Personalised and Precision Medicine in Cancer Clinical Trials: Panacea for Progress or Pandora's Box?

Cancer clinical trials have been one of the key foundations for significant advances in oncology. However, there is a clear recognition within the academic, care delivery and pharmaceutical/biotech communities that our current model of clinical trial discovery and development is no longer fit for purpose. Delivering transformative cancer care should increasingly be our mantra, rather than maintaining the status quo of, at best, the often miniscule incremental benefits that are observed with many current clinical trials. As we enter the era of precision medicine for personalised cancer care (precision and personalised medicine), it is important that we capture and utilise our greater understanding of the biology of disease to drive innovative approaches in clinical trial design and implementation that can lead to a step change in cancer care delivery. A number of advances have been practice changing (e.g. imatinib mesylate in chronic myeloid leukaemia, Herceptin in erb-B2-positive breast cancer), and increasingly we are seeing the promise of a number of newer approaches, particularly in diseases like lung cancer and melanoma. Targeting immune checkpoints has recently yielded some highly promising results. New algorithms that maximise the effectiveness of clinical trials, through for example a multi-stage, multi-arm type design are increasingly gaining traction. However, our enthusiasm for the undoubted advances that have been achieved are being tempered by a realisation that these new approaches may have significant cost implications. This article will address these competing issues, mainly from a European perspective, highlight the problems and challenges to healthcare systems and suggest potential solutions that will ensure that the cost/value rubicon is addressed in a way that allows stakeholders to work together to deliver optimal cost-effective cancer care, the benefits of which can be transferred directly to our patients.

Contribution of genetic and environmental effects on lens thickness: the Guangzhou Twin Eye study.

PURPOSE:

This study investigated the heritability of lens thickness (LT) and relative lens thickness (LT/axial length, rLT) measured by Lenstar among Chinese children and adolescents in the Guangzhou Twin Eye study.

METHODS:

Twins aged 8 to 22 years were enrolled from the Guangzhou Twin Registry. A series of LT and axial length (AL) measurements using the Lenstar were taken for each twin. Zygosity was confirmed by genotyping in all same-sex twin pairs. Heritability was assessed by structural variance component genetic modeling, after adjustment for age and sex with the Mx program.

RESULTS:

Seven hundred sixty-eight twin pairs (482 monozygotic [MZ] and 286 dizygotic [DZ] twins) were available for data analysis. The mean (standard deviation) LT and rLT were 3.45 (0.18) mm and 0.142 (0.01), respectively. The intraclass correlation coefficients (ICCs) for LT were 0.90 for the MZ and 0.39 for the DZ twins; and those for rLT were 0.90 for the MZ and 0.40 for the DZ twins, respectively. The best-fitting model yielded 89.5% (95% CI: 87.8%-91.0%) of additive genetic effects and 10.5% (95% CI: 9.0%-12.2%) of unique environmental effects for LT, and 89.3% (95% CI: 89.2%-89.3%) of additive genetic effects and 10.7% (95% CI: 10.7%-11.4%) of unique environmental effects for rLT.

CONCLUSIONS:

This study confirms that the LT in young healthy subjects may be mainly affected by additive genetic factors. High heritability remains even when the data are corrected for the influence of AL with the use of rLT.

Integrated techno-economic and environmental assessments of sixty scenarios for co-firing biomass with coal and natural gas

Displacement of fossil fuel-based power through biomass co-firing could reduce the greenhouse gas (GHG) emissions from fossil fuels. In this study, data-intensive techno-economic models were developed to evaluate different co-firing technologies as well as the configurations of these technologies. The models were developed to study 60 different scenarios involving various biomass feedstocks (wood chips, wheat straw, and forest residues) co-fired either with coal in a 500 MW subcritical pulverized coal (PC) plant or with natural gas in a 500 MW natural gas combined cycle (NGCC) plant to determine their technical potential and costs, as well as to determine environmental benefits. The results obtained reveal that the fully paid-off coal-fired power plant co-fired with forest residues is the most attractive option, having levelized costs of electricity (LCOE) of $53.12–$54.50/MW h and CO2 abatement costs of $27.41–$31.15/tCO2. When whole forest chips are co-fired with coal in a fully paid-off plant, the LCOE and CO2 abatement costs range from $54.68 to $56.41/MW h and $35.60 to $41.78/tCO2, respectively. The LCOE and CO2 abatement costs for straw range from $54.62 to $57.35/MW h and $35.07 to $38.48/tCO2, respectively.

Lake Kumphawapi revisited – The complex climatic and environmental record of a tropical wetland in NE Thailand

Kumphawapi, which is Thailand’s largest natural freshwater lake, contains a >10,000-year-long climatic and environmental archive. New data sets (stratigraphy, chronology, hydrogen isotopes, plant macrofossil and charcoal records) for two sedimentary sequences are here combined with earlier multi-proxy studies to provide a comprehensive reconstruction of past climatic and environmental changes for Northeast Thailand. Gradually higher moisture availability due to a strengthening of the summer monsoon led to the formation of a large shallow lake in the Kumphawapi basin between >10,700 and c. 7000 cal. BP. The marked increase in moisture availability and lower evaporation between c. 7000 and 6400 cal. BP favoured the growth and expansion of vegetation in and around the shallow lake. The increase in biomass led to gradual overgrowing and infilling, to an apparent lake level lowering and to the development of a wetland. Multiple hiatuses are apparent in all investigated sequences between c. 6500 and 1400 cal. BP and are explained by periodic desiccation events of the wetland and erosion due to the subsequent lake level rise. The rise in lake level, which started c. 2000 cal. BP and reached shallower parts c. 1400 cal. BP, is attributed to an increase in effective moisture availability. The timing of hydroclimatic conditions during the past 2000 years cannot be resolved because of chronological limitations.