The Selection Exerted by Oil Contamination on Mangrove Fungal Communities

Mangrove ecosystems are tropical environments that are characterized by the interaction between the land and the sea. As such, this ecosystem is vulnerable to oil spills. Here, we show a culture-independent survey of fungal communities that are found in the sediments of the following two mangroves that are located on the coast of Sao Paulo State (Brazil): (1) an oil-spill-affected mangrove and (2) a nearby unaffected mangrove. Samples were collected from each mangrove forest at three distinct locations (transect from sea to land), and the samples were analyzed by quantitative PCR and internal transcribed spacer (ITS)-based PCR-DGGE analysis. The abundance of fungi was found to be higher in the oil-affected mangrove. Visual observation and correspondence analysis (CA) of the ITS-based PCR-DGGE profiles revealed differences in the fungal communities between the sampled areas. Remarkably, the oil-spilled area was quite distinct from the unaffected sampling areas. On the basis of the ITS sequences, fungi that are associated with the Basidiomycota and Ascomycota taxa were most common and belonged primarily to the genera Epicoccum, Nigrospora, and Cladosporium. Moreover, the Nigrospora fungal species were shown to be sensitive to oil, whereas a group that was described as "uncultured Basidiomycota" was found more frequently in oil-contaminated areas. Our results showed an increase in fungal abundance in the oil-polluted mangrove regions, and these data indicated potential fungal candidates for remediation of the oil-affected mangroves.

Vascular wall stem cells. Selection and conditioning of progenitors useful for cell therapy. A pathological case study

The arterial wall contains MSCs with mesengenic and angiogenic abilities. These multipotent precursors have been isolated from variously-sized human adult segments, belying the notion that vessel wall is a relatively quiescent tissue. Recently, our group identified in normal human arteries a vasculogenic niche and subsequently isolated and characterized resident MSCs (VW-MSCs) with angiogenic ability and multilineage potential. To prove that VW-MSCs are involved in normal and pathological vascular remodeling, we used a long-term organ culture system; this method was of critical importance to follow spontaneous 3-D vascular remodeling without any influence of blood cells. Next we tried to identify and localize in situ the VW-MSCs and to understand their role in the vascular remodeling in failed arterial homografts. Subsequently, we isolated this cell population and tested in vitro their multilineage differentiation potential through immunohistochemical, immunofluorescence, RT-PCR and ultrastructural analysis. From 25-30cm2 of each vascular wall homograft sample, we isolated a cell population with MSCs properties; these cells expressed MSC lineage molecules (CD90, CD44, CD105, CD29, CD73), stemness (Notch-1, Oct-4, Sca-1, Stro-1) and pericyte markers (NG2) whilst were negative for hematopoietic and endothelial markers (CD34, CD133, CD45, KDR, CD146, CD31 and vWF). MSCs derived from failed homografts (H-MSCs) exhibited adipogenic, osteogenic and chondrogenic potential but scarce propensity to angiogenic and leiomyogenic differentiation. The present study demonstrates that failed homografts contain MSCs with morphological, phenotypic and functional MSCs properties; H-MSCs are long-lived in culture, highly proliferating and endowed with prompt ability to differentiate into adipocytes, osteocytes and chondrocytes; compared with VW-MSCs from normal arteries, H-MSCs show a failure in angiogenic and leiomyogenic differentiation. A switch in MSCs plasticity could be the basis of pathological remodeling and contribute to aneurysmal failure of arterial homografts. The study of VW-MSCs in a pathological setting indicate that additional mechanisms are involved in vascular diseases; their knowledge will be useful for opening new therapeutic options in cardiovascular diseases.

How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA study of the Swiss Working Group of Breast- and Gynecopathologists

