Rapid decline in estimated glomerular filtration rate in sickle cell anemia: Results of a multicenter pooled analysis

Chronic kidney disease (CKD), typically defined as kidney damage or decreased kidney function for 3 or more months, is common in sickle cell disease (SCD). Increasing evidence suggests that the glomerulopathy of SCD is progressive. CKD is associated with increased mortality in SCD. Based on single center studies, we previously reported on the high prevalence of rapid decline in kidney function, defined as estimated glomerular filtration rate (eGFR) loss >3.0 mL/min/1.73 m2per year, in SCD. In the present study, we further examine rapid eGFR decline in sickle cell anemia, using a pooled analysis of patients to better characterize factors associated with such decline and its association with mortality

Longitudinal study of glomerular hyperfiltration in adults with sickle cell anemia: a multicenter pooled analysis

Glomerular hyperfiltration is common in young sickle cell anemia patients and precedes development of overt kidney disease. In this multicenter pooled cohort, we characterized hyperfiltration and its decline to normal range in adult patients. Glomerular filtration rate (GFR) was estimated using the creatinine-based 2009 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation omitting race adjustment and the 2021 CKD-EPI equation. Using CKD-EPI–2009, 506 patients had baseline estimated GFR (eGFR) $90 mL/min per 1.73 m2, median age of 24 (interquartile range [IQR], 19-34) years and 5.17 years of follow-up. The prevalence of hyperfiltration (eGFR$140 and $130 mL/min per 1.73 m2 for men and women, respectively) was 38.3%. Using CKD-EPI–2009, baseline hyperfiltration was less likely with older age (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.73-0.83; P, .0001), male sex (OR, 0.32; 95% CI, 0.18-0.58; P 5 .0002), and higher weight (OR, 0.96; 95% CI, 0.94-0.99; P 5 .001). Using CKD-EPI–2021, hyperfiltration was similarly less likely with older age (OR, 0.75; 95% CI, 0.70-0.81; P, .0001), male sex (OR, 0.24; 95% CI, 0.13-0.44; P, .0001), and higher weight (OR, 0.97; 95% CI, 0.95-0.99; P 5 .004). In patients with baseline hyperfiltration, eGFR declined to normal values at a median age of 26.2 years. Using CKD-EPI–2009, this decline was associated with male sex (HR, 2.20; 95% CI, 1.26-3.87; P 5 .006), systolic blood pressure (hazard ratio [HR], 1.02; 95% CI, 1.01-1.04; P 5 .01), and hydroxyurea use (HR, 1.74; 95% CI, 1.002-3.03; P 5 .05). Using CKD-EPI–2021, decline of eGFR to normal was only associated with male sex (HR, 3.39; 95% CI, 2.01-5.69; P, .0001). Decline to normal eGFR range from hyperfiltration occurs earlier in males, those on hydroxyurea, and with higher systolic blood pressure

Hamstring muscles: Architecture and innervation

Knowledge of the anatomical organization of the hamstring muscles is necessary to understand their functions, and to assist in the development of accurate clinical and biomechanical models. The hamstring muscles were examined by dissection in six embalmed human lower limbs with the purpose of clarifying their gross morphology. In addition to obtaining evidence for or against anatomical partitioning ( as based on muscle architecture and pattern of innervation), data pertaining to architectural parameters such as fascicular length, volume, physiological cross-sectional area, and tendon length were collected. For each muscle, relatively consistent patterns of innervation were identified between specimens, and each was unique with respect to anatomical organization. On the basis of muscle architecture, three regions were identified within semimembranosus. However, this was not completely congruent with the pattern of innervation, as a primary nerve branch supplied only two regions, with the third region receiving a secondary branch. Semitendinosus comprised two distinct partitions arranged in series that were divided by a tendinous inscription. A singular muscle nerve or a primary nerve branch innervated each partition. In the biceps femoris long head the two regions were supplied via a primary nerve branch which divided into two primary branches or split into a series of branches. Being the only muscle to cross a single joint, biceps femoris short head consisted of two distinct regions demarcated by fiber direction, with each innervated by a separate muscle nerve. Architecturally, each muscle differed with respect to parameters such as physiological cross-sectional area, fascicular length and volume, but generally all partitions within an individual muscle were similar in fascicular length. The long proximal and distal tendons of these muscles extended into the muscle bellies thereby forming elongated musculotendinous junctions. Copyright (C) 2005 S. Karger AG, Basel

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

Drying colloidal systems: laboratory models for a wide range of applications

The drying of complex fluids provides a powerful insight into phenomena that take place on time and length scales not normally accessible. An important feature of complex fluids, colloidal dispersions and polymer solutions is their high sensitivity to weak external actions. Thus, the drying of complex fluids involves a large number of physical and chemical processes. The scope of this review is the capacity to tune such systems to reproduce and explore specific properties in a physics laboratory. A wide variety of systems are presented, ranging from functional coatings, food science, cosmetology, medical diagnostics and forensics to geophysics and art

