Multiply imputing missing values arising by design in transplant survival data

In this article, we address a missing data problem that occurs in transplant survival studies. Recipients of organ transplants are followed up from transplantation and their survival times recorded, together with various explanatory variables. Due to differences in data collection procedures in different centers or over time, a particular explanatory variable (or set of variables) may only be recorded for certain recipients, which results in this variable being missing for a substantial number of records in the data. The variable may also turn out to be an important predictor of survival and so it is important to handle this missing‐by‐design problem appropriately. Consensus in the literature is to handle this problem with complete case analysis, as the missing data are assumed to arise under an appropriate missing at random mechanism that gives consistent estimates here. Specifically, the missing values can reasonably be assumed not to be related to the survival time. In this article, we investigate the potential for multiple imputation to handle this problem in a relevant study on survival after kidney transplantation, and show that it comprehensively outperforms complete case analysis on a range of measures. This is a particularly important finding in the medical context as imputing large amounts of missing data is often viewed with scepticism

Multicentre randomised controlled trial: protocol for Plasma-Lyte Usage and Assessment of Kidney Transplant Outcomes in Children (PLUTO)

INTRODUCTION: Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplantation. When severe, this can lead to complications including seizures, cerebral oedema and death. Relatively large volumes of intravenous fluid are administered to children perioperatively in order to establish perfusion to the donor kidney, the majority of which are from living and deceased adult donors. Hypotonic intravenous fluid is commonly used in the post-transplant period due to clinicians' concerns about the sodium, chloride and potassium content of isotonic alternatives when administered in large volumes.Plasma-Lyte 148 is an isotonic, balanced intravenous fluid that contains sodium, chloride, potassium and magnesium with concentrations equivalent to those of plasma. There is a physiological basis to expect that Plasma-Lyte 148 will reduce the incidence of clinically significant electrolyte and acid-base abnormalities in children following kidney transplantation compared with current practice.The aim of the Plasma-Lyte Usage and Assessment of Kidney Transplant Outcomes in Children (PLUTO) trial was to determine whether the incidence of clinically significantly abnormal plasma electrolyte levels in paediatric kidney transplant recipients will be different with the use of Plasma-Lyte 148 compared with intravenous fluid currently administered. METHODS AND ANALYSIS: PLUTO is a pragmatic, open-label, randomised controlled trial comparing Plasma-Lyte 148 to current care in paediatric kidney transplant recipients, conducted in nine UK paediatric kidney transplant centres.A total of 144 children receiving kidney transplants will be randomised to receive either Plasma-Lyte 148 (the intervention) intraoperatively and postoperatively, or current fluid. Apart from intravenous fluid composition, all participants will receive standard clinical transplant care.The primary outcome measure is acute hyponatraemia in the first 72 hours post-transplant, defined as laboratory plasma sodium concentration of <135 mmol/L. Secondary outcomes include symptoms of acute hyponatraemia, other electrolyte and acid-base imbalances and transplant kidney function.The primary outcome will be analysed using a logistic regression model adjusting for donor type (living vs deceased donor), patient weight (<20 kg vs ≥20 kg pretransplant) and transplant centre as a random effect. ETHICS AND DISSEMINATION: The trial received Health Research Authority approval on 20 January 2020. Findings will be presented to academic groups via national and international conferences and peer-reviewed journals. The patient and public involvement group will play an important part in disseminating the study findings to the public domain

PreImplantation Trial of Histopathology In renal Allografts (PITHIA): a stepped-wedge cluster randomised controlled trial protocol.

INTRODUCTION: Most potential kidney transplant donors in the UK are aged over 60 years, yet increasing donor age is associated with poorer graft survival and function. Urgent preimplantation kidney biopsy can identify chronic injury, and may aid selection of better 'quality' kidneys from this group. However, the impact of biopsy on transplant numbers remains unproven. The PreImplantation Trial of Histopathology In renal Allografts (PITHIA) study will assess whether the introduction of a national, 24 hours, digital histopathology service increases the number, and improves outcomes, of kidneys transplanted in the UK from older deceased donors. METHODS AND ANALYSIS: PITHIA is an open, multicentre, stepped-wedge cluster randomised study, involving all UK adult kidney transplant centres. At 4-monthly intervals, a group of 4-5 randomly selected clusters (transplant centres) will be given access to remote, urgent, digital histopathology (total intervention period, 24 months). The trial has two primary end points: it is powered for an 11% increase in the proportion of primary kidney offers from deceased donors aged over 60 years that are transplanted, and a 6 mL/min increase in the estimated glomerular filtration rate of recipients at 12 months post-transplant. This would equate to an additional 120 kidney transplants performed in the UK annually. Trial outcome data will be collected centrally via the UK Transplant Registry held by NHS Blood and Transplant (NHSBT) and will be analysed using mixed effects models allowing for clustering within centres and adjusting for secular trends. An accompanying economic evaluation will estimate the cost-effectiveness of the service to the National Health Service. ETHICS AND DISSEMINATION: The study has been given favourable ethical opinion by the Cambridge South Research Ethics Committee and is approved by the Health Research Authority. We will present our findings at key transplant meetings, publish results within 4 years of the trial commencing and support volunteers at renal patient groups to disseminate the trial outcome. TRIAL REGISTRATION NUMBER: ISRCTN11708741; Pre-results.nih

Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis.

