Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset

Purpose: To evaluate the efficacy of a single intravitreal injection of rAAV2/2-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON). Design: RESCUE is a multicenter, randomized, double-masked, sham-controlled, phase 3 clinical trial. Participants: Subjects with the m.11778G>A mitochondrial DNA mutation and vision loss ≤6 months from onset in 1 or both eyes were included. Methods: Each subject's right eye was randomly assigned (1:1) to treatment with rAAV2/2-ND4 (single injection of 9 × 1010 viral genomes in 90 μl) or to sham injection. The left eye received the treatment not allocated to the right eye. Main Outcome Measures: The primary end point was the difference of the change from baseline in best-corrected visual acuity (BCVA) between rAAV2/2-ND4–treated and sham-treated eyes at week 48. Other outcome measures included contrast sensitivity, Humphrey visual field perimetry, retinal anatomic measures, and quality of life. Follow-up extended to week 96. Results: Efficacy analysis included 38 subjects. Mean age was 36.8 years, and 82% were male. Mean duration of vision loss at time of treatment was 3.6 months and 3.9 months in the rAAV2/2-ND4–treated eyes and sham-treated eyes, respectively. Mean baseline logarithm of the minimum angle of resolution (logMAR) BCVA (standard deviation) was 1.31 (0.52) in rAAV2/2-ND4–treated eyes and 1.26 (0.62) in sham-treated eyes, with a range from −0.20 to 2.51. At week 48, the difference of the change in BCVA from baseline between rAAV2/2-ND4–treated and sham-treated eyes was −0.01 logMAR (P = 0.89); the primary end point of a −0.3 logMAR (15-letter) difference was not met. The mean BCVA for both groups deteriorated over the initial weeks, reaching the worst levels at week 24, followed by a plateau phase until week 48, and then an improvement of +10 and +9 Early Treatment Diabetic Retinopathy Study letters equivalent from the plateau level in the rAAV2/2-ND4–treated and sham-treated eyes, respectively. Conclusions: At 96 weeks after unilateral injection of rAAV2/2-ND4, LHON subjects carrying the m.11778G>A mutation treated within 6 months after vision loss achieved comparable visual outcomes in the injected and uninjected eyes

DOE-NSF-NIH Workshop on Opportunities in THz Science, February 12-14, 2004

This is the report of the Workshop on Opportunities in THz Science, held on February 12-14, 2004 in Arlington, VA. This workshop brought together researchers who use or produce THz radiation for physics, chemistry, biology, medicine, and materials science to discuss new research opportunities and common resource needs. The charge from the sponsors of the workshop was to focus on basic science questions within these disciplines that have and can be answered using THz radiation

Predicting Solar Cell Performance from Terahertz and Microwave Spectroscopy

Mobilities and lifetimes of photogenerated charge carriers are core properties of photovoltaic materials and can both be characterized by contactless terahertz or microwave measurements. Here, the expertise from fifteen laboratories is combined to quantitatively model the current voltage characteristics of a solar cell from such measurements. To this end, the impact of measurement conditions, alternate interpretations, and experimental inter laboratory variations are discussed using a Cs,FA,MA Pb I,Br 3 halide perovskite thin film as a case study. At 1 sun equivalent excitation, neither transport nor recombination is significantly affected by exciton formation or trapping. Terahertz, microwave, and photoluminescence transients for the neat material yield consistent effective lifetimes implying a resistance free JV curve with a potential power conversion efficiency of 24.6 . For grainsizes above amp; 8776;20 nm, intra grain charge transport is characterized by terahertz sum mobilities of amp; 8776;32 cm2 V amp; 8722;1 s amp; 8722;1. Drift diffusion simulations indicate that these intra grain mobilities can slightly reduce the fill factor of perovskite solar cells to 0.82, in accordance with the best realized devices in the literature. Beyond perovskites, this work can guide a highly predictive characterization of any emerging semiconductor for photovoltaic or photoelectrochemical energy conversion. A best practice for the interpretation of terahertz and microwave measurements on photovoltaic materials is presente

Time-resolved infrared absorption study of cyclopentadienyl manganese tricarbonyl derivatives: Chelation of pendant sulfides in acetonitrile

The chelation dynamics of [Mn{η 5-C 5H 4C(O)R}(CO) 3] complexes 1 (R = CH 2(SCH 3)), 2 (R = CH(SCH 3) 2), and 3 (R = C(SCH 3) 3) in room-temperature acetonitrile solution have been investigated on the picosecond time scale by UV-pump IR-probe transient absorption spectroscopy. Similar to the previously observed behavior in n-heptane solution, irradiation of 3 in acetonitrile at 289 nm induces CO loss to exclusively yield a Mn-S chelated dicarbonyl product. Unlike the behavior of 1 and 2 in n-hexane and n-heptane solutions, UV excitation of either 1 or 2 in acetonitrile solution induces CO loss to also exclusively yield the chelated products, with no evidence of a competing solvation pathway. All three complexes exhibit ultrafast chelation in \u3c13 ps. Faster vibrational cooling in acetonitrile vs alkane solutions suggests stronger solute-solvent interaction, perhaps via hydrogen bonding. Ring-opening resulting from continuous irradiation of the pendant sulfide\u27s chelates, [Mn{η 5-C 5H 4C(O)CH(SCH 3) 2-κS}(CO) 2] (4) and [Mn{η 5-C 5H 4C(O)C(SCH 3) 3-κS}(CO) 2] (5), is also discussed. © 2006 American Chemical Society

Ultrafast chelation dynamics of model photoswitches: Cyclopentadienyl manganese and arene chromium tricarbonyl derivatives with pendant sulfides

The chelation dynamics of [Mn{η5-C5H 4C(O)R}(CO)3] and [Cr{η6-C 6H5C(O)R}(CO)3] (R=CH2(SCH 3), CH(SCH3)2, C(SCH3)3) in solution were investigated on the picosecond timescale by UV-pump IR-probe transient absorption spectroscopy. Tailoring the side chain structure and solvent environment influences the reaction rates and chelation pathways. © 2007 Springer-Verlag

Ultrafast Chelation Dynamics of Cyclopentadienyl Manganese Tricarbonyl Derivatives with Pendant Sulfides

The photoinduced dynamics of two new [η5-C5H 4C(O)R]Mn(CO)3 complexes 2 (R = CH(SCH3) 2) and 3 (R = C(SCH3)3) have been investigated in n-heptane solution on the ps to μs time scale by UV-pump IR-probe twransient absorption spectroscopy. Irradiation of 2 at 266 or 289 nm induces CO loss to yield two initial products in approximately equal abundance, assigned by their CO-stretching bands to be a heptane solvate of the unsaturated Mn fragment and a ring-formed product in which the pendant sulfide moiety is coordinated to the metal center. In direct analogy with the previously observed behavior of [η5-C5H4C(O)CH 2(SCH3)]Mn(CO)3 (1), the solvate reacts through a secondary pathway to afford the S-bound product within 200 ns. Irradiation of 3 under identical conditions yields the chelated product exclusively, with no evidence of a competing solvation pathway