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KDIGO 2025 clinical practice guideline for the evaluation, management, and treatment of autosomal dominant polycystic kidney disease (ADPKD): executive summary
The Kidney Disease: Improving Global Outcomes (KDIGO) 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) represents the first KDIGO guideline on this subject. Its scope includes nomenclature, diagnosis, prognosis, and prevalence; kidney manifestations; chronic kidney disease (CKD) management and progression, kidney failure, and kidney replacement therapy; therapies to delay progression of kidney disease; polycystic liver disease; intracranial aneurysms and other extrarenal manifestations; lifestyle and psychosocial aspects; pregnancy and reproductive issues; pediatric issues; and approaches to the management of people with ADPKD. The guideline has been developed with patient partners, clinicians, and researchers around the world, with the goal to generate a useful resource for healthcare providers and patients by providing actionable recommendations. The development of this guideline followed an explicit process of evidence review and appraisal, based on a rigorous, formal systematic literature review. The strength of recommendations follows the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The guideline also provides practice points serving to direct clinical care or activities relating to areas for which a systematic review was not conducted. Limitations of the evidence are discussed. Research recommendations to address gaps in knowledge, and implications for policy and payment, are provided. The guideline targets a broad audience of healthcare providers, people living with ADPKD, and stakeholders involved in the various aspects of ADPKD care
‘Thanks to technology’: discourse, care and technology in England
Discourses and how they construct policy ‘problems’ delimit ‘solutions’, including the scale, shape and structure of services. This article discusses how the adult social care sector in England is presented as a policy problem, with the greater use of technology the associated ‘common-sense’ solution – both to the ‘crisis of care’ in a society with an ageing population and as a means to stimulate the national economy. It draws upon critical discourse analysis to examine English policy documents and other government texts published between 2020 and 2022. In doing so, it de-objectivises and de-universalises semiotic claims around care and technology and explores omitted alternatives. In discourse, ageing and care are framed as both problems to be solved and opportunities for entrepreneurship. Technologies are bound together with efficiency, with limited exploration of how use of the former necessarily entails the latter. Technology is, in addition, presented as agentic, inevitable and unassailable, closing off debates as to whether other, less seemingly ‘innovative’ options for reform and change could entail more favourable outcomes. Discourse thus limits the role of the state to stimulating the environment required for technological advancement
Rapid assessment of the osteogenic capacity of hydroxyapatite/aragonite using a murine tibial periosteal ossification model
Biomaterials are widely used as orthopaedic implants and bone graft substitutes. We aimed to develop a rapid osteogenic assessment method using a murine tibial periosteal ossification model to evaluate the bone formation/remodelling potential of a biomaterial within 2–4 weeks. A novel hydroxyapatite/aragonite (HAA) biomaterial was implanted into C57BL/6 mice juxtaskeletally between the tibia and tibialis anterior muscle. Rapid intramembranous bone formation was observed at 14 days, with 4- to 8-fold increases in bone thickness and callus volume in comparison with sham-operated animals (p < 0.0001), followed by bone remodelling and a new layer of cortical bone formation by 28 days after implantation. The addition of zoledronate, a clinically-utilised bisphosphonate, to HAA, promoted significantly more new bone formation than HAA alone over 28 days (p < 0.01). The osteogenic potential of HAA was further confirmed by implanting into a 3.5 mm diameter femoral cancellous bone defect in rats and a 5 mm diameter femoral cortical bone defect in minipigs. To understand the biodegradation and the cellular activity at the cell/biomaterial interfaces, non-decalcified specimens were resin embedded and sections subjected to combined scanning electron microscopy (SEM)/electron backscatter diffraction (EBSD)/energy dispersive X-ray spectrometry (EDS) analysis. We conclude that murine tibial periosteal ossification is a novel method for rapid assessment of the interaction of bioactive materials with osteogenic tissues. This study also highlights that combining calcium carbonate with hydroxyapatite enhances biodegradation and osteogenesis
In vivo spontaneous Ca2+ activity in the pre-hearing mammalian cochlea
The refinement of neural circuits towards mature function is driven during development by patterned spontaneous calcium-dependent electrical activity. In the auditory system, this sensory-independent activity arises in the pre-hearing cochlea and regulates the survival and refinement of the auditory pathway. However, the origin and interplay of calcium signals during cochlear development is unknown in vivo. Here we show how calcium dynamics in the cochlear neuroepithelium of live pre-hearing mice shape the activity of the inner hair cells (IHCs) and their afferent synapses. Both IHCs and supporting cells (SCs) generate spontaneous calcium-dependent activity. Calcium waves from SCs synchronise the activity of nearby IHCs, which then spreads longitudinally recruiting several additional IHCs via a calcium wave-independent mechanism. This synchronised IHC activity in vivo increases the probability of afferent terminal recruitment. Moreover, the modiolar-to-pillar segregation in sound sensitivity of mature auditory nerve fibres appears to be primed at pre-hearing ages
Investigating the changes in residential location and commute patterns during the pandemic using smart card data
