Cumulative Activity Research Articles

Патогенетическое значение мембранных и метаболических нарушений при бронхитах у детей

Study Objective: To study the features of intracellular and extracellular free-radical oxidation (FRO) processes with reference to the cellular membrane condition in various clinical forms of paediatric bronchitis. Study Design: prospective cohort study. Materials and Methods. The study included 237 children aged 2 to 15.5 years old with bronchitis. The patients were divided into three groups depending on the clinical form of bronchitis: acute bronchitis (AB) — 91 children (mean age: 9.8 years old); acute obstructive bronchitis (AOB) — 32 children (mean age: 7.5 years old); and recurrent bronchitis (RB) — 14 children (mean age: 10.2 years old). The control group included 43 conditionally healthy children (mean age: 9.5 years old). We conducted clinical examination, as well as standard instrumental and laboratory tests and interviewed all children. We studied FRO activity (using spontaneous and zymozan-induced luminol-depend chemicoluminescence, ICL), cumulative serum antioxidant activity (AOA), and ceruleoplasmin (CP). Red-cell membranes permeability by sodium was measured using determination of the maximum rate of Na+-Li+-exchange transport (ET) in RBC. Study Results. All patients demonstrated increased rate of Na+-Li+-ET, with the mean value in AB being 232 ± 7.0 (р < 0.05), in OAB — 269 ± 10.0 (р < 0.05), in RB — 328 ± 11.0 μmol Li (р < 0.01). In AB, ICL level was relatively constant vs. normal value irrespective of the disease phase (137.61 ± 22.3 counts/min/1,000 PMNL). In early OAB, ICL was significantly more active (up to 208.98 ± 7.6 counts/min/1,000 PMNL) which normalised later at clinical recovery. In patients with RB, peak ICL was as low as 107.06 ± 26.42 counts/min/1,000 PMNL; at clinical recovery, the value was even lower — 66.41 ± 8.9 counts/min/1,000 PMNL (р < 0.001 vs. healthy children). In acute phase of all forms of the disease, we recorded a significant raise in malondialdehyde; however, its peak concentration was seen in patients with RB; the value was significantly different not only from controls, but also from patients with AB and OAB; and at clinical stabilisation, the value reached 3.72 ± 0.08 μmol (р < 0.05). Patients with AB at recovery had the cumulative AOA of 39.9 ± 0.59% (р < 0.05); however, the control value was not achieved (42.39 ± 0.49%). CP levels were raised as well and reached 64.98 ± 0.43 mg%, but did not differ significantly from the initial value. In OAB, the cumulative OAO did not reach its peak value. Its mean value remained the same. In patients with RB, the cumulative AOA did not reach the normal value, but also reduced a lot (р < 0.05), together with reduced serum CP concentration from 60.20 ± 0.52 mg% to 57.83 ± 0.41 mg% (р < 0.05). Conclusion. Persistence and intensity of membrane and metabolic shifts in children with bronchitis are of great significance in the pathogenesis of a recurrent inflammation in bronchi and can be used as prediction criteria of the disease, allowing to set up a management plan. Keywords: children, bronchitis, free-radical oxidation of lipids, ion exchange system, antioxidant activity, ceruleoplasmin.

Surveillance of Respiratory Syncytial Virus in Children Aged 0-5 years in Côte d'Ivoire

Acute Respiratory Infections (ARI) are, after malaria, the second most common cause of consultation of children in health facilities in Côte d'Ivoire. Viral etiology points to Respiratory Syncytial Virus (RSV) as the primary cause of these acute respiratory infections. In order to better assist health workers in diagnosing the virus, a study on the epidemiology, seasonality and clinical signs associated with RSV acute respiratory infections was conducted over four consecutive years. During these years, nasopharyngeal samples were collected from 5648 children aged 0-5 years, in different geographical areas of the country, following a survey form for analysis by real-time PCR, to detect the virus and describe its epidemiological characteristics. Our results revealed 564 (9.98%) RSV positive children. A number of 181 (32.09%) were positive in inpatients, and 383 (67.91%) in outpatients. The 0-12 month age group was the most affected with 51.95% of positive cases. Cumulative monthly RSV activity for the 4 years of the study was relatively lower during the months of January to March and higher during the months of May to September. This distribution of RSV was superimposed on rainfall during these study years. Our work has also linked RSV positivity to the presence of clinical signs, including fever, cough, diarrhoea and vomiting. These results give scientific tools to health personnel to better orient their diagnosis and also a better rational use in the prescription of medication, notably the stopping of unjustified antibiotic therapy.

