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3. Polyclonal Regulatory T Cell Therapy for Control of Inflammation in Kidney Transplants

Author

Chandran, S, Tang, Q, Sarwal, M, Laszik, ZG, Putnam, AL, Lee, K, Leung, J, Nguyen, V, Sigdel, T, Tavares, EC, Yang, JYC, Hellerstein, M, Fitch, M, Bluestone, JA, and Vincenti, F

Subjects
Organ Transplantation, Clinical Research, Kidney Disease, Clinical Trials and Supportive Activities, Transplantation, Prevention, Evaluation of treatments and therapeutic interventions, Development of treatments and therapeutic interventions, 6.1 Pharmaceuticals, 5.2 Cellular and gene therapies, Renal and urogenital, Adolescent, Adult, Aged, Female, Follow-Up Studies, Glomerular Filtration Rate, Graft Rejection, Graft Survival, Humans, Inflammation, Isoantigens, Kidney Failure, Chronic, Kidney Function Tests, Kidney Transplantation, Male, Middle Aged, Pilot Projects, Postoperative Complications, Prognosis, Risk Factors, T-Lymphocytes, Regulatory, Tissue Donors, Young Adult, cellular biology, clinical trial, immune regulation, immunobiology, immunosuppressant - polyclonal preparations, kidney transplantation/nephrology, protocol biopsy, rejection: subclinical, translational research/science, Medical and Health Sciences, Surgery
Abstract

Early subclinical inflammation in kidney transplants is associated with later graft fibrosis and dysfunction. Regulatory T cells (Tregs) can reverse established inflammation in animal models. We conducted a pilot safety and feasibility trial of autologous Treg cell therapy in three kidney transplant recipients with subclinical inflammation noted on 6-month surveillance biopsies. Tregs were purified from peripheral blood and polyclonally expanded ex vivo using medium containing deuterated glucose to label the cells. All patients received a single infusion of ~320 × 106 (319, 321, and 363.8 × 106 ) expanded Tregs. Persistence of the infused Tregs was tracked. Graft inflammation was monitored with follow-up biopsies and urinary biomarkers. Nearly 1 × 109 (0.932, 0.956, 1.565 × 109 ) Tregs were successfully manufactured for each patient. There were no infusion reactions or serious therapy-related adverse events. The infused cells demonstrated patterns of persistence and stability similar to those observed in non-immunosuppressed subjects receiving the same dose of Tregs. Isolation and expansion of Tregs is feasible in kidney transplant patients on immunosuppression. Infusion of these cells was safe and well tolerated. Future trials will test the efficacy of polyclonal and donor alloantigen-reactive Tregs for the treatment of inflammation in kidney transplants.

Published
2017

6. Photon number resolution using a time-multiplexed single-photon detector

Author

Fitch, M. J., Jacobs, B. C., Pittman, T. B., and Franson, J. D.

Subjects
Quantum Physics
Abstract

Photon number resolving detectors are needed for a variety of applications including linear-optics quantum computing. Here we describe the use of time-multiplexing techniques that allows ordinary single photon detectors, such as silicon avalanche photodiodes, to be used as photon number-resolving detectors. The ability of such a detector to correctly measure the number of photons for an incident number state is analyzed. The predicted results for an incident coherent state are found to be in good agreement with the results of a proof-of-principle experimental demonstration., Comment: REVTeX4, 6 pages, 8 eps figures, v2: minor changes, v3: changes in response to referee report, appendix added, 1 reference added

Published
2003
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7. Heralded Two-Photon Entanglement from Probabilistic Quantum Logic Operations on Multiple Parametric Down-Conversion Sources

Author

Pittman, T. B., Donegan, M. M., Fitch, M. J., Jacobs, B. C., Franson, J. D., Kok, P., Lee, H., and Dowling, J. P.