Adjuvant chemotherapy decisions in breast cancer are increasingly based on the pathologist's assessment of tumor proliferation. The Swiss Working Group of Gyneco- and Breast Pathologists has surveyed inter- and intraobserver consistency of Ki-67-based proliferative fraction in breast carcinomas. Methods Five pathologists evaluated MIB-1-labeling index (LI) in ten breast carcinomas (G1, G2, G3) by counting and eyeballing. In the same way, 15 pathologists all over Switzerland then assessed MIB-1-LI on three G2 carcinomas, in self-selected or pre-defined areas of the tumors, comparing centrally immunostained slides with slides immunostained in the different laboratoires. To study intra-observer variability, the same tumors were re-examined 4 months later. Results The Kappa values for the first series of ten carcinomas of various degrees of differentiation showed good to very good agreement for MIB-1-LI (Kappa 0.56–0.72). However, we found very high inter-observer variabilities (Kappa 0.04–0.14) in the read-outs of the G2 carcinomas. It was not possible to explain the inconsistencies exclusively by any of the following factors: (i) pathologists' divergent definitions of what counts as a positive nucleus (ii) the mode of assessment (counting vs. eyeballing), (iii) immunostaining technique, and (iv) the selection of the tumor area in which to count. Despite intensive confrontation of all participating pathologists with the problem, inter-observer agreement did not improve when the same slides were re-examined 4 months later (Kappa 0.01–0.04) and intra-observer agreement was likewise poor (Kappa 0.00–0.35). Conclusion Assessment of mid-range Ki-67-LI suffers from high inter- and intra-observer variability. Oncologists should be aware of this caveat when using Ki-67-LI as a basis for treatment decisions in moderately differentiated breast carcinomas.

A Stellar Census of the Tucana-Horologium Moving Group

We report the selection and spectroscopic confirmation of 129 new late-type (SpT = K3-M6) members of the Tucana-Horologium moving group, a nearby (d similar to 40 pc), young (tau similar to 40 Myr) population of comoving stars. We also report observations for 13 of the 17 known Tuc-Hor members in this spectral type range, and that 62 additional candidates are likely to be unassociated field stars; the confirmation frequency for new candidates is therefore 129/191 = 67%. We have used radial velocities, Ha emission, and Li-6708 absorption to distinguish between contaminants and bona fide members. Our expanded census of Tuc-Hor increases the known population by a factor of similar to 3 in total and by a factor of similar to 8 for members with SpT >= K3, but even so, the K-M dwarf population of Tuc-Hor is still markedly incomplete. Our expanded census allows for a much more detailed study of Tuc-Hor than was previously feasible. The spatial distribution of members appears to trace a two-dimensional sheet, with a broad distribution in X and Y, but a very narrow distribution (+/- 5 pc) in Z. The corresponding velocity distribution is very small, with a scatter of +/- 1.1 km s(-1) about the mean UVW velocity for stars spanning the entire 50 pc extent of Tuc-Hor. We also show that the isochronal age (tau similar to 20-30 Myr) and the lithium depletion boundary age (tau similar to 40 Myr) disagree, following the trend in other pre-main-sequence populations for isochrones to yield systematically younger ages. The H alpha emission line strength follows a trend of increasing equivalent width with later spectral type, as is seen for young clusters. We find that moving group members have been depleted of measurable lithium for spectral types of K7.0-M4.5. None of our targets have significant infrared excesses in the WISE W3 band, yielding an upper limit on warm debris disks of F < 0.7%. Finally, our purely kinematic and color-magnitude selection procedure allows us to test the efficiency and completeness for activity-based selection of young stars. We find that 60% of K-M dwarfs in Tuc-Hor do not have ROSAT counterparts and would have been omitted in X-ray-selected samples. In contrast, GALEX UV-selected samples using a previously suggested criterion for youth achieve completeness of 77% and purity of 78%, and we suggest new SpT-dependent selection criteria that will yield > 95% completeness for tau similar to 40 Myr populations with GALEX data available.

Impact of drug-eluting stent selection on long-term clinical outcomes in patients treated for unprotected left main coronary artery disease: the sirolimus vs paclitaxel drug-eluting stent for left main registry (SP-DELFT)

AIM: To compare the long-term relative efficacy and safety of SES and PES in patients undergoing percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) disease and to evaluate the role of lesion location and stenting technique in determining outcomes. METHODS AND RESULTS: From April 2002 to April 2004, 288 consecutive patients who underwent elective PCI with DES implantation for de novo lesions on ULMCA have been retrospectively selected and analyzed in seven European and US tertiary care centers. All patients had a minimum follow-up of 3 years. SES was used in 152 patients while 136 received PES. Isolated ostial-shaft disease was present in 27% of patients. Distal LM disease (73%) was treated with single and double stent approach in 29.5% and 43.4% of patients respectively. After 3 years, rates of survival free from any of the events investigated, were independent from lesion location and stenting approach and did not differ significantly between SES and PES groups. Freedom from MACE (SES vs. PES) was 76.3% vs. 83.1% in the ostial/shaft group, 80.3% vs. 72.8% in the distal-single stent group and 67.1% vs. 66.2% in the distal-double stent group. Definite stent thrombosis occurred only in 1(0.3%) patient at 439 days. CONCLUSIONS: In elective patients who underwent PCI for de novo lesions in the ostium, shaft or distal ULMCA, long-term clinical outcomes with SES and PES use were similar independently of lesion location and stenting technique.