Dispersion relations for gravity waves in a deep fluid: second sound in a stormy sea

We consider the nonlinear processes of interaction between a random field of short deep gravity waves and a deep long gravity wave, as well as the effects of nonlinear interactions among the driven short waves. The interactions are characterized by two types of invariants. First, the short waves posses an adiabatic invariant as regards the interaction with the long waves. Second, a collision between short waves conserved frequency and wave vector. As a consequence of these invariants, extra degrees of freedom appear. This results in a two-fluid description at the surface of the liquid for the mean flow of the long wave plus a distribution of waves. The two-fluid theory implies a spectrum of oscillations of the surface where, besides the usual gravity waves, there exists a surface mode with longitudinal oscillation. The regimes of validity of this hydrodynamic description are discussed, and the solutions for the dispersion relation are also presented. The power spectrum of a stormy sea is derived within the framework on nonlinear wave interactions. Finally, we comment on the relevance of the results to phase-velocity measurement is a wind-wave laboratory experiment, as well as possible experiments to observe the theoretically predicted new mode.Department of Energy, Office of Basic Energy Sciences, Divisio of Engineering and Geoscience, National Research Council and the Naval Postgraduate School Direct Funded Research ProgramApproved for public release; distribution is unlimited

Cuenco cónico abierto de base redondeada (Mastos) y umbo hacia el interior. Detalle del interior - DSCN5646

Proyectos del Plan Nacional I+D+I con referencias PB94-0129, PB97-1132, BHA 2002-00138, HUM 2006-06250/HISTProyectos de la CAM con referencias 06/0020/1997, 06/0094/1998, 06/0090/2000, 06/0043/2001Programa Consolider-Ingenio 2010 con sigla CSD2007-00058NoInstituto Valencia de Don JuanCastellar de Santiago (Ciudad Real)Cuenco cónico abierto de base redondeada (Mastos) y umbo hacia el interior. Detalle del interio

Development of a TrainingSet of ContemporarySalt-Marsh Foraminiferafor Late Holocene SeaLevel Reconstructions in southeastern Australia

We collected contemporary foraminiferal training sets from two salt marshes to enable more precise and accurate proxy historical sea-level reconstructions from southeastern Australia. Combined with an existing training set from Tasmania, this new regional set consists of 112 samples and 16 species of foraminifera, of which 13 are agglutinated. Cluster analyses group the regional training set into a high–elevation cluster, dominated by Trochamminita salsa, a mid–elevation cluster, dominated by Entzia macrescens and Trochammina inflata, and a mid–low elevation cluster dominated by Miliammina fusca and tidal-flat species. We develop transfer functions using local and regional training sets and assess their performance. Our resulting site-specific and chosen regional models are capable of predicting sea level with decimetre-scale precision (95% confidence intervals of 0.12–0.22 m). These results are comparable to other examples from around the world. When developing regional training sets, we advocate that the similarity in the environmental settings (particularly salinity) should be assessed as an alternative way of grouping sites, rather than simply using spatial proximity. We compare our findings with global results and conclude that salt marshes along microtidal coasts yield models with the lowest vertical uncertainties. Studies with the lowest uncertainties are located in the western Pacific and the western Atlantic, whereas those from the eastern Atlantic generally have larger tidal ranges and carry larger vertical uncertainties. Our models expand the existing region available for sea-level reconstruction and can be used to generate new late Holocene sea-level reconstructions across southeastern Australia

The effect of potato variety mixtures on epidemics of late blight, in relation to plot size and level of resistance

Potatoes of a number of varieties of contrasting levels of resistance were planted in pure or mixed stands in four experiments over 3 years. Three experiments compared the late blight severity and progress in mixtures with that in pure stands. Disease on susceptible or moderately resistant varieties typical of those in commercial use was similar in mixtures and pure stands. In 2 of 3 years, there were slight reductions on cv. Sante, which is moderately susceptible, in mixture with cv. Cara, which is moderately resistant. Cara was unaffected by this mixture. Mixtures of an immune or near-immune partner with Cara or Sante substantially reduced disease on the latter. The effect of the size of plots of individual varieties or mixtures on blight severity was compared in two experiments. Larger plots had a greater area under the disease progress curve, but the average rate of disease progress was greater in smaller plots; this may be because most disease progress took place later, under more favourable conditions, in the smaller plots. In one experiment, two planting densities were used. Density had no effect on disease and did not interact with mixture effects. The overall conclusion is that, while mixtures of potato varieties may be desirable for other reasons, they do not offer any improvement on the average of the disease resistance of the components