Subjects
Quantum Physics
Abstract

An ideal controlled-NOT gate followed by projective measurements can be used to identify specific Bell states of its two input qubits. When the input qubits are each members of independent Bell states, these projective measurements can be used to swap the post-selected entanglement onto the remaining two qubits. Here we apply this strategy to produce heralded two-photon polarization entanglement using Bell states that originate from independent parametric down-conversion sources, and a particular probabilistic controlled-NOT gate that is constructed from linear optical elements. The resulting implementation is closely related to an earlier proposal by Sliwa and Banaszek [quant-ph/0207117], and can be intuitively understood in terms of familiar quantum information protocols. The possibility of producing a ``pseudo-demand'' source of two-photon entanglement by storing and releasing these heralded pairs from independent cyclical quantum memory devices is also discussed., Comment: 5 pages, 4 figures; submitted to IEEE Journal of Selected Topics in Quantum Electronics, special issue on "Quantum Internet Technologies"

Published
2003
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8. Experimental Controlled-NOT Logic Gate for Single Photons in the Coincidence Basis

Author

Pittman, T. B., Fitch, M. J., Jacobs, B. C, and Franson, J. D.

Subjects
Quantum Physics
Abstract

We report a proof-of-principle demonstration of a probabilistic controlled-NOT gate for single photons. Single-photon control and target qubits were mixed with a single ancilla photon in a device constructed using only linear optical elements. The successful operation of the controlled-NOT gate relied on post-selected three-photon interference effects which required the detection of the photons in the output modes., Comment: 4 pages, 4 figures; minor changes

Published
2003
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9. High-fidelity quantum logic operations using linear optical elements

Author

Franson, J. D., Donegan, M. M., Fitch, M. J., Jacobs, B. C., and Pittman, T. B.

Subjects
Quantum Physics
Abstract

Knill, Laflamme, and Milburn [Nature 409, 46 (2001)] have shown that quantum logic operations can be performed using linear optical elements and additional ancilla photons. Their approach is probabilistic in the sense that the logic devices fail to produce an output with a failure rate that scales as 1/n, where n is the number of ancilla. Here we present an alternative approach in which the logic devices always produce an output with an intrinsic error rate that scales as 1/n^2,which may have several advantages in quantum computing applications., Comment: 13 pages, 3 figures

Published
2002
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10. Dispersion cancellation and non-classical noise reduction for large photon-number states

Author

Fitch, M. J. and Franson, J. D.

Subjects
Quantum Physics
Abstract

Nonlocal dispersion cancellation is generalized to frequency-entangled states with large photon number N. We show that the same entangled states can simultaneously exhibit a factor of 1/sqrt(N) reduction in noise below the classical shot noise limit in precise timing applications, as was previously suggested by Giovannetti, Lloyd and Maccone (Nature v412 (2001) p417). The quantum-mechanical noise reduction can be destroyed by a relatively small amount of uncompensated dispersion and entangled states of this kind have larger timing uncertainties than the corresponding classical states in that case. Similar results were obtained for correlated states, anti-correlated states, and frequency-entangled coherent states, which shows that these effects are a fundamental result of entanglement., Comment: 8 pages, 4 figures, REVTeX 4, submitted to Phys. Rev. A, v2: minor changes in response to referee report, fig3 fixed

Published
2002
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11. Electro-Optic Sampling of Transient Fields from the passage of High-Charge Electron Bunches

Author

Fitch, M. J., Melissinos, A. C., Colestock, P. L., Carneiro, J. -P., Edwards, H. T., and Hartung, W. H.

Subjects
Physics - Accelerator Physics, Physics - Instrumentation and Detectors
Abstract

When a relativistic electron bunch traverses a structure, strong electric fields are induced in its wake. We present measurements of the electric field as a function of time as measured at a fixed location in the beam line. For a 12 nC bunch of duration 4.2 ps FWHM, the peak field is measured >0.5 MV/m. Time resolution of ~5 ps is achieved using electro-optic sampling with a lithium tantalate (LiTaO_3) crystal and a short-pulse infrared laser synchronized to the beam. We present measurements under several different experimental conditions and discuss the influence of mode excitation in the structure., Comment: 3 pages, 5 figures, LINAC2000 MOC05, LaTeX2e

Published
2000

12. Compression of High-Charge Electron Bunches

Author

Fitch, M. J., Melissinos, A. C., Barov, N., Carneiro, J. -P., Edwards, H. T., and Hartung, W. H.

