Causal, Bayesian, & non-parametric modeling of the SARS-CoV-2 viral load distribution vs. patient's age.

The viral load of patients infected with SARS-CoV-2 varies on logarithmic scales and possibly with age. Controversial claims have been made in the literature regarding whether the viral load distribution actually depends on the age of the patients. Such a dependence would have implications for the COVID-19 spreading mechanism, the age-dependent immune system reaction, and thus for policymaking. We hereby develop a method to analyze viral-load distribution data as a function of the patients' age within a flexible, non-parametric, hierarchical, Bayesian, and causal model. The causal nature of the developed reconstruction additionally allows to test for bias in the data. This could be due to, e.g., bias in patient-testing and data collection or systematic errors in the measurement of the viral load. We perform these tests by calculating the Bayesian evidence for each implied possible causal direction. The possibility of testing for bias in data collection and identifying causal directions can be very useful in other contexts as well. For this reason we make our model freely available. When applied to publicly available age and SARS-CoV-2 viral load data, we find a statistically significant increase in the viral load with age, but only for one of the two analyzed datasets. If we consider this dataset, and based on the current understanding of viral load's impact on patients' infectivity, we expect a non-negligible difference in the infectivity of different age groups. This difference is nonetheless too small to justify considering any age group as noninfectious.

Machine intelligence decrypts ß-lapachone as an allosteric 5-lipoxygenase inhibitor.

Using machine learning, targets were identified for ß-lapachone. Resorting to biochemical assays, ß-lapachone was validated as a potent, ligand efficient, allosteric and reversible modulator of 5-lipoxygenase (5-LO). Moreover, we provide a rationale for 5-LO modulation and show that inhibition of 5-LO is relevant for the anticancer activity of ß-lapachone. This work demonstrates the power of machine intelligence to deconvolute complex phenotypes, as an alternative and/or complement to chemoproteomics and as a viable general approach for systems pharmacology studies.

Exposure of treating physician to radiation during prostate brachytherapy using iodine-125 seeds: dose measurements on both hands with thermoluminescence dosimeters.

BACKGROUND AND PURPOSE: Only sparse reports have been made about radiation exposure of the treating physician during prostate seed implantation. Therefore, thermoluminescence dosimeter (TLD) measurements on the index fingers and the backs of both hands were conducted. MATERIAL AND METHODS: Stranded iodine-125 seeds with a mean apparent activity of 27.4 MBq per seed were used. During application, the treating physician manipulated the loaded needle with the index fingers, partially under fluoroscopic control. Four physicians with varying experience treated 24 patients. The radiation exposure was determined with TLD-100 chips attached to the index fingertips and the backs of hands. Radiation exposure was correlated with the physician's experience. RESULTS: The average brachytherapy duration by the most experienced physician was 19.2 min (standard deviation sigma = 1.2 min; novices: 34.8 min [sigma = 10.2 min]). The mean activity was 1,703 MBq (sigma = 123 MBq), applied with 16.3 needles (sigma = 2.5 needles; novices: 1,469 MBq [sigma = 229 MBq]; 16.8 needles [sigma = 2.3 needles]). The exposure of the finger of the "active hand" and the back of the hand amounted to 1.31 mSv (sigma = 0.54 mSv) and 0.61 mSv (sigma = 0.23 mSv), respectively (novices: 2.07 mSv [sigma = 0.86 mSv] and 1.05 mSv [sigma = 0.53 mSv]). CONCLUSION: If no other radiation exposure needs to be considered, an experienced physician can perform about 400 applications per year without exceeding the limit of 500 mSv/year; for novices, the corresponding figure is about 200.

[Results of quality controls for individual doses to patients in radiation oncology]. / Ergebnisse von Qualitätskontrollen der individuellen Patientendosen in der Radioonkologie.

