Predicting the dengue cluster outbreak dynamics in Yogyakarta, Indonesia: a modelling study.

Background: Human mobility and climate conditions are recognised key drivers of dengue transmission, but their combined and individual role in the local spatiotemporal clustering of dengue cases is not well understood. This study investigated the effects of human mobility and weather conditions on dengue risk in an urban area in Yogyakarta, Indonesia. Methods: We established a Bayesian spatiotemporal model for neighbourhood outbreak prediction and evaluated the performances of two different approaches for constructing an adjacency matrix: one based on geographical proximity and the other based on human mobility patterns. We used population, weather conditions, and past dengue cases as predictors using a flexible distributed lag approach. The human mobility data were estimated based on proxies from social media. Unseen data from February 2017 to January 2020 were used to estimate the one-month ahead prediction accuracy of the model. Findings: When human mobility proxies were included in the spatial covariance structure, the model fit improved in terms of the log score (from 1.748 to 1.561) and the mean absolute error (from 0.676 to 0.522) based on the validation data. Additionally, showed only few observations outside the credible interval of predictions (1.48%) and weather conditions were not found to contribute additionally to the clustering of cases at this scale. Interpretation: The study shows that it is possible to make highly accurate predictions of the within-city cluster dynamics of dengue using mobility proxies from social media combined with disease surveillance data. These insights are important for proactive and timely outbreak management of dengue. Funding: Swedish Research Council Formas, Umeå Centre for Global Health Research, Swedish Council for Working Life and Social Research, Swedish research council VINNOVA and Alexander von Humboldt Foundation (Germany).

European projections of West Nile virus transmission under climate change scenarios.

West Nile virus (WNV), a mosquito-borne zoonosis, has emerged as a disease of public health concern in Europe. Recent outbreaks have been attributed to suitable climatic conditions for its vectors favoring transmission. However, to date, projections of the risk for WNV expansion under climate change scenarios is lacking. Here, we estimate the WNV-outbreaks risk for a set of climate change and socioeconomic scenarios. We delineate the potential risk-areas and estimate the growth in the population at risk (PAR). We used supervised machine learning classifier, XGBoost, to estimate the WNV-outbreak risk using an ensemble climate model and multi-scenario approach. The model was trained by collating climatic, socioeconomic, and reported WNV-infections data (2010-22) and the out-of-sample results (1950-2009, 2023-99) were validated using a novel Confidence-Based Performance Estimation (CBPE) method. Projections of area specific outbreak risk trends, and corresponding population at risk were estimated and compared across scenarios. Our results show up to 5-fold increase in West Nile virus (WNV) risk for 2040-60 in Europe, depending on geographical region and climate scenario, compared to 2000-20. The proportion of disease-reported European land areas could increase from 15% to 23-30%, putting 161 to 244 million people at risk.  Across scenarios, Western Europe appears to be facing the largest increase in the outbreak risk of WNV. The increase in the risk is not linear but undergoes periods of sharp changes governed by climatic thresholds associated with ideal conditions for WNV vectors. The increased risk will require a targeted public health response to manage the expansion of WNV with climate change in Europe.

Nowcasting COVID-19 Statistics Reported with Delay: A Case-Study of Sweden and the UK.

The COVID-19 pandemic has demonstrated the importance of unbiased, real-time statistics of trends in disease events in order to achieve an effective response. Because of reporting delays, real-time statistics frequently underestimate the total number of infections, hospitalizations and deaths. When studied by event date, such delays also risk creating an illusion of a downward trend. Here, we describe a statistical methodology for predicting true daily quantities and their uncertainty, estimated using historical reporting delays. The methodology takes into account the observed distribution pattern of the lag. It is derived from the "removal method"-a well-established estimation framework in the field of ecology.

Single-cell quantification and dose-response of cytosolic siRNA delivery.

Endosomal escape and subsequent cytosolic delivery of small interfering RNA (siRNA) therapeutics is believed to be highly inefficient. Since it has not been possible to quantify cytosolic amounts of delivered siRNA at therapeutic doses, determining delivery bottlenecks and total efficiency has been difficult. Here, we present a confocal microscopy-based method to quantify cytosolic delivery of fluorescently labeled siRNA during lipid-mediated delivery. This method enables detection and quantification of sub-nanomolar cytosolic siRNA release amounts from individual release events with measures of quantitation confidence for each event. Single-cell kinetics of siRNA-mediated knockdown in cells expressing destabilized eGFP unveiled a dose-response relationship with respect to knockdown induction, depth and duration in the range from several hundred to thousands of cytosolic siRNA molecules. Accurate quantification of cytosolic siRNA, and the establishment of the intracellular dose-response relationships, will aid the development and characterization of novel delivery strategies for nucleic acid therapeutics.

