Adjusting for selection bias in assessing treatment effect estimates from multiple subgroups

This paper discusses a number of methods for adjusting treatment effect estimates in clinical trials where differential effects in several subpopulations are suspected. In such situations, the estimates from the most extreme subpopulation are often overinterpreted. The paper focusses on the construction of simultaneous confidence intervals intended to provide a more realistic assessment regarding the uncertainty around these extreme results. The methods from simultaneous inference are compared with shrinkage estimates arising from Bayesian hierarchical models by discussing salient features of both approaches in a typical application.     

Morphological changes in senescing adult male sockeye salmon (Oncorhynchus nerka Walbaum)

Mature male sockeye salmon ( Oncorhynchus nerka Walbaum) were measured, tagged and released into a gravel holding pond adjacent to the spawning site, then remeasured when dead for possible changes in shape or size. Body length, depth, snout length and caudal peduncle thickness decreased at the end of life, 1–2 weeks later.     

微波加热时基托树脂收缩量的研究

目的,针对基托树脂固化的特性,探讨微波加热对树脂收缩量的影响。方法:采用四种常用基托树脂,分别采取单纯微波固化和微波加压固化聚合后,测定开盒后一周内树脂的聚合收缩情况。结果:两种固化方法收缩量均较小,适应性强。微波加压固化虽收缩量相对稍大但收缩均匀各树脂间无显著差异。结论:微波加热固化清洁高效,基托树脂结构致密,收缩量小,是今后树脂固化的一个发展方向。     

Changes in the Ultrastructure of the Gelatinous Matrix of Meloidogyne javanica During Dehydration

The fine structure of the gelatinous matrix of Meloidogyne javanica in both moist and dry states was studied by means of chemical fixation and thin sectioning techniques and the freeze-etch method. The matrix consists of an irregular meshwork when hydrated and a uniform granular mass of much greater density when dehydrated. The spaces in the hydrated meshwork are presumed to contain water. The change from a hydrated to a dehydrated state is accompanied by an overall shrinkage and hardening of the egg mass with a change in color from yellow to reddish-orange. The possible functions of this unusual glycoprotein are discussed.     

利用微波固定组织的收缩率

目的探讨利用微波辐射固定、微波辐射与固定液结合固定组织的收缩程度。方法将组织分成40组,用一定强度的微波辐射或一定强度的微波辐射与不同固定液结合方法固定动物组织,并制做石蜡组织切片和HE染色,在此过程中测定各步骤前后的组织块体积,计算出收缩率。结果与结论一定强度的微波辐射和一些微波辐射与固定液结合方法固定的组织收缩率低,这些组织的切片具有细胞质均匀,染色鲜艳,细胞核大而清晰的良好效果。     

Intracellular Cl? Dependence of Na-H Exchange in Barnacle Muscle Fibers under Normotonic and Hypertonic Conditions

We previously showed that shrinking a barnacle muscle fiber (BMF) in a hypertonic solution (1,600 mosM/kg) stimulates an amiloride-sensitive Na-H exchanger. This activation is mediated by a G protein and requires intracellular Cl⁻. The purpose of the present study was to determine (a) whether Cl⁻ plays a role in the activation of Na-H exchange under normotonic conditions (975 mosM/kg), (b) the dose dependence of [Cl⁻]_i for activation of the exchanger under both normo- and hypertonic conditions, and (c) the relative order of the Cl⁻- and G-protein-dependent steps. We acid loaded BMFs by internally dialyzing them with a pH-6.5 dialysis fluid containing no Na⁺ and 0–194 mM Cl⁻. The artificial seawater bathing the BMF initially contained no Na⁺. After dialysis was halted, adding 50 mM Na⁺ to the artificial seawater caused an amiloride-sensitive pH_i increase under both normo- and hypertonic conditions. The computed Na-H exchange flux (J _Na-H) increased with increasing [Cl⁻]_i under both normo- and hypertonic conditions, with similar apparent K _m values (∼120 mM). However, the maximal J _Na-H increased by nearly 90% under hypertonic conditions. Thus, activation of Na-H exchange at low pH_i requires Cl⁻ under both normo- and hypertonic conditions, but at any given [Cl⁻]_i, J _Na-H is greater under hyper- than normotonic conditions. We conclude that an increase in [Cl⁻]_i is not the primary shrinkage signal, but may act as an auxiliary shrinkage signal. To determine whether the Cl⁻-dependent step is after the G-protein-dependent step, we predialyzed BMFs to a Cl⁻-free state, and then attempted to stimulate Na-H exchange by activating a G protein. We found that, even in the absence of Cl⁻, dialyzing with GTPγS or AlF₃, or injecting cholera toxin, stimulates Na-H exchange. Because Na-H exchange activity was absent in control Cl⁻-depleted fibers, the Cl⁻-dependent step is at or before the G protein in the shrinkage signal-transduction pathway. The stimulation by AlF₃ indicates that the G protein is a heterotrimeric G protein.     

