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Introduction: Contemporary dosing strategies for rabbit anti-thymocyte globulin (rATG) in kidney transplantation aim to reduce cumulative exposure, minimizing long-term adverse events. The use of ideal body weight-based dosing has been trialed, however concern for increased rejection post-transplant exists due to lower doses of rATG. Research Questions: The primary aim of this study was to compare rejection rates between rATG dosing protocols using actual body weight and ideal body weight and secondarily to evaluate cost savings following protocol implementation. Design: This was a retrospective study surrounding implementation of an ideal body weight-based dosing protocol for rATG. We compared 75 kidney transplant recipients in whom rATG was dosed based on actual body weight (pre-protocol group) to 64 in whom dosing was based on ideal body weight (post-protocol group), following a nine-month washout. Results: The mean cumulative rATG dose in the pre-protocol group was 6.3 mg/kg of actual body weight. When ideal body weight was used in the post-protocol group, the mean dose was 4.5 mg/kg of actual body weight. The rejection rate was 18.7% pre-protocol and 23.4% postprotocol, which did not represent a statistically significant difference (p = 0.491). The actual annual cost savings after protocol implementation exceeded $162,000, approximately $2,500 per patient. Conclusion: Results suggest ideal body weight-based dosing of rATG may reduce exposure and cost, without significantly impacting the risk of rejection in kidney transplant recipients. More studies are needed to confirm these findings.

BACKGROUND: In patients exposed to high-dose methotrexate (HDMTX; ≥1g/m(2)) with a history of elevated methotrexate (MTX) concentrations during previous doses, it is unclear whether prescribing high-dose leucovorin (HDLV) rescue limits future high levels or reduces the likelihood of acute kidney injury (AKI). METHODS: This retrospective, single-center study longitudinally followed adult lymphoma patients treated with HDMTX between 1/1/2011 and 10/31/2017 from diagnosis until 30 days after the last HDMTX dose. Endpoints included elevated MTX concentrations at 48 h (≥1.0 μmol/L) and incident AKI after each HDMTX dose. RESULTS: The 321 included patients had a median (IQR) age of 65 (57, 72) years, 190 (59%) were male, and 293 (91%) were Caucasian. There were 1558 HDMTX doses [median (IQR) 3 (2, 6) doses per patient] prescribed with 265 (83%) patients receiving more than one MTX dose. Those receiving HDLV rescue were more likely to have an elevated MTX concentration after that dose (OR = 2.69, 95% CI: 1.75–4.11, p < 0.001). Receiving HDLV rescue was associated with a greater likelihood of AKI after MTX (OR = 2.18, 95% CI: 1.38–3.43, p < 0.001). Hospital LOS was longer in those prescribed empiric HDLV rescue after MTX than those prescribed standard leucovorin with an estimated difference of 1.1 days, (95% CI: 0.5–1.7, p < 0.001). CONCLUSION: Sequential HDMTX doses are associated with a significant incidence of elevated MTX levels and AKI during lymphoma management. HDLV rescue prescribed during subsequent MTX doses in patients with a previously elevated level was not associated with improved safety outcomes. The optimal supportive care strategy following HDMTX administration requires further investigation.

Many families seek medical care at pediatric urgent care centers. The objective of this study was to determine social and unintentional injury risks reported by these families.This cross-sectional study surveyed a convenience sample of guardians of patients 1 to 5 years of age presenting to our pediatric urgent care, 9/10/21 to 2/25/22. Outcomes were the number of reported social and unintentional injury risks. Predictors and covariates included child and parent demographic characteristics and a neighborhood socioeconomic deprivation index. Chi-square, Student's t test, Pearson's correlation tests, and multinominal regression were used.A total of 273 guardians (and children) were included; 245 of guardians (89.7%) were female; 137 (50.2%) of included children identified as Black. Approximately 60% reported ≥1 social risk; 31.5% reported ≥3. Approximately 90% reported ≥1 unintentional injury risk; 57.9% reported ≥3. There were significant associations between social risk presence and Black race, public/no insurance, and neighborhood deprivation (all P.05). There were no significant associations between unintentional injury risks and assessed predictors. Black guardians were more likely than those of other races to report a greater number of social risks (adjusted odds ratio [AOR] 2.90, 95% confidence interval [CI] 1.50, 5.58 for ≥3 vs 0 risk). Children with public/no insurance compared to private insurance were more likely to experience a greater number of social risks (AOR 3.34, 95% CI 1.42, 7.84 for ≥3 vs 0 risks).Many presenting to pediatric urgent cares experience social and unintentional injury risks. Risk identification may guide equitable responses.

