While clozapine has risks, relative risk of fatality is overestimated. The UK pharmacovigilance programme is efficient, but comparisons with other drugs can mislead because of reporting variations. Clozapine actually lowers mortality, partly by reducing schizophrenia-related suicides, but preventable deaths still occur. Clozapine should be used earlier and more widely, but there should be better monitoring and better management of toxicity.

We study the endothermic reaction and flow of a granular solid reactant, where energy for the reaction is provided by a counter-current flow of hot gases through the porous reactant bed. Research into reacting flows typically focusses on exothermic combustion processes. However, endothermic processes are common in the metallurgy industry, including the production of cement, silicon and rutile titanium dioxide. Several common features are observed in experimental and numerical studies of these processes, including critical temperatures of the reactant at which the chemical reaction begins, and regions of the reactor with uniform reactant temperature. Motivated specifically by the processes in a silicon furnace, we analyse a model of endothermic, reacting counter-current flow using the method of matched asymptotic expansions. Assuming the Péclet number in the solid is large, we explore the full range of values for the dimensionless inter-phase heat-transfer rate, finding six distinguished limits. In all limits, we find a diffusive boundary layer in which there is a fast chemical reaction rate due to the high temperatures, analogous to exothermic flame fronts. Outside this region, the counter-current flow is crucial to the chemical processes. For intermediate values of the heat-transfer rate, we find the same qualitative properties as those observed across the metallurgy industry, and we quantify the dependence of these properties on the flow rate and heat-transfer rate. In the limit of large heat-transfer coefficient, we derive the single-temperature limit, in which the solution structure is dependent on the direction of net heat flux through the domain.

Silicon is produced in submerged arc furnaces which are heated by electric currents passing through the furnace. It is important to understand the distribution of heating within the furnace in order to accurately model the silicon production process, yet many existing studies neglect aspects of this current flow. In the present paper, we formulate a model that couples the electrical current to thermal, material flow and chemical processes in the furnace. We then exploit disparate timescales to homogenise the model over the timescale of the alternating current, deriving averaged equations for the slow evolution of the system. Our numerical simulations predict a minimum applied current that is required in order to obtain steady-state solutions of the homogenised model and show that for high enough applied currents, two spatially heterogeneous steady-state solutions exist, with distinct crater sizes. We show that the system evolves to the steady state with a larger crater radius and explain this behaviour in terms of the overall power balance typically found within a furnace. We find that the industrial practice of stoking furnaces increases the overall rate of material consumption in the furnace, thereby improving the efficiency of silicon production.

We read with interest the recent editorial, “The Hennepin Ketamine Study,” by Dr. Samuel Stratton commenting on the research ethics, methodology, and the current public controversy surrounding this study.1 As researchers and investigators of this study, we strongly agree that prospective clinical research in the prehospital environment is necessary to advance the science of Emergency Medical Services (EMS) and emergency medicine. We also agree that accomplishing this is challenging as the prehospital environment often encounters patient populations who cannot provide meaningful informed consent due to their emergent conditions. To ensure that fellow emergency medicine researchers understand the facts of our work so they may plan future studies, and to address some of the questions and concerns in Dr. Stratton’s editorial, the lay press, and in social media,2 we would like to call attention to some inaccuracies in Dr. Stratton’s editorial, and to the lay media stories on which it appears to be based.

Ho JD, Cole JB, Klein LR, Olives TD, Driver BE, Moore JC, Nystrom PC, Arens AM, Simpson NS, Hick JL, Chavez RA, Lynch WL, Miner JR. The Hennepin Ketamine Study investigators’ reply. Prehosp Disaster Med. 2019;34(2):111–113

Our current global food system – from food production to consumption, including manufacture, packaging, transport, retail and associated businesses – is responsible for extensive negative social and environmental impacts which threaten the long-term well-being of society. This has led to increasing calls from science–policy organizations for major reform and transformation of the global food system. However, our knowledge regarding food system transformations is fragmented and this is hindering the development of co-ordinated solutions. Here, we collate recent research across several academic disciplines and sectors in order to better understand the mechanisms that ‘lock-in’ food systems in unsustainable states.