A Rapid and Efficient Estimation Procedure for the Negative Binomial Distribution

This paper presents a new noniterative procedure for estimating the parameters of a negative binomial distribution. The procedure uses the first moment equation and an equation based on the weighted sample mean, with weights ω_x∝ α^z. The selection of a value for α is examined. A simulation study has been carried out and also the method has been applied to the 35 data sets analysed by Martin and Katti (1965, Biometrics) in order to compare it with the method of moments and with the method of maximum likelihood (ML). We conclude that the new procedure has greater relative efficiency than the method of moments; it gives estimates which are consistently close to ML and are easy to calculate.     

Physical changes in specimens of five species of Cyprinidae preserved in ethanol and frozen

Preservation in 30% ethanol and freezing to a temperature of ?20 ± 2° C is an appropriate method for measurement of fish eggs, larvae and juveniles. Egg diameter of the common carp Cyprinus carpio increased insignificantly by 1·32% after preservation compared with live size. The total length (L_T) of 1 day post‐hatching (dph) larvae as well as the standard length (LS) of 16 dph larvae of C. carpio increased significantly (2·95 and 1·50%, respectively) after preservation. Egg diameter as well as the L_T of 1 dph larvae of barbel Barbus barbus increased significantly after preservation, by 1·74 and 1·96%, respectively over their original size. The standard length (L_S) of 14 dph larvae of B. barbus as well as juveniles of B. barbus, crucian carp Carassius carassius, common nase Chondrostoma nasus and tench Tinca tinca decreased significantly after preservation (?0·56 to ?5·54%), whereas their body mass increased significantly (11·46–18·57%). Preserved eggs of C. carpio and B. barbus were hard, round and transparent. The larvae and juveniles of examined fishes, preserved in frozen ethanol, were straight, flexible and easily measurable after 60 days. Integrity of body surface and fins, as well as preservation of colours were much better in larvae or juveniles frozen and thawed only once than in specimens frozen and thawed thrice. Cooling in 30% ethanol to a temperature of 6 ± 2° C and freezing in water to a temperature of ?20 ± 2° C are not appropriate preservation methods for eggs and larvae of C. carpio (1 and 16 dph).     

Improved Identification of Parameters in the Wolgograd Growth Model for Sugar Beets

Starting point of the investigations is the time-invariant Wolgograd model applied to a sample of sugar beets. To overcome the weak multicollinearity of the model in its logarithmic form, a ridge-type estimator is applied which uses prior information on the unknown regression coefficients. This is done by introducing the biased minimax-linear estimator. To judge the goodness of the estimates there are calculated the minimax risks of the MILE and the OLSE as well as the estimated maximal crop yields.     

西安市学生中从膝部长骨干骺融合推算身高与年龄的回归方程

本文根据西安市2612名学生的活体测量和1361例的X线拍片观察,得出了应用膝部长骨的干骺融合程度及某些线性度量推算身高与年龄的三十个回归方程和相应的误差,同时,对得出的方程进行了讨论。     