Kristen M Peterson, Carrie E Huisingh, Christopher Girkin, Cynthia Owsley, Lindsay A Rhodes Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA Background: The purpose of this study was to determine the factors associated with glaucoma patients’ satisfaction with their medical care by fellowship-trained glaucoma specialists in an urban tertiary referral clinic in the US.Methods: A total of 110 established patients aged ≥60 years with a diagnosis of either primary open angle glaucoma, glaucoma suspect, or ocular hypertension monitored by an ophthalmologist with fellowship training in glaucoma were enrolled at an academic, urban, tertiary referral eye clinic. Enrolled patients were administered a general demographics questionnaire along with a Patient Satisfaction Questionnaire-18 (PSQ-18), a Likert scale validated tool. The seven dimensions of patient satisfaction from the PSQ-18 were summarized for the sample overall and by the patients’ age, race, employment status, education level, distance travelled from home address to clinic, and glaucoma therapy type. Two-sample t-tests were used to compare group means. Spearman correlation coefficients were used to correlate satisfaction scores with peripheral vision and visual acuity function.Results: Overall, the general satisfaction scores were high (mean 4.62). Patients ≥70 years of age had lower general satisfaction with their care (mean 4.5 vs 4.8, p=0.03), the interpersonal manner of their appointment (mean 4.7 vs 4.9, p=0.009), and with their time spent with their doctor (mean 4.4 vs 4.7, p=0.03) than patients aged 60–69 years. Non-European descent patients (47% African descent and 1% other of sample) were more satisfied with the time they spent with the doctor (mean 4.7 vs 4.4, p=0.04) and with the communication during the appointment (mean 4.8 vs 4.6, p=0.04) than European descent patients (52% of sample). Patients with a higher level of education (>high school degree) were less satisfied with the accessibility and convenience of the appointment (mean 4.3 vs ≤ high school, 4.6, p=0.02). There were no statistically significant differences in patient satisfaction based upon employment status, distance travelled to clinic, prior glaucoma therapy, or visual function.Conclusion: Overall, across all dimensions of the PSQ-18, patients were highly satisfied with the care they received at the urban tertiary care glaucoma clinic. Keywords: patient satisfaction, glaucoma, tertiary care, access to care, adherence, barriers to care

Background Allogeneic hematopoietic cell transplantation (allo-HCT) allows for the possibility of cure in patients (pts) with Non-Hodgkin Lymphoma (NHL) as it provides an immunologic graft-versus-lymphoma effect. Non-relapse mortality (NRM) was prohibitive in myeloablative regimens, but technical advances with the advent of reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) regimens have decreased these rates. RIC regimens are generally associated with more toxicity and higher NRM than NMA regimens. Though studies showed both approaches are safe and effective, there is lack of direct comparison between these different intensities in NHL. Methods This retrospective study identified pts aged ≥ 18 years who underwent allo-HCT for relapsed/refractory NHL between 3/2008-6/2017 at our center. Outcomes were compared between pts who received NMA and RIC conditioning, with intensity defined per CIBMTR. Progression-free survival (PFS) was the primary outcome. Secondary outcomes included overall survival (OS) and non-relapse mortality (NRM). Additional outcomes included rates of acute GVHD at Day 100, chronic GVHD, and CMV reactivation at Day 100. Regimen intensity and other variables significant by univariate analysis were included in the multivariate analysis Results For the 144 pts identified, median age was 56 years (range, 19-79). More pts received NMA regimens (n=80, 56%) and most did not undergo prior autologous HCT (n=103, 72%). NMA regimens were given more frequently to pts with indolent B-cell lymphoma and were more likely to receive ATG and/or rituximab (p = 0.008, p Conclusion Our study suggests that there are comparable and favorable outcomes between RIC and NMA regimens in allo-HCT for NHL with careful patient and regimen selection. Further studies are needed to better define criteria in choosing between NMA and RIC allo-HCT regimens for pts with NHL.

The cornea is the most frequently transplanted tissue in the human body. The primary cause of corneal graft failure is immune rejection, a highly complex sequence of innate and adaptive immune responses that interact to promote tissue destruction. As our understanding of the effector pathways that drive allograft rejection has deepened, so too has our comprehension of the diverse immunoregulatory mechanisms that restrain the effector response and promote graft tolerance. This chapter reviews the incidence, the risk factors and the cellular and molecular mechanisms that underlie corneal allograft rejection. The amalgam of anatomical features, immune cells, and immunoregulatory factors that promote tolerance and immune quiescence are described. Finally, possibilities for future therapeutic approaches to promote graft survival are considered.

