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Accuracy of glomerular filtration rate estimation using creatinine and cystatin C for monitoring moderate chronic kidney disease in adults: prospective, longitudinal, cohort study
No full textObjectives To provide evidence on the longitudinal accuracy of glomerular filtration rate (GFR) estimating equations that include creatinine and cystatin C to monitor patients with moderate chronic kidney disease.Design Prospective, longitudinal, cohort study.Setting Primary, secondary, and tertiary care across six centres in England, 1 April 2014 to 31 December 2017.Participants 1229 adults (≥18 years) with moderate chronic kidney disease (creatinine estimated GFR of 30-59 mL/min/1.73 m2 for at least three successive months before recruitment).Main outcome measures Ability of estimating equations to monitor GFR over three years, with slope deviations from reference measured GFR (iohexol clearance) within ±3 mL/min/1.73 m2/year indicating agreement. Ability of GFR estimating equations to detect disease progression (ie, a reduction in measured GFR of ≥25% with a reduction in disease category).Results After three years, 875 participants had measured and estimated GFR data recorded at the start and end of the study and comprised the study cohort. Median measured GFR decreased from 48.1 mL/min/1.73 m2 at baseline to 43.6 mL/min/1.73 m2 at three years. GFR was estimated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and European Kidney Function Consortium (EKFC) estimating equations. Median change in measured GFR exceeded median change in estimated GFR for all equations. All equations achieved agreement with change in measured GFR in >72.5% of participants. Dual biomarker equations showed better agreement with change in measured GFR (CKD-EPIcreatinine-cystatin 78.6% of individuals, 95% confidence interval 75.8% to 81.3%; CKD-EPI(2021)creatinine-cystatin 78.1%, 75.2% to 80.8%; and EKFCcreatinine-cystatin 80.2%, 77.4% to 82.8%) than CKD-EPIcreatinine (73.1%, 70.1% to 76.1%) (all P90.4%) for identifying progression of chronic kidney disease.Conclusions Underestimation of the reduction in GFR by estimated GFR requires further investigation. Equations that included both creatinine and cystatin C more accurately monitored change in measured GFR than equations based on one biomarker. Increased use of combined biomarker equations in clinical practice could improve disease monitoring and potentially clinical care
Recognizing future generations under the International Covenant on Economic, Social and Cultural Rights: An overdue reappraisal
Full text linkIn the face of multiple threats to humanity’s future existence and well-being, international law is increasingly evolving in the direction of recognizing human rights obligations towards future generations (FG). This article explores whether the leading international human rights treaty protecting economic, social, and cultural rights, the International Covenant on Economic, Social, and Cultural Rights, can be understood and interpreted to apply to FG. It finds that, although FG were not expressly contemplated as rights holders at the time of the Covenant’s drafting, a teleological and evolutionary interpretation of the Covenant supports the recognition of obligations towards FG. The article proceeds to argue that, whilst the recognition of obligations towards FG under the Covenant represents a welcome development, it must be accompanied by a fundamental reappraisal of many of the foundational doctrines of the International Covenant on Economic, Social, and Cultural Rights. The direction that this reappraisal should take is explored in the context of two key doctrines—progressive realization and the maximum of available resources
Conjugated bilirubin in chronic liver disease: an underutilised prognostic biomarker?—a narrative review
Full text linkBackground and Objective: Chronic liver disease (CLD) is a major global health burden, often progressing to cirrhosis, decompensation, and hepatocellular carcinoma. Prognostic models typically rely on serum total bilirubin. However, recent evidence suggests that conjugated bilirubin (C-BIL) may offer superior prognostic utility in assessing disease severity and outcomes in CLD. This narrative review aims toexamine the emerging evidence supporting C-BIL as a prognostic and disease stratification biomarker across various clinical contexts, where it has demonstrated enhanced predictive accuracy over traditional measures.Methods: A comprehensive, non-systematic review of the published literature was undertaken using major bibliographic databases and predefined keywords. Relevant studies were selected based on the following criteria: English-language publications, studies conducted in human populations, and articles with clear clinical applicability. Emphasis was placed on studies evaluating C-BIL in prognostic or disease-stratification contexts within chronic liver disease.Key content and findings: Emerging evidence indicates that incorporation of C-BIL into clinical prognostic models may enhance risk stratification and support more informed clinical decision-making in CLD. Elevated C-BIL appears to reflect impaired hepatocellular excretory function and fibrosis-related biliary obstruction. In addition, recent studies suggest that hepatocyte senescence may represent an additional, biologically plausible mechanism underpinning its prognostic relevance.Conclusions: This review highlights the potential clinical utility of C-BIL as a prognostic biomarker in CLD. While existing evidence supports its role in disease stratification and outcome prediction, further prospective validation and mechanistic studies are required before C-BIL can be adopted as a standardcomponent of prognostic assessment in CLD