Subjects
Physics - Accelerator Physics
Abstract

The A0 Photoinjector at Fermilab can produce high charge (10-14 nC) electron bunches of low emittance (20 pi mm-mrad for 12 nC). We have undertaken a study of the optimal compression conditions. Off-crest acceleration in the 9-cell capture cavity induces an energy-time correlation, which is rotated by the compressor chicane (4 dipoles). The bunch length is measured using streak camera images of optical transition radiation. We present measurements under various conditions, including the effect of the laser pulse length (2 ps sigma Gaussian vs. 10 ps FWHM flat top). The best compression to date is for a 13.2 nC bunch with sigma = 0.63 mm (1.89 ps), which corresponds to a peak current of 2.8 kA., Comment: 3 pages, 5 figures, LINAC2000 MOB16, LaTeX2e

Published
2000

14. The passenger hypothesis: HIV exploits CD4 T-cell homeostasis to promote long-term persistence of its reservoirs

Author

Reeves, D., Bacchus-Souffan, C., Fitch, M., Symons, J., Abdel-Mohsen, M., Hoh, R., Ahn, H., Deeks, S., Lewin, S., Hellerstein, M., McCune, J.M., Hunt, P., and Schiffer, J.

Subjects
Antiviral agents -- Patient outcomes, CD4 lymphocytes -- Health aspects, Cell differentiation -- Health aspects, Host-virus relationships, HIV infection -- Development and progression -- Drug therapy, Health
Abstract

Background: The reservoir of latently infected CD4+ T cells ensures HIV persistence during suppressive antiretroviral therapy (ART). The proliferation of reservoir cells carries provirus along as a passenger and produces [...]

Published
2021
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15. Additional file 1 of Exploring patient experiences with a telehealth approach for the PRO-ACTIVE trial intervention in head and neck cancer patients

Author

Khan, M. M., Manduchi, B., Rodriguez, V., Fitch, M. I., Barbon, C. E. A., McMillan, H., Hutcheson, K. A., and Martino, R.

Abstract

Additional file 1. PRO-ACTIVE Ancillary 01 – Telehealth Study Interview Script, Exploring patient experiences with a telehealth approach for the PRO-ACTIVE trial intervention in head and neck cancer patients.

Published
2022
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17. The efficacy, challenges, and facilitators of telemedicine in post-treatment cancer survivorship care: an overview of systematic reviews

Author

Chan, R.J., primary, Crichton, M., additional, Crawford-Williams, F., additional, Agbejule, O.A., additional, Yu, K., additional, Hart, N.H., additional, de Abreu Alves, F., additional, Ashbury, F.D., additional, Eng, L., additional, Fitch, M., additional, Jain, H., additional, Jefford, M., additional, Klemanski, D., additional, Koczwara, B., additional, Loh, K., additional, Prasad, M., additional, Rugo, H., additional, Soto-Perez-de-Celis, E., additional, van den Hurk, C., additional, and Chan, A., additional

Published
2021
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22. Relationship between CD4 T cell turnover, cellular differentiation and HIV persistence during ART

Author

Bacchus-Souffan, C., Fitch, M., Symons, J., Abdel-Mohsen, M., Reeves, D.B., Hoh, R., Stone, M., Hiatt, J., Kim, P., Chopra, A., Ahn, H., York, V.A., Cameron, D.L., Hecht, F.M., Martin, J.N., Yukl, S.A., Mallal, S., Cameron, P.U., Deeks, S.G., Schiffer, J.T., Lewin, S.R., Hellerstein, M.K., McCune, J.M., Hunt, P.W., Bacchus-Souffan, C., Fitch, M., Symons, J., Abdel-Mohsen, M., Reeves, D.B., Hoh, R., Stone, M., Hiatt, J., Kim, P., Chopra, A., Ahn, H., York, V.A., Cameron, D.L., Hecht, F.M., Martin, J.N., Yukl, S.A., Mallal, S., Cameron, P.U., Deeks, S.G., Schiffer, J.T., Lewin, S.R., Hellerstein, M.K., McCune, J.M., and Hunt, P.W.

