Exploiting nonsystematic covariate monitoring to broaden the scope of evidence about the causal effects of adaptive treatment strategies

In studies based on electronic health records (EHR), the frequency of covariate monitoring can vary by covariate type, across patients, and over time, which can limit the generalizability of inferences about the effects of adaptive treatment strategies. In addition, monitoring is a health intervention in itself with costs and benefits, and stakeholders may be interested in the effect of monitoring when adopting adaptive treatment strategies. This paper demonstrates how to exploit nonsystematic covariate monitoring in EHR‐based studies to both improve the generalizability of causal inferences and to evaluate the health impact of monitoring when evaluating adaptive treatment strategies. Using a real world, EHR‐based, comparative effectiveness research (CER) study of patients with type II diabetes mellitus, we illustrate how the evaluation of joint dynamic treatment and static monitoring interventions can improve CER evidence and describe two alternate estimation approaches based on inverse probability weighting (IPW). First, we demonstrate the poor performance of the standard estimator of the effects of joint treatment‐monitoring interventions, due to a large decrease in data support and concerns over finite‐sample bias from near‐violations of the positivity assumption (PA) for the monitoring process. Second, we detail an alternate IPW estimator using a no direct effect assumption. We demonstrate that this estimator can improve efficiency but at the potential cost of increase in bias from violations of the PA for the treatment process.     

细胞直接重编程:从一种终末分化细胞直接重编程为另一种终末分化细胞

细胞的直接重编程是指将一种终末分化细胞直接转变为另一种终末分化细胞,这一转变不经过诱导多能干细胞阶段和去分化、再分化等过程。最近的一系列研究结果已经证明了这一研究方法的可行性,这些研究进展不仅为重编程的分子机制研究提供了新视角,也为加速重编程细胞的临床应用带来了希望。本文综述了将成纤维细胞直接重编程为神经细胞、肝细胞、心肌细胞及造血细胞的研究进展,探讨了这一研究方法存在的问题以及将来在该领域的研究方向。     

Use of palm-oil by-products in chicken and rabbit feeds: effect on the fatty acid and tocol composition of meat, liver and plasma

This study was undertaken in the framework of a larger European project dealing with the characterization of fat co- and by-products from the food chain, available for feed uses. In this study, we compare the effects, on the fatty acid (FA) and tocol composition of chicken and rabbit tissues, of the addition to feeds of a palm fatty acid distillate, very low in trans fatty acids (TFA), and two levels of the corresponding hydrogenated by-product, containing intermediate and high levels of TFA. Thus, the experimental design included three treatments, formulated for each species, containing the three levels of TFA defined above. Obviously, due to the use of hydrogenated fats, the levels of saturated fatty acids (SFA) show clear differences between the three dietary treatments. The results show that diets high in TFA (76 g/kg fat) compared with those low in TFA (4.4 g/kg fat) led to a lower content of tocopherols and tocotrienols in tissues, although these differences were not always statistically significant, and show a different pattern for rabbit and chicken. The TFA content in meat, liver and plasma increased from low-to-high TFA feeds in both chicken and rabbit. However, the transfer ratios from feed were not proportional to the TFA levels in feeds, reflecting certain differences according to the animal species. Moreover, feeds containing fats higher in TFA induced significant changes in tissue SFA, monounsaturated fatty acids and polyunsaturated fatty acids composition, but different patterns can be described for chicken and rabbit and for each type of tissue.     

Effects of feed restriction on fertility in female rats

BACKGROUND: Feed restriction with its resultant body weight loss impacts the rodent estrous cycle; however, the manifestation of these changes in a regulatory study design has not been documented. This study reports the effects of feed restriction in the context of an FDA regulatory submission. METHODS: Adult female rats (n = 20/group; weighing approximately 200 g each) were provided rodent chow ad lib (control) or at 20, 15, 10, or 7.5 g/rat/day (g/day) during a 2-week pre-mating phase, throughout the mating phase, and up to gestation day (GD) 7. On GD 8, all animals were provided ad lib feed until necropsy on GD 14. Estrous cyclicity, mating, and fertility parameters were evaluated. RESULTS: Ad lib rats consumed approximately 20 and 28 g/day during the pre-mating and gestation phases, respectively. All measured fertility parameters in the 20 g/day group were similar to control values. In the 15 g/day group, body weight was reduced by 16% at 2 weeks, prolonged diestrus occurred, and fertility was compromised due to reductions in corpora lutea. Within 2 weeks, mean body weight in groups receiving < or = 10 g/day was reduced by > or = 29% compared to ad lib values, and overt changes in estrous cyclicity, mating, and fertility occurred. The 7.5 g/day group was not sustainable beyond the pre-mating phase. CONCLUSIONS: For this study type, feed intake at < or = 50% ad lib values (< or = 10 g/day) was inadequate due to the magnitude and rapidity of body weight effects. Estrous parameters appeared slightly more sensitive than functional measures, as body weight changes of approximately 16% appeared near the threshold of changing routinely calculated estrous cycle parameters and were later associated with reduced fertility. In general, body weight differences of 10-15% by themselves were not adverse to normal reproduction (20 g/day).     

