrasonically estimated IMF content was reached which resulted in considerably different growth and carcass characteristics. The Angus group showed a growth rate similar to Simmental and Charolais while Limousin grew slower, became oldest and provided the heaviest carcasses and best conformation. Angus carcasses showed the lowest weight but the highest fatness score. Marbling was equal for all breeds. Angus and Charolais provided pale meat with low haem iron content. Angus and Limousin beef was more tender on sensory assessment than Simmental beef, corresponding to differences found in shear force (non-significant) and myofibrillar fragmentation index measured at 48 h post mortem. Flavour was similar among breed groups while juiciness was highest for Limousin and lowest for Angus. The juicier beef simultaneously showed the highest drip but the lowest cooking losses. In conclusion, clear differences in meat quality were observed between breeds despite similar IMF contents.

Urinary caffeine after coffee consumption and heat dehydration.

This study evaluated the effect of heat-induced dehydration on urinary caffeine excretion after the consumption of a strong coffee solution. Following ingestion of coffee (caffeine 4.9+/-0.1 [SE] mg/kg, 3-4 cups), ten healthy males were intermittently exposed to heat in a sauna until they had lost 2.9 % of lean mass. On a separate occasion, they consumed the same amount of coffee but remained quiet and euhydrated (control). Urine flow was reduced 7-fold in dehydration. At these low excretion rates (< 30 ml/h), caffeine concentration was negatively correlated with flow. Peak urinary caffeine (Cmax) was 7.6 +/- 0.4 (SE) microg/ml in dehydration and 7.1 +/- 0.2 microg/ml in the control (p > 0.05). Compared with the control, dehydration delayed Cmax by 1 hour, maintained higher saliva caffeine concentration (6.1 vs 5.2 microg/ml, p < 0.05) and a lower saliva paraxanthine/caffeine ratio (p < 0.001). The 24h-recovery of caffeine in urine was reduced (1.2 vs 2.8% of dose, p < 0.001), however at least 2.6% of dose were lost in sweat. These results suggest that the rise in circulating caffeine due to delayed metabolic clearance was partly opposed by a sizeable elimination in sweat. Therefore, heat dehydration did not lead to higher concentration of caffeine in urine after coffee ingestion.

Could a satellite-based navigation system (GPS) be used to assess the physical activity of individuals on earth?

OBJECTIVES: To test whether the Global Positioning System (GPS) could be potentially useful to assess the velocity of walking and running in humans. SUBJECT: A young man was equipped with a GPS receptor while walking running and cycling at various velocity on an athletic track. The speed of displacement assessed by GPS, was compared to that directly measured by chronometry (76 tests). RESULTS: In walking and running conditions (from 2-20 km/h) as well as cycling conditions (from 20-40 km/h), there was a significant relationship between the speed assessed by GPS and that actually measured (r = 0.99, P < 0.0001) with little bias in the prediction of velocity. The overall error of prediction (s.d. of difference) averaged +/-0.8 km/h. CONCLUSION: The GPS technique appears very promising for speed assessment although the relative accuracy at walking speed is still insufficient for research purposes. It may be improved by using differential GPS measurement.

Adhesion of colonization factor antigen II-positive enterotoxigenic Escherichia coli strains to human enterocytelike differentiated HT-29 cells: a basis for host-pathogen interactions in the gut.

Enterotoxigenic Escherichia coli are the most common cause of travelers' and infant diarrhea in less-developed countries. In the present work, among several metabolically labeled human diarrheagenic E. coli strains, enterotoxigenic strains expressing colonization factor antigen II were shown to bind to HT-29 intestinal cell monolayers when these cells were grown in conditions promoting their enterocytic differentiation. Indirect immunofluorescence with fimbrial antisera revealed that pathogen attachment was associated with the production of a specific bacterial adhesin, the E. coli surface antigen CS3. Scanning and transmission electron micrographs showed an apical pattern of colonization, characteristic of enterotoxigenic E. coli infections. The above data were consistent with all observations previously made with human enterocytes obtained from intestinal biopsies. The lectin-carbohydrate nature of this cell-cell recognition mechanism was also established. Bacterial binding to differentiated HT-29 cells was inhibited by a mixture of newborn meconium glycopeptides. By coating the cell layers with the plant agglutinin from Evonymus europaea, pathogen attachment was also prevented. Binding of 125I-labeled CS3 adhesin and E. europaea agglutinin to brush border membrane proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to nitrocellulose revealed three bands of about 30, 20, and 13 kilodaltons, which acted as receptors for both bacterial and plant lectins. These data suggest that the sugar units to which the bacterial colonization factor CS3 binds are synthesized as carbohydrate chains of three brush border membrane glycoproteins in HT-29 cells by a differentiation-specific pathway.

Specific and nonspecific inhibition of adhesion of oral actinomyces and streptococci to erythrocytes and polystyrene by caseinoglycopeptide derivatives.

Various caseinoglycopeptide derivatives prepared from mammalian milk were evaluated as inhibitors of hemagglutinations mediated by Actinomyces viscosus Ny1, Streptococcus sanguis OMZ9, and, for comparative purposes, plant lectins from Arachis hypogaea and Bauhinia purpurea. It was found that recognition of the beta-D-galactose-(1----3)-2-acetamido-2-deoxy-D-galactose carbohydrate chain by Actinomyces viscosus Ny1 organisms and Arachis hypogaea and B. purpurea agglutinins had similar structural requirements; in all cases, the desialylated bovine caseinoglycomacropeptide, on which several units of the above mentioned disaccharide are clustered, behaved as the most potent hemagglutination inhibitor. By contrast, none of the preparations tested inhibited erythrocyte agglutination by S. sanguis OMZ9. Thus, the desialylated bovine caseinoglycomacropeptide acts as a potent and specific inhibitor of oral Actinomyces adhesion to cell membranes (a soft surface) and could be used as a probe for the study of recognition mechanisms mediated by Actinomyces galactose-binding lectins. During the present study, both native and desialylated variants of the same bovine glycomacropeptide also totally prevented the adhesion of Actinomyces viscosus Ny1, S. sanguis OMZ9, and S. mutans OMZ176 to polystyrene surfaces. Comparative evaluations of various structurally different compounds gave the following results. Neither mono- nor disaccharides related to caseinoglycopeptide carbohydrates prevented adhesion; highly positively or negatively charged polypeptides and polysaccharides were either not or only moderately active. Besides these glycomacropeptides, an inhibitory activity was also exhibited by other mucin-type glycoproteins carrying short O-linked carbohydrate chains (including bovine submaxillary mucin), polyethylene glycol, and bovine serum albumin. Consequently, caseinoglycopeptide prevention of oral bacterial adhesion to polystyrene tubes (a hard surface) takes place with no species specificity and can be compared to nonspecific inhibition exhibited by various polymers with very different structural characteristics.