Background: Prolonged methotrexate (MTX) exposure following high-dose methotrexate (HDMTX; ≥1g/m2) occurs in up to 33% of patients and potentially compromises management through increased renal and systemic toxicities.(Pinedo et al, 1977, Joerger et al, 2012) MTX-associated acute kidney injury (AKI) occurs in 5% to 30% of patients.(May et al, 2014) Rescue leucovorin dose escalation in response to an elevated 48-hour MTX concentration or serum creatinine rise is standard-of-care to reduce adverse events. The practice of preemptive leucovorin dose increases in patients with elevated MTX concentrations or previous AKI during prior MTX doses has unclear outcomes. Methods: This retrospective, single-center, cohort study was approved by the Mayo Clinic IRB and performed in accordance with the ethical standards of the 1964 Declaration of Helsinki. We identified patients newly initiated on HDMTX for management of lymphoma between 1/1/2011 and 10/31/2017 at Mayo Clinic in Rochester, MN. Patients were followed longitudinally until HDMTX was discontinued. The primary endpoint was the proportion of patients with an elevated MTX concentration (MTX > 1.0 mcmol/L) at 48 hours for the initial cycle. Secondary endpoints included the incidence of AKI (Kellum et al, 2012) and whether preemptively increased leucovorin doses during subsequent cycles of HDMTX impacted the incidence of a repeated episode of an elevated 48-hour MTX concentration, decreased incidence of AKI, or decreased hospital length of stay (LOS) compared to patients with standard leucovorin dosing (25mg intravenous every 6 hours until MTX < 0.1 mcmol/L). Results: The 321 included patients had a median (IQR) age of 65 (57, 72) years, 190 (59%) were male, and 293 (91%) were Caucasian. Baseline demographics and clinical characteristics are depicted in table 1 with those who had elevated MTX levels during their initial cycle more likely to be Male, Caucasian, have a higher BSA, have Primary DLBCL of the CNS, have bone marrow involvement, have a higher baseline SCr, higher total bilirubin, and lower albumin. The median (IQR) grams of the initial MTX dose was 6.3 (4.3, 7.5) for 84 patients (26%) receiving MTX for prophylaxis and was 12.8 grams (7.5, 16.8) for the 237 patients (74%) receiving MTX as treatment. Chemotherapy regimen distribution included 43 patients (13%) receiving HDMTX 8 grams/m2 monotherapy, 162 patients (50%) receiving HDMTX 8 grams/m2 with Rituximab and Temozolomide (MRT), and 96 patients (30%) receiving HDMTX 3.5 grams/m2 in combination with R-CHOP. Patients received a median of 3 MTX doses (IQR:2 doses, 6 doses). A total of 83 patients (36%) had an elevated MTX concentration after their first MTX dose, and the overall incidence of elevated MTX concentrations was 22% following a total of 1558 MTX doses. Preemptively increasing the leucovorin dose (based on the prior MTX concentration) was associated with a 34% rate of elevated MTX concentrations (160/466 cycles). Giving standard leucovorin (based on the prior MTX concentration) was associated with a 12% rate of elevated MTX concentration (84/713 cycles). Those with a preemptively increased leucovorin dose were more likely to have an elevated MTX concentration in that cycle (OR=2.84, 95% CI: 2.03-3.97, p Conclusion: HDMTX leads to a significant incidence of elevated serum 48hr MTX levels and AKI, 22% and 18%, respectively. Rather than protective, we found that preemptively increased leucovorin doses used during subsequent cycles did not improve the incidence of delayed elimination, reduce the incidence of AKI, or shorten hospital LOS per MTX dose. Further investigation is needed to optimize dosing strategies and supportive measures following MTX administration for management of lymphoma patients. Disclosures Barreto: FAST Biomedical, Inc: Consultancy. Leung:Takeda: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Aduro: Membership on an entity's Board of Directors or advisory committees; Omeros: Research Funding.

The goal of this study was to determine the composition and diversity of microorganisms associated with bioaerosols in a heavily trafficked metropolitan subway environment. We collected bioaerosols by fluid impingement on several New York City subway platforms and associated sites in three sampling sessions over a 1.5-year period. The types and quantities of aerosolized microorganisms were determined by culture-independent phylogenetic analysis of small-subunit rRNA gene sequences by using both Sanger (universal) and pyrosequencing (bacterial) technologies. Overall, the subway bacterial composition was relatively simple; only 26 taxonomic families made up ∼75% of the sequences determined. The microbiology was more or less similar throughout the system and with time and was most similar to outdoor air, consistent with highly efficient air mixing in the system. Identifiable bacterial sequences indicated that the subway aerosol assemblage was composed of a mixture of genera and species characteristic of soil, environmental water, and human skin commensal bacteria. Eukaryotic diversity was mainly fungal, dominated by organisms of types associated with wood rot. Human skin bacterial species (at 99% rRNA sequence identity) included the Staphylococcus spp. Staphylococcus epidermidis (the most abundant and prevalent commensal of the human integument), S. hominis , S. cohnii , S. caprae , and S. haemolyticus , all well-documented human commensal bacteria. We encountered no organisms of public health concern. This study is the most extensive culture-independent survey of subway microbiota so far and puts in place pre-event information required for any bioterrorism surveillance activities or monitoring of the microbiological impact of recent subway flooding events.

The environments we humans encounter daily are sources of exposure to diverse microbial communities, some of potential concern to human health. In this study, we used culture-independent technology to investigate the microbial composition of biofilms inside showerheads as ecological assemblages in the human indoor environment. Showers are an important interface for human interaction with microbes through inhalation of aerosols, and showerhead waters have been implicated in disease. Although opportunistic pathogens commonly are cultured from shower facilities, there is little knowledge of either their prevalence or the nature of other microorganisms that may be delivered during shower usage. To determine the composition of showerhead biofilms and waters, we analyzed rRNA gene sequences from 45 showerhead sites around the United States. We find that variable and complex, but specific, microbial assemblages occur inside showerheads. Particularly striking was the finding that sequences representative of non-tuberculous mycobacteria (NTM) and other opportunistic human pathogens are enriched to high levels in many showerhead biofilms, >100-fold above background water contents. We conclude that showerheads may present a significant potential exposure to aerosolized microbes, including documented opportunistic pathogens. The health risk associated with showerhead microbiota needs investigation in persons with compromised immune or pulmonary systems.

Fire detection systems located in aircraft cargo compartments are currently based only on smoke detectors. They generate about 200 false alarms per year for US registered aircraft. The number of false alarms is growing as more planes are outfitted with smoke detectors and air travel expands. Moreover, the survivability of an aircraft in a fire scenario depends on the early detection of the fire. A fire detection system is developed based on the simultaneous measurements of carbon monoxide, carbon dioxide, and smoke. The combination of the rates of rise of smoke and either carbon monoxide or carbon dioxide concentration provides a potential fire alarm algorithm to increase the reliability of aircraft smoke detectors, and to reduce the time to alarm. The fire detection system with the alarm algorithm detected fires that were not alarmed by smoke sensors, and alarmed in shorter times than smoke sensors operating alone.