Accuracy of a Bayesian technique to estimate position and activity of orphan gamma-ray sources by mobile gamma spectrometry: Influence of imprecisions in positioning systems and computational approximations.

The purpose of this study was to investigate the effects of experimental data on performance of a developed Bayesian algorithm tailored for orphan source search, estimating which parameters affect the accuracy of the algorithm. The algorithm can estimate the position and activity of a gamma-ray point source from experimental mobile gamma spectrometry data. Bayesian estimates were made for source position and activity using mobile gamma spectrometry data obtained from one 123% HPGe detector and two 4-l NaI(Tl) detectors, considering angular variations in counting efficiency for each detector. The data were obtained while driving at 50 km/h speed past the sources using 1 s acquisition interval in the detectors. It was found that deviations in the recorded coordinates of the measurements can potentially increase the uncertainty in the position of the source 2 to 3 times and slightly decrease the activity estimations by about 7%. Due to the various sources of uncertainty affecting the experimental data, the maximum predicted relative deviations of the activity and position of the source remained about 30% regardless of the signal-to-noise ratio of the data. It was also found for the used vehicle speed of 50 km/h and 1 s acquisition time, that if the distance to the source is greater than the distance travelled by the detector during the acquisition time, it is possible to use point approximations of the count-rate function in the Bayesian likelihood with minimal deviations from the integrated estimates of the count-rate function. This approximation reduces the computational demands of the algorithm increasing the potential for applying this method in real-time orphan source search missions.

Artificial intelligence to predict West Nile virus outbreaks with eco-climatic drivers.

Background: In Europe, the frequency, intensity, and geographic range of West Nile virus (WNV)-outbreaks have increased over the past decade, with a 7.2-fold increase in 2018 compared to 2017, and a markedly expanded geographic area compared to 2010. The reasons for this increase and range expansion remain largely unknown due to the complexity of the transmission pathways and underlying disease drivers. In a first, we use advanced artificial intelligence to disentangle the contribution of eco-climatic drivers to WNV-outbreaks across Europe using decade-long (2010-2019) data at high spatial resolution. Methods: We use a high-performance machine learning classifier, XGBoost (eXtreme gradient boosting) combined with state-of-the-art XAI (eXplainable artificial intelligence) methodology to describe the predictive ability and contribution of different drivers of the emergence and transmission of WNV-outbreaks in Europe, respectively. Findings: Our model, trained on 2010-2017 data achieved an AUC (area under the receiver operating characteristic curve) score of 0.97 and 0.93 when tested with 2018 and 2019 data, respectively, showing a high discriminatory power to classify a WNV-endemic area. Overall, positive summer/spring temperatures anomalies, lower water availability index (NDWI), and drier winter conditions were found to be the main determinants of WNV-outbreaks across Europe. The climate trends of the preceding year in combination with eco-climatic predictors of the first half of the year provided a robust predictive ability of the entire transmission season ahead of time. For the extraordinary 2018 outbreak year, relatively higher spring temperatures and the abundance of Culex mosquitoes were the strongest predictors, in addition to past climatic trends. Interpretation: Our AI-based framework can be deployed to trigger rapid and timely alerts for active surveillance and vector control measures in order to intercept an imminent WNV-outbreak in Europe. Funding: The work was partially funded by the Swedish Research Council FORMAS for the project ARBOPREVENT (grant agreement 2018-05973).

Robust joint modelling of longitudinal and survival data: Incorporating a time-varying degrees-of-freedom parameter.

Monitoring of individual biomarkers has the potential of explaining the hazard of survival outcomes. In practice, these measurements are intermittently observed and are known to be subject to substantial measurement error. Joint modelling of longitudinal and survival data enables us to associate intermittently measured error-prone biomarkers with risks of survival outcomes and thus plays an important role in the analysis of medical data. Most of the joint models available in the literature have been built on the Gaussian assumption. This makes them sensitive to outliers. In this work, we study a range of robust models to address this issue. Of particular interest is the common occurrence in medical data that outliers can occur with different frequencies over time, for example, in the period when patients adjust to treatment changes. Motivated by the analysis of data gathered from patients with primary biliary cirrhosis, a new model with a time-varying robustness is introduced. Through both the motivating example and a simulation study, this research not only stresses the need to account for longitudinal outliers in the analysis of medical data and in joint modelling research but also highlights the bias and inefficiency from not properly estimating the degrees-of-freedom parameter. This work presents a number of methods in addition to the time-varying robustness, and each method can be fitted using the R package robjm.

Ghost QTL and hotspots in experimental crosses: novel approach for modeling polygenic effects.

