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Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and one of the most common causes of end-stage kidney disease. Multiple clinical manifestations, such as enlarged kidneys filled with growing cysts, hypertension, and multiple extrarenal complications, including liver cysts, intracranial aneurysms, and cardiac valvular disease, show that ADPKD is a systemic disorder. New information derived from clinical research using molecular genetics and advanced imaging techniques has provided enhanced tools for assessing the diagnosis and prognosis for individual patients and their families. Phase 3 randomised, placebo-controlled clinical trials have clarified aspects of disease management and a disease-modifying therapeutic drug is now available for patients with high risk of rapid disease progression. These developments provide a strong basis on which to make clear recommendations about the management of affected patients and families. Implementation of these advances has the potential to delay kidney failure, reduce the symptom burden, lessen the risk of cardiovascular complications, and prolong life.

Declining groundwater levels are common in parts of the western US, but their impact on the ability of wells to pump groundwater is not known. Here we collate groundwater well records for the western United States and present the recorded locations, depths, and purposes of more than two million groundwater wells constructed between 1950 and 2015. We then use the well records to estimate the percentage of wells that were dry during the years 2013-2015. During the two year period, dry wells were concentrated in rural areas with high agricultural productivity, such as parts of the California Central Valley and the High Plains. Our results support anecdotal evidence that wells used for domestic purposes are more susceptible to drying than wells used for agricultural purposes throughout California's Central Valley because the former tend to be shallower. However, this is not the case in all regions. Our findings suggest that declining groundwater levels are threatening drinking water reliability and agricultural productivity, and consequently, have key implications for both domestic and agricultural water security. Ongoing reductions to groundwater storage are drying groundwater wells in the western US, and this manifestation of water scarcity warrants innovative groundwater management transcending status quos.

In a trial involving patients with later-stage ADPKD, the V 2 -receptor antagonist tolvaptan resulted in a slower decline than placebo in the estimated GFR over a 1-year period, which may slow the onset of end-stage kidney disease.

Non-structural elements represent most of the total construction cost of typical buildings. A significant portion of the total losses in recent earthquakes worldwide, has been attributed to damage to non-structural elements. Damage to non-structural elements occurs at low levels of ground shaking, and can significantly affect the post-earthquake functionality of buildings. However, in Europe, limited prescriptions are provided in the codes for seismic design of non-structural elements and this may partially explain why it is so common for these elements to perform poorly during earthquakes. This paper describes the observed damage to non-structural elements following the 2016 Central Italy earthquake. The most commonly damaged elements were partition walls, ceiling systems, non-structural vaults, chimneys, and storage racks. As a result, it was highlighted the need to introduce seismic regulations devoted to improving the seismic performance of non-structural elements and to reduce the associated economic losses, loss of functionality, and potential threats to life safety.

In patients with autosomal dominant polycystic kidney disease, the rate of increase in total kidney volume was not slowed by lisinopril and telmisartan, as compared with lisinopril and placebo, but was slowed with rigorous blood-pressure control. Autosomal dominant polycystic kidney disease (ADPKD) is characterized by gradual cyst enlargement over a period of decades before the loss of kidney function. 1 – 3 Total kidney volume in ADPKD is accurately measured with the use of magnetic resonance imaging (MRI). 4 – 6 Hypertension occurs early 6 , 7 and is associated with progression to end-stage renal disease (ESRD) and death from cardiovascular causes in patients with ADPKD. 8 , 9 Immunohistologic studies 10 , 11 and clinical studies 12 , 13 support a central role of the renin–angiotensin–aldosterone system (RAAS) in the pathogenesis of hypertension in patients with ADPKD. Activation of the RAAS may promote renal-cyst growth by means . . .

Key Points Intracranial aneurysms (IAs) are the most common vascular manifestation of autosomal dominant polycystic kidney disease (ADPKD) Individuals with ADPKD and increased risk of IA—including those with a family or personal history of IA or subarachnoid haemorrhage—should undergo screening Other vascular abnormalities in ADPKD include aneurysms and dissections of the thoracic aorta, coronary arteries and cervicocephalic arteries, aortic root dilatation and cerebral dolichoectasia; screening is not usually indicated Asymptomatic IAs detected by screening are frequently small and have a low risk of rupture Intervention, either surgical or endovascular, is indicated based on the size and location of the aneurysm The relationship between PKD1 and PKD2 mutations and the development of vascular abnormalities is undefined; modifier genes that increase TGF-β signalling might increase the risk of vascular complications in ADPKD Vascular abnormalities, particularly those associated with rupture of intracranial aneurysms (IAs) or arterial dissections are among the most serious complications of autosomal dominant polycystic kidney disease (ADPKD). In this article, the authors discuss the pathophysiological mechanisms that might be involved in the development of vascular complications in patients with ADPKD and review strategies for screening, diagnosis and treatment of IAs in this population. Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Relentless cyst growth substantially enlarges both kidneys and culminates in renal failure. Patients with ADPKD also have vascular abnormalities; intracranial aneurysms (IAs) are found in ∼10% of asymptomatic patients during screening and in up to 25% of those with a family history of IA or subarachnoid haemorrhage. As the genes responsible for ADPKD— PKD1 and PKD2 —have complex integrative roles in mechanotransduction and intracellular calcium signalling, the molecular basis of IA formation might involve focal haemodynamic conditions exacerbated by hypertension and altered flow sensing. IA rupture results in substantial mortality, morbidity and poor long-term outcomes. In this Review, we focus mainly on strategies for screening, diagnosis and treatment of IAs in patients with ADPKD. Other vascular aneurysms and anomalies—including aneurysms of the aorta and coronary arteries, cervicocephalic and thoracic aortic dissections, aortic root dilatation and cerebral dolichoectasia—are less common in this population, and the available data are insufficient to recommend screening strategies. Treatment decisions should be made with expert consultation and be based on a risk–benefit analysis that takes into account aneurysm location and morphology as well as patient age and comorbidities.

