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1.
Sci Rep ; 13(1): 20611, 2023 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-37996453

RESUMEN

The recently observed FLASH effect describes the observation of normal tissue protection by ultra-high dose rates (UHDR), or dose delivery in a fraction of a second, at similar tumor-killing efficacy of conventional dose delivery and promises great benefits for radiotherapy patients. Dedicated studies are now necessary to define a robust set of dose application parameters for FLASH radiotherapy and to identify underlying mechanisms. These studies require particle accelerators with variable temporal dose application characteristics for numerous radiation qualities, equipped for preclinical radiobiological research. Here we present the DRESDEN PLATFORM, a research hub for ultra-high dose rate radiobiology. By uniting clinical and research accelerators with radiobiology infrastructure and know-how, the DRESDEN PLATFORM offers a unique environment for studying the FLASH effect. We introduce its experimental capabilities and demonstrate the platform's suitability for systematic investigation of FLASH by presenting results from a concerted in vivo radiobiology study with zebrafish embryos. The comparative pre-clinical study was conducted across one electron and two proton accelerator facilities, including an advanced laser-driven proton source applied for FLASH-relevant in vivo irradiations for the first time. The data show a protective effect of UHDR irradiation up to [Formula: see text] and suggests consistency of the protective effect even at escalated dose rates of [Formula: see text]. With the first clinical FLASH studies underway, research facilities like the DRESDEN PLATFORM, addressing the open questions surrounding FLASH, are essential to accelerate FLASH's translation into clinical practice.


Asunto(s)
Neoplasias , Protones , Animales , Humanos , Dosificación Radioterapéutica , Pez Cebra , Neoplasias/radioterapia , Radiobiología
2.
Phys Med Biol ; 68(18)2023 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-37579761

RESUMEN

Objective.Laser plasma-based accelerators (LPAs) of protons can contribute to research of ultra-high dose rate radiobiology as they provide pulse dose rates unprecedented at medical proton sources. Yet, LPAs pose challenges regarding precise and accurate dosimetry due to the high pulse dose rates, but also due to the sources' lower spectral stability and pulsed operation mode. Forin vivomodels, further challenges arise from the necessary small field dosimetry for volumetric dose distributions. For these novel source parameters and intended applications, a dosimetric standard needs to be established.Approach.In this work, we present a dosimetry and beam monitoring framework forin vivoirradiations of small target volumes with LPA protons, solving aforementioned challenges. The volumetric dose distribution in a sample (mean dose value and lateral/depth dose inhomogeneity) is provided by combining two independent dose measurements using radiochromic films (dose rate-independent) and ionization chambers (dose rate-dependent), respectively. The unique feature of the dosimetric setup is beam monitoring with a transmission time-of-flight spectrometer to quantify spectral fluctuations of the irradiating proton pulses. The resulting changes in the depth dose profile during irradiation of anin vivosample are hence accessible and enable pulse-resolved depth dose correction for each dose measurement.Main results.A first successful small animal pilot study using an LPA proton source serves as a testcase for the presented dosimetry approach and proves its performance in a realistic setting.Significance.With several facilities worldwide either setting up or already using LPA infrastructure for radiobiological studies with protons, the importance of LPA-adapted dosimetric frameworks as presented in this work is clearly underlined.


Asunto(s)
Protones , Radiometría , Animales , Proyectos Piloto , Radiometría/métodos , Rayos Láser , Radiobiología , Dosimetría por Película/métodos
3.
Nat Commun ; 14(1): 4009, 2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37419912

RESUMEN

Laser plasma-based particle accelerators attract great interest in fields where conventional accelerators reach limits based on size, cost or beam parameters. Despite the fact that particle in cell simulations have predicted several advantageous ion acceleration schemes, laser accelerators have not yet reached their full potential in producing simultaneous high-radiation doses at high particle energies. The most stringent limitation is the lack of a suitable high-repetition rate target that also provides a high degree of control of the plasma conditions required to access these advanced regimes. Here, we demonstrate that the interaction of petawatt-class laser pulses with a pre-formed micrometer-sized cryogenic hydrogen jet plasma overcomes these limitations enabling tailored density scans from the solid to the underdense regime. Our proof-of-concept experiment demonstrates that the near-critical plasma density profile produces proton energies of up to 80 MeV. Based on hydrodynamic and three-dimensional particle in cell simulations, transition between different acceleration schemes are shown, suggesting enhanced proton acceleration at the relativistic transparency front for the optimal case.


