Lattice sites of ion-implanted Li in diamond

Published in: Appl. Phys. Lett. 66 (1995) 2733-2735 citations recorded in [Science Citation Index] Abstract: Radioactive Li ions were implanted into natural IIa diamonds at temperatures between 100 K and 900 K. Emission channelling patterns of a-particles emitted in the nuclear decay of 8Li (t1/2 = 838 ms) were measured and, from a comparison with calculated emission channelling and blocking effects from Monte Carlo simulations, the lattice sites taken up by the Li ions were quantitatively determined. A fraction of 40(5)% of the implanted Li ions were found to be located on tetrahedral interstitial lattice sites, and 17(5)% on substitutional sites. The fractions of implanted Li on the two lattice sites showed no change with temperature, indicating that Li diffusion does not take place within the time window of our measurements.

Adverse Drug Reactions in Children—A Systematic Review

Adverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Properties of low dislocation density metal crystals

This thesis describes the growth, X-ray diffraction assessment and tensile deformation properties of dislocation-free copper single crystals. As such it has been possible to conveniently section the work carried out into these three main areas within this thesis. Consequently, each chapter may be read almost independently of the others with references and further work suggestions being incorporated at the end of each chapter. This format, it is felt, does not disjoint the work: rather, it enables the central theme (i.e. the title of this thesis) to be developed in a much more continuously clear way than is normally apparent in a thesis where conclusions, further work suggestions and references are not drawn together until the end of the volume. Chapter I opens with a brief outline of the crystal growth methods which could have been used to produce low dislocation density (andlt;106 cm/cm3) crystals by utilising the three fundamental phase transitions, i.e. solid to solid, vapour to solid and liquid to solid. The Czochralski method is then discussed in detail since it was used by the author to produce dislocation-free copper single crystals. The technological problems in obtaining such crystals are extensively enumerated and solutions presented. For instance, melt surface vibrations were eliminated by using a continuous flow of cooling water, by standing the complete crystal puller on a bed of foam, and by rigidly clamping the R.F. coil. It is emphasised that these technological problems must be solved before the scientific aspects of the growth of dislocation-free crystals can be studied. It is further shown that the author's modified crystal growing technique can be reliably used to grow dislocation-free crystals of copper each time, providing adequate care is taken over growth rates (andasymp;1.2 cm/hr); specimen shape (a long thin "double-neck" must precede the required crystal to eliminate dislocations propagating from the seed and to act as a heat flow resistance); and crystal cooling rates (a long "tail" allowed the crystal to reach the ambient temperature slowly thereby minimising dislocation by thermal stresses and/or vacancy condensation). In the future, it is suggested, an automated crystal pulling system would be advantageous and a study of crystal growth in a synchrotron X-ray beam could be potentially definitive experiment on crystal growth. Chapter II looks at the theoretical aspects of Czochralski crystal growth with the aid of a new model which has been analysed on the Oxford University Computer. The model assumes a crystal-neck-seed configuration to be "sitting" on a liquid and examines the influence of geometric changes of the seed-neck-crystal and of radiation changes on the temperature gradients, primarily at the growth front. Four elements were chosen for study in this way: Si, Ge, Ag, Cu, i.e. four elements which have been grown dislocation-free. It was found that the seed size and shape played a small part in determining the interfacial temperature gradients, DTc(0), of all the elements. The neck, however, could have a marked influence on DTc(0) values in metals but not so much in semiconductor crystals. By geometric control alone it was found that the best way to reduce DTc(0) values was to grow a large diameter crystal. The influence of radiation losses was found to be marked for semiconductor crystals but not for metal crystals. Finally, it is concluded that to minimise DTc(0) values then the seed and neck must be long and thin and the crystal fat. These results fit in well with experimental knowledge. Further work to be carried out could consider the influence of a varying ambient temperature and convective heat losses on the interfacial temperature gradients. Chapter III is concerned with the interaction of X-rays with perfect crystals. The Lang-Borrmann X-ray topography technique is examined, and the experimental methods used to obtain X-ray topographs taken throughout this work are discussed. The major part of the chapter takes up the discussion of the theoretical interaction of X-rays with a perfect