Patch selection by wintering white-tailed deer : consequences for eastern hemlock regeneration at local and landscape scales

Tsuga canadensis (eastern hemlock) is a highly shade-tolerant, late-successional, and long-lived conifer species found throughout eastern North America. It is most often found in pure or nearly pure stands, because highly acidic and nutrient poor forest floor conditions are thought to favor T. canadensis regeneration while simultaneously limiting the establishment of some hardwood species with greater nutrient requirements. Once a common species, T. canadensis is currently experiencing widescale declines across its range. The hemlock woolly adelgid (Adelges tsugae) is decimating the population across its eastern distribution. Across the Upper Great Lakes region, where the adelgid is currently being held at bay by cold winter temperatures, T. canadensis has been experiencing failures in regeneration attributed, in part, to herbivory by white-tailed deer (Odocoileus virginianus). Deer utilize T. canadensis stands as winter habitat in areas of high snow depth. Tsuga canadensis, once a major component of these forests, currently exists at just a fraction of its pre-settlement abundance due to historic logging and contemporary forest management practices, and what remains is found in small remnant patches surrounded by second- and third-growth deciduous forests. The deer population across the region, however, is likely double that of pre-European settlement times. In this dissertation I explore the relationship between white-tailed deer use of T. canadensis as winter habitat and the effect this use is having on regeneration and forest succession. For this research I quantified stand composition and structure and abiotic variables of elevation and snow depth in 39 randomly selected T. canadensis stands from across the western Upper Peninsula of Michigan. I also quantified composition and the configuration of the landscapes surrounding these stands. I measured relative deer use of T. canadensis stands as pellet group piles deposited in each stand during each of three consecutive winters, 2005-06, 2006-07, and 2007-08. The results of this research suggest that deer use of T. canadensis stands as winter habitat is influenced primarily by snow depth, elevation, and the composition and configuration of the greater landscapes surrounding these stands. Specifically, stands with more heterogeneous landscapes surrounding them (i.e., a patchy mosaic of conifer, deciduous, and open cover) had higher relative deer use than stands surrounded by homogenous deciduous forest cover. Additionally, the intensity of use and the number of stands used was greater in years with higher average snow depth. Tsuga canadensis regeneration in these stands was negatively associated with deer use and Acer saccharum (sugar maple) basal area. Of the 39 stands, 17 and 22 stands had no T. canadensis regeneration in small and large sapling categories, respectively. Acer saccharum was the most common understory tree species, and the importance of A. saccharum in the understory (stems < 10 cm dbh) of the stands was positively associated with overstory A. saccharum dominance. Tsuga canadensis establishment was associated with high-decay coarse woody debris and moss, and deciduous leaf litter inputs in these stands may be limiting access to these important microsites. Furthermore, A. saccharum is more tolerant to the effects of deer herbivory than T. canadensis, giving A. saccharum a competitive advantage in stands being utilized as winter habitat by deer. My research suggests that limited microsite availability, in conjunction with deer herbivory, may be leading to an erosion in T. canadensis patch stability and an altered successional trajectory toward one of A. saccharum dominance, an alternately stable climax species.

Better conduct of clinical trials: the control group in critical care trials

OBJECTIVE: To review trial design issues related to control groups. DESIGN: Review of the literature with specific reference to critical care trials. MAIN RESULTS AND CONCLUSIONS: Performing randomized controlled trials in the critical care setting presents specific problems: studies include patients with rapidly lethal conditions, the majority of intensive care patients suffer from syndromes rather than from well-definable diseases, the severity of such syndromes cannot be precisely assessed, and the treatment consists of interacting therapies. Interactions between physiology, pathophysiology, and therapies are at best marginally understood and may have a major impact on study design and interpretation of results. Selection of the right control group is crucial for the interpretation and clinical implementation of results. Studies comparing new interventions with current ones or different levels of current treatments have the problem of the necessity of defining "usual care." Usual care controls without any constraints typically include substantial heterogeneity. Constraints in the usual therapy may help to reduce some variation. Inclusion of unrestricted usual care groups may help to enhance safety. Practice misalignment is a novel problem in which patients receive a treatment that is the direct opposite of usual care, and occurs when fixed-dose interventions are used in situations where care is normally titrated. Practice misalignment should be considered in the design and interpretation of studies on titrated therapies.

