Projections of human kinship for all countries.

Demographers have long attempted to project future changes in the size and composition of populations, but have ignored what these processes will mean for the size, composition, and age distribution of family networks. Kinship structures matter because family solidarity-a crucial source of informal care for millions of people around the world-is conditional on kin being alive. Here, we present innovative projections of biological kin for the 1950 to 2100 period and discuss what they imply for the availability of informal care. Overall, we project that the number of living kin for individuals will decline dramatically worldwide. While a 65-yo woman in 1950 could expect to have 41 living kin, a 65-yo woman in 2095 is projected to have just 25 [18.8 to 34.7] relatives (lower and upper 80% projection intervals). This represents a 38% [15 to 54] global decline. The composition of family networks is also expected to change, with the numbers of living grandparents and great-grandparents markedly increasing, and the numbers of cousins, nieces and nephews, and grandchildren declining. Family networks will age considerably, as we project a widening age gap between individuals and their kin due to lower and later fertility and longer lifespans. In Italy, for example, the average age of a grandmother of a 35-yo woman is expected to increase from 77.9 y in 1950 to 87.7 y [87.1 to 88.5] in 2095. The projected changes in kin supply will put pressure on the already stretched institutional systems of social support, as more individuals age with smaller and older family networks.

Estimates from 31 countries show the significant impact of COVID-19 excess mortality on the incidence of family bereavement.

Excess mortality associated with the COVID-19 pandemic has led many to experience the loss of family members, with significant negative outcomes. We quantify the extent to which these population-wide rates of kin loss represent a departure from levels expected in the absence of COVID-19 excess mortality and consider which demographic groups are most likely to be affected. Results for biological kin in 31 countries indicate dramatic increases in excess kin loss associated with excess mortality and follow a generational pattern consistent with COVID-19 mortality risk by age. During periods of high excess mortality, the number of younger individuals losing a grandparent increased by up to 845 per 100,000, or 1.2 times expected levels (for individuals aged 30 to 44 y in the United Kingdom in April 2020), while the number of older individuals losing a sibling increased by up to 511 per 100,000 or 1.15 times (for individuals aged 65 y and over in Poland in November 2020). Our monthly multicountry estimates of excess kin loss complement existing point estimates of the number of individuals bereaved by COVID-19 mortality [Verdery et al., Proc. Natl. Acad. Sci. U.S.A. 117, 17695-17701 (2020); Kidman et al., JAMA Pediatr. 175, 745-746 (2021); Hillis et al., Lancet 398, 391-402 (2021)] and highlight the role of heterogeneous excess mortality in shaping country experiences.

Development and application of a dynamic transmission model of health systems' preparedness and response to COVID-19 in twenty-six Latin American and Caribbean countries.

The global impact of COVID-19 has challenged health systems across the world. This situation highlighted the need to develop policies based on scientific evidence to prepare the health systems and mitigate the pandemic. In this scenario, governments were urged to predict the impact of the measures they were implementing, how they related to the population's behavior, and the capacity of health systems to respond to the pandemic. The overarching aim of this research was to develop a customizable and open-source tool to predict the impact of the expansion of COVID-19 on the level of preparedness of the health systems of different Latin American and the Caribbean countries, with two main objectives. Firstly, to estimate the transmission dynamics of COVID-19 and the preparedness and response capacity of health systems in those countries, based on different scenarios and public policies implemented to control, mitigate, or suppress the spread of the epidemic. Secondly, to facilitate policy makers' decisions by allowing the model to adjust its parameters according to the specific pandemic trajectory and policy context. How many infections and deaths are estimated per day?; When are the peaks of cases and deaths expected, according to the different scenarios?; Which occupancy rate will ICU services have along the epidemiological curve?; When is the optimal time increase restrictions in order to prevent saturation of ICU beds?, are some of the key questions that the model can respond, and is publicly accessible through the following link: http://shinyapps.iecs.org.ar/modelo-covid19/. This open-access and open code tool is based on a SEIR model (Susceptible, Exposed, Infected and Recovered). Using a deterministic epidemiological model, it allows to frame potential scenarios for long periods, providing valuable information on the dynamics of transmission and how it could impact on health systems through multiple customized configurations adapted to specific characteristics of each country.