Prediction of treatment response to transarterial radioembolization of liver metastases: Radiomics analysis of pre-treatment cone-beam CT: A proof of concept study

PurposeTo investigate the potential of texture analysis and machine learning to predict treatment response to transarterial radioembolization (TARE) on pre-interventional cone-beam computed tomography (CBCT) images in patients with liver metastases. Materials and MethodsIn this IRB-approved retrospective single-center study 36 patients with a total of 104 liver metastases (56 % male, mean age 61.1 ± 13 years) underwent CBCT prior to TARE and follow-up imaging 6 months after therapy. Treatment response was evaluated according to RECIST version 1.1 and dichotomized into disease control (partial response/stable disease) versus disease progression (progressive disease). After target lesion segmentation, 104 radiomics features corresponding to seven different feature classes were extracted with the pyRadiomics package. After dimension reduction machine learning classifications were performed on a custom artificial neural network (ANN). Ten-fold cross validation on a previously unseen test data set was performed. ResultsThe average administered cumulative activity from TARE was 1.6 Gbq (± 0.5 Gbq). At a mean follow-up of 5.9 ± 0.8 months disease control was achieved in 82 % of metastases. After dimension reduction, 15 of 104 (15 %) texture analysis features remained for further analysis. On a previously unseen set of liver metastases the Multilayer Perceptron ANN yielded a sensitivity of 94.2 %, specificity of 67.7 % and an area-under-the receiver operating characteristics curve of 0.85. ConclusionOur study indicates that texture analysis-based machine learning may has potential to predict treatment response to TARE using pre-treatment CBCT images of patients with liver metastases with high accuracy.

Comparative study on application of 177Lu-labeled rituximab, tetulomab, cetuximab and huA33 monoclonal antibodies to targeted radionuclide therapy

Purpose Dose coefficients from rituximab, tetulomab, cetuximab, and huA33 monoclonal antibodies labelled with the radionuclide 177Lu were estimated for human organs and tumours via a theoretical simulation based on experimental results. Methods The real experimental results were obtained from radiopharmaceutical distribution in hairless mice. Using the Sparks and Aydogan method, the cumulated activity for humans was recalculated. The simulation was used to assess the behaviour of MAbs labelled with 177Lu after injection into the human body. The average absorbed doses were calculated for the most exposed organs and tissues. Results The huA33 monoclonal antibodies (MAbs) labelled with 177Lu (Lu-rituximab, Lu-tetulomab, Lu-cetuximab, and Lu-huA33), presented the maximum nuclear transformation per Bq intake for the main organs (blood, kidneys, liver, lung, and spleen, as well as for a tumour) The absorbed dose in the liver is three times lower for Lu-huA33 compared to the other drugs. In the case of cetuximab, the spleen received the lowest dose compared to the other drugs. The dependencies on absorbed dose for the alveolar, bronchioles, bone surface, heart wall, kidneys, liver, lung, lymphatic nodes, and spleen, are presented. For tumours, the absorbed dose for each drug is calculated separately for a sphere of unit volume by using the information on the injected dose. Conclusion, The ratios of the dose coefficient for the tumour to each organ, indicate that lutetium-177 can be recommended for targeted radionuclide therapy since the dose per tumour is much greater than the dose per organ.

Internal dosimetry of [99m Tc]NTP15-5 radiotracer for cartilage imaging in preclinical and clinical models using the GATE Monte Carlo platform.

