Key predictors of food security and nutrition in Africa: a spatio-temporal model-based study.

There is voluminous literature on Food Security in Africa. This study explicitly considers the spatio-temporal factors in addition to the usual FAO-based metrics in modeling and understanding the dynamics of food security and nutrition across the African continent. To better understand the complex trajectory and burden of food insecurity and nutrition in Africa, it is crucial to consider space-time factors when modeling and interpreting food security. The spatio-temporal anova model was found to be superior(employing statistical criteria) to the other three models from the spatio-temporal interaction domain models. The results of the study suggest that dietary supply adequacy, food stability, and consumption status are positively associated with severe food security, while average food supply and environmental factors have negative effects on Food Security and Nutrition. The findings also indicate that severe food insecurity and malnutrition are spatially and temporally correlated across the African continent. Spatio-temporal modeling and spatial mapping are essential components of a comprehensive practice to reduce the burden of severe food insecurity. likewise, any planning and intervention to improve the average food supply and environment to promote sustainable development should be regional instead of one size fit all.

Study on association factors of intestinal infectious diseases based-Bayesian spatio-temporal model.

BACKGROUND: Intestinal infectious diseases (IIDs) are a significant public health issue in China, and the incidence and distribution of IIDs vary greatly by region and are affected by various factors. This study aims to describe the spatio-temporal trends of IIDs in the Chinese mainland and investigate the association between socioeconomic and meteorological factors with IIDs. METHODS: In this study, IIDs in mainland China from 2006 to 2017 was analyzed using data obtained from the China Center for Disease Control and Prevention. Spatio-temporal mapping techniques was employed to visualize the spatial and temporal distribution of IIDs. Additionally, mean center and standard deviational ellipse analyses were utilized to examine the spatial trends of IIDs. To investigate the potential associations between IIDs and meteorological and socioeconomic variables, spatiotemporal zero-inflated Poisson and negative binomial models was employed within a Bayesian framework. RESULTS: During the study period, the occurrence of most IIDs has dramatically reduced, with uneven reductions in different diseases. Significant regional differences were found among IIDs and influential factors. Overall, the access rate to harmless sanitary toilets (ARHST) was positively associated with the risk of cholera (RR: 1.73, 95%CI: 1.08-2.83), bacillary dysentery (RR: 1.32, 95%CI: 1.06-1.63), and other intestinal infectious diseases (RR: 1.88, 95%CI: 1.52-2.36), and negatively associated with typhoid fever (RR: 0.66, 95%CI: 0.51-0.92), paratyphoid fever (RR: 0.71, 95%CI: 0.55-0.92). Urbanization is only associated with hepatitis E (RR: 2.48, 95%CI: 1.12-5.72). And GDP was negatively correlated with paratyphoid fever (RR: 0.82, 95%CI: 0.70-0.97), and bacillary dysentery (RR: 0.77, 95%CI: 0.68-0.88), and hepatitis A (RR: 0.84, 95%CI: 0.73-0.97). Humidity showed positive correlation with some IIDs except for amoebic dysentery (RR: 1.64, 95%CI: 1.23-2.17), while wind speed showed a negative correlation with most IIDs. High precipitation was associated with an increased risk of typhoid fever (RR: 1.52, 95%CI: 1.09-2.13), and high temperature was associated with an increased risk of typhoid fever (RR: 2.82, 95%CI: 2.06-3.89), paratyphoid fever (RR: 2.79, 95%CI: 2.02-3.90), and HMFD (RR: 1.34, 95%CI: 1.01-1.77). CONCLUSIONS: This research systematically and quantitatively studied the effect of socioeconomic and meteorological factors on IIDs, which provided causal clues for future studies and guided government planning.

The impact of national and international travel on spatio-temporal transmission of SARS-CoV-2 in Belgium in 2021.

BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly spread over the world and caused tremendous impacts on global health. Understanding the mechanism responsible for the spread of this pathogen and the impact of specific factors, such as human mobility, will help authorities to tailor interventions for future SARS-CoV-2 waves or newly emerging airborne infections. In this study, we aim to analyze the spatio-temporal transmission of SARS-CoV-2 in Belgium at municipality level between January and December 2021 and explore the effect of different levels of human travel on disease incidence through the use of counterfactual scenarios. METHODS: We applied the endemic-epidemic modelling framework, in which the disease incidence decomposes into endemic, autoregressive and neighbourhood components. The spatial dependencies among areas are adjusted based on actual connectivity through mobile network data. We also took into account other important factors such as international mobility, vaccination coverage, population size and the stringency of restriction measures. RESULTS: The results demonstrate the aggravating effect of international travel on the incidence, and simulated counterfactual scenarios further stress the alleviating impact of a reduction in national and international travel on epidemic growth. It is also clear that local transmission contributed the most during 2021, and municipalities with a larger population tended to attract a higher number of cases from neighboring areas. CONCLUSIONS: Although transmission between municipalities was observed, local transmission was dominant. We highlight the positive association between the mobility data and the infection spread over time. Our study provides insight to assist health authorities in decision-making, particularly when the disease is airborne and therefore likely influenced by human movement.

Study on the Construction of a Time-Space Four-Dimensional Combined Imaging Model and Moving Target Location Prediction Model.

Time-space four-dimensional motion target localization is a fundamental and challenging task in the field of intelligent driving, and an important part of achieving the upgrade in existing target localization technologies. In order to solve the problem of the lack of localization of moving targets in a spatio-temporal four-dimensional environment in the existing spatio-temporal data model, this paper proposes an optical imaging model in the four-dimensional time-space system and a mathematical model of the object-image point mapping relationship in the four-dimensional time-space system based on the central perspective projection model, combined with the one-dimensional "time" and three-dimensional "space". After adding the temporal dimension, the imaging system parameters are extended. In order to solve the nonlinear mapping problem of complex systems, this paper proposes to construct a time-space four-dimensional object-image mapping relationship model based on a BP artificial neural network and demonstrates the feasibility of the joint time-space four-dimensional imaging model theory. In addition, indoor time-space four-dimensional localization prediction experiments verify the performance of the model in this paper. The maximum relative error rates of the predicted motion depth values, time values, and velocity values of this localization method compared with the real values do not exceed 0.23%, 2.03%, and 1.51%, respectively.

Assessing personal exposure to COVID-19 transmission in public indoor spaces based on fine-grained trajectory data: A simulation study.

The coronavirus disease 2019 (COVID-19) pandemic has posed substantial challenges to worldwide health systems in quick response to epidemics. The assessment of personal exposure to COVID-19 in enclosed spaces is critical to identifying potential infectees and preventing outbreaks. However, traditional contact tracing methods rely heavily on a manual interview, which is costly and time consuming given the large population involved. With advanced indoor localisation techniques, it is possible to collect people's footprints accurately by locating their smartphones. This study presents a new framework for the assessment of personal exposure to COVID-19 carriers using their fine-grained trajectory data. An integral model was established to quantify the exposure risk, in which the spatial and temporal decay effects are simultaneously considered when modelling the airborne transmission of COVID-19. Regarding the obstacle effect of the indoor layout on airborne transmission, a weight graph based on the space syntax technique was further introduced to constrain the transmission strength between subspaces that are less inter-visible. The proposed framework was demonstrated by a simulation study, in which external comparison and internal analysis were conducted to justify its validity and robustness in different scenarios. Our method is expected to promote the efficient identification of potential infectees and provide an extensible spatial-temporal model to simulate different control measures and examine their effectiveness in a built environment.

Double-wavelet transform for multi-subject resting state functional magnetic resonance imaging data.

