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1.  Distance Dependent Interhelical Couplings of Organic Rods Incorporated in DNA 4-Helix Bundles 
Bioconjugate chemistry  2009;20(8):1538-1546.
The synthesis of a conjugated linear organic module containing terminal salicylaldehyde groups and a central activated ester, designed for conjugation to amino-modified oligonucleotides, is presented. The organic module has a phenylene-ethynylene backbone and is highly fluorescent. It is conjugated to oligonucleotides sequences and incorporated into specific locations in a well-defined DNA 4-helix bundle (4-HB). The DNA-nanostructure offers precise location control of the organic modules which allows for selective interhelical coupling reactions. In this study metal-salen formation as well as dihydrazone formation are used to covalently interlink the organic modules. Both coupling reactions are highly dependent on the distances between the organic modules in the 4-HB. Neighbouring modules dimerize easier whereas more distanced modules are less prone to react, even when the linkers are extended. The dimeric products are characterized by denaturing PAGE, HPLC and MALDI TOF mass spectrometry.
PMCID: PMC3412156  PMID: 19572635
DNA-directed chemistry; DNA-nanostructures; Organic synthesis; Hydrazone; Metal-salen
2.  Cost-effectiveness of ranibizumab in treatment of diabetic macular oedema (DME) causing visual impairment: evidence from the RESTORE trial 
To evaluate the cost-effectiveness of ranibizumab as either monotherapy or combined with laser therapy, compared with laser monotherapy, in the treatment of diabetic macular oedema (DME) causing visual impairment from a UK healthcare payer perspective.
A Markov model simulated long-term outcomes and costs of treating DME in one eye (BCVA ≤75 letters) based on data from the RESTORE Phase III trial. Outcomes measured in quality-adjusted life-years (QALYs) were simulated for a 15-year time horizon based on 12-month follow-up from RESTORE and published long-term data. Costs included treatment, disease monitoring, visual impairment and blindness (at 2010 price levels).
Ranibizumab monotherapy resulted in a 0.17 QALY gain at an incremental cost of £4191 relative to laser monotherapy, yielding an incremental cost-effectiveness ratio (ICER) of £24 028. Probabilistic sensitivity analysis showed a 64% probability of being cost-effective at a threshold of £30 000 per QALY. Combined ranibizumab and laser therapy resulted in a 0.13 QALY gain at an incremental cost of £4695 relative to laser monotherapy (ICER £36 106; 42% probability of ICER <£30 000).
Based on RESTORE 1-year follow-up data, ranibizumab monotherapy appears to be cost-effective relative to laser monotherapy, the current standard of care. Cost-effectiveness of combination therapy is less certain. Ongoing studies will further inform on disease progression and the need for additional ranibizumab treatment.
PMCID: PMC3329632  PMID: 22399690
Ranibizumab; diabetic macular oedema; visual impairment; cost-effectiveness; macula; treatment medical; clinical trial; epidemiology; public health; vision; retina

Results 1-2 (2)