Effects of spatial variation in dose delivery: what can we learn from radon-related lung cancer studies?

Exposure to radon progeny results in heterogeneous dose distributions in many different spatial scales. The aim of this review is to provide an overview on the state of the art in epidemiology, clinical observations, cell biology, dosimetry, and modelling related to radon exposure and its association with lung cancer, along with priorities for future research. Particular attention is paid on the effects of spatial variation in dose delivery within the organs, a factor not considered in radiation protection. It is concluded that a multidisciplinary approach is required to improve risk assessment and mechanistic understanding of carcinogenesis related to radon exposure. To achieve these goals, important steps would be to clarify whether radon can cause other diseases than lung cancer, and to investigate radon-related health risks in children or persons at young ages. Also, a better understanding of the combined effects of radon and smoking is needed, which can be achieved by integrating epidemiological, clinical, pathological, and molecular oncology data to obtain a radon-associated signature. While in vitro models derived from primary human bronchial epithelial cells can help to identify new and corroborate existing biomarkers, they also allow to study the effects of heterogeneous dose distributions including the effects of locally high doses. These novel approaches can provide valuable input and validation data for mathematical models for risk assessment. These models can be applied to quantitatively translate the knowledge obtained from radon exposure to other exposures resulting in heterogeneous dose distributions within an organ to support radiation protection in general.

[Self-assessment of daily activities using the Duruöz Hand Index-Validation of the German translation]. / Selbstbeurteilung von Alltagsaktivitäten mittels Duruöz-Hand-Index ­ Validierung der deutschen Übersetzung.

BACKGROUND: Independence in activities of daily living depends to a large extent on the upper extremities; however, the instruments widely used in geriatrics to assess self-care abilities do not allow a focus on this body region. In order to map the fluctuating course of hand function-dependent daily living skills with a self-assessment instrument, rheumatologists have developed the Duruöz Hand Index (DHI). OBJECTIVE: The German translation authorized by Duruöz was tested for its applicability in the assessment of geriatric outpatient and day hospital patients and test quality criteria were determined. MATERIAL AND METHODS: Study participants completed the DHI three times. A postgraduate student blinded to the results performed an anamnesis and examination. The geriatric team made an inter-professional assessment of hand function-related daily living skills twice with at least 2­week intervals. RESULTS: Data collection was performed from 16 November 2016 to 27 April 2017 on 101 geriatric day hospital or outpatient patients. Retest reliability was high (0.937), as was internal consistency (Cronbach's α 0.949). Difficulty with activities of daily living correlated more closely with joint mobility (Keitel Index) and fine motor skills (20 cents test) than with hand strength. CONCLUSION: The DHI provides a survey of difficulties with activities of daily living that is focused on the upper extremities. Because about one in three patients required assistance (answering follow-up questions, reading aloud) despite the exclusion of patients with more severely impaired cognition and vision, the examiner should remain present.

Dosimetric Comparison of Exposure Pathways to Human Organs and Tissues in Radon Therapy.

Three therapeutic applications are presently prescribed in the radon spas in Gastein, Austria: exposure to radon in a thermal bath, exposure to radon vapor in an exposure chamber (vapor bath), and exposure to radon in the thermal gallery, a former mine. The radiological exposure pathways to human organs and tissues in these therapeutic radon applications are inhalation of radon and radon progeny via the lungs, radon transfer from water or air through the skin, and radon-progeny deposition on the skin in water or air. The objectives of the present study were to calculate radon and radon-progeny doses for selected organs and tissues for the different exposure pathways and therapeutic applications. Doses incurred in red bone marrow, liver, kidneys, and Langerhans cells in the skin may be correlated with potential therapeutic benefits, while doses to the lungs and the basal cells of the skin indicate potential carcinogenic effects. The highest organ doses among the three therapeutic applications were produced in the thermal gallery by radon progeny via inhalation, with lung doses of 5.0 mSv, and attachment to the skin, with skin doses of 4.4 mSv, while the radon contribution was less significant. For comparison, the primary exposure pathways in the thermal bath are the radon uptake through the skin, with lung doses of 334 µSv, and the radon-progeny attachment to the skin, with skin doses of 216 µSv, while the inhalation route can safely be neglected.

Predictions of inter- and intra-lobar deposition patterns of inhaled particles in a five-lobe lung model.

