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Ternary nitride phase space holds great potential for new functional materials, as suggested by computational predictions of yet-to-be discovered stable phases. Here, we report a metathesis route to bulk powders of MgZrN2and the solid solutions MgxZr2–xN2(0 < x< 1). These ternary phases only result when lower temperature reactions are used, in contrast to previous work using the similar Mg-based metathesis reactions that resulted in the formation of exclusively ZrN. Thermochemical calculations illustrate why lower temperature metathesis reactions yield the incorporation of Mg, while higher temperature ceramic reactions yield exclusively ZrN. Experimental in situX-ray diffraction of metathesis reactions during heating reveals two stages in the reaction pathway: initial consumption of the precursors to make an amorphous product (Trxn> 350 °C) followed by crystallization at higher temperatures (Trxn> 500 °C). Changing the ratio of the metathesis precursors (Mg2NCl and ZrCl4) controllably varies the composition of MgxZr2–xN2, which crystallizes as a cation-disordered rock salt, as evidenced by high-resolution synchrotron X-ray diffraction, electron microscopy, and bulk compositional analysis. Variation in composition leads to a gradual metal-to-insulator transition with increasing x, similar to other reports of analogous thin film specimens produced by combinatorial sputtering. Meanwhile, the optical behavior of these powders suggests nanoscale compositional inhomogeneity, as signatures of ZrN-like absorption are detectable even in Mg-rich samples. This metathesis approach appears to be generalizable to the synthesis of bulk ternary nitride materials.

Objectives:The International Ascites Club (IAC) recently defined Stage 1 acute kidney injury (AKI) for cirrhosis as an acute increase in serum creatinine (SCr) by ≥0.3 mg/dl or by ≥50% in <48 h from a stable value within 3 months. The baseline SCr may influence AKI risk and patient outcomes. The objective of this study is to determine in cirrhosis whether the baseline SCr has any effect on the in-hospital AKI course and patient survival.Methods:North American Consortium for the Study of End-Stage Liver Disease is a consortium of tertiary-care hepatology centers prospectively enroling non-elective cirrhotic inpatients. Patients with different baseline SCr levels (≤0.5, 0.51–1.0, 1.01–1.5, >1.5 mg/dl) were evaluated for the development of AKI, and compared for AKI outcomes and 30-day survival.Results:653 hospitalized cirrhotics (56.7±10years, 64% men, 30% with infection) were included. The incidence of AKI was 47% of enrolled patients. Patients with higher baseline SCr were more likely to develop AKI, with significantly higher delta and peak SCr (P<0.001) than the other groups, more likely to have a progressive AKI course (P<0.0001), associated with a significantly reduced 30-day survival (P<0.0001). Multivariate logistic regression showed that the delta SCr during an AKI episode to be the strongest factor impacting AKI outcomes and survival (P<0.001), with a delta SCr of 0.70 mg/dl having a 68% sensitivity and 80% specificity for predicting 30-day mortality.Conclusions:Admitted cirrhotic patients with higher baseline SCr are at higher risk for in-hospital development of AKI, and more likely to have AKI progression with reduced survival. Therefore, such patients should be closely monitored and treated promptly for their AKI.

Evaluar parámetros morfológicos de papila y capa de fibras nerviosas de la retina (CFNR) explorados con el HRT3 y el GDx-VCC en población normal y analizar correlaciones con variables demográficas.

Context:GH stimulation testing is limited by poor specificity and reproducibility in identifying GH deficiency. Intravenous line placement (IVP) in pediatrics may be a stimulus for GH secretion.Objective:The objective of the study was to determine whether the measurement of GH at baseline as well as 15 and 30 minutes after IVP detects additional patients with sufficient peak GH concentrations who are not identified by a subsequent insulin tolerance test (ITT).Methods:The ITT protocol was modified to include GH measurement at the time of IVP (t = 0) and 15 (t = 15) and 30 (t = 30) minutes later. Insulin was administered at t = 30, and an ITT was performed as per standard protocols. Children were grouped according to the indication for ITT: initial evaluation of GH deficiency (group 1); and GH deficiency at transition to adulthood (group 2).Results:Ninety-seven patients were included (76 in group 1, 21 in group 2). Of these, 27 (28%) had a peak GH concentration of 7 ng/mL or greater (19 in group 1, eight in group 2) either after IVP or ITT. Thirteen subjects (11 in group 1, two in group 2) had GH concentrations of 7 ng/mL or greater after IVP, without exceeding this on a subsequent ITT. Among the 11 group 1 patients, three of these GH peaks of 7 ng/mL or greater occurred at t = 0, 5 at t = 15, and 5 at t = 30, including one patient who had a peak GH of 7 ng/mL or greater at all three time points.Conclusion:Some children will not have a sufficient GH response to pharmacological stimuli but will have a robust response to IVP. We recommend GH measurement after IVP in children undergoing GH stimulation testing, particularly when there is a delay between IVP and the administration of the pharmacological stimulus.

