Phelpschurchill6639

to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .The origins of the regenerative nature of antlers, being branched and deciduous apophyseal appendages of frontal bones of cervid artiodactyls, have long been associated with permanent evolutionary precursors. In this study, we provide novel insight into growth modes of evolutionary early antlers. We analysed a total of 34 early antlers affiliated to ten species, including the oldest known, dating from the early and middle Miocene (approx. selleckchem 18 to 12 million years old) of Europe. Our findings provide empirical data from the fossil record to demonstrate that growth patterns and a regular cycle of necrosis, abscission and regeneration are consistent with data from modern antlers. The diverse histological analyses indicate that primary processes and mechanisms of the modern antler cycle were not gradually acquired during evolution, but were fundamental from the earliest record of antler evolution and, hence, explanations why deer shed antlers have to be rooted in basic histogenetic mechanisms. The previous interpretation that proximal circular protuberances, burrs, are the categorical traits for ephemerality is refuted.A 61-year-old female patient presented to the emergency room with nausea. Laboratory findings revealed metabolic acidosis, which had to be associated with a sodium-glucose co-transporter‑2 (SGLT2) inhibitor. Due to increasing prescription rates of SGLT2 inhibitors for diabetes mellitus, congestive heart failure or chronic renal insufficiency, a growing numbers of cases of SGLT2 inhibitor-associated ketoacidosis should be expected. Calculating the anion gap can provide orientation in the case of acidosis of unknown origin. Presumably, a relevant proportion of such cases of ketoacidosis is currently being overlooked or its diagnosis delayed.Infections affect morbidity and mortality of patients suffering from rheumatic diseases in an important way. link2 Risk of infection is influenced generally by age and existing comorbidities as well as especially by activity of the rheumatic disease and immunosuppressive treatment. Correspondingly best possible reduction of disease activity and elimination or at least successful treatment of comorbidities are able to reduce infection risk. Patients at high risk of infection should be identified and be monitored in an intensified way. Furthermore risk is influenced by antirheumatic treatment, e.g. enhanced by long-term glucocorticoid treatment, reduced by optimisied use of disease-modifying antirheumatic drugs leading to best possible disease control. Finally protective antibiotic or antiviral treatment (e.g. in case of latent tuberculosis or hepatitis) as well as optimised vaccination status are able to reduce risk of infection further.

Follicle-stimulating hormone (FSH) concentrations increase during the perimenopausal transition and remain high after menopause. Loss of bone mineral density (BMD) and gain of bone marrow adiposity (BMA) and body fat mass also occur during this time. In mice, blocking the action of FSH increases bone mass and decreases fat mass.

To investigate the associations between endogenous FSH levels and BMD, BMA, and body composition in older adults, independent of estradiol and testosterone levels.

Older adults from the AGES-Reykjavik Study, an observational cohort study.

Areal BMD, total body fat, and lean mass were measured with dual-energy x-ray absorptiometry. Lumbar vertebral BMA was measured by 1H-magnetic resonance spectroscopy. Volumetric BMD and visceral and subcutaneous adipose tissue (VAT, SAT) areas were measured with quantitative computed tomography. The least squares means procedure was used to determine sex hormone-adjusted associations between quartiles of serum FSH and BMD, BMA, and body composition.

In women (N = 238, mean age 81 years), those in the highest FSH quartile, compared with the lowest quartile, had lower adjusted mean spine integral BMD (-8.6%), lower spine compressive strength index (-34.8%), higher BMA (+8.4%), lower weight (-8.4%), lower VAT (-17.6%), lower lean mass (-6.1%), and lower fat mass (-11.9%) (all P < 0.05). In men, FSH level was not associated with any outcome.

Older postmenopausal women with higher FSH levels have higher BMA, but lower BMD and lower fat and lean mass, independent of estradiol and testosterone levels. Longitudinal studies are needed to better understand the underlying mechanisms.

Older postmenopausal women with higher FSH levels have higher BMA, but lower BMD and lower fat and lean mass, independent of estradiol and testosterone levels. Longitudinal studies are needed to better understand the underlying mechanisms.

The recent years have witnessed significant therapeutic advances for patients on hemodialysis. We evaluated temporal changes in treatments practices and survival rates among incident hemodialysis patients.

Observational study of patients initiating hemodialysis in Sweden 2006-2015. Trends of hemodialysis-related practices, medications, and routine laboratory biomarkers were evaluated. The incidence of death and major cardiovascular events (MACE) across calendar years were compared against the age-sex-matched general population. Via Cox regression, we explored whether adjustment for implementation of therapeutic advances modified observed survival and MACE risks.

Among 6,612 patients, age and sex were similar, but the burden of co-morbidities increased over time. The proportion of patients receiving treatment by hemodiafiltration, >3 sessions/week, lower ultrafiltration rate, and working fistulas increased progressively, as did use of non-calcium phosphate binders, cinacalcet, and vitamin D3. The standardized 1-year mortality decreased from 13.2% in 2006/07 to 11.1% in 2014/15. The risk of death decreased by 6% (HR 0.94, 95% CI 0.90-0.99) every two years, and the risk of MACE by 4% (HR 0.96; 0.92-1.00). Adjustment for changes in treatment characteristics abrogated these associations (HR 1.00; 0.92-1.09 for death and 1.00; 0.94-1.06 for MACE). Compared with the general population, the risk of death declined from 6 times higher 2006/2007 [standardized incidence rate ratio, sIRR 6.0 (5.3-6.9)], to 5.6 higher 2014/15 [sIRR 5.57 (4.8-6.4)].

