A novel model fitted to multiple life stages of malaria for assessing efficacy of transmission-blocking interventions.

BACKGROUND: Transmission-blocking interventions (TBIs) aim to eliminate malaria by reducing transmission of the parasite between the host and the invertebrate vector. TBIs include transmission-blocking drugs and vaccines that, when given to humans, are taken up by mosquitoes and inhibit parasitic development within the vector. Accurate methodologies are key to assess TBI efficacy to ensure that only the most potent candidates progress to expensive and time-consuming clinical trials. Measuring intervention efficacy can be problematic because there is substantial variation in the number of parasites in both the host and vector populations, which can impact transmission even in laboratory settings. METHODS: A statistically robust empirical method is introduced for estimating intervention efficacy from standardised population assay experiments. This method will be more reliable than simple summary statistics as it captures changes in parasite density in different life-stages. It also allows efficacy estimates at a finer resolution than previous methods enabling the impact of the intervention over successive generations to be tracked. A major advantage of the new methodology is that it makes no assumptions on the population dynamics of infection. This enables both host-to-vector and vector-to-host transmission to be density-dependent (or other) processes and generates easy-to-understand estimates of intervention efficacy. RESULTS: This method increases the precision of intervention efficacy estimates and demonstrates that relying on changes in infection prevalence (the proportion of infected hosts) alone may be insufficient to capture the impact of TBIs, which also suppress parasite density in secondarily infected hosts. CONCLUSIONS: The method indicates that potentially useful, partially effective TBIs may require multiple infection cycles before substantial reductions in prevalence are observed, despite more rapidly suppressing parasite density. Accurate models to quantify efficacy will have important implications for understanding how TBI candidates might perform in field situations and how they should be evaluated in clinical trials.

Stan: A Probabilistic Programming Language.

Stan is a probabilistic programming language for specifying statistical models. A Stan program imperatively defines a log probability function over parameters conditioned on specified data and constants. As of version 2.14.0, Stan provides full Bayesian inference for continuous-variable models through Markov chain Monte Carlo methods such as the No-U-Turn sampler, an adaptive form of Hamiltonian Monte Carlo sampling. Penalized maximum likelihood estimates are calculated using optimization methods such as the limited memory Broyden-Fletcher-Goldfarb-Shanno algorithm. Stan is also a platform for computing log densities and their gradients and Hessians, which can be used in alternative algorithms such as variational Bayes, expectation propagation, and marginal inference using approximate integration. To this end, Stan is set up so that the densities, gradients, and Hessians, along with intermediate quantities of the algorithm such as acceptance probabilities, are easily accessible. Stan can be called from the command line using the cmdstan package, through R using the rstan package, and through Python using the pystan package. All three interfaces support sampling and optimization-based inference with diagnostics and posterior analysis. rstan and pystan also provide access to log probabilities, gradients, Hessians, parameter transforms, and specialized plotting.

Phenology varies with phylogeny but not by trophic level with climate change.

Shifts in phenology with climate change can lead to asynchrony between interacting species, with cascading impacts on ecosystem services. Previous meta-analyses have produced conflicting results on whether asynchrony has increased in recent decades, but the underlying data have also varied-including in species composition, interaction types and whether studies compared data grouped by trophic level or compared shifts in known interacting species pairs. Here, using updated data from previous studies and a Bayesian phylogenetic model, we found that species have advanced an average of 3.1 days per decade across 1,279 time series across 29 taxonomic classes. We found no evidence that shifts vary by trophic level: shifts were similar when grouped by trophic level, and for species pairs when grouped by their type of interaction-either as paired species known to interact or as randomly paired species. Phenology varied with phylogeny (λ = 0.4), suggesting that uneven sampling of species may affect estimates of phenology and potentially phenological shifts. These results could aid forecasting for well-sampled groups but suggest that climate change has not yet led to widespread increases in phenological asynchrony across interacting species, although substantial biases in current data make forecasting for most groups difficult.

Does quantum uncertainty have a place in everyday applied statistics?

We are sympathetic to the general ideas presented in the article by Pothos & Busemeyer (P&B): Heisenberg's uncertainty principle seems naturally relevant in the social and behavioral sciences, in which measurements can affect the people being studied. We propose that the best approach for developing quantum probability models in the social and behavioral sciences is not by directly using the complex probability-amplitude formulation proposed in the article, but rather, more generally, to consider marginal probabilities that need not be averages over conditionals.

Workflow techniques for the robust use of bayes factors.

Inferences about hypotheses are ubiquitous in the cognitive sciences. Bayes factors provide one general way to compare different hypotheses by their compatibility with the observed data. Those quantifications can then also be used to choose between hypotheses. While Bayes factors provide an immediate approach to hypothesis testing, they are highly sensitive to details of the data/model assumptions and it's unclear whether the details of the computational implementation (such as bridge sampling) are unbiased for complex analyses. Here, we study how Bayes factors misbehave under different conditions. This includes a study of errors in the estimation of Bayes factors; the first-ever use of simulation-based calibration to test the accuracy and bias of Bayes factor estimates using bridge sampling; a study of the stability of Bayes factors against different MCMC draws and sampling variation in the data; and a look at the variability of decisions based on Bayes factors using a utility function. We outline a Bayes factor workflow that researchers can use to study whether Bayes factors are robust for their individual analysis. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

An evidence synthesis approach for combining different data sources illustrated using entomological efficacy of insecticides for indoor residual spraying.