Since the implementation of a formalized MELD exception policy for portopulmonary hypertension, the majority of patients awarded such points have not met criteria for such exception points due to missing or incomplete data, highlighting the need to revise portopulmonary hypertension exception policies and the process by which such exceptions are awarded.

An excerpt from the conservations of Ivan Menchov and Igor Lenchov, while doing their repertory linguistic method is presented.

NFS/N-sldmice harbor a spontaneous autosomal recessive mutation, sld(sublingual gland differentiation arrest) and histologically display attenuated mucous cell expression in sublingual glands (Hayashi et al. Am J Pathol132: 187–191, 1988). Because altered serous demilune cell expression is unknown, we determined the phenotypic expression of this cell type in mutants. Moreover, we evaluated whether absence of glycoconjugate staining in 3-day-old mutant glands is related to disruption in apomucin gene expression and/or to posttranslational glycosylation events. Serous cell differentiation is unaffected, determined morphologically and by serous cell marker expression (PSP, parotid secretory protein; and Dcpp, demilune cell and parotid protein). Conversely, apical granules in “atypical” exocrine cells of mutant glands are PSP and mucin negative, but contain abundant SMGD (mucous granule marker). Age-related appearance of mucous cells is associated with expression of apomucin gene products, whereas SMGD expression is unaltered. “Atypical” cells thus appear specified to a mucous cell fate but do not synthesize mucin glycoproteins unless selectively induced postnatally, indicating the sldmutation disrupts apomucin transcriptional regulation and/or decreases apomucin mRNA stability.

NFS/N-sld mice harbor a spontaneous autosomal recessive mutation, sld (sublingual gland differentiation arrest) and histologically display attenuated mucous cell expression in sublingual glands (Hayashi et al. Am J Pathol 132: 187-191, 1988). Because altered serous demilune cell expression is unknown, we determined the phenotypic expression of this cell type in mutants. Moreover, we evaluated whether absence of glycoconjugate staining in 3-day-old mutant glands is related to disruption in apomucin gene expression and/or to posttranslational glycosylation events. Serous cell differentiation is unaffected, determined morphologically and by serous cell marker expression (PSP, parotid secretory protein; and Dcpp, demilune cell and parotid protein). Conversely, apical granules in "atypical" exocrine cells of mutant glands are PSP and mucin negative, but contain abundant SMGD (mucous granule marker). Age-related appearance of mucous cells is associated with expression of apomucin gene products, whereas SMGD expression is unaltered. "Atypical" cells thus appear specified to a mucous cell fate but do not synthesize mucin glycoproteins unless selectively induced postnatally, indicating the sld mutation disrupts apomucin transcriptional regulation and/or decreases apomucin mRNA stability.

Epithelial tight junctions form a regulated barrier that seals the paracellular space and prevents mixing of luminal contents with the interstitium. This barrier is composed of a group of proteins including the putative “sealing” protein occludin that appears to bind directly to a cytoplasmic junction protein, ZO-1. To study the interaction and regulation of these two components when paracellular integrity is altered, we assessed protein expression and immunofluorescent (IF) localization of ZO-1 and occludin in a rat model of hepatocyte tight junction damage induced by common bile duct ligation (CBDL). Protein levels were detected in liver by immunoblotting and IF localization by 3-dimensional reconstruction of serial 0.5-micron confocal microscopic optical sections. As previously described, ZO-1 protein levels progressively increased to threefold control levels 9 days after CBDL. In contrast, occludin protein levels decreased by 50% within 2 days after CBDL and returned to control values by 9 days. In control IF sections, ZO-1 and occludin colocalized, forming thin continuous staining outlining canaliculi. After CBDL, ZO-1 staining appeared discontinuous, and a punctate pericanalicular accumulation of signal developed around junctional areas. Occludin staining was also discontinuous after CBDL, but, in contrast to ZO-1, was not punctate and remained localized either in a linear fashion along canalicular margins or in a homogeneous fashion in immediately surrounding areas. CBDL results in changes in the expression and localization of the putative tight junction sealing protein occludin in hepatocytes that are distinct from those observed for the peripheral membrane tight junction protein ZO-1.(ABSTRACT TRUNCATED AT 250 WORDS)

