Evaluation of the IgG antibody response to SARS CoV-2 infection and performance of a lateral flow immunoassay: cross-sectional and longitudinal analysis over 11 months.

OBJECTIVE: To evaluate the dynamics and longevity of the humoral immune response to SARS-CoV-2 infection and assess the performance of professional use of the UK-RTC AbC-19 Rapid Test lateral flow immunoassay (LFIA) for the target condition of SARS-CoV-2 spike protein IgG antibodies. DESIGN: Nationwide serological study. SETTING: Northern Ireland, UK, May 2020-February 2021. PARTICIPANTS: Plasma samples were collected from a diverse cohort of individuals from the general public (n=279), Northern Ireland healthcare workers (n=195), pre-pandemic blood donations and research studies (n=223) and through a convalescent plasma programme (n=183). Plasma donors (n=101) were followed with sequential samples over 11 months post-symptom onset. MAIN OUTCOME MEASURES: SARS-CoV-2 antibody levels in plasma samples using Roche Elecsys Anti-SARS-CoV-2 IgG/IgA/IgM, Abbott SARS-CoV-2 IgG and EuroImmun IgG SARS-CoV-2 ELISA immunoassays over time. UK-RTC AbC-19 LFIA sensitivity and specificity, estimated using a three-reference standard system to establish a characterised panel of 330 positive and 488 negative SARS-CoV-2 IgG samples. RESULTS: We detected persistence of SARS-CoV-2 IgG antibodies for up to 10 months post-infection, across a minimum of two laboratory immunoassays. On the known positive cohort, the UK-RTC AbC-19 LFIA showed a sensitivity of 97.58% (95.28% to 98.95%) and on known negatives, showed specificity of 99.59% (98.53 % to 99.95%). CONCLUSIONS: Through comprehensive analysis of a cohort of pre-pandemic and pandemic individuals, we show detectable levels of IgG antibodies, lasting over 46 weeks when assessed by EuroImmun ELISA, providing insight to antibody levels at later time points post-infection. We show good laboratory validation performance metrics for the AbC-19 rapid test for SARS-CoV-2 spike protein IgG antibody detection in a laboratory-based setting.

Effect of Moderate Red Wine versus Vodka Consumption on Inflammatory Markers Related to Cardiovascular Disease Risk: A Randomized Crossover Study.

Objective: Few interventions have tested the effects of different alcohol types on cardiovascular risk biomarkers. The aim of this study was to investigate the effects of red wine versus vodka on inflammatory and vascular health-related biomarkers.Methods: In a crossover study, participants were randomized to receive either red wine or vodka (3 units/day) for 2 weeks. Following a 2-week washout period, participants then consumed the alternate alcoholic drink for 2 weeks. Fasting blood samples were collected just prior to and at the end of each 2-week period. A total of 13 inflammatory and vascular health biomarkers were assessed.Results: A total of 77 of 85 recruited healthy men completed the study. Leptin levels were significantly raised after each intervention (p ≤ 0.01). APO A1 significantly increased following vodka, but not red wine, intervention (p ≤ 0.01). A significant difference between the interventions was noted for adiponectin only (p ≤ 0.01), although neither of the within-group changes were statistically significant (p > 0.01).Conclusions: The current study found significantly increased levels of leptin following both red wine and vodka consumption, increased levels of APO A1 following vodka consumption, and significant difference between both interventions for adiponectin only. Further studies are needed to investigate the effects of longer-term alcohol consumption on inflammatory and vascular health biomarkers.

Confirmation of a realistic reactor model for BNCT dosimetry at the TRIGA Mainz.

