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A virtual trial to identify cardiovascular biomarkers for differentiating diabetic and hypertensive kidney disease
Full text linkPurpose
A diagnostic challenge in the management of chronic kidney disease (CKD) is distinguishing diabetic kidney disease (DKD) from hypertensive kidney disease (HKD) in patients with coexisting diabetes mellitus (DM) and hypertension (HTN), because accurate diagnosis often depends on renal biopsy as a reference standard. This study proposes a modeling approach to identify cardiovascular biomarkers for differentiating DKD from HKD.
Methods
An existing whole-body circulation model of the vascular tree was extended with a detailed renal circulation network to predict biomarkers measured at different locations. The model parameterized sex, age, and disease factors and was used to conduct virtual clinical trials that identified individual and combined biomarkers for DKD-HKD differentiation. Biomarkers were identified with univariate and multivariate analysis and characterized with the area under the receiver operating characteristic curve (AUC).
Results
Results show that the strongest individual biomarker that is commonly used in clinical practice is pulsatility index (PI) measured in the main renal artery, with an AUC of 0.87. Among all evaluated two-biomarker combinations, PI and resistive index (RI) measured in the same artery achieved the highest classification performance (AUC 0.94). In comparison, the highest performance among three-biomarker combinations (AUC 0.96) is achieved by mean blood flow rate, systolic blood flow rate, and diastolic flow rate.
Conclusion
This modeling work suggests that cardiovascular biomarkers can assist in differentiating DKD and HKD, and proposes specific hypotheses that form a strong rationale for targeted clinical trials. If confirmed, these methods could enable non-invasive assessment of renal vascular alterations associated with DKD and HKD, reducing reliance on kidney biopsies for diagnostic evaluation
Introduction: social innovation and the Sustainable Development Goals (SDGs)
No full textSocial innovation has an important role to play in achieving the UN 2030 Agenda for Sustainable Development and the 17 Sustainable Development Goals (SDGs). Yet, knowledge of how, where, and even if this occurs remains limited and scattered across disciplines. This Edward Elgar Companion aims to contribute to addressing this problem, providing scholarly insights and implications for policy and practice. This chapter introduces the Companion. It begins by reviewing and positioning the Companion and its chapters in the context of extant literature, debates, and practice. This includes defining key terms―particularly social innovation. We propose a novel ‘propeller’ conceptualization of social innovation and the SDGs, which constitutes a key scholarly contribution of the chapter and which we use to structure the rest of the Companion. We conclude the chapter by introducing the different chapters in the book and offering possible directions for future scholarship
Resolving consecutive excited-state evolution in Fe-amido chromophores by wide-band optical transient absorption spectroscopy
Full text linkA detailed understanding of excited-state evolution is critical to realizing the full potential of abundant-metal coordination complex photosensitizers. Here, we show how wide-band optical transient absorption spectroscopy (oTA) can delineate the complete energy relaxation pathway of the photoexcited state of Fe(II) polypyridyl complexes supported by benzannulated diarylamido ligands. By covering a broader spectral region from 370 to 1200 nm, we resolve consecutive evolution of a photoexcited Fe-amido chromophore from an initially generated singlet ‘π-antibonding-to-ligand’ charge transfer (1PALCT) excited state to a long-lived metal-centred quintet (5MC) via both a 3PALCT and what we assign as a 3MC state. Notably, we identify spin-parity transformations by observing photogeneration of the 1PALCT followed by its conversion into a 3PALCT state, and the subsequent 3MC-to-5MC transformation via observation of an isosbestic point in the oTA spectral dynamics. The state-to-state transformations are accompanied by coherent oscillations which are impulsive Raman-induced, originating in the ground state. Combining high-resolution, wide-band oTA experiments with the unique absorptive properties of diarylamido ligand–metal complexes, we are thus able, for the first time, to trace the complete deactivation trajectory of an iron(II) polypyridyl sensitizer using optical spectroscopy