Commute trips typically constitute a major share of weekday trips made in urban areas. Hence, commute distances and modes of travel usage are closely linked with the level of transport sustainability of a city. The COVID-19 pandemic has resulted in a significant change in commute patterns – the length and frequency of commute trips and the usage rate of public transport in particular. To ensure the long-term sustainability of transport in a world faced with the persistent threat of potential pandemics, it is crucial to understand these changes. This paper empirically examines how the residential locations and commute patterns of a segment of subway commuters in Beijing changed during the peak of the COVID-19 pandemic. Passively generated smart card data from 8,792,539 subway users were used to quantify the relative impact of different factors contributing to these changes. The results indicate a notable trend of residential relocation towards the city centre that is opposite to the trend of moving away from city centres observed in some other countries. Further, it is observed that the pandemic has acted as a catalyst for individuals with long commute times (over 45 min) to reconsider their locations, aiming to reduce commuting time. Consequently, such relocations lead to an average commute time reduction. The findings contribute to advancing existing knowledge related to the long-term mobility and sustainability implications of the pandemic, some of which are expected to be transferable to future pandemic contexts
Reproducible methods for modeling combined public transport and cycling trips and associated benefits: Evidence from the biclaR tool
A high proportion of car trips can be replaced by a combination of public transit and cycling for the first-and-last mile. This paper estimates the potential for cycling combined with public transit as a substitute for car trips in the Lisbon metropolitan area and assesses its socio-environmental impacts using open data and open source tools. A decision support tool that facilitates the design and development of a metropolitan cycling network was developed (biclaR). The social and environmental impacts were assessed using Health World Organization tools. The impacts of shifting car trips to public transport were also estimated and monetized. The results show that 10 % of all trips could be made by cycling in combination with public transport. Shifting to cycling for the shorter first and last mile stages can reduce annual CO₂eq emissions from 3000 to 7500 tons/day, while for the public transport leg, the transfer from car avoids of up to 20,500 tons of CO₂eq emissions per year. The estimated socio-environmental benefits are of €125 million to €325 million over 10 years. This evidence can support policymakers to prioritize interventions that reduce the reliance on private motor vehicles
Genomic insights into the biogeography and evolution of Galápagos iguanas
Galápagos iguanas are a monophyletic group endemic to the Galápagos archipelago, comprising the marine iguana Amblyrhynchus cristatus and three species of land iguanas: Conolophus subcristatus, C. pallidus and C. marthae. The biogeographic history of the land species in relation to their current distributions remains uncertain, in particular the origins of C. marthae, which is restricted to a small area of the northern part of Isabela Island. The classification of C. pallidus as a separate species has also been debated.
We analyzed DNA sequences (RADseq) to reconstruct demographic histories of selected local populations of all Galápagos iguana species and estimate their divergence times within a multispecies coalescent framework. Our results indicate an early date for the colonization of Galápagos by iguanas, relative to island formation, at ca. 10 Mya, and support a recent split of C. marthae via allopatric speciation, after the emergence of Isabela Island, at ca. 0.57 Mya. We find contrasting demographic histories in C. marthae and the syntopic population of C. subcristatus, suggesting competitive interaction between these species. We also confirm that the divergence of C. pallidus from C. subcristatus is recent (0.09 Mya) and close in time to the split between populations of C. subcristatus from different islands. Our genetic data support recent census estimates indicating a relatively small current effective population size (Ne) in all the studied populations. Our findings shed light on the evolutionary history of Galápagos iguanas and emphasize the need for targeted conservation strategies
Novel fibre-rich breads yield improved glucose release curves and are well accepted by children in primary school breakfast clubs
Background: The average fibre consumption of 4–10-year-old children in the UK is 14.6 g per day, with only 14% of these children reaching the 20 g recommended by the SACN (UK Scientific Advisory Committee on Nutrition), and this ‘fibre gap’ may be most pronounced in communities with the lowest socioeconomic status. School breakfast clubs target children from disadvantaged communities, but their provision may favour lower-fibre foods, due to perceptions that children will reject higher-fibre foods. Our research programme aims to increase the fibre density, digestive-metabolic quality and acceptability of school breakfast provision. Methods: In Study 1, we examined the in vitro digestion of four novel bread products, to determine the relationship between fibre content and glucose release profile, and assess their suitability for sustaining school activity. In Study 2, we introduced the Prograins breads, alongside higher-fibre breakfast cereals and fresh fruit, to primary school breakfast clubs. Results: The Prograins bread products yielded lower peaks and more sustained glucose release curves than the ‘standard’ white bread control. Many children liked and chose the intervention foods, and the average fibre content of children’s breakfasts increased. Conclusions: We conclude from this study that nutritious, fibre-rich bread products can be acceptable to children and that higher-fibre breakfast provision is feasible, and we recommend larger-scale intervention and assessment to validate these real-world findings
GnIH secreted by green light exposure, regulates bone mass through the activation of Gpr147
Reproductive hormones associated with the hypothalamic-pituitary-gonadal (HPG) axis are closely linked to bone homeostasis. In this study, we demonstrate that Gonadotropin inhibitory hormone (GnIH, one of the key reproductive hormones upstream of the HPG axis) plays an indispensable role in regulating bone homeostasis and maintaining bone mass. We find that deficiency of GnIH or its receptor Gpr147 leads to a significant reduction in bone mineral density (BMD) in mice primarily by enhancement of osteoclast activation in vivo and in vitro. Mechanistically, GnIH/Gpr147 inhibits osteoclastogenesis by the PI3K/AKT, MAPK, NF-κB and Nfatc1 signaling pathways. Furthermore, GnIH treatment was able to alleviate bone loss in aging, ovariectomy (OVX) or LPS-induced mice. Moreover, the therapy using green light promotes the release of GnIH and rescues OVX-induced bone loss. In humans, serum GnIH increases and bone resorption markers decrease after green light exposure. Therefore, our study elucidates that GnIH plays an important role in maintaining bone homeostasis via modulating osteoclast differentiation and demonstrates the potential of GnIH therapy or green light therapy in preventing osteoporosis