Measuring the dose in bone for spine stereotactic body radiotherapy.

PURPOSE: Current quality assurance of radiotherapy involving bony regions generally utilises homogeneous phantoms and dose calculations, ignoring the challenges of heterogeneities with dosimetry problems likely occurring around bone. Anthropomorphic phantoms with synthetic bony materials enable realistic end-to-end testing in clinical scenarios. This work reports on measurements and calculated corrections required to directly report dose in bony materials in the context of comprehensive end-to-end dosimetry audit measurements (63 plans, 6 planning systems). MATERIALS AND METHODS: Radiochromic film and microDiamond measurements were performed in an anthropomorphic spine phantom containing bone equivalent materials. Medium dependent correction factors, kmed, were established using 6 MV and 10 MV Linear Accelerator Monte Carlo simulations to account for the detectors being calibrated in water, but measuring in regions of bony material. Both cortical and trabecular bony material were investigated for verification of dose calculations in dose-to-medium (Dm,m) and dose-to-water (Dw,w) scenarios. RESULTS: For Dm,m calculations, modelled correction factors for cortical and trabecular bone in film measurements, and for trabecular bone in microDiamond measurements were 0.875(±0.1%), 0.953(±0.3%) and 0.962(±0.4%), respectively. For Dw,w calculations, the corrections were 0.920(±0.1%), 0.982(±0.3%) and 0.993(±0.4%), respectively. In the audit, application of the correction factors improves the mean agreement between treatment plans and measured microDiamond dose from -2.4%(±3.9%) to 0.4%(±3.7%). CONCLUSION: Monte Carlo simulations provide a method for correcting the dose measured in bony materials allowing more accurate comparison with treatment planning system doses. In verification measurements, algorithm specific correction factors should be applied to account for variations in bony material for calculations based on Dm,m and Dw,w.

Estimaciones de esperanza de vida al nacer en áreas menores de la región pampeana / Estimativas de esperança de vida ao nascer em áreas menores da região pampeana / Estimates of life expectancy at birth in minor areas of the Pampean region

Para determinar el nivel y las diferencias de mortalidad entre los departamentos de Argentina entre 2009 y 2011, aplicamos y comparamos estimaciones de esperanza de vida al nacer en la región pampeana. Usamos tres métodos de suavizado: un enfoque bayesiano, un método de tablas de vida relacional y un enfoque indirecto de los niveles de mortalidad, en los departamentos de la región. Los resultados permiten ordenar los departamentos de las provincias de acuerdo con su esperanza de vida (con intervalos de confianza estadísticos) y calcular indicadores de desigualdad intraprovincial. Encontramos que la provincia de Buenos Aires fue la de mayor dispersión medida por el rango y el coeficiente de variación. El artículo contribuye a la discusión y aplicaciones de modelos alternativos para estimar la mortalidad local y proporciona la posibilidad de analizar los patrones espaciales para comprender los resultados demográficos individuales relacionados con características geográficas y socioeconómicas asociadas.

Para determinar o nível e as diferenças de mortalidade entre os departamentos da Argentina para o período de 2009 a 2011, aplicamos e comparamos as estimativas de expectativa de vida ao nascer na região pampeana. Usamos três métodos de suavização: uma abordagem bayesiana, uma abordagem de tabela de vida relacional e uma abordagem indireta para os níveis de mortalidade, em 218 departamentos da região. Os resultados permitem ordenar os departamentos das províncias de acordo com a sua esperança de vida (com intervalos de confiança estatísticos) e calcular indicadores de desigualdade intraprovincial. Constatamos que a província de Buenos Aires foi a que apresentou maior dispersão medida pela amplitude e coeficiente de variação. O artigo contribui para a discussão e aplicação de modelos alternativos para estimar a mortalidade em nível local e oferece a possibilidade de analisar os padrões espaciais essenciais para a compreensão dos resultados demográficos individuais relacionados às características geográficas e socioeconômicas associadas, bem como uma ferramenta para orientar planos de desenvolvimento e alocação de recursos.

