Guy Brock

The R package clValid contains functions for validating the results of a clustering analysis. There are three main types of cluster validation measures available, "internal", "stability", and "biological". The user can choose from nine clustering algorithms in existing R packages, including hierarchical, K-means, self-organizing maps (SOM), and model-based clustering. In addition, we provide a function to perform the self-organizing tree algorithm (SOTA) method of clustering. Any combination of validation measures and clustering methods can be requested in a single function call. This allows the user to simultaneously evaluate several clustering algorithms while varying the number of clusters, to help determine the most appropriate method and number of clusters for the dataset of interest. Additionally, the package can automatically make use of the biological information contained in the Gene Ontology (GO) database to calculate the biological validation measures, via the annotation packages available in Bioconductor. The function returns an object of S4 class "clValid", which has summary, plot, print, and additional methods which allow the user to display the optimal validation scores and extract clustering results.

OBJECTIVE: To evaluate our experience with more than 500 minimally invasive hepatic procedures. SUMMARY BACKGROUND DATA: Recent data have confirmed the safety and efficacy of minimally invasive liver surgery. Despite these reports, no programmatic approach to minimally invasive liver surgery has been proposed. METHODS: We retrospectively reviewed all patients who underwent a minimally invasive procedure for the management of hepatic tumors between January 2001 and April 2008. Patients were divided into 3 groups: laparoscopy with intraoperative ultrasound and biopsy only, laparoscopic radiofrequency ablation (RFA), and minimally invasive resection. To compare the various forms of surgery, we analyzed the incidence of complications, tumor recurrence, mortality, and cost. Statistical analysis was performed using chi(2) analysis, Student t test, Kaplan-Meier survival analysis with the log-rank test, and multivariable Cox models. RESULTS: A total of 590 minimally invasive hepatic procedures were performed during 489 operative interventions. The representative tumor histologies were: hepatocellular carcinoma (HCC; N = 210), colorectal carcinoma (N = 40), miscellaneous liver metastases (N = 42), biliary cancer (N = 20), and benign tumors (N = 176). Thirty-five patients underwent laparoscopic ultrasound and confirmatory biopsy alone; 201 patients underwent 240 laparoscopic RFAs, and 253 patients underwent 306 minimally invasive resections. Conversion rates to open surgery for the RFA and resection group were 2% overall. One hundred ninety-nine (40.6%) patients were cirrhotic; 31 resections were performed in cirrhotic patients. Complication and mortality rates for RFA and resection were comparable (11% vs. 16%, and 1.5% vs. 1.6%). However, complication rates (14% vs. 29%; P = 0.02) and mortality (0.3% vs. 9.7%; P = 0.006) rates were higher in the cirrhotic versus noncirrhotic resection group. Overall recurrence rates for RFA and resection groups were 24% and 23%, respectively. Local recurrence rates were higher in the RFA group (6.3% versus 1.5%; P < 0.06). Overall patient survival differed between HCC patients receiving RFA alone and those receiving RFA and OLT (P < 0.0001). Overall survival for cancer patients receiving RFA versus resection differed significantly when unadjusted for other covariates (P = 0.01), and remained marginally significant in a multivariable model (P = 0.056). CONCLUSIONS: Minimally invasive hepatic surgery has become a viable alternative to open hepatic surgery. Our present data are equivalent or superior to those encountered in any large open series. Our experience with RFA confirms a low local recurrence rate and an excellent technique for bridging patients to transplantation. Morbidity and mortality rates for minimally invasive hepatic resections in cirrhotics, is similar to other reported open resection series. This series confirmed excellent interim survival rates after laparoscopic HR and superiority over RFA in the treatment of cancer, with significantly lower local tumor recurrence rate.

BACKGROUND: High-level occupational exposures to some industrial chemicals have been associated with liver diseases, including nonalcoholic fatty liver disease (NAFLD). However, the potential role of low-level environmental pollution on liver disease in the general population has not been evaluated. OBJECTIVE: We determined whether environmental pollutants are associated with an elevation in serum alanine aminotransferase (ALT) activity and suspected NAFLD in U.S. adults. METHODS: This cross-sectional cohort study evaluated adult participants without viral hepatitis, hemochromatosis, or alcoholic liver disease from the National Health and Nutrition Examination Survey (NHANES) for 2003-2004. ALT elevation was defined in men as ≥ 37 IU/L (age 18-20 years) and ≥ 48 IU/L (age ≥ 21 years) and in women as ≥ 30 IU/L (age 18-20 years) and ≥ 31 IU/L (age ≥ 21 years). Adjusted odds ratios (ORs) for ALT elevation were determined across exposure quartiles for 17 pollutant subclasses comprising 111 individual pollutants present with at least a 60% detection rate. Adjustments were made for age, race/ethnicity, sex, body mass index, poverty income ratio, and insulin resistance. Individual pollutants from subclasses associated with ALT elevation were subsequently analyzed. RESULTS: The overall prevalence of ALT elevation was 10.6%. Heavy metals and polychlorinated biphenyls (PCBs) were associated with dose-dependent increased adjusted ORs for ALT elevation. Within these subclasses, increasing whole-blood levels of lead and mercury and increasing lipid-adjusted serum levels of 20 PCBs were individually associated with ALT elevation. CONCLUSIONS: PCB, lead, and mercury exposures were associated with unexplained ALT elevation, a proxy marker of NAFLD, in NHANES 2003-2004 adult participants.

The R package clValid contains functions for validating the results of a clustering analysis. There are three main types of cluster validation measures available, “internal”, “stability”, and “biological”. The user can choose from nine clustering algorithms in existing R packages, including hierarchical, K-means, self-organizing maps (SOM),&#13;\nand model based clustering. In addition, we provide a function to perform the self-organizing tree algorithm (SOTA) method of clustering. Any combination of validation measures and clustering methods can be requested in a single function call. This allows the user to simultaneously&#13;\nevaluate several clustering algorithms while varying the&#13;\nnumber of clusters, to help determine the most appropriate method and number of clusters for the dataset of interest. Additionally, the package can automatically make use of the biological information contained in the Gene Ontology (GO) database to calculate the biological validation measures, via the annotation packages available in Bioconductor. The function returns an object of S4 class clValid, which has&#13;\nsummary, plot, print, and additional methods which allow the user to display the optimal validation scores and extract clustering results.

Nuclear Factor of Activated T-cells (NF-AT) is a crucial transcription factor required for T-cell expression of interleukin 2. Purified NF-AT contains 45-kDa and 90-kDa subunits (Corthésy, B., and Kao, P. N. (1994) J. Biol. Chem. 269, 20682-20690). Partial internal amino acid sequences derived from each subunit indicate that these proteins are novel. The amino acid sequences were used to clone the cDNAs encoding each subunit. The cDNAs predict proteins of novel structures: NF45 has limited similarity to prokaryotic transcription factor sigma-54 and to human DNA topoisomerase II; NF90 has limited similarity to Drosophila Staufen in a domain predicted to bind double-stranded RNA. RNA encoding NF45 and NF90 exists in nonstimulated Jurkat T-cells and in all other cell types examined (HeLa, HepG2, K562). Immunofluorescence microscopy was used to demonstrate that both proteins are located in the nucleus of Jurkat T-cells. Clones NF45 and NF90 with a polyhistidine fusion tag were transiently expressed and processed in the native environment of Jurkat T-cells. Histidine-tagged NF45 and NF90 proteins, affinity-purified on nickel chelate columns, encode a NF-AT DNA-binding activity that is enhanced following T-cell stimulation, and this enhancement is blocked when T-cells are stimulated in the presence of cyclosporin A or FK506.