This study aims to perform dosimetry for [99m Tc]NTP15-5 radiotracer used in imaging of articular cartilage in rabbits and humans. The radiotracer (covered by a world patent WO 01/00621 A1) has been proposed in the previous years for the study of cartilage in osteoarthritis diseases. A sensitive imaging approach is essential to quantify osteoarthritis progression and monitor response to new therapies. [99m Tc]NTP15-5 binds to cartilage proteoglycans whose decreased content is associated to a loss of biomedical function of cartilage. We have implemented the whole dosimetry study concerning this new radiotracer for rabbits and humans using the GATE Monte Carlo platform. Absorbed doses to critical organs are determined using the MIRD formalism. Biodistribution data are obtained by organ sampling, measuring the activity in organs for three rabbits sacrificed at various times postadministration, and by SPECT/CT imaging at different times after injection. Most important sources are cartilages (in knees and intervertebral discs), due to localization together with the liver and kidneys due to excretion of the agent. S-values are calculated from rabbit's CT scan and human CT scan using the GATE v8.0 Monte Carlo platform. Cumulated activity in humans is extrapolated from animals using the %kg-dose/g method. Particular attention is given to dose calculation in bones, bone marrow and organs at risk. The dosimetry performed in rabbits shows highest absorbed doses for liver and kidneys with respectively 22.5 and 43.8µGy per MBq of injected activity. In humans, we found absorbed doses for a maximum injected activity of 15MBq/kg, that is, 1050MBq for an adult of 70kgs of 9.03mGy for kidneys and 4.16mGy for knee cartilages. Effective dose is 2.69µSv/MBq. The dosimetry profile of [99m Tc]NTP15-5 in the context of preclinical trials is of major importance in order to make sure that organs at risk are not overexposed. GATE provides all the capability needed to calculate dose profiles for internal dosimetry. The extrapolation of the dose for a human model is a first step towards clinical trials.

Effects of cumulated outdoor activity on wildlife habitat use

Humans profoundly affect animal distributions by directly competing for space, not only transforming, but actively using their habitat. Anthropogenic disturbance is usually measured via structural proxies such as infrastructure and land use that overlook the impact of human presence, or functional disturbance. In this study, we propose a methodology unifying two paradigms, human mobility and animal movement, to fill this gap. We developed a novel spatially-explicit index of anthropic disturbance, the Cumulative Outdoor activity Index (COI), and validated it with ground truth observations derived from camera trapping (r = +0.63, p < 0.001). Building on previous work from Peters et al. (2015, Biol. Cons. 186, 123–133) on a Critically Endangered brown bear population in the Alps, we used Resource Selection Analysis to assess the influence of different forms of anthropogenic disturbance on the relative probability of habitat selection. The intensity of COI provided an effective measure of functional anthropogenic disturbance, and it outperformed all alternative and commonly-used proxies of structural disturbance in predicting bear habitat use. Our predictions suggest that brown bear shrinks its ecological niche as a consequence of intense human use of otherwise suitable habitat. These constraints may limit the potential range expansion of bears to establish a viable Alpine-Dinaric metapopulation. Conclusive conservation and future land use planning towards human-wildlife coexistence should account for the functional presence of humans on the landscape. The proposed COI could help determine where mitigation measures should be enforced.

An evaluation of the relationship between the degree of entheseal changes and the severity of osteodegenerative processes at fibrocartilaginous entheses.

An enthesis refers to the interface at which a tendon or a ligament integrates into the periosteum. Its morphology can be influenced by intrinsic factors such as sex, age, and extrinsic factors such as levels of activity, which will in turn impact on bone remodeling and lead to morphological changes. In bioarcheology, entheseal changes have had a long tradition of being used for the reconstruction of past activities. The literature has shown that in some cases of osteoarthritis, entheseal changes are associated with osteoarthritic manifestations. This work aims to evaluate the relationship between the degree of entheseal changes and the severity of osteodegenerative processes. The studied materials consisted of 30 humeri and 30 femora from the osteological collection at St George's University of London. Intensities of both entheseal changes and osteodegenerative processes were macroscopically assessed and scored. The difference in scores of entheseal changes between osteoarthritic groups and nonosteoarthritic groups is statistically significant at a confidence level of 95% (α=.05) for both the humeri and femora. Results show a positive correlation between the degree of entheseal changes and the severity of osteodegenerative processes in the femora, suggesting that enthesis may play a role in osteoarthritis. Findings from this work supports the proposed hypothesis that the degree of entheseal changes and the severity of osteoarthritic manifestation are related. This work contributes to current knowledge that osteoarthritis is a disease involving the whole joint; the enthesis could potentially be a target for the diagnosis of osteoarthritis.

Effects of physical activity on quality of life and physical function in postoperative patients with gastrointestinal cancer.