Coexistence of two mitochondrial DNA haplotypes in Japanese populations of Hypera postica (Col., Curculionidae)

Abstract:  In Japan, the alfalfa weevil, Hypera postica , was first recorded in 1982 from Fukuoka and Okinawa Prefectures and has been spreading to many other prefectures. The weevil seriously infests the Chinese milk vetch, Astragalus sinicus , one of the most important honey resources for honeybees in Japan. Direct sequencing of partial mitochondrial DNA and PCR-RFLP data for alfalfa weevil individuals indicated the coexistence of two haplotypes at various localities in Japan. Molecular phylogenetic analysis for H. postica haplotypes and strains indicated that the two Japanese haplotypes had not derived from a single genetic origin. Based on the results, special comments are made on biological control measures using introduced parasitic waSPS.     

Production and potential applications of a xylanase from a new strain of Streptomyces cuspidosporus

Enzyme production by a new mesophilic Streptomyces isolate was investigated which grew optimally on 1% (w/v) xylan and 10% (w/v) wheat bran at pH 7 and 37 °C. Xylan induced only CMCase (0.29 U/ml) besides xylanase (22–35 U/ml, 40–49 U/mg protein). Wheat bran induced xylanase (105 U/ml, 17.5 U/mg protein), CMCase (0.74 U/ml), -xylosidase (0.009 U/ml), -glucosidase (0.026 U/ml), -L-arabinofuranosidase (0.049 U/ml), amylase (1.6 U/ml) and phytase (0.432 U/ml). The isolate was amenable to solid state cultivation and produced increased levels of xylanase (146 U/ml, 28 U/mg protein). The pH and temperature optima of the crude xylanase activity were 5.5 and 65 °C respectively. The pI was 6.0 as determined by PEG precipitation. The crude enzyme was applied in treatment of paper pulp and predigestion of poultry feed and was found to be effective in releasing sugars from both and soluble phosphorus from the latter.     

Nutritional composition of black soldier fly larvae feeding on agro-industrial by-products

Black soldier fly (BSF) larvae, Hermetia illucens L. (Diptera: Stratiomyidae), bio-convert organic side streams into high-quality biomass, the composition of which largely depends on the side stream used. In the present study, BSF larvae were reared on feed substrates composed of dried brewers’ spent grains, each supplemented with either water, waste brewer’s yeast, or a mixture of waste brewer’s yeast and cane molasses to obtain 12 different substrates: barley/water, barley/yeast, barley/yeast/molasses, malted barley/water, malted barley/yeast, malted barley/yeast/molasses, malted corn/water, malted corn/yeast, malted corn/yeast/molasses, sorghum-barley/water, sorghum-barley/yeast, and sorghum-barley/yeast/molasses. The crude protein, fat, ash, and mineral contents of the BSF larvae fed each feed substrate were quantified by chemical analyses. The effect of substrate, supplementation, and their interaction on crude protein, fat, and ash contents of BSF larval body composition was significant. Calcium, phosphorus, and potassium were the most abundant macrominerals in the larvae and their concentrations differed significantly among substrates. These findings provide important information to support the use of BSF larval meal as potential new source of nutrient-rich and sustainable animal feed ingredients to substitute expensive and scarce protein sources such as fishmeal and soya bean meal.     

Sensitive fluorescence in situ hybridization signal detection in maize using directly labeled probes produced by high concentration DNA polymerase nick translation

The signal produced by fluorescence in situ hybridization (FISH) often is inconsistent among cells and sensitivity is low. Small DNA targets on the chromatin are difficult to detect. We report here an improved nick translation procedure for Texas red and Alexa Fluor 488 direct labeling of FISH probes. Brighter probes can be obtained by adding excess DNA polymerase I. Using such probes, a 30 kb yeast transgene, and the rp1, rp3 and zein multigene clusters were clearly detected.     

GOOD GENES AND DIRECT SELECTION IN THE EVOLUTION OF MATING PREFERENCES

A model is used to study quantitatively the impact of a good genes process and direct natural selection on the evolution of a mating preference. The expression of a male display trait is proportional to genetic quality, which is determined by the number of deleterious mutations a male carries throughout his genome. Genetic variances and covariances, including the covariance between the preference and male trait that drives the good genes process, are allowed to evolve under an infinitesimal model. Results suggest that the good genes process generates only weak indirect selection on preferences, with an effective selection intensity of a few percent or less. If preferences are subject to direct natural selection of the intensity observed for other characters, the good genes process alone is not expected to exaggerate the male trait by more than a few phenotypic standard deviations, contrary to what is observed in highly sexually selected species. Good genes can, however, cause substantial exaggeration if preference genes are nearly selectively neutral. Alternatively, direct selection on preference genes, acting on mating behavior itself or on the genes' pleiotropic effects, can cause mating preferences and male display traits to be exaggerated by any degree. Direct selection of preference genes may therefore play an important role in species that show extreme sexual selection.