To determine the level and differences in mortality among departments of Argentina between 2009 and 2011, we applied and compared estimates of life expectancy at birth in the Pampean Region. We used three smoothing methods: a Bayesian approach, a relational life table approach, and an indirect approach to mortality levels, in 218 departments of the region. The results allow ordering the departments of the provinces according to life expectancy (with statistical confidence intervals) and calculating indicators of intraprovincial inequality. We found that the province of Buenos Aires was the one with the highest dispersion measured by the range and the coefficient of variation. The article contributes to the discussion and application of alternative models to estimate mortality at the local level and provides the possibility of analyzing spatial patterns essential to understanding the individual demographic outcomes related to associated geographic and socioeconomic characteristics, as well as a tool to guide development plans and allocate resources.

A comparison of IROC and ACDS on-site audits of reference and non-reference dosimetry.

PURPOSE: Consistency between different international quality assurance groups is important in the progress toward similar standards and expectations in radiotherapy dosimetry around the world, and in the context of consistent clinical trial data from international trial participants. This study compares the dosimetry audit methodology and results of two international quality assurance groups performing a side-by-side comparison at the same radiotherapy department, and interrogates the ability of the audits to detect deliberately introduced errors. METHODS: A comparison of the core dosimetry components of reference and non-reference audits was conducted by the Imaging and Radiation Oncology Core (IROC, Houston, USA) and the Australian Clinical Dosimetry Service (ACDS, Melbourne, Australia). A set of measurements were conducted over 2 days at an Australian radiation therapy facility in Melbourne. Each group evaluated the reference dosimetry, output factors, small field output factors, percentage depth dose (PDD), wedge, and off-axis factors according to their standard protocols. IROC additionally investigated the Electron PDD and the ACDS investigated the effect of heterogeneities. In order to evaluate and compare the performance of these audits under suboptimal conditions, artificial errors in percentage depth dose (PDD), EDW, and small field output factors were introduced into the 6 MV beam model to simulate potential commissioning/modeling errors and both audits were tested for their sensitivity in detecting these errors. RESULTS: With the plans from the clinical beam model, almost all results were within tolerance and at an optimal pass level. Good consistency was found between the two audits as almost all findings were consistent between them. Only two results were different between the results of IROC and the ACDS. The measurements of reference FFF photons showed a discrepancy of 0.7% between ACDS and IROC due to the inclusion of a 0.5% nonuniformity correction by the ACDS. The second difference between IROC and the ACDS was seen with the lung phantom. The asymmetric field behind lung measured by the ACDS was slightly (0.3%) above the ACDS's pass (optimal) level of 3.3%. IROC did not detect this issue because their measurements were all assessed in a homogeneous phantom. When errors were deliberately introduced neither audit was sensitive enough to pick up a 2% change to the small field output factors. The introduced PDD change was flagged by both audits. Similarly, the introduced error of using 25° wedge instead of 30° wedge was detectible in both audits as out of tolerance. CONCLUSIONS: Despite different equipment, approach, and scope of measurements in on-site audits, there were clear similarities between the results from the two groups. This finding is encouraging in the context of a global harmonized approach to radiotherapy quality assurance and dosimetry audit.

Survey of 5 mm small-field output factor measurements in Australia.

The Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) held a comparison exercise in April 2016 where participants came to ARPANSA and measured the output factor of a nominal 5 mm cone attached to the ARPANSA Elekta Synergy (Elekta, Crawley, UK) linear accelerator. The goal of the exercise was to compare the consistency and methods used by independent medical physicists in measuring small-field output factors. ARPANSA provided a three-dimensional scanning tank for detector setup and positioning, but the participants were required to measure the output factor with their own detectors. No information regarding output factors previously measured was supplied to participants to make each result as independent as possible. Fifteen groups travelled to ARPANSA bringing a wide range of detectors and methods. A total of 30 measurements of the output factor were made. The standard deviation of the measurements (excluding one expected outlier from an uncorrected ionization chamber measurement) was 3.6%. The results provide an insight into the consistency of small-field dosimetry being performed in Australia and New Zealand at the present time.

Dosimetric end-to-end tests in a national audit of 3D conformal radiotherapy.

