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61.
62.
We consider studies of cohorts of individuals after a critical event, such as an injury, with the following characteristics. First, the studies are designed to measure "input" variables, which describe the period before the critical event, and to characterize the distribution of the input variables in the cohort. Second, the studies are designed to measure "output" variables, primarily mortality after the critical event, and to characterize the predictive (conditional) distribution of mortality given the input variables in the cohort. Such studies often possess the complication that the input data are missing for those who die shortly after the critical event because the data collection takes place after the event. Standard methods of dealing with the missing inputs, such as imputation or weighting methods based on an assumption of ignorable missingness, are known to be generally invalid when the missingness of inputs is nonignorable, that is, when the distribution of the inputs is different between those who die and those who live. To address this issue, we propose a novel design that obtains and uses information on an additional key variable-a treatment or externally controlled variable, which if set at its "effective" level, could have prevented the death of those who died. We show that the new design can be used to draw valid inferences for the marginal distribution of inputs in the entire cohort, and for the conditional distribution of mortality given the inputs, also in the entire cohort, even under nonignorable missingness. The crucial framework that we use is principal stratification based on the potential outcomes, here mortality under both levels of treatment. We also show using illustrative preliminary injury data that our approach can reveal results that are more reasonable than the results of standard methods, in relatively dramatic ways. Thus, our approach suggests that the routine collection of data on variables that could be used as possible treatments in such studies of inputs and mortality should become common. 相似文献
63.
Understanding the genetic structure of a population is essential to its conservation and management. We report the level of genetic diversity and determine the population structure of a cryptic deep ocean cetacean, the Gray''s beaked whale (Mesoplodon grayi). We analysed 530 bp of mitochondrial control region and 12 microsatellite loci from 94 individuals stranded around New Zealand and Australia. The samples cover a large area of the species distribution (~6000 km) and were collected over a 22-year period. We show high genetic diversity (h=0.933–0.987, π=0.763–0.996% and Rs=4.22–4.37, He=0.624–0.675), and, in contrast to other cetaceans, we found a complete lack of genetic structure in both maternally and biparentally inherited markers. The oceanic habitats around New Zealand are diverse with extremely deep waters, seamounts and submarine canyons that are suitable for Gray''s beaked whales and their prey. We propose that the abundance of this rich habitat has promoted genetic homogeneity in this species. Furthermore, it has been suggested that the lack of beaked whale sightings is the result of their low abundance, but this is in contrast to our estimates of female effective population size based on mitochondrial data. In conclusion, the high diversity and lack of genetic structure can be explained by a historically large population size, in combination with no known exploitation, few apparent behavioural barriers and abundant habitat. 相似文献
64.
Summary We derive regression estimators that can compare longitudinal treatments using only the longitudinal propensity scores as regressors. These estimators, which assume knowledge of the variables used in the treatment assignment, are important for reducing the large dimension of covariates for two reasons. First, if the regression models on the longitudinal propensity scores are correct, then our estimators share advantages of correctly specified model‐based estimators, a benefit not shared by estimators based on weights alone. Second, if the models are incorrect, the misspecification can be more easily limited through model checking than with models based on the full covariates. Thus, our estimators can also be better when used in place of the regression on the full covariates. We use our methods to compare longitudinal treatments for type II diabetes mellitus. 相似文献
65.
Cynthia Cheng Chadd W. Lee Constantine Daskalakis 《Journal of visualized experiments : JoVE》2015,(104)
Capillaroscopy is a non-invasive, efficient, relatively inexpensive and easy to learn methodology for directly visualizing the microcirculation. The capillaroscopy technique can provide insight into a patient’s microvascular health, leading to a variety of potentially valuable dermatologic, ophthalmologic, rheumatologic and cardiovascular clinical applications. In addition, tumor growth may be dependent on angiogenesis, which can be quantitated by measuring microvessel density within the tumor. However, there is currently little to no standardization of techniques, and only one publication to date reports the reliability of a currently available, complex computer based algorithms for quantitating capillaroscopy data.1 This paper describes a new, simpler, reliable, standardized capillary counting algorithm for quantitating nailfold capillaroscopy data. A simple, reproducible computerized capillaroscopy algorithm such as this would facilitate more widespread use of the technique among researchers and clinicians. Many researchers currently analyze capillaroscopy images by hand, promoting user fatigue and subjectivity of the results. This paper describes a novel, easy-to-use automated image processing algorithm in addition to a reproducible, semi-automated counting algorithm. This algorithm enables analysis of images in minutes while reducing subjectivity; only a minimal amount of training time (in our experience, less than 1 hr) is needed to learn the technique. 相似文献
66.