BACKGROUND: Prospective malaria public health interventions are initially tested for entomological impact using standardised experimental hut trials. In some cases, data are collated as aggregated counts of potential outcomes from mosquito feeding attempts given the presence of an insecticidal intervention. Comprehensive data i.e. full breakdowns of probable outcomes of mosquito feeding attempts, are more rarely available. Bayesian evidence synthesis is a framework that explicitly combines data sources to enable the joint estimation of parameters and their uncertainties. The aggregated and comprehensive data can be combined using an evidence synthesis approach to enhance our inference about the potential impact of vector control products across different settings over time. METHODS: Aggregated and comprehensive data from a meta-analysis of the impact of Pirimiphos-methyl, an indoor residual spray (IRS) product active ingredient, used on wall surfaces to kill mosquitoes and reduce malaria transmission, were analysed using a series of statistical models to understand the benefits and limitations of each. RESULTS: Many more data are available in aggregated format (N = 23 datasets, 4 studies) relative to comprehensive format (N = 2 datasets, 1 study). The evidence synthesis model had the smallest uncertainty at predicting the probability of mosquitoes dying or surviving and blood-feeding. Generating odds ratios from the correlated Bernoulli random sample indicates that when mortality and blood-feeding are positively correlated, as exhibited in our data, the number of successfully fed mosquitoes will be under-estimated. Analysis of either dataset alone is problematic because aggregated data require an assumption of independence and there are few and variable data in the comprehensive format. CONCLUSIONS: We developed an approach to combine sources from trials to maximise the inference that can be made from such data and that is applicable to other systems. Bayesian evidence synthesis enables inference from multiple datasets simultaneously to give a more informative result and highlight conflicts between sources. Advantages and limitations of these models are discussed.

Toward a principled Bayesian workflow in cognitive science.

Experiments in research on memory, language, and in other areas of cognitive science are increasingly being analyzed using Bayesian methods. This has been facilitated by the development of probabilistic programming languages such as Stan, and easily accessible front-end packages such as brms. The utility of Bayesian methods, however, ultimately depends on the relevance of the Bayesian model, in particular whether or not it accurately captures the structure of the data and the data analyst's domain expertise. Even with powerful software, the analyst is responsible for verifying the utility of their model. To demonstrate this point, we introduce a principled Bayesian workflow (Betancourt, 2018) to cognitive science. Using a concrete working example, we describe basic questions one should ask about the model: prior predictive checks, computational faithfulness, model sensitivity, and posterior predictive checks. The running example for demonstrating the workflow is data on reading times with a linguistic manipulation of object versus subject relative clause sentences. This principled Bayesian workflow also demonstrates how to use domain knowledge to inform prior distributions. It provides guidelines and checks for valid data analysis, avoiding overfitting complex models to noise, and capturing relevant data structure in a probabilistic model. Given the increasing use of Bayesian methods, we aim to discuss how these methods can be properly employed to obtain robust answers to scientific questions. All data and code accompanying this article are available from https://osf.io/b2vx9/. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Analysing the distance decay of community similarity in river networks using Bayesian methods.

The distance decay of community similarity (DDCS) is a pattern that is widely observed in terrestrial and aquatic environments. Niche-based theories argue that species are sorted in space according to their ability to adapt to new environmental conditions. The ecological neutral theory argues that community similarity decays due to ecological drift. The continuum hypothesis provides an intermediate perspective between niche-based theories and the neutral theory, arguing that niche and neutral factors are at the opposite ends of a continuum that ranges from competitive to stochastic exclusion. We assessed the association between niche-based and neutral factors and changes in community similarity measured by Sorensen's index in riparian plant communities. We assessed the importance of neutral processes using network distances and flow connection and of niche-based processes using Strahler order differences and precipitation differences. We used a hierarchical Bayesian approach to determine which perspective is best supported by the results. We used dataset composed of 338 vegetation censuses from eleven river basins in continental Portugal. We observed that changes in Sorensen indices were associated with network distance, flow connection, Strahler order difference and precipitation difference but to different degrees. The results suggest that community similarity changes are associated with environmental and neutral factors, supporting the continuum hypothesis.

Synergy in anti-malarial pre-erythrocytic and transmission-blocking antibodies is achieved by reducing parasite density.

Anti-malarial pre-erythrocytic vaccines (PEV) target transmission by inhibiting human infection but are currently partially protective. It has been posited, but never demonstrated, that co-administering transmission-blocking vaccines (TBV) would enhance malaria control. We hypothesized a mechanism that TBV could reduce parasite density in the mosquito salivary glands, thereby enhancing PEV efficacy. This was tested using a multigenerational population assay, passaging Plasmodium berghei to Anopheles stephensi mosquitoes. A combined efficacy of 90.8% (86.7-94.2%) was observed in the PEV +TBV antibody group, higher than the estimated efficacy of 83.3% (95% CrI 79.1-87.0%) if the two antibodies acted independently. Higher PEV efficacy at lower mosquito parasite loads was observed, comprising the first direct evidence that co-administering anti-sporozoite and anti-transmission interventions act synergistically, enhancing PEV efficacy across a range of TBV doses and transmission intensities. Combining partially effective vaccines of differing anti-parasitic classes is a pragmatic, powerful way to accelerate malaria elimination efforts.