PURPOSE: In order to build up a reliable dose monitoring system for boron neutron capture therapy (BNCT) applications at the TRIGA reactor in Mainz, a computer model for the entire reactor was established, simulating the radiation field by means of the Monte Carlo method. The impact of different source definition techniques was compared and the model was validated by experimental fluence and dose determinations. METHODS: The depletion calculation code origen2 was used to compute the burn-up and relevant material composition of each burned fuel element from the day of first reactor operation to its current core. The material composition of the current core was used in a mcnp5 model of the initial core developed earlier. To perform calculations for the region outside the reactor core, the model was expanded to include the thermal column and compared with the previously established attila model. Subsequently, the computational model is simplified in order to reduce the calculation time. Both simulation models are validated by experiments with different setups using alanine dosimetry and gold activation measurements with two different types of phantoms. RESULTS: The mcnp5 simulated neutron spectrum and source strength are found to be in good agreement with the previous attila model whereas the photon production is much lower. Both mcnp5 simulation models predict all experimental dose values with an accuracy of about 5%. The simulations reveal that a Teflon environment favorably reduces the gamma dose component as compared to a polymethyl methacrylate phantom. CONCLUSIONS: A computer model for BNCT dosimetry was established, allowing the prediction of dosimetric quantities without further calibration and within a reasonable computation time for clinical applications. The good agreement between the mcnp5 simulations and experiments demonstrates that the attila model overestimates the gamma dose contribution. The detailed model can be used for the planning of structural modifications in the thermal column irradiation channel or the use of different irradiation sites than the thermal column, e.g., the beam tubes.

Detector to detector corrections: a comprehensive experimental study of detector specific correction factors for beam output measurements for small radiotherapy beams.

PURPOSE: The aim of the present study is to provide a comprehensive set of detector specific correction factors for beam output measurements for small beams, for a wide range of real time and passive detectors. The detector specific correction factors determined in this study may be potentially useful as a reference data set for small beam dosimetry measurements. METHODS: Dose response of passive and real time detectors was investigated for small field sizes shaped with a micromultileaf collimator ranging from 0.6 × 0.6 cm(2) to 4.2 × 4.2 cm(2) and the measurements were extended to larger fields of up to 10 × 10 cm(2). Measurements were performed at 5 cm depth, in a 6 MV photon beam. Detectors used included alanine, thermoluminescent dosimeters (TLDs), stereotactic diode, electron diode, photon diode, radiophotoluminescent dosimeters (RPLDs), radioluminescence detector based on carbon-doped aluminium oxide (Al2O3:C), organic plastic scintillators, diamond detectors, liquid filled ion chamber, and a range of small volume air filled ionization chambers (volumes ranging from 0.002 cm(3) to 0.3 cm(3)). All detector measurements were corrected for volume averaging effect and compared with dose ratios determined from alanine to derive a detector correction factors that account for beam perturbation related to nonwater equivalence of the detector materials. RESULTS: For the detectors used in this study, volume averaging corrections ranged from unity for the smallest detectors such as the diodes, 1.148 for the 0.14 cm(3) air filled ionization chamber and were as high as 1.924 for the 0.3 cm(3) ionization chamber. After applying volume averaging corrections, the detector readings were consistent among themselves and with alanine measurements for several small detectors but they differed for larger detectors, in particular for some small ionization chambers with volumes larger than 0.1 cm(3). CONCLUSIONS: The results demonstrate how important it is for the appropriate corrections to be applied to give consistent and accurate measurements for a range of detectors in small beam geometry. The results further demonstrate that depending on the choice of detectors, there is a potential for large errors when effects such as volume averaging, perturbation and differences in material properties of detectors are not taken into account. As the commissioning of small fields for clinical treatment has to rely on accurate dose measurements, the authors recommend the use of detectors that require relatively little correction, such as unshielded diodes, diamond detectors or microchambers, and solid state detectors such as alanine, TLD, Al2O3:C, or scintillators.

Dosimetry auditing procedure with alanine dosimeters for light ion beam therapy.

