Statistical inference for self-designing clinical trials with a one-sided hypothesis

In the process of monitoring clinical trials, it seems appealing to use the interim findings to determine whether the sample size originally planned will provide adequate power when the alternative hypothesis is true, and to adjust the sample size if necessary. In the present paper, we propose a flexible sequential monitoring method following the work of Fisher (1998), in which the maximum sample size does not have to be specified in advance. The final test statistic is constructed based on a weighted average of the sequentially collected data, where the weight function at each stage is determined by the observed data prior to that stage. Such a weight function is used to maintain the integrity of the variance of the final test statistic so that the overall type I error rate is preserved. Moreover, the weight function plays an implicit role in termination of a trial when a treatment difference exists. Finally, the design allows the trial to be stopped early when the efficacy result is sufficiently negative. Simulation studies confirm the performance of the method.     

Exceptional Photosynthetic Performance of Capparis spinosa L. Under Adverse Conditions of Mediterranean summer

Diurnal and seasonal fluctuations in water potential (), stomatal conductance (g _s), transpiration rate (E), and net photosynthetic rate (P _N) were monitored in Capparis spinosa L., a Mediterranean plant growing during summer, i.e. at the period considered the most stressful for local plant life. In spite of the complete absence of rain, exhibited a modest drop at midday (–2.7 MPa), but was fully recovered overnight, indicating sufficient access to water sources. The stomata remained open throughout the day and season and the high E resulted in leaf temperatures up to 3.9 °C below air temperature. Additionally, P _N of the fully exposed leaves was higher than 25 mol m^–2 s^–1 for more than 10 h per day throughout the summer growth period. No symptoms of photooxidative stress were shown, as judged by maximum photosystem 2 photochemical efficiency (F_v/F_m) and the function of xanthophyll cycle. Indeed, diurnal inter-conversions of the xanthophyll cycle components were modest during the summer and a more intensive function of the cycle was only evident during leaf senescence in autumn. In comparison with a semi-deciduous and an evergreen sclerophyll co-existing in the same ecosystem, C. spinosa assimilated up to 3.4 times more CO₂ per m² during its growth period (May to October) and up to 1.8 times more on an annual basis.     

The evolutionary gain of spliceosomal introns: sequence and phase preferences

Theories regarding the evolution of spliceosomal introns differ in the extent to which the distribution of introns reflects either a formative role in the evolution of protein-coding genes or the adventitious gain of genetic elements. Here, systematic methods are used to assess the causes of the present-day distribution of introns in 10 families of eukaryotic protein-coding genes comprising 1,868 introns in 488 distinct alignment positions. The history of intron evolution inferred using a probabilistic model that allows ancestral inheritance of introns, gain of introns, and loss of introns reveals that the vast majority of introns in these eukaryotic gene families were not inherited from the most recent common ancestral genes, but were gained subsequently. Furthermore, among inferred events of intron gain that meet strict criteria of reliability, the distribution of sites of gain with respect to reading-frame phase shows a 5:3:2 ratio of phases 0, 1 and 2, respectively, and exhibits a nucleotide preference for MAG GT (positions -3 to +2 relative to the site of gain). The nucleotide preferences of intron gain may prove to be the ultimate cause for the phase bias. The phase bias of intron gain is sufficient to account quantitatively for the well-known 5:3:2 bias in phase frequencies among extant introns, a conclusion that holds even when taxonomic heterogeneity in phase patterns is considered. Thus, intron gain accounts for the vast majority of extant introns and for the bias toward phase 0 introns that previously was interpreted as evidence for ancient formative introns.     

Recent intron gain in elongation factor-1alpha of colletid bees (Hymenoptera: Colletidae)

We discovered the presence of a unique spliceosomal intron in the F1 copy of elongation factor-1alpha (EF-1alpha) restricted to the bee family Colletidae (Hymenoptera: Apoidae). The intron ranges in size from 101 to 1044 bp and shows no positional sliding. Our data also demonstrate the complete absence of this intron from exemplars representing all other bee families, as well as from close hymenopteran relatives. A review of the literature finds that this intron is likewise absent from all other arthropods for which data are available. This provides unambiguous evidence for a relatively recent intron insertion event in the colletid common ancestor and, at least in this specific instance, lends support to the introns-late hypothesis. The comparative distribution of this novel intron also supports the monophyly of Colletidae and the exclusion of the Stenotritidae from this family, providing an example of the potential of some introns to act as robust markers of shared descent.     

Analyzing a randomized trial on breast self-examination with noncompliance and missing outcomes

Recently, instrumental variables methods have been used to address non-compliance in randomized experiments. Complicating such analyses is often the presence of missing data. The standard model for missing data, missing at random (MAR), has some unattractive features in this context. In this paper we compare MAR-based estimates of the complier average causal effect (CACE) with an estimator based on an alternative, nonignorable model for the missing data process, developed by Frangakis and Rubin (1999, Biometrika, 86, 365-379). We also introduce a new missing data model that, like the Frangakis-Rubin model, is specially suited for models with instrumental variables, but makes different substantive assumptions. We analyze these issues in the context of a randomized trial of breast self-examination (BSE). In the study two methods of teaching BSE, consisting of either mailed information about BSE (the standard treatment) or the attendance of a course involving theoretical and practical sessions (the new treatment), were compared with the aim of assessing whether teaching programs could increase BSE practice and improve examination skills. The study was affected by the two sources of bias mentioned above: only 55% of women assigned to receive the new treatment complied with their assignment and 35% of the women did not respond to the post-test questionnaire. Comparing the causal estimand of the new treatment using the MAR, Frangakis-Rubin, and our new approach, the results suggest that for these data the MAR assumption appears least plausible, and that the new model appears most plausible among the three choices.     