Divergent selection during speciation of Lake Malawi cichlid fishes inferred from parallel radiations in nuptial coloration

Repeated evolution of the same phenotypic difference during independent episodes of speciation is strong evidence for selection during speciation. More than 1,000 species of cichlids, >10% of the world's freshwater fish species, have arisen within the past million years in Lakes Malawi and Victoria in eastern Africa. Many pairs of closely related sympatric species differ in their nuptial coloration in very similar ways. Nuptial coloration is important in their mate choice, and speciation by sexual selection on genetically or ecologically constrained variation in nuptial coloration had been proposed, which would repeatedly produce similar nuptial types in different populations, a prediction that was difficult to test in the absence of population-level phylogenies. We measured genetic similarity between individuals within and between populations, species, and lake regions by typing 59 individuals at >2,000 polymorphic genetic loci. From these data, we reconstructed, to our knowledge, the first larger species level phylogeny for the most diverse group of Lake Malawi cichlids. We used the genetic and phylogenetic data to test the divergent selection scenario against colonization, character displacement, and hybridization scenarios that could also explain diverse communities. Diversity has arisen by replicated radiations into the same color types, resulting in phenotypically very different, yet closely related, species within and phenotypically highly similar yet unrelated sets of species between regions, which is consistent with divergent selection during speciation and is inconsistent with colonization and character displacement models.

Endovascular treatment for acute ischemic stroke patients: implications and interpretation of IMS III, MR RESCUE, and SYNTHESIS EXPANSION trials: A report from the Working Group of International Congress of Interventional Neurology

OBJECTIVE The results of Interventional Management of Stroke (IMS) III, Magnetic Resonance and REcanalization of Stroke Clots Using Embolectomy (MR RESCUE), and SYNTHESIS EXPANSION trials are expected to affect the practice of endovascular treatment for acute ischemic stroke. The purpose of this report is to review the components of the designs and methods of these trials and to describe the influence of those components on the interpretation of trial results. METHODS A critical review of trial design and conduct of IMS III, MR RESCUE, and SYNTHESIS EXPANSION is performed with emphasis on patient selection, shortcomings in procedural aspects, and methodology of data ascertainment and analysis. The influence of each component is estimated based on published literature including multicenter clinical trials reporting on endovascular treatment for acute ischemic stroke and myocardial infarction. RESULTS We critically examined the time interval between symptom onset and treatment and rates of angiographic recanalization to differentiate between "endovascular treatment" and "parameter optimized endovascular treatment" as it relates to the IMS III, MR RESCUE, and SYNTHESIS EXPANSION trials. All the three trials failed to effectively test "parameter optimized endovascular treatment" due to the delay between symptom onset and treatment and less than optimal rates of recanalization. In all the three trials, the magnitude of benefit with endovascular treatment required to reject the null hypothesis was larger than could be expected based on previous studies. The IMS III and SYNTHESIS EXPANSION trials demonstrated that rates of symptomatic intracerebral hemorrhages subsequent to treatment are similar between IV thrombolytics and endovascular treatment in matched acute ischemic stroke patients. The trials also indirectly validated the superiority/equivalence of IV thrombolytics (compared with endovascular treatment) in patients with minor neurological deficits and those without large vessel occlusion on computed tomographic/magnetic resonance angiography. CONCLUSIONS The results do not support a large magnitude benefit of endovascular treatment in subjects randomized in all the three trials. The possibility that benefits of a smaller magnitude exist in certain patient populations cannot be excluded. Large magnitude benefits can be expected with implementation of "parameter optimized endovascular treatment" in patients with ischemic stroke who are candidates for IV thrombolytics.

Total Tumor Volume and Alpha Fetoprotein for selection of transplant candidates with hepatocellular carcinoma: A prospective validation.

