Partiality, revisited: the partiality monad as a quotient inductive-inductive type

Capretta's delay monad can be used to model partial computations, but it has the "wrong" notion of built-in equality, strong bisimilarity. An alternative is to quotient the delay monad by the "right" notion of equality, weak bisimilarity. However, recent work by Chapman et al. suggests that it is impossible to define a monad structure on the resulting construction in common forms of type theory without assuming (instances of) the axiom of countable choice. Using an idea from homotopy type theory - a higher inductive-inductive type - we construct a partiality monad without relying on countable choice. We prove that, in the presence of countable choice, our partiality monad is equivalent to the delay monad quotiented by weak bisimilarity. Furthermore we outline several applications

Natural mutations of human XDH promote the nitrite (NO2 −)-reductase capacity of xanthine oxidoreductase: A novel mechanism to promote redox health?

Several rare genetic variations of human XDH have been shown to alter xanthine oxidoreductase (XOR) activity leading to impaired purine catabolism. However, XOR is a multi-functional enzyme that depending upon the environmental conditions also expresses oxidase activity leading to both O2·- and H2O2 and nitrite (NO2−) reductase activity leading to nitric oxide (·NO). Since these products express important, and often diametrically opposite, biological activity, consideration of the impact of XOR mutations in the context of each aspect of the biochemical activity of the enzyme is needed to determine the potential full impact of these variants. Herein, we show that known naturally occurring hXDH mutations do not have a uniform impact upon the biochemical activity of the enzyme in terms of uric acid (UA), reactive oxygen species (ROS) and nitric oxide ·NO formation. We show that the His1221Arg mutant, in the presence of xanthine, increases UA, O2·- and NO generation compared to the WT, whilst the Ile703Val increases UA and ·NO formation, but not O2·-. We speculate that this change in the balance of activity of the enzyme is likely to endow those carrying these mutations with a harmful or protective influence over health that may explain the current equipoise underlying the perceived importance of XDH mutations. We also show that, in presence of inorganic NO2−, XOR-driven O2·- production is substantially reduced. We suggest that targeting enzyme activity to enhance the NO2−-reductase profile in those carrying such mutations may provide novel therapeutic options, particularly in cardiovascular disease

Photodissociation dynamics of methyl iodide probed using femtosecond extreme ultraviolet photoelectron spectroscopy

Femtosecond pump-probe photoelectron spectroscopy measurements using an extreme ultraviolet probe have been made on the photodissociation dynamics of UV (269 nm) excited CH3I. The UV excitation leads to population of the 3Q0 state which rapidly dissociates. The dissociation is manifested as shifts in the measured photoelectron kinetic energy that map the extending C-I bond. The increased energy available in the XUV probe relative to a UV probe means the dynamics are followed over the chemically important region as far as C-I bond lengths of approximately 4 Å

International Federation for Emergency Medicine model curriculum for medical student education in emergency medicine

There is a critical and growing need for emergency physicians and emergency medicine resources worldwide. To meet this need, physicians must be trained to deliver time-sensitive interventions and life-saving emergency care. Currently, there is no internationally recognized, standard curriculum that defines the basic minimum standards for emergency medicine education. To address this lack, the International Federation for Emergency Medicine (IFEM) convened a committee of international physicians, health professionals, and other experts in emergency medicine and international emergency medicine development to outline a curriculum for foundation training of medical students in emergency medicine. This curriculum document represents the consensus of recommendations by this committee. The curriculum is designed with a focus on the basic minimum emergency medicine educational content that any medical school should be delivering to its students during their undergraduate years of training. It is not designed to be prescriptive, but to assist educators and emergency medicine leadership in advancing physician education in basic emergency medicine content. The content would be relevant, not just for communities with mature emergency medicine systems, but also for developing nations or for nations seeking to expand emergency medicine within current educational structures. We anticipate that there will be wide variability in how this curriculum is implemented and taught, reflecting the existing educational milieu, the resources available, and the goals of the institutions’ educational leadership