Metabolic investigations prevent liver transplantation in two young children with citrullinemia type I

Acute liver failure may be caused by a variety of disorders including inborn errors of metabolism. In those cases, rapid metabolic investigations and adequate treatment may avoid the need for liver transplantation. We report two patients who presented with acute liver failure and were referred to our center for liver transplantation work-up. Urgent metabolic investigations revealed citrullinemia type I. Treatment for citrullinemia type I avoided the need for liver transplantation. Acute liver failure as a presentation of citrullinemia type I has not previously been reported in young children. Although acute liver failure has occasionally been described in other urea cycle disorders, these disorders may be underestimated as a cause. Timely diagnosis and treatment of these disorders may avoid liver transplantation and improve clinical outcome. Therefore, urea cycle disorders should be included in the differential diagnosis in young children presenting with acute liver failure

Melting, Solidification, and Crystallization of a Thermoplastic Polyurethane as a Function of Hard Segment Content

Thermoplastic polyurethanes (TPU) with varying hard segment contents (HSC) are monitored during melting and solidifying (20 K/min , Tmax = 220 ° C) by small-angle and wide-angle X-ray scattering (WAXS and SAXS). Hard segments: MDI/BD. Soft segments: PTHF1000. The neat materials are injection-molded, having small amorphous hard domains (chord length d⎯⎯h ∼ 35% show sharp Bragg peaks and larger hard domains ( d⎯⎯h > 7 nm ). When heated, small domains melt, but crystallization in the remaining large domains is not detected. Upon cooling, large agglomerates segregate first, which crystallize immediately. Segregation starts for HSC = 42% at 160 °C and for HSC = 75% at 210 °C. When HSC ≤ 30%, the morphologies before and after are similar, but afterward, many hard blocks are dissolved in the soft phase at the expense of the hard domain fraction. In heating and cooling the melts, multiple homogenization and segregation processes are observed, which are explained by the agglomeration of hard blocks of different lengths in the colloidal fluid

Kimball's Prudence and Two-Fund Separation as Determinants of Mutual Fund Performance Evaluation

Kimball's Prudence and Two-Fund Separation as Determinants of Mutual Fund Performance EvaluationWe consider investors with mean-variance-skewness preferences who aim at selecting one out of F different funds and combining it optimally with the riskless asset and direct stock holdings. Direct stock holdings are either exogenously or endogenously determined. In our theoretical section, we derive and discuss several performance measures for the investor's decision problems with a central role of Kimball's (1990) prudence and of several variants of Sharpe and Treynor measures. In our empirical section, we show that the distinction between exogenous and endogenous stock holding is less important than the issue of skewness preferences. The latter are most relevant for fund rankings, when an investor's skewness preferences are not derived from cubic HARA utility so that the two-fund separation theorem is not valid. (JEL G11

Sirtuin1 stimulates the proliferation and the expression of glycolysis genes in pancreatic neoplastic lesions

Metabolic reprogramming is a feature of neoplasia and tumor growth. Sirtuin 1 (SIRT1) is a lysine deacetylase of multiple targets including metabolic regulators such as p53. SIRT1 regulates metaplasia in the pancreas. Nevertheless, it is unclear if SIRT1 affects the development of neoplastic lesions and whether metabolic gene expression is altered.To assess neoplastic lesion development, mice with a pancreas-specific loss of Sirt1 (Pdx1-Cre;Sirt1-lox) were bred into a KrasG12D mutant background (KC) that predisposes to the development of pancreatic intra-epithelial neoplasia (PanIN) and ductal adenocarcinoma (PDAC). Similar grade PanIN lesions developed in KC and KC;Sirt1-lox mice but specifically early mucinous PanINs occupied 40% less area in the KC;Sirt1-lox line, attributed to reduced proliferation. This was accompanied by reduced expression of proteins in the glycolysis pathway, such as GLUT1 and GAPDH.The stimulatory effect of SIRT1 on proliferation and glycolysis gene expression was confirmed in a human PDAC cell line. In resected PDAC samples, higher proliferation and expression of glycolysis genes correlated with poor patient survival. SIRT1 expression per se was not prognostic but low expression of Cell Cycle and Apoptosis Regulator 2 (CCAR2), a reported SIRT1 inhibitor, corresponded to poor patient survival.These findings open perspectives for novel targeted therapies in pancreatic cancer