Jump starting pathogen evolution: Mycobacteria are mostly environmental saprotrophs, but during human history, some have become our pathogens. In the past 50 years or so, intractable and virulent infections of Mycobacterium abscessus have emerged in people with cystic fibrosis. Bryant et al. investigated how these mycobacteria have evolved into human pathogens so quickly (see the Perspective by Brugha and Spencer). Chronic infections in the lung offer plenty of evolutionary scope for the emergence of virulent clones after horizontal gene transfer and hypermutation. Pathogens are acquired by environmental contamination, which leaves open a window for clinical control because the most virulent clones survive poorly outside the body. Therefore, immediate treatment and enhanced infection-control measures for M. abscessus cases could reduce opportunities for the evolution of direct person-to-person transmission. Science , this issue p. eabb8699 ; see also p. 465

A measurement setup is designed and constructed to experimentally investigate the thermohydraulic performance of a novel direct rotor cooling method for an interior permanent magnet synchronous machine, where oil is pumped through weight saving channels of the rotor iron close to the magnets. The setup consist of a stationary rotor assembly where heat is dissipated in an aluminum sleeve surrounding the rotor outer surface. Measurements are performed for different oil inlet temperatures, flow rates and heat losses. It is shown that tangential temperature variations can be neglected and axial variations are as expected. The conductive resistance within the rotor assembly is similar for each measurement point as the differences are within the measurement uncertainty. The convective resistance decreases with an increasing flow rate, inlet temperature and heat dissipation. From correlations in scientific literature, it is expected that the convective resistance will further reduce with increasing rotational speed of the rotor. A comparison of these results to a standard hollow shaft cooling method shows a great potential of the novel direct rotor cooling method to further increase the power density of electric machines.

Therapeutic drug monitoring (TDM) of elexacaftor/tezacaftor/ivacaftor (ETI) remains challenging due to a lack of clarity around the parameters that govern ETI plasma concentrations, whilst the use of concomitant CYP3A inducers rifabutin and rifampicin is not recommended. We present the complexities of TDM for ETI performed in a person with cystic fibrosis and refractory Mycobacterium abscessus pulmonary disease. Utilising National Association of Testing Authorities (NATA) accredited assays and target considerations published by the Therapeutic Goods Administration (TGA), Australia, ETI plasma concentration variability was monitored over the course of an acute admission with added complexity from an antibiotic regimen including rifabutin, a moderate cytochrome P450 3A (CYP3A) inducer, and clofazimine, a mild CYP3A inhibitor. This case highlights the challenges surrounding ETI TDM in the context of acute severe illness, malnutrition, chronic infection, and drug-to-drug interactions. The marked clinical improvement seen, alongside sustained ETI plasma concentrations and suppressed sweat chloride levels on serial testing, provided reassurance of the use of ETI and rifabutin concomitantly in this case, and highlights the potential utility of TDM in helping guide clinical practice. Though a current barrier to the application of TDM includes ETI only being available as a fixed dose combination.

N,N'‐dimethyl‐4,4'bipyridinium dichloride (Paraquat) is a potent herbicide used widely in agriculture. We report the effects of an ingestion of paraquat by a 28 year old male with cystic fibrosis and the diagnostic and management challenges this posed in both the acute and longer term setting. We describe the effects of direct paraquat toxicity on the lung tissue secondary to aspiration and review the long‐term sequelae of paraquat, namely osteonecrosis. Our case is the first to describe osteonecrosis of the knee in the context of paraquat toxicity. Survival following ingestion remains poor with a high associated mortality. However, timely treatment with NAC and immunosuppression may impact on survival. In those patients who do survive the acute phase post ingestion, follow‐up over years may be required to detect the long‐term effects of paraquat on bone health.