Adaptive treatment and robust control.

A control theory perspective on determination of optimal dynamic treatment regimes is considered. The aim is to adapt statistical methodology that has been developed for medical or other biostatistical applications to incorporate powerful control techniques that have been designed for engineering or other technological problems. Data tend to be sparse and noisy in the biostatistical area and interest has tended to be in statistical inference for treatment effects. In engineering fields, experimental data can be more easily obtained and reproduced and interest is more often in performance and stability of proposed controllers rather than modeling and inference per se. We propose that modeling and estimation should be based on standard statistical techniques but subsequent treatment policy should be obtained from robust control. To bring focus, we concentrate on A-learning methodology as developed in the biostatistical literature and H∞ -synthesis from control theory. Simulations and two applications demonstrate robustness of the H∞ strategy compared to standard A-learning in the presence of model misspecification or measurement error.

Role of mitotic control in spermatogenesis.

OBJECTIVE: To study the correlation between the incidence of sex chromosome aneuploidies in the somatic cells and spermatozoa in karyotypically normal infertile men and fertile donors. DESIGN: A prospective, phase two, controlled study. SETTING: A teaching Hospital Reproductive Medicine and Medical Genetics Units. PATIENT(S): Ten patients with idiopathic oligozoospermia and 10 sperm donors with proven fertility, all with a normal karyotype 46, XY. INTERVENTION(S): Multicolor fluorescence in situ hybridization (FISH) of peripheral blood lymphocytes and spermatozoa using a probe cocktail containing the alpha satellite DXZ1 for the X centromere, DYZ1 for the heterochromatic region of the long arm of the Y, and cosmids D21S259, D21S341, and D21S342 for Down syndrome critical region of chromosome 21. MAIN OUTCOME MEASURE(S): The incidence of chromosome X, Y, and 21 aneuploidies in peripheral lymphocytes and spermatozoa in both groups. RESULT(S): The incidence of aneuploidies related to chromosomes X, Y, and 21 were significantly higher in peripheral lymphocytes and spermatozoa of infertile men compared with donors. There was a positive correlation between the incidence of chromosome aneuploidies in the somatic cells and sperm in all men. CONCLUSION(S): These findings provide suggestive evidence for the importance of mitosis in spermatogenesis and the role of mitotic instability in unexplained oligozoospermia.

Evaluation of the role of mitotic instability in karyotypically normal men with oligozoospermia.

OBJECTIVE: To estimate the incidence of sex chromosome aneuploidies in the somatic cells of karyotypically normal infertile men and fertile donors. DESIGN: A prospective, two-phase, controlled study. SETTING: Reproductive medicine and medical genetics units of a teaching hospital. PATIENT(S): Ten patients with oligozoospermia and 10 sperm donors with proved fertility, all with a normal karyotype 46 XY. INTERVENTION(S): Multicolor fluorescence in situ hybridization (FISH) of peripheral blood lymphocytes using a probe cocktail containing the alpha satellites DXZ1 for the X centromere and DYZ1 for the heterochromatic region of the long arm of the Y and the radiolabeled alpha satellite D18Z1 for chromosome 18. MAIN OUTCOME MEASURE(S): The incidence of sex chromosome aneuploidies in both groups. RESULT(S): A 13-fold increase in sex chromosome aneuploidies was observed in the somatic cells of infertile men with "unexplained" oligozoospermia compared to donors (P=.008). CONCLUSION(S): These findings provide suggestive evidence for the existence of an inherent mitotic instability in men with unexplained oligozoospermia.

Isolation and characterization of polymorphic microsatellite loci for the three-toed box turtle (Terrapene carolina triunguis) and cross-amplification in other Terrapene species.

We isolated and characterized eight polymorphic microsatellite loci for a Texas population of three-toed box turtle, Terrapene carolina triunguis, using a refined hybridization capture procedure. All eight primer pairs amplified successfully at all loci in seven Texas ornate box turtles (T. ornata ornata). Due to the decline and conservation concerns of North American box turtles, these isolated microsatellites may be a most valuable tool for evaluating baseline population genetic structure for threatened box turtle populations.

Trimethylamine oxide transport across plasma membranes of elasmobranch erythrocytes.

The aim of this study was to characterize the erythrocyte cell membrane transport of trimethylamine oxide (TMAO) in the little skate, Raja erincea. Uptake of TMAO occurs by two processes, Na(+)-dependent and Na(+)-independent. 2,4 dinitrophenol (2,4 DNP), a known ATP synthesis inhibitor, inhibited TMAO uptake, suggesting the involvement of the Na(+)/K(+)-ATP pump in Na(+)-dependent TMAO transport. Na(+)-independent TMAO uptake was stimulated by cell swelling when erythrocytes were incubated in hypotonic elasmobranch incubation medium. Swelling-activated, Na(+)-independent TMAO uptake was inhibited by the anion transport inhibitors quinine and 4, 4'-diisthiocyanostilbene-2,2'-disulfonic acid (DIDS), two blockers of the swelling-activated osmolyte channel in skate erythrocytes. TMAO efflux was stimulated by hypotonic stress in the erythrocytes of the spiny dogfish, Squalus acanthias. DIDS also inhibited this efflux, indicating that TMAO is transported by the organic osmolyte channel in the erythrocytes of this elasmobranch as well. J. Exp. Zool. 284:605-609, 1999.