The rise of antibiotic-resistant bacteria has led to an urgent need for rapid detection of drug resistance in clinical samples, and improvements in global surveillance. Here we show how de Bruijn graph representation of bacterial diversity can be used to identify species and resistance profiles of clinical isolates. We implement this method for Staphylococcus aureus and Mycobacterium tuberculosis in a software package ('Mykrobe predictor') that takes raw sequence data as input, and generates a clinician-friendly report within 3 minutes on a laptop. For S. aureus, the error rates of our method are comparable to gold-standard phenotypic methods, with sensitivity/specificity of 99.1%/99.6% across 12 antibiotics (using an independent validation set, n=470). For M. tuberculosis, our method predicts resistance with sensitivity/specificity of 82.6%/98.5% (independent validation set, n=1,609); sensitivity is lower here, probably because of limited understanding of the underlying genetic mechanisms. We give evidence that minor alleles improve detection of extremely drug-resistant strains, and demonstrate feasibility of the use of emerging single-molecule nanopore sequencing techniques for these purposes

Peace and Justice through a Feminist Lens: Gender Justice and the Women’s Court for the Former Yugoslavia

Post-conflict interventions to ‘deal with’ violent pasts have moved from exception to global norm. Early efforts to achieve peace and justice were critiqued as ‘gender-blind’—for failing to address sexual and gender-based violence, and neglecting the gender-specific interests and needs of women in transitional settings. The advent of UN Security Council resolutions on ‘Women, Peace and Security’ provided a key policy framework for integrating both women and gender issues into transitional justice processes and mechanisms. Despite this, gender justice and equality in (post-)conflict settings remain largely unachieved. This article explores efforts to attain gender-just peace in post-conflict Bosnia and Herzegovina (BiH). It critically examines the significance of a recent ‘bottom-up’ truth-telling project—the Women’s Court for the former Yugoslavia—as a locally engaged approach to achieving justice and redress for women impacted by armed conflict. Drawing on participant observation, documentary analysis, and interviews with women activists, the article evaluates the successes and shortcomings of responding to gendered forms of wartime violence through truth-telling. Extending Nancy Fraser’s tripartite model of justice to peacebuilding contexts, the article advances notions of recognition, redistribution and representation as crucial components of gender-just peace. It argues that recognizing women as victims and survivors of conflict, achieving a gender-equitable distribution of material and symbolic resources, and enabling women to participate as agents of transitional justice processes are all essential for transforming the structural inequalities that enable gender violence and discrimination to materialize before, during, and after conflict

Hormonal and behavioural effects of motorboat noise on wild coral reef fish

This is the final version. Available on open access from Elsevier via the DOI in this recordAnthropogenic noise is an emergent ecological pollutant in both terrestrial and aquatic habitats. Human population growth, urbanisation, resource extraction, transport and motorised recreation lead to elevated noise that affects animal behaviour and physiology, impacting individual fitness. Currently, we have a poor mechanistic understanding of the effects of anthropogenic noise, but a likely candidate is the neuroendocrine system that integrates information about environmental stressors to produce regulatory hormones; glucocorticoids (GCs) and androgens enable rapid individual phenotypic adjustments that can increase survival. Here, we carried out two field-based experiments to investigate the effects of short-term (30 min) and longer-term (48 h) motorboat-noise playback on the behaviour, GCs (cortisol) and androgens of site-attached free-living orange-fin anemonefish (Amphiprion chrysopterus). In the short-term, anemonefish exposed to motorboat-noise playback showed both behavioural and hormonal responses: hiding and aggression increased, and distance moved out of the anemone decreased in both sexes; there were no effects on cortisol levels, but male androgen levels (11-ketotestosterone and testosterone) increased. Some behaviours showed carry-over effects from motorboat noise after it had ceased, and there was no evidence for a short-term change in response to subsequent motorboat-noise playback. Similarly, there was no evidence that longer-term exposure led to changes in response: motorboat noise had an equivalent effect on anemonefish behaviour and hormones after 48 h as on first exposure. Longer-term noise exposure led to higher levels of cortisol in both sexes and higher testosterone levels in males, and stress-responses to an additional environmental challenge in both sexes were impaired. Circulating androgen levels correlated with aggression, while cortisol levels correlated with hiding, demonstrating in a wild population that androgen/glucocorticoid pathways are plausible proximate mechanisms driving behavioural responses to anthropogenic noise. Combining functional and mechanistic studies are crucial for a full understanding of this global pollutant.Natural Environment Research Council (NERC)Agence National de la RechercheContrat de Projets Etat - Polynésie françaiseCNR

Lu-Hf isotope evidence for the provenance of Permian detritus in accretionary complexes of western Patagonia and the northern Antarctic Peninsula region