BACKGROUND AND PURPOSE: Independent dosimetry audits improve quality and safety of radiation therapy. This work reports on design and findings of a comprehensive 3D conformal radiotherapy (3D-CRT) Level III audit. MATERIALS AND METHODS: The audit was conducted as onsite audit using an anthropomorphic thorax phantom in an end-to-end test by the Australian Clinical Dosimetry Service (ACDS). Absolute dose point measurements were performed with Farmer-type ionization chambers. The audited treatment plans included open and half blocked fields, wedges and lung inhomogeneities. Audit results were determined as Pass Optimal Level (deviations within 3.3%), Pass Action Level (greater than 3.3% but within 5%) and Out of Tolerance (beyond 5%), as well as Reported Not Scored (RNS). The audit has been performed between July 2012 and January 2018 on 94 occasions, covering approximately 90% of all Australian facilities. RESULTS: The audit pass rate was 87% (53% optimal). Fifty recommendations were given, mainly related to planning system commissioning. Dose overestimation behind low density inhomogeneities by the analytical anisotropic algorithm (AAA) was identified across facilities and found to extend to beam setups which resemble a typical breast cancer treatment beam placement. RNS measurements inside lung showed a variation in the opposite direction: AAA under-dosed a target beyond lung and over-dosed the lung upstream and downstream of the target. Results also highlighted shortcomings of some superposition and convolution algorithms in modelling large angle wedges. CONCLUSIONS: This audit showed that 3D-CRT dosimetry audits remain relevant and can identify fundamental global and local problems that also affect advanced treatments.

Remote beam output audits: a global assessment of results out of tolerance.

BACKGROUND AND PURPOSE: Remote beam output audits, which independently measure an institution's machine calibration, are a common component of independent radiotherapy peer review. This work reviews the results and trends of these audit results across several organisations and geographical regions. MATERIALS AND METHODS: Beam output audit results from the Australian Clinical Dosimetry Services, International Atomic Energy Agency, Imaging and Radiation Oncology Core, and Radiation Dosimetry Services were evaluated from 2010 to the present. The rate of audit results outside a +/-5% tolerance was evaluated for photon and electron beams as a function of the year of irradiation and nominal beam energy. Additionally, examples of confirmed calibration errors were examined to provide guidance to clinical physicists and auditing bodies. RESULTS: Of the 210,167 audit results, 1323 (0.63%) were outside of tolerance. There was a clear trend of improved audit performance for more recent dates, and while all photon energies generally showed uniform rates of results out of tolerance, low (6 MeV) and high (≥18 MeV) energy electron beams showed significantly elevated rates. Twenty nine confirmed calibration errors were explored and attributed to a range of issues, such as equipment failures, errors in setup, and errors in performing the clinical reference calibration. Forty-two percent of these confirmed errors were detected during ongoing periodic monitoring, and not at the time of the first audit of the machine. CONCLUSIONS: Remote beam output audits have identified, and continue to identify, numerous and often substantial beam calibration errors.

Methodology to assess quality of estimated disturbances in active disturbance rejection control structure for mechanical system.

A methodology to assess the quality of estimation of disturbances in mechanical systems, by state observers, in the control structure with active compensation of disturbances (ADRC) is presented. Evaluation is carried out by four performance indices that depend on the steady-state error between reference signals and output of the plant. These indices are related with the accuracy and precision of the closed loop system in the sense of norms L2 and L∞, for a set of reference signals representing the typical operating conditions of the mechanism. The effectiveness of the methodology is illustrated with the quality assessment of the estimated disturbance of five state observers to control of a simple pendulum and validated on a SCARA robot arm.

