Hepatocellular Carcinoma and Associated Clinical Features in Latino and Caucasian Patients from a Single Center.

INTRODUCTION AND AIM:Hepatocellular carcinoma (HCC) is the most common type of liver cancer in adults and has seen a rapid increase in incidence in the United States. Racial and ethnic differences in HCC incidence have been observed, with Latinos showing the greatest increase over the past four decades, highlighting a concerning health disparity. The goal of the present study was to compare the clinical features at the time of diagnosis of HCC in Latino and Caucasian patients. MATERIAL AND METHODS:We retrospectively screened a total of 556 charts of Latino and Caucasian patients with HCC. RESULTS:The mean age of HCC diagnosis was not significantly different between Latinos and Caucasians, but Latinos presented with higher body mass index (BMI). Rates of hypertension, diabetes, and hyperlipidemia were similar in the two groups. The most common etiology of liver disease was alcohol drinking in Latinos, and chronic hepatitis C in Caucasian patients. Non-Alcoholic Steatohepatitis (NASH) was the associated diagnosis in 8.6% of Latinos and 4.7% of Caucasians. Interestingly, alpha-fetoprotein (AFP) levels at time of diagnosis were higher in Latino patients compared to Caucasians, but this difference was evident only in male patients. Multifocal HCC was slightly more frequent in Latinos, but the two groups had similar cancerous vascular invasion. Latino patients also presented with higher rates of both ascites and hepatic encephalopathy. CONCLUSION:Latino and Caucasian patients with HCC present with a different profile of etiologies, but cancer features appear to be more severe in Latinos

Straddle design of spiral bevel and hypoid pinions and gears

The design of spiral bevel and hypoid gears that have a shaft extended from both sides of the cone apex (straddle design) is considered. A main difficulty of such a design is determining the length and diameter of the shaft that might be undercut by the head cutter during gear tooth generation. A method that determines the free space available for the gear shaft is proposed. The approach avoids collision between the shaft being designed and the head cutter during tooth generation. The approach is illustrated with a numerical example

Computerized inspection of gear tooth surfaces

An approach is proposed that uses coordinate measurements of the real surface of spiral bevel gears to determine the actual machine tool setting applied during the gear manufacturing process. The deviations of the real surface from the theoretical one are also determined. Adjustments are then applied by machine tool corrections to minimize these surface deviations. This is accomplished by representing the real surface analytically in the same Gaussian coordinates as the theoretical surface

Process parameter development for the scaled generation of stem cell-derived pancreatic endocrine cells

Please click Additional Files below to see the full abstract

Cost-Effectiveness Analysis of Early Reading Programs: A Demonstration With Recommendations for Future Research

We review the value of cost-effectiveness analysis for evaluation and decision making with respect to educational programs and discuss its application to early reading interventions. We describe the conditions for a rigorous cost-effectiveness analysis and illustrate the challenges of applying the method in practice, providing examples of programs for which we have estimated costs, but find effectiveness data lacking in comparability. We provide a demonstration of how cost-effectiveness analysis can be applied to two early reading programs: the Wilson Reading System and Corrective Reading. We use existing effectiveness data from an experimental evaluation in which the programs were implemented under similar conditions and the use of common outcomes measures for both programs yielded data that are comparable. We combine these data with cost data we collected using the ingredients method to calculate cost-effectiveness ratios for the alphabetics domain. A complete picture of the relative cost-effectiveness of each program could be provided if effectiveness metrics were available for fluency, vocabulary, and comprehension. We highlight the obstacles to applying cost-effectiveness analysis more frequently and recommend strategies for improving the availability of the requisite data

Interaction of Dendritic Cells with Skin Endothelium: A New Perspective on Immunosurveillance

The goal of this study was to determine the mechanisms by which dendritic cells (DCs) in blood could interact with endothelium, a prerequisite to extravasation into tissues. Our results indicate that DCs express both HECA-452–reactive and nonreactive isoforms of P-selectin glycoprotein ligand 1 (PSGL-1) and can tether and roll efficiently on E- and P-selectin under flow conditions in vitro. Freshly isolated blood DCs were further observed to roll continuously along noninflamed murine dermal endothelium in vivo. This interaction is strictly dependent on endothelial selectins, as shown by experiments with blocking antibodies and with E- and P-selectin–deficient mice. We hypothesize that DCs in blood are constitutively poised at the interface of blood and skin, ready to extravasate upon induction of inflammation, and we showed that cutaneous inflammation results in a rapid recruitment of DCs from the blood to tissues. We propose that this is an important and previously unappreciated element of immunosurveillance