When Words Meet Visuals: How Content Composition Drives Social Media Engagement for Marketer-Generated Content
Full text linkHow does the balance between text and pictorial content in marketer-generated social media posts affect user engagement? The authors address this question by using computer vision and natural language processing tools to extract the visual and textual features of 34,610 organic brand posts from Facebook and Instagram. Using a confounding-and-cluster-robust causal forests model, they test how the balance of text and picture affects social media engagement across content and visual contexts. Results show that posts with greater emphasis on overlay text over pictorial content tend to have fewer likes and comments. However, the performance of text-oriented posts improves if text is more centered, informative, emotionally positive, and congruent with the pictorial content and if the picture contains fewer prominent objects or less information such as social cues. They quantify how incremental changes in such content composition affect social media engagement. These findings set forth evidence-based principles for optimizing text and picture balance in marketer-generated content and provide actionable guidelines on whether, where, when, and how to present text on an image. This research highlights the potential for transforming content and media creation from an imprecise art form into an empirical science nested within a data-driven visual optimization framework
Genetic subtypes associated with multiple sclerosis severity and response to treatment
Full text linkBackground Predicting response to treatment and long-term disability in multiple sclerosis (MS) remains challenging. In other complex diseases, combining genetic risk variants has enabled the detection of relevant clinical endophenotypes associated with important outcomes, but this strategy has never been applied to MS.Methods We applied unsupervised hierarchical clustering to genomic risk scores in a prospective Welsh MS cohort (n=1455) and replicated the findings in the postmortem Netherlands Brain Bank (NBB) MS (NBB-MS) cohort (n=272). Disease progression was assessed using survival analysis to determine the time to Expanded Disability Status Scale (EDSS) milestones.Results Three genomic clusters were identified, each with similar genetic profiles. Baseline demographics did not differ between clusters. Welsh patients in cluster 1 attained EDSS 6 and EDSS 8 significantly later than clusters 2 and 3 (by 6 years, p=3×10−3 and 13 years, p=0.02, respectively). These findings were replicated in the NBB-MS cohort (6-year delay to EDSS 6 for cluster 1 vs 2, p=0.04). Genomic clustering independently predicted disease progression (HRs 1.3–2.0, all p<0.05), beyond established risk factors. Clusters 2 and 3 showed a greater annual increase in T2 lesion load on serial MR imaging (p=0.04). In cluster 2, patients receiving disease-modifying treatments had delayed progression to EDSS 6 (p=3×10−³), while no such benefit was observed in clusters 1 or 3. Cluster 2 patients also had earlier onset of symptoms, including dysphagia (p=0.02) and spasticity (p=8×10−⁴) in the NBB-MS cohort.Conclusions Genetic clustering reveals clinically meaningful MS subtypes with distinct prognoses and treatment responses, highlighting its potential role in precision medicine for MS management
NETosis in ischemic stroke: Mechanisms, implications, and therapeutic prospects
Full text linkIschemic stroke remains a major global health burden, with secondary mechanisms of injury playing a critical role in initiation and progression of long-term neurological outcomes. Among these, the formation of neutrophil extracellular traps (NETosis) has gained significant traction as a key process that links innate immune activation with thrombotic and inflammatory damage in stroke. Shortly after the onset of cerebral ischemia, neutrophils rapidly infiltrate the affected tissue and undergo NETosis in response to Damage Associated Molecular Pattern (DAMPs) and inflammatory cues, releasing NET structures that interact with platelets, endothelial cells, and coagulation pathways. These NET components promote thrombus formation, enhance its structural stability, and confer resistance to fibrinolytic therapies, all while aggravating blood–brain barrier (BBB) breakdown, neuronal injury, and downstream neuroinflammatory cascades disturbing gut-brain axis and post stroke recovery.Clinical and pre-clinical investigations have shown that NET-related markers such as citrullinated histone H3, Myeloperoxidase (MPO)–DNA complexes, and circulating cell-free DNA are closely associated with stroke severity, infarct burden, and poorer clinical recovery, supporting their use as potential prognostic indicators. Experimental strategies aimed at inhibiting NET formation or accelerating its dissolution, including DNase-I administration, Peptidyl arginine deiminase 4 (PAD4) inhibition, and blockade of MPO activity, have demonstrated neuroprotective effects by reducing infarct size, preserving BBB function, and enhancing functional outcomes in animal models. Despite these encouraging findings, translating NET-targeted therapies into clinical practice remains complex due to the diversity of patient profiles and comorbidities that are weighing down translation efforts. This review highlights the central contribution of NETosis to stroke-related thrombosis, BBB disruption, and sustained inflammation, while emphasising the evolving potential of NET-focused interventions as future therapeutic tools in Ischemic stroke
