Parameter estimation and inference for stochastic reaction-diffusion systems: application to morphogenesis in D. melanogaster

Background: Reaction-diffusion systems are frequently used in systems biology to model developmental and signalling processes. In many applications, count numbers of the diffusing molecular species are very low, leading to the need to explicitly model the inherent variability using stochastic methods. Despite their importance and frequent use, parameter estimation for both deterministic and stochastic reaction-diffusion systems is still a challenging problem. Results: We present a Bayesian inference approach to solve both the parameter and state estimation problem for stochastic reaction-diffusion systems. This allows a determination of the full posterior distribution of the parameters (expected values and uncertainty). We benchmark the method by illustrating it on a simple synthetic experiment. We then test the method on real data about the diffusion of the morphogen Bicoid in Drosophila melanogaster. The results show how the precision with which parameters can be inferred varies dramatically, indicating that the ability to infer full posterior distributions on the parameters can have important experimental design consequences. Conclusions: The results obtained demonstrate the feasibility and potential advantages of applying a Bayesian approach to parameter estimation in stochastic reaction-diffusion systems. In particular, the ability to estimate credibility intervals associated with parameter estimates can be precious for experimental design. Further work, however, will be needed to ensure the method can scale up to larger problems

Changes in Prescribing by Provider Type Following a State Prescription Opioid Restriction Law

Background: Many states have implemented opioid days’ supply restriction policies, leading to reductions in opioid prescribing. Although research within certain provider types exist, no study has evaluated a restriction policy by various provider types. Objective: To evaluate changes in opioid utilization following a days’ supply restriction policy stratified by provider type: surgery, emergency medicine, primary care, specialty care, and dentistry. Design: Interrupted time series (ITS) Participants: Opioid prescription claims of patients in a private health plan serving a large Florida employer from 1/1/2015 to 3/31/2019. Provider types were determined using the Healthcare Provider Taxonomy Code associated with the national provider identifier (NPI). Interventions: Florida’s opioid restriction policy implemented on July 1, 2018. Main Measures: Changes in mean morphine milligram equivalent (MMEs), mean days’ supply, and mean number of units dispensed per opioid prescription before and after policy implementation. Key Results: There were 10,583 opioid initial prescriptions dispensed. Treating providers were classified as surgery (16.4%; n = 1732), emergency care (14.3%; n = 1516), primary care (21.2%; n = 2241), specialty care (11.4%; n = 1207), and dentistry providers (23.7%; n = 2511). Significant reductions in mean days’ supply were observed across most provider types ranging from 14% reduction for dentistry providers to 41% reduction for specialty care providers. Significant changes were observed for emergency care and specialty care providers with a 30% (p = 0.001)and 29% (p < 0.001) reduction in mean MME, respectively, and a 27% (p = 0.040) reduction in mean number of units dispensed in emergency care providers, after implementation. Pre-implementation trends in opioid prescribing varied by provider type impacting the effects of the opioid days’ supply restriction policy. Conclusions: Pre-policy opioid prescribing varied by provider type with a differential impact on mean MMEs, mean days’ supply, and mean number of units dispensed per prescription following implementation

Lifetime distributions in the methods of non-equilibrium statistical operator and superstatistics

A family of non-equilibrium statistical operators is introduced which differ by the system age distribution over which the quasi-equilibrium (relevant) distribution is averaged. To describe the nonequilibrium states of a system we introduce a new thermodynamic parameter - the lifetime of a system. Superstatistics, introduced in works of Beck and Cohen [Physica A \textbf{322}, (2003), 267] as fluctuating quantities of intensive thermodynamical parameters, are obtained from the statistical distribution of lifetime (random time to the system degeneracy) considered as a thermodynamical parameter. It is suggested to set the mixing distribution of the fluctuating parameter in the superstatistics theory in the form of the piecewise continuous functions. The distribution of lifetime in such systems has different form on the different stages of evolution of the system. The account of the past stages of the evolution of a system can have a substantial impact on the non-equilibrium behaviour of the system in a present time moment.Comment: 18 page

Vortex merger near a topographic slope in a homogeneous rotating fluid

This work is a contribution to the PHYSINDIEN research program. It was supported by CNRS-RFBR contract PRC 1069/16-55-150001.The effect of a bottom slope on the merger of two identical Rankine vortices is investigated in a two dimensional, quasi-geostrophic, incompressible fluid. When two cyclones initially lie parallel to the slope, and more than two vortex diameters away from the slope, the critical merger distance is unchanged. When the cyclones are closer to the slope, they can merge at larger distances, but they lose more mass into filaments, thus weakening the efficiency of merger. Several effects account for this: the topographic Rossby wave advects the cyclones, reduces their mutual distance and deforms them. This along shelf wave breaks into filaments and into secondary vortices which shear out the initial cyclones. The global motion of fluid towards the shallow domain and the erosion of the two cyclones are confirmed by the evolution of particles seeded both in the cyclone sand near the topographic slope. The addition of tracer to the flow indicates that diffusion is ballistic at early times. For two anticyclones, merger is also facilitated because one vortex is ejected offshore towards the other, via coupling with a topographic cyclone. Again two anticyclones can merge at large distance but they are eroded in the process. Finally, for taller topographies, the critical merger distance is again increased and the topographic influence can scatter or completely erode one of the two initial cyclones. Conclusions are drawn on possible improvements of the model configuration for an application to the ocean.PostprintPeer reviewe

SJS/TEN 2019: From Science to Translation

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe