Browsing by Author "Sierro, F"

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    P219 / #908 - advancements in NCEPT: animal study outcomes and technological developments toward clinical application
    (Elsevier, 2024-06) Hirayama, R; Tashima, H; Hamato, A; Howell, NR; Sierro, F; Kielly, M; Caracciolo, A; Franklin, DR; Guatelli, S; Yamaya, T; Rosenfeld, AB; Fiorini, C; Carminati, M; Safavi-Naeini, M
    Background and aims: Neutron Capture Enhanced Particle Therapy (NCEPT) represents a promising advancement in cancer treatment, utilising neutron capture agents (NCAs) to enhance therapeutic efficacy of proton/heavy ion radiation. This work focuses on animal experiments and concurrent technological developments aimed at translating NCEPT into clinical practice. Methods: Animal studies were conducted to assess the therapeutic impact of NCEPT. Baseline dose response of U87MG xenograft Balb/c nu/nu mice to 12C and 4He ion radiation was evaluated at HIMAC (February 2021, January 2022). NCEPT dose-response experiments with 10B-BPA as the NCA and using the same animal model were conducted in two campaigns in 2023. 200 mice were irradiated with helium or carbon ions across four dose levels (0 Gy, 5 Gy, 10 Gy, and 15 Gy, n = 6 mice/ion/dose); tumour growth was measured at different time points. In parallel, a scintillator-based detector for measurement of photon spectrum changes due to neutron capture was developed and evaluated in simulations and experiments with boron-loaded PMMA targets irradiated by helium/carbon ion beams. Results: Baseline experiments showed expected dose-response relationships, with tumour response and measured neutron fluence informing the NCEPT study protocol. NCEPT experiments demonstrated significant tumour volume reductions (33%/46% for helium/carbon ion irradiation, respectively) and delays in tumour growth relative to baseline. The prototype detector measured increases in the area of the 478 keV peak by 26%/45% for helium/carbon beams, respectively, compared to simulation-based values of 57%/45%. >65% of these photons originated from 10B captures in the detector's PCB, highlighting the need for neutron shielding and boron-free materials in detector construction. The linear increase in neutron capture photons at 10B concentrations up to 20000 ppm, with potential for detection down to 100 ppm using temporal windowing, paves the way for a SPECT-like neutron capture imaging system, crucial for NCEPT quality assurance. Conclusion: The combined animal study outcomes and technological advancements underscore the potential of NCEPT as a highly effective cancer therapy. The progress in dosimetry and imaging techniques mark significant steps toward the clinical translation of NCEPT, promising improved patient outcomes in cancer treatment. © 2024 Elsevier B.V. Open Access under a CC-BY-NC-ND 4.0 licence
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    The water chemistry and microbiome of household wells in Medawachchiya, Sri Lanka, an area with high prevalence of chronic kidney disease of unknown origin (CKDu)
    (Springer Nature, 2020-10-26) McDonough, LK; Meredith, KT; Nikagolla, C; Middleton, RJ; Tan, JK; Ranasinghe, AV; Sierro, F; Banati, RB
    Chronic kidney disease (CKD) of unknown etiology (CKDu) mostly affects agricultural communities in Central America, South Asia, Africa, but likely also in North America and Australia. One such area with increased CKDu prevalence is the Medawachchiya District Secretariat Division of the Anuradhapura District in the North Central Province of Sri Lanka. Recent research has focused on the presence of various microbial pathogens in drinking water as potential causal or contributing factors to CKDu, yet no study to date has performed a more comprehensive microbial and water chemistry assessment of household wells used for domestic water supply in areas of high CKDu prevalence. In this study, we describe the chemical composition and total microbial content in 30 domestic household wells in the Medawachchiya District Secretariat Division. While the chemical composition in the tested wells mostly lies within standard drinking water limits, except for high levels of fluoride (F), magnesium (Mg), sodium (Na), chloride (Cl) and calcium (Ca) in some samples, we find a frequent presence of cyanotoxin-producing Microcystis, confirming earlier studies in Sri Lanka. Since the total microbial content of drinking water also directly influences the composition of the human gut microbiome, it can be considered an important determinant of health. Several bacterial phyla were previously reported in the gut microbiome of patients with CKD. Using these bacteria phyla to define operational taxonomic units, we found that these bacteria also occur in the microbiome of the sampled well water. Based on available environmental data, our study demonstrates associations between the abundances of these bacteria with geographical distribution, well water temperature and likely fertilizer use in the local surface water catchment area of the individual household wells. Our results reinforce the recommendation that household wells with stagnant or infrequently used water should be purged prior to use for drinking water, bathing and irrigation. The latter is suggested because of the reported potential accumulation of bacterial toxins by agricultural crops. The observation that bacteria previously found in chronic kidney disease patients are also present in household wells requires a more detailed systematic study of both the human gut and drinking water microbiomes in CKDu patients, in relation to disease prevalence and progression. © 2020 The Authors - Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License.