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The Diabetes Care in Haemodialysis (DiH) working group aims to improve the care of people with diabetes mellitus on the haemodialysis unit by supporting the implementation of the 2016 JBDS guidelines. In order to support the implementation of the guideline recommendations the DiH working group have established a set of standards, developed an audit tool to demonstrate adherence to standards, and have developed educational support for haemodialysis staff both online and delivered face-to-face. We publish audit findings from five distinct haemodialysis units, highlighting the impact of the educational programme on the achievement of guideline standards. We also report the impact of the COVID-19 pandemic on diabetes care and quality improvement.

People receiving peritoneal dialysis (PrPD) tend to be physically inactive, with consequent adverse outcomes including increased mortality, reduced technique, and hospitalization free survival. Exercise is a form of planned physical activity which has the potential to improve these outcomes. Feasibility studies suggest that exercise interventions are safe in PrPD. However, the uptake of exercise is low. In this review, we explore the benefits of exercise in this population, noting the limitations in the existing evidence. We highlight the challenges and uncertainties associated with exercise, including the perceptions of patients and clinicians. Finally, the opportunities for increasing exercise uptake are discussed, alongside future research priorities.

This paper seeks to articulate a series of worries surrounding the seeming convergence of recent critical work on animism with contemporary calls to decolonise thought. Sometimes referred to as the 'new animism', these recent approaches valuably question traditional and mainstream notions of Western rationality, perform important critical reforms of formerly dominant anthropological and epistemological perspectives, and open up questions concerning the pervasiveness of something like animism within Western/ modern thought and culture. On the one hand, these effects may be seen as complementing a decolonising imperative. On the other hand, they may also risk contributing to processes of less fundamental epistemological reform, whereby certain elements of the 'European paradigm of modernity/ rationality' (Anibal Quijano) are allowed to remain intact. Prominent among these elements, following Sylvia Wynter, is the constructed figure of 'Man' around which colonial modernity has built and extended itself. In order to pursue these worries, the paper explores key characteristics of what may be considered, according to the terms it has itself established, the animist character of aspects of Western modernity/rationality. It is argued that a widespread acceptance of the reality and validity of the culturally specific figure of Man as representative of all humans, is dependent on a form of animistic investment on the part of European and Western modernity referred to as 'Manimism'. Worrying/being worried about Manimism does not necessitate the abandonment of so-called new-animist work, but may form a worthwhile complement to it, especially in light of the historical capacity of Man and Manimism to survive major socio-political and epistemological challenges and upheavals.

Since the breakthrough of kidney replacement therapy, increases in life expectancy for patients with end-stage kidney disease have been limited. However, patients have become increasingly vocal that, although mortality and life expectancy matter to them, the quality of their life, and particularly the relief of symptoms associated with their treatment, are in many cases more important. The majority of dialysis-associated symptoms and adverse effects do not currently have any approved treatments in this patient population, with the few treatments that are available used off-label, frequently without proven efficacy, yet still potentially adding further adverse effects to patients’ current symptom burden. This article will illustrate how understanding the pathophysiology of a single, particularly burdensome symptom of dialysis (chronic kidney disease-associated pruritus) resulted in the design, development and regulatory approval of a treatment for that symptom. The pathway described here can be applied to other symptoms associated with dialysis, meaning that if we cannot add years to patients’ lives, we can at least add life to their remaining years.

ObjectivesTo assess the applicability of risk factors for severe COVID-19 defined in the general population for patients on haemodialysis.SettingA retrospective cross-sectional study performed across thirty four haemodialysis units in midlands of the UK.ParticipantsAll 274 patients on maintenance haemodialysis who tested positive for SARS-CoV-2 on PCR testing between March and August 2020, in participating haemodialysis centres.ExposureThe utility of obesity, diabetes status, ethnicity, Charlson Comorbidity Index (CCI) and socioeconomic deprivation scores were investigated as risk factors for severe COVID-19.Main outcomes and measuresSevere COVID-19, defined as requiring supplemental oxygen or respiratory support, or a C reactive protein of ≥75 mg/dL (RECOVERY trial definitions), and its association with obesity, diabetes status, ethnicity, CCI, and socioeconomic deprivation.Results63.5% (174/274 patients) developed severe disease. Socioeconomic deprivation associated with severity, being most pronounced between the most and least deprived quartiles (OR 2.81, 95% CI 1.22 to 6.47, p=0.015), after adjusting for age, sex and ethnicity. There was no association between obesity, diabetes status, ethnicity or CCI with COVID-19 severity. We found no evidence of temporal evolution of cases (p=0.209) or clustering that would impact our findings.ConclusionThe incidence of severe COVID-19 is high among patients on haemodialysis; this cohort should be considered high risk. There was strong evidence of an association between socioeconomic deprivation and COVID-19 severity. Other risk factors that apply to the general population may not apply to this cohort.