This study was to clarify changes in physical function and quality of life (QOL) for postoperative, and to examine the influence of the amount of physical activity on these variables. This study included 29 patients who underwent gastrointestinal cancer surgery. The QOL measurement was used to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for preoperative and 2nd and 4th postoperative weeks. Physical function measured knee extension strength, 4 m walk time, 5 times sit-to-stand test, and 6-minute walk for preoperative and 1st and 2nd postoperative weeks. The amount of physical activity score was based on METs-hours, which is estimated from cumulative physical activity. As basic characteristics were investigated cancer stage, comorbidities and complications, and operative. Statistical analysis was repeated measures analysis of variance was performed to observe postoperative changes in physical function and QOL. Furthermore, stepwise multiple regression analysis was used to the parameters of physical function and QOL affected by the physical activity score were investigated. Physical function decreased postoperatively and generally improved 2nd postoperative week. Though scores on the QOL functional scales improved, some items did not improve sufficiently. Multiple regression analysis showed that physical activity score had an effect on constipation and emotion functioning. Improvement in symptom scales is not sufficient in a short period of time, and they need to be followed up by increasing the amount of physical activity and promoting instantaneous exercise.

Labeling of ethylenediamine tetramethylene phosphonate with 153Sm and 177Lu,Comparison Study

Background 177Lu and 153Sm are perspective radionuclides in terms of applying to nuclear medicine. High-energy beta particles and the relative half-life of the radionuclide are used to achieve an effective palliative treatment of bone metastases. Materials and methods The absorbed doses in different organs and tissues of 177Lu and 153Sm in ionic form and labeled with EDTMP are determined by IDAC-Dose 2.1 (Internal Dose Assessment by Computer) software and WinAct software which used to calculate cumulative activity. 177Lu and 153Sm are lanthanide radionuclide which actively accumulates in liver and bone when used in ionic form. In the case of labeling with EDTMP, the distribution and elimination of the drug occur according to the kinetics of a carrier, EDTMP. The using of osteotropic (Describing any drug etc. that is attracted to, and targets bone) complex allows creating a large dose in the pathological areas and minimizing damages in healthy organs and tissues. Results The effective dose per administered activity is 0.189 mSv/MBq for 177Lu-ionic form, 0.232 mSv/MBq for 153Sm-ionic form and 0.242 mSv/MBq for 177Lu-EDTMP and 0.139 mSv/MBq for 153sm-EDTMP. Conclusion 177Lu and 153Sm labeled with EDTMP are decreasing the liver dose absorption and increasing the bone surface absorption for more effective treatment and minimize side effects.

A Thorough Examination of Morning Activity Patterns in Adults with Arthritis and Healthy Controls Using Actigraphy Data

Background: Wearable sensors allow researchers to remotely capture digital health data, including physical activity, which may identify digital biomarkers to differentiate healthy and clinical cohorts. To date, research has focused on high-level data (e.g., overall step counts) which may limit our insights to whether people move differently, rather than how they move differently. Objective: This study therefore aimed to use actigraphy data to thoroughly examine activity patterns during the first hours following waking in arthritis patients (n = 45) and healthy controls (n = 30). Methods: Participants wore an Actigraph GT9X Link for 28 days. Activity counts were analysed and compared over varying epochs, ranging from 15 min to 4 h, starting with waking in the morning. The sum, and a measure of rate of change of cumulative activity in the period immediately after waking (area under the curve [AUC]) for each time period, was calculated for each participant, each day, and individual and group means were calculated. Two-tailed independent t tests determined differences between the groups. Results: No differences were seen for summed activity counts across any time period studied. However, differences were noted in the AUC analysis for the discrete measures of relative activity. Specifically, within the first 15, 30, 45, and 60 min following waking, the AUC for activity counts was significantly higher in arthritis patients compared to controls, particularly at the 30 min period (t = –4.24, p = 0.0002). Thus, while both cohorts moved the same amount, the way in which they moved was different. Conclusion: This study is the first to show that a detailed analysis of actigraphy variables could identify activity pattern changes associated with arthritis, where the high-level daily summaries did not. Results suggest discrete variables derived from raw data may be useful to help identify clinical cohorts and should be explored further to determine if they may be effective clinical biomarkers.