Conventional regions of interest (ROIs)-level resting state fMRI (functional magnetic resonance imaging) response analyses do not rigorously model the underlying spatial correlation within each ROI. This can result in misleading inference. Moreover, they tend to estimate the temporal covariance matrix with the assumption of stationary time series, which may not always be valid. To overcome these limitations, we propose a double-wavelet approach that simplifies temporal and spatial covariance structure because wavelet coefficients are approximately uncorrelated under mild regularity conditions. This property allows us to analyze much larger dimensions of spatial and temporal resting-state fMRI data with reasonable computational burden. Another advantage of our double-wavelet approach is that it does not require the stationarity assumption. Simulation studies show that our method reduced false positive and false negative rates by properly taking into account spatial and temporal correlations in data. We also demonstrate advantages of our method by using resting-state fMRI data to study the difference in resting-state functional connectivity between healthy subjects and patients with major depressive disorder.

Multiple sclerosis incidence rate in southern Iran: a Bayesian epidemiological study.

BACKGROUND: Multiple Sclerosis (MS) remains to be a public health challenge, due to its unknown biological mechanisms and clinical impacts on young people. The prevalence of this disease in Iran is reported to be 5.30 to 74.28 per 100,000-person. Because of high prevalence of this disease in Fars province, the purpose of this study was to assess the spatial pattern of MS incidence rate by modeling both the associations s of spatial dependence between neighboring regions and risk factors in a Bayesian Poisson model, which can lead to the improvement of health resource allocation decisions. METHOD: Data from 5468 patients diagnosed with MS were collected, according to the McDonald's criteria. New cases of MS were reported by the MS Society of Fars province from 1991 until 2016. The association between the percentage of people with low vitamin D intake, smoking, abnormal BMI and alcohol consumption in addition to spatial structure in a Bayesian spatio-temporal hierarchical model were used to determine the relative risk and trend of MS incidence rate in 29 counties of Fars province. RESULTS: County-level crude incidence rates ranged from 0.22 to 11.31 cases per 100,000-person population. The highest relative risk was estimated at 1.80 in the county of Shiraz, the capital of Fars province, while the lowest relative risk was estimated at 0.11 in Zarindasht county in southern of Fars. The percentages of vitamin D supplementation intake and smoking were significantly associated with the incidence rate of MS. The results showed that 1% increase in vitamin D supplementation intake is associated with 2% decrease in the risk of MS and 1% increase in smoking is associated with 16% increase in the risk of MS. CONCLUSION: Bayesian spatio-temporal analysis of MS incidence rate revealed that the trend in the south and south east of Fars province is less steep than the mean trend of this disease. The lower incidence rate was associated with a higher percentage of vitamin D supplementation intake and a lower percentage of smoking. Previous studies have also shown that smoking and low vitamin D, among all covariates or risk factors, might be associated with high incidence of MS.

Modelling and predicting the spatio-temporal spread of cOVID-19 in Italy.

BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first detected in China at the end of 2019 and it has since spread in few months all over the World. Italy was one of the first Western countries who faced the health emergency and is one of the countries most severely affected by the pandemic. The diffusion of Coronavirus disease 2019 (COVID-19) in Italy has followed a peculiar spatial pattern, however the attention of the scientific community has so far focussed almost exclusively on the prediction of the evolution of the disease over time. METHODS: Official freely available data about the number of infected at the finest possible level of spatial areal aggregation (Italian provinces) are used to model the spatio-temporal distribution of COVID-19 infections at local level. An endemic-epidemic time-series mixed-effects generalized linear model for areal disease counts has been implemented to understand and predict spatio-temporal diffusion of the phenomenon. RESULTS: Three subcomponents characterize the fitted model. The first describes the transmission of the illness within provinces; the second accounts for the transmission between nearby provinces; the third is related to the evolution of the disease over time. At the local level, the provinces first concerned by containment measures are those that are not affected by the effects of spatial neighbours. On the other hand, the component accounting for the spatial interaction with surrounding areas is prevalent for provinces that are strongly involved by contagions. Moreover, the proposed model provides good forecasts for the number of infections at local level while controlling for delayed reporting. CONCLUSIONS: A strong evidence is found that strict control measures implemented in some provinces efficiently break contagions and limit the spread to nearby areas. While containment policies may potentially be more effective if planned considering the peculiarities of local territories, the effective and homogeneous enforcement of control measures at national level is needed to prevent the disease control being delayed or missed as a whole. This may also apply at international level where, as it is for the European Union or the United States, the internal border checks among states have largely been abolished.

