Quantitative performance characterization of three-dimensional noncontact fluorescence molecular tomography

© 2016 The Authors.Fluorescent proteins and dyes are routine tools for biological research to describe the behavior of genes, proteins, and cells, as well as more complex physiological dynamics such as vessel permeability and pharmacokinetics. The use of these probes in whole body in vivo imaging would allow extending the range and scope of current biomedical applications and would be of great interest. In order to comply with a wide variety of application demands, in vivo imaging platform requirements span from wide spectral coverage to precise quantification capabilities. Fluorescence molecular tomography (FMT) detects and reconstructs in three dimensions the distribution of a fluorophore in vivo. Noncontact FMT allows fast scanning of an excitation source and noninvasive measurement of emitted fluorescent light using a virtual array detector operating in free space. Here, a rigorous process is defined that fully characterizes the performance of a custom-built horizontal noncontact FMT setup. Dynamic range, sensitivity, and quantitative accuracy across the visible spectrum were evaluated using fluorophores with emissions between 520 and 660 nm. These results demonstrate that high-performance quantitative three-dimensional visible light FMT allowed the detection of challenging mesenteric lymph nodes in vivo and the comparison of spectrally distinct fluorescent reporters in cell culture

Fluctuations of radiation from a chaotic laser below threshold

Radiation from a chaotic cavity filled with gain medium is considered. A set of coupled equations describing the photon density and the population of gain medium is proposed and solved. The spectral distribution and fluctuations of the radiation are found. The full noise is a result of a competition between positive correlations of photons with equal frequencies (due to stimulated emission and chaotic scattering) which increase fluctuations, and a suppression due to interaction with a gain medium which leads to negative correlations between photons. The latter effect is responsible for a pronounced suppression of the photonic noise as compared to the linear theory predictions.Comment: 7 pages, 5 figures; expanded version, to appear in Phys. Rev.

Localized Random Lasing Modes and a New Path for Observing Localization

We demonstrate that a knowledge of the density-of-states and the eigenstates of a random system without gain, in conjunction with the frequency profile of the gain, can accurately predict the mode that will lase first. Its critical pumping rate can be also obtained. It is found that the shape of the wavefunction of the random system remains unchanged as gain is introduced. These results were obtained by the time-independent transfer matrix method and finite-difference-time-domain (FDTD) methods. They can be also analytically understood by generalizing the semi-classical Lamb theory of lasing in random systems. These findings provide a new path for observing the localization of light, such as looking for mobility edge and studying the localized states. %inside the random systems..Comment: Sent to PRL. 3 figure

The role of the exit in the initial screening of investment opportunities: The case of business angel syndicate gatekeepers

The exit process has been largely ignored in business angel research.. The practitioner community identifies the difficulty in achieving exits as the most pressing problem for investors. This has been attributed to the failure of investors to adopt an exit-centric approach to investing. The validity of this claim is examined via a study of the investment approach of 21 ‘gatekeepers’ (managers) of angel groups in Scotland and Northern Ireland. Most gatekeepers say that they do consider the exit when they invest. However, this is contradicted by a verbal protocol analysis which indicates that the exit is not a significant consideration in their initial screening process. The small number of exits achieved by the groups is consistent with the general lack of an exit-centric approach to investing. Only three groups exhibit evidence of a strong exit-centric approach to investing. The lack of exits may have a negative impact on the level of future angel investment activity

Theory for the photon statistics of random lasers

A theory for the photon statistics of a random laser is presented. Noise is described by Langevin operators, where both fluctuations of the electromagnetic field and of the medium are included. The theory is valid for all lasers with small outcoupling when the laser cavity is large compared to the wavelength of the radiation. The theory is applied to a chaotic laser cavity with a small opening. It is known that a large number of modes can be above threshold simultaneously in such a cavity. It is shown the amount of fluctuations is increased compared to the Poissonian value by an amount that depends on that number

Autofluorescence insensitive imaging using upconverting nanocrystals in scattering media

Autofluorescence is a nuisance in the field of fluorescence imaging and tomography of exogenous molecular markers in tissue, degrading the quality of the collected data. In this letter, we report autofluorescence insensitive imaging using highly efficient upconverting nanocrystals (NaYF4: Yb3+ /Tm3+) in a tissue phantom illuminated with near- infrared radiation of 85 mW/cm(2). It was found that imaging with such nanocrystals leads to an exceptionally high contrast compared to traditional downconverting fluorophores due to the absence of autofluorescence. Upconverting nanocrystals may be envisaged as important biological markers for tissue imaging purposes. c 2008 American Institute of Physics. [DOI: 10.1063/1.3005588

One-year infliximab administration for the treatment of chronic refractory pouchitis

Abstract Aim To determine the efficacy of infliximab in the treatment of chronic refractory pouchitis, following ileo-pouch anal anastomosis (IPAA) for ulcerative colitis (UC). Methods Seven patients (4 females, 3 males) with chronic refractory pouchitis were included in an open study. Pouchitis was diagnosed by clinical plus endoscopic and histological criteria. Three patients also had fistulae (pouch-bladder in 1 and perianal in 2). Extraintestinal manifestations were also present in 4 patients (erythema nodosum in 2, arthralgiae in 2). All patients were refractory to standard therapy. Crohn's disease was carefully excluded in all patients after re-evaluation of the history and examination of the small bowel with enteroclysis or small bowel capsule endoscopy. Patients received Infliximab 5 mg/kg at 0, 2 and 6 weeks and thereafter every 2 months for 1 year. Clinical response was classified as complete, partial, and no response. Fistulae closure was classified as complete, partial, and no closure. The pouchitis disease activity index (PDAI) was also used as an outcome measure. Results Clinically, all patients improved. After 1 year of follow-up, 5 of the 7 patients had a complete clinical response, and 2 of the 3 patients with a fistula had complete fistulae closure. At the end of the follow-up period the median PDAI dropped from 11 (baseline) (range, 10-14) to 5 (range, 3-8). Extraintestinal manifestations were in complete remission at the end of the followup period as well. Conclusions Our results indicate that infliximab may be recommended for the treatment of chronic refractory pouchitis complicated or not by fistulae following IPAA for UC

Sex- and age-specific trends in mortality from suicide and undetermined death in Germany 1991–2002

BACKGROUND: Over the last decade, significant downward linear time trends in suicide mortality were observed in most Western countries. To date, it is not established whether those favourable time trends developed homogeneously for sex and age groups and how they were affected by the number of undetermined deaths. METHODS: Data on suicide mortality and undetermined death from 1991 to 2002 in Germany were obtained from the German Federal Statistical Office. For each year, the age-standardised suicide rate (SR), undetermined death rate (UDR) and total rate (SR+UDR) was calculated by direct standardisation separately for men and women. Time trends were analyzed by Poisson regression estimating the average annual percentage change (AAPC) of the rates for sex and four age groups (15–24, 25–44, 45–74, ≥ 75 years). RESULTS: A significant decline of the SR was observed in all age groups but was less pronounced among the younger ages, particularly among men aged 15–24 years (AAPC -0.7%, p = 0.041). The SR in the oldest male age group (≥ 75 years) declined much stronger (AAPC -3.5%, p < 0.001). In women, the AAPC of the SR ranged from -1.7% to -4.6%. The average annual percentage changes in the age groups 25 – 74 years did not differ substantially for SR and SR+UDR. In contrast, due to an increase of undetermined deaths for subjects ≥ 75 years, time trends in this age group were affected by the number of undetermined deaths, especially in women. CONCLUSION: Observing downward trends in suicide mortality with lower declines for younger subjects, prevention strategies should focus in particular on younger subjects