The selection of liver transplant candidates with hepatocellular carcinoma (HCC) is currently validated based on Milan criteria. The use of extended criteria has remained a matter of debate, mainly because of the absence of prospective validation. The present prospective study recruited patients according to the previously proposed Total Tumor Volume (TTV ≤115 cm(3) )/alpha fetoprotein (AFP ≤400 ng/ml) score. Patients with AFP >400 ng/ml were excluded, and as such the Milan group was modified to include only patients with AFP <400 ng/ml; these patients were compared to patients beyond Milan, but within TTV/AFP. From January 2007 to March 2013, 233 patients with HCC were listed for liver transplantation. Of them, 195 patients were within Milan, and 38 beyond Milan but within TTV/AFP. The average follow-up from listing was 33,9 ±24,9 months. The risk of drop-out was higher for patients beyond Milan but within TTV/AFP (16/38, 42,1%), than for patients within Milan (49/195, 25,1%, p=0,033). In parallel, intent-to-treat survival from listing was lower in the patients beyond Milan (53,8% vs. 71,6% at four years, p<0,001). After a median waiting time of 8 months, 166 patients were transplanted, 134 patients within Milan criteria, and 32 beyond Milan but within TTV/AFP. They demonstrated acceptable and similar recurrence rates (4,5% vs. 9,4%, p=0,138) and post-transplant survivals (78,7% vs. 74,6% at four years, p=0,932). CONCLUSION Based on the present prospective study, HCC liver transplant candidate selection could be expanded to the TTV (≤115 cm(3) )/AFP (≤400 ng/ml) criteria in centers with at least 8-month waiting time. An increased risk of drop-out on the waiting list can be expected but with equivalent and satisfactory post-transplant survival. This article is protected by copyright. All rights reserved.

Inhibition of DNA polymerase reaction by pyrimidine nucleotide analogues lacking the 2-keto group

To investigate the influence of the pyrimidine 2-keto group on selection of nucleotides for incorporation into DNA by polymerases, we have prepared two C nucleoside triphosphates that are analogues of dCTP and dTTP, namely 2-amino-5-(2'-deoxy-beta-d-ribofuranosyl)pyridine-5'-triphosphate (d*CTP) and 5-(2'-deoxy- beta-d-ribofuranosyl)-3-methyl-2-pyridone-5'-triphosphate (d*TTP) respectively. Both proved strongly inhibitory to PCR catalysed by Taq polymerase; d*TTP rather more so than d*CTP. In primer extension experiments conducted with either Taq polymerase or the Klenow fragment of Escherichia coli DNA polymerase I, both nucleotides failed to substitute for their natural pyrimidine counterparts. Neither derivative was incorporated as a chain terminator. Their capacity to inhibit DNA polymerase activity may well result from incompatibility with the correctly folded form of the polymerase enzyme needed to stabilize the transition state and catalyse phosphodiester bond formation.

Explosive speciation rates and unusual species richness in haplochromine cichlid fishes: Effects of sexual selection

Ancient lakes are often unusually species rich, mostly as a result of radiation and species-flock formation having taken place in only one or a few of many taxa present. Understanding why some taxa radiate and others do not is at the heart of understanding biodiversity. In this chapter I discuss possible explanations for disproportionally large species numbers in some cichlid fish lineages in East African Great Lakes: the halochromine cichlid fishes in Lakes Victoria and Malawi. I show that speciation rates in this group are higher than in any other lacustrine fish radiation. Against this background, I review hypotheses put forward to explain diversity in cichlid species flocks. The evolution of species diversity requires three processes: speciation, ecological radiation and anatomical diversification, and it is wrong to consider hypotheses that are relevant to different processes as alternatives to each other. The African cichlid species flocks show unusually high ecological species packing in several phylogenetic groups and unusually high speciation rates in haplochromines. Therefore, it maybe concluded that at least two evolutionary models are required to explain the difference between cichlid diversity and other fish diversity in East African Lakes: one for speciation in haplochromines and one for coexistence. Subsequently I review work on speciation in haplochromines, and in particular studies aimed at testing the hypothesis of speciation by sexual selection. Haplochromines have a polygynous mating system, conducive to sexual selection, but other polygynous cichlids are not particularly species rich. This suggests that more than just strong sexual selection is required to explain haplochromine species richness. Recent palaeoecological evidence undermines the previously popular hypotheses that explained the species richness of Lake Victoria in terms of speciation under varying natural or sexual selection regimes in satellite lakes or in isolated lake basins. I summarize experimental and comparative studies, which provide evidence for two mechanisms of sympatric speciation by disruptive sexual selection on polymorphic coloration. Such modes of speciation may explain (i) the high speciation rates in colour polymorphic lineages of haplochromine cichlids under conditions where colour variation is visible in clear water, and (ii) in combination with factors that affect population survival, the unusual species richness in haplochromine species flocks. I argue that sexual selection, if disruptive, can accelerate the pace of adaptive radiation because the resultant genetic population fragmentation allows a much increased rate of differential response to disruptive natural selection. Hence, the ecological pattern of diversity resembles that produced by disruptive natural selection, with the difference that disruptive sexual selection continues to cause (gross) speciation even after niche space is saturated. This may explain the unusually high numbers of very closely related and ecologically similar species in haplochromine species flocks. The role of disruptive sexual selection is twofold: it not only causes speciation, but also maintains reproductive isolation in sympatry between species that have evolved in sympatry or allopatry. Therefore, the maintenance of diversity in species flocks that originated through sexual selection depends on the persistence of the selection regime within the environmental signal space under which that diversity evolved.