Background: Our objective was to determine whether a tailored, stage-matched educational intervention, guided by the transtheoretical model (TTM), would increase rates of repeat-screening mammography. Design Setting/Participants: A total of 1324 women (N=1026 after attrition) aged 50 to 74 years were recruited from a staff-model health maintenance organization. Some of the women were not due for mammograms at the time of recruitment. Intervention: Women were randomly assigned to one of three intervention conditions: Group 1, no educational materials (usual care); Group 2, standard materials; and Group 3, stage-matched/tailored materials. Women in Groups 2 and 3 received a mailed education packet after both a baseline and a follow-up telephone interview. All women in Group 2 received the same materials regardless of differences in baseline mammography-related attitudes and behaviors. Each woman in Group 3 received materials based on her stage of adoption for mammography and TTM constructs. Main Outcome: Using clinical records, repeat screening was defined as receipt of a second mammogram within 14 months after obtaining an initial postbaseline mammogram. Results: Women in Group 3 were more likely to obtain repeat-screening mammograms than women in Group 1 (44.2% vs 35.8%; adjusted rate ratio = 1.29, 95% confidence interval [CI]=1.11–1.46; adjusted rate difference = 0.06, 95% CI=−0.01–0.13). The screening percentage in Group 2 was intermediate (39.3%), and did not differ from either Group 3 or Group 1. Conclusions: The effect of the stage-matched/tailored intervention was sustained for repeat screening, although no educational materials were delivered to coincide with the timing for a second mammogram. However, the stage-matched/tailored intervention was not sufficient to have a substantial impact on screening beyond the effect of standard educational materials. Future interventions may need to administer “booster” sessions to increase repeat screenings.

Mid-infrared transient absorption (“pump−probe”) measurements on the amide I band of myoglobin in D2O and in a glass-forming D2O/glycer(ol-d3) solvent mixture reveal very rapid vibrational energy r...

The two purposes of this investigation were: (a) to examine whether an association existed between stages of adopting regular mammography and decision-making constructs from the Transtheoretical Model (TTM) of behavior change, and (b) to determine whether any such associations would be found for each of the two ways of defining the stages-of-adoption. One method integrated past screening history with a report of future intention for screening; the other method used a single item with predetermined response categories. Data were from the baseline survey of 1,323 women aged 50–74 who were recruited as part of an intervention study through a local Health Maintenance Organization. Results showed that both ways of defining stages of adopting regular mammography were associated with decisional balance and processes-of-change. The method that integrated past history plus intention provided somewhat better discrimination among stages. Women who were labeled as being at “Risk of Relapse,” and those who said they waited for a “Provider’s Recommendation,” may be useful groups to add to the set of stages that have been employed so far by the TTM. In addition, a tendency to avoid the health care system in general was used as a process-of-change to complement the mammography-specific processes.

Aizhu Tao,1,3 Kristen A Peterson,2 Hong Jiang,1 Yilei Shao,1,3 Jianguang Zhong,1,4 Frank C Carey,2 Elias P Rosen,2 Jianhua Wang11Bascom Palmer Eye Institute, University of Miami, Miami, FL, USA; 2Southwest Sciences, Inc, Santa Fe, NM, USA; 3School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang, People's Republic of China; 4Department of Ophthalmology, Hangzhou First People's Hospital, Hangzhou, People's Republic of ChinaAbstract: We used a unique combination of four state-of-the-art technologies to achieve a high performance spectral domain optical coherence tomography system suitable for imaging the entire ocular surface. An ultra-high resolution, extended depth range, full-phase interferometry, and high-speed complementary metal-oxide semiconductor transistor camera detection provided unprecedented performance for the precise quantification of a wide range of the ocular surface. We demonstrated the feasibility of this approach by obtaining high-speed and high-resolution images of a model eye beyond the corneal–scleral junction. Surfaces determined from the images with a segmentation algorithm demonstrated excellent accuracy and precision.Keywords: ocular surface, complex, full range, optical coherence tomography

Picosecond mid-IR pump-probe measurements of vibrational relaxation (VR) of CO bound to the active sites of wild-type and mutant myoglobins (Mb) reveal that an approximately linear relationship exists between the protein matrix-induced CO frequency shift and the VR rate. This relation parallels a similar linear relationship seen in a series of heme model compounds where Fe was replaced by Ru and Os. The VR rate of CO in the Mb is sensitive only to the magnitude of protein-induced carbonyl frequency shifts and apparently is not sensitive to the specific details of how the shift is induced, e.g., hydrogen bonding to CO or electrostatic interactions in the heme pocket. CO VR is insensitive to substantial changes in protein structure that do not affect the CO vibrational frequency. These observations suggest that the mechanism of carbon monoxide VR in heme proteins such as Mb occurs by through-﷿-bond anharmonic coupling, which, as shown in prior work, is also the dominant coupling in the model compounds. The experiments indicate that differing protein structures influence VR of CO bound at the active site not by opening and closing channels for vibrational energy flow from CO to the protein but by affecting the rate of energy flow from CO to heme. The rates are determined by the extent of back-bonding, which determines the magnitude of through-﷿-bond anharmonic coupling between CO and heme. The back-bonding and, therefore, the extent of anharmonic coupling are influenced by the electric fields in the heme pocket, which likely differ in the proteins studied here.