Abstract

The precise role of CD4 T cell turnover in maintaining HIV persistence during antiretroviral therapy (ART) has not yet been well characterized. In resting CD4 T cell subpopulations from 24 HIV-infected ART-suppressed and 6 HIV-uninfected individuals, we directly measured cellular turnover by heavy water labeling, HIV reservoir size by integrated HIV-DNA (intDNA) and cell-associated HIV-RNA (caRNA), and HIV reservoir clonality by proviral integration site sequencing. Compared to HIV-negatives, ART-suppressed individuals had similar fractional replacement rates in all subpopulations, but lower absolute proliferation rates of all subpopulations other than effector memory (TEM) cells, and lower plasma IL-7 levels (p = 0.0004). Median CD4 T cell half-lives decreased with cell differentiation from naïve to TEM cells (3 years to 3 months, p<0.001). TEM had the fastest replacement rates, were most highly enriched for intDNA and caRNA, and contained the most clonal proviral expansion. Clonal proviruses detected in less mature subpopulations were more expanded in TEM, suggesting that they were maintained through cell differentiation. Earlier ART initiation was associated with lower levels of intDNA, caRNA and fractional replacement rates. In conclusion, circulating integrated HIV proviruses appear to be maintained both by slow turnover of immature CD4 subpopulations, and by clonal expansion as well as cell differentiation into effector cells with faster replacement rates.

Published
2021

23. The efficacy, challenges, and facilitators of telemedicine in post-treatment cancer survivorship care : an overview of systematic reviews

Author

Chan, R. J., Crichton, M., Crawford-Williams, F., Agbejule, O. A., Yu, K., Hart, N. H., de Abreu Alves, F., Ashbury, F. D., Eng, L., Fitch, M., Jain, H., Jefford, M., Klemanski, D., Koczwara, B., Loh, K., Prasad, M., Rugo, H., Soto-Perez-de-Celis, E., van den Hurk, C., Chan, A., other, and, Chan, R. J., Crichton, M., Crawford-Williams, F., Agbejule, O. A., Yu, K., Hart, N. H., de Abreu Alves, F., Ashbury, F. D., Eng, L., Fitch, M., Jain, H., Jefford, M., Klemanski, D., Koczwara, B., Loh, K., Prasad, M., Rugo, H., Soto-Perez-de-Celis, E., van den Hurk, C., Chan, A., and other, and

Abstract

Background: Telemedicine services have been increasingly used to facilitate post-treatment cancer survivorship care, including improving access; monitoring health status, health behaviors, and symptom management; enhancing information exchange; and mitigating the costs of care delivery, especially since the COVID-19 pandemic. To inform guidance for the use of telemedicine in the post-COVID era, the aim of this overview of systematic reviews (SRs) was to evaluate the efficacy of, and survivor engagement in, telemedicine interventions in the post-treatment survivorship phase, and to consider implementation barriers and facilitators. Methods: PubMed, Cochrane CENTRAL, CINAHL, Embase, and Web of Science databases were searched. SRs that examined the use of telemedicine in the post-treatment phase of cancer survivorship, published between January 2010 and April 2021, were included. Efficacy data were synthesized narratively. Implementation barriers and facilitators were synthesized using the Consolidated Framework for Implementation Research. Results: Twenty-nine SRs were included. A substantive body of evidence found telemedicine to benefit the management of psychosocial and physical effects, particularly for improving fatigue and cognitive function. There was a lack of evidence on the use of telemedicine in the prevention and surveillance for recurrences and new cancers as well as management of chronic medical conditions. This overview highlights a range of diverse barriers and facilitators at the patient, health service, and system levels. Conclusions: This review highlights the benefits of telemedicine in addressing psychosocial and physical effects, but not in other areas of post-treatment cancer survivorship care. This large review provides practical guidance for use of telemedicine in post-treatment survivorship care.