Esperanza de vida saludable según prevalencia de limitaciones permanentes, Argentina 2009-2010 / Life expectancy free of disabilities by prevalence of permanent limitations, Argentina 2009-2010

INTRODUCCIÓN: a medida que se desplaza la mortalidad hacia edades avanzadas y predomina la morbilidad por enfermedades crónicas no transmisibles, la esperanza de vida al nacer resulta insuficiente para estimar el estado de salud de las poblaciones, cuyos integrantes pueden padecer durante períodos prolongados las secuelas de enfermedades discapacitantes. En estos escenarios, la esperanza de vida libre de limitaciones permanentes (EVLLP) y con limitacionespermanentes (EVCLP) constituyen indicadores recomendados paraevaluar las condiciones de salud. OBJETIVOS: Estimar la EVLLP porenfermedades físicas o cognitivas para Argentina en 2010. MÉTODOS: Se utilizó el método Sullivan para calcular ambos indicadores. La información básica se obtuvo del Censo Nacional de Población, Hogares y Viviendas de 2010. Se realizaron cálculos de EVLLP y EVCLP al nacer y por edades para la población argentina en 2010. También se elaboró un indicador de impacto de las limitaciones sobre la esperanza de vida para valorar las diferencias halladas. RESULTADOS: Se conocieron las diferencias provinciales en el perfil de salud-discapacidad según sexoy el impacto de la discapacidad en el curso de vida completo segúnprovincias y sexo. CONCLUSIONES: Se espera que las mujeres vivan más años libres de limitaciones, pero con mayor carga potencial de limitaciones permanentes. La Ciudad Autónoma de Buenos Aires es la jurisdicción con mayor EVLLP y con menor carga potencial de discapacidad, mientras que la provincia con mayor impacto dediscapacidad es Jujuy.

INTRODUCTION: as mortality shifts to extreme ages, and morbidity from chronic non-communicable diseasespredominates, life expectancy at birth is not enough to assess the overall health status of populations, whose members may suffer the consequences for long periods of disabling diseases. In these scenarios, indicators like life expectancy free of disabilities (LEFD) and with disabilities (LEWD) arerecommended to evaluate population health conditions. OBJECTIVES: To estimate the LEFD due to physical or cognitive diseases for Argentina in 2010. METHODS: Sullivan methodwas used to calculate both indicators. The basic information was obtained from the 2010 Census of Argentina. LEFD and LEWD at birth and specific ages for the Argentine populationwere calculated. An indicator about impact of the disability on life expectancy was developed to assess the differences found RESULTS:. The study revealed provincial differencesrelated to health and disease profile by sex as well as the impact of the disability on the whole life course by provinces and sex.. CONCLUSIONS: Women are expected to live free of limitations longer than men, but with a higher load of permanent disabilities. Buenos Aires City is the jurisdictionwith the highest life expectancy free of disability and with the lowest potential load, while the province with the greatest impact of disability is Jujuy.

National dosimetric audit network finds discrepancies in AAA lung inhomogeneity corrections.

This work presents the Australian Clinical Dosimetry Service's (ACDS) findings of an investigation of systematic discrepancies between treatment planning system (TPS) calculated and measured audit doses. Specifically, a comparison between the Anisotropic Analytic Algorithm (AAA) and other common dose-calculation algorithms in regions downstream (≥2cm) from low-density material in anthropomorphic and slab phantom geometries is presented. Two measurement setups involving rectilinear slab-phantoms (ACDS Level II audit) and anthropomorphic geometries (ACDS Level III audit) were used in conjunction with ion chamber (planar 2D array and Farmer-type) measurements. Measured doses were compared to calculated doses for a variety of cases, with and without the presence of inhomogeneities and beam-modifiers in 71 audits. Results demonstrate a systematic AAA underdose with an average discrepancy of 2.9 ± 1.2% when the AAA algorithm is implemented in regions distal from lung-tissue interfaces, when lateral beams are used with anthropomorphic phantoms. This systemic discrepancy was found for all Level III audits of facilities using the AAA algorithm. This discrepancy is not seen when identical measurements are compared for other common dose-calculation algorithms (average discrepancy -0.4 ± 1.7%), including the Acuros XB algorithm also available with the Eclipse TPS. For slab phantom geometries (Level II audits), with similar measurement points downstream from inhomogeneities this discrepancy is also not seen.

Long term OSLD reader stability in the ACDS level one audit.