Vibrational relaxation of carbon monoxide bound to a series of metalloporphyrin complexes (M-(coproporphyrinate-I tetraisopropyl ester)(CO)(pyridine); M = Fe, Ru, Os) was measured using picosecond infrared pump-probe experiments. The vibrational relaxation rates ((1–2.5) × 10 10 s −1 ) increased with increasing mass of the metal ion. This effect is opposite that predicted by through-σ-bond models and is interpreted as arising from a through-π-bond coupling between the CO vibrational fundamental and porphyrin vibrations.

Time-resolved infrared (TRIR) techniques have been employed to study the reactions of carbon monoxide with the cytochrome alpha 3-Cu(B) site of cytochrome c oxidase (CcO). The ligation dynamics immediately following photodissociation have been investigated using picosecond TRIR spectroscopy and linear dichroism. The rate of photoinitiated transfer of CO from cytochrome alpha 3 to CuB was measured directly by monitoring the development of the transient CuBCO absorption. In less than 1 ps, a stationary CuBCO spectrum develops, which together with the CO infrared linear dichroism is constant until the CO dissociates from CuB on a microsecond time scale. These observations indicate that the CO is transferred between metals and reaches its equilibrium conformation in less than 1 ps. This unprecedented ligand transfer rate has profound implications with regard to the structure and dynamics of the cytochrome alpha 3-CuB site, the functional architecture of the protein, and coordination dynamics in general.

A complication of Fourier domain optical coherence tomography (OCT) methods, such as spectral domain and swept source OCT, is the complex conjugate ambiguity due to inverse Fourier transform of real-valued data. As a result, the image is symmetric to the zero plane, and only half of the theoretical imaging depth range is used to avoid overlapping "mirror images" that confuse the image. We have previously demonstrated harmonic detection in a video-rate spectral domain OCT system using a high speed line scan camera. Harmonic detection removes the complex conjugate ambiguity by providing the real and imaginary components of the spectral interferogram. In this work, we show that harmonic detection is easily applied to swept source OCT to remove the complex conjugate ambiguity while maintaining the imaging performance of the original swept source instrument. Harmonic detection swept source OCT allows simultaneous experimental determination of the real and imaginary components of each spectral interferogram without the need to measure consecutive A-scans at differing phase. This harmonic detection swept source optical coherence tomography system exhibits 110 dB sensitivity, up to 55 dB dynamic range, ≥ 50 dB complex conjugate rejection, and operates at the full 16 kHz sweep rate of the swept source laser for real-time video rate imaging.

Real-time video-rate imaging using harmonically detected Fourier domain OCT is demonstrated using an 800 nm light source and a silicon line scan camera. At an imaging rate of 11.7 B-scans (1024 pixels × 256 pixels) per second, the measured complex conjugate artifact suppression is 30–35 dB, the sensitivity is 121 dB, and the dynamic range is about 60 dB. Keywords: optical coherence tomography; medical and biological imaging 1. INTRODUCTION Fourier domain optical coherence tomography (FDOCT) has lately become an attractive alternative to conventional time domain OCT (TDOCT) because it has been demonstrated, both theoretically and experimentally, that FDOCT has a sensitivity advantage over TDOCT at a given imaging speed. 1-3 Also, FDOCT is the most promising technique to become a basis for emerging spectroscopically resolved OCT. 4-6 However, a major drawback of FDOCT that limits its practical use is the complex conjugate ambiguity, which is inherent to real Fourier transforms. Because of this artifact, an FDOCT image obtained from a real valued spectral interferogram is always symmetrical with respect to the zero plane (zero phase delay) of the interferometer. To avoid ambiguity in interpretation of the image, the zero plane must be positioned outside of the imaged sample. Thus, only one half of the imaging depth range is useful in practice. Resolving the complex conjugate ambiguity would double the imaging depth range and provide additional flexibility by allowing arbitrary positioning of the zero plane, e.g. , moving it inside the sample. The problems of obtaining the full complex interferogram and resolving the complex conjugate ambiguity in FDOCT have been addressed using different approaches, including phase-shifting methods

Time‐resolved fluorescence depolarization has been used to measure electronic excitation transport among naphthyl chromophores in polymeric glasses. 2‐ethylnaphthalene randomly distributed in PMMA and 2‐vinylnaphthalene/methyl methacrylate copolymer in PMMA were studied. It was found that excitation transport is dispersive at all temperatures studied, from 50 K to room temperature, i.e., the extent of transfer depends on the excitation wavelength within the S0–S1 absorption band. A theory based on the nondispersive, Forster mechanism for excitation transfer has been developed to describe dispersive transport. Good agreement between the theoretical and experimental results are achieved without resorting to adjustable parameters. Both the theory and experiment show that, for the observable used here, excitation at a certain wavelength, called the ‘‘magic wavelength,’’ results in a time dependence that is identical to the Forster nondispersive result, i.e., dispersive transport appears to vanish.

