Quantifying association of early proteinuria and estimated glomerular filtration rate changes with long-term kidney failure in C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis using the United Kingdom RaDaR Registry.

Introduction: C3 glomerulopathy (C3G) and immune-complex membranoproliferative glomerulonephritis (IC-MPGN) are rare disorders that frequently result in kidney failure over the long-term. Presently, there are no disease-specific treatments approved for these disorders, although there is much interest in the therapeutic potential of complement inhibition. However, the limited duration and necessarily small size of controlled trials means there is a need to quantify how well short-term changes in estimated glomerular filtration rate (eGFR) and proteinuria predict the clinically important outcome of kidney failure.

Selecting performance indicators for farms and ranches engaged in collaborative agroecosystem research.

The pace of global change complicates the assessment of the outcomes of agricultural management, hindering decision-making by producers, researchers, and consumers. The Long-Term Agroecosystem Research Network (LTAR) is in a unique position to advance monitoring to inform decision-making. Here, we describe how the network selected performance indicators designed to measure the trade-offs from various farming and ranching approaches.

The prevalence of immunoglobulin A nephropathy in the European Union and the impact of the COVID-19 pandemic: an estimation approach utilizing the kidney biopsy frequency.

Background: Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis, requiring a kidney biopsy for diagnosis. This study aimed to estimate the prevalence of primary IgAN within the European Union (EU) and investigate the potential impact of the coronavirus disease 2019 (COVID-19) pandemic on kidney biopsy rates and IgAN diagnosis frequency.

Methods: We conducted four comprehensive literature searches to identify data on the IgAN prevalence and incidence, native kidney biopsy rates and COVID-19 impact on these metrics.

Optimizing sampling across transect-based methods improves the power of agroecological monitoring data.

Transect-based monitoring has long been a valuable tool in ecosystem monitoring to measure multiple ecosystem attributes. The line-point intercept (LPI), vegetation height, and canopy gap intercept methods comprise a set of core methods, which provide indicators of ecosystem condition. However, users often struggle to design a sampling strategy that optimizes the ability to detect ecological change using transect-based methods.

Factor B as a therapeutic target for the treatment of complement-mediated diseases.

The complement system, consisting of three initiating pathways-classical, lectin and alternative, is an important part of innate immunity. Dysregulation of the complement system is implicated in the pathogenesis of several autoimmune and inflammatory diseases. Therapeutic inhibition of the complement system has been recognized as a viable approach to drug development and has been successful with the approval of a small number of complement inhibitors for diseases such as paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, neuromyelitis optica, myasthenia gravis and geographic atrophy.

Iptacopan Reduces Proteinuria and Stabilizes Kidney Function in C3 Glomerulopathy.

Introduction: C3 glomerulopathy (C3G) is a complex, chronic, ultra rare, progressive primary glomerulonephritis, resulting from alternative complement pathway overactivation, leading to kidney failure in most patients, and frequent recurrence in transplants. Iptacopan (LNP023) is an oral, proximal complement inhibitor specifically targeting factor B, that selectively inhibits the alternative complement pathway.

Methods: This was a phase 2 extension study of 26 adult patients with native kidney (cohort A), or recurrent C3G (post kidney transplantation; cohort B) receiving open label iptacopan.

Kidney Transplantation in Children and Adolescents With C3 Glomerulopathy or Immune Complex Membranoproliferative Glomerulonephritis: An International Survey of Current Practice.

Background: Approximately 50% of patients with chronic kidney disease due to C3 glomerulopathy (C3G) or primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN) will require dialysis and/or kidney transplantation (KTx) within the first 10 years of disease onset. Currently, there are no guidelines regarding the indications for KTx or post-transplant management.

Methods: We therefore initiated an international online survey via Survey Monkey on C3G and IC-MPGN in children with CKD stage 5.

Combinatorial Fc modifications for complementary antibody functionality.

Therapeutic monoclonal antibodies (mAbs) can be functionally enhanced via Fc engineering. To determine whether pairs of mAbs with different Fc modifications can be combined for functional complementarity, we investigated the activity of two HIV-1 mAb libraries, each equipped with 60 engineered Fc variants. Our findings demonstrate that the impact of Fc engineering on Fc functionality is dependent on the specific Fab clone.

Kidney transplantation in children and adolescents with C3 glomerulopathy or immune complex membranoproliferative glomerulonephritis: a real-world study within the CERTAIN research network.

Background: Complement 3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN) are ultra-rare chronic kidney diseases with an overall poor prognosis, with approximately 40-50% of patients progressing to kidney failure within 10 years of diagnosis. C3G is characterized by a high rate of disease recurrence in the transplanted kidney. However, there is a lack of published data on clinical outcomes in the pediatric population following transplantation.

The LTAR Grazing Land Common Experiment at the Jornada Experimental Range: Old genetics, new precision technologies, and adaptive value chains.

Rangelands and the supply chains connected to them are central to the agrifood systems of the Southwestern United States. Local ranchers are simultaneously arid lands managers, herd managers, and marketing managers. To stay in business, they must adapt to unpredictable forage resources and markets while conserving soils and vegetation resources for the long term.

Natural Variation in HIV-1 Entry Kinetics Map to Specific Residues and Reveal an Interdependence Between Attachment and Fusion.