Spatio-temporal analysis of socio-economic characteristics for pulmonary tuberculosis in Sichuan province of China, 2006-2015.

BACKGROUND: The disease burden caused by pulmonary tuberculosis (TB) in Sichuan province still persisted at a high level, and large spatial variances were presented across regional distribution disparities. The socio-economic factors were suspected to affect the population of TB notification, we aimed to describe TB case notification rate (CNR) and identify which factors influence TB epidemic are necessary for the prevention and control of the disease in Sichuan province. METHODS: A retrospective cross-sectional study and an ecological spatial analysis was conducted to quantify the presence and location of spatial clusters of TB by the Moran's I index and examined these patterns with socio-economic risk factors by hierarchical Bayesian spatio-temporal model. RESULTS: A total of 630,009 pulmonary TB cases were notified from 2006 to 2015 in 181 counties of Sichuan province. The CNR decreased year by year since 2007, from 88.70 to 61.37 per 100,000 persons. The spatial heterogeneities of CNR were observed during the study periods. Global Moran's I index varied from 0.23 to 0.44 with all P-value < 0.001. The Bayesian spatio-temporal model with parametric spatio-temporal interactions was chosen as the best model according to the minimum of Deviance Information Criterion (DIC)(19,379.01), and in which the quadratic form of time was taken. The proportion of age group and education year were all associated with CNR after adjusting the spatial effect, temporal effect and spatio-temporal interactions. TB CNR increased by 10.2% [95% credible interval (CI): 6.7-13.7%] for every 1-standard-deviation increase in proportion of age group and decreased by 23% (95% CI: 13.7-32.7%) for every 1-standard-deviation increase in education year. CONCLUSIONS: There were spatial clusters of TB notification rate in Sichuan province from 2006 to 2015, and heavy TB burden was mainly attributed to aging and low socioeconomic status including poor education. Thus, it is more important to pay more attention to the elderly population and improve socioeconomic status including promoting education level in Sichuan province to reduce the TB burden.

A Review of Multi-Compartment Infectious Disease Models.

Multi-compartment models have been playing a central role in modelling infectious disease dynamics since the early 20th century. They are a class of mathematical models widely used for describing the mechanism of an evolving epidemic. Integrated with certain sampling schemes, such mechanistic models can be applied to analyse public health surveillance data, such as assessing the effectiveness of preventive measures (e.g. social distancing and quarantine) and forecasting disease spread patterns. This review begins with a nationwide macromechanistic model and related statistical analyses, including model specification, estimation, inference and prediction. Then, it presents a community-level micromodel that enables high-resolution analyses of regional surveillance data to provide current and future risk information useful for local government and residents to make decisions on reopenings of local business and personal travels. r software and scripts are provided whenever appropriate to illustrate the numerical detail of algorithms and calculations. The coronavirus disease 2019 pandemic surveillance data from the state of Michigan are used for the illustration throughout this paper.

Assessing the effect of containment measures on the spatio-temporal dynamic of COVID-19 in Italy.