Electronic excitation transport among naphthyl chromophores in low concentration on isolated chains of poly(2-vinylnaphthalene-co-methyl methacrylate) dispersed in both PMMA and PVAc is monitored by time-resolved fluorescence depolarization spectroscopy. Analysis of the results with a theory for excitation transport in finite volume systems allows the quantitative determination of the root-mean-square radius of gyration ((R g 2 ) 1/2 ) of PMMA in the two hosts. The results for bulk PMMA agree with expected values for PMMA in a θ solvent. A significant decrease in (R g 2 ) 1/2 for isolated PMMA chains is observed in the PMMA/PVAc blend

A combination of two optical methods — Fourier-domain optical coherence tomography (FD-OCT) and photo-stimulated luminescence piezo-spectroscopy (PLPS) is used as a non-destructive evaluation (NDE) tool for thermal barrier coatings (TBC). This research is focused on NDE of electron beam physical vapor deposition (EB-PVD) TBC’s. FD-OCT is an interferometric technique, which uses spectrally broadband visible or infrared light to obtain spectrally resolved interferograms of the light that is back-scattered from subsurface structures and defects (e.g., interfaces, cracks, voids) in optically translucent material. When the Fourier transform is applied to the interferogram, a depth-resolved image of the back-scattering sites is obtained. FD-OCT is shown to be a useful NDE tool that can profile the top coat-metal substrate interface and measure the top coat thickness. Also, it has the potential of assessing microcracking and spallation damage. PLPS provides quantitative information on stress in the thermally grown oxide (TGO) by measuring the spectral shifts in the laser-induced luminescence spectra of the Cr3+ ions present in the TGO. When combined, the PLPS and FD-OCT methods can provide a set of important input parameters for the TBC remaining life predicting model. Ultimately they will collect spatially resolved data on matching spatial domains. The two optical methods are applied to thermally cycled EB-PVD TBC samples. The experimental results are compared to destructive inspection data.Copyright © 2007 by ASME

Fourier domain optical coherence tomography (FD-OCT) is an interferometric imaging technique that allows imaging to depths of a few mm in scattering biological tissues with high resolution of the order of 1-10 μm. However, the usefulness of FD-OCT is limited by background and autocorrelation interference terms that reduce the sensitivity and by phase ambiguity that halves the useful imaging depth range. These limitations can be overcome by obtaining the full, complex spectral interferogram. Simultaneous detection of the imaginary and real terms is obtained by phase modulating the reference arm of the interferometer and detecting at the first and second harmonics. A mathematical derivation of harmonically detected FD-OCT and experimental measurements showing that phase ambiguity artifacts can be suppressed by up to 70 dB are presented. The method provides efficient suppression of the complex conjugate, dc, and autocorrelation artifacts and has low sensitivity to phase noise. Beyond the removal of artifacts, the ability to obtain the full, complex interferogram is key to the development of spectrally resolved FD-OCT which would add depth-resolved spectroscopic detail to the structural information.

A new method of resolving the complex conjugate ambiguity in FD-OCT, where the quadrature components of the interferogram are obtained by simultaneous acquisition of the first and second harmonics of the phase-modulated interferogram, is presented.

Backscatter gas imaging uses laser absorption spectroscopy to detect the presence of a gas by illuminating a region with light from an infrared laser and imaging the returned light. Contrast can be enhanced by comparing the back-scattered intensity on and off the absorption feature. Wavelength modulation spectroscopy can provide just such a capability, but the detector signal must be processed with a lock-in amplifier, which is incompatible or prohibitively expensive with most array detectors. Images can be recorded using a single photodiode by spatially modulating the laser or the detected image. This paper describes initial experiments to demonstrate the feasibility of a combined wavelength- and spatially- modulated gas imager. It is based on a single near-infrared laser, a single detector, lock-in detection, and a commercial micromirror array. The gases imaged include water vapor, mono-deuterated water vapor, acetylene and hydrogen cyanide. Doppler imaging is demonstrated using heterodyne detection and spatial image modulation.

We present a new detection method for confocal fluorescence microscopy that simultaneously performs fluorescence lifetime measurement in multiple spectrally resolved channels. By detecting two physical characteristics, discrimination of fluorescent labels may be improved.

Differential spectral interferometry is a straightforward modification of spectral interferometry that allows an AC data acquisition mode and results in substantial improvement of the imaging dynamic range. Applications to biological imaging will be presented.

A Michelson-type spectral interferometer that uses a common beam path for the reference and the sample arms is described. This optical arrangement is more compact and stable than the more commonly used dual-arm interferometer and is well suited for frequency-domain optical coherence tomography of biological samples. With a 16-bit CCD camera, the instrument has sufficient dynamic range and resolution for imaging to depths of 2 mm in scattering biological materials. Images obtained with this spectral interferometer are presented, including cross-sectional images in a Xenopus laevis tadpole.

Differential spectral interferometry (DSI), a novel technique for biomedical imaging is proposed. The method combines the high dynamic range of time-domain OCT with inherently parallel low-bandwidth image acquisition of frequency-domain OCT. Perspectives for medical applications are discussed.