Asunto(s)
Hidrógeno , Protones , Rayos Láser , Aceleradores de Partículas , Aceleración
4.
Light Sci Appl ; 12(1): 71, 2023 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-36914618

RESUMEN

Laser-driven ion sources are a rapidly developing technology producing high energy, high peak current beams. Their suitability for applications, such as compact medical accelerators, motivates development of robust acceleration schemes using widely available repetitive ultraintense femtosecond lasers. These applications not only require high beam energy, but also place demanding requirements on the source stability and controllability. This can be seriously affected by the laser temporal contrast, precluding the replication of ion acceleration performance on independent laser systems with otherwise similar parameters. Here, we present the experimental generation of >60 MeV protons and >30 MeV u-1 carbon ions from sub-micrometre thickness Formvar foils irradiated with laser intensities >1021 Wcm2. Ions are accelerated by an extreme localised space charge field ≳30 TVm-1, over a million times higher than used in conventional accelerators. The field is formed by a rapid expulsion of electrons from the target bulk due to relativistically induced transparency, in which relativistic corrections to the refractive index enables laser transmission through normally opaque plasma. We replicate the mechanism on two different laser facilities and show that the optimum target thickness decreases with improved laser contrast due to reduced pre-expansion. Our demonstration that energetic ions can be accelerated by this mechanism at different contrast levels relaxes laser requirements and indicates interaction parameters for realising application-specific beam delivery.

5.
Sci Rep ; 12(1): 21488, 2022 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-36509788

RESUMEN

Application experiments with laser plasma-based accelerators (LPA) for protons have to cope with the inherent fluctuations of the proton source. This creates a demand for non-destructive and online spectral characterization of the proton pulses, which are for application experiments mostly spectrally filtered and transported by a beamline. Here, we present a scintillator-based time-of-flight (ToF) beam monitoring system (BMS) for the recording of single-pulse proton energy spectra. The setup's capabilities are showcased by characterizing the spectral stability for the transport of LPA protons for two beamline application cases. For the two beamline settings monitored, data of 122 and 144 proton pulses collected over multiple days were evaluated, respectively. A relative energy uncertainty of 5.5% (1[Formula: see text]) is reached for the ToF BMS, allowing for a Monte-Carlo based prediction of depth dose distributions, also used for the calibration of the device. Finally, online spectral monitoring combined with the prediction of the corresponding depth dose distribution in the irradiated samples is demonstrated to enhance applicability of plasma sources in dose-critical scenarios.

6.
Cities ; 131: 104004, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36189109

RESUMEN

Well before the Covid-19 pandemic, rapidly growing cities of the global South were at the epicenter of multiple converging crises affecting food systems. Globally, government lockdown responses to the disease triggered shocks which cascaded unevenly through urban food systems, exacerbating food insecurity. Cities worldwide developed strategies to mitigate shocks, but research on statecraft enabling food systems resilience is sparse. Addressing this gap, we analyse the case of the African metropolis of Cape Town, where lockdown disrupted livelihoods, mobility and food provision, deepening food insecurity. Employing a vital systems security lens, we show how civil society and state networks mobilised to mitigate and adapt to lockdown impacts. Building on preceding institutional transformations, civil society and state collaborated to deliver emergency food aid, while advocacy networks raised food on the political agenda, formulated proposals, and navigated these through a widened policy window. Emergency statecraft assembled networks and regulatory instruments to secure food systems, enhance preparedness for future disruptions and present opportunities for transition towards more sustainable food systems. However, current food systems configuration enabled powerful actors to resist deeper transformation while devolving impacts to community networks. Despite resilient vested interests and power disparities, advocacy coalitions can anticipate and leverage crises to incrementally advance transformational, pro-poor statecraft.

7.
Nutrients ; 14(14)2022 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-35889848

RESUMEN

Small Island Developing States (SIDS) have high burdens of nutrition-related chronic diseases. This has been associated with lack of access to adequate and affordable nutritious foods and increasing reliance on imported foods. Our aim in this study was to investigate dietary patterns and food insecurity and assess their associations with socio-demographic characteristics and food sources. We recruited individuals aged 15 years and above from rural and urban areas in Fiji (n = 186) and St. Vincent and the Grenadines (SVG) (n = 147). Data collection included a 24 h diet recall, food source questionnaire and the Food Insecurity Experience Scale. We conducted latent class analysis to identify dietary patterns, and multivariable regression to investigate independent associations with dietary patterns. Three dietary patterns were identified: (1) low pulses, and milk and milk products, (2) intermediate pulses, and milk and milk products and (3) most diverse. In both SIDS, dietary pattern 3 was associated with older age, regularly sourcing food from supermarkets and borrowing, exchanging, bartering or gifting (BEB). Prevalence of food insecurity was not statistically different across dietary patterns. In both SIDS, food insecurity was higher in those regularly sourcing food from small shops, and in SVG, lower in those regularly using BEB. These results complement previous findings and provide a basis for further investigation into the determinants of dietary patterns, dietary diversity and food insecurity in these settings.


Asunto(s)
Abastecimiento de Alimentos , Animales , Humanos , Dieta , Leche , Determinantes Sociales de la Salud
8.
Sci Rep ; 12(1): 7287, 2022 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-35508489

RESUMEN

Due to the non-linear nature of relativistic laser induced plasma processes, the development of laser-plasma accelerators requires precise numerical modeling. Especially high intensity laser-solid interactions are sensitive to the temporal laser rising edge and the predictive capability of simulations suffers from incomplete information on the plasma state at the onset of the relativistic interaction. Experimental diagnostics utilizing ultra-fast optical backlighters can help to ease this challenge by providing temporally resolved inside into the plasma density evolution. We present the successful implementation of an off-harmonic optical probe laser setup to investigate the interaction of a high-intensity laser at [Formula: see text] peak intensity with a solid-density cylindrical cryogenic hydrogen jet target of [Formula: see text] diameter as a target test bed. The temporal synchronization of pump and probe laser, spectral filtering and spectrally resolved data of the parasitic plasma self-emission are discussed. The probing technique mitigates detector saturation by self-emission and allowed to record a temporal scan of shadowgraphy data revealing details of the target ionization and expansion dynamics that were so far not accessible for the given laser intensity. Plasma expansion speeds of up to [Formula: see text] followed by full target transparency at [Formula: see text] after the high intensity laser peak are observed. A three dimensional particle-in-cell simulation initiated with the diagnosed target pre-expansion at [Formula: see text] and post processed by ray tracing simulations supports the experimental observations and demonstrates the capability of time resolved optical diagnostics to provide quantitative input and feedback to the numerical treatment within the time frame of the relativistic laser-plasma interaction.

9.
Nutrients ; 12(11)2020 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-33143309

RESUMEN

Small Island Developing States (SIDS) have high and increasing rates of diet-related diseases. This situation is associated with a loss of food sovereignty and an increasing reliance on nutritionally poor food imports. A policy goal, therefore, is to improve local diets through improved local production of nutritious foods. Our aim in this study was to develop methods and collect preliminary data on the relationships between where people source their food, their socio-demographic characteristics and dietary quality in Fiji and Saint Vincent and the Grenadines (SVG) in order to inform further work towards this policy goal. We developed a toolkit of methods to collect individual-level data, including measures of dietary intake, food sources, socio-demographic and health indicators. Individuals aged ≥15 years were eligible to participate. From purposively sampled urban and rural areas, we recruited 186 individuals from 95 households in Fiji, and 147 individuals from 86 households in SVG. Descriptive statistics and multiple linear regression were used to investigate associations. The mean dietary diversity score, out of 10, was 3.7 (SD1.4) in Fiji and 3.8 (SD1.5) in SVG. In both settings, purchasing was the most common way of sourcing food. However, 68% (Fiji) and 45% (SVG) of participants regularly (>weekly) consumed their own produce, and 5% (Fiji) and 33% (SVG) regularly consumed borrowed/exchanged/bartered food. In regression models, independent positive associations with dietary diversity (DD) were: borrowing/exchanging/bartering food (ß = 0.73 (0.21, 1.25)); age (0.01 (0.00, 0.03)); and greater than primary education (0.44 (0.06, 0.82)). DD was negatively associated with small shop purchasing (-0.52 (95% CIs -0.91, -0.12)) and rural residence (-0.46 (-0.92, 0.00)). The findings highlight associations between dietary diversity and food sources and indicate avenues for further research to inform policy actions aimed at improving local food production and diet.