The distortion product otoacoustic emission (DPOAE) corresponding to the frequency f 2 -f 1 displays stereotyped, time-varying amplitude alterations during continuous primary tone stimulation. The origin of these alterations is unknown; however, evidence that efferent neurons contribute little to the changes has been presented (Kujawa et al., 1994a, 1995; Lowe and Robertson, 1995). The present investigation examines the hypothesis that these alterations in f 2 -f 1 amplitude are a reflection of local, Ca-dependent mechanisms involving the outer hair cell (OHC) response to sustained stimulation. Experiments were performed using urethane-anesthetized guinea pigs with sectioned middle ear muscles. Intracochlear perfusion was employed to reversibly lower perilymph Ca levels and to introduce antagonists and agonists of L-type Ca channels. Manipulations that lowered available Ca (zero Ca artificial perilymph; zero Ca with BAPTA) or that blocked its entry into the cell via L-type Ca channels (nimodipine) reduced, prevented or reversed the perstimulatory changes in f 2 -f 1 DPOAE amplitude. These perilymph manipulations also reduced the overall amplitude of this distortion component while perfusion of an L-type Ca channel agonist (Bay K 8644) increased its amplitude. Mg did not substitute for Ca, suggesting that these are not merely divalent cation effects. Results are consistent with the hypothesis that continuous stimulation-related changes in f 2 -f 1 DPOAE amplitude are sensitive to perilymph Ca levels and to the function of L-type Ca channels. However, nimodipine also reduced the endocochlear potential (EP) and Bay K 8644 increased the EP. The sensitivity of both the perstimulatory changes in f 2 -f 1 DPOAE amplitude and the EP to the latter drugs leaves their site(s) of action unresolved.

We have previously shown that intranasal infection of mice with mouse hepatitis virus (MHV) strain UAB (MHV-UAB) increases their resistance to Salmonella typhimurium injected intravenously 6 days later. To study how salmonella resistance was induced, BALB/cAnNCr mice were infected with salmonella strains carrying specific genetic alterations. One set of studies compared the effect of MHV infection on subsequent salmonella infections with AroA- (avirulent) and Aro+ (virulent) salmonellae. Unlike its effect on Aro+ salmonellae, MHV failed to reduce the number of AroA- salmonellae recovered from mice. Because AroA- S. typhimurium shows almost no growth in vivo, this failure indicated that the effect of MHV on salmonella resistance required growth of the infecting salmonellae. In other studies, the effect of MHV infection on both growth and killing were monitored simultaneously in mice with growing salmonellae carrying a single copy of the temperature-sensitive pHSG422 plasmid, which is unable to replicate in vivo. MHV infection reduced salmonella growth but caused no increase in salmonella killing. MHV infection of mice given wild-type salmonellae also resulted in no increase in salmonella killing 4 h after salmonella challenge. These studies demonstrate that MHV-UAB infection increases host resistance to salmonellae by enhancing suppression of bacterial growth instead of by increasing the amount of salmonella killing.

The authors present some of the simulation tools available to IC technology and circuit designers and discuss their importance in a Design For Manufacturability (DFM) strategy. It is demonstrated how these simulators, when combined with Design Of Experiment (DOE) and Response Surface Methodology (RSM), can be used to increase engineering knowledge while at the same time reducing the number of simulations required to optimise a process. The idea of contour plotting response distribution parameters to help determine robust manufacturing conditions is also introduced together with a methodology of using simulation results to rapidly produce histograms of response distributions. An environment to help automate the above approach is presented, and its use as part of a DFM strategy is illustrated through an example of a process/device optimisation.

