An unexpected rearrangement giving a new thiosubstituted carbohydrate

A new thiosubstituted ‘d-arabino’-type derivative was obtained from an open carbohydrate via a cascade of four consecutive transformations in a single reaction process. Molecular orbital computations were also performed to explain the stereochemical outcome of the reaction.     

THE LANDE–KIRKPATRICK MECHANISM IS THE NULL MODEL OF EVOLUTION BY INTERSEXUAL SELECTION: IMPLICATIONS FOR MEANING,HONESTY, AND DESIGN IN INTERSEXUAL SIGNALS

The Fisher‐inspired, arbitrary intersexual selection models of Lande (1981) and Kirkpatrick (1982) , including both stable and unstable equilibrium conditions, provide the appropriate null model for the evolution of traits and preferences by intersexual selection. Like the Hardy–Weinberg equilibrium, the Lande–Kirkpatrick (LK) mechanism arises as an intrinsic consequence of genetic variation in trait and preference in the absence of other evolutionary forces. The LK mechanism is equivalent to other intersexual selection mechanisms in the absence of additional selection on preference and with additional trait‐viability and preference‐viability correlations equal to zero. The LK null model predicts the evolution of arbitrary display traits that are neither honest nor dishonest, indicate nothing other than mating availability, and lack any meaning or design other than their potential to correspond to mating preferences. The current standard for demonstrating an arbitrary trait is impossible to meet because it requires proof of the null hypothesis. The LK null model makes distinct predictions about the evolvability of traits and preferences. Examples of recent intersexual selection research document the confirmationist pitfalls of lacking a null model. Incorporation of the LK null into intersexual selection will contribute to serious examination of the extent to which natural selection on preferences shapes signals.     

The weighted generalized estimating equations approach for the evaluation of medical diagnostic test at subunit level

Sensitivity and specificity are common measures used to evaluate the performance of a diagnostic test. A diagnostic test is often administrated at a subunit level, e.g. at the level of vessel, ear or eye of a patient so that the treatment can be targeted at the specific subunit. Therefore, it is essential to evaluate the diagnostic test at the subunit level. Often patients with more negative subunit test results are less likely to receive the gold standard tests than patients with more positive subunit test results. To account for this type of missing data and correlation between subunit test results, we proposed a weighted generalized estimating equations (WGEE) approach to evaluate subunit sensitivities and specificities. A simulation study was conducted to evaluate the performance of the WGEE estimators and the weighted least squares (WLS) estimators (Barnhart and Kosinski, 2003) under a missing at random assumption. The results suggested that WGEE estimator is consistent under various scenarios of percentage of missing data and sample size, while the WLS approach could yield biased estimators due to a misspecified missing data mechanism. We illustrate the methodology with a cardiology example.     

A novel design for estimating relative accuracy of screening tests when complete disease verification is not feasible

The accuracy (sensitivity and specificity) of a new screening test can be compared with that of a standard test by applying both tests to a group of subjects in which disease status can be determined by a gold standard (GS) test. However, it is not always feasible to administer a GS test to all study subjects. For example, a study is planned to determine whether a new screening test for cervical cancer ("ThinPrep") is better than the standard test ("Pap"), and in this setting it is not feasible (or ethical) to determine disease status by biopsy in order to identify women with and without disease for participation in a study. When determination of disease status is not possible for all study subjects, the relative accuracy of two screening tests can still be estimated by using a paired screen-positive (PSP) design in which all subjects receive both screening tests, but only have the GS test if one of the screening tests is positive. Unfortunately in the cervical cancer example, the PSP design is also infeasible because it is not technically possible to administer both the ThinPrep and Pap at the same time. In this article, we describe a randomized paired screen-positive (RPSP) design in which subjects are randomized to receive one of the two screening tests initially, and only receive the other screening test and GS if the first screening test is positive. We derive maximum likelihood estimators and confidence intervals for the relative accuracy of the two screening tests, and assess the small sample behavior of these estimators using simulation studies. Sample size formulae are derived and applied to the cervical cancer screening trial example, and the efficiency of the RPSP design is compared with other designs.     