This trial tested single versus dual inhibition of the renin–angiotensin–aldosterone system in ADPKD. ACE-inhibitor monotherapy controlled blood pressure in most patients. Adding an angiotensin II–receptor blocker did not alter the decline in estimated GFR. Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney cysts. 1 Hypertension develops early in patients with ADPKD and is associated with the progression of disease. 2 The renin–angiotensin–aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in patients with ADPKD. 2 – 7 Angiotensin-converting–enzyme (ACE) inhibitors slow the progression of renal dysfunction in nondiabetic kidney diseases. 8 , 9 On the basis of these data, the use of ACE inhibitors as first-line agents to treat hypertension in patients with ADPKD has become standard clinical practice, although no randomized, clinical trials of sufficient size and quality have shown their superiority . . .

From 2022 March 18 to 21, NOAA Active Region (AR) 12967 was tracked simultaneously by Solar Orbiter at 0.35 au and Hinode/EIS at Earth. During this period, strong blueshifted plasma upflows were observed along a thin, dark corridor of open magnetic field originating at the AR’s leading polarity and continuing toward the southern extension of the northern polar coronal hole. A potential field source surface model shows large lateral expansion of the open magnetic field along the corridor. Squashing factor Q-maps of the large-scale topology further confirm super-radial expansion in support of the S-web theory for the slow wind. The thin corridor of upflows is identified as the source region of a slow solar wind stream characterized by ∼300 km s−1 velocities, low proton temperatures of ∼5 eV, extremely high density >100 cm−3, and a short interval of moderate Alfvénicity accompanied by switchback events. When the connectivity changes from the corridor to the eastern side of the AR, the in situ plasma parameters of the slow solar wind indicate a distinctly different source region. These observations provide strong evidence that the narrow open-field corridors, forming part of the S-web, produce some extreme properties in their associated solar wind streams.

These recommendations were systematically developed on behalf of the Network for Early Onset Cystic Kidney Disease (NEOCYST) by an international group of experts in autosomal dominant polycystic kidney disease (ADPKD) from paediatric and adult nephrology, human genetics, paediatric radiology and ethics specialties together with patient representatives. They have been endorsed by the International Pediatric Nephrology Association (IPNA) and the European Society of Paediatric Nephrology (ESPN). For asymptomatic minors at risk of ADPKD, ongoing surveillance (repeated screening for treatable disease manifestations without diagnostic testing) or immediate diagnostic screening are equally valid clinical approaches. Ultrasonography is the current radiological method of choice for screening. Sonographic detection of one or more cysts in an at-risk child is highly suggestive of ADPKD, but a negative scan cannot rule out ADPKD in childhood. Genetic testing is recommended for infants with very-early-onset symptomatic disease and for children with a negative family history and progressive disease. Children with a positive family history and either confirmed or unknown disease status should be monitored for hypertension (preferably by ambulatory blood pressure monitoring) and albuminuria. Currently, vasopressin antagonists should not be offered routinely but off-label use can be considered in selected children. No consensus was reached on the use of statins, but mTOR inhibitors and somatostatin analogues are not recommended. Children with ADPKD should be strongly encouraged to achieve the low dietary salt intake that is recommended for all children.This Consensus Statement developed on behalf of the Network for Early Onset Cystic Kidney Disease provides guidance on counselling, diagnosing and monitoring children with autosomal dominant polycystic kidney disease based on current evidence and a multi-stakeholder discussion of ethical issues.

A Hybrid Vlasov–Maxwell (HVM) model is presented and recent results about the link between kinetic effects and turbulence are reviewed. Using five-dimensional (2D in space and 3D in the velocity space) simulations of plasma turbulence, it is found that kinetic effects (or non-fluid effects) manifest through the deformation of the proton velocity distribution function (DF), with patterns of non-Maxwellian features being concentrated near regions of strong magnetic gradients. The direction of the proper temperature anisotropy, calculated in the main reference frame of the distribution itself, has a finite probability of being along or across the ambient magnetic field, in general agreement with the classical definition of anisotropy T ⊥/T ∥ (where subscripts refer to the magnetic field direction). Adopting the latter conventional definition, by varying the global plasma beta (β) and fluctuation level, simulations explore distinct regions of the space given by T ⊥/T ∥ and β∥, recovering solar wind observations. Moreover, as in the solar wind, HVM simulations suggest that proton anisotropy is not only associated with magnetic intermittent events, but also with gradient-type structures in the flow and in the density. The role of alpha particles is reviewed using multi-ion kinetic simulations, revealing a similarity between proton and helium non-Maxwellian effects. The techniques presented here are applied to 1D spacecraft-like analysis, establishing a link between non-fluid phenomena and solar wind magnetic discontinuities. Finally, the dimensionality of turbulence is investigated, for the first time, via 6D HVM simulations (3D in both spaces). These preliminary results provide support for several previously reported studies based on 2.5D simulations, confirming several basic conclusions. This connection between kinetic features and turbulence open a new path on the study of processes such as heating, particle acceleration, and temperature-anisotropy, commonly observed in space plasmas.