Can we safely reduce the administration of 131-iodine in patients with differentiated thyroid cancer? \u2013 experience of the Brugmann hospital in Brussels

Background131-iodine (131I) administration after surgery remains a standard practice in differentiated thyroid cancer (DTC). In 2014, the American Thyroid Association presented new guidelines for the staging and management of DTC, including no systematic 131I in patients at low-risk of recurrence and a reduced 131I activity in intermediate risk.The present study aims at evaluating the rate of response to treatment following this new therapeutic management compared to our previous treatment strategy in patients with DTC of different risks of recurrence.MethodsPatients treated and followed up for DTC according to the 2014-ATA guidelines (Group 2) were compared to those treated between 2007 and 2014 (Group 1) in terms of general characteristics, risk of recurrence (based on the 2015-ATA recommendations), preparation to 131I administration, cumulative administered 131I activity and response to treatment.ResultsIn total, 136 patients were included: 78 in Group 1 and 58 in Group 2. The two groups were not statistically different in terms of clinical characteristics nor risk stratification: 42.3% in Group 1 and 31% in Group 2 were classified as low risk, 38.5 and 48.3% as intermediate risk and 19.2 and 20.7% as high risk (P = 0.38). Two patients (one in each group) with distant metastases were excluded from the analysis.Preparation to 131I administration consisted in rhTSH stimulation in 23.4% of the patients in Group 1 and 100% in Group 2 (p < 0.001).131I was administered to 46/77 patients (59.7%) in Group 1 (5 at low risk of recurrence) and 38/57 patients (66.7%) in Group 2 (0 with a low risk). Among the patients treated by 131I, median cumulative activity was significantly higher in Group 1 (3.70GBq [100 mCi] range 1.11–11.1 GBq [30–300 mCi]) than in Group 2 (1.11 GBq [30 mCi], range 1.11–7.4 GBq [30–200 mCi], P < 0.001). Complete response was found in 90.9% in Group 1 vs. 96.5% in Group 2 (P = 0.20).ConclusionsUsing the 2015-ATA evidence-based guidelines for the management of DTC, meaning no 131I administration in low-risk patients, a low activity in intermediate and even high risk patients, and a systematic use of rhTSH stimulation before 131I therapy allowed us to reduce significantly the median administered 131I activity, with a similar rate of complete therapeutic response.

Childhood trauma and dysregulation of multiple biological stress systems in adulthood: Results from the Netherlands Study of Depression and Anxiety (NESDA)

BackgroundChildhood trauma (CT) is a risk factor for depressive and anxiety disorders. Although dysregulated biological stress systems may underlie the enduring effect of CT, the relation between CT and separate and cumulative activity of the major stress systems, namely, the hypothalamic-pituitary-adrenal (HPA)-axis, the immune-inflammatory system, and the autonomic nervous system (ANS), remains inconclusive. MethodsIn the Netherlands Study of Depression and Anxiety (NESDA, n = 2778), we determined whether self-reported CT (as assessed by the Childhood Trauma Interview) was associated with separate and cumulative markers of the HPA-axis (cortisol awakening response, evening cortisol, dexamethasone suppression test cortisol), the immune-inflammatory system (C-reactive protein, interleukin-6, tumor necrosis factor-α), and the ANS (heart rate, respiratory sinus arrhythmia, pre-ejection period) in adulthood. ResultsAlmost all individuals with CT (n = 1330) had either current or remitted depressive and/or anxiety disorder (88.6%). Total-sample analyses showed little evidence for CT being significantly associated with the separate or cumulative stress systems’ activity in adulthood. These findings were true for individuals with and without depressive and/or anxiety disorders. To maximize contrast, individuals with severe CT were compared to healthy controls without CT. This yielded slight, but significantly higher levels of cortisol awakening response (AUCg, β = .088, p = .007; AUCi, β = .084, p = .010), cumulative HPA-axis markers (β = .115, p = .001), C-reactive protein (β = .055, p = .032), interleukin-6 (β = .053, p = .038), cumulative inflammation (β = .060, p = .020), and cumulative markers across all systems (β = .125, p = .0003) for those with severe CT, partially explained by higher rates of smoking, body mass index, and chronic diseases. ConclusionWhile our findings do not provide conclusive evidence on CT directly dysregulating stress systems, individuals with severe CT showed slight indications of dysregulations, partially explained by an unhealthy lifestyle and poorer health.

