Double Inverse‐Weighted Estimation of Cumulative Treatment Effects Under Nonproportional Hazards and Dependent Censoring

Summary In medical studies of time‐to‐event data, nonproportional hazards and dependent censoring are very common issues when estimating the treatment effect. A traditional method for dealing with time‐dependent treatment effects is to model the time‐dependence parametrically. Limitations of this approach include the difficulty to verify the correctness of the specified functional form and the fact that, in the presence of a treatment effect that varies over time, investigators are usually interested in the cumulative as opposed to instantaneous treatment effect. In many applications, censoring time is not independent of event time. Therefore, we propose methods for estimating the cumulative treatment effect in the presence of nonproportional hazards and dependent censoring. Three measures are proposed, including the ratio of cumulative hazards, relative risk, and difference in restricted mean lifetime. For each measure, we propose a double inverse‐weighted estimator, constructed by first using inverse probability of treatment weighting (IPTW) to balance the treatment‐specific covariate distributions, then using inverse probability of censoring weighting (IPCW) to overcome the dependent censoring. The proposed estimators are shown to be consistent and asymptotically normal. We study their finite‐sample properties through simulation. The proposed methods are used to compare kidney wait‐list mortality by race.     

MEASUREMENTS OF NATURAL SELECTION ON FLORAL TRAITS IN WILD RADISH (RAPHANUS RAPHANISTRUM). II. SELECTION THROUGH LIFETIME MALE AND TOTAL FITNESS

It has often been suggested that selection on floral traits in hermaphroditic plants should occur primarily through differences in male fitness. However, measurements of selection on floral traits through differences in lifetime male fitness have been lacking. We measured selection on a variety of wild radish floral traits using lifetime male fitness measures derived from genetic paternity analysis. These male fitness estimates were then combined with estimates of lifetime female fitness of the same plants to produce measurements of selection based on lifetime total fitness. Contrary to the prediction above, there was no strong evidence for selection on floral morphology through male fitness differences in any of the three years of the study, but there was strong selection for increased flower size through female fitness differences in one year. The main determinant of both male and female fitness in all years was flower number; this lead to moderately positive correlations between male and female fitness in all three years.     

Determination of Photoreceptor Cell Spectral Sensitivity in an Insect Model from In Vivo Intracellular Recordings

Intracellular recording is a powerful technique used to determine how a single cell may respond to a given stimulus. In vision research, intracellular recording has historically been a common technique used to study sensitivities of individual photoreceptor cells to different light stimuli that is still being used today. However, there remains a dearth of detailed methodology in the literature for researchers wishing to replicate intracellular recording experiments in the eye. Here we present the insect as a model for examining eye physiology more generally. Insect photoreceptor cells are located near the surface of the eye and are therefore easy to reach, and many of the mechanisms involved in vision are conserved across animal phyla. We describe the basic procedure for in vivo intracellular recording of photoreceptor cells in the eye of a butterfly, with the goal of making this technique more accessible to researchers with little prior experience in electrophysiology. We introduce the basic equipment needed, how to prepare a live butterfly for recording, how to insert a glass microelectrode into a single cell, and finally the recording procedure itself. We also explain the basic analysis of raw response data for determining spectral sensitivity of individual cell types. Although our protocol focuses on determining spectral sensitivity, other stimuli (e.g., polarized light) and variations of the method are applicable to this setup.     

Evidence of inbreeding depression but not inbreeding avoidance in a natural house sparrow population

Inbreeding is common in small and threatened populations and often has a negative effect on individual fitness and genetic diversity. Thus, inbreeding can be an important factor affecting the persistence of small populations. In this study, we investigated the effects of inbreeding on fitness in a small, wild population of house sparrows (Passer domesticus) on the island of Aldra, Norway. The population was founded in 1998 by four individuals (one female and three males). After the founder event, the adult population rapidly increased to about 30 individuals in 2001. At the same time, the mean inbreeding coefficient among adults increased from 0 to 0.04 by 2001 and thereafter fluctuated between 0.06 and 0.10, indicating a highly inbred population. We found a negative effect of inbreeding on lifetime reproductive success, which seemed to be mainly due to an effect of inbreeding on annual reproductive success. This resulted in selection against inbred females. However, the negative effect of inbreeding was less strong in males, suggesting that selection against inbred individuals is at least partly sex specific. To examine whether individuals avoided breeding with close relatives, we compared observed inbreeding and kinship coefficients in the population with those obtained from simulations of random mating. We found no significant differences between the two, indicating weak or absent inbreeding avoidance. We conclude that there was inbreeding depression in our population. Despite this, birds did not seem to actively avoid mating with close relatives, perhaps as a consequence of constraints on mating possibilities in such a small population.     

Determinants of reproductive success in dominant female meerkats

1. In cooperative societies with high reproductive skew, selection on females is likely to operate principally through variation in the probability of acquiring dominant status and variation in reproductive success while dominant. Despite this, few studies of cooperative societies have investigated the factors that influence which females become dominant, and/or their reproductive output while in the dominant position. 2. Here we use long-term data from a wild meerkats population to describe variation in the breeding success of dominant female meerkats Suricata suricatta and investigate its causes. 3. Female meerkats compete intensely for breeding positions, and the probability of acquiring the breeding role depends upon a female's age in relation to competitors and her weight, both at the time of dominance acquisition and early in life. 4. Once dominant, individual differences in breeding success depend principally on the duration of dominance tenure. Females remain for longer in the dominant position if they are heavier than their competitors at the start of dominance, and if the number of adult female competitors at the start is low. 5. Female breeding success is also affected by variation in fecundity and pup survival, both of which increase with group size. After controlling for these effects, female body weight has a positive influence on breeding rate and litter size, while the number of adult female competitors reduces litter survival. 6. These findings suggest that selection for body weight and competitive ability will be high in female meerkats, which may moderate their investment in cooperative activities. We suggest that similar consequences of competition may occur among females in other cooperative societies where the benefits of attaining dominance status are high.     