This paper aims at investigating empirically whether and to what extent the containment measures adopted in Italy had an impact in reducing the diffusion of the COVID-19 disease across provinces. For this purpose, we extend the multivariate time-series model for infection counts proposed in Paul and Held (Stat Med 30(10):118-1136, 2011) by augmenting the model specification with B-spline regressors in order to account for complex nonlinear spatio-temporal dynamics in the propagation of the disease. The results of the model estimated on the time series of the number of infections for the Italian provinces show that the containment measures, despite being globally effective in reducing both the spread of contagion and its self-sustaining dynamics, have had nonlinear impacts across provinces. The impact has been relatively stronger in the northern local areas, where the disease occurred earlier and with a greater incidence. This evidence may be explained by the shared popular belief that the contagion was not a close-to-home problem but rather restricted to a few distant northern areas, which, in turn, might have led individuals to adhere less strictly to containment measures and lockdown rules.

A model of brain morphological changes related to aging and Alzheimer's disease from cross-sectional assessments.

In this study we propose a deformation-based framework to jointly model the influence of aging and Alzheimer's disease (AD) on the brain morphological evolution. Our approach combines a spatio-temporal description of both processes into a generative model. A reference morphology is deformed along specific trajectories to match subject specific morphologies. It is used to define two imaging progression markers: 1) a morphological age and 2) a disease score. These markers can be computed regionally in any brain region. The approach is evaluated on brain structural magnetic resonance images (MRI) from the ADNI database. The model is first estimated on a control population using longitudinal data, then, for each testing subject, the markers are computed cross-sectionally for each acquisition. The longitudinal evolution of these markers is then studied in relation with the clinical diagnosis of the subjects and used to generate possible morphological evolutions. In the model, the morphological changes associated with normal aging are mainly found around the ventricles, while the Alzheimer's disease specific changes are located in the temporal lobe and the hippocampal area. The statistical analysis of these markers highlights differences between clinical conditions even though the inter-subject variability is quite high. The model is also generative since it can be used to simulate plausible morphological trajectories associated with the disease. Our method quantifies two interpretable scalar imaging biomarkers assessing respectively the effects of aging and disease on brain morphology, at the individual and population level. These markers confirm the presence of an accelerated apparent aging component in Alzheimer's patients but they also highlight specific morphological changes that can help discriminate clinical conditions even in prodromal stages. More generally, the joint modeling of normal and pathological evolutions shows promising results to describe age-related brain diseases over long time scales.

Image-based spatio-temporal model of drug delivery in a heterogeneous vasculature of a solid tumor - Computational approach.

The solute transport distribution in a tumor is an important criterion in the evaluation of the cancer treatment efficacy. The fraction of killed cells after each treatment can quantify the therapeutic effect and plays as a helpful tool to evaluate the chemotherapy treatment schedules. In the present study, an image-based spatio-temporal computational model of a solid tumor is provided for calculation of interstitial fluid flow and solute transport. Current model incorporates heterogeneous microvasculature for angiogenesis instead of synthetic mathematical modeling. In this modeling process, a comprehensive model according to Convection-Diffusion-Reaction (CDR) equations is employed due to its high accuracy for simulating the binding and the uptake of the drug by tumor cells. Based on the velocity and the pressure distribution, transient distribution of the different drug concentrations (free, bound, and internalized) is calculated. Then, the fraction of killed cells is obtained according to the internalized concentration. Results indicate the dependence of the drug distribution on both time and space, as well as the microvasculature density. Free and bound drug concentration have the same trend over time, whereas, internalized and total drug concentration increases over time and reaches a constant value. The highest amount of concentration occurred in the tumor region due to the higher permeability of the blood vessels. Moreover, the fraction of killed cells is approximately 78.87% and 24.94% after treatment with doxorubicin for cancerous and normal tissues, respectively. In general, the presented methodology may be applied in the field of personalized medicine to optimize patient-specific treatments. Also, such image-based modeling of solid tumors can be used in laboratories that working on drug delivery and evaluating new drugs before using them for any in vivo or clinical studies.

A predictive spatio-temporal model for bovine Babesiosis epidemic transmission.