Deep learning models to map osteocyte networks from confocal microscopy can successfully distinguish between young and aged bone
Full text linkOsteocytes, the most abundant and mechanosensitive cells in bone tissue, play a pivotal role in bone homeostasis and mechano-responsiveness, orchestrating the delicate balance between bone formation and resorption under daily activity. Studying osteocyte connectivity and understanding their intricate arrangement within the lacunar canalicular network is essential for unravelling bone physiology, which is significantly disrupted during ageing. Much work has been carried out to investigate this relationship, often involving high resolution microscopy of discrete fragments of this network, alongside advanced computational modelling of individual cells. However, traditional methods of segmenting and measuring osteocyte connectomics are time-consuming and labour-intensive, often hindered by human subjectivity and limited throughput. In this study, we explored the application of deep learning and computer vision techniques to automate the segmentation and measurement of osteocyte connectomics, enabling more efficient and accurate analysis. For this specific application, once trained, the analysis was completed within 10 seconds, compared to manual segmentation time of 130 hours. We compared a number of state-of-the-art computer vision models (U-Nets and Vision Transformers) to successfully segment the osteocyte network, finding that an Attention U-Net model can accurately segment and measure 81.8% of osteocytes and 42.1% of dendritic processes, when compared to manual labelling. While further development is required, we demonstrated that this degree of accuracy is already sufficient to distinguish between bones of young (2-month-old) and aged (36-month-old) mice, as well as partially capturing the degeneration induced by genetic modification of osteocytes. Comparison of the model predictions with manual measurements showed no significant difference, indicating that, with additional training, such deep learning algorithms could be trained to human-level accuracy when measuring the osteocyte network. By harnessing the power of these advanced technologies, further developments will likely shed light on the complexities of osteocyte networks with ever-increasing efficiency
How close is too close? The practice and politics of lived experience in contemporary art, academic history and the medical humanities
Full text linkPatient experiences of polymyalgia rheumatica: a qualitative narrative literature review
Full text linkObjectives
PMR is a common inflammatory condition characterized by pain and stiffness in the shoulders and hips. Patient experiences of PMR remain underexplored and often diverge significantly from clinician perspectives, contributing to the overall burden of the disease. This review forms part of an ongoing project conducted by the PMR Working Group of Outcome Measures in Rheumatology (OMERACT) with the aim of exploring patient views of ‘relapse’ and ‘remission’.
Methods
A comprehensive search was conducted across four electronic databases (Ovid MEDLINE, Ovid EMBASE, The Cochrane Library and CINAHL) from database inception to 31/01/2025, to identify qualitative studies reporting patient experience in PMR. Study quality was appraised using the Critical Appraisal Skills Programme qualitative tool, and thematic synthesis used to integrate findings.
Results
Five studies met inclusion criteria and thematic analysis revealed three overarching themes: (1) the pathway to diagnosis, (2) managing uncertainty and (3) challenges to everyday life. Subthemes provided deeper insights into patient experiences, including delays in help-seeking due to the rationalization of symptoms, and complex responses to glucocorticoid treatment, described by participants as a ‘double-edged sword’, offering rapid improvement in symptoms but also causing significant distress. Notably, commonly used clinical terms such as ‘relapse’ and ‘remission’ were often inconsistent with how patients described their own experiences, underscoring a gap between clinical definitions and patient experiences.
Conclusion
This qualitative narrative literature review reveals the unique challenges of disease management and the complex realities of long-term glucocorticoid use. These findings highlight the urgent need for more patient-centred approaches to care and support.
Key messages
Patients often delay seeking care by normalizing symptoms.
Glucocorticoids rapidly relieve PMR symptoms but cause distressing side effects and emotional uncertainty for patients.