Enhanced anaerobic co-digestion of waste activated sludge and food waste by sulfidated microscale zerovalent iron: Insights in direct interspecies electron transfer mechanism

The enhancement of zerovalent iron (ZVI) on anaerobic digestion (AD) has been proved, but there are still some problems that constrain the large-scale application of ZVI, such as the destruction of cell membrane and the inhibition of methanogenesis led by rapid H2 accumulation. Aiming at these problems, sulfidated microscale zerovalent iron (S-mZVI) was employed to evaluate its effect on anaerobic co-digestion (AcoD) of waste activated sludge (WAS) and food waste (FW). Experimental results showed that S-mZVI promoted the direct interspecies electron transfer (DIET) between specific bacteria and methanogens, resulting in higher methane yield. At S-mZVI 10 g/L, the cumulative methane yield and ETS activity reached 264.78 mL/g-VS and 24.62 mg INTF/(g-TS h), which was 1.33 and 1.83 times that of blank. Microbiological analysis demonstrated that the abundance of DIET-related microorganisms such as Syntrophomonas, Methanosarcina and Methanobacterium increased with the increasing dosage of S-mZVI.

Quantification of internal dosimetry in PET patients: individualized Monte Carlo vs generic phantom-based calculations.

PurposeThe purpose of this work is to calculate individualized dose distributions in patients undergoing 18F‐FDG PET/CT studies through a methodology based on full Monte Carlo (MC) simulations and PET/CT patient images, and to compare such values with those obtained by employing nonindividualized phantom‐based methods.MethodsWe developed a MC‐based methodology for individualized internal dose calculations, which relies on CT images (for organ segmentation and dose deposition), PET images (for organ segmentation and distributions of activities), and a biokinetic model (which works with information provided by PET and CT images) to obtain cumulated activities. The software vGATE version 8.1. was employed to carry out the Monte Carlo calculations. We also calculated deposited doses with nonindividualized phantom‐based methods (Cristy–Eckerman, Stabin, and ICRP‐133).ResultsMedian MC‐calculated dose/activity values are within 0.01–0.03 mGy/MBq for most organs, with higher doses delivered especially to the bladder wall, major vessels, and brain (medians of 0.058, 0.060, 0.066 mGy/MBq, respectively). Comparison with values obtained with nonindividualized phantom‐based methods has shown important differences in many cases (ranging from −80% to + 260%). These differences are significant (p < 0.05) for several organs/tissues, namely, remaining tissues, adrenals, bladder wall, bones, upper large intestine, heart, pancreas, skin, and stomach wall.ConclusionsThe methodology presented in this work is a viable and useful method to calculate internal dose distributions in patients undergoing medical procedures involving radiopharmaceuticals, individually, with higher accuracy than phantom‐based methods, fulfilling the guidelines provided by the European Council directive 2013/59/Euratom.

Dosimetric methodology for 131I therapy for benign thyroid diseases

Treatment with 131I is one of the standard treatments for benign thyroid disease. In most cases, the prescribed dose is specific for the same disease. Inspired by external radiotherapy, the emergence of personalized pre-therapeutic dosimetry in nuclear medicine departments makes it possible to adapt to the patient's diseases and physiology; more specific to its kinetics of iodine distribution. By personalizing the prescribed activity, dosimetry makes it possible to comply with the ALARA principle in metabolic radiotherapy while at the same time preserving the therapeutic objective. Post-treatment dosimetry permits to validate the methodology and, by recording the dose actually delivered to the organs surrounding the target volume, to contribute to the understanding of the dose-effect relationship. A re-reading of the MIRD formalism guidelines is important as this document lists the procedure to be followed in thyroid dosimetry. Defining the sensitivity, calculating the S factors, estimating the cumulative activity and residence times and then calculating the dose are the different steps presented. The need to switch from fixed dose prescription to personalized prescription seems to be evident. Several studies in progress as well as the emergence of new software compiling all the information essential for its implementation will permit nuclear medicine departments to involve themselves more easily into the process.

Study on a Continuous Measurement Method for Unattached Radon Progeny.