Can ancient colour polymorphisms explain why some cichlid lineages speciate rapidly under disruptive sexual selection?

It is not sufficiently understood why some lineages of cichlid fishes have proliferated in the Great Lakes of East Africa much more than anywhere else in the world, and much faster than other cichlid lineages or any other group of freshwater fish. Recent field and experimental work on Lake Victoria haplochromines suggests that mate choice-mediated disruptive sexual selection on coloration, that can cause speciation even in the absence of geographical isolation, may explain it. We summarize the evidence and propose a hypothesis for the genetics of coloration that may help understand the phenomenon. By detl ning colour patterns by hue and arrangement of hues on the body, we could assign almost all observed phenotypes of Lake Victoria cichlids to one of three female («plain», «orange blotched», «black and white») and three male («blue», «red-ventrum», «reddorsum») colour patterns. These patterns diagnose species but frequently eo-occur also as morphs within the same population, where they are associated with variation in mate preferences, and appear to be transient stages in speciation. Particularly the male patterns occur in almost every genus of the species flock. We propose that the patterns and their association into polymorphisms express an ancestral trait that is retained across speciation. Our model for male colour pattern assumes two structural loci. When both are switched off, the body is blue. When switched on by a cascade of polymorphic regulatory genes, one expresses a yellow to red ventrum, the other one a yellow to red dorsum. The expression of colour variation initiates speciation. The blue daughter species will inherit the variation at the regulatory genes that can, without new mutational events, purely by recombination, again expose the colour polymorphism, starting the process anew. Very similar colour patterns also dominate among the Mbuna of Lake Malawi. In contrast, similar colour polymorphisms do not exist in the lineages that have not proliferated in the Great Lakes. The colour pattern polymorphism may be an ancient trait in the lineage (or lineages) that gave rise to the two large haplochromine radiations. We propose two tests of our hypothesis.

Bayesian doubly optimal group sequential designs for randomized clinical trials

When conducting a randomized comparative clinical trial, ethical, scientific or economic considerations often motivate the use of interim decision rules after successive groups of patients have been treated. These decisions may pertain to the comparative efficacy or safety of the treatments under study, cost considerations, the desire to accelerate the drug evaluation process, or the likelihood of therapeutic benefit for future patients. At the time of each interim decision, an important question is whether patient enrollment should continue or be terminated; either due to a high probability that one treatment is superior to the other, or a low probability that the experimental treatment will ultimately prove to be superior. The use of frequentist group sequential decision rules has become routine in the conduct of phase III clinical trials. In this dissertation, we will present a new Bayesian decision-theoretic approach to the problem of designing a randomized group sequential clinical trial, focusing on two-arm trials with time-to-failure outcomes. Forward simulation is used to obtain optimal decision boundaries for each of a set of possible models. At each interim analysis, we use Bayesian model selection to adaptively choose the model having the largest posterior probability of being correct, and we then make the interim decision based on the boundaries that are optimal under the chosen model. We provide a simulation study to compare this method, which we call Bayesian Doubly Optimal Group Sequential (BDOGS), to corresponding frequentist designs using either O'Brien-Fleming (OF) or Pocock boundaries, as obtained from EaSt 2000. Our simulation results show that, over a wide variety of different cases, BDOGS either performs at least as well as both OF and Pocock, or on average provides a much smaller trial. ^