Hepatitis C viral evolution in genotype 1 treatment-naïve and treatment-experienced patients receiving telaprevir-based therapy in clinical trials

Background: In patients with genotype 1 chronic hepatitis C infection, telaprevir (TVR) in combination with peginterferon and ribavirin (PR) significantly increased sustained virologic response (SVR) rates compared with PR alone. However, genotypic changes could be observed in TVR-treated patients who did not achieve an SVR. Methods: Population sequence analysis of the NS3•4A region was performed in patients who did not achieve SVR with TVR-based treatment. Results: Resistant variants were observed after treatment with a telaprevir-based regimen in 12% of treatment-naïve patients (ADVANCE; T12PR arm), 6% of prior relapsers, 24% of prior partial responders, and 51% of prior null responder patients (REALIZE, T12PR48 arms). NS3 protease variants V36M, R155K, and V36M+R155K emerged frequently in patients with genotype 1a and V36A, T54A, and A156S/T in patients with genotype 1b. Lower-level resistance to telaprevir was conferred by V36A/M, T54A/S, R155K/T, and A156S variants; and higher-level resistance to telaprevir was conferred by A156T and V36M+R155K variants. Virologic failure during telaprevir treatment was more common in patients with genotype 1a and in prior PR nonresponder patients and was associated with higher-level telaprevir-resistant variants. Relapse was usually associated with wild-type or lower-level resistant variants. After treatment, viral populations were wild-type with a median time of 10 months for genotype 1a and 3 weeks for genotype 1b patients. Conclusions: A consistent, subtype-dependent resistance profile was observed in patients who did not achieve an SVR with telaprevir-based treatment. The primary role of TVR is to inhibit wild-type virus and variants with lower-levels of resistance to telaprevir. The complementary role of PR is to clear any remaining telaprevir-resistant variants, especially higher-level telaprevir-resistant variants. Resistant variants are detectable in most patients who fail to achieve SVR, but their levels decline over time after treatment

Improving Early Literacy: Cost-Effectiveness Analysis of Effective Reading Programs

This study is a cost-effectiveness analysis of seven early literacy programs that have all been previously identified as effective at improving reading outcomes for students in Grades K-3. We use the ingredients method to collect cost data for each program and compare the cost-effectiveness of programs serving students in the same grade level

The role of ARX in human pancreatic endocrine specification

The in vitro differentiation of human embryonic stem cells (hESCs) offers a model system to explore human development. Humans with mutations in the transcription factor Aristaless Related Homeobox (ARX) often suffer from the syndrome X-linked lissencephaly with ambiguous genitalia (XLAG), affecting many cell types including those of the pancreas. Indeed, XLAG pancreatic islets lack glucagon and pancreatic polypeptide-positive cells but retain somatostatin, insulin, and ghrelin-positive cells. To further examine the role of ARX in human pancreatic endocrine development, we utilized genomic editing in hESCs to generate deletions in ARX. ARX knockout hESCs retained pancreatic differentiation capacity and ARX knockout endocrine cells were biased toward somatostatin-positive cells (94% of endocrine cells) with reduced pancreatic polypeptide (rarely detected), glucagon (90% reduced) and insulin-positive (65% reduced) lineages. ARX knockout somatostatin-positive cells shared expression patterns with human fetal and adult δ-cells. Differentiated ARX knockout cells upregulated PAX4, NKX2.2, ISL1, HHEX, PCSK1, PCSK2 expression while downregulating PAX6 and IRX2. Re-expression of ARX in ARX knockout pancreatic progenitors reduced HHEX and increased PAX6 and insulin expression following differentiation. Taken together these data suggest that ARX plays a key role in pancreatic endocrine fate specification of pancreatic polypeptide, somatostatin, glucagon and insulin positive cells from hESCs

Diffractive shadowing of coherent polarization radiation

We report on the study of shadowing of electromagnetic fields radiated in the Terahertz (THz) region from two consecutive sources of coherent diffraction and transition radiation. In these conditions, the formation length is predicted to be $\leq$ 100 m, and shadowing effects should result in an almost complete suppression of radiated fields within distances of the order of tens of centimeters. We experimentally measured that shadowing effects disappear for distances significantly shorter than those predicted. We propose a new model that explains our experimental observations by taking into account 3D diffraction effects. These findings will have a positive impact on the beneficial use of consecutive radiators both for the generation of intense electromagnetic radiation and for beam diagnostics using coherent polarization radiation from ultra-relativistic charged particles