BACKGROUND AND PURPOSE: In the next few years the number of facilities providing ion beam therapy with scanning beams will increase. An auditing process based on an end-to-end test (including CT imaging, planning and dose delivery) could help new ion therapy centres to validate their entire logistic chain of radiation delivery. An end-to-end procedure was designed and tested in both scanned proton and carbon ion beams, which may also serve as a dosimetric credentialing procedure for clinical trials in the future. The developed procedure is focused only on physical dose delivery and the validation of the biological dose is out of scope of the current work. MATERIALS AND METHODS: The audit procedure was based on a homogeneous phantom that mimics the dimension of a head (20 × 20 × 21 cm(3)). The phantom can be loaded either with an ionisation chamber or 20 alanine dosimeters plus 2 radiochromic EBT films. Dose verification aimed at measuring a dose of 10Gy homogeneously delivered to a virtual-target volume of 8 × 8 × 12 cm(3). In order to interpret the readout of the irradiated alanine dosimeters additional Monte Carlo simulations were performed to calculate the energy dependent detector response of the particle fluence in the alanine detector. A pilot run was performed with protons and carbon ions at the Heidelberg Ion Therapy facility (HIT). RESULTS: The mean difference of the absolute physical dose measured with the alanine dosimeters compared with the expected dose from the treatment planning system was -2.4 ± 0.9% (1σ) for protons and -2.2 ± 1.1% (1σ) for carbon ions. The measurements performed with the ionisation chamber indicate this slight underdosage with a dose difference of -1.7% for protons and -1.0% for carbon ions. The profiles measured by radiochromic films showed an acceptable homogeneity of about 3%. CONCLUSIONS: Alanine dosimeters are suitable detectors for dosimetry audits in ion beam therapy and the presented end-to-end test is feasible. If further studies show similar results, this dosimetric audit could be implemented as a credentialing procedure for clinical proton and carbon beam delivery.

Copper surfaces reduce the rate of healthcare-acquired infections in the intensive care unit.

OBJECTIVE. Healthcare-acquired infections (HAIs) cause substantial patient morbidity and mortality. Items in the environment harbor microorganisms that may contribute to HAIs. Reduction in surface bioburden may be an effective strategy to reduce HAIs. The inherent biocidal properties of copper surfaces offer a theoretical advantage to conventional cleaning, as the effect is continuous rather than episodic. We sought to determine whether placement of copper alloy-surfaced objects in an intensive care unit (ICU) reduced the risk of HAI. DESIGN. Intention-to-treat randomized control trial between July 12, 2010, and June 14, 2011. SETTINg. The ICUs of 3 hospitals. PATIENTS. Patients presenting for admission to the ICU. METHODS. Patients were randomly placed in available rooms with or without copper alloy surfaces, and the rates of incident HAI and/or colonization with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) in each type of room were compared. RESULTS. The rate of HAI and/or MRSA or VRE colonization in ICU rooms with copper alloy surfaces was significantly lower than that in standard ICU rooms (0.071 vs 0.123; P = .020). For HAI only, the rate was reduced from 0.081 to 0.034 (P = .013). CONCLUSIONs. Patients cared for in ICU rooms with copper alloy surfaces had a significantly lower rate of incident HAI and/or colonization with MRSA or VRE than did patients treated in standard rooms. Additional studies are needed to determine the clinical effect of copper alloy surfaces in additional patient populations and settings.

Correction factors for ionization chamber dosimetry in CyberKnife: machine-specific, plan-class, and clinical fields.

PURPOSE: The aim of this work is the application of the formalism for ionization chamber reference dosimetry of small and nonstandard fields [R. Alfonso, P. Andreo, R. Capote, M. S. Huq, W. Kilby, P. Kjäll, T. R. Mackie, H. Palmans, K. Rosser, J. Seuntjens, W. Ullrich, and S. Vatnitsky, "A new formalism for reference dosimetry of small and nonstandard fields," Med. Phys. 35, 5179-5186 (2008)] to the CyberKnife robotic radiosurgery system. Correction factors for intermediate calibration fields, a machine-specific reference field (msr) and two plan-class specific reference fields (pcsr), have been studied. Furthermore, the applicability of the new formalism to clinical dosimetry has been analyzed through the investigation of two clinical treatments. METHODS: PTW31014 and Scanditronix-Wellhofer CC13 ionization chamber measurements were performed for the fields under investigation. Absorbed dose to water was determined using alanine reference dosimetry, and experimental correction factors were calculated from alanine to ionization chamber readings ratios. In addition, correction factors were calculated for the intermediate calibration fields and one of the clinical treatment fields using the Monte Carlo method and these were compared with the experimental values. RESULTS: Overall correction factors deviating from unity by approximately 2% were obtained from both measurements and simulations, with values below and above unity for the studied intermediate calibration fields and clinical fields for the ionization chambers under consideration. Monte Carlo simulations yielded correction factors comparable with those obtained from measurements for the machine-specific reference field, although differences from 1% to 3.3% were observed between measured and calculated correction factors for the composite intermediate calibration fields. Dose distribution inhomogeneities are thought to be responsible for such discrepancies. CONCLUSIONS: The differences found between overall correction factors associated with the proposed intermediate calibration fields and the clinical fields under investigation show that depending on the clinical field and the detector used, either a machine-specific reference field or a plan-class specific reference field is more representative for the clinical field. Given the experimental and numerical uncertainties and the small number of clinical fields considered in this study the significance of these observations is limited and it remains unclear for the CyberKnife if there would be a significant gain in using a pcsr field rather than a msr field as reference field for relative dosimetry.