Average protein density is a molecular-weight-dependent function

The mass density of proteins is a relevant basic biophysical quantity. It is also a useful input parameter, for example, for three-dimensional structure determination by protein crystallography and studies of protein oligomers in solution by analytic ultracentrifugation. We have performed a critical analysis of published, theoretical, and experimental investigations about this issue and concluded that the average density of proteins is not a constant as often assumed. For proteins with a molecular weight below 20 kDa, the average density exhibits a positive deviation that increases for decreasing molecular weight. A simple molecular-weight-depending function is proposed that provides a more accurate estimate of the average protein density.     

Foraging efficiency of juvenile bluegill, Lepomis macrochirus, among different vegetated habitats

Optimal foraging theory is devoted to understanding how organisms maximize net energy gain. However, both the theory and empirical studies lack critical components, such as effects of environmental variables across habitats. We addressed the hypothesis that energetic returns of juvenile bluegill are affected by environmental variables characteristic of the vegetated habitats. Predicted optimal diet breadths were calculated and compared to prey items eaten by juvenile bluegill to determine if bluegill were foraging to maximize energetic gain. Differences in habitat profitability among vegetated sites were determined by comparing predictions of maximized energetic return rates (cals^-1) with prey contents of bluegill stomachs. Sizes of most prey items eaten by juvenile bluegill throughout the vegetated sites were smaller than the predicted optimal diet breadths. However, inclusion of smaller prey items in the diet did not seem to affect rate of energetic gain. Energetic return rates were maximized at the 1.5 and 2mm prey size classes and declined only slightly with inclusion of smaller prey sizes. Predicted energetic return rates and average mass in bluegill stomachs were related negatively. Average mass in bluegill stomachs also was associated negatively with Elodea canadensis stem densities and percent of light transfer, suggesting that foraging efficiency of bluegill decreased as plant density and percent of light increased. Results of our research indicate that maximization of energetic return rates is dependent upon availability of prey sizes that contribute to optimal foraging. Thus, determination of those habitats that provide the highest availability of benthic invertebrate prey with the least interference by stems is critical. Enhanced foraging capabilities can promote recruitment, faster growth, better body condition and survival.     

Daily rhythms of emergence of small invertebrates inhabiting shallow subtidal zones: A comparative investigation at four locations in Japan

Many small invertebrates inhabit the shallow subtidal zone and some of them emerge at times into the water column. The daily timing of their emergence is affected by the day/night and tidal cycles, and shows various patterns of synchrony with these cyclical factors, depending on the species. To detect possible regional differences in their emergence patterns, sampling was carried out at four locations in Japan: a boreal sea (Akkeshi), a temperate sea (Sugashima), an inland sea (Ushimado) and a subtropical sea (Iriomote-jima). The emergence patterns of major taxa were examined by visual inspection and by two statistical methods (periodogram and autocorrelogram). The composition of the taxa collected by the pump system, mostly crustaceans, was similar in each location. The number of taxa that emerged revealed a day/night rhythm in every location. This characteristic was clearest at Iriomote-jima and least clear at Sugashima. The daily fluctuation in the number of individuals in each taxon varied widely, from very clearly nocturnal to weakly diurnal patterns. In Iriomote-jima, the major taxa all showed well-demarcated nocturnal patterns, so these patterns were classified as either level N₂ or N₃ with regard to the degree of synchrony with the day/night cycle. With regard to the synchrony with the tide, the majority of patterns in all locations showed a double-tidal interval. Many patterns were slightly modified by the tidal cycle. These patterns were classified as level T₁ or T₂ with regard to the degree of synchrony with the tidal cycle. The synchrony with the tide was comparatively strong at Ushimado. The synchrony with day/night and tidal cycles varied even within the same species or closely related species. In benthic invertebrates, hiding or resting in the bottom substrates and swimming in the water column would occur alternatively. In planktonic animals, aggregation near the bottom and dispersal in the water column would occur alternatively. The daily timing of such activities may be synchronized with the day/night and tidal cycles to various degrees among species or populations, resulting in a wide variety of emergence patterns in subtidal small invertebrates. This type of behavior is not daily (diel) vertical migration; it should rather be called daily emergence/dispersal. Strong winds, rough waves and unknown seasonal factors would also affect emergence patterns. Furthermore, the transparency of the seawater may also strongly affect these patterns. Nocturnal patterns may be an adaptation to avoid vulnerability to sighted predators. Variation of synchrony with the tide indicates that by definition, the tidal rhythm can only be distinguished from the day/night rhythm. Hence, the daily patterns that are weakly modified by the tides (levels T₁ and T₂) should be called the tidal rhythms. As the period of such rhythms cannot be determined exactly by using statistical methods, lengthy field investigations and visual inspection of each pattern is essential to assess the influence of tides.     

The seasonal daily travel in a group of Sichuan snub-nosed monkey (Pygathrix roxellana) in Shennongjia Nature Reserve,China

The seasonal daily travel of a group of snub-nosed monkey (Pygathrix roxellana) was investigated using the group’s straight-line distance method. The group was followed from dawn to dusk for 30 consecutive days during each season to encompass all aspects of daily travel patterns. The results showed that in Summer and Autumn, the mean daily travel distance (m) was significantly longer than in Winter and Spring. There was no significant difference in the mean daily travel distance between Summer and Autumn or between Winter and Autumn. The mean travel distance (m/hr) during daytime was significantly higher in Summer and Autumn than in Spring, and in Autumn than in Winter. The travel of the group in all seasons had similar patterns. Traveling showed morning and afternoon peaks, with a rest period at the noon in a day. Seasonal food availability, length of daytime, and mean travel distance (m/hr) during daytime might have contributed to the different daily travel distances in different seasons.