Asunto(s)
Encuestas sobre Dietas , Dieta , Alimentos , Islas , Política Nutricional , Adolescente , Adulto , Femenino , Fiji/epidemiología , Geografía , Salud , Humanos , Hipertensión/epidemiología , Masculino , Análisis Multivariante , Obesidad/epidemiología , San Vicente y las Grenadinas/epidemiología , Adulto Joven
11.
Sci Rep ; 10(1): 9118, 2020 06 04.
Artículo en Inglés | MEDLINE | ID: mdl-32499539

RESUMEN

Intense laser-driven proton pulses, inherently broadband and highly divergent, pose a challenge to established beamline concepts on the path to application-adapted irradiation field formation, particularly for 3D. Here we experimentally show the successful implementation of a highly efficient (50% transmission) and tuneable dual pulsed solenoid setup to generate a homogeneous (laterally and in depth) volumetric dose distribution (cylindrical volume of 5 mm diameter and depth) at a single pulse dose of 0.7 Gy via multi-energy slice selection from the broad input spectrum. The experiments were conducted at the Petawatt beam of the Dresden Laser Acceleration Source Draco and were aided by a predictive simulation model verified by proton transport studies. With the characterised beamline we investigated manipulation and matching of lateral and depth dose profiles to various desired applications and targets. Using an adapted dose profile, we performed a first proof-of-technical-concept laser-driven proton irradiation of volumetric in-vitro tumour tissue (SAS spheroids) to demonstrate concurrent operation of laser accelerator, beam shaping, dosimetry and irradiation procedure of volumetric biological samples.

12.
Sci Rep ; 9(1): 6714, 2019 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-31040311

RESUMEN

The shape of a wave carries all information about the spatial and temporal structure of its source, given that the medium and its properties are known. Most modern imaging methods seek to utilize this nature of waves originating from Huygens' principle. We discuss the retrieval of the complete kinetic energy distribution from the acoustic trace that is recorded when a short ion bunch deposits its energy in water. This novel method, which we refer to as Ion-Bunch Energy Acoustic Tracing (I-BEAT), is a refinement of the ionoacoustic approach. With its capability of completely monitoring a single, focused proton bunch with prompt readout and high repetition rate, I-BEAT is a promising approach to meet future requirements of experiments and applications in the field of laser-based ion acceleration. We demonstrate its functionality at two laser-driven ion sources for quantitative online determination of the kinetic energy distribution in the focus of single proton bunches.

13.
Nat Commun ; 9(1): 5292, 2018 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-30546015

RESUMEN

Extreme field gradients intrinsic to relativistic laser-interactions with thin solid targets enable compact MeV proton accelerators with unique bunch characteristics. Yet, direct control of the proton beam profile is usually not possible. Here we present a readily applicable all-optical approach to imprint detailed spatial information from the driving laser pulse onto the proton bunch. In a series of experiments, counter-intuitively, the spatial profile of the energetic proton bunch was found to exhibit identical structures as the fraction of the laser pulse passing around a target of limited size. Such information transfer between the laser pulse and the naturally delayed proton bunch is attributed to the formation of quasi-static electric fields in the beam path by ionization of residual gas. Essentially acting as a programmable memory, these fields provide access to a higher level of proton beam manipulation.

14.
Sci Rep ; 5: 12459, 2015 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-26212024

RESUMEN

A laser-driven, multi-MeV-range ion beamline has been installed at the GSI Helmholtz center for heavy ion research. The high-power laser PHELIX drives the very short (picosecond) ion acceleration on µm scale, with energies ranging up to 28.4 MeV for protons in a continuous spectrum. The necessary beam shaping behind the source is accomplished by applying magnetic ion lenses like solenoids and quadrupoles and a radiofrequency cavity. Based on the unique beam properties from the laser-driven source, high-current single bunches could be produced and characterized in a recent experiment: At a central energy of 7.8 MeV, up to 5 × 10(8) protons could be re-focused in time to a FWHM bunch length of τ = (462 ± 40) ps via phase focusing. The bunches show a moderate energy spread between 10% and 15% (ΔE/E0 at FWHM) and are available at 6 m distance to the source und thus separated from the harsh laser-matter interaction environment. These successful experiments represent the basis for developing novel laser-driven ion beamlines and accessing highest peak intensities for ultra-short MeV-range ion bunches.

