Background Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or in coma. Methods We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2·5mgs or 0·9% saline placebo intravenously every 8 h irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days treatment, which ever came first. Delirium was assessed using the confusion assessment method - for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14-day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. Findings 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11] days; p= 0·53). The most common adverse events were oversedation (11 patients in the haloperidol group vs. six in the placebo) and QTc prolongation (seven in haloperidol group and six in the placebo group). No patient had a serious adverse event related to study drug. Interpretation These results do not support the hypothesis that haloperidol modifies duration of delirium in critically ill patients. Although haloperidol can be used safely in this population of patients, pending the results of trials in progress, the use of intravenous haloperidol should be reserved for the short-term management of acute agitation. Funding National Institute for Health Research

Theoretical predictions of the magnetic anisotropy of antiferromagnetic materials are demanding due to a lack of experimental techniques which are capable of a direct measurement of this quantity. At the same time it is highly significant due to the use of antiferromagnetic components in magneto-resistive sensor devices where the stability of the antiferromagnet is of upmost relevance. We perform an ab-initio study of the ordered phases of IrMn and IrMn3, the most widely used industrial antiferromagnets. Calculating the form and the strength of the magnetic anisotropy allows the construction of an effective spin model, which is tested against experimental measurements regarding the magnetic ground state and the Néel temperature. Our most important result is the extremely strong second order anisotropy for IrMn3 appearing in its frustrated triangular magnetic ground state, a surprising fact since the ordered L12 phase has a cubic symmetry. We explain this large anisotropy by the fact that cubic symmetry is locally broken for each of the three Mn sub-lattices. While the magnetic anisotropy (MA) of ferromagnets is a well investigated quantity, both experimentally as well as theoretically, it is much less understood in case of antiferromagnets. This lack of knowledge is on the one hand due to a lack of experimental techniques which are capable of a direct measurement of this quantity. On the other hand, theoretical first principles calculations of magnetic anisotropy effects are quite challenging as they require the use of fully relativistic spin density functional theory.Interest in the MA of antiferromagnets comes from the fact that these compounds are important components of GMR sensors used, e.g., in hard disc read heads. Antiferromagnetic materials are employed in these devices to form antiferromagnet/ferromagnet bilayers exhibiting exchange bias 1 , a shift of the hysteresis loop of the ferromagnet, providing a pinned layer which fixes the magnetization of the reference layer of a GMR sensor. The stability of the antiferromagnet is most crucial for the stability of exchange bias and hence the functioning of the device 2,3 . Industrially the antiferromagnet IrMn is widely used because of the large exchange bias and thermal stability that can be obtained with this material.From experimental investigations of the exchange bias effect it is concluded that IrMn must have a rather large MA. Recent estimates of the MA of IrMn concerned the mean blocking temperature T B , the temperature at which the exchange bias shift changes sign upon thermal activation. From T B the intrinsic MA can be inferred if the particle size distribution is known; such a procedure has recently been reported and the room temperature MA energy of IrMn was estimated at 5.5×10 6 erg/cc 4 and even 2.8×10 7 erg/cc 5 depending on the seed layer and, consequently, the texture of the IrMn.In this letter, we address several features of the MA of IrMn alloys starting from first principles. In terms of simple symmetry considerations we predict the form...

This paper summarises the theory and functionality behind Questaal, an open-source suite of codes for calculating the electronic structure and related properties of materials from first principles. The formalism of the linearised muffin-tin orbital (LMTO) method is revisited in detail and developed further by the introduction of short-ranged tight-binding basis functions for full-potential calculations. The LMTO method is presented in both Green's function and wave function formulations for bulk and layered systems. The suite's full-potential LMTO code uses a sophisticated basis and augmentation method that allows an efficient and precise solution to the band problem at different levels of theory, most importantly density functional theory, LDA+U , quasi-particle self-consistent GW and combinations of these with dynamical mean field theory. This paper details the technical and theoretical bases of these methods, their implementation in Questaal, and provides an overview of the code's design and capabilities. framework of an extension to the linear muffin-tin orbital (LMTO) technique including a highly precise and efficient full-potential implementation. An advanced fully-relativistic, non-collinear implementation based on the atomic sphere approximation is used for calculating transport and magnetic properties.

In order to derive tensorial exchange interactions and local magnetic anisotropies in itinerant magnetic systems, an approach combining the Spin-Cluster Expansion with the Relativistic Disordered Local Moment scheme is introduced. The theoretical background and computational aspects of the method are described in detail. The exchange interactions and site resolved anisotropy contributions for the IrMn3/Co(111) interface, a prototype for an exchange bias system, are calculated including a large number of magnetic sites from both the antiferromagnet and ferromagnet. Our calculations reveal that the coupling between the two subsystems is fairly limited to the vicinity of the interface. The magnetic anisotropy of the interface system is discussed, including effects of the Dzyaloshinskii-Moriya interactions that appear due to symmetry breaking at the interface.