OBJECTIVE: To develop a stochastic five-lobe lung model and to compute particle deposition fractions in the five lobes, considering anatomical as well as ventilatory asymmetry. MATERIALS AND METHODS: The stochastic five-lobe lung model was derived from an existing stochastic model for the whole lung, which implicitly contains information on the lobar airway structure. Differences in lobar ventilation and sequential filling of individual lobes were simulated by a stochastic lobar ventilation model. Deposition fractions of inhaled unit density particles in the five lobes were calculated by an updated version of the Monte Carlo deposition code Inhalation, Deposition, and Exhalation of Aerosols in the Lung (IDEAL). RESULTS: Simulations for defined exposure and breathing conditions revealed that the two lower lobes receive higher deposition and the two upper lobes lower deposition, compared to the average deposition for the whole lung. The resulting inter-lobar distribution of deposition fractions indicated that the non-uniform lung morphometry is the dominating effect, while non-uniform ventilation only slightly enhances the lobar differences. The relation between average lobe-specific deposition fractions and corresponding average values for the whole lung allowed the calculation of lobe-specific deposition weighting factors. DISCUSSION: Comparison with limited deposition measurements for upper vs. lower (U/L) and left vs. right (L/R) lobes revealed overall agreement between experimental and theoretical data. Calculations of the L/R deposition ratio for inhaled aerosol boli confirmed the hypothesis of Möller et al. that the right lung is less able to expand at the end of a breath because of the restrictive position of the liver.

[Diagnosis and treatment of vascular dementia]. / Vaskulär bedingte Demenzen erkennen und behandeln.

Vascular dementias (VD, due to the various expressions of VD the plural form is used) are the second most common form of dementia after Alzheimer's dementia. These dementias play an important role especially in geriatric patients. They can occur due to acute events (e.g. stroke) and due to slowly progressive cerebrovascular damage. This article focuses on VD due to cortical and strategic infarcts, microangiopathic infarcts with lacunae as well as intracerebral bleeding. In addition to the clinical description and radiological findings, a special focus is on education, prevention and rehabilitation aspects.

Experimentally determined deposition of ambient urban ultrafine particles in the respiratory tract of children.

A critical element of the risk assessment of exposure to airborne ambient ultrafine particles (UFP) is the quantification of respiratory tract deposition (RTD) of the particles, which is intrinsically challenging, particularly at the population scale. In this study, we used a recently proposed method to experimentally determine the RTD of urban UFP in a large group of children exposed to these particles in a school setting in Brisbane, Australia. Children are one of the most susceptible population groups; However, little is known about the deposition of UFP from urban traffic in their airways. In order to advance the knowledge in this field, the objectives of this study were: to determine the deposition of ambient urbane UFP in large number children, to catergorize the source of inhaled UFPs and hence to assess the contribution of air pollution sources to the deposition. RTD was measured in children aged 8-11 at primary schools using a flow-through chamber bag system. First, the inhaled and exhaled air was separated; then the particle number size distribution and particle number concentration were measured. The sources of inhaled UFP were categorized according to their particle number size distribution by a K means cluster technique. A total of 128 children from five schools performed the RTD measurement. The mean total deposition fraction of urban UFP in all children was 0.59 ± 0.10. Inhaled UFP were categorized into two groups: traffic and urban background, with the GMD of corresponding particle number size distribution of 20 nm and 40 nm, respectively. The total deposition fraction (mean ± SD) of UFP from these two groups was 0.68 ± 0.09 for traffic and 0.55 ± 0.08 for urban background respectively. This is the first study in which RTD was measured in a large group of children inhaling real urban UFP. First, we proved that this novel method can indeed be applied easily and quickly to a large group of people. Second, we quantified the RTD of children, thus providing an important input to the risk assessment for exposure to UFP.

Regional Deposition: Deposition Models.

Modeling particle deposition in the human lung requires information about the morphology of the lung in terms of simple geometric units, e.g., characterizing bronchial airways by straight cylindrical tubes. Five different regional deposition models are discussed in this section with respect to morphometric lung models and related mathematical modeling techniques: 1) one-dimensional cross-section or "trumpet" model, 2) deterministic symmetric generation or "single-path" model, 3) deterministic asymmetric generation or "multiple-path" model, 4) stochastic asymmetric generation or "multiple-path" model, and 5) single-path computational fluid and particle dynamics (CFPD) model. Current deposition models can predict the following regional deposition quantities relevant for the administration of medical aerosols: 1) regional bronchial and alveolar deposition, 2) generational lung deposition, 3) lobar deposition, 4) generational lobar deposition, and 5) generational surface deposition. Although deposition fractions predicted by the different models depend on the selection of a specific morphometric lung model and a specific set of analytical deposition equations, all models predict the same trends as functions of particle diameter and breathing parameters. In general, the overall agreement between the modeling predictions obtained by the various deposition models and the available experimental evidence indicates that current deposition models correctly predict regional and generational deposition.

[Hyponatremia in older persons (II)-A clear treatment : How to detect tricks and avoid pitfalls]. / Hyponatriämie im Alter (II) ­ eine klare Therapie : Tücken erkennen und Fallstricke umgehen.