Helicobacter pylori infection and colorectal cancer risk: a meta-analysis

BACKGROUND: Several studies suggested an association between Helicobacter pylori infection and colorectal carcinoma or adenoma risk. However, different authors reported quite varying estimates. We carried out a systematic review and meta-analysis of published studies investigating this association and paid special attention to the possibility of publication bias and sources of heterogeneity between studies. Materials and METHODS: An extensive literature search and cross-referencing were performed to identify all published studies. Summary estimates were obtained using random-effects models. The presence of possible publication bias was assessed using different statistical approaches. RESULTS: In a meta-analysis of the 11 identified human studies, published between 1991 and 2002, a summary odds ratio of 1.4 (95% CI, 1.1-1.8) was estimated for the association between H. pylori infection and colorectal cancer risk. The graphical funnel plot appeared asymmetrical, but the formal statistical evaluations did not provide strong evidence of publication bias. The proportion of variation of study results because of heterogeneity was small (36.5%). CONCLUSIONS: The results of our meta-analysis are consistent with a possible small increase in risk of colorectal cancer because of H. pylori infection. However, the possibility of some publication bias cannot be ruled out, although it could not be statistically confirmed. Larger, better designed and better controlled studies are needed to clarify the situation.     

Across‐taxa incongruence in patterns of collecting bias

If biological collections tend to be taken near accessible areas, and the number of such areas is limited, then we should expect a similar spatial distribution of collecting effort across taxa. Alternatively, if researchers working on a given taxon pick collection localities based on idiosyncratic criteria, then there should be no spatial similarity in collecting effort. This study compares the spatial distribution of collecting effort for plants and birds in Amazonia. Collection localities were transformed into a Thiessen network where polygon size works as a surrogate for collecting effort. A correlation between botanical and ornithological datasets, with an adjustment for spatial autocorrelation, showed little congruence in the spatial distribution of collecting effort between the two taxa. This incongruence of the distribution of collection effort among taxa suggests that the identification of priority areas for research, and correction for Wallacean and Linnean shortfalls based on taxon‐specific studies, should not be generalized.     

Independent axes of genetic variation and parallel evolutionary divergence of opercle bone shape in threespine stickleback

Evolution of similar phenotypes in independent populations is often taken as evidence of adaptation to the same fitness optimum. However, the genetic architecture of traits might cause evolution to proceed more often toward particular phenotypes, and less often toward others, independently of the adaptive value of the traits. Freshwater populations of Alaskan threespine stickleback have repeatedly evolved the same distinctive opercle shape after divergence from an oceanic ancestor. Here we demonstrate that this pattern of parallel evolution is widespread, distinguishing oceanic and freshwater populations across the Pacific Coast of North America and Iceland. We test whether this parallel evolution reflects genetic bias by estimating the additive genetic variance-covariance matrix (G) of opercle shape in an Alaskan oceanic (putative ancestral) population. We find significant additive genetic variance for opercle shape and that G has the potential to be biasing, because of the existence of regions of phenotypic space with low additive genetic variation. However, evolution did not occur along major eigenvectors of G, rather it occurred repeatedly in the same directions of high evolvability. We conclude that the parallel opercle evolution is most likely due to selection during adaptation to freshwater habitats, rather than due to biasing effects of opercle genetic architecture.     

Ethics, ambiguity aversion, and the review of complex translational clinical trials

Clinical trials of novel agents often present several layers of ethical challenge. Because time and resources for ethical and safety review are limited, how investigators, IRBs, and regulators allocate attention to a trial's various safety dimensions itself represents a critical ethical question. In what follows, I use the example of a Parkinson's disease gene transfer trial to show how risks involving unknown probabilities or outcomes (ambiguity), might sometimes draw attention away from risks that involve known probabilities or outcomes. This potentially undermines the goal of 'systematic and nonarbitrary analysis of risk' during ethical review. To counteract the possible effects of such attention biases, I propose that reviewers develop 'cognitive aids' like lists and, where appropriate, set aside time to discuss non-ambiguous risks. I also propose further research for addressing and understanding how attention allocation, emotion, and ambiguity influence ethical decision-making.     

Multilocus estimation of selfing and its heritability

We describe a new method of estimating the selfing rate (S) in a mixed mating population based on a population structure approach that accounts for possible intergenerational correlation in selfing rate, giving rise to an estimate of the upper limit for heritability of selfing rate (h(2)). A correlation between generations in selfing rate is shown to affect one- and two-locus probabilities of identity by descent. Conventional estimates of selfing rate based on a population structure approach are positively biased by intergenerational correlation in selfing. Multilocus genotypes of individuals are used to give maximum-likelihood estimates of S and h(2) in the presence of scoring artifacts. Our multilocus estimation of selfing rate and its heritability (MESH) method was tested with simulated data for a range of conditions. Selfing rate estimates from MESH have low bias and root mean squared error, whereas estimates of the heritability of selfing rate have more uncertainty. Increasing the number of individuals in a sample helps to reduce bias and root mean squared error more than increasing the number of loci of sampled individuals. Improved estimates of selfing rate, as well as estimates of its heritability, can be obtained with this method, although a large number of loci and individuals are needed to achieve best results.