Sustained reduction of microbial burden on common hospital surfaces through introduction of copper.

The contribution of environmental surface contamination with pathogenic organisms to the development of health care-associated infections (HAI) has not been well defined. The microbial burden (MB) associated with commonly touched surfaces in intensive care units (ICUs) was determined by sampling six objects in 16 rooms in ICUs in three hospitals over 43 months. At month 23, copper-alloy surfaces, with inherent antimicrobial properties, were installed onto six monitored objects in 8 of 16 rooms, and the effect that this application had on the intrinsic MB present on the six objects was assessed. Census continued in rooms with and without copper for an additional 21 months. In concert with routine infection control practices, the average MB found for the six objects assessed in the clinical environment during the preintervention phase was 28 times higher (6,985 CFU/100 cm(2); n = 3,977 objects sampled) than levels proposed as benign immediately after terminal cleaning (<250 CFU/100 cm(2)). During the intervention phase, the MB was found to be significantly lower for both the control and copper-surfaced objects. Copper was found to cause a significant (83%) reduction in the average MB found on the objects (465 CFU/100 cm(2); n = 2714 objects) compared to the controls (2,674 CFU/100 cm(2); n = 2,831 objects [P < 0.0001]). The introduction of copper surfaces to objects formerly covered with plastic, wood, stainless steel, and other materials found in the patient care environment significantly reduced the overall MB on a continuous basis, thereby providing a potentially safer environment for hospital patients, health care workers (HCWs), and visitors.

Correction factors for A1SL ionization chamber dosimetry in TomoTherapy: machine-specific, plan-class, and clinical fields.

PURPOSE: Recently, an international working group on nonstandard fields presented a new formalism for ionization chamber reference dosimetry of small and nonstandard fields [Alfonso et al., Med. Phys. 35, 5179-5186 (2008)] which has been adopted by AAPM TG-148. This work presents an experimental determination of the correction factors for reference dosimetry with an Exradin A1SL thimble ionization chamber in a TomoTherapy unit, focusing on: (i) machine-specific reference field, (ii) plan-class-specific reference field, and (iii) two clinical treatments. METHODS: Ionization chamber measurements were performed in the TomoTherapy unit for intermediate (machine-specific and plan-class-specific) calibration fields, based on the reference conditions defined by AAPM TG-148, and two clinical treatments (lung and head-and-neck). Alanine reference dosimetry was employed to determine absorbed dose to water at the point of interest for the fields under investigation. The corresponding chamber correction factors were calculated from alanine to ionization chamber measurements ratios. RESULTS: Two different methods of determining the beam quality correction factor k(Q,Q(0) ) for the A1SL ionization chamber in this TomoTherapy unit, where reference conditions for conventional beam quality determination cannot be met, result in consistent values. The observed values of overall correction factors obtained for intermediate and clinical fields are consistently around 0.98 with a typical expanded relative uncertainty of 2% (k = 2), which when considered make such correction factors compatible with unity. However, all of them are systematically lower than unity, which is shown to be significant when a hypothesis test assuming a t-student distribution is performed (p=1.8×10(-2)). Correction factors k(Q(clin),Q(pcsr) ) (f(clin),f(pcsr) ) and k(Q(clin),Q(msr) ) (f(clin),f(msr) ), which are needed for the computation of field factors for relative dosimetry of clinical beams, have been found to be very close to unity for two clinical treatments. CONCLUSIONS: The results indicate that the helical field deliveries in this study (including two clinical fields) do not introduce changes on the ion chamber correction factors for dosimetry. For those two specific clinical cases, ratios of chamber readings accurately represent field output factors. The values observed here for intermediate calibration fields are in agreement with previously published data based on alanine dosimetry but differ from values recently reported obtained via radiochromic dosimetry.

Dose determination using alanine detectors in a mixed neutron and gamma field for boron neutron capture therapy of liver malignancies.