The main purpose of this paper is to analyze a new dynamical model pertaining to bovine Babesiosis transmission, and investigate its consequent morphology. We present and study various ramifications of our mathematical model for bovine Babesiosis spread, given, firstly, by a temporal system of ordinary differential equations and, finally, by a spatio-temporal system consisting of reaction-diffusion equations. Diffusion terms are incorporated into the model, using specific derivations for both infected ticks and infected bovines. Furthermore, mechanisms for the nearest neighbors' infection are integrated into the model. We determine mathematically the basic reproduction number R0 via the next-generation matrix. Then, we analyze the stability of the equilibria and the effects of the mobility of infectious agents, being they either ticks or bovines. Finally, model-based analytical-numerical results are obtained and displayed in graphical profiles. The results of the proposed model and the health ramifications are then raised, discussed and validated.

Double-wavelet transform for multisubject task-induced functional magnetic resonance imaging data.

The goal of this article is to model multisubject task-induced functional magnetic resonance imaging (fMRI) response among predefined regions of interest (ROIs) of the human brain. Conventional approaches to fMRI analysis only take into account temporal correlations, but do not rigorously model the underlying spatial correlation due to the complexity of estimating and inverting the high dimensional spatio-temporal covariance matrix. Other spatio-temporal model approaches estimate the covariance matrix with the assumption of stationary time series, which is not always feasible. To address these limitations, we propose a double-wavelet approach for modeling the spatio-temporal brain process. Working with wavelet coefficients simplifies temporal and spatial covariance structure because under regularity conditions, wavelet coefficients are approximately uncorrelated. Different wavelet functions were used to capture different correlation structures in the spatio-temporal model. The main advantages of the wavelet approach are that it is scalable and that it deals with nonstationarity in brain signals. Simulation studies showed that our method could reduce false-positive and false-negative rates by taking into account spatial and temporal correlations simultaneously. We also applied our method to fMRI data to study activation in prespecified ROIs in the prefontal cortex. Data analysis showed that the result using the double-wavelet approach was more consistent than the conventional approach when sample size decreased.

Spatial heterogeneity contributes more to portfolio effects than species variability in bottom-associated marine fishes.

Variance of community abundance will be reduced relative to its theoretical maximum whenever population densities fluctuate asynchronously. Fishing communities and mobile predators can switch among fish species and/or fishing locations with asynchronous dynamics, thereby buffering against variable resource densities (termed 'portfolio effects', PEs). However, whether variation among species or locations represent the dominant contributor to PE remains relatively unexplored. Here, we apply a spatio-temporal model to multidecadal time series (1982-2015) for 20 bottom-associated fishes in seven marine ecosystems. For each ecosystem, we compute the reduction in variance over time in total biomass relative to its theoretical maximum if species and locations were perfectly correlated (total PE). We also compute the reduction in variance due to asynchrony among species at each location (species PE) or the reduction due to asynchrony among locations for each species (spatial PE). We specifically compute total, species and spatial PE in 10-year moving windows to detect changes over time. Our analyses revealed that spatial PE are stronger than species PE in six of seven ecosystems, and that ecosystems where species PE is constant over time can exhibit shifts in locations that strongly contribute to PE. We therefore recommend that spatial and total PE be monitored as ecosystem indicators representing risk exposure for human and natural consumers.

Estimating partial regulation in spatiotemporal models of community dynamics.

Niche-based approaches to community analysis often involve estimating a matrix of pairwise interactions among species (the "community matrix"), but this task becomes infeasible using observational data as the number of modeled species increases. As an alternative, neutral theories achieve parsimony by assuming that species within a trophic level are exchangeable, but generally cannot incorporate stabilizing interactions even when they are evident in field data. Finally, both regulated (niche) and unregulated (neutral) approaches have rarely been fitted directly to survey data using spatiotemporal statistical methods. We therefore propose a spatiotemporal and model-based approach to estimate community dynamics that are partially regulated. Specifically, we start with a neutral spatiotemporal model where all species follow ecological drift, which precludes estimating pairwise interactions. We then add regulatory relations until model selection favors stopping, where the "rank" of the interaction matrix may range from zero to the number of species. A simulation experiment shows that model selection can accurately identify the rank of the interaction matrix, and that the identified spatiotemporal model can estimate the magnitude of species interactions. A 40-yr case study for the Gulf of St. Lawrence marine community shows that recovering grey seals have an unregulated and negative relationship with demersal fishes. We therefore conclude that partial regulation is a plausible approximation to community dynamics using field data and hypothesize that estimating partial regulation will be expedient in future analyses of spatiotemporal community dynamics given limited field data. We conclude by recommending ongoing research to add explicit models for movement, so that meta-community theory can be confronted with data in a spatiotemporal statistical framework.

