The Singapore Liver Cancer Recurrence (SLICER) Score for Relapse Prediction in Patients with Surgically Resected Hepatocellular Carcinoma

Background and Aims

Surgery is the primary curative option in patients with hepatocellular carcinoma (HCC). Current prognostic models for HCC are developed on datasets of primarily patients with advanced cancer, and may be less relevant to resectable HCC. We developed a postoperative nomogram, the Singapore Liver Cancer Recurrence (SLICER) Score, to predict outcomes of HCC patients who have undergone surgical resection.

Methods

Records for 544 consecutive patients undergoing first-line curative surgery for HCC in one institution from 1992–2007 were reviewed, with 405 local patients selected for analysis. Freedom from relapse (FFR) was the primary outcome measure. An outcome-blinded modeling strategy including clustering, data reduction and transformation was used. We compared the performance of SLICER in estimating FFR with other HCC prognostic models using concordance-indices and likelihood analysis.

Results

A nomogram predicting FFR was developed, incorporating non-neoplastic liver cirrhosis, multifocality, preoperative alpha-fetoprotein level, Child-Pugh score, vascular invasion, tumor size, surgical margin and symptoms at presentation. Our nomogram outperformed other HCC prognostic models in predicting FFR by means of log-likelihood ratio statistics with good calibration demonstrated at 3 and 5 years post-resection and a concordance index of 0.69. Using decision curve analysis, SLICER also demonstrated superior net benefit at higher threshold probabilities.

Conclusion

The SLICER score enables well-calibrated individualized predictions of relapse following curative HCC resection, and may represent a novel tool for biomarker research and individual counseling.     

Parametric stabilization of biological coordination: a theoretical model

In human coordination studies information from the environment may not only pace rhythmic behavior, but also contribute to the observed dynamics, e.g. aphenomenon known as anchoring in the literature. For the paradigmatic caseof bimanual coordination we study these contributions mathematically and develop a model of the interaction between the limb's intrinsic dynamics and environmental signals from a metronome in terms of oscillator equations. We discuss additive versus multiplicative metronomeimpact and show the latter to be more appropriate.Our model describes single limb-metronome interaction, as well as multilimb-metronome interaction. We establish a parametricstabilization term which preserves the characteristicsof bimanual coordination and additionally explains the varyingstability of movement under different metronome conditions, the frequency dependence of the amplitudes of finger movements, anchoring phenomena andgeometries of phase space trajectories. Predictions of our model are tested against experimental observations.     

Utilization of rice husks as a feedstock for preparation of activated carbon by microwave induced KOH and K2CO3 activation

Rice husk (RH), an abundant by-product of rice milling, was used for the preparation of activated carbon (RHAC) via KOH and K(2)CO(3) chemical activation. The activation process was performed at the microwave input power of 600 W for 7 min. RHACs were characterized by low temperature nitrogen adsorption/desorption, scanning electron microscopy and Fourier transform infrared spectroscopy. The adsorption behavior was examined using methylene blue as adsorbate. The K(2)CO(3)-activated sample showed higher yield and better pore structures and adsorption capacity development than the KOH-activated sample, with a BET surface area, total pore volume and monolayer adsorption capacity of 1165 m(2)/g, 0.78 cm(3)/g and 441.52 mg/g, respectively. The results revealed the feasibility of microwave heating for preparation of high surface area activated carbons from rice husks via K(2)CO(3) activation.     

Pilot sequencing of onion genomic DNA reveals fragments of transposable elements,low gene densities,and significant gene enrichment after methyl filtration

Sequencing of the onion (Allium cepa) genome is challenging because it has one of the largest nuclear genomes among cultivated plants. We undertook pilot sequencing of onion genomic DNA to estimate gene densities and investigate the nature and distribution of repetitive DNAs. Complete sequences from two onion BACs were AT rich (64.8%) and revealed long tracts of degenerated retroviral elements and transposons, similar to other larger plant genomes. Random BACs were end sequenced and only 3 of 460 ends showed significant (e < -25) non-organellar hits to the protein databases. The BAC-end sequences were AT rich (63.4%), similar to the completely sequenced BACs. A total of 499,997 bp of onion genomic DNA yielded an estimated mean density of one gene per 168 kb, among the lowest reported to date. Methyl filtration was highly effective relative to random shotgun reads in reducing frequencies of anonymous sequences from 82 to 55% and increasing non-organellar protein hits from 4 to 42%. Our results revealed no evidence for gene-dense regions and indicated that sequencing of methyl-filtered genomic fragments should be an efficient approach to reveal genic sequences in the onion genome.     

Concentrations of heavy metals in maternal and umbilical cord blood

Concentrations of lead, cadmium, methylmercury and total mercury were measured in maternal and umbilical cord blood using graphite atomic absorption spectrometry. Two essential metals, copper and zinc, were also determined using ion chromatography. Lead, copper and zinc were found to be lower in the cord blood, whereas methylmercury and total mercury were higher in cord blood than in maternal blood. Little differences were noted for cadmium in maternal and cord blood. Significant positive correlations were observed between the concentrations in maternal and cord blood with regard to lead (correlation coefficient, r = 0.44), copper (r = 0.34), zinc (r = 0.29), methylmercury (r = 0.44) and total mercury (r = 0.58). These results suggest that, like essential metals, most heavy metals can move rather freely across the human placenta. The potential health effects of heavy metal transfer from mothers to young infants cannot be discounted.     

Competitive inhibition of cytochrome P-450scc by (22R)- and (22S)-22-aminocholesterol. Side-chain stereochemical requirements for C-22 amine coordination to the active-site heme

Two diastereomeric aminocholesterols, (22R)-22-aminocholesterol and (22S)-22-aminocholesterol, are both found to be potent inhibitors of the biosynthesis of pregnenolone from cholesterol by purified bovine mitochondrial P-450scc. Both steroids are competitive versus cholesterol, but the stereochemically correct analog (22R)-22-aminocholesterol is bound approximately 1000 times more tightly than (22S)-22-aminocholesterol. The dissociation constants are 25 nM and 13 microM, respectively. Direct comparisons between spectroscopic and enzymatic properties of the two enzymesterol complexes and the 22-amino-23,24-bisnor-5-cholen-3 beta-ol complex are made, underlining the importance of the stereochemistry at the C-22 position.     

Resource Limitation,Controphic Ostracod Density and Larval Mosquito Development

Aquatic environments can be restricted with the amount of available food resources especially with changes to both abiotic and biotic conditions. Mosquito larvae, in particular, are sensitive to changes in food resources. Resource limitation through inter-, and intra-specific competition among mosquitoes are known to affect both their development and survival. However, much less is understood about the effects of non-culicid controphic competitors (species that share the same trophic level). To address this knowledge gap, we investigated and compared mosquito larval development, survival and adult size in two experiments, one with different densities of non-culicid controphic conditions and the other with altered resource conditions. We used Aedes camptorhynchus, a salt marsh breeding mosquito and a prominent vector for Ross River virus in Australia. Aedes camptorhynchus usually has few competitors due to its halo-tolerance and distribution in salt marshes. However, sympatric ostracod micro-crustaceans often co-occur within these salt marshes and can be found in dense populations, with field evidence suggesting exploitative competition for resources. Our experiments demonstrate resource limiting conditions caused significant increases in mosquito developmental times, decreased adult survival and decreased adult size. Overall, non-culicid exploitation experiments showed little effect on larval development and survival, but similar effects on adult size. We suggest that the alterations of adult traits owing to non-culicid controphic competition has potential to extend to vector-borne disease transmission.