Ghost quantitative trait loci (QTL) are the false discoveries in QTL mapping, that arise due to the "accumulation" of the polygenic effects, uniformly distributed over the genome. The locations on the chromosome that are strongly correlated with the total of the polygenic effects depend on a specific sample correlation structure determined by the genotypes at all loci. The problem is particularly severe when the same genotypes are used to study multiple QTL, e.g. using recombinant inbred lines or studying the expression QTL. In this case, the ghost QTL phenomenon can lead to false hotspots, where multiple QTL show apparent linkage to the same locus. We illustrate the problem using the classic backcross design and suggest that it can be solved by the application of the extended mixed effect model, where the random effects are allowed to have a nonzero mean. We provide formulas for estimating the thresholds for the corresponding t-test statistics and use them in the stepwise selection strategy, which allows for a simultaneous detection of several QTL. Extensive simulation studies illustrate that our approach eliminates ghost QTL/false hotspots, while preserving a high power of true QTL detection.

Bayesian algorithm to estimate position and activity of an orphan gamma source utilizing multiple detectors in a mobile gamma spectrometry system.

To avoid harm to the public and the environment, lost ionizing radiation sources must be found and brought back under the regulatory control as soon as possible. Usually, mobile gamma spectrometry systems are used in such search missions. It is possible to estimate the position and activity of point gamma sources by performing Bayesian inference on the measurement data. The aim of this study was to theoretically investigate the improvements in the Bayesian estimations of the position and activity of a point gamma source due to introduction of data from multiple detectors with angular variations of efficiency. Three detector combinations were tested-a single 123% HPGe detector, single 4l NaI (Tl) detector and a 123% HPGe with 2x4l NaI (Tl) detector combination-with and without angular efficiency variations for each combination resulting in six different variants of the Bayesian algorithm. It was found that introduction of angular efficiency variations of the detectors did improve the accuracy of activity estimation slightly, while introduction of data from additional detectors lowered the signal-to-noise ratio threshold of the system significantly, increasing the stability and accuracy of the estimated source position and activity, for a given signal-to-noise ratio.

Predation by avian insectivores on caterpillars is linked to leaf damage on oak (Quercus robur).

Birds that are foraging in tree canopies can cause a substantial decrease in arthropod numbers. Trees may benefit from avian insectivores attacking insect herbivores. In a field study, we tested whether the intensity of bird predation on caterpillars is linked quantitatively to leaf damage caused by insect herbivores, a hypothesized relationship that previously was poorly investigated. Artificial caterpillars were placed in the lower part of oak trees (Quercus robur) in urban and suburban sites across the city of Gothenburg, Sweden. Two days later, we recorded the survival: the pooled predation rate was 11.5% (5.7% day-1). Mean predation rate per tree was 10.4%. Mean leaf damage, i.e. leaf area eaten by insect herbivores, per tree was 5.7% but there was large variation between trees. We found a significant negative relationship between survival probability of caterpillars and leaf damage in an analysis using a mixed model logistic regression. This suggests that caterpillars are at high risk of bird attacks in trees with a high degree of leaf damage and avian insectivores may increase the foraging effort in the foliage of such oak trees. Our findings concerning the quantitative relationship between the predator-prey interactions and plant damage suggested tentatively that the survival probability of caterpillars decreases rapidly at 15-20% leaf damage in lower part of oak canopies. Furthermore, our findings add credence to the idea of using artificial caterpillars as a means to obtain standardized comparisons of predation rates in various habitats.

BayesFlow: latent modeling of flow cytometry cell populations.

BACKGROUND: Flow cytometry is a widespread single-cell measurement technology with a multitude of clinical and research applications. Interpretation of flow cytometry data is hard; the instrumentation is delicate and can not render absolute measurements, hence samples can only be interpreted in relation to each other while at the same time comparisons are confounded by inter-sample variation. Despite this, most automated flow cytometry data analysis methods either treat samples individually or ignore the variation by for example pooling the data. A key requirement for models that include multiple samples is the ability to visualize and assess inferred variation, since what could be technical variation in one setting would be different phenotypes in another. RESULTS: We introduce BayesFlow, a pipeline for latent modeling of flow cytometry cell populations built upon a Bayesian hierarchical model. The model systematizes variation in location as well as shape. Expert knowledge can be incorporated through informative priors and the results can be supervised through compact and comprehensive visualizations. BayesFlow is applied to two synthetic and two real flow cytometry data sets. For the first real data set, taken from the FlowCAP I challenge, BayesFlow does not only give a gating which would place it among the top performers in FlowCAP I for this dataset, it also gives a more consistent treatment of different samples than either manual gating or other automated gating methods. The second real data set contains replicated flow cytometry measurements of samples from healthy individuals. BayesFlow gives here cell populations with clear expression patterns and small technical intra-donor variation as compared to biological inter-donor variation. CONCLUSIONS: Modeling latent relations between samples through BayesFlow enables a systematic analysis of inter-sample variation. As opposed to other joint gating methods, effort is put at ensuring that the obtained partition of the data corresponds to actual cell populations, and the result is therefore directly biologically interpretable. BayesFlow is freely available at GitHub.