UNLABELLED: Boron Neutron Capture Therapy for liver malignancies is being investigated at the University of Mainz. One important aim is the set-up of a reliable dosimetry system. Alanine dosimeters have previously been applied for dosimetry of mixed radiation fields in antiproton therapy, and may be suitable for measurements in mixed neutron and gamma fields. MATERIAL AND METHODS: Two experiments have been carried out in the thermal column of the TRIGA Mark II reactor at the University of Mainz. Alanine dosimeters have been irradiated in a phantom and in liver tissue. RESULTS: For the interpretation and prediction of the dose for each pellet, beside the results of the measurements, calculations with the Monte Carlo code FLUKA are presented here. For the phantom, as well as for the liver tissue, the measured and calculated dose and flux values are in good agreement. DISCUSSION: Alanine dosimeters, in combination with flux measurements and Monte Carlo calculations with FLUKA, suggest that it is possible to establish a system for monitoring the dose in a mixed neutron and gamma field for BNCT and other applications in radiotherapy.

Dose response of alanine detectors irradiated with carbon ion beams.

PURPOSE: The dose response of the alanine detector shows a dependence on particle energy and type when irradiated with ion beams. The purpose of this study is to investigate the response behavior of the alanine detector in clinical carbon ion beams and compare the results to model predictions. METHODS: Alanine detectors have been irradiated with carbon ions with an energy range of 89-400 MeV/u. The relative effectiveness of alanine has been measured in this regime. Pristine and spread out Bragg peak depth-dose curves have been measured with alanine dosimeters. The track structure based alanine response model developed by Hansen and Olsen has been implemented in the Monte Carlo code FLUKA and calculations were compared to experimental results. RESULTS: Calculations of the relative effectiveness deviate less than 5% from the measured values for monoenergetic beams. Measured depth-dose curves deviate from predictions in the peak region, most pronounced at the distal edge of the peak. CONCLUSIONS: The used model and its implementation show a good overall agreement for quasi-monoenergetic measurements. Deviations in depth-dose measurements are mainly attributed to uncertainties of the detector geometry implemented in the Monte Carlo simulations.

A national dosimetric audit of IMRT.

BACKGROUND AND PURPOSE: A dosimetric audit of IMRT has been carried out within the UK between June 2009 and March 2010 in order to provide an independent check of safe implementation and to identify problems in the modelling and delivery of IMRT. METHODS AND MATERIALS: A mail based audit involving film and alanine dosimeters was utilized. Measurements were made for each individual field in an IMRT plan isocentrically in a flat water-equivalent phantom at a depth of 5cm. The films and alanine dosimeters were processed and analysed centrally; additional ion chamber measurements were made by each participating centre. RESULTS: 57 of 62 centres participated, with a total of 78 plans submitted. For the film measurements, all 176 fields from the less complex IMRT plans (including prostate and breast plans) achieved over 95% pixels passing a gamma criterion of 3%/3mm within the 20% isodose. For the more complex IMRT plans (mainly head and neck) 8/245 fields (3.3%) achieved less than 95% pixels passing a 4%/4mm gamma criterion. Of the alanine measurements, 4/78 (5.1%) of the measurements differed by >5% from the dose predicted by the treatment planning system. Three of these were large deviations of -77.1%, -29.1% and 14.1% respectively. Excluding the three measurements outside 10%, the mean difference was 0.05% with a standard deviation of 1.5%. The out of tolerance results have been subjected to further investigations. CONCLUSIONS: A dosimetric audit has been successfully carried out of IMRT implementation by over 90% of UK radiotherapy departments. The audit shows that modelling and delivery of IMRT is accurate, suggesting that the implementation of IMRT has been carried out safely.

Control and mitigation of healthcare-acquired infections: designing clinical trials to evaluate new materials and technologies.