A method that does not require changing wire screens is proposed to achieve continuous measurement of unattached radon progeny. This method uses cumulative activity functions to deduct the influence of previous measurements from the current measurements on the sampling wire screen. The continuous measurement method was compared with a single measurement method, including relative deviations, uncertainties, and fluctuation range, which indicated the effectiveness of the cumulative activity functions applied to the continuous measurement method. The establishment of a continuous measurement method based on alpha spectroscopy provides technical support for the monitoring device.

Cellular S values in spindle-shaped cells: a dosimetry study on more realistic cell geometries using Geant4-DNA Monte Carlo simulation toolkit

Cellular dosimetry plays a crucial role in radiobiology and evaluation of the relative merits of radiopharmaceuticals used for targeted radionuclide therapy. The present study aims to investigate the effects of various cell geometries on dosimetric characteristics of several Auger emitters distributed in different subcellular compartments using Monte Carlo simulation. The Geant4-DNA extension of the Geant4 Monte Carlo simulation toolkit was employed to calculate the mean absorbed dose per unit cumulated activity (S value) for different subcellular distributions of several Auger electron-emitting theranostic radionuclides including 99mTc, 111In, 123I, 125I, and 201Tl. The simulations were carried out in various single-cell models of liquid water including spherical, ellipsoidal, spherical spindle, and ellipsoidal spindle cell models. The latter two models which are generalized from the first two models were inspired by the morphologies of spindle-shaped (fusiform) cells, and were developed to provide more realistic modeling of this common geometry observed in many healthy and cancerous cells. Evaluation of the S values calculated for the examined cell models reveals that the differences are small (less than 9%) for the cell ← cell, cell ← cell surface, and nucleus ← nucleus source-target combinations. However, moderate discrepancies are seen (up to 28%) when the nucleus is considered as the target, as well as the radioactivity is either internalized into the cytoplasm or bound to the cell membrane. The findings of the present work suggest that the assumption of spherical cell geometry may provide reasonably accurate estimates of the cellular/nuclear dose for the considered Auger emitters, even for spindle-shaped cells. Of course, this approximation should be used with caution for the nucleus ← cytoplasm and nucleus ← cell surface configurations, since the S-value sensitivity to the cell geometry is somewhat significant in these cases.

Assessing potential trade-offs between the lower back and shoulders: influence of lift training intervention on joint demands

Background. Many of the approaches available for modifying manual materials handling (MMH) exertion emphasize lower back protection but often do not consider how interventions affect other body regions. This study focused on the influence of lift training on resultant joint moments and muscular demand trade-offs between the lower back and shoulders during MMH tasks. Methods. Three recommended lifting techniques (straddle lift, pivot technique and tripod lift) were compared to a priori (untrained) self-selected lifting techniques. Results. Mean and cumulative resultant moments indicated that using the lifting techniques evaluated in this investigation protected the shoulders more than the lower back. Mean and peak shoulder muscle activity also decreased following training (p < 0.05). Although there were no peak and mean changes to lower back muscle activity (p>0.05), there was a significant decrease in cumulative lower back muscle activity (p < 0.05). Reported perceived exertion values decreased following training across the lifting techniques for all evaluated body regions (p < 0.05). Conclusion. Overall, the recommended MMH techniques protected both the lower back and the shoulders, and no exposure trade-offs between them were identified.

Exploring Reference Values for Hair Cortisol: Hair Weight versus Hair Protein.

As a marker of cumulative cortisol activity, hair cortisol has received attention in clinical and methodological research. Currently, it is common practice to relate hair cortisol concentration (HCC) to hair weight. The present paper explores hair protein concentration (HPC) as another possible reference value for HCC. For n = 18 hair samples cut from the posterior vertex, the HCC, HPC, and hair sample weight were determined, and the cortisol-to-weight and cortisol-to-protein ratios were calculated. Correlations were analyzed between HCC, HPC, and hair sample weight as well as between the cortisol-to-weight and cortisol-to-protein ratios. Hair sample weight and HPC were included as independent variables in a stepwise linear regression model to predict HCC. HCC and HPC did not correlate significantly (r = .393, p = .106); however, the correlation between HCC and hair sample weight was significant (r = .520, p = .027). HPC and hair sample weight (r = .605, p = .008) as well as the cortisol-to-weight and cortisol-to-protein ratios (r = .858, p < .000) showed a high correlation. Hair sample weight was the better predictor of HCC (β = .520, p = .027) than HPC (β = .125, p = .657). The results indicate that hair sample weight is the more suitable reference value for HCC. Thus, the standard cortisol-to-weight ratio should be used as the preferred expression for cumulative cortisol activity measured in scalp hair. However, calculating the cortisol-to-protein ratio can be considered as an alternative if the hair sample weight is not available.