The Australian Clinical Dosimetry Service (ACDS) has demonstrated the capacity to perform a basic dosimetry audit on all radiotherapy clinics across Australia. During the ACDS's three and a half year trial the majority of the audits were performed using optically stimulated luminescence dosimeters (OSLD) mailed to facilities for exposure to a reference dose, and then returned to the ACDS for analysis. This technical note investigates the stability of the readout process under the large workload of the national dosimetry audit. The OSLD readout uncertainty contributes to the uncertainty of several terms of the dose calculation equation and is a major source of uncertainty in the audit. The standard deviation of four OSLD readouts was initially established at 0.6 %. Measurements over 13 audit batches--each batch containing 200-400 OSLDs--showed variability (0.5-0.9 %) in the readout standard deviation. These shifts have not yet necessitated a change to the audit scoring levels. However, a standard deviation in OSLD readouts greater than 0.9 % will change the audit scoring levels. We identified mechanical wear on the OSLD readout adapter as a cause of variability in readout uncertainty, however, we cannot rule out other causes. Additionally we observed large fluctuations in the distribution of element correction factors (ECF) for OSLD batches. We conclude that the variability in the width of the ECF distribution from one batch to another is not caused by variability in readout uncertainty, but rather by variations in the OSLD stock.

A 2D ion chamber array audit of wedged and asymmetric fields in an inhomogeneous lung phantom.

PURPOSE: The Australian Clinical Dosimetry Service (ACDS) has implemented a new method of a nonreference condition Level II type dosimetric audit of radiotherapy services to increase measurement accuracy and patient safety within Australia. The aim of this work is to describe the methodology, tolerances, and outcomes from the new audit. METHODS: The ACDS Level II audit measures the dose delivered in 2D planes using an ionization chamber based array positioned at multiple depths. Measurements are made in rectilinear homogeneous and inhomogeneous phantoms composed of slabs of solid water and lung. Computer generated computed tomography data sets of the rectilinear phantoms are supplied to the facility prior to audit for planning of a range of cases including reference fields, asymmetric fields, and wedged fields. The audit assesses 3D planning with 6 MV photons with a static (zero degree) gantry. Scoring is performed using local dose differences between the planned and measured dose within 80% of the field width. The overall audit result is determined by the maximum dose difference over all scoring points, cases, and planes. Pass (Optimal Level) is defined as maximum dose difference ≤3.3%, Pass (Action Level) is ≤5.0%, and Fail (Out of Tolerance) is >5.0%. RESULTS: At close of 2013, the ACDS had performed 24 Level II audits. 63% of the audits passed, 33% failed, and the remaining audit was not assessable. Of the 15 audits that passed, 3 were at Pass (Action Level). The high fail rate is largely due to a systemic issue with modeling asymmetric 60° wedges which caused a delivered overdose of 5%-8%. CONCLUSIONS: The ACDS has implemented a nonreference condition Level II type audit, based on ion chamber 2D array measurements in an inhomogeneous slab phantom. The powerful diagnostic ability of this audit has allowed the ACDS to rigorously test the treatment planning systems implemented in Australian radiotherapy facilities. Recommendations from audits have led to facilities modifying clinical practice and changing planning protocols.

Angular dependence of the response of the nanoDot OSLD system for measurements at depth in clinical megavoltage beams.