The aim of this continuing medical education (CME) article (part II) is to describe the particular challenge of the treatment of hyponatremia, which occurs in older patients. This part II follows on from part I concerning the diagnosis in the previous volume. A staged approach is necessary. The best treatment is always when the underlying cause can be eliminated. Hyponatremia in older patients is mainly induced by the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. The authors use a concept for the first, second and third line strategy: (1) changing or discontinuation of drugs, (2) fluid restriction and (3) tolvaptan medication. The algorithm for treatment should be simple. It also contains recommendations for the correction rate. Caution is also needed in order to avoid the occurrence of an osmotic demyelination syndrome (ODS).

[Hyponatremia in older persons (part I)-keep diagnosis simple : How to detect tricks and avoid pitfalls]. / Hyponatriämie im Alter (Teil I) ­ Diagnose leicht gemacht : Tücken erkennen und Fallstricke umgehen.

Old age is a strong independent risk factor for hyponatremia. Dizziness, fatigue, reduced vigilance, cognitive impairment, gait deficits, nausea, vomiting, headache, falls, osteoporosis and fractures, coma and seizures are more frequent and severe than in middle-aged patients. Hyponatremia is mainly caused by the syndrome of inappropriate antidiuretic hormone (SIADH) secretion and also including drugs. Hyponatremia is multifactorial in a significant proportion of older patients. Hyponatremia requires a staged diagnostic approach to identify the underlying cause. The aim of this continuing medical education (CME) report (part I) is to emphasize the special challenges in the diagnostics of hyponatremia, which occur in older patients. Diagnostics should be kept simple. A special algorithm is presented. Part II concerning treatment will follow.

Neurogeriatrics-a vision for improved care and research for geriatric patients with predominating neurological disabilities.

Geriatric medicine is a rapidly evolving field that addresses diagnostic, therapeutic and care aspects of older adults. Some disabilities and disorders affecting cognition (e.g. dementia), motor function (e.g. stroke, Parkinson's disease, neuropathies), mood (e.g. depression), behavior (e.g. delirium) and chronic pain disorders are particularly frequent in old subjects. As knowledge about these age-associated conditions and disabilities is steadily increasing, the integral implementation of neurogeriatric knowledge in geriatric medicine and specific neurogeriatric research is essential to develop the field. This article discusses how neurological know-how could be integrated in academic geriatric medicine to improve care of neurogeriatric patients, to foster neurogeriatric research and training concepts and to provide innovative care concepts for geriatric patients with predominant neurological conditions and disabilities.

CELLULAR DOSE DISTRIBUTIONS OF INHALED RADON PROGENY AMONG DIFFERENT LOBES OF THE HUMAN LUNG.

Basal and secretory cell doses in the different lobes of the human lung following inhalation of short-lived radon progeny were calculated for a five-lobe asymmetric, stochastic lung model, considering the non-uniform ventilation of the lobes. Dose calculations for defined exposure conditions revealed that the upper lobes receive higher doses than the average bronchial dose for the whole lung, with the right upper lobe receiving the highest dose. The resulting inter-lobar distribution of cellular bronchial doses indicated that the non-uniform lung morphometry is the dominating factor, while non-uniform ventilation only slightly enhances the lobar differences. The comparison of average lobe-specific bronchial doses with the average bronchial dose for the whole lung allows the calculation of lobe-specific dose weighting factors, which can be used to convert average bronchial doses based on symmetric airway generation or bronchial compartment models to lobar bronchial doses.

Internal microdosimetry of alpha-emitting radionuclides.

At the tissue level, energy deposition in cells is determined by the microdistribution of alpha-emitting radionuclides in relation to sensitive target cells. Furthermore, the highly localized energy deposition of alpha particle tracks and the limited range of alpha particles in tissue produce a highly inhomogeneous energy deposition in traversed cell nuclei. Thus, energy deposition in cell nuclei in a given tissue is characterized by the probability of alpha particle hits and, in the case of a hit, by the energy deposited there. In classical microdosimetry, the randomness of energy deposition in cellular sites is described by a stochastic quantity, the specific energy, which approximates the macroscopic dose for a sufficiently large number of energy deposition events. Typical examples of the alpha-emitting radionuclides in internal microdosimetry are radon progeny and plutonium in the lungs, plutonium and americium in bones, and radium in targeted radionuclide therapy. Several microdosimetric approaches have been proposed to relate specific energy distributions to radiobiological effects, such as hit-related concepts, LET and track length-based models, effect-specific interpretations of specific energy distributions, such as the dual radiation action theory or the hit-size effectiveness function, and finally track structure models. Since microdosimetry characterizes only the initial step of energy deposition, microdosimetric concepts are most successful in exposure situations where biological effects are dominated by energy deposition, but not by subsequently operating biological mechanisms. Indeed, the simulation of the combined action of physical and biological factors may eventually require the application of track structure models at the nanometer scale.