Color image detection by biomolecular photoreceptor using bacteriorhodopsin-based complex LB films

A biomolecular photoreceptor consisting of bacteriorhodopsin (bR)-based complex Langmuir–Blodgett (LB) films was developed for color image detection. By mimicking the functions of the pigments in retina of human visual system, biomolecules with photoelectric conversion function were chosen and used as constituents for an artificial photoreceptor. bR and flavin were deposited onto the patterned (9-pixelized) ITO glass by LB technique. A 9-pixel biomolecular photoreceptor was fabricated with a sandwich-type structure of ITO/LB films/electrolyte gel/Pt. Since each functional molecule shows its own response characteristic according to the light illumination in the visible region, the simplified knowledge-based algorithm for interpretation of the incident light wavelength (color) was proposed based on the basic rule describing the relationship between the photoelectric response characteristics and the incident light wavelength. When simple color images were projected onto the photoreceptor, the primary colors in visible light region, red, green, and blue were clearly recognized, and the projected color images were fairly well reproduced onto the color monitor by the proposed photoreceptor with the knowledge-based algorithm. It is concluded that the proposed device has a capability of recognizing the color images and can be used as a model system to simulate the information processing function of the human visual system.     

Visual information processing using bacteriorhodopsin-based complex LB films

Image extraction and visual information processing using bacteriorhodopsin (bR)-based bioelectronic devices is presented. Image extraction was achieved using a photoreceptor consisting of bR and spiropyran films. The undesired signals from the photoreceptor were automatically eliminated from the whole signal by spiropyran films acting as an optical noise filter that increases the target signal to an undesired signal ratio. For the information processing, the photoreceptor consisting of bR and lipid films deposited with different configurations was used and the target signals were processed to achieve the pattern recognition. The pattern recognition was based on not only the response variability of bacteriorhodopsin, induced by different film configurations, but also on the initial learning process. The input patterns were predicted by simple calculation with the known signals through the initial learning process.     

Deposition behavior and photoelectrochemical characteristics of chlorophylla Langmuir-Blodgett films

The deposition behavior and photoelectric response characteristics of chlorophylla (Chla) monolayers and multilayers were investigated under various film fabrication conditions. Chla LB films were deposited onto quartz and pretreated ITO glass substrates under several fabrication conditions, including surface pressure and number of layers. The absorption spectra of Chla in a solution state and solid-like state (LB films) were fairly consistent with each other, and two absorption peaks were found at 678 and 438 nm, respectively. The prepared Chla LB films were set into an electrochemistry cell equipped with a Pt plate as the counter electrode, and the photoelectric response characteristics were obtained and analyzed relative to the light illumination. By considering the resulting photocurrents, the optimal fabrication conditions for Chla LB films were determined as 20 mN/m of surface pressure and 20 layers. The action spectrum of the Chla LB films was obtained in the visible region, and was found to be in good agreement with the absorption spectrum. The possible application of the proposed system as a constituent of an artificial color recognition device was suggested based on combining with the photoelectric conversion property of another lightsensitive biological pigment.     

Characterization of two adenosine analogs as fluorescence probes in RNA

The fluorescence properties of two adenosine analogs, 2-(3-phenylpropyl)adenosine [A-3CPh] and 2-(4-phenylbutyl)adenosine [A-4CPh], are reported. As monomers, the quantum yields and the mean lifetimes are 0.011 and 6.22 ns for A-3CPh and 0.007 and 7.13 ns for A-4CPh, respectively. Surprisingly, the quantum yields of the two probes are enhanced 11- to 82-fold upon incorporation into RNA, while the mean lifetimes decrease 23–40%. The data suggest that a subpopulation of molecules is responsible for the fluorescence characteristics and that the distribution of emitting and non-emitting structures is altered upon incorporation of the probes into RNA. Thus, although both adenosine analogs have low quantum yields as monomers, their fluorescence signals are significantly enhanced in RNA. Thermodenaturation experiments and CD spectroscopy indicate that incorporation of the adenosine analogs into three different RNAs does not alter their global structure or stability. Therefore, these probes should be useful for probing events occurring close to the site of modification.     

Heavy metal contamination and health risk assessment in drinking water of Sistan and Baluchistan,Southeastern Iran

Access to safe and clean drinking water is an essential element of healthy life also known as the primary human needs. The present study was conducted to investigate heavy metal (HM) concentrations of drinking water. Excess health risk of HM (Cr, Pb, and Cd) intake is related to the drinking water consumption in local population. HMs concentrations were analyzed by using graphite furnace atomic absorption spectrometer and were compared with permissible limits regulated by country and World Health Organization (WHO). The hazard quotient (HQ) and Excess Lifetime Cancer Risk (ELCR) were determined to show the carcinogenic and non-carcinogenic effects of HMs, respectively. HQs were found in the order of Pb > Cd > Cr and subsequently HI index was also estimated for all HM in two age groups (children and adults). The comparisons indicate no possibility of non-carcinogenic effects to the local population. The values for ELCR were found in the order of Cr > Cd > Pb. The ELCR index was found above acceptable risk levels for chromium and cadmium in both children and adults groups. Furthermore, intermetal correlation results revealed that heavy metals have common sources resulting from geogenic and anthropogenic activities and these are major sources of water contamination in Sistan and Baluchestan province.