Police Custody Arrest Reasons: Offence Category Reference Tool
No full textThis reference tool provides a standardised classification of arrest reason descriptions into offence categories, developed through analysis of electronic police custody record data from eight police forces in England and Wales. It is designed to support researchers, police forces, and other agencies working with police custody data to classify arrest reasons consistently and efficiently
“It’s very hard to feel accepted when a whole country screams that they don’t want you here”: Minorities’ Experiences of the UK 2024 Summer Riots
Full text linkResearch on civil unrest often centres on general populations, obscuring minority experiences. Understanding the experiences of marginalised groups becomes imperative when these periods are centred around marginalised identities, as with rising anti-immigration-based unrest. This qualitative study examines how ethnically and religiously minoritised adults in the United Kingdom experienced the Summer 2024 riots, a period marked by widespread anti-immigration sentiments, riots, and intergroup tensions. Twenty-one semi-structured interviews were transcribed and analysed using inductive, reflexive thematic analysis. Four themes captured participants' accounts. First, governing meaning and order: platforms, news, and local networks circulated warnings, rumours, and corrections that shaped expectations and behaviour. Second, living on alert: perceived threat prompted safety planning, curtailed mobility, and other micro-adaptations in daily routines. Third, legible bodies: visibility via phenotype, dress, and religious symbols patterned uneven exposure, while limited ‘passing’ afforded conditional protection. Fourth, conditional belonging: participants narrated ambivalence toward national symbols and calibrated when and how to express Britishness. Across interviews, respondents reported sustained emotional strain, cautious behavioural change, and identity work structured by recognition and visibility. Findings highlight how online and offline environments intertwine to organise everyday life during unrest and suggest implications for platform governance, community safety planning, and culturally responsive mental-health support
Telerehabilitation for early-stage Parkinson's disease: A randomized controlled feasibility trial of individualised real-time physiotherapy delivered via a videoconference platform
Full text linkIntroductionExercise can improve outcomes for people with Parkinson's. Telerehabilitation (TR) may lower costs and maximise clinician time but its efficacy for gait and balance in early Parkinson's is uncertain. We conducted a randomized controlled feasibility trial of individualised real-time physiotherapy delivered via videoconference.MethodsWe recruited people with early (<4 years’ duration) Parkinson's from 2 English NHS hospitals. The TR group had 1 × 60 min, 4 × 30 min video calls and 2 × 10 min calls. These calls occurred within 12 weeks of randomization. Experienced physiotherapists prescribed individualized exercises. The usual care group received standard exercise advice from their physician. Physical activity was measured using Fitbit Inspire. A qualitative process evaluation was undertaken.Results84 people were screened, 64 were eligible and 40 recruited. 21 and 19 were randomized to TR and usual care respectively. 90% of study instruments were completed per protocol.Median [interquartile range; IQR] change in Unified Parkinson's Disease Rating Scale (UPDRS) at six months was −3.5 [−8 to 2.5] for the TR group and 7 [0 to 17] for usual care, effect size (Cohen's D = −0.537). Median [IQR] change in weekly step count was 4215 [−8769 to 19664] for the TR group versus −2185 [−10764 to 3143] for usual care (Cohen's D = 0.198). Participants found the intervention acceptable. Most participants were confident in using the videoconference systems.ConclusionA definitive trial of TR for early Parkinson's is feasible. UPDRS and step count are suitable outcomes
Deteriorating leather bindings: an FTIR and SEM study
Full text linkDeteriorated leathers display greater spatial inhomogeneity of spectral features than undeteriorated leathers when examined non-destructively with attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. A new ratio of peak heights was developed as a way of numerically categorising the level of deterioration that is applicable to whole leather-bound tomes or strips and scrapings. In addition, ATR-FTIR spectroscopy can be used to distinguish between types of tannins in leathers in a non-destructive way. This could impact on conservation methods and allow identification of the geographic origins of tannins used in the leather trade in the past centuries. Complementary scanning electron microscopy (SEM) analysis revealed for the first time that the characteristic red rot powder is made of short and thin collagen fibres. SEM analysis did not show the grain pattern that could identify the animal origin of a tome. Furthermore, the aspects of red rot deterioration observed with SEM, such as surface erosion, tangling of fibres, and loss of matrix cohesion, appeared very similar to non-red rot deterioration (hydrolysis, oxidation and gelatinisation). Both FTIR and SEM analysis showed that a thick top layer of dye can disguise signs of deterioration, but the fibres below this layer show expected deterioration
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