The degree of inhomogeneity of the absorbed cell nucleus doses in the bronchial region of the human respiratory tract.

Inhalation of short-lived radon progeny is an important cause of lung cancer. To characterize the absorbed doses in the bronchial region of the airways due to inhaled radon progeny, mostly regional lung deposition models, like the Human Respiratory Tract Model (HRTM) of the International Commission on Radiological Protection, are used. However, in this model the site specificity of radiation burden in the airways due to deposition and fast airway clearance of radon progeny is not described. Therefore, in the present study, the Radact version of the stochastic lung model was used to quantify the cellular radiation dose distribution at airway generation level and to simulate the kinetics of the deposited radon progeny resulting from the moving mucus layer. All simulations were performed assuming an isotope ratio typical for an average dwelling, and breathing mode characteristic of a healthy adult sitting man. The study demonstrates that the cell nuclei receiving high doses are non-uniformly distributed within the bronchial airway generations. The results revealed that the maximum of the radiation burden is at the first few bronchial airway generations of the respiratory tract, where most of the lung carcinomas of former uranium miners were found. Based on the results of the present simulations, it can be stated that regional lung models may not be fully adequate to describe the radiation burden due to radon progeny. A more realistic and precise calculation of the absorbed doses from the decay of radon progeny to the lung requires deposition and clearance to be simulated by realistic models of airway generations.

Mixed-gas CH4/CO2/CO detection based on linear variable optical filter and thermopile detector array.

This paper presents the design, fabrication, and characterization of a middle-infrared (MIR) linear variable optical filter (LVOF) and thermopile detectors that will be used in a miniaturized mixed gas detector for CH4/CO2/CO measurement. The LVOF was designed as a tapered-cavity Fabry-Pérot optical filter, which can transform the MIR continuous spectrum into multiple narrow band-pass spectra with peak wavelength in linear variation. Multi-layer dielectric structures were used to fabricate the Bragg reflectors on the both sides of tapered cavity as well as the antireflective film combined with the function of out-of-band rejection. The uncooled thermopile detectors were designed and fabricated as a multiple-thermocouple suspension structure using micro-electro-mechanical system technology. Experimentally, the LVOF exhibits a mean full-width-at-half-maximum of 400 nm and mean peak transmittance of 70% at the wavelength range of 2.3~5 µm. The thermopile detectors exhibit a responsivity of 146 µV/°C at the condition of room temperature. It is demonstrated that the detectors can achieve the quantification and identification of CH4/CO2/CO mixed gas.

Functional movement disorders in neurogeriatric inpatients : Underdiagnosed, often comorbid to neurodegenerative disorders and treatable.

BACKGROUND: The proportion of patients with functional movement disorders (FMD) is particularly high in neurology clinics. Treatment options have not been consistently developed, not well evaluated and not validated. This article presents the preliminary data on the prevalence and treatment response of patients with FMD who were treated within the framework of an early rehabilitative geriatric complex treatment at a university hospital for neurology. METHODS: From July 2017 to November 2018 the prevalence, demographic and clinical parameters, and response to treatment of FMD patients were documented and compared to non-FMD patients treated at the neurogeriatric ward of the University Hospital Schleswig-Holstein, in Kiel. Clinical endpoints were the Short Physical Performance Battery (SPPB) for mobility and the Barthel index for instrumented activity of daily life (iADL). RESULTS: The prevalence of FMD was 11% (19/175) and predominantly observed in women (74%). Of the FMD patients nine also had a diagnosis of either idiopathic Parkinson's disease (N = 7), dementia with Lewy bodies (N = 1) or progressive supranuclear palsy (N = 1). At admission, neither the SPPB nor the iADL differed significantly between FMD and non-FMD patients. The treatment response was comparable between the groups: SPPB change was +0.3±1.8 (mean, standard deviation) in FMD and +0.4±1.9 in non-FMD patients (p = 0.83). The iADL change was +19±15 in FMD and +18±17 in non-FMD (p = 0.83). CONCLUSION: The prevalence of FMD was unexpectedly high in the neurogeriatric ward of a German university hospital. There were comparable impairments and responses to multidisciplinary treatment in mobility and iADL between FMD and non-FMD geriatric patients, suggesting that specific and informed treatment provided by a multidisciplinary geriatric team is effective in geriatric FMD patients. Further studies of this underdiagnosed disorder in older age are warranted.