Sixty-five gene-based risk score classifier predicts overall survival in hepatocellular carcinoma

Clinical application of the prognostic gene expression signature has been delayed due to the large number of genes and complexity of prediction algorithms. In the current study we aimed to develop an easy-to-use risk score with a limited number of genes that can robustly predict prognosis of patients with hepatocellular carcinoma (HCC). The risk score was developed using Cox coefficient values of 65 genes in the training set (n = 139) and its robustness was validated in test sets (n = 292). The risk score was a highly significant predictor of overall survival (OS) in the first test cohort (P = 5.6 × 10(-5), n = 100) and the second test cohort (P = 5.0 × 10(-5) , n = 192). In multivariate analysis, the risk score was a significant risk factor among clinical variables examined together (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.13-1.64; P = 0.001 for OS). CONCLUSION: The risk score classifier we have developed can identify two clinically distinct HCC subtypes at early and late stages of the disease in a simple and highly reproducible manner across multiple datasets.     

The impact of unrecognized bipolar disorders among patients treated for depression with antidepressants in the fee-for-services California Medicaid (Medi-Cal) program: a 6-year retrospective analysis

INTRODUCTION: The cost of unrecognized bipolar disorders over time is unknown. METHODS: Ten years of data from the California Medicaid program were used to identify depressed patients initiating new episodes of antidepressant therapy and with 6+ years of post-treatment data. Recognized bipolar (RBP) patients received a BP diagnosis or used mood stabilizers in the pre-index period. Unrecognized bipolar (UBP) patients received an initial BP diagnosis or used a mood stabilizer in the post-index period. Depression-only (MDD) patients had no BP diagnosis or mood stabilizer use. Three analyses were conducted: (1) regression models of cost per year, (2) a regression model of aggregate cost over 6 years and (3) a time trend analysis of the costs for UBP patients. RESULTS: 14,809 patients were identified: RBP 14.5%, UBP 28.2% and MDD 57.3%. The growth in costs per month for UBP patients over 6 years (171%) far exceeds the growth for RBP and MDD patients (82% and 95%, respectively). RBP and MDD patients cost 2316 dollars and 1681 dollars less per year in the 6th year relative to UBP patients (p<0.0001 for both estimates). The cost per month increased by 91 dollars for each month of delayed diagnosis (p=0.011). Costs for UBP patients increased by 10 dollars per month prior to their initial BP diagnosis (p<0.001) and by -1.01 dollars thereafter (p=0.006 for the change in slope). LIMITATIONS: Classification of patients based on diagnosis or mood stabilizer use using paid claims data is inexact. CONCLUSIONS: Early diagnosis of bipolar disorders may significantly reduce health care cost.     

Analysis of technological innovation and environmental performance improvement in aviation sector

The past oil crises have caused dramatic improvements in fuel efficiency in all industrial sectors. The aviation sector-aircraft manufacturers and airlines-has also made significant efforts to improve the fuel efficiency through more advanced jet engines, high-lift wing designs, and lighter airframe materials. However, the innovations in energy-saving aircraft technologies do not coincide with the oil crisis periods. The largest improvement in aircraft fuel efficiency took place in the 1960s while the high oil prices in the 1970s and on did not induce manufacturers or airlines to achieve a faster rate of innovation. In this paper, we employ a historical analysis to examine the socio-economic reasons behind the relatively slow technological innovation in aircraft fuel efficiency over the last 40 years. Based on the industry and passenger behaviors studied and prospects for alternative fuel options, this paper offers insights for the aviation sector to shift toward more sustainable technological options in the medium term. Second-generation biofuels could be the feasible option with a meaningful reduction in aviation's lifecycle environmental impact if they can achieve sufficient economies of scale.     

Changes in electroencephalographic power and bicoherence spectra according to depth of dexmedetomidine sedation in patients undergoing spinal anesthesia

Background: Assessment the depth of dexmedetomidine sedation using electroencephalographic (EEG) features can improve the quality of procedural sedation. Previous volunteer studies of dexmedetomidine-induced EEG changes need to be validated, and changes in bicoherence spectra during dexmedetomidine sedation has not been revealed yet. We aimed to investigate the dexmedetomidine-induced EEG change using power spectral and bicoherence analyses in the clinical setting.Patients and Methods: Thirty-six patients undergoing orthopedic surgery under spinal anesthesia were enrolled in this study. Dexmedetomidine sedation was conducted by the stepwise increase in target effect site concentration (Ce) while assessing sedation levels. Bispectral index (BIS) and frontal electroencephalography were recorded continuously, and the performance of BIS and changes in power and bicoherence spectra were analyzed with the data from the F3 electrode.Results: The prediction probability values for detecting different sedation levels were 0.847, 0.841, and 0.844 in BIS, 95% spectral edge frequency, and dexmedetomidine Ce, respectively. As the depth of sedation increased, δ power increased, but high β and γ power decreased significantly (P <0.001). α and spindle power increased significantly under light and moderate sedation (P <0.001 in light vs baseline and deep sedation; P = 0.002 and P <0.001 in moderate sedation vs baseline and deep sedation, respectively). The bicoherence peaks of the δ and α-spindle regions along the diagonal line of the bicoherence matrix emerged during moderate and deep sedation. Peak bicoherence in the δ area showed sedation-dependent increases (29.93%±7.38%, 36.72%±9.70%, 44.88%±12.90%; light, moderate, and deep sedation; P = 0.008 and P <0.001 in light sedation vs moderate and deep sedation, respectively; P = 0.007 in moderate sedation vs deep sedation), whereas peak bicoherence in the α-spindle area did not change (22.92%±4.90%, 24.72%±4.96%, and 26.96%±8.42%, respectively; P=0.053).Conclusions: The increase of δ power and the decrease of high-frequency power were associated with the gradual deepening of dexmedetomidine sedation. The δ bicoherence peak increased with increasing sedation level and can serve as an indicator reflecting dexmedetomidine sedation levels.     