PURPOSE: The purpose of this investigation was to assess the angular dependence of a commercial optically stimulated luminescence dosimeter (OSLD) dosimetry system in MV x-ray beams at depths beyond d(max) and to find ways to mitigate this dependence for measurements in phantoms. METHODS: Two special holders were designed which allow a dosimeter to be rotated around the center of its sensitive volume. The dosimeter's sensitive volume is a disk, 5 mm in diameter and 0.2 mm thick. The first holder rotates the disk in the traditional way. It positions the disk perpendicular to the beam (gantry pointing to the floor) in the initial position (0°). When the holder is rotated the angle of the disk towards the beam increases until the disk is parallel with the beam ("edge on," 90°). This is referred to as Setup 1. The second holder offers a new, alternative measurement position. It positions the disk parallel to the beam for all angles while rotating around its center (Setup 2). Measurements with five to ten dosimeters per point were carried out for 6 MV at 3 and 10 cm depth. Monte Carlo simulations using GEANT4 were performed to simulate the response of the active detector material for several angles. Detector and housing were simulated in detail based on microCT data and communications with the manufacturer. Various material compositions and an all-water geometry were considered. RESULTS: For the traditional Setup 1 the response of the OSLD dropped on average by 1.4% ± 0.7% (measurement) and 2.1% ± 0.3% (Monte Carlo simulation) for the 90° orientation compared to 0°. Monte Carlo simulations also showed a strong dependence of the effect on the composition of the sensitive layer. Assuming the layer to completely consist of the active material (Al2O3) results in a 7% drop in response for 90° compared to 0°. Assuming the layer to be completely water, results in a flat response within the simulation uncertainty of about 1%. For the new Setup 2, measurements and Monte Carlo simulations found the angular dependence of the dosimeter to be below 1% and within the measurement uncertainty. CONCLUSIONS: The dosimeter system exhibits a small angular dependence of approximately 2% which needs to be considered for measurements involving other than normal incident beams angles. This applies in particular to clinical in vivo measurements where the orientation of the dosimeter is dictated by clinical circumstances and cannot be optimized as otherwise suggested here. When measuring in a phantom, the proposed new setup should be considered. It changes the orientation of the dosimeter so that a coplanar beam arrangement always hits the disk shaped detector material from the thin side and thereby reduces the angular dependence of the response to within the measurement uncertainty of about 1%. This improvement makes the dosimeter more attractive for clinical measurements with multiple coplanar beams in phantoms, as the overall measurement uncertainty is reduced. Similarly, phantom based postal audits can transition from the traditional TLD to the more accurate and convenient OSLD.

Remote auditing of radiotherapy facilities using optically stimulated luminescence dosimeters.

PURPOSE: On 1 July 2012, the Australian Clinical Dosimetry Service (ACDS) released its Optically Stimulated Luminescent Dosimeter (OSLD) Level I audit, replacing the previous TLD based audit. The aim of this work is to present the results from this new service and the complete uncertainty analysis on which the audit tolerances are based. METHODS: The audit release was preceded by a rigorous evaluation of the InLight® nanoDot OSLD system from Landauer (Landauer, Inc., Glenwood, IL). Energy dependence, signal fading from multiple irradiations, batch variation, reader variation, and dose response factors were identified and quantified for each individual OSLD. The detectors are mailed to the facility in small PMMA blocks, based on the design of the existing Radiological Physics Centre audit. Modeling and measurement were used to determine a factor that could convert the dose measured in the PMMA block, to dose in water for the facility's reference conditions. This factor is dependent on the beam spectrum. The TPR20,10 was used as the beam quality index to determine the specific block factor for a beam being audited. The audit tolerance was defined using a rigorous uncertainty calculation. The audit outcome is then determined using a scientifically based two tiered action level approach. Audit outcomes within two standard deviations were defined as Pass (Optimal Level), within three standard deviations as Pass (Action Level), and outside of three standard deviations the outcome is Fail (Out of Tolerance). RESULTS: To-date the ACDS has audited 108 photon beams with TLD and 162 photon beams with OSLD. The TLD audit results had an average deviation from ACDS of 0.0% and a standard deviation of 1.8%. The OSLD audit results had an average deviation of -0.2% and a standard deviation of 1.4%. The relative combined standard uncertainty was calculated to be 1.3% (1σ). Pass (Optimal Level) was reduced to ≤2.6% (2σ), and Fail (Out of Tolerance) was reduced to >3.9% (3σ) for the new OSLD audit. Previously with the TLD audit the Pass (Optimal Level) and Fail (Out of Tolerance) were set at ≤4.0% (2σ) and >6.0% (3σ). CONCLUSIONS: The calculated standard uncertainty of 1.3% at one standard deviation is consistent with the measured standard deviation of 1.4% from the audits and confirming the suitability of the uncertainty budget derived audit tolerances. The OSLD audit shows greater accuracy than the previous TLD audit, justifying the reduction in audit tolerances. In the TLD audit, all outcomes were Pass (Optimal Level) suggesting that the tolerances were too conservative. In the OSLD audit 94% of the audits have resulted in Pass (Optimal level) and 6% of the audits have resulted in Pass (Action Level). All Pass (Action level) results have been resolved with a repeat OSLD audit, or an on-site ion chamber measurement.