BACKGROUND: Along with the treatment equipment and the planning system the individual doses to the patient also have to be part of quality assurance. To make sure that the dose application to the patient is correct, a two-step concept is used: the check of the planned dose and the in vivo dosimetry. METHODS: In contrast to the treatment planning where the necessary parameters for a desirable dose distribution and dose are determined in the target volume, the dose in the ICRU point is calculated from the individual setup parameters. This is done by using an Excel Macro program. Additionally, on the occasion of the first treatment session, the entrance dose on the patient surface is measured for each separate treatment field with a semiconductor diode. This dose is compared to the reference value from the treatment planning. RESULTS: Given a tolerance level of 4% for the correspondence of the doses in the ICRU point, 2.1% of the photon treatment plans showed a bigger deviation. The tolerance of the deviation of the measured entrance dose from the dose calculated in the treatment planning was set to +/- 5% for photons without wedge and to +/- 10% for photons with wedge or for electrons. 14% of all treatment fields exceeded the given tolerances without taking possible repeated measurements into account. The corresponding figures for photon fields without wedge, with wedge and for electron fields were 19%, 6% and 9%, respectively. CONCLUSION: Patient-related checks are essential since transcription and setup errors cannot be excluded. The checks have to be simple, meaningful and unambiguous. One must assume their independence of the individual and the method. If the tolerances are exceeded, actions have to be taken. This has to be taken into account when the tolerances are established.

[MLC positioning checks and calibration with a portal imaging system]. / Prüfung und Kalibration der MLC-Positionierung mit einem portalen Bildgebungssystem.

For checking the leaf positions of a MLC (Multi Leaf Collimator) images are acquired with an EPID (Electronic Portal Imaging Device) and then evaluated with a programme (MLC check) developed in-house. During image acquisition a Perspex tray with two metal markers of known position (in the radiation field) is inserted in the satellite tray holder. After determination of the marker positions within the image coordinate system, the image can be transformed to the radiation field coordinate system. This allows the exact determination of the leaf tip positions relative to the radiation field. This evaluation can be applied to images of arbitrary field shapes, provided they were acquired in the same geometry (EPID position, gantry and collimator angles). The entire measurement procedure is based on images in bmp (Windows Bitmap) format, with a 1024 x 1024 matrix and a pixel depth of 24 bit (8 bit per color channel). A suitable marker plate can be manufactured without sophisticated workload; thus the method may be easily and cost effectively adapted at other locations.

Long-term outcomes after intracoronary Beta-irradiation for in-stent restenosis in bare-metal stents.

OBJECTIVE: We sought to characterize the long-term outcomes of patients undergoing intracoronary brachytherapy using Beta- irradiation (Beta-BT). BACKGROUND: Beta-BT is effective in reducing angiographic restenosis as well as target vessel revascularization (TVR) in patients with in-stent restenosis (ISR) after bare-metal stenting (BMS). METHODS: 81 consecutive patients undergoing Beta-BT for ISR (irradiated length 32 [32-54] mm) after BMS in native vessels (n = 79) or saphenous vein grafts (n = 2) between 2001 and 2003 were followed. Major cardiac events (MACE), including cardiac death, nonfatal myocardial infarction (MI), and TVR occurring > 1 year or > 1 year were assessed 5.2 (4.4-5.6) years after the index procedure. RESULTS: During the entire follow-up period, the total MACE rate was 49.4%. Within the first year and at > 1 year, MACE rates were 25.9% and 23.5%, cardiac death occurred in 2.4% and 6.2%, and nonfatal MI in 6.2% and 12.3% for annual cardiac death/MI rates of 8.7% at < 1 year and 4.1% thereafter. TVR was required in 19% at < 1 year and in 16% of patients later on. The only independent predictor of MACE occurring < 1 year was an irradiated vessel length > 32 mm (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.10-6.78; p = 0.03). The best, albeit not statistically significant, predictor of MACE occurring at > 1 year was the presence of diabetes mellitus (OR 2.49, 95% CI 0.94-6.57; p = 0.07). CONCLUSIONS: Patients undergoing Beta-BT for ISR after BMS carry a substantial risk of MACE also beyond the first year, with annual cardiac death and nonfatal MI rates of 1.5% and 2.9% up to 5 years postprocedure.

[Determination of organ doses and effective doses in radiooncology]. / Bestimmung von Organdosen und effektiven Dosen in der Radioonkologie.

BACKGROUND AND PURPOSE: With an increasing chance of success in radiooncology, it is necessary to estimate the risk from radiation scatter to areas outside the target volume. The cancer risk from a radiation treatment can be estimated from the organ doses, allowing a somewhat limited effective dose to be estimated and compared. MATERIAL AND METHODS: The doses of the radiation-sensitive organs outside the target volume can be estimated with the aid of the PC program PERIDOSE developed by van der Giessen. The effective doses are determined according to the concept of ICRP, whereby the target volume and the associated organs related to it are not taken into consideration. RESULTS: Organ doses outside the target volume are generally < 1% of the dose in the target volume. In some cases, however, they can be as high as 3%. The effective doses during radiotherapy are between 60 and 900 mSv, depending upon the specific target volume, the applied treatment technique, and the given dose in the ICRU point. CONCLUSION: For the estimation of the radiation risk, organ doses in radiooncology can be calculated with the aid of the PC program PERIDOSE. While evaluating the radiation risk after ICRP, for the calculation of the effective dose, the advanced age of many patients has to be considered to prevent that, e.g., the high gonad doses do not overestimate the effective dose.