One method to grow artificial body tissue is to place a porous scaffold seeded with cells, known as a tissue construct, into a rotating bioreactor filled with a nutrient-rich fluid. The flow within the bioreactor is affected by the movement of the construct relative to the bioreactor which, in turn, is affected by the hydrodynamical and gravitational forces the construct experiences. The construct motion is thus coupled to the flow within the bioreactor. Over the time scale of a few hours, the construct appears to move in a periodic orbit but, over tens of hours, the construct drifts from periodicity. In the biological literature, this effect is often attributed to the change in density of the construct that occurs via tissue growth. In this paper, we show that weak inertia can cause the construct to drift from its periodic orbit over the same time scale as tissue growth. We consider the coupled flow and construct motion problem within a rotating high-aspect-ratio vessel bioreactor. Using an asymptotic analysis, we investigate the case where the Reynolds number is large but the geometry of the bioreactor yields a small reduced Reynolds number, resulting in a weak inertial effect. In particular, to accurately couple the bioreactor and porous flow regions, we extend the nested boundary layer analysis of Dalwadi et al. (J. Fluid Mech., vol. 798, 2016, pp. 88–139) to include moving walls and the thin region between the porous construct and the bioreactor wall. This allows us to derive a closed system of nonlinear ordinary differential equations for the construct trajectory, from which we show that neglecting inertia results in periodic orbits; we solve the inertia-free problem analytically, calculating the periodic orbits in terms of the system parameters. Using a multiple-scale analysis, we then systematically derive a simpler system of nonlinear ordinary differential equations that describe the long-time drift of the construct due to the effect of weak inertia. We investigate the bifurcations of the construct trajectory behaviour, and the limit cycles that appear when the construct is less dense than the surrounding fluid and the rotation rate is large enough. Thus, we are able to predict when the tissue construct will drift towards a stable limit cycle within the bioreactor and when it will drift out until it hits the bioreactor edge.

Experiments with similar experimental design, soil, and planting date were conducted between 1975 and 1979 to evaluate the interference of jimsonweed on soybeans and cotton in Alabama (AL), Arkansas (AR), and Mississippi (MS). Jimsonweed densities were 0, 4, 8, 16, 32, and 64 plants 12 m−1 of row. Because of variation in rainfall patterns, geographic region influenced jimsonweed interference in cotton but not in soybeans. Even though jimsonweed interference was reduced by lack of rainfall, jimsonweed was more competitive in the less competitive cotton than in soybeans. Jimsonweed at 64 plants 12 m−1 of row was more competitive with cotton than soybeans, causing a 56 and 16% yield reduction, respectively. Position of jimsonweed to the soybean row did not influence competitiveness. Interspecific interference with soybeans caused one-third more reduction in jimsonweed fresh weight and capsules per plant than interspecific interference with cotton. The potential for jimsonweed to become a problem in southern soybeans is less than its potential in cotton because of the competitive ability of soybeans to reduce the growth and reproductive potential of jimsonweed.

The method of matched asymptotic expansions is used to study the canonical problem of steady laminar flow through a narrow two-dimensional channel blocked by a tight-fitting finite-length highly permeable porous obstacle. We investigate the behaviour of the local flow close to the interface between the single-phase and porous regions (governed by the incompressible Navier–Stokes and Darcy flow equations, respectively). We solve for the flow in these inner regions in the limits of low and high Reynolds number, facilitating an understanding of the nature of the transition from Poiseuille to plug to Poiseuille flow in each of these limits. Significant analytical progress is made in the high Reynolds number limit, and we explore in detail the rich boundary layer structure that occurs. We derive general results for the interfacial stress and for the conditions that couple the flow in the outer regions away from the interface. We consider the three-dimensional generalization to unsteady laminar flow through and around a tight-fitting highly permeable cylindrical porous obstacle within a Hele-Shaw cell. For the high Reynolds number limit, we give the coupling conditions and interfacial stress in terms of the outer flow variables, allowing information from a nonlinear three-dimensional problem to be obtained by solving a linear two-dimensional problem. Finally, we illustrate the utility of our analysis by considering the specific example of time-dependent forced far-field flow in a Hele-Shaw cell containing a porous cylinder with a circular cross-section. We determine the internal stress within the porous obstacle, which is key for tissue engineering applications, and the interfacial stress on the boundary of the porous obstacle, which has applications to biofilm erosion. In the high Reynolds number limit, we demonstrate that the fluid inertia can result in the cylinder experiencing a time-independent net force, even when the far-field forcing is periodic with zero mean.

We consider the inertia-dominated rise of a meniscus around a vertical circular cylinder. Previous experiments and scaling analysis suggest that the height of the meniscus, $h_{m}$, grows with the time following the initiation of rise, $t$, like $h_{m}\propto t^{1/2}$. This is in contrast to the rise on a vertical plate, which obeys the classic capillary–inertia scaling $h_{m}\propto t^{2/3}$. We highlight a subtlety in the scaling analysis that yielded $h_{m}\propto t^{1/2}$ and investigate the consequences of this subtlety. We develop a potential flow model of the dynamic problem, which we solve using the finite element method. Our numerical results agree well with previous experiments but suggest that the correct early time behaviour is, in fact, $h_{m}\propto t^{2/3}$. Furthermore, we show that at intermediate times the dynamic rise of the meniscus is governed by two parameters: the contact angle and the cylinder radius measured relative to the capillary length scale, $t^{2/3}$. This result allows us to collapse previous experimental results with different cylinder radii (but similar static contact angles) onto a single master curve.