Gradual implementation of therapeutic advances over the last decade was associated with a parallel reduction in short-term risk of death and MACE among hemodialysis patients.

Gradual implementation of therapeutic advances over the last decade was associated with a parallel reduction in short-term risk of death and MACE among hemodialysis patients.

Polygenic scores have become a central tool in human genetics research. LDpred is a popular method for deriving polygenic scores based on summary statistics and a matrix of correlation between genetic variants. However, LDpred has limitations that may reduce its predictive performance.

Here we present LDpred2, a new version of LDpred that addresses these issues. We also provide two new options in LDpred2 a "sparse" option that can learn effects that are exactly 0, and an "auto" option that directly learns the two LDpred parameters from data. We benchmark predictive performance of LDpred2 against the previous version on simulated and real data, demonstrating substantial improvements in robustness and predictive accuracy compared to LDpred1. We then show that LDpred2 also outperforms other polygenic score methods recently developed, with a mean AUC over the 8 real traits analyzed here of 65.1%, compared to 63.8% for lassosum, 62.9% for PRS-CS and 61.5% for SBayesR. Note that LDpred2 provides more accurate polygenic scores when run genome-wide, instead of per chromosome.

LDpred2 is implemented in R package bigsnpr.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.In the complement system, the opsonin C3b binds to the bacterial cell surface and mediates the opsonophagocytosis. However, the cell wall protein SdrE of Staphylococcus aureus inhibits the C3b activity by recruiting the complement regulatory protein factor H (fH). SdrE binds to fH via its N-terminal N2N3 domain, which are also found in six other staphylococcal cell wall proteins. In this study, we report that not only the N2N3 domain of SdrE but also those of ClfA, FnbpA, and FnbpB can bind to fH. When immobilized on a microplate, the N2N3 domains recruited fH and enhanced the factor I (fI)-mediated cleavage of C3b. When mixed with fH and S. aureus cells, the N2N3 domains inhibited the fH binding to S. link3 aureus cells and reduced the fI-mediated C3b cleavage on the bacterial cell surface. The F(ab)'2 fragments of the rabbit N2N3 antibodies also inhibited the fH-binding to the S. aureus cell surface. When added to human blood, the N2N3 antibodies or the N2N3 domain proteins significantly increased the bactericidal activity. Based on these results, we conclude that, in S. aureus, not only SdrE but also ClfA, FnbpA, and FnbpB can contribute to the inhibition of C3b-mediated opsonophagocytosis.Adrenocortical Carcinoma (ACC) is a rare endocrine tumor with poor overall prognosis and 1.5-fold overrepresentation in females. In children, ACC is associated with inherited cancer syndromes with 50-80% of childhood-ACC associated with TP53 germline variants. ACC in adolescents and young adults (AYA) is rarely due to germline TP53, IGF2, PRKAR1A and MEN1 variants. We analyzed exome sequencing data from 21 children (39y) with ACC, and retained all pathogenic, likely pathogenic, and highly prioritized variants of uncertain significance. We engineered a stable lentiviral-mutant ACC cell line, harboring an EGFR variant (p.Asp1080Asn) from a 21-year-old female without germline-TP53-variant and with aggressive ACC. We found that 4.8% of the children (P = 0.004) and 6.2% of AYA (P less then  0.0001), all-female participants, harbored germline EGFR variants, compared to only 0.3% of the control group. Expanding our analysis to the RTK-RAS-MAPK pathway, we found that the RTK genes have the highest number of highly prioritized germline variants in these individuals amongst all three arms of this pathway. We showed EGFR mutant cells migrate faster and are characterized by a stem-like phenotype compared to wild type cells. While EGFR inhibitors did not affect the stemness of mutant cells, Sunitinib, a multireceptor tyrosine kinase inhibitor, significantly reduced their stem-like behavior. Our data suggest that EGFR could be a novel underlying germline predisposition factor for ACC, especially in the Childhood-AYA (C-AYA) population. Further clinical validation can improve precision oncology management of this disease, which is known to have limited therapeutic options.

Private practice and academic surgery careers vary significantly in their daily routine, compensation schemes, and definition of productivity. Data are needed regarding the practice characteristics and job satisfaction of these career paths for surgeons and trainees to make informed career decisions and to identify modifiable factors that may be associated with the health of the surgical workforce.

To obtain and compare the differences in practice characteristics and career satisfaction measures between academic and private practice surgeons.

In this cross-sectional survey performed from June 4 to August 1, 2018, an online survey accommodating smartphone, tablet, and desktop formats was distributed by email to 25 748 surgeons who were actively practicing fellows of the American College of Surgeons; had completed a general surgery residency or categorical fellowship in plastic, cardiothoracic, or vascular surgery; and had an active email address on file.

Demographic, training, and current practice characteristics were obtained, and satisfaction measures were measured on a 5-point Likert scale and compared by surgeon type.