[Shielding during dental X-ray examinations. Effectiveness of radiation protection measures for patients during X-ray examinations]. / Abschirmungen bei zahnärztlichen Röntgenaufnahmen. Zur Wirksamkeit von Strahlenschutzmitteln bei Röntgenaufnahmen am Patienten.

During dental X-ray examinations, lead rubber shields such as neck protections or half aprons are commonly used to protect the patient against unnecessary radiation. However, they are practically of no use to the patient as it has been shown by the present measurements. The scatter radiation produced in the body of the patient creates organ doses outside of the collimated radiation field. Other radiation protection measures are more effective and should be considered, although the doses are usually low.

Image quality from high-resolution CT of the lung: comparison of axial scans and of sections reconstructed from volumetric data acquired using MDCT.

OBJECTIVE: Our objective was to compare the image quality of reconstructed thin sections obtained from a 16-MDCT scanner with that of axial high-resolution CT scans of the same patient. SUBJECTS AND METHODS: Fifty consecutive patients referred for CT of the chest underwent 16-MDCT and, subsequently, axial high-resolution CT. The volumetric raw data from the MDCT scans were reconstructed into slices 2-mm thick using a high-spatial-frequency reconstruction algorithm. Two blinded reviewers independently rated the images from both methods for subjective image-quality criteria. The results were tested for statistical significance using Wilcoxon's signed rank test, and p values of less than 0.05 were considered significant. The effective dose for axial high-resolution CT and volumetric MDCT was calculated. RESULTS: Motion artifacts were significantly more common on high-resolution CT scans than on reconstructed thin-section images (p < 0.001). The two methods differed significantly in lung attenuation (p = 0.008), mainly because of the presence of ground-glass opacities. The assessment of ground-glass attenuation was superior on axial high-resolution CT. The effective doses were 3.8 mSv for MDCT and 0.9 mSv for high-resolution CT. CONCLUSION: Reconstructed high-resolution images generated from a single MDCT data acquisition are of comparable quality to images obtained using conventional axial high-resolution CT. However, contiguous MDCT is not recommended for diseases showing predominantly ground-glass patterns, because axial high-resolution CT delineates ground-glass attenuation significantly better.

[Dose exposure from analog and digital full mouth radiography and panoramic radiography]. / Strahlenexposition von analogen und digitalen Zahnstaten und Panoramaschichtaufnahmen.

The present study investigated the dose exposition in the head and neck region by use of analog and digital radiographic dental systems. Four radiographic devices were tested: panoramic radiography (analog and digital) and 14-image full-mouth-survey (FMS, analog and digital). Organ doses were measured on a Rando-phantom by use of CaF2-dosimeters according to the IRCP-guidelines and the effective doses calculated. The results were the following: the value of E was lowest in digital FMS (41 microSv) and highest in analog FMS (78 microSv), i.e. dose was reduced by 47% by using a digital device. In panoramic radiography, doses were 17% lower using digital technique (digital 45 microSv vs. analog 54 pSv). Thus, FMS is no longer associated with higher doses than orthopantomography when conventional films are replaced by digital techniques.

[State of measures of quality assurance for radiotherapy units in Switzerland]. / Zum Stand der Qualitätssicherungsmassnahmen an Röntgentherapieanlagen in der Schweiz.

In Switzerland 57 X-ray therapy units are in operation at present. According to the Swiss Ordinance on Radiation Protection, a quality-assurance program must regularly be applied in to these units. However, as the Swiss X-ray Ordinance gives explicit control parameters only for diagnostic units, the present article issues proposals for the realization of a quality-assurance program for the therapy units. In this regard, it is distinguished between checks performed by technical personnel of the X-ray manufacturers and checks performed by a medical physicist with corresponding qualification, or under his supervision. The so-called mentor project for the performance of annual constancy checks in institutes without medical physicists is also taken into account. These proposals should be helpful for the discussion and clarification of competencies, hence contributing to standardization of control practices in Switzerland.