Towards accurate estimation of the proportion of true null hypotheses in multiple testing

Background

Biomedical researchers are now often faced with situations where it is necessary to test a large number of hypotheses simultaneously, eg, in comparative gene expression studies using high-throughput microarray technology. To properly control false positive errors the FDR (false discovery rate) approach has become widely used in multiple testing. The accurate estimation of FDR requires the proportion of true null hypotheses being accurately estimated. To date many methods for estimating this quantity have been proposed. Typically when a new method is introduced, some simulations are carried out to show the improved accuracy of the new method. However, the simulations are often very limited to covering only a few points in the parameter space.

Results

Here I have carried out extensive in silico experiments to compare some commonly used methods for estimating the proportion of true null hypotheses. The coverage of these simulations is unprecedented thorough over the parameter space compared to typical simulation studies in the literature. Thus this work enables us to draw conclusions globally as to the performance of these different methods. It was found that a very simple method gives the most accurate estimation in a dominantly large area of the parameter space. Given its simplicity and its overall superior accuracy I recommend its use as the first choice for estimating the proportion of true null hypotheses in multiple testing.

Beyond the United States and Japan: Testing Yamagishi's emancipation theory of trust across 31 nations

We examined the relationship between Individualism/Collectivism and generalized social trust across 31 European nations participating in the European Social Survey. Using multi-level regression analyses, the current study provides the first empirical investigation of the effects of cultural norms of Individualism/Collectivism on generalized social trust while accounting for individuals' own cultural orientations within the same analysis. The results provide clear support for Yamagishi and Yamagishi (1994) emancipation theory of trust, showing a significant and positive relationship between Individualism/Collectivism and generalized social trust, over and above the effect of a country political history of communism and ethnic heterogeneity. Having controlled for individual effects of Individualism/Collectivism it is clear that the results of the current analysis cannot be reduced to an individual-level explanation, but must be interpreted within the context Of macrosocial processes. We conclude by discussing potential mechanisms that could explain why national individualism is more likely to foster trust among people than collectivism.

Testing quantum contextuality of continuous-variable states

We investigate the violation of noncontextuality by a class of continuous-variable states, including variations of entangled coherent states and a two-mode continuous superposition of coherent states. We generalize the Kochen-Specker (KS) inequality discussed by Cabello [A. Cabello, Phys. Rev. Lett. 101, 210401 (2008)] by using effective bidimensional observables implemented through physical operations acting on continuous-variable states, in a way similar to an approach to the falsification of Bell-Clauser-Horne-Shimony-Holt inequalities put forward recently. We test for state-independent violation of KS inequalities under variable degrees of state entanglement and mixedness. We then demonstrate theoretically the violation of a KS inequality for any two-mode state by using pseudospin observables and a generalized quasiprobability function.

Cement mantle fatigue failure in total hip replacement: Experimental and computational testing

One possible loosening mechanism of the femoral component in total hip replacement is fatigue cracking of the cement mantle. A computational method capable of simulating this process may therefore be a useful tool in the preclinical evaluation of prospective implants. In this study, we investigated the ability of a computational method to predict fatigue cracking in experimental models of the implanted femur construct. Experimental specimens were fabricated such that cement mantle visualisation was possible throughout the test. Two different implant surface finishes were considered: grit blasted and polished. Loading was applied to represent level gait for two million cycles. Computational (finite element) models were generated to the same geometry as the experimental specimens, with residual stress and porosity simulated in the cement mantle. Cement fatigue and creep were modelled over a simulated two million cycles. For the polished stem surface finish, the predicted fracture locations in the finite element models closely matched those on the experimental specimens, and the recorded stem displacements were also comparable. For the grit blasted stem surface finish, no cement mantle fractures were predicted by the computational method, which was again in agreement with the experimental results. It was concluded that the computational method was capable of predicting cement mantle fracture and subsequent stem displacement for the structure considered. (C) 2006 Elsevier Ltd. All rights reserved.

The pace of Holocene vegetation change - testing for synchronous developments

Mid to high latitude forest ecosystems have undergone several major compositional changes during the Holocene. The temporal and spatial patterns of these vegetation changes hold potential information to their causes and triggers. Here we test the hypothesis that the timing of vegetation change was synchronous on a sub-continental scale, which implies a common trigger or a step-like change in climate parameters. Pollen diagrams from selected European regions were statistically divided into assemblage zones and the temporal pattern of the zone boundaries analysed. The results show that the temporal pattern of vegetation change was significantly different from random. Times of change cluster around8.2, 4.8, 3.7, and 1.2 ka, while times of higher than average stability were found around 2.1 and 5.1 ka.Compositional changes linked to the expansion of Corylus avellana and Alnus glutinosa centre around 10.6 and 9.5 ka, respectively. A climatic trigger initiating these changes may have occurred 0.5 to 1 ka earlier, respectively. The synchronous expansion of C. avellana and A. glutinosa exemplify that dispersal is not necessarily followed by population expansion. The partly synchronous, partly random expansion of A. glutinosa in adjacent European regions exemplifies that sudden synchronous population expansions are not species specific traits but vary regionally.