Clinical terms like relapse and remission often misalign with patient experiences, requiring more patient-centred language
Enzymatic degradation of proteinaceous Pickering particles – A strategy to induce demulsification
No full textThis study aimed to understand the demulsification of Pickering emulsions using a particle dissolution approach, i.e., reducing the size of the stabilizing particles by their enzymatic degradation. We proposed that trypsin would kinetically reduce the size of model whey protein microgel particles (WPM), particle size being a key factor in reducing the desorption energy of Pickering particles leading to droplet coalescence. The capability of trypsin to digest WPM (50 vol%) was monitored under various enzyme to WPM ratio, duration of enzymatic treatment, enzyme concentration and static versus dynamic enzyme addition. Results showed that trypsinolysis led to a notable decrease in the size of the WPM (~40%) but not their complete dissolution. A similar trend was observed in the interfacial shear viscosity, which was kinetically driven. The trypsin-induced particle degradation resulted in droplet coalescence only at the higher enzyme concentrations and demonstrated the potential of this method as a demulsification strategy
Holocene palaeoenvironmental reconstruction of sea level, coastal and vegetation changes along the southern Solway Firth, United Kingdom
Full text linkHolocene relative sea level (RSL) changes were reconstructed from four sites along the less-studied southern Solway Firth. A multiproxy approach, including lithostratigraphical and biostratigraphical analyses, combined with radiocarbon dating, produced ten sea level index points (SLIPs). These SLIPs constrained Holocene RSL changes in the region between ~8300 cal BP and ~6018 cal BP and captured the Main Postglacial Transgression. These ten new points are combined with the ten pre-existing SLIPS from the southern Solway Firth to greatly refine the trend of Holocene RSL changes across this region. The Main Postglacial Transgression was shown to occur between ~8320 and 7500 cal BP, reaching a highstand of 3.26 ± 0.56 mOD. The new data were combined with 73 existing SLIPS from two sites around the northern Solway Firth and compared to RSL predictions from glacial isostatic modelling. Comparison between the corrected SLIPs and RSL predictions using British and Irish ice sheet reconstructions showed that the timing of the Main Postglacial Transgression is best captured with a hybrid model for the presence of thick and thin ice sheets. Pollen analysis at Cowgate Farm and Herd Hill provided a record of vegetation and coastal changes, acting as a chronostratigraphic marker when compared to published pollen records of the region. The records show a general transition from saltmarsh to reed swamp, then peat bog as RSL declined through the mid to late Holocene, with some indications of human clearance in the Bronze Age
Learning by trespass: Walking and reading and making commons in the Peak District
Full text linkIn this article, we consider a two-week workshop conducted with the European Architecture Student Assembly (EASA) in August 2023 to reflect on how creative practices might be drawn on to both learn about and learn the art of paying attention to the commons. We do so specifically in relation to land rights in Sheffield and the Peak District in England where the workshop was held. Following Linebaugh, we approach commons not as a thing but rather as (made by) a set of practices. We are also guided by Stengers who urges us to ‘learn the art of paying attention to’ the commons. We draw these provocations together to consider what we did during the workshop — walking(+trespassing), reading(+mapping), making(+repairing) — approaching these activities as practices of commoning. We also reflect on a set of creative responses made by participants to document the workshop (pamphlets, videos, and sound pieces). We consider how the activities and responses offered a way to learn about the topic of commons and land rights and how we fostered a particular bodily and emotional attunement to our experiences that we refer to as learning the art of paying attention to. We further explore how making the creative responses not only documented the workshop but was a key part of learning. The process enabled an opening up of critical questions, imaginaries and speculation and, in this, was also a generative practice of commoning. We argue that, faced with the erosion of the commons, if we can learn to pay attention, these practices can teach us that there are potentials for making otherwise
Long‐term risk of acute pancreatitis in patients with celiac disease: a nationwide population‐based cohort study
Full text linkBackground
Large-scale studies on the association between celiac disease (CeD) and acute pancreatitis (AP) are scarce.
Objectives
To investigate the long-term risks of incident and recurrent AP in patients with CeD.
Methods
Through the Swedish nationwide histopathology cohort Epidemiology Strengthened by Histopathology Reports in Sweden, we collected data on biopsy-confirmed CeD diagnosed between 1969 and 2023 (n = 57,221) and matched them with general population reference individuals (n = 279,126) by birth year, sex, calendar year, and county. Cox regression estimated average adjusted hazard ratios (aHRs) for incident and recurrent AP over time, whereas flexible parametric survival models assessed time-varying incident risks.
Results
During a median follow-up of 15.5 years, incident AP occurred in 549 patients with CeD (incidence rate [IR]: 58.7/100,000 person-years), and 1732 reference individuals (IR: 37.8). The multivariable-adjusted hazard for incident AP was consistently increased in patients with CeD compared with reference individuals (aHR = 1.42 [95% confidence intervals {CI}: 1.28–1.58]), resulting in one extra incident AP event per 185 CeD patients during the first 25 years after diagnosis. Increased incident risks were observed for gallstone- and non-gallstone-related AP, and severe AP, but not alcohol-related AP. Conversely, in study participants who had survived a first AP episode, CeD was not associated with an increased risk for recurrent AP (aHR = 0.85 [0.67–1.08]). Sensitivity analyses, including a sibling comparison, confirmed the main findings.
Conclusion
CeD is linked to a moderately increased long-term risk of incident AP, but not to recurrent AP after the first episode. Clinicians should be aware of this increased risk and counsel patients with CeD on AP risk factors
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