Single-shot spatial frequency modulation for imaging.

Spatial frequency modulation for imaging (SPIFI) has traditionally employed a time-varying spatial modulation of the excitation beam. Here, for the first time to our knowledge, we introduce single-shot SPIFI, where the spatial frequency modulation is imposed across the entire spatial bandwidth of the optical system simultaneously enabling single-shot operation.

Repeatability of nasal allergen challenge results: Further validation of the allergic rhinitis clinical investigator collaborative protocols.

BACKGROUND: Nasal allergen challenge (NAC) models have been used to study allergic rhinitis and new therapies. Symptoms and biological samples can be evaluated at time points after allergen exposure. OBJECTIVE: To verify protocol repeatability and adequate interval between allergen exposures. METHODS: Ten ragweed allergic participants were exposed to incrementally increasing dosages of ragweed allergen intranasally until they achieved a total nasal symptom score (TNSS) of 8 of 12 and a peak nasal inspiratory flow (PNIF) of 50% reduction or more from baseline. Three weeks later, participants were challenged with a cumulative dose equal to the sum of all the allergen doses received at screening. TNSS and PNIF were recorded at regular intervals, including a 24-hour assessment. A subsequent visit was conducted after a further 3 weeks. Nasal secretion samples were collected for cytokine and eosinophil quantification. RESULTS: Nine participants completed all visits. TNSS and PNIF responses followed previous patterns, with an initial peak at 30 minutes followed by a gradual decline. Most participants reported similar patterns at both NAC visits, although some did not demonstrate the same phenotype at both visits. Some experienced a secondary symptom increase 24 hours after NAC. Eosinophil and cytokine sections followed a similar pattern at both NAC visits. CONCLUSION: NAC is an adequate method for modeling AR in humans, demonstrating appropriate repeatability of symptoms, nasal mucosal eosinophil, and cytokines. The 24-hour time point, previously not studied in our model, may be beneficial in evaluation of long-acting medications. This three-week interval NAC model will be beneficial for studies in which before and after treatment comparisons are desired.

Imaging by integrating stitched spectrograms.

A new diffractive imaging technique called Imaging By Integrating Stitched Spectrograms (IBISS) is presented. Both the data collection and phase retrieval algorithm used in IBISS are direct extensions of frequency resolved optical gating to higher dimensions. Data collection involves capturing an array of diffraction patterns generated by scanning a sample across a coherent beam of light. Phase retrieval is performed using the Principal Components Generalized Projections Algorithm (PCGPA) by reducing the four dimensional data set of images to two remapped two-dimensional sets. The technique is successfully demonstrated using a Helium Neon laser to image a 350µm wide sample with 12µm resolution.

Emerging siRNA Design Principles and Consequences for Biotransformation and Disposition in Drug Development.

After two decades teetering at the intersection of laboratory tool and therapeutic reality, with two siRNA drugs now clinically approved, this modality has finally come into fruition. Consistent with other emerging modalities, initial proof-of-concept efforts concentrated on coupling pharmacologic efficacy with desirable safety profiles. Consequently, thorough investigations of siRNA absorption, distribution, metabolism, and excretion (ADME) properties are lacking. Advancing ADME knowledge will aid establishment of in vitro-in vivo correlations and pharmacokinetic-pharmacodynamic relationships to optimize candidate selection through discovery and translation. Here, we outline the emerging siRNA design principles and discuss the consequences for siRNA disposition and biotransformation. We propose a conceptual framework for siRNA ADME evaluation, contextualizing the site of biotransformation product formation with PK-PD modulation, and end with a discussion around safety and regulatory considerations and future directions for this modality.

Analysis of LV lead position in cardiac resynchronization therapy using different imaging modalities.

OBJECTIVES: This study sought to evaluate whether left ventricular (LV) lead position in cardiac resynchronization therapy (CRT) can be determined by myocardial deformation imaging during LV pacing and to compare imaging techniques for analysis of LV lead position. BACKGROUND: LV lead position has a significant impact on effectiveness of CRT, but clinically applicable methods to determine LV lead position are less defined. METHODS: In 56 patients (53 +/- 5 years, 34 men) undergoing CRT, fluoroscopy and 2 myocardial deformation imaging-based approaches were applied to determine the LV lead position. Myocardial deformation imaging-based techniques were used to determine 1) the segment with maximal temporal difference of peak circumferential strain before and while on biventricular CRT; and 2) the segment with earliest peak systolic circumferential strain during pure LV pacing. Twelve-month echocardiography was performed to determine LV remodeling and improvement in function. Optimal LV lead position was defined as concordance or immediate neighboring of the determined LV lead position to the segment with latest systolic strain prior to CRT. RESULTS: LV lead position determined during LV pacing correlated to the position determined by fluoroscopy (kappa = 0.761). Patients with optimal LV lead position had greater improvement in LV ejection fraction and decrease in end-diastolic volume than those with nonoptimal LV lead position (12 +/- 4% vs. 7 +/- 3%, p < 0.001, and 28 +/- 13 ml vs. 14 +/- 8 ml, p < 0.001, respectively). Determination of the LV lead position based on myocardial deformation imaging during LV pacing showed greater discriminatory power for improvement of ejection fraction (difference optimal vs. nonoptimal lead position group: 4.64 +/- 1.01 ml; p < 0.001) than deformation imaging with biventricular pacing (3.03 +/- 1.08 ml; p = 0.007) and fluoroscopy (2.22 +/- 1.12 ml; p = 0.053). CONCLUSIONS: Myocardial deformation imaging during LV pacing allows determination of the LV lead position in CRT. Improvement in LV function and remodeling as indicators of optimal LV lead position can be best predicted by LV lead position analysis during LV pacing. (Left Ventricular Lead Position in Cardiac Resynchronization Therapy; NCT00748735).

What to do when your technology is good but a licence is terminated.

One of the biggest challenges in the biotech industry is to secure sufficient funding to support product or technology development. Partnering with companies that have cash and expertise - which, for the most part are larger biotech or pharmaceutical industries - may for many small biotech companies be more appealing than dealing with the financial community - venture capitalists and the like. The risk to the small biotech, however, is enormous because the partner may decide to return the rights to the product. This event usually leaves the product in limbo and the technology used to develop it tainted because of uncertainty regarding the real reasons for the return and the assumption in the world at large that there is something wrong with the product/technology. Thus, the licensor is left in the dark and is faced with 'what's next?' Here our company's strategy to overcome the terminated licence disaster or alternatively to take advantage of the terminated licence opportunity is described.