BACKGROUND AND AIMS Individuals hospitalized with hyperkalaemia (HK) and chronic kidney disease (CKD) are at very high risk of HK recurrence, which often requires hospital re-admission [1]. Recurrent HK events have a significant impact on healthcare resource utilization (HCRU) and costs [2]. Several approaches, such as reduction in dietary potassium (K+), reduction or discontinuation of diuretic and renin-angiotensin-aldosterone system inhibitor (RAASi), or oral K+ binders may be used to manage HK in the outpatient setting. Sodium zirconium cyclosilicate (SZC) is an orally administered, non-absorbed, highly selective K+ binder approved for the treatment of HK in adults. In phase 3 trials, after achieving normokalaemia (NK), individualized once-daily SZC therapy maintained normal range serum K+ levels for up to 1 year in adult outpatients [3]. However, it is unknown if SZC prevents HK recurrence compared with standard of care (SoC). Here, we present the rationale and design of the phase 4 CONTINUITY study (D9480C00023), which will compare the efficacy of continued SZC treatment, as part of the post-discharge medication regimen, with SoC, in maintaining NK and reducing HK-related hospital admissions and emergency department (ED) visits. METHOD CONTINUITY is a randomized controlled, open-label, parallel-group, multicentre study in participants with CKD treated for HK while in hospital, to be conducted in 30–50 study sites across four to seven European countries. The study will comprise both an in-hospital and an outpatient (post-discharge) phase (Figure). During the in-hospital phase, all participants will be treated with SZC to correct HK (SZC 10 g three times daily, up to 72 h) and maintain NK (SZC from 5 g every other day to 10 g once daily) as per local label for 2–14 days. At discharge, participants with NK established on an SZC maintenance dose will be randomised (1:1) to either SZC per local label (Arm A) or SoC per local practice (Arm B); participants intended to be discharged with a K+ binder will not be randomized and will be discontinued from the study. Following randomization, participants enter the outpatient phase and will be monitored for 180 days post-discharge via seven planned follow-up visits or phone calls, followed by a site visit at 7 days after end of treatment (Figure). Participants will be screened to yield 506 entering the in-hospital phase, resulting in 430 participants discharged and randomized (215 per arm) and 344 evaluable participants. Adults (≥18 years) with stage 3b–5 CKD or eGFR CONCLUSION CONTINUITY is the first study to examine the efficacy of extended use of a novel K+ binder post-discharge compared with SoC, on the maintenance of NK and reduced HCRU among patients with HK, with CKD stage 3b–5. This study will address the importance of maintaining NK after discharge in routine clinical practice, and the impact of improved management of patients with CKD and HK.

PurposeThis paper argues that policymakers and academics should place more emphasis on maximising the additional benefit created by entrepreneurial support programs and impact investments. It demonstrates a robust approach to advancing this field of research by using qualitative methods to determine the variables that may predict the additional benefit a firm will gain from funding.Design/methodology/approachThe research is based on 60 semi-structured interviews averaging 1.5 h each; 45 with entrepreneurs that did or did not receive funding from a business plan competition in Nigeria, 15 with relevant elites. Detailed World Bank panel data on program participants further validated responses and supported conclusions.FindingsNumerous factors that may explain additional benefit were uncovered, including those that vary the need for external funding and those that vary access to it.Research limitations/implicationsQualitative methods explored variables previously assumed to be unobservable. Future studies are necessary to test the results quantitatively.Social implicationsUnderstanding the characteristics that indicate ex ante which firms would most benefit from support will help policymakers, impact investors and development institutions to more effectively allocate capital.Originality/valueThis paper addresses the paucity of research into increasing additional impact and demonstrates the value of pursuing it. Methods used to suggest additionality variables for such programs and many of the factors highlighted are unique to this study. The research is also based on unique access to the participants and un-anonymised data from a significant World Bank study, and on substantially more interviews than previous papers.

