Filter inference: A scalable nonlinear mixed effects inference approach for snapshot time series data.

Variability is an intrinsic property of biological systems and is often at the heart of their complex behaviour. Examples range from cell-to-cell variability in cell signalling pathways to variability in the response to treatment across patients. A popular approach to model and understand this variability is nonlinear mixed effects (NLME) modelling. However, estimating the parameters of NLME models from measurements quickly becomes computationally expensive as the number of measured individuals grows, making NLME inference intractable for datasets with thousands of measured individuals. This shortcoming is particularly limiting for snapshot datasets, common e.g. in cell biology, where high-throughput measurement techniques provide large numbers of single cell measurements. We introduce a novel approach for the estimation of NLME model parameters from snapshot measurements, which we call filter inference. Filter inference uses measurements of simulated individuals to define an approximate likelihood for the model parameters, avoiding the computational limitations of traditional NLME inference approaches and making efficient inferences from snapshot measurements possible. Filter inference also scales well with the number of model parameters, using state-of-the-art gradient-based MCMC algorithms such as the No-U-Turn Sampler (NUTS). We demonstrate the properties of filter inference using examples from early cancer growth modelling and from epidermal growth factor signalling pathway modelling.

Thrombolysis of bowel obstruction? A thought-provoking presentation of a common surgical pathology.

We present a unique case of bowel obstruction with a hiatus hernia causing atypical chest pain with dynamic ST-segment elevation in a regional Australian emergency department. The ST elevation only resolved after nasogastric decompression of the bowel obstruction. Early thrombolysis of presumed myocardial infarction led to upper gastrointestinal tract bleeding that could have been avoided with timely diagnosis. An extensive review of literature, in addition to our case report, suggests bowel obstruction is a differential diagnosis for patients who have inferior pattern ST elevation but normal troponin presenting with atypical chest pain, nausea, vomiting and previous abdominal surgery.

Risk of Plasmodium falciparum infection in south-west Burkina Faso: potential impact of expanding eligibility for seasonal malaria chemoprevention.

Burkina Faso has one of the highest malaria burdens in sub-Saharan Africa despite the mass deployment of insecticide-treated nets (ITNs) and use of seasonal malaria chemoprevention (SMC) in children aged up to 5 years. Identification of risk factors for Plasmodium falciparum infection in rural Burkina Faso could help to identify and target malaria control measures. A cross-sectional survey of 1,199 children and adults was conducted during the peak malaria transmission season in the Cascades Region of south-west Burkina Faso in 2017. Logistic regression was used to identify risk factors for microscopically confirmed P. falciparum infection. A malaria transmission dynamic model was used to determine the impact on malaria cases averted of administering SMC to children aged 5-15 year old. P. falciparum prevalence was 32.8% in the study population. Children aged 5 to < 10 years old were at 3.74 times the odds (95% CI = 2.68-5.22, P < 0.001) and children aged 10 to 15 years old at 3.14 times the odds (95% CI = 1.20-8.21, P = 0.02) of P. falciparum infection compared to children aged less than 5 years old. Administration of SMC to children aged up to 10 years is predicted to avert an additional 57 malaria cases per 1000 population per year (9.4% reduction) and administration to children aged up to 15 years would avert an additional 89 malaria cases per 1000 population per year (14.6% reduction) in the Cascades Region, assuming current coverage of pyrethroid-piperonyl butoxide ITNs. Malaria infections were high in all age strata, although highest in children aged 5 to 15 years, despite roll out of core malaria control interventions. Given the burden of infection in school-age children, extension of the eligibility criteria for SMC could help reduce the burden of malaria in Burkina Faso and other countries in the region.

Neutral syndrome.

Neutral models of evolution assume the absence of natural selection. Formerly confined to ecology and evolutionary biology, neutral models are spreading. In recent years they've been applied to explaining the diversity of baby names, scientific citations, cryptocurrencies, pot decorations, literary lexica, tumour variants and much more besides. Here, we survey important neutral models and highlight their similarities. We investigate the most widely used tests of neutrality, show that they are weak and suggest more powerful methods. We conclude by discussing the role of neutral models in the explanation of diversity. We suggest that the ability of neutral models to fit low-information distributions should not be taken as evidence for the absence of selection. Nevertheless, many studies, in increasingly diverse fields, make just such claims. We call this tendency 'neutral syndrome'.

Scale-Free Analysis of Intraoperative ECoG During Awake Craniotomy for Glioma.

BACKGROUND: Electrocorticography (ECoG) has been utilized in many epilepsy cases however, the use of this technique for evaluating electrophysiological changes within tumoral zones is spare. Nonetheless, epileptic activities seem to arise from the neocortex surrounding the gliomas suggesting a link between epileptogenesis and glioma cell infiltration in the peritumoral area. The purpose of this study was to implement novel scale-free measures to assess how cortical physiology is altered by the presence of an invasive brain tumor. METHODS: Twelve patients undergoing an awake craniotomy for resection of a supratentorial glioma were included. ECoG data over the main tumor and the exposed surroundings was acquired intra-operatively just prior to tumor resection. Six of the patients presented with seizures and had data acquired both in the awake and anesthetic state. The corresponding anatomical location of each electrode in relation to the macroscopically-detectable tumor was recorded using the neuronavigation system based on structural anatomical images obtained pre-operatively. The electrodes were classified into tumoral, healthy or peritumoral based on the macroscopically detectable tumoral tissue from the pre-operative structural MRI. RESULTS: The electrodes overlying the tumoral tissue revealed higher power law exponent (PLE) values across tumoral area compared to the surrounding tissues. The difference between the awake and anesthetic states was significant in the tumoral and healthy tissue (p < 0.05) but not in the peritumoral tissue. The absence of a significant PLE reduction in the peritumoral tissue from the anesthetic to the awake state could be considered as an index of the presence or absence of infiltration of tumor cells into the peritumoral tissue. CONCLUSIONS: The current study portrays for the first time distinct power law exponent features in the tumoral tissue, which could provide a potential novel electrophysiological marker in the future. The distinct features seen in the peritumoral tissue of gliomas seem to indicate the area where both the onset of epileptiform activity and the tumor infiltration take place.

Trends in comparative efficacy and safety of malaria control interventions for maternal and child health outcomes in Africa: a study protocol for a Bayesian network meta-regression exploring the effect of HIV and malaria endemicity spectrum.

INTRODUCTION: Unprecedented global efforts to prevent malaria morbidity and mortality in sub-Saharan Africa have saved hundreds of thousands of lives across the continent in the last two decades. This study aims to determine how the comparative efficacy and safety of available malaria control interventions intended to improve maternal and child health outcomes have changed over time considering the varied epidemiological contexts on the continent. METHODS: We will review all randomised controlled trials that investigated malaria control interventions in pregnant women in sub-Saharan Africa and were published between January 1980 and December 2018. We will subsequently use network meta-regression to estimate temporal trends in the relative and absolute efficacy and safety of Intermittent Preventive Treatments, Intermittent Screening and Treatments, Insecticide-treated bed nets, and their combinations, and predict their ranking according to their relative and absolute efficacy and safety over time. Our outcomes will include 12 maternal and 7 child mortality and morbidity outcomes, known to be associated with either malaria infection or control. We will use intention-to-treat analysis to derive our estimates and meta-regression to estimate temporal trends and the effect modification by HIV infection, malaria endemicity and Plasmodium falciparum resistance to sulfadoxine-pyrimethamine, while adjusting for multiple potential confounders via propensity score calibration. PROSPERO REGISTRATION NUMBER: CRD42018095138.