Hospitals clean environmental surfaces to lower microbial contamination and reduce the likelihood of transmitting infections. Despite current cleaning and hand hygiene protocols, hospital-acquired infections (HAIs) continue to result in a significant loss of life and cost the U.S. healthcare system an estimated $45 billion annually. Stainless steel and chrome are often selected for hospital touch surfaces for their "clean appearance," comparatively smooth finish, resistance to standard cleaners, and relative effectiveness for removing visible dirt during normal cleaning. Designers use wood surfaces for aesthetics; plastic surfaces have become increasingly endemic for their relative lower initial cost; and "antimicrobial agents" are being incorporated into a variety of surface finishes.This paper concentrates on environmental surface materials with a history of bactericidal control of infectious agents and focuses on the methods necessary to validate their effectiveness in healthcare situations. Research shows copper-based metals to have innate abilities to kill bacteria in laboratory settings, but their effectiveness in patient care environments has not been adequately investigated. This article presents a research methodology to expand the evidence base from the laboratory to the built environment. For such research to have a meaningful impact on the design/specifying community, it should assess typical levels of environmental pathogens (i.e., surface "cleanliness") as measured by microbial burden (MB); evaluate the extent to which an intervention with copper-based materials in a randomized clinical trial affects the level of contamination; and correlate how the levels of MB affect the incidence of infections acquired during hospital stays.

The relationship between microvascular endothelial function and carotid-radial pulse wave velocity in patients with mild hypertension.

Carotid-radial pulse wave velocity (CRPWV) can be measured rapidly using applanation tonometry and significantly higher values have been reported among patients with risk factors for vascular disease. Forearm blood flow responses to intrabrachial infusion of acetylcholine independently predict cardiovascular morbidity among hypertensive patients. We aimed to examine the relationship between CRPWV, a potentially informative, noninvasive measure and this more established parameter of arterial health. One hundred and fifteen mildly hypertensive individuals (67% men, mean (± SD) age 54 ± 8 years, mean (± SD) blood pressure (BP) 143 ± 16/83 ± 12 mmHg) were recruited from a weekly medical outpatient clinic. Each volunteer had CRPWV measured using sequential tonometry before forearm blood flow responses to intra-arterial, endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) vasodilators were assessed. There was a significant negative correlation between CRPWV and maximum forearm blood flow response to acetylcholine (r = -0.225, p = 0.016). This association remained significant in a multiple regression analysis (ß = -0.213, p = 0.034). Mean arterial pressure and weight were additional independent predictors of CRPWV in this model. There was no such relationship between CRPWV and response to sodium nitroprusside (r = 0.088, p = 0.349). In patients with mild hypertension, a poor forearm blood flow response to acetylcholine independently predicted faster CRPWV, thus linking an established measure of microvascular endothelial function with a noninvasive index of conduit vessel stiffness.

Dose calculation in biological samples in a mixed neutron-gamma field at the TRIGA reactor of the University of Mainz.

To establish Boron Neutron Capture Therapy (BNCT) for non-resectable liver metastases and for in vitro experiments at the TRIGA Mark II reactor at the University of Mainz, Germany, it is necessary to have a reliable dose monitoring system. The in vitro experiments are used to determine the relative biological effectiveness (RBE) of liver and cancer cells in our mixed neutron and gamma field. We work with alanine detectors in combination with Monte Carlo simulations, where we can measure and characterize the dose. To verify our calculations we perform neutron flux measurements using gold foil activation and pin-diodes. Material and methods. When L-α-alanine is irradiated with ionizing radiation, it forms a stable radical which can be detected by electron spin resonance (ESR) spectroscopy. The value of the ESR signal correlates to the amount of absorbed dose. The dose for each pellet is calculated using FLUKA, a multipurpose Monte Carlo transport code. The pin-diode is augmented by a lithium fluoride foil. This foil converts the neutrons into alpha and tritium particles which are products of the (7)Li(n,α)(3)H-reaction. These particles are detected by the diode and their amount correlates to the neutron fluence directly. Results and discussion. Gold foil activation and the pin-diode are reliable fluence measurement systems for the TRIGA reactor, Mainz. Alanine dosimetry of the photon field and charged particle field from secondary reactions can in principle be carried out in combination with MC-calculations for mixed radiation fields and the Hansen & Olsen alanine detector response model. With the acquired data about the background dose and charged particle spectrum, and with the acquired information of the neutron flux, we are capable of calculating the dose to the tissue. Conclusion. Monte Carlo simulation of the mixed neutron and gamma field of the TRIGA Mainz is possible in order to characterize the neutron behavior in the thermal column. Currently we also speculate on sensitizing alanine to thermal neutrons by adding boron compounds.