Protein-protein interactions (PPIs) play a crucial role in the regulation of protein activity, and are therefor of great importance in biology. Interactions between proteins require a certain degree of specificity, as the functional regulation of a protein needs to occur within a particular signal cascade and cannot be triggered by non-native interactions. At the same time, most PPIs are dominated by long- range coulombic interactions, which attract positively and negatively charged proteins, or patches of a protein, towards each other. In cases where the secondary structures of the two interacting proteins in infinite dilution are complementary towards the formation of the active complex, the association rate constant becomes diffusion-limited. However, many active protein complexes require some degree of conformational sampling after the formation of the initial encounter, which adds a second rate-limiting step.xvThe work presented herein details the molecular association and regulatory mechanisms of three unique protein complexes. The primary methods that I employed in this dissertation include two forms of atomistic dynamics simulations, specifically molecular dynamics (MD) and Brownian dynamics (BD), which I use both separately and in tandem. First, I discuss my BD/MD generated model of the cytochrome P450cin/Cindoxin complex. Very few crystal structures exist of cytochrome P450 protein complexes. Our BD/MD complex allowed us to characterize the electron transfer pathway in the P450cin/Cindoxin complex. In another case where a complex crystal structure was previously solved, the Leishmania major peroxidase-cytochrome c complex, BD simulations helped to reveal the first encounter site that plays a role in the formation of the active complex. Finally, I detail the regulation of the water channel protein, aquaporin 0 (AQP0) by external calcium concentration, phosphorylation, and pH.

A trio of themes recur across prominent Western theories of laughter: violence, the human/nonhuman, and error. The paper traces this trio through a series of frequently cited paradigms for understanding laughter, including superiority, incongruity and relief theories, Henri Bergson’s theory of laughter and V. S. Ramachandran’s false alarm theory; and argues that it reflects a shared, if partially submerged concern with the instability and demise of a particular figure of the human, one that is circumscribed by the culturally specific (if globally influential) values of Eurocentric/Western thought, largely corresponding to Sylvia Wynter’s ‘Man’. This suggests that laughter has an ambiguous immanent potential for both undermining and/or reasserting, de- and/or restabilising the illusion of Man’s universalizing drive to identify itself with the human per se. James Burton, ‘The Animal That Laughs at Itself: False False Alarms about the End of “Man”’, in Errans: Going Astray, Being Adrift, Coming to Nothing, ed. by Christoph F. E. Holzhey and Arnd Wedemeyer, Cultural Inquiry, 24 (Berlin: ICI Berlin Press, 2022), pp. 49-74

Recognizing the imperative to evaluate species recovery and conservation impact, in 2012 the International Union for Conservation of Nature (IUCN) called for development of a "Green List of Species" (now the IUCN Green Status of Species). A draft Green Status framework for assessing species' progress toward recovery, published in 2018, proposed 2 separate but interlinked components: a standardized method (i.e., measurement against benchmarks of species' viability, functionality, and preimpact distribution) to determine current species recovery status (herein species recovery score) and application of that method to estimate past and potential future impacts of conservation based on 4 metrics (conservation legacy, conservation dependence, conservation gain, and recovery potential). We tested the framework with 181 species representing diverse taxa, life histories, biomes, and IUCN Red List categories (extinction risk). Based on the observed distribution of species' recovery scores, we propose the following species recovery categories: fully recovered, slightly depleted, moderately depleted, largely depleted, critically depleted, extinct in the wild, and indeterminate. Fifty-nine percent of tested species were considered largely or critically depleted. Although there was a negative relationship between extinction risk and species recovery score, variation was considerable. Some species in lower risk categories were assessed as farther from recovery than those at higher risk. This emphasizes that species recovery is conceptually different from extinction risk and reinforces the utility of the IUCN Green Status of Species to more fully understand species conservation status. Although extinction risk did not predict conservation legacy, conservation dependence, or conservation gain, it was positively correlated with recovery potential. Only 1.7% of tested species were categorized as zero across all 4 of these conservation impact metrics, indicating that conservation has, or will, play a role in improving or maintaining species status for the vast majority of these species. Based on our results, we devised an updated assessment framework that introduces the option of using a dynamic baseline to assess future impacts of conservation over the short term to avoid misleading results which were generated in a small number of cases, and redefines short term as 10 years to better align with conservation planning. These changes are reflected in the IUCN Green Status of Species Standard.Reconociendo que era imperativo evaluar la recuperación de especies y el impacto de la conservación, la Unión Internacional para la Conservación de la Naturaleza (UICN) convocó en 2012 al desarrollo de una “Lista Verde de Especies” (ahora el Estatus Verde de las Especies de la UICN). Un marco de referencia preliminar de una Lista Verde de Especies para evaluar el progreso de las especies hacia la recuperación, publicado en 2018, proponía 2 componentes separados pero interconectados: un método estandarizado (i.e., medición en relación con puntos de referencia de la viabilidad de especies, funcionalidad y distribución antes del impacto) para determinar el estatus de recuperación actual (puntuación de recuperación de la especie) y la aplicación de ese método para estimar impactos en el pasado y potenciales de conservación basados en 4 medidas (legado de conservación, dependencia de conservación, ganancia de conservación y potencial de recuperación). Probamos el marco de referencia con 181 especies representantes de diversos taxa, historias de vida, biomas, y categorías (riesgo de extinción) en la Lista Roja de la IUCN. Con base en la distribución observada de la puntuación de recuperación de las especies, proponemos las siguientes categorías de recuperación de la especie: totalmente recuperada, ligeramente mermada, moderadamente mermada, mayormente mermada, gravemente mermada, extinta en estado silvestre, e inderterminada. Cincuenta y nueve por ciento de las especies se consideraron mayormente o gravemente mermada. Aunque hubo una relación negativa entre el riesgo de extinción y la puntuación de recuperación de la especie, la variación fue considerable. Algunas especies en las categorías de riesgo bajas fueron evaluadas como más lejos de recuperarse que aquellas con alto riesgo. Esto enfatiza que la recuperación de especies es diferente conceptualmente al riesgo de extinción y refuerza la utilidad del Estado Verde de las Especies de la UICN para comprender integralmente el estatus de conservación de especies. Aunque el riesgo de extinción no predijo el legado de conservación, la dependencia de conservación o la ganancia de conservación, se correlacionó positivamente con la potencial de recuperación. Solo 1.7% de las especies probadas fue categorizado como cero en los 4 indicadores de impacto de la conservación, lo que indica que la conservación ha jugado, o jugará, un papel en la mejoría o mantenimiento del estatus de la especie la gran mayoría de ellas. Con base en nuestros resultados, diseñamos una versión actualizada del marco de referencia para la evaluación que introduce la opción de utilizar una línea de base dinámica para evaluar los impactos futuros de la conservación en el corto plazo y redefine corto plazo como 10 años.