Published
2021

24. Relationship between CD4 T cell turnover, cellular differentiation and HIV persistence during ART

Author

O'Doherty, U, Bacchus-Souffan, C, Fitch, M, Symons, J, Abdel-Mohsen, M, Reeves, DB, Hoh, R, Stone, M, Hiatt, J, Kim, P, Chopra, A, Ahn, H, York, VA, Cameron, DL, Hecht, FM, Martin, JN, Yukl, SA, Mallal, S, Cameron, PU, Deeks, SG, Schiffer, JT, Lewin, SR, Hellerstein, MK, McCune, JM, Hunt, PW, O'Doherty, U, Bacchus-Souffan, C, Fitch, M, Symons, J, Abdel-Mohsen, M, Reeves, DB, Hoh, R, Stone, M, Hiatt, J, Kim, P, Chopra, A, Ahn, H, York, VA, Cameron, DL, Hecht, FM, Martin, JN, Yukl, SA, Mallal, S, Cameron, PU, Deeks, SG, Schiffer, JT, Lewin, SR, Hellerstein, MK, McCune, JM, and Hunt, PW

Abstract

The precise role of CD4 T cell turnover in maintaining HIV persistence during antiretroviral therapy (ART) has not yet been well characterized. In resting CD4 T cell subpopulations from 24 HIV-infected ART-suppressed and 6 HIV-uninfected individuals, we directly measured cellular turnover by heavy water labeling, HIV reservoir size by integrated HIV-DNA (intDNA) and cell-associated HIV-RNA (caRNA), and HIV reservoir clonality by proviral integration site sequencing. Compared to HIV-negatives, ART-suppressed individuals had similar fractional replacement rates in all subpopulations, but lower absolute proliferation rates of all subpopulations other than effector memory (TEM) cells, and lower plasma IL-7 levels (p = 0.0004). Median CD4 T cell half-lives decreased with cell differentiation from naïve to TEM cells (3 years to 3 months, p<0.001). TEM had the fastest replacement rates, were most highly enriched for intDNA and caRNA, and contained the most clonal proviral expansion. Clonal proviruses detected in less mature subpopulations were more expanded in TEM, suggesting that they were maintained through cell differentiation. Earlier ART initiation was associated with lower levels of intDNA, caRNA and fractional replacement rates. In conclusion, circulating integrated HIV proviruses appear to be maintained both by slow turnover of immature CD4 subpopulations, and by clonal expansion as well as cell differentiation into effector cells with faster replacement rates.

Published
2021

25. The Relationship Between Present-Centered Awareness and Attention, Burnout, and Compassion Fatigue in Oncology Health Professionals

Author

Hegel, J, Halkett, GKB, Schofield, P, Rees, CS, Heritage, B, Suleman, S, Inhestern, L, Butler, T, Fitch, M, Breen, LJ, Hegel, J, Halkett, GKB, Schofield, P, Rees, CS, Heritage, B, Suleman, S, Inhestern, L, Butler, T, Fitch, M, and Breen, LJ

Abstract

OBJECTIVES: Oncology health professionals experience high levels of burnout and compassion fatigue, affecting their health and the care they provide. This study aimed to establish whether present-centered awareness and attention (a component of mindfulness) is uniquely associated with burnout and compassion fatigue in oncology professionals. METHODS: An international sample of oncology professionals (n = 118) completed an online questionnaire with validated measures of present-centered awareness and attention, empathy, compassion fatigue, and burnout. Hierarchical multiple regressions were used to model relations among the independent variable (present-centered awareness and attention) and the criterion variables of burnout (disengagement, exhaustion) and compassion fatigue (compassion satisfaction, compassion burnout, secondary traumatic stress) after statistically controlling for empathy, age, gender, years of experience, and patient contact hours. RESULTS: Mean hours of patient contact per week was 23.52 (SD = 13.62), with 26 (22.03%) reporting 40 h or more. Higher hours of patient contact per week were positively associated with secondary traumatic stress. Present-centered awareness and attention was associated with lower disengagement, lower emotional exhaustion, higher compassion satisfaction, lower secondary traumatic stress, and lower compassion burnout. In each model, present-centered awareness accounted for unique variance after controlling for age, gender, years of experience, patient contact hours per week, and empathy scores. The amount of unique variance accounted for by present-centered awareness ranged from 4 to 10%. CONCLUSIONS: Oncology professionals reporting higher levels of present-centered awareness and attention reported higher compassion satisfaction and lower secondary traumatic stress, compassion burnout, exhaustion, and disengagement. Promoting present-centered awareness may be a mechanism that contributes to less burnout in oncology profe

Published
2021

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