High power narrow linewidth discrete mode laser diode integrated with a curved semiconductor optical amplifier emitting at 2051 nm.

We report on a 2.051 µm InxGaAs/InP-based discrete mode laser diode monolithically integrated with a curved tapered semiconductor optical amplifier for CO2 sensing applications. At a heat-sink temperature of 0°C, the laser emits a record InP value of more than 35 mW continuous-wave output power in a single longitudinal mode.

Landscape of current and emerging cell therapy clinical trials in the UK: current status, comparison to global trends and future perspectives.

Cell Therapy Clinical Trial and Preclinical Research databases have been established by the Cell Therapy Catapult to document current and future cell therapy clinical trials in the UK. We identified 41 ongoing trials in April 2014, an increase of seven trials from April 2013. In addition, we identified 45 late-stage preclinical research projects. The majority of the clinical trials are early phase, primarily led by academic groups. The leading therapeutic areas are cancer, cardiology and neurology. The trends in the UK are also seen globally. As the field matures, more later phase and commercial studies will emerge and the challenges will likely evolve into how to manufacture sufficient cell quantities, manage complex logistics for multi-center trials and control cost.

Intensity-modulated stereotactic radiosurgery for arteriovenous malformations: guidance for treatment planning.

BACKGROUND: Stereotactic Radiosurgery (SRS) is a common tool used to treat Arteriovenous Malformations (AVMs) in anatomical locations associated with a risk of surgical complications. Despite high rates of clinical effectiveness, SRS carries a risk of toxicity as a result of radiation injury to brain tissue. The use of intensity-modulated radiotherapy (IMRT) has increased because it may lead to improved PTV conformity and better Normal Tissue (NT) sparing compared to 3D Conformal Radiotherapy (3DCRT). The aim of this study was twofold: 1) to develop simple patient stratification rules for the recommendation of IMRT planning strategies over 3DCRT in the treatment of AVMs with SRS; and 2) to estimate the impact of IMRT in terms of toxicity reduction using retrospectively reported data for symptomatic radiation injury following SRS. METHODS: Thirty-one AVM patients previously treated with 3DCRT were replanned in a commercial treatment planning system using 3DCRT and static gantry IMRT with identical beam arrangements. The radiotherapy planning metrics analyzed included AVM volume, diameter, and volume to surface area ratio. The dosimetric endpoints analyzed included conformity index improvements and NT sparing measured by the maximum NT dose, and the volume of surrounding tissue that received 7Gy and 12Gy. RESULTS: Our analysis revealed stratified subsets of patients for IMRT that were associated with improved conformity, and those that were associated with decreased doses to normal tissue. The stratified patients experienced an improvement in conformity index by -6-68%, a reduction in the maximum NT dose by -0.5-12.3%, a reduction in the volume of NT receiving 7Gy by 1-8 cc, and a reduction in the volume of NT receiving 12Gy by 0-3.7 cc. The reduction in NT receiving 12Gy translated to a theoretical decrease in the probability of symptomatic injury by 0-9.3%. CONCLUSIONS: This work indicates the potential for significant patient improvements when treating AVMs and provides rules to predict which patients are likely to benefit from IMRT.

Tropism ablation and stealthing of oncolytic adenovirus enhances systemic delivery to tumors and improves virotherapy of cancer.

Intravenous delivery of therapeutic virus particles remains a major goal for virotherapy of metastatic cancer. Avoiding phagocytic capture and unwanted infection of nontarget cells is essential for extended plasma particle kinetics, and simply ablating one or the other does not give extended plasma circulation. Here we show that polymer coating of adenovirus type 5 (Ad5) can combine with predosing strategies or Kupffer cell ablation to achieve systemic kinetics with a half-life >60 min, allowing ready access to peripheral tumors. Accumulation of virus particles within tumor nodules is proportional to the area under the plasma concentration/time curve. Polymer coating wild-type Ad5 in this way is known to decrease hepatic toxicity, increasing the dose of virus particles that can be safely administered. Using polymer-coating technology to deliver a replicating Ad5 systemically, virus replication and transgene expression was almost totally confined to tumor tissues, giving a much improved therapeutic index compared with uncoated virus, and complete control of human HepG2 tumor xenografts.