Estimation of Conditional Power for Cluster-Randomized Trials with Interval-Censored Endpoints

Cluster-randomized trials (CRTs) of infectious disease preventions often yield correlated, interval-censored data: dependencies may exist between observations from the same cluster, and event occurrence may be assessed only at intermittent clinic visits. This data structure must be accounted for when conducting interim monitoring and futility assessment for CRTs. In this article, we propose a flexible framework for conditional power estimation when outcomes are correlated and interval-censored. Under the assumption that the survival times follow a shared frailty model, we first characterize the correspondence between the marginal and cluster-conditional survival functions, and then use this relationship to semiparametrically estimate the cluster-specific survival distributions from the available interim data. We incorporate assumptions about changes to the event process over the remainder of the trial---as well as estimates of the dependency among observations in the same cluster---to extend these survival curves through the end of the study. Based on these projected survival functions we generate correlated interval-censored observations, and then calculate the conditional power as the proportion of times (across multiple full-data generation steps) that the null hypothesis of no treatment effect is rejected. We evaluate the performance of the proposed method through extensive simulation studies, and illustrate its use on a large cluster-randomized HIV prevention trial

Strip-Seeding of Red Clover, Lucerne, Alsike Clover, White Clover and Sainfoin into Grassland in Central Europe

Strip-seeding of legumes into grassland improves forage quality and adds fixed nitrogen (N) to grassland, which decreases the need for mineral N

Repeated Strip-Seeding of a Legume-Grass Mixture into Permanent Grassland in the Czech Republic

Although ruminants do not belong to the main consumers of protein supplements, there is a possibility to decrease the use of feed grain by increasing the protein content in the forage from permanent grassland. This paper describes strip-sowing of a legume-grass mixture. Saved protein supplements can then be used for feeding pigs and poultry

The Influence of Fertiliser Application to Strip-Sown Grasslands on Herbage Production and Quality

To increase the productivity of dairy cattle in the Czech Republic requires an improvement in herbage quality and an increase in the net energy of herbage. The decrease in cattle numbers by 50 % and the expansion of the grassland area both result in a surplus of feedstuffs of low quality. Introduction of strip-seeding of legumes and grasses into grasslands in interaction with fertilisation provides a possible solution to this problem

Cyanobacteria of the thermal spring at Pancharevo, Sofia, Bulgaria

Eight taxa of cyanobacteria were identified in the thermal spring at Pancharevo (in the Sofia basin, Bulgaria). As well as the widespread Lyngbya thermalis, Phormidesmis molle (syn. Phormidium molle), Phormidium papyraceum, Phormidium corium and Mastigocladus laminosus, four species were identified for the first time in Bulgaria: Calothrix thermalis, Gloeocapsa gelatinosa, Leibleinia epiphytica and Symploca thermalis

Semiparametric Multivariate Accelerated Failure Time Model with Generalized Estimating Equations

The semiparametric accelerated failure time model is not as widely used as the Cox relative risk model mainly due to computational difficulties. Recent developments in least squares estimation and induced smoothing estimating equations provide promising tools to make the accelerate failure time models more attractive in practice. For semiparametric multivariate accelerated failure time models, we propose a generalized estimating equation approach to account for the multivariate dependence through working correlation structures. The marginal error distributions can be either identical as in sequential event settings or different as in parallel event settings. Some regression coefficients can be shared across margins as needed. The initial estimator is a rank-based estimator with Gehan's weight, but obtained from an induced smoothing approach with computation ease. The resulting estimator is consistent and asymptotically normal, with a variance estimated through a multiplier resampling method. In a simulation study, our estimator was up to three times as efficient as the initial estimator, especially with stronger multivariate dependence and heavier censoring percentage. Two real examples demonstrate the utility of the proposed method

Prolonged interglacial warmth during the Last Glacial in northern Europe

Few fossil-based environmental and climate records in northern Europe are dated to Marine Isotope Stage (MIS) 5a around 80 ka BP. We here present multiple environmental and climate proxies obtained from a lake sequence of MIS 5a age in the Sokli basin (northern Finland). Pollen/spores, plant macrofossils, NPPs (e.g. green algae), bryozoa, diatoms and chironomids allowed an exceptionally detailed reconstruction of aquatic and telmatic ecosystem successions related to the development of the Sokli Ice Lake and subsequent infilling of a relatively small and shallow lake confined to the Sokli basin. A regional vegetation development typical for the early half of an interglacial is recorded by the pollen, stomata and plant macrofossil data. Reconstructions of July temperatures based on pollen assemblages suffer from a large contribution of local pollen from the lake's littoral zone. Summer temperatures reaching present-day values, inferred for the upper part of the lake sequence, however, agree with the establishment of pine-dominated boreal forest indicated by the plant fossil data. Habitat preferences also influence the climate record based on chironomids. Nevertheless, the climate optima of the predominant intermediate- to warm-water chironomid taxa suggest July temperatures exceeding present-day values by up to several degrees, in line with climate inferences from a variety of aquatic and wetland plant indicator species. The disequilibrium between regional vegetation development and warm, insolation-forced summers is also reported for Early Holocene records from northern Fennoscandia. The MIS 5a sequence is the last remaining fossil-bearing deposit in the late Quaternary basin infill at Sokli to be studied using multi-proxy evidence. A unique detailed climate record for MIS 5 is now available for formerly glaciated northern Europe. Our studies indicate that interglacial conditions persisted into MIS 5a, in agreement with data for large parts of the European mainland, shortening the Last Glacial by some 50 ka to MIS 4-2.Peer reviewe