Flora Zagouri Theodoros N. Sergentanis Maria Gazouli Constantine Dimitrakakis Alexandra Tsigginou Irene Papaspyrou Dimosthenis Chrysikos Maria Lymperi George C. Zografos Aris Antsaklis Meletios-Athanassios Dimopoulos Christos A. Papadimitriou 《Molecular biology reports》2013,40(8):5035-5040
This case control study aims to investigate the role of MMP-2 ?1306C > T polymorphism as a potential risk factor and possible prognostic marker for breast cancer in a South European population. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy controls were recruited. MMP-2 ?1306C > T polymorphism was genotyped; multivariate logistic regression as well as Cox regression analysis were performed. MMP-2 ?1306C > T status was not associated with breast cancer risk either at the total sample or at the subanalyses on premenopausal and postmenopausal women. At the survival analysis, a trend towards a favorable association between MMP-2 ?1306C > T allele and disease-free survival as well as overall survival was observed. Regarding subanalyses on ER-negative and ER-positive cases, the favorable association implicating MMP-2 ?1306C > T allele was particularly evident among ER-positive cases; no significant associations emerged among ER-negative cases. MMP-2 ?1306C > T polymorphism does not seem to be a risk factor for breast cancer in South European population; however, a trend towards a favorable association with survival has been observed. 相似文献
67.
68.
The regulatory subunit 1-alpha (RIalpha) of protein kinase A (PKA) and the mTOR kinase are involved in a common pathway regulating mammalian autophagy. RIalpha was found to localize on Rab7-positive late endosomes and on LC3-positive autophagosomal membranes in cultured cells. RIalpha was also shown to physically interact with mTOR kinase and affect its phosphorylation and activity. In this addendum, we further explore the subcellular distribution of mTOR related to RIalpha and LC3. We present experiments showing that mTOR colocalizes with RIalpha-, Rab7- and LC3-positive membranes in cultured cells. Because RIalpha regulates the phosphorylation and activity of mTOR kinase, which we now show localizes on autophagosomal membranes, the possibility emerges that the RIalpha-mTOR complex acts at the level of autophagosome maturation. 相似文献
69.
Sztalryd C Bell M Lu X Mertz P Hickenbottom S Chang BH Chan L Kimmel AR Londos C 《The Journal of biological chemistry》2006,281(45):34341-34348
Ectopic accumulation of lipid droplets in non-adipose tissues correlates with the degree of insulin resistance in these tissues. Emerging evidence indicates that lipid droplets are specialized organelles that participate in lipid metabolism and intracellular trafficking. These properties are thought to derive from the lipid droplet-associated PAT protein family (perilipin, ADFP, and Tip47). The functions of the ubiquitously distributed adipose differentiation-related protein (ADFP) and Tip47 remain unknown. To evaluate the roles of ADFP and Tip47 in lipid biogenesis and metabolism, ADFP null and wild type (wt) clonal cell lines were established from ADFP null and wt mice, respectively. In ADFP null cells, Tip47 was identified as the sole lipid droplet-associated protein from the PAT family by mass spectroscopy, which was further confirmed by immunoblotting and immunocytochemistry. Following incubation with oleic acid, ADFP null cells were able to form lipid droplets to the same extent as wt cells. No statistical differences between the two cell types were observed in NEFA uptake or lipolysis. Small interference RNAs (siRNAs) against Tip47 were found to down-regulate protein levels for Tip47 by 85%. ADFP null cells treated with Tip47 siRNA retained the ability to form lipid droplets but to a lesser extent and shunted the utilization of exogenously added NEFA from triglycerides to phospholipids. These data support the hypothesis that Tip47 plays an important role in lipid metabolism. Tip47 and ADFP in peripheral tissues may play a critical role in regulating the formation and turnover, and hence metabolic consequences, of ectopic fat. 相似文献
70.
Jose M. Martínez-Sánchez Montse Ballbè Marcela Fu Juan C. Martín-Sánchez Mark Gottlieb Esteve Saltó Constantine I. Vardavas Richard Daynard Gregory N. Connolly Esteve Fernández 《PloS one》2014,9(12)