The potential role of caveolin-1 in inhibition of aquaporins during the AVD

BACKGROUND INFORMATION: During apoptosis, the first morphological change is a distinct cell shrinkage known as the AVD (apoptotic volume decrease). This event is driven by a loss of intracellular K(+), which creates an osmotic gradient, drawing water out of the cell through AQPs (aquaporins). Loss of water in balance with K(+) would create a shrunken cell with an equivalent intracellular concentration of K(+) ([K(+)](i) = 140 mM). However, we have previously shown that the [K(+)](i) of the shrunken apoptotic cell is 35 mM, and this level is absolutely essential for the activation of apoptotic enzymes. We have recently found that AQPs are inactivated following the AVD, so that continued loss of K(+) will reduce the intracellular concentration to this critical level. Using thymocytes, we have investigated the expression profile and regulation of the AQP family members. RESULTS: In the present study, we have found that AQP1, AQP8 and AQP9 are present in non-apoptotic thymocytes and localized primarily to the plasma membrane. Expression and localization did not change when these cells were induced to undergo apoptosis by growth factor withdrawal for 24 h. To explore other possible mechanisms by which these water channels are inactivated, we investigated their association with CAV-1 (caveolin-1), binding to which is known to inactivate a variety of proteins. We found that CAV-1 is present in thymocytes and that this protein co-localizes with a portion of AQP1 in normal (non-apoptotic) thymocytes. However, thymocytes induced to undergo apoptosis greatly increase their AQP1/CAV-1 association. CONCLUSIONS: Taken together, these results indicate that AQPs are localized to the plasma membrane of shrunken apoptotic thymocytes where increased binding to CAV-1 potentially inactivates them. AQP inactivation, coupled with continued K(+) efflux, then allows the [K(+)](i) to decrease to levels conducive for the activation of downstream apoptotic enzymes and the completion of the apoptotic cascade.     

Licht- und elektronenmikroskopische Untersuchungen über die Reversibilität von Kernmembranschrumpfungen des Ependyms im Hypothalamus der Ratte,hervorgerufen durch langdauernde Thiobarbiturat-Narkose

Zusammenfassung Im Ependym des Hypothalamus wurde das Verhalten der Zellkern-Membran nach ausgedehnter intraperitonealer Thiobarbiturat-Narkose untersucht. Die Kernmembran ist gefaltet, der Zellkern zeigt Zeichen von Schrumpfung. Diese Veränderung ist reversibel und wird nicht von der mit der Narkose verbundenen Entwässerung verursacht. Elektronenmikroskopische Untersuchungen lassen einen normalen Stoffwechsel vermuten, Zeichen von Pyknose fehlen.

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Light and electron microscopic studies on the reversibility of nuclear membrane shrinkage in hypothalamic ependymal cells of the rat, caused by continuous thiobarbiturate narcosis

Summary Effects on the nuclear membrane were investigated in hypothalamic ependymal cells of the rat during prolonged intraperitoneal thiobarbiturate narcosis. The nuclear membrane of the nucleus was folded and the nucleus showed signs of shrinkage. These alterations were reversible and did not depend on the dehydration which developed during the narcosis. Ultrastructural signs and the absence of pyknosis suggested that metabolism during nuclear shrinkage may be normal.

Herrn Prof. Dr. Dr. h. c. W. Bargmann zum 65. Geburtstag gewidmet.     

New Enzyme-based Process Direction to Prevent Wool Shrinking without Substantial Tensile Strength Loss

In this paper a new enzymatic process direction is described for obtaining machine washable wool with acceptable quality. In general, application of protease enzyme technology in wool processing results in considerable loss of tensile strength by diffusion of the enzyme into the interior of wool fibers. To overcome this disadvantage enzymatic activity has been more targeted to the outer surface of the scales by improving the susceptibility of the outer surface scale protein for proteolytic degradation. This has been realized by a pretreatment of wool with hydrogen peroxide at alkaline pH in the presence of high concentrations of salt.     

Bayesian shrinkage estimation of high dimensional causal mediation effects in omics studies

Causal mediation analysis aims to examine the role of a mediator or a group of mediators that lie in the pathway between an exposure and an outcome. Recent biomedical studies often involve a large number of potential mediators based on high-throughput technologies. Most of the current analytic methods focus on settings with one or a moderate number of potential mediators. With the expanding growth of -omics data, joint analysis of molecular-level genomics data with epidemiological data through mediation analysis is becoming more common. However, such joint analysis requires methods that can simultaneously accommodate high-dimensional mediators and that are currently lacking. To address this problem, we develop a Bayesian inference method using continuous shrinkage priors to extend previous causal mediation analysis techniques to a high-dimensional setting. Simulations demonstrate that our method improves the power of global mediation analysis compared to simpler alternatives and has decent performance to identify true nonnull contributions to the mediation effects of the pathway. The Bayesian method also helps us to understand the structure of the composite null cases for inactive mediators in the pathway. We applied our method to Multi-Ethnic Study of Atherosclerosis and identified DNA methylation regions that may actively mediate the effect of socioeconomic status on cardiometabolic outcomes.