Potomac Photonics (United States)

Rapid and robust strategies to evaluate the efficacy and effectiveness of novel and existing pharmacotherapeutic interventions (repurposed treatments) in future pandemics are required. Observational “real‐world studies” (RWS) can report more quickly than randomized controlled trials (RCTs) and would have value were they to yield reliable results. Both RCTs and RWS were deployed during the coronavirus disease 2019 (COVID‐19) pandemic. Comparing results between them offers a unique opportunity to determine the potential value and contribution of each. A learning review of these parallel evidence channels in COVID‐19, based on quantitative modeling, can help improve speed and reliability in the evaluation of repurposed therapeutics in a future pandemic. Analysis of all‐cause mortality data from 249 observational RWS and RCTs across eight treatment regimens for COVID‐19 showed that RWS yield more heterogeneous results, and generally overestimate the effect size subsequently seen in RCTs. This is explained in part by a few study factors: the presence of RWS that are imbalanced for age, gender, and disease severity, and those reporting mortality at 2 weeks or less. Smaller studies of either type contributed negligibly. Analysis of evidence generated sequentially during the pandemic indicated that larger RCTs drive our ability to make conclusive decisions regarding clinical benefit of each treatment, with limited inference drawn from RWS. These results suggest that when evaluating therapies in future pandemics, (1) large RCTs, especially platform studies, be deployed early; (2) any RWS should be large and should have adequate matching of known confounders and long follow‐up; (3) reporting standards and data standards for primary endpoints, explanatory factors, and key subgroups should be improved; in addition, (4) appropriate incentives should be in place to enable access to patient‐level data; and (5) an overall aggregate view of all available results should be available at any given time.

Background: The EValuating U-500R Infusion Versus Injection in Type 2 Diabetes Mellitus (VIVID) study compared two methods of U-500R insulin delivery, continuous subcutaneous insulin infusion (CSII) and multiple daily injection (MDI), for 26 weeks in people with type 2 diabetes (T2D) requiring high doses of insulin. To assess glycemic variability (GV) and time in range (TIR), a subset of participants performed masked continuous glucose monitoring (CGM). Methods: VIVID participants were adults who had insulin requirements of >200 but ≤600 U/day and A1C 7.5% to 12%. Participants performed masked CGM for seven consecutive days on each of three occasions: before weeks 0 (baseline), 14, and 26. The primary objective was to compare GV between CSII and MDI groups, based on change from baseline of within-day standard deviation (SDw) of CGM glucose. Results: Of 54 participants enrolled, 41 with evaluable data were analyzed (17 and 24 in CSII and MDI groups, respectively). The CSII group had a significantly greater reduction from baseline in mean SDw of glucose (45.0 to 38.2 mg/dL [-8.1 mg/dL]) compared with the MDI group (47.0 to 45.8 [-0.4 mg/dL]; P = 0.047). TIR 70-180 mg/dL glucose increased significantly from baseline in the CSII group only, from 59.8% to 73.1% (change +12.9%, P < 0.05), but was not significantly different between groups. There were no significant between-group differences in the endpoint mean glucose or A1C. Conclusions: In the VIVID CGM substudy of U-500R in people with T2D requiring high doses of insulin, participants using CSII significantly reduced GV compared with MDI. CSII also significantly increased TIR with no difference between groups.

The use of laser direct-write technology is demonstrated for rapid turnaround redistribution of pads on known good integrated circuit dice. The technology, which is suitable for rapid prototyping of advanced electronic packages, employs an automated laser ablation system with wavelength at 355nm to pattern thin copper films to form the interconnect and vias in the polyimide interlevel insulator. The ablation tool is designed to directly accept the CAD data and write the metallization and via level patterns with excellent (/spl plusmn/3/spl mu/m) layer-to-layer registration. This process is maskless and, except for cleaning steps, does not require patterning by wet chemical etching. The implementation of a change in the design can be done rapidly and involves modifying the CAD data, downloading it to the laser ablation tool, and fabricating a part according to the new design. This paper illustrates the use of laser direct-write ablation for fabrication of via chain test structures and redistribution of pads on functional integrated circuits on singulated dice. Comparable electrical test results were obtained between structures fabricated using laser ablation technology and those fabricated on full 150-mm diameter wafers using conventional photolithography and etch processes.