Molecular testing of respiratory swabs aids early recognition of meningococcal disease in children

Early meningococcal disease (MD) diagnosis is difficult. We assessed rapid molecular testing of respiratory specimens. We performed genotyping of respiratory swabs, blood, and cerebrospinal fluid from children with suspected disease and nasal swabs (NSs) from matched controls. Thirty-nine of 104 suspected cases had confirmed disease. Four controls were carriers. Throat swab ctrA and porA testing for detection of disease gave a sensitivity of 81% (17/21), specificity of 100% (44/44), positive predictive value (PPV) of 100% (17/17), negative predictive value (NPV) of 92% (44/48), and relative risk of 12. NS ctrA and porA testing gave a sensitivity of 51% (20/39), specificity of 95% (62/65), PPV of 87% (20/23), NPV of 77% (62/81), and relative risk of 4. Including only the 86 NSs taken within 48 h of presentation, the results were sensitivity of 60% (18/30), specificity of 96% (54/56), PPV of 90% (18/20), NPV of 82% (54/66), and relative risk of 5. Swab type agreement was excellent (kappa 0.80, P

Political Violence and Child Adjustment in Northern Ireland: Testing Pathways in a Social-Ecological Model Including Single- and Two-Parent Families

Moving beyond simply documenting that political violence negatively impacts children, we tested a social ecological hypothesis for relations between political violence and child outcomes. Participants were 700 mother child (M = 12.1 years, SD = 1.8) dyads from 18 working-class, socially deprived areas in Belfast, Northern Ireland, including single- and two-parent families. Sectarian community violence was associated with elevated family conflict and children's reduced security about multiple aspects of their social environment (i.e., family, parent child relations, and community), with links to child adjustment problems and reductions in prosocial behavior. By comparison, and consistent with expectations, links with negative family processes, child regulatory problems, and child outcomes were less consistent for nonsectarian community violence. Support was found for a social ecological model for relations between political violence and child outcomes among both single- and two-parent families, with evidence that emotional security and adjustment problems were more negatively affected in single-parent families. The implications for understanding social ecologies of political violence and children's functioning are discussed.

Testing a social ecological model for relations between political violence and child adjustment in Northern Ireland

Relations between political violence and child adjustment are matters of international concern. Past research demonstrates the significance of community, family, and child psychological processes in child adjustment, supporting study of interrelations between multiple social ecological factors and child adjustment in contexts of political violence. Testing a social ecological model, 300 mothers and their children (M = 12.28 years, SD = 1.77) from Catholic and Protestant working class neighborhoods in Belfast, Northern Ireland, completed measures or community discord, family relations, and children's regulatory processes (i.e., emotional security) and outcomes. Historical political violence in neighborhoods based on objective records (i.e., politically motivated deaths) were related to family members' reports of current sectarian antisocial behavior and nonsectarian antisocial behavior. Interparental conflict and parental monitoring and children's emotional security about both the community and family contributed to explanatory pathways for relations between sectarian antisocial behavior in communities and children's adjustment problems. The discussion evaluates support for social ecological models for relations between political violence and child adjustment and its implications for understanding relations in other parts of the world.

Parenting Control in Contexts of Political Violence: Testing Bidirectional Relations Between Violence Exposure and Control in Post-Accord Belfast

Objective. The authors examined bidirectional relations between youth exposure to sectarian and nonsectarian antisocial behavior and mothers' efforts to control youths' exposure to community violence in Belfast, Northern Ireland. Design. Mother-child dyads (N = 773) were interviewed in their homes twice over 2 years regarding youths' exposure to sectarian and nonsectarian community antisocial behavior and mothers' use of control strategies, including behavioral and psychological control. Results. Youths' exposure to nonsectarian antisocial behavior was related to increases in mothers' use of behavioral and psychological control strategies over time, controlling for earlier levels of these constructs. Reflecting bidirectional relations, mothers' behavioral control strategies were associated with youths' reduced exposure to nonsectarian and sectarian antisocial behavior over time, whereas psychological control was not related to reduced exposure. Conclusion. Only nonsectarian community violence was associated longitudinally with mothers' increased use of control strategies, and only behavioral control strategies were effective in reducing youths' exposure to community antisocial behavior, including sectarian and nonsectarian antisocial behavior.

Testing the role of sensory systems in the migratory heading of a songbird

The identification of the sensory cues and mechanisms by which migratory birds are able to reach the same breeding and wintering grounds year after year has eluded biologists despite more than 50 years of intensive study. While a number of environmental cues have been proposed to play a role in the navigation of birds, arguments still persist about which cues are essential for the experience based navigation shown by adult migrants. To date, few studies have tested the sensory basis of navigational cues used during actual migration in the wild: mainly laboratory based studies or homing during the non-migratory season have been used to investigate this behaviour. Here we tested the role of olfactory and magnetic cues in the migration of the catbird (Dumetella carolinensis) by radio tracking the migration of birds with sensory manipulations during their actual migratory flights. Our data suggest that adult birds treated with zinc sulphate to produce anosmia were unable to show the same orientation as control adults, and instead reverted to a direction similar to that shown by juveniles making their first migration. The magnetic manipulation had no effect on the orientation of either adults or juveniles. These results allow us to propose that the olfactory sense may play a role in experience based migration in adult catbirds. While the olfactory sense has been shown to play a role in the homing of pigeons and other birds, this is the first time it has been implicated in migratory orientation.