Our objective was to determine whether a tailored, stage-matched educational intervention, guided by the transtheoretical model (TTM), would increase rates of repeat-screening mammography. DESIGN SETTING/PARTICIPANTS: A total of 1324 women (N=1026 after attrition) aged 50 to 74 years were recruited from a staff-model health maintenance organization. Some of the women were not due for mammograms at the time of recruitment.Women were randomly assigned to one of three intervention conditions: Group 1, no educational materials (usual care); Group 2, standard materials; and Group 3, stage-matched/tailored materials. Women in Groups 2 and 3 received a mailed education packet after both a baseline and a follow-up telephone interview. All women in Group 2 received the same materials regardless of differences in baseline mammography-related attitudes and behaviors. Each woman in Group 3 received materials based on her stage of adoption for mammography and TTM constructs.Using clinical records, repeat screening was defined as receipt of a second mammogram within 14 months after obtaining an initial postbaseline mammogram.Women in Group 3 were more likely to obtain repeat-screening mammograms than women in Group 1 (44.2% vs 35.8%; adjusted rate ratio = 1.29, 95% confidence interval [CI]=1.11-1.46; adjusted rate difference = 0.06, 95% CI=-0.01-0.13). The screening percentage in Group 2 was intermediate (39.3%), and did not differ from either Group 3 or Group 1.The effect of the stage-matched/tailored intervention was sustained for repeat screening, although no educational materials were delivered to coincide with the timing for a second mammogram. However, the stage-matched/tailored intervention was not sufficient to have a substantial impact on screening beyond the effect of standard educational materials. Future interventions may need to administer "booster" sessions to increase repeat screenings.

We describe a novel pump-probe optical method, based on a Sagnac (anti-resonant ring) interferometer, which removes over 99% of the DC background light inherent in normal, two beam pump-probe measurements. Suppression of the DC component is critical for pumpprobe imaging applications. In addition, this method greatly increases the signal-to-noise ratio compared with normal, two beam pump-probe measurements. The technique is demonstrated by detection of Rb atoms aspirated into a flame. The placement of the flame near the center of the ring interferometer reduces noise caused by flame turbulence.

The population lifetime of the amide I vibration (v10 fundamental, ca. 1650 cm-1) in the protein myoglobin in D2O has been determined by picosecond infrared pump- probe spectroscopy using the Stanford mid-infrared free electron laser to be 1.3 +/- 0.2 ps. In a glass forming mixture of deuterated glycerol and D2O, the vibrational lifetime was found to increase from 1.3 +/- 0.2 ps at 310 K to 1.8 +/- 0.2 ps at 10 K. In addition to determining the time-scale of vibrational relaxation, we also observed multi-level vibrational excitation which has implications regarding the anharmonicity and homogeneous linewidth of the mode.

We have made direct measurements of the vibrational lifetimes of carbonmonoxide (CO) bound at the active site of wildtype myoglobin [1] and myoglobin with single residue mutations in the binding pocket. Measurements were also made for CO bound to water soluble metalloporphyrins with differing metals and peripheral substituents. A pump-probe technique using tunable microjoule pulses from an infrared free-electron laser was used to monitor the loss of vibrational energy from the CO ligand with 2 picosecond time resolution. Recovery to the CO vibrational ground state in both the protein and soluble porphyrin systems occurs in the range from 10 to 30 picoseconds. The vibrational lifetime of CO bound to myoglobin is essentially independent of temperature from 20 to 300 K.

Vibrational lifetimes of CO bound to myoglobin and to a water-soluble Fe:porphyrin were measured by ps infrared experiments. Vibrational relaxation rates are found to depend on protein conformational substate and porphyrin substitution. We have made direct measurements of molecular energy transfer at the active site of a protein using intense tunable mid-IR pulses from a free-electron laser to measure the loss of vibrational energy from CO bound to a bare water soluble heme and CO bound to the active sites of different conformational substates of myoglobin. Vibrational relaxation rates are found to depend on protein conformational substate and porphyrin substitution.

A free-electron laser (FEL) microscope has been constructed to perform spatially and spectrally resolved pump/probe experiments in single living cells. Picosecond infrared FEL pulses are absorbed by the sample and rapidly converted to heat. Excitation of localized fluorescent reporter molecules using a UV/VIS probe beam leads to thermally induced alterations in the radiative signal. Fluorescence-detected infrared (FDIR) spectra are generated from regions proximal to reporter molecules by varying the FEL pump wavelength. Sub- wavelength spatial resolution is a composite function of media thermal properties and probe selectivity.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Ultra-fast time-resolved infrared spectroscopy is discussed as a tool for investigating protein dynamics. Due to continuing developments in laser technology, researchers have recently begun to take advantage of the utility of vibrational spectroscopies as structural probes in studying the fast timescale dynamics of complex macromolecular systems. The structural complexity of proteins necessitates a wide range of infrared frequencies and timescales in order to obtain a detailed understanding of their conformational dynamics. Free electron lasers are uniquely well suited to this task, as designs are possible which provide ultra-short coherent light pulses throughout the infrared spectral region. Studies planned for the Stanford Picosecond FEL Center on reaction dynamics in the trans-membrane cytochrome oxidase proteins and protein folding in polypeptides are described. These serve as examples of the contributions free electron lasers will make in the fields of biochemistry and biophysics.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Significant advances have been made in the design and characterization of molecular assemblies, which, when photolyzed, undergo intramolecular electron or energy transfer. Time-resolved resonance Raman spectroscopy has been successfully applied to the study of excited states and molecular assemblies, but time-resolved infrared spectroscopy is particularly well-suited for complexes containing ligands such as CO or CN. Unlike the transient Raman experiment, infrared spectroscopy does not rely on resonance enhancement in the excited state since the metal-CO and -CN stretching vibrations have high oscillator strengths, providing high sensitivity. We describe here a novel application of the technique to the elucidation of intramolecular energy transfer in the ligand-bridged complex [(phen)(CO)[sub 3]Re[sup I](NC) Ru[sup II](CN) (bpy)[sub 2]][sup +] (phen is 1, 10-phenanthroline; bpy is 2,2'-bipyridine). These results show that the transient infrared technique can be a powerful tool for the elucidation of oxidation state and mechanisms involving photochemical intermediates by direct observation of ligand vibrations. 15 refs., 2 figs.