A prototype workstation has been developed that allows the fabrication of passive electronic components at low temperatures using a laser direct-write process. The work station combines a variety of laser processing techniques onto a single, integrated platform. These techniques include material deposition, laser micromachining, laser sintering, and laser trimming. One particular process, referred to as 'mill and fill', combines the laser micromachining ability of the tool with 'off-the-shelf' conductor pastes to allow the fabrication of high density metalization at very low temperatures. The present work describes the details of the 'mill and fill' process and shows examples of prototype devices fabricated using this technique.

ABSTRACTWe demonstrate a laser direct-write method, a maskless process that transfers material directly from a ribbon to a substrate. This process offers the promise of fabricating passive electronic micro-components at a high speed with high spatial resolution. We are developing a workstation implementing this direct-write method, which integrates deposition, direct laser sintering, and micromachining capability on a single machine. Using this workstation we have deposited micro-patterns of conducting lines and resistors on alumina and polyimide substrates under ambient conditions that exhibit good electrical properties and substrate adhesion. From preliminary studies of laser sintering it was found that a wide range of sintering conditions may be used to arrive at silver conducting lines (∼60 µm × 10 µm) on alumina substrate with resistivity in the range of 5 to 10 times the resistivity of bulk silver. Preliminary results also indicate direct laser sintering of cermet resistor material can yield reproducible resistance values.

We have combined a technique for the lift-off of thin diamond films from a bulk diamond with a technique for engraving diamond with a focused excimer laser to produce free-standing single-crystal diamond microstructures. One microcomponent that has been produced is a 12 tooth gear ∼400 μm in diameter and ∼13 μm thick. Other microstructures have also been demonstrated, showing the versatility of this method. This process should be applicable to producing diamond microcomponents down to spatial dimensions (width and thickness) of a few micrometers.

Small, high-repetition-rate waveguide excimer lasers enable new approaches to pattern and shape generation by ultraviolet photoablation. Using a tabletop microfabrication system that integrates a waveguide excimer laser with vision and motion control systems, we have generated three dimensional structures through direct-write photoablation of polyimide substrates.

An inverse scattering formulation for retrieving three-dimensional profiles of dielectric permittivity is presented. It yields quantitative dielectric images of a target, with resolution limited only by signal-to-noise ratio, and not by wavelength or diffraction. To overcome the wavelength limitation, scattering data in the near zone are utilized, and a method of least-mean-square and singular value decomposition is used to stabilize the matrix inversion. Results from computer simulation with an electrostatic model are shown to provide good images. As the electrostatic field is equivalent to an electrodynamic field with infinite wavelength, it illustrates the possibility of imaging by inverse scattering with resolution unlimited by wavelength. >

We report the results of experiments demonstrating stimulated Brillouin scattering (SBS) and phase conjugation of a single-line HF laser. The 2.91 μm was selected by an intracavity grating yielding up to 3J in a 1.5-μS pulse. The flat-flat optical cavity was carefully aligned to maximize far-field intensity and the resulting spot diameter was found to be near the diffraction limit. The magnified far-field intensity profiles were imaged with film burns and with a linear pyroelectric array. This high spatial quality beam was intentionally distorted by passing it through a roughened NaCl window and the distortion was verified by examining the far-field intensity profile. This distorted beam was then focused into a cell containing xenon at 45 atm. The resulting SBS reflection passed back through the NaCl aberrator and the diffraction-limited far-field intensity profile of this reflected beam was found to be restored. This demonstration of random phase aberration and reconstruction of the laser beam provides evidence that the SBS reflection is the phase conjugate of the input beam. (12min)