A strategy for screening the important effects in a multivariable response function is presented. An optimisation algorithm is developed, which searches for the optimum of the function in the subspace of the important variables. The application of these methods is illustrated with a known nonlinear 23 variable function. The technique is applied to the design of an NMOS process which depends on 35 factors.

Cryptosporidial infections in severe combined immune deficient (SCID) mice produce a chronic disease state which in the later stages leads to extraintestinal involvement and hepatic dysfunction. To further characterize the infection dynamics in this model and monitor the changes in the hepatic system, a dose titration of the oocyst inoculum was performed and alkaline phosphatase levels in the sera were assayed. Ten SCID mice per dose were inoculated with 10(3), 10(4), 10(5), 10(6), or 10(7) oocysts. Oocyst shedding in the feces was quantified by microscopic enumeration. Mice inoculated with 10(6) oocysts and those inoculated with 10(7) oocysts demonstrated similar oocyst shedding patterns, but the 10(7)-oocyst group exhibited signs of distress (e.g., weight loss and icterus) earlier. The intensity of the infection increased markedly approximately 14 days postinoculation (p.i.) and continued to increase steadily over the next 6 weeks. Inoculation with lower oocyst doses produced a delay in patency (e.g., it occurred 7 days later with the 10(5)-oocyst inoculum and 14 days later with the 10(4)-oocyst inoculum). Mean serum alkaline phosphatase levels in the 10(7)-oocyst group were more than twice control values at 5 weeks p.i. and continued to increase over the next 8 weeks. Oocyst doses and alkaline phosphatase levels were positively correlated with hepatobiliary colonization (r = 0.71) and liver necrosis (r = 0.65) at 13 weeks p.i. A strong positive correlation between hepatobiliary colonization and liver necrosis at 13 weeks p.i. (r = 0.87) was observed.

The effects of WR-2721 [S-2-(3-aminopropylaminoethyl)phosphorothioic acid] in two in vivo and in vitro models of experimental hypercalcemia in the rat were examined. Chronic WR-2721 administration by osmotic minipump (250 mg/kg/24 hr) reduced serum calcium from 12.0 +/- 0.1 to 9.5 +/- 1.0 mg/dl (P less than .01) in rats receiving 1,25-(OH)2 Vitamin D3. Control rats receiving Vitamin D without WR-2721 had a rise in serum calcium to 13.4 +/- 0.2 mg/dl over the same 5-day period. In an experimental form of humoral hypercalcemia of malignancy, the Walker carcinosarcoma tumor-implanted rat, WR-2721 reduced serum calcium from 13.6 +/- 0.3 to 8.4 +/- 0.6 mg/dl by 5 to 6 days (P less than .001). In vitro bone resorption assays utilizing fetal rat long bones in organ culture showed complementary results. WR-2721 (10(-4) M) blocked bone resorption (assayed as percentage of 45Ca release) induced by both conditioned medium derived from cell lines of Walker carcinosarcoma (7.6 +/- 1.4 vs. 24.0 +/- 1.8%, P less than .01) and by addition of 1,25-(OH)2 Vitamin D3 (10(-8) M) (9.8 +/- 0.8 vs. 17.3 +/- 1.0%, P less than .01). These results suggest that WR-2721 may be effective in controlling clinical hypercalcemia due to excess bone resorption.

Monoclonal and monospecific antibodies were used to characterize a major Mycoplasma pulmonis surface antigen complex, V-1. Heterogeneity of V-1 was detected among strains and a high frequency of variation was detected within subclones of single strains. Analysis of 18 different strains showed that no two displayed identical electrophoretic immunoblot patterns for V-1. Analysis of 50 filter clones from an individual strain (not previously filter cloned) revealed at least 10 different V-1 patterns. The two most frequently occurring patterns were expressed by 36% and 24%, respectively, of the total population. Serial subcloning (four separate series) of several of these original clones showed that the average rate of V-1 variation was 2 x 10(-3) per cell per generation. Immunoblots with different anti-V-1 monoclonal antibodies demonstrated that there were both structurally and antigenically different forms of this antigen. Also, two-dimensional polyacrylamide gel analyses showed that different forms of V-1 could vary in charge. This potential for variability in a major surface antigen of mycoplasmas could have important implications as to how the organism interacts with its host.