15.
Med Phys ; 40(8): 082104, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23927341

RESUMEN

PURPOSE: Clinical QA in teletherapy as well as the characterization of experimental radiation sources for future medical applications requires effective methods for measuring three-dimensional (3D) dose distributions generated in a water-equivalent medium. Current dosimeters based on ionization chambers, diodes, thermoluminescence detectors, radiochromic films, or polymer gels exhibit various drawbacks: High quality 3D dose determination is either very sophisticated and expensive or requires high amounts of effort and time for the preparation or read out. New detectors based on scintillator blocks in combination with optical tomography are studied, since they have the potential to facilitate the desired cost-effective, transportable, and long-term stable dosimetry system that is able to determine 3D dose distributions with high spatial resolution in a short time. METHODS: A portable detector prototype was set up based on a plastic scintillator block and four digital cameras. During irradiation the scintillator emits light, which is detected by the fixed cameras. The light distribution is then reconstructed by optical tomography, using maximum-likelihood expectation maximization. The result of the reconstruction approximates the 3D dose distribution. First performance tests of the prototype using laser light were carried out. Irradiation experiments were performed with ionizing radiation, i.e., bremsstrahlung (6 to 21 MV), electrons (6 to 21 MeV), and protons (68 MeV), provided by clinical and research accelerators. RESULTS: Laser experiments show that the current imaging properties differ from the design specifications: The imaging scale of the optical systems is position dependent, ranging from 0.185 mm/pixel to 0.225 mm/pixel. Nevertheless, the developed dosimetry method is proven to be functional for electron and proton beams. Induced radiation doses of 50 mGy or more made 3D dose reconstructions possible. Taking the imaging properties into account, determined dose profiles are in agreement with reference measurements. An inherent drawback of the scintillator is the nonlinear light output for high stopping-power radiation due to the quenching effect. It impacts the depth dose curves measured with the dosimeter. For single Bragg peak distributions this leads to a peak to plateau ratio of 2.8 instead of 4.5 for the reference ionization chamber measurement. Furthermore, the transmission of the clinical bremsstrahlung beams through the scintillator leads to the saturation of one camera, making dose reconstructions in that case presently not feasible. CONCLUSIONS: It is shown that distributions of scintillation light generated by proton or electron beams can be reconstructed by the dosimetry system within minutes. The quenching apparent for proton irradiation, and the yet not precisely determined position dependency of the imaging scale, require further investigation and corrections. Upgrading the prototype with larger or inorganic scintillators would increase the detectable proton and electron energy range. The presented results show that the determination of 3D dose distributions using scintillator blocks and optical tomography is a promising dosimetry method.


Asunto(s)
Radiometría/instrumentación , Conteo por Cintilación/instrumentación , Tomografía Óptica , Electrones , Rayos Láser , Protones , Dosis de Radiación , Factores de Tiempo
16.
PLoS One ; 8(1): e55544, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23383220

RESUMEN

The South African population faces many of the global concerns relating to micronutrient deficiency and the impact this has on health and well-being. Moreover, there is a high prevalence of HIV infection, compounded by a high level of co-infection with TB.This pilot study evaluates the impact of a fortified supplementary food on the health and well-being of a cohort of crèche children, aged 3 to 6, and adult TB patients drawn from the Presidential Node of Alexandra, Johannesburg, South Africa. A further aim of this study was to evaluate the sensitivity and validity of non-invasive indicators of nutritional status in a field-based population sample.The investigational product, e'Pap, is supported by extensive anecdotal evidence that whole grain cereals with food-style nutrients constitute an effective supplementary food for those suffering from the effects of food insecurity, poor health and well-being, and coping with TB and HIV infection.The results indicate a beneficial effect of e'Pap for both study populations, and particularly for adult TB patients, whose baseline data reflected severe food insecurity and malnutrition in the majority of cases. There is evidence to suggest statistically significant improvements in key micronutrient levels, well-being and energy, hand-grip strength, the Bioelectrical Impedance Analysis (BIA) Illness Marker, and certain clinical indicators. Although Body Mass Index (BMI) and Mid Upper Arm Circumference (MUAC) are frequently used as standard measures to evaluate the efficacy of nutritional interventions, these indicators were not sufficiently sensitive in this study. Nor does weight gain necessarily indicate improved nutritional status. Hand-grip strength, lean body mass, and the BIA Illness Marker seem to be more useful indicators of change in nutritional status.


Asunto(s)
Suplementos Dietéticos , Alimentos Fortificados , Desnutrición/epidemiología , Desnutrición/etiología , Tuberculosis/complicaciones , Tuberculosis/epidemiología , Adulto , Antropometría , Análisis Químico de la Sangre , Composición Corporal , Preescolar , Coinfección , Femenino , Abastecimiento de Alimentos , Infecciones por VIH , Fuerza de la Mano , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Estado Nutricional , Proyectos Piloto , Sudáfrica/epidemiología , Adulto Joven
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