crystal set to diffract such X-rays. It is demonstrated that for a plane-wave incident on a cylindrical crystal, for the boundary condition to be satisfied the dispersion surface tie-points are displaced as the crystal traverses the incident X-ray beam. Thus the crystal wave-vectors no longer exactly satisfy the Bragg condition. This effect, was never unambiguously monitored experimentally because of the incident beam divergence. It is suggested that a future study could consider this problem in more detail. The Takagi-Taupin-Uragami generalised X-ray diffraction theory is reviewed and then used to calculate the intensity in the diffracted beam of a traverse topograph from a perfect cylindrical copper crystal. This computer simulation is also compared to an experimental condition. In both cases it is found that the Bragg surface of the crystal produces a very intense reflection whilst the remainder of the crystal gives a much reduced diffracted intensity in comparison. This asymmetric profile is interpreted in terms of absorption mechanisms which are strong at the centre of the crystal but not at the surface. The general agreement between theory and experiment is considered to be good although a few discrepancies arose, e.g. the lateral extent of the Bragg surface peak was found to be larger for the experiment than for the theory. Continued research in this area must explore further these small discrepancies; and it is suggested that a possible line of future study would be to examine theoretically and experimentally the X-ray diffraction from dislocation-free cylindrical crystals which possess low absorption coefficients (e.g. aluminium, silicon) for harder radiations (e.g. MoKandprop;1, AgKandprop;1). It should then be possible to produce interference fringes and then it should be possible to examine the effects of a strain gradient on fringe spacing and visibility. Chapter IV sets out to discuss the tensile deformation behaviour of [1and#773;2and#773;3] growth axis, dislocation-free, chromium plated copper single crystals. This is done using the results from two sets of coupled experiments: an Instron deformation study and a synchrotron deformation investigation. It is first shown that chromium plating can destroy the perfection of the crystal unless care is exercised over plating temperatures and times. It was finally found that after plating for 10 seconds at 55C (andasymp;1 andmu;m of Cr deposited) that there was no indication of lattice dislocation. The stress-strain curve of a chromium plated dislocation-free copper crystal (Cr thickness and#8815;1 andmu;m) is shown to exhibit a yield point commensurate with that for a non-plated, dislocation-free copper crystal, i.e. andasymp;90 g/mm2. The work hardening curve is shown to be comprised of three distinct regions: an initial rapid work hardening rate; a transitionary work hardening rate; and a stabilised work hardening rate up to a shear strain of 6%. In straining the crystal through these regions the work hardening rate progressively decreased. For a plated crystal which is dislocation-free initially it is shown that serrations in the flow curve occur, whilst for all other crystals these are shown to be absent. Such serrations are argued to occur by a source suppression and new source operation mechanism during the early deformation stages (andasymp;1% shear strain), and then by a crack formation mechanism at the copper-chromium interface during the later stages of deformation. The initial work hardening rates (andasymp;18 kg/mm2) were found to be independent of coating thickness (0.5 andmu;m and 1 andmu;m) but in the latter two regions the thicker coating imparted a higher work hardening rate to the crystal than the thinner layer, e.g. for a 0.5 andmu;m chromium layer the work hardening rate was andasymp;1.65 kg/mm2 in region iii and for a 1 andmu;m chromium layer it was 2.97 kg/mm2 in region iii. It is tentatively suggested that the chromium layer affected mobile dislocation motion rather than dislocation generation. The synchrotron work produced no evidence to support the argument that dislocation motion up the elastic line took place. Yielding was found to occur at a stress level similar to that measured in the Instron work. The complex stress system imposed by the deformation jig and the lack of resolution rendered it impossible to decide where the dislocation sources were located. Further increases in the load on the crystal produced double slip and this was argued to prematurely occur because of the combination of torsion, bending and tension which the crystal experienced. Certain interfacial dislocation activity was registered but this was not readily analysed in terms of surface sources. The yielding behaviour was inhomogeneous and appeared to be remote from the few slip bands induced by specimen transport. After yielding evidence was found for dislocation pile-up at the centre of the crystal. It is pointed out that future studies should use a better design of deformation jig so as to apply only a tensile stress to the crystal. Plating thickness and specimen size could be further explored.</p