Exploring the solvent extraction of rhodium and gold

This work explores the solvent extraction of precious metals, specifically rhodium and gold, from chloride solution, with the aims of understanding how existing extractants work and designing new extractants. A wide variety of analytical techniques are employed, demonstrating how they can be used together to assess extraction ability and provide insight into the identity of the extracted species. Computational techniques are also used; their implementation, often in conjunction with experiment, can identify the interactions which allow extraction to occur and explain differences in extraction behaviour. Chapter 3 focuses on understanding how amidoamine extractants interact with the Rh(III) complexes present in chloride solution and thus enable their extraction. Experimental analysis shows that at low concentrations of Rh(III), the extracted species is RhCl5(H2O).(LH)2, but at high concentrations a di-nuclear species, Rh2Cl9.(LH)3, is present in the organic phase and on aging an inner-sphere complex, RhCl3L, can form. The mode of extraction is found to differ from that of a simple amine-based extractant. Computational modelling explores the extraction behaviour of a series of amidoamine extractants, finding they have different anion binding modes depending on the number of intra-extractant hydrogen bonds they can form. This results in bis- and tris-amidoamines having a more suitable binding mode for the Rh(III) aquo-chloridometalate compared to a mono-amidoamine, which has a more suitable binding mode for chloride. Calculated formation energies are broadly in agreement with experimental results and suggest selectivity for [RhCl5(H2O)]2− over chloride is the source of the success of this class of extractants. This work presents a full mode of action analysis of the bis-amidoamine and rationalises why the amidoamine reagents were the first effective Rh(III) extractants from chloride solution: they are proton-chelating reagents, which can adopt a binding mode that is selective for larger, more charge-diffuse anions. Building on the work of Chapter 3, a theoretical screening study of other mono- and bisamidoamines (or amido-quaternary ammonium compounds) is presented in Chapter 4. Different potential binding modes of the molecules are explored computationally, and it is found that, where possible, N-H to anion binding is generally more favourable than intramolecule proton chelation and C-H to anion binding, with only one exception to this rule. Interestingly, this exception proves to have the most favourable energy of exchanging chloride for [RhCl5(H2O)]2−, suggesting that it would be the most effective at extracting the Rh(III) metalate. All other molecules are theoretically poorer extractants of Rh(III) and, based on a comparison of the energies of formation, it appears that the reason for this is less favourable association with [RhCl5(H2O)]2−, more favourable association with chloride, or a combination of the two. This work highlights the importance of a favourable C-H to anion, or “soft”, binding mode in the selective extraction of Rh(III) metalate over chloride, and how small structural changes to the extractant can drastically alter the favourability of this type of binding mode. Chapter 5 explores the possibility of using polyamine-based Rh precipitants or reagents based on them for Rh extraction. It is found that “precipitant” molecules with long chain Rgroups added are capable of extracting Rh(III) metalate very well, even from solutions of high HCl concentration. At high HCl concentrations, the most likely Rh(III) species extracted from the aqueous phase is [RhCl6]3−, with which the extractant is expected to associate in the outer-sphere. In contrast, it is found that an inner-sphere complex forms upon extraction from solutions of very low chloride concentrations. Extraction from mixed Rh(III)/Pt(IV) aqueous solutions is also investigated, but no selectivity for Rh(III) over Pt(IV) is found. Rh(III) stripping from the loaded organic is investigated using a number of reagents, with ammonium hydroxide solution found to be the most effective. The reagent designed and tested has the potential to be used for the solvent extraction of Rh industrially, offering extraction at the higher HCl concentrations typically used in existing metal recovery flowsheets. Industrially, Au(III) solvent extraction from chloride solution is well established, however, some of the reagents used are still not well understood. Chapter 6 aims to explain the extraction mechanism, and particularly the role of water, in Au(III) recovery with an industrial reagent via classical molecular dynamics simulations, which allow the assembly of the extracted species to be viewed and analysed. Experimental conditions can be modelled, but, in addition, so can other, non-experimental conditions to permit a better understanding of the extraction behaviour. Analysis of the output structures suggests that water’s primary role in extraction is as the positive charge carrier. In some systems, where chloride is considered as the anion, the water partially hydrates the extracted anion, acting as a mediating agent between the electronegative functional groups on the extractant and the anion. This new insight into the nature of the extraction assemblies provides a greater understanding of the role of water in the extraction mechanism, and the means by which the extractant transports [AuCl4]‒ into the organic phase, information which can be used for informed modification of existing extraction processes and development of new reagents

Rationale and study design of the MINERVA study: Multicentre Investigation of Novel Electrocardiogram Risk markers in Ventricular Arrhythmia prediction-UK multicentre collaboration

Introduction The purpose of this study is to assess the ability of two new ECG markers (Regional Repolarisation Instability Index (R2I2) and Peak Electrical Restitution Slope) to predict sudden cardiac death (SCD) or ventricular arrhythmia (VA) events in patients with ischaemic cardiomyopathy undergoing implantation of an implantable cardioverter defibrillator for primary prevention indication. Methods and analysis Multicentre Investigation of Novel Electrocardiogram Risk markers in Ventricular Arrhythmia prediction is a prospective, open label, single blinded, multicentre observational study to establish the efficacy of two ECG biomarkers in predicting VA risk. 440 participants with ischaemic cardiomyopathy undergoing routine first time implantable cardioverter-defibrillator (ICD) implantation for primary prevention indication are currently being recruited. An electrophysiological (EP) study is performed using a non-invasive programmed electrical stimulation protocol via the implanted device. All participants will undergo the EP study hence no randomisation is required. Participants will be followed up over a minimum of 18 months and up to 3 years. The first patient was recruited in August 2016 and the study will be completed at the final participant follow-up visit. The primary endpoint is ventricular fibrillation or sustained ventricular tachycardia >200 beats/min as recorded by the ICD. The secondary endpoint is SCD. Analysis of the ECG data obtained during the EP study will be performed by the core lab where blinding of patient health status and endpoints will be maintained. Ethics and dissemination Ethical approval has been granted by Research Ethics Committees Northern Ireland (reference no. 16/NI/0069). The results will inform the design of a definitive Randomised Controlled Trial (RCT). Dissemination will include peer reviewed journal articles reporting the qualitative and quantitative results, as well as presentations at conferences and lay summaries