Unlabelled: HIV-1 entry kinetics reflect the fluid motion of the HIV envelope glycoprotein through at least three major structural configurations that drive virus-cell membrane fusion. The lifetime of each state is an important component of potency for inhibitors that target them. We used the time-of-addition inhibitor assay and a novel analytical strategy to define the kinetics of pre-hairpin exposure (using T20) and co-receptor engagement (via.

A new framework for evaluating dust emission model development using dichotomous satellite observations of dust emission.

Dust models are essential for understanding the impact of mineral dust on Earth's systems, human health, and global economies, but dust emission modelling has large uncertainties. Satellite observations of dust emission point sources (DPS) provide a valuable dichotomous inventory of regional dust emissions. We develop a framework for evaluating dust emission model performance using existing DPS data before routine calibration of dust models.

Evaluating the Acceptability, Swallowability, and Palatability of Film-Coated Mini-Tablet Formulation in Young Children: Results from an Open-Label, Single-Dose, Cross-Over Study.

Mini-tablets are advantageous over liquid formulations in overcoming challenges related to stability, taste, and dosage. This open-label, single-dose, cross-over study investigated the acceptability and safety of drug-free, film-coated mini-tablets in children aged 1 month-6 years (stratified: 4-6 years, 2-<4 years, 1-<2 years, 6-<12 months, and 1-<6 months), and their preference for swallowing either a high quantity of 2.0 mm or a low quantity of 2.

Synergistic soil, land use, and climate influences on wind erosion on the Colorado Plateau: Implications for management.

Two decades of drought in the southwestern USA are spurring concerns about increases in wind erosion, dust emissions, and associated impacts on ecosystems, agriculture, human health, and water supply. Different avenues of investigation into primary drivers of wind erosion and dust have yielded mixed results depending on the spatial and temporal sensitivity of the evidence. We monitored passive aeolian sediment traps from 2017 to 2020 across eighty-one sites near Moab, Utah to understand patterns of sediment flux.

Satellites reveal Earth's seasonally shifting dust emission sources.

Establishing mineral dust impacts on Earth's systems requires numerical models of the dust cycle. Differences between dust optical depth (DOD) measurements and modelling the cycle of dust emission, atmospheric transport, and deposition of dust indicate large model uncertainty due partially to unrealistic model assumptions about dust emission frequency. Calibrating dust cycle models to DOD measurements typically in North Africa, are routinely used to reduce dust model magnitude.

Expert guidance on the multidisciplinary management of cystinosis in adolescent and adult patients.

Cystinosis, a rare autosomal recessive lysosomal storage disorder, results in an abnormal accumulation of the amino acid cystine in multiple organs and tissues of the body. Renal symptoms typically develop in the first few months of life, with extra-renal manifestations becoming apparent over the next 10-20 years, which require coordinated multidisciplinary care. Here, we describe a consensus-based guidance to support the management of adolescents and adults living with cystinosis.

The pediatric glucocorticoid toxicity index.

Objectives: To develop a Pediatric glucocorticoid toxicity index (pGTI), a standardized, weighted clinical outcome assessment that measures change in glucocorticoid (GC) toxicity over time.

Methods: Fourteen physician experts from 7 subspecialties participated. The physician experts represented multiple subspecialties in which GCs play a major role in the treatment of inflammatory disease: nephrology, rheumatology, oncology, endocrinology, genetics, psychiatry, and maternal-fetal medicine.

Economic Evaluation of Using Daily Prednisolone versus Placebo at the Time of an Upper Respiratory Tract Infection for the Management of Children with Steroid-Sensitive Nephrotic Syndrome: A Model-Based Analysis.

Background: Childhood steroid-sensitive nephrotic syndrome is a frequently relapsing disease with significant short- and long-term complications, leading to high healthcare costs and reduced quality of life for patients. The majority of relapses are triggered by upper respiratory tract infections (URTIs) and evidence shows that daily low-dose prednisolone at the time of infection may reduce the risk of relapse.

Objective: The aim of this study was to assess the cost effectiveness of a 6-day course of low-dose prednisolone at the start of a URTI when compared with placebo.

Thomas Drysdale Buchanan, MD, and the Birth of Academic Anesthesiology.

Thomas Drysdale Buchanan, MD (1876-1940), founding president of the American Board of Anesthesiology, was the first person in the United States to hold the title "Professor of Anesthesiology" in a medical school faculty position dedicated exclusively to the specialty. An 1897 graduate of New York Medical College, Dr Buchanan joined the faculty of his alma mater in 1902 in response to demands by medical students and recent graduates for a dedicated instructor in anesthesia. Within a decade, the instructorship had become a professorship, and Dr Buchanan was on his way to distinction as one of the founders of academic anesthesiology.

Functional Compartmentalization of Antibodies in the Central Nervous System During Chronic HIV Infection.

The central nervous system (CNS) has emerged as a critical HIV reservoir. Thus, interventions aimed at controlling and eliminating HIV must include CNS-targeted strategies. Given the inaccessibility of the brain, efforts have focused on cerebrospinal fluid (CSF), aimed at defining biomarkers of HIV-disease in the CNS, including HIV-specific antibodies.