High-resolution visualization of airspace structures in intact mice via synchrotron phase-contrast X-ray imaging (PCXI).

Anatomical visualization of airspace-containing organs in intact small animals has been limited by the resolution and contrast available from current imaging methods such as X-ray, micro-computed tomography and magnetic resonance imaging. Determining structural relationships and detailed anatomy has therefore relied on suitable fixation, sectioning and histological processing. More complex and informative analyses such as orthogonal views of an organ and three-dimensional structure visualizations have required different animals and image sets, laboriously processed to gather this complementary structural information. Precise three-dimensional anatomical views have always been difficult to achieve in small animals. Here we report the ability of phase-contrast synchrotron X-ray imaging to provide detailed two- and three-dimensional visualization of airspace organ structures in intact animals. Using sub-micrometre square pixel charge-coupled device array detectors, the structure and anatomy of hard and soft tissues, and of airspaces, is readily available using phase-contrast synchrotron X-ray imaging. Moreover, software-controlled volume-reconstructions of tomographic images not only provide unsurpassed image clarity and detail, but also selectable anatomical views that cannot be obtained with established histological techniques. The morphology and structure of nasal and lung airways and the middle ear are illustrated in intact mice, using two- and three-dimensional representations. The utility of phase-contrast synchrotron X-ray imaging for noninvasively localizing objects implanted within airspaces, and the detection of gas bubbles transiting live airways, are other novel features of this visualization methodology. The coupling of phase-contrast synchrotron X-ray imaging technology with software-based reconstruction techniques holds promise for novel and high-resolution non-invasive examination of airspace anatomy in small animal models.

Imaging lung aeration and lung liquid clearance at birth.

Aeration of the lung and the transition to air-breathing at birth is fundamental to mammalian life and initiates major changes in cardiopulmonary physiology. However, the dynamics of this process and the factors involved are largely unknown, because it has not been possible to observe or measure lung aeration on a breath-by-breath basis. We have used the high contrast and spatial resolution of phase contrast X-ray imaging to study lung aeration at birth in spontaneously breathing neonatal rabbits. As the liquid-filled fetal lungs provide little absorption or phase contrast, they are not visible and only become visible as they aerate, allowing a detailed examination of this process. Pups were imaged live from birth to determine the timing and spatial pattern of lung aeration, and relative levels of lung aeration were measured from the images using a power spectral analysis. We report the first detailed observations and measurements of lung aeration, demonstrating its dependence on inspiratory activity and body position; dependent regions aerated at much slower rates. The air/liquid interface moved toward the distal airways only during inspiration, with little proximal movement during expiration, indicating that trans-pulmonary pressures play an important role in airway liquid clearance at birth. Using these imaging techniques, the dynamics of lung aeration and the critical role it plays in regulating the physiological changes at birth can be fully explored.

Adverse effects of observational studies when examining adverse outcomes of drugs: case-control studies with low prevalence of exposure.

OBJECTIVES: The case-control study is commonly used to examine adverse drug events, in which prevalence of exposure in the source population is frequently very low. The objective of the current study was to examine the bias inherent in the odds ratio assessing the association between exposure and an adverse outcome when prevalence of exposure in the source population is extremely low. DESIGN: Monte Carlo simulations examined the effect of sample size, exposure prevalence, and magnitude of the underlying odds ratio on the bias of the estimated risk ratio, and the power to detect a non-zero risk ratio. RESULTS: Once the underlying odds ratio was at least four, the adverse effects of low prevalence of exposure was minimal. Studies with small sample sizes and low prevalence of exposure, coupled with small to moderate effect sizes, can result in biased estimates of association between exposure and disease status. With a sample size of 200 and an exposure prevalence of 0.5% in the control population, the bias in the estimated odds ratio can be as large as 115%. However, bias becomes negligible as sample size becomes large (n > or = 2000), even when prevalence of exposure is very low. Once the expected number of exposed controls is at least eight, the bias in the estimated odds ratio was no more than 5%. CONCLUSIONS: Studies with small sample sizes and low prevalence of exposure, coupled with small to moderate effect sizes can result in biased estimates of association between exposure status and adverse drug effects. However, bias becomes negligible as sample size becomes large.