Differences in Brain Function and Changes with Intervention in Children with Poor Spelling and Reading Abilities

Previous fMRI studies in English-speaking samples suggested that specific interventions may alter brain function in language-relevant networks in children with reading and spelling difficulties, but this research strongly focused on reading impaired individuals. Only few studies so far investigated characteristics of brain activation associated with poor spelling ability and whether a specific spelling intervention may also be associated with distinct changes in brain activity patterns. We here investigated such effects of a morpheme-based spelling intervention on brain function in 20 children with comparatively poor spelling and reading abilities using repeated fMRI. Relative to 10 matched controls, children with comparatively poor spelling and reading abilities showed increased activation in frontal medial and right hemispheric regions and decreased activation in left occipito-temporal regions prior to the intervention, during processing of a lexical decision task. After five weeks of intervention, spelling and reading comprehension significantly improved in the training group, along with increased activation in the left temporal, parahippocampal and hippocampal regions. Conversely, the waiting group showed increases in right posterior regions. Our findings could indicate an increased left temporal activation associated with the recollection of the new learnt morpheme-based strategy related to successful training

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Social cartographies as performative devices in research on higher education

In this article, we review social cartography as a methodological approach to map and collectively engage diverse perspectives within the study of higher education. We illustrate the uses of this approach by drawing on our own experiences engaging it as part of an international research project about the effects of the convergence of globalization and economic crises in higher education. We offer several examples of how social cartography can enable agonistic collaboration amongst existing positions, as well as open up new spaces and possibilities for alternative futures in higher education

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

Experimental manipulation of air temperature in captivity appears unsuitable for evaluating fecal glucocorticoid metabolite responses of wild-caught birds to heat exposure

Noninvasive measurement of stress-related alterations in fecal glucocorticoid metabolite (fGCM) concentrations has considerable potential for quantifying physiological responses to very hot weather in free-ranging birds, but practical considerations related to sampling will often make this method feasible only for habituated study populations. Here we evaluate an alternate approach, the use of experimentally manipulated thermal environments for evaluating stress responses to high environmental temperatures in wild-caught birds housed in captivity. Using an enzyme immunoassay utilizing antibodies against 5ß-pregnane-3a,11ß,21- triol-20-one-CMO∶BSA (tetrahydrocorticosterone), we quantified fGCMs in captive individuals of three southern African arid-zone species (southern pied babblers [Turdoides bicolor], white-browed sparrow-weavers [Plocepasser mahali], and southern yellow-billed hornbills [Tockus leucomelas]) experiencing daily air temperature maxima (Tmax) ranging from 307–327C to 427–447C. For none of the three species did Tmax emerge as a significant predictor of elevated fGCM concentrations, and no stress response to simulated hot weather was evident. The apparent lack of a stress response to Tmaxp427C in captive southern pied babblers contrasts with linear increases in fGCMs at Tmax 1 387C in free-ranging conspecifics. The lack of an effect of Tmax on fGCM levels may potentially be explained by several factors, including differences in operative temperatures and the availability of water and food between free-ranging and captive settings or the stress effect of captivity itself. Our results suggest that experimental manipulations of thermal environments experienced by wild-caught captive birds have limited usefulness for testing hypotheses concerning the effects of hot weather events on fGCM (and, by extension, glucocorticoid) concentrations.The National Research Foundation of South Africahttp://www.press.uchicago.edu/ucp/journals/journal/pbz.html2022-07-22pm2022Mammal Research Institut

Permissible variation in the 3' non-coding region of the haemagglutinin genome segment of the H5N1 candidate influenza vaccine virus NIBRG-14 [corrected].

The candidate H5N1 vaccine virus NIBRG-14 was created in response to a call from the World Health Organisation in 2004 to prepare candidate vaccine viruses (CVVs) to combat the threat of an H5N1 pandemic. NIBRG-14 was created by reverse genetics and is composed of the neuraminidase (NA) and modified haemagglutinin (HA) genes from A/Vietnam/1194/2004 and the internal genes of PR8, a high growing laboratory adapted influenza A(H1N1) strain. Due to time constraints, the non-coding regions (NCRs) of A/Vietnam/1194/2004 HA were not determined prior to creating NIBRG-14. Consequently, the sequence of the primers used to clone the modified A/Vietnam/1194/2004 HA was based upon previous experience of cloning H5N1 viruses. We report here that the HA 3' NCR sequence of NIBRG-14 is different to that of the parental wild type virus A/Vietnam/1194/2004; however this does not appear to impact on its growth or antigen yield. We introduced additional small changes into the 3'NCR of NIBRG-14; these had only minor effects on viral growth and antigen content. These findings may serve to assure the influenza vaccine community that generation of CVVs using best-guess NCR sequences, based on sequence alignments, are likely to produce robust viruses