Although a number of authors have used diagrams extensively in their studies of Navya-Nyāya, they have done so to explain and illustrate concepts, not with the goal of reasoning with the diagrams themselves. Adherents of diagrammatic reasoning have made claims for its potential by pointing to key structural correspondences between diagrams and logical concepts, arguably lacking in sentential representations, and describing these relations using concepts such as “well matchedness” and “iconicity”. A canonical example of this iconicity is the use of Euler diagrams to depict categorical syllogisms. Since the meaning of expressions in Indian logic differs in so many important ways from logic in the Western tradition, the use or adaptation of diagrams developed in the latter would seem to preclude iconicity. Thus, the development of diagrams which reflect the nature of inference in Navya-Nyāya, which centres on the anumāna inference schema, is motivated. In this paper we extend Ganeri’s method of depicting the Vaiśeṣika ontology with graphs to include syntax intended to expose the nature of anumāna. The diagrams are given a formal basis: i.e. abstract syntax, inference rules defined abstractly and a graph-theoretic semantics. These are the first formalised logical diagrams that aim to reflect the nature of the anumāna inference. This paper lays the way for further work in extending the formalism to cover more of Navya-Nyāya, and in exploring a dialogue between properties of the formalism and of Navya-Nyāya.

Extension and intension are two ways of indicating the fundamental meaning of a concept. The extent of a concept, C, is the set of objects which correspond to C whereas the intent of C is the collection of attributes that characterise it. Thus, intension defines the set of objects corresponding to C without naming them individually. Mathematicians switch comfortably between these perspectives but the majority of logical diagrams deal exclusively in extension. Euler diagrams indicate sets using curves to depict their extent in a way that intuitively matches the relations between the sets. What happens when we use spatial diagrams to depict intension? What can we infer about the intension of a concept given its extension, and vice versa? We present the first steps towards addressing these questions by defining extensional and intensional Euler diagrams and translations between the two perspectives. We show that translation in either direction leads to a loss of information, yet preserves important semantic properties. To conclude, we explain how we expect further exploration of the relationship between the two perspectives could shed light on connections between diagrams, extension, intension, and well-matchedness.