Structured models of cell migration incorporating molecular binding processes.

The dynamic interplay between collective cell movement and the various molecules involved in the accompanying cell signalling mechanisms plays a crucial role in many biological processes including normal tissue development and pathological scenarios such as wound healing and cancer. Information about the various structures embedded within these processes allows a detailed exploration of the binding of molecular species to cell-surface receptors within the evolving cell population. In this paper we establish a general spatio-temporal-structural framework that enables the description of molecular binding to cell membranes coupled with the cell population dynamics. We first provide a general theoretical description for this approach and then illustrate it with three examples arising from cancer invasion.

Model-guided identification of a therapeutic strategy to reduce hyperammonemia in liver diseases.

BACKGROUND & AIMS: Recently, spatial-temporal/metabolic mathematical models have been established that allow the simulation of metabolic processes in tissues. We applied these models to decipher ammonia detoxification mechanisms in the liver. METHODS: An integrated metabolic-spatial-temporal model was used to generate hypotheses of ammonia metabolism. Predicted mechanisms were validated using time-resolved analyses of nitrogen metabolism, activity analyses, immunostaining and gene expression after induction of liver damage in mice. Moreover, blood from the portal vein, liver vein and mixed venous blood was analyzed in a time dependent manner. RESULTS: Modeling revealed an underestimation of ammonia consumption after liver damage when only the currently established mechanisms of ammonia detoxification were simulated. By iterative cycles of modeling and experiments, the reductive amidation of alpha-ketoglutarate (α-KG) via glutamate dehydrogenase (GDH) was identified as the lacking component. GDH is released from damaged hepatocytes into the blood where it consumes ammonia to generate glutamate, thereby providing systemic protection against hyperammonemia. This mechanism was exploited therapeutically in a mouse model of hyperammonemia by injecting GDH together with optimized doses of cofactors. Intravenous injection of GDH (720 U/kg), α-KG (280 mg/kg) and NADPH (180 mg/kg) reduced the elevated blood ammonia concentrations (>200 µM) to levels close to normal within only 15 min. CONCLUSION: If successfully translated to patients the GDH-based therapy might provide a less aggressive therapeutic alternative for patients with severe hyperammonemia.

A stochastic spatio-temporal (SST) model to study cell-to-cell variability in HIV-1 infection.

Although HIV viremia in infected patients proceeds in a manner that may be accounted for by deterministic mathematical models, single virus-cell encounters following initial HIV exposure result in a variety of outcomes, only one of which results in a productive infection. The development of single molecule tracking techniques in living cells allows studies of intracellular transport of HIV, but it remains less clear what its impact may be on viral integration efficiency. Here, we present a stochastic intracellular mathematical model of HIV replication that incorporates microtubule transport of viral components. Using this model, we could study single round infections and observe how viruses entering cells reach one of three potential fates - degradation of the viral RNA genome, formation of LTR circles, or successful integration and establishment of a provirus. Our model predicts global trafficking properties, such as the probability and the mean time for a HIV viral particle to reach the nuclear pore. Interestingly, our model predicts that trafficking determines neither the probability or time of provirus establishment - instead, they are a function of vRNA degradation and reverse transcription reactions. Thus, our spatio-temporal model provides novel insights into the HIV infection process and may constitute a useful tool for the identification of promising drug targets.