OP0040 ANTI-CITRULLINATED PROTEIN AUTOANTIBODIES ARE ASSOCIATED WITH ONGOING SYSTEMIC BONE LOSS IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS TREATED ACCORDING TO THE PRINCIPLES OF TREAT-TO-TARGET AND TIGHT-CONTROL

Background:Anti-citrullinated protein antibodies (ACPA) are a major risk factor for local and systemic bone loss in patients with rheumatoid arthritis (RA). We previously demonstrated that early RA patients at disease presentation already show reduced systemic bone mineral density (BMD) in association with ACPA-positivity (1). Whether the negative impact of ACPA on bone continues over time despite treatment institution is however unknown.Objectives:To investigate longitudinally the course of systemic bone loss in patients with early RA after institution of treatment with disease modifying anti-rheumatic drugs (DMARDs) according to the principles of treat-to-target and tight-control.Methods:The study population included 100 consecutive early RA patients (&lt;12 months of symptoms) recruited at our Early Arthritis inception cohort and already evaluated for systemic BMD at disease presentation before treatment start (1). After diagnosis, patients were prospectively followed-up at three-months intervals upon initiation of therapy with conventional synthetic DMARDs (methotrexate in 85% of the cases) aimed at the achievement of low disease activity (LDA, 28-joints disease activity score [DAS28] &lt;3.2). BMD was re-assessed after 24 months at the lumbar spine (L1-L4) and hip by the same dual X-ray absorptiometry (DXA) equipment used at baseline. Differences in BMD from baseline were evaluated in relation to demographic and clinical variables (listed in Table 1).Table.Predictors of bone mineral density changes over 24 months% change in BMDlumbar spinetotal hipfemoral neckrprprpAge0.2690.0080.0690.500.2580.01female gender0.0850.42-0.0230.54-0.1210.23menopause0.1370.200.0670.530.0870.41disease duration0.0740.470.0440.670.0160.87cumulative DAS280.0180.860.0020.870.0110.91time to LDA0.1420.16-0.0230.76-0.0440.66time to remission0.0350.74-0.0020.97-0.0110.91ACPA-0.2510.010.1260.22-0.1300.04RF-0.1130.270.1110.280.0010.99months of bisphosphonates0.3680.0030.1710.090.2910.04cumulative steroids-0.1430.16-0.0070.78-0.0090.93months of bDMARDs-0.1630.11-0.0540.48-0.0630.54Results:The study population was mainly composed of females (84%), of whom 64.3% were in post-menopause; the mean (SD) age was 57.4 (13.5) years. Median (IQR) symptoms duration before treatment start was 14 (9-24) weeks. Fourty-three percent of the patients was ACPA positive. After 24 months of treatment, LDA was achieved in 79% of the cases, and remission in 46%; 17.7% of the patients had initiated a biological DMARD. At DXA re-scanning, the BMD at the lumbar spine and total hip remained largely unchanged, whilst at the femoral neck decreased from 0.726 g/cm2 to 0.713 g/cm2 (mean difference [SD] -0.013 [0.056], p=0.02). Predictors of BMD changes at different sites are shown in Table 1. The cumulative dose of prednisone was borderline significant for more BMD loss at the lumbar spine. Cumulative disease activity did not significantly affect BMD changes. Rather, ACPA-positive patients had higher percent changes at both the lumbar spine and the femoral neck. In multivariable analyses, ACPA remained associated with more BMD loss even when adjusting for confounders (age, gender, cumulative steroids, bisphosphonate treatment) (r -0.126, p=0.04 at the lumbar spine; r -0.126, p=0.04 at the femoral neck).Conclusion:Treatment of patients with early RA according to treat-to-target strategies prevents systemic bone loss. However, despite optimal disease control, ACPA positivity continues to be associated with progressive decline in systemic BMD.