Lu–Hf isotope data are presented for dated Permian zircon grains from six samples of the latest Palaeozoic to Jurassic low-grade metasedimentary rocks of western Patagonia and the northern Antarctic Peninsula, as well as from potential source rocks in the North Patagonian Massif. The results for the metasedimentary rocks yield εHf values mostly between −15 and +4 (130 analyses), with a dominant range (more than 85%) of −6 to +1, indicating provenance from Permian magmatic rocks that incorporated continental crust with a significant residence time. Other zircon grains record more negative εHf values indicating derivation from yet more mature crustal sources. Permian subvolcanic granites in the North Patagonian massif appear to be the closest large source area and dated zircon grains from eight samples of these granites yield initial of εHf values of −12 to +4 (45 measurements), 84% of which fall between −6 and +1, the range shown by the metasediments. However, the North Patagonian massif also contains some more juvenile Permian–Carboniferous components not seen in the metasediments, so that this may not be the primary or unique source. These granites are considered to represent the southernmost extension of the Choiyoi igneous province, which contains abundant Permian rhyolites that crop out on the eastern side of the Andes in central Argentina, for which unpublished Hf isotope data yield a very similar range to that of the metasediments. The widespread nature of the Choiyoi volcanic rocks and the predominance of Permian zircon could make this a more favoured source for the detrital grains. Hf isotope data reinforce the uniformity of the provenance of the turbidite detrital zircons and confirm the Choiyoi igneous province and the Permian granitic rocks of the North Patagonian Massif as feasible sources. They further confirm the dominantly crustal origin of the Permian magmas. A source region involving mixing of, for example, crustal materials of Panafrican/Brasiliano and Grenvillian ages, together with a minor but significant subduction-related magmatic input, is an isotopically feasible explanation and is broadly consistent with the provenance of pre-Permian crust in this region, but the proportions of such a mixture must have remained relatively constant. This supports the proposal that recently recognised but widespread Permian magmatism in Patagonia represents voluminous crustal melting in response to subducted slab break-off. The results are also consistent with the premise that the Antarctic Peninsula and southern Patagonia were closely located from Permian to Jurassic times, receiving detritus from the same source

Book reviews

Transnational Corporations and the Global Economy. Edited by Richard Kozul-Wright and Robert Rowthorn. Basingstoke: Macmillan (for United Nations University and World Institute for Development Economics Research), 1998. Pp.448. �55. ISBN 0 333 68957 7 The New Global Economy and Developing Countries: Making Openness Work. By Dani Rodrik. Washington, DC: Overseas Development Council, 1999. Pp.x + 168. $13.95. ISBN 1 56517 027 X Information, Management and Participation: A New Approach from Public Health in Brazil. By Francesco Notarbartolo Di Villarosa London and Portland, OR: Frank Cass, 1998. Pp.xxiii + 145. �19.50/$24.50. ISBN 0 7146 4353 X Informal Politics: Street Vendors and the State in Mexico City. By John Cross. Stanford, CA: Stanford University Press, 1998. Pp.x + 272. �35 and �11.95. ISBN 08047 3060 1 and 3062 8 Evaluation Frameworks for Development Programmes and Projects. By R. Dale. New Delhi: Sage Publications, 1998. Pp.151. �25 and �11.99. ISBN 0 7619 9239 1 and 9240 5 Tourism, Development and Growth: The Challenge of Sustainability. Edited by Salah Wahab and John J. Pigram. London: Routledge, 1997. Pp.320. �50 and �15.99. ISBN 0 415 16001 4 and 16002 2 Tourism and Economic Development in Asia and Australasia. Edited by Frank M. Go and Carson L. Jenkins. London: Cassell, 1997. Pp.384. �60 and �18.99. ISBN 1 85567 417 3 and 567 6 Tourism and Sustainability: New Tourism in the Third World. By Martin Mowforth and Ian Munt. London: Routledge, 1997. Pp.384. �50 and �16.99. ISBN 0 415 13763 2 and 13764 0 Sustainable Rural Development By Andrew Shepherd.Basingstoke: Macmillan, 1998. Pp.304. �40 and �12.99. ISBN 0333 66484 1 and 66485 X Collaboration in International Rural Development: A Practitioner's Handbook. By George H. Axinn and Nancy W. Axinn. London and New Delhi: Sage, 1997. Pp.336. �27.50 and �13. ISBN 0761 99200 6 and 92014 Learning from Somalia: The Lessons of Armed Humanitarian Intervention. Edited by Walter Clarke and Jeffrey Herbst. Oxford: Westview, 1997. Pp.xi + 276. �11.95 and �41.50. ISBN 0 8133 2794 6 and 2793 8 Between Development and Destruction: An Enquiry into the Causes of Conflict in Post-Colonial States. Edited by Luc Van de Goor, Kumar Rupesinghe and Paul Sciarone. Basingstoke: Macmillan Press, 1996. Pp.xx + 376. �14.99. ISBN 1 0333 65038 7