Significant advances have been made in the design and characterization of molecular assemblies which, upon photoexcitation, undergo intramolecular electron or energy transfer.1 These reactions have typically been followed by transient electronic absorption spectroscopy. This technique, however, suffers from the disadvantage that absorption bands tend to be broad and featureless which can lead to ambiguous interpretation in complex assemblies, especially where there is more than one absorbing chromophore. Time-resolved resonance Raman spectroscopy has been applied to the study of excited states,2 but time-resolved infrared spectroscopy (TRIR) is particularly well-suited to probing complexes containing ligands such as CO or CN which are bound to the metal.3 Unlike the transient Raman experiment, TRIR does not rely on resonance enhancement in the excited state since the metal-CO and -CN stretching vibrations have large oscillator strength providing high sensitivity. We describe here a novel application of TRIR spectroscopy to the elucidation of intramolecular energy transfer in the ligand-bridged complex, [(phen)(CO)3ReI(NC)RuII(CN)(bpy)2]+ (phen is 1,10-phenanthroline, bpy is 2,2'-bipyridine),4 representing the first application of the technique to a process of this type.

Cytochrome c oxidase (CcO), an enzyme which catalyzes the reduction of dioxygen to water in the terminal step of the respiratory chain, combines several fundamental chemical processes in performing its function; electron, proton and ligand transfers.[1] The coordination chemistry and ligation dynamics of the cytochrome a 3-CuB site, where O2 and other small molecules such as CO, NO and isocyanates can bind, are essential to the function of the enzyme.[2] The sensitivity of the vibrational frequencies and bandwidths of small molecules to changes in coordination and environment makes infrared spectroscopy uniquely useful as a probe for those processes, particularly at CUB +, which generally is not observable by other spectroscopies. [1,2] Recent time-resolved infrared (TRIR) and visible absorption measurements have shown that coordination to CuB + is an obligatory mechanistic stop for CO entering the cytochrome a 3 heme site and departing the protein after photodissociation. [2] The timescale (> 10−7 s) of the TRIR measurements, however, precluded observation of the ligation dynamics immediately following photodissociation. Here we report a picosecond timescale TRIR study of these events. The results reveal that the photoinitiated ligand transfer of CO from Fea3 2+ to CuB +, which are believed to lie 4–5 A apart [1], occurs within 1 ps.

Time-resolved electronic absorption, infrared, resonance Raman, and magnetic circular dichroism spectroscopies are applied to characterization of the intermediate which is formed within 20 ps after photodissociation of CO from cytochrome a3 of reduced cytochrome oxidase. This intermediate decays with the same halflife (ca. 1 microsecond(s)) as the post- photodissociation CuB+-CO species previously observed by time-resolved infrared. The transient UV-Vis spectra, kinetics, infrared, and Raman evidence suggest that an endogenous ligand is transferred from CuB to Fea3 when CO binds to CuB, forming a cytochrome a3 species with axial ligation which differs from the reduced unliganded enzyme. The time-resolved magnetic circular dichroism results suggest that this transient is high spin and therefore five coordinate. Thus it is inferred that the ligand from CuB binds on the distal side of cytochrome a3 and displaces the proximal histidine imidazole. This remarkable mechanistic feature is an additional aspect of the previously proposed 'ligand shuttle' activity of the CuB/Fea3 pair. The authors suggest that the ligand shuttle may play a functional role in redox-linked proton translocation by the enzyme. More detail on this work is presented elsewhere.© (1991) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Time-resolved infrared spectroscopy (TRIRS) has been employed to study the reactions of small molecules with the cytochrome a3-CuB site of cytochrome c oxidase (CcO). All phases of these reactions have been investigated, from ultrafast phenomena (hundreds of femtoseconds) to relatively slow processes (milliseconds). The ligation dynamics immediately following photodissociation have been studied using a TRIRS technique with time resolution of less than 1 ps. The rate of photoinitiated transfer of CO from Fea32+ to CuB+ was measured directly by monitoring the development of the transient CuB+-CO absorption. The development of a stationary CuB+ spectrum which is constant until the CO dissociates from CuB+ occurs in less than 1 ps, indicating that the photoinitiated transfer of CO is remarkably fast. This unprecedented ligand transfer rate has profound implications with regard to the structure and dynamics of the cytochrome a3-CuB site, the functional architecture of the protein and coordination dynamics in general. The photodissociation and recombination of CN- has also been studied using a real-time TRIR technique. The CN- recombination rate of 430 s-1 is consistent with a recombination pathway similar to the one we have previously proposed for CO, in which a long-lived barrier to recombination is formed by the binding of an endogenous ligand L to Fea32+. The authors suggest the rate determining step for CN- recombination is the thermal dissociation of the Fea32+-L bond.