Ileal pouch-anal anastomosis (IPAA) is a common surgical treatment for ulcerative colitis. Afferent limb stenosis is an infrequent complication following IPAA, suggesting underlying Crohn's disease (CD). We hypothesized that CD-related single nucleotide polymorphisms (SNPs) are associated with afferent limb stenosis.Afferent limb stenosis and CD control group patients were recruited from a prospective institutional inflammatory bowel disease database and associated biobank. Patient demographics, Montreal classification, and medication use were recorded. Ten SNPs associated with stricturing Crohn's disease were examined in genomic DNA and compared among afferent limb stenosis, stricturing CD, and non-stricturing CD controls.Twenty-seven afferent limb stenosis and 162 CD control group patients (108 stricturing, 54 non-stricturing) were identified. Patients were gender and race matched. Afferent limb stenosis and stricturing CD controls were younger at diagnosis (Montreal A1/A2 vs. A3) compared to non-stricturing CD controls (both p0.05). The majority of afferent limb stenosis patients were non-smokers compared to CD controls (74% vs. 36%, p0.01) and did not use biologic therapies (4% vs. 37%, p0.001). The FUT2 G allele was more frequent in afferent limb stenosis and stricturing CD controls compared to non-stricturing CD controls (both p0.05). The NOD2 T allele was more frequent in stricturing CD controls compared to afferent limb stenosis and non-stricturing CD controls (both p0.05).Afferent limb stenosis patients are phenotypically similar to stricturing CD controls, but differ with lower smoking rates and lower NOD2 allele frequency. Such differences could contribute to the presentation delay with a stricturing phenotype. Selective SNP assessment may help categorize patients likely to develop afferent limb stenosis.

Spider diagrams are based on Euler and Venn/Peirce diagrams, forming a system which is as expressive as monadic first order logic with equality. Rather than being primarily intended for logicians, spider diagrams were developed at the end of the 1990s in the context of visual modelling and software specification. We examine the original goals of the designers, the ways in which the notation has evolved and its connection with the philosophical origins of the logical diagrams of Euler, Venn and Peirce on which spider diagrams are based. Using Peirce’s concepts and classification of signs, we analyse the ways in which different sign types are exploited in the notation. Our hope is that this analysis may be of interest beyond those readers particularly interested in spider diagrams, and act as a case study in deconstructing a simple visual logic. Along the way, we discuss the need for a deeper semiotic engagement in visual modelling.

Logical diagrams are known to have certain advantages over sentential notations for particular reasoning tasks: using a diagram may make logical consequences directly evident, when these consequences are “hidden” in an equivalently expressive sentential language. This phenomenon is known as a “free ride” or “observational advantage”. Where does this advantage come from, and why? We answer this question by distinguishing two general kinds of logical languages: occurrence-referential languages, in which sameness of reference (for sentential and predicate variables) is determined by the sameness of variable occurrence, and type-referential languages, in which sameness of variable type determines sameness of reference. We explain that it is the occurrence-referential nature of some languages that explains for their observational advantage over equivalently expressive type-referential languages.

This paper presents an empirical study to determine whether alterations to graphical features (colour and size) of automatically generated LineSets improve task performance. LineSets are used to visualise sets and networks. The increasingly common nature of such data suggests that having effective visualisations is important. Unlike many approaches to set and network visualisation, which often use concave or convex shapes to represent sets alongside graphs, LineSets use lines overlaid on a graph. LineSets have been shown to be advantageous over shape-based approaches. However, the graphical properties of LineSets have not been fully explored. Our results suggest that automatically drawn LineSets can be significantly improved for certain tasks through the considered use of colour alongside size variations applied to their graphical elements. In particular, we show that perceptually distinguishable colours, lines of varying width, and nodes of varying diameter lead to improved task performance in automatically laid-out LineSets.

Collaboration with all members of the multidisciplinary team remains a key focus for the British Renal Society, and this year's conference theme looks at ways in which health professionals specialising in kidney care can tackle inequalities in the health service. Helen Hurst and James Burton, the programme co-chairs, discuss the highlights of the forthcoming event.

The parasite is widely conceived as a negative figure that takes without giving; perceived as an agent of corruption and destruction, it is subjected to programmes of eradication and expulsion across cultural, economic, political and ethical contexts. This paper offers an alternative approach to the status of parasitic relations in light of Michel Serres’s The Parasite, elaborated through ethnographic research into the after-hours culture and hidden economy of London’s Borough Market. We highlight the mutual dependence of agents in host-parasite networks according to what we term ‘general parasitism’, while inquiring into its ethical potential. Ultimately, we argue that while taking into account the near ubiquity of parasitic relations cannot form the basis for any concrete axiomatic ethical paradigm, it should at least encourage an ethics of hesitation before judgement when faced with any apparent instance of parasitism: to presume that parasitism is undesirable and unethical is itself undesirable and unethical.