Review of Suicide Prevention Programs: Massachusetts,United States,in Comparison with Seoul

Suicide is a tragedy that has massive impact on society. In order to prevent suicide, active government intervention is necessary. The suicide rate in Seoul is rapidly increasing and is more than five times higher than that in the state of Massachusetts (MA) during the last decade, especially in the elderly. The suicide prevention program of MA is one of the most effective suicide prevention programs in the United States. The program views suicide as a preventable public health problem, and emphasizes treatment of depression and de-stigmatization of mental health illnesses to prevent suicide. Also, through active collaboration with mental health professionals, they try to identify at-risk populations and help them to get medical interventions. The program also actively collaborates with the regional coalition program and the Samaritans in taking care of the elderly, and supports the elderly in feeling worthwhile after retirement by helping them to work for communities as volunteers. For its part, the Seoul suicide prevention program puts more emphasis on "life respect culture" and "emotional support to high risk individuals by regular visiting". The annual budget of the Seoul suicide prevention program is one-quarter and that for mental health is about one-twentieth that of MA. Considering the high suicide rate and lower mental health service usage in Seoul, it is crucial to raise awareness of depression and decrease the stigma on mental illnesses. Furthermore, educational efforts with long-term investment in research on suicide are necessary.     

Conditioned secretome of adipose-derived stem cells improves dextran sulfate sodium-induced colitis in mice

BACKGROUNDInflammatory bowel diseases (IBD) is related to uncontrolled immune response. Currently, there is no successful treatment for significant improvement in IBD. Stem cells display their therapeutic effects through their repopulating capacity or secreting factors. AIMTo investigate the effects of conditioned mouse adipose-derived stem cells (mADSCs) secretome on colitis-induced mice. METHODSmADSCs were isolated from adipose tissue of C57BL/6 mice. Conditioned mADSCs secrectome was obtained by culturing of mADSCs with lipopolysaccharides (LPS, 1 μg/mL) for 24 h. Acute colitis was induced by 2% dextran sulfate sodium (DSS) drinking water for 7 d and then normal drinking water for 4 d. The mice were treated with normal culture medium (NM group), conditioned mADSCs secretome (CM group) or mADSCs (SC group). The length of colon and histopatholgy of colon tissues were evaluated. The mRNA expression levels of inflammatory cytokines in colon tissue and the serum interleukin (IL)-6 levels were determined. RESULTSThe isolated mADSCs maintained the mADSCs specific gene expression profiles during experiment. The conditioned mADSCs secretome released by the treatment of mADSCs with LPS contained mainly inflammatory chemokines, colony-stimulating factors and inflammatory cytokines. The loss of body weight and reduction in colon length were ameliorated in the CM group. The conditioned mADSCs secretome reduced the histological score in colon tissue. The expression of IL-1b and IL-6 mRNAs in colon tissues significantly inhibited in the CM group compared to SC group and NM group, respectively. The elevation of serum IL-6 levels was also ameliorated in the CM group. These results indicate that the conditioned mADSCs secretome suppressed the synthesis of inflammatory cytokines in damaged colon tissue and the elevation of serum IL-6 concentration in DSS-induced miceCONCLUSIONConditioned mADSCs secretome might play regenerative roles by the suppression of IL-6 in serum and tissue during acute colitis, and may be more effective than stem cells themselves in the regeneration of colon tissue.     

Comparisons of hypertension-related costs from multinational clinical studies

BACKGROUND: This study identifies and compares the individual cost components of hospital and ambulatory services that manage the care of hypertensive patients in eight countries: the US, the UK, France, Spain, Germany, Italy, Canada and Australia. METHODS: Hypertension-related costs are classified according to four major cardiovascular events: (i) acute myocardial infarction; (ii) congestive heart failure; (iii) stroke; and (iv) renal failure, which was subdivided into renal failure treated by dialysis and renal failure treated by kidney transplantation. To make cross-country costs comparisons, we used the DRG codes used in the US and DRG-like codes from each country. US cost information was obtained from hypertension data available from the literature and health economics researchers. For costs in other countries, we consulted with national health economics experts in each country, used analyses by the Research Triangle Institute, and performed Medline and international literature searches. When available, we obtained information from the countries' public and private nationally representative data sources. For cross-country currency adjustments, all currencies were converted using the Purchasing Power Parities from the Organisation for Economic Cooperation and Development, and then converted into inflation-adjusted year 2000 US dollars. RESULTS: There exists considerable variation in hypertension-related costs from multinational clinical studies. This study documents that costs are generally higher in the US than in other countries; however, this is not always true. In particular, costs of treating heart failure in France and the costs of renal failure without transplantation in Germany and the UK are relatively high. DISCUSSION: While analysing multinational hypertensive cost data, this study also addresses the impact of cross-country cost variations on cost analyses. During the last decade, drug-development researchers have drawn extensively upon multinational trials to resolve enrollment problems and drug-registration issues. At the same time, formulary decision-makers are increasingly demanding multinational cost-effectiveness analyses of the clinical differences found between drug-treatment regimens. Since these data are typically not captured by randomised clinical trials, standard cost estimates must be applied to the clinical trials' resource data, although such standardised calculations do not necessarily account for clinical and cost variations between countries. CONCLUSION: This paper serves as an instrument for identifying which national and event cost data are comparable for analysis as well as highlighting specific problem areas for cost data integration. Although the study focuses on hypertension-related costs, its results may provide insight for multinational cost comparisons of other diseases where similar hospitalisation costs may be analysed.