Image processing tools for the validation of CryoEM maps.

The number of maps deposited in public databases (Electron Microscopy Data Bank, EMDB) determined by cryo-electron microscopy has quickly grown in recent years. With this rapid growth, it is critical to guarantee their quality. So far, map validation has primarily focused on the agreement between maps and models. From the image processing perspective, the validation has been mostly restricted to using two half-maps and the measurement of their internal consistency. In this article, we suggest that map validation can be taken much further from the point of view of image processing if 2D classes, particles, angles, coordinates, defoci, and micrographs are also provided. We present a progressive validation scheme that qualifies a result validation status from 0 to 5 and offers three optional qualifiers (A, W, and O) that can be added. The simplest validation state is 0, while the most complete would be 5AWO. This scheme has been implemented in a website https://biocomp.cnb.csic.es/EMValidationService/ to which reconstructed maps and their ESI can be uploaded.

Antiretroviral treatment outcomes among late HIV presenters initiating treatment with integrase inhibitors or protease inhibitors.

OBJECTIVES: The aim of the study was to investigate the efficacy and safety of first-line antiretroviral therapy (ART) with integrase inhibitor (INI) or protease inhibitor (PI)-based regimens in patients with low CD4 cell counts and/or an AIDS-defining disease. METHODS: We conducted a retrospective, multicentre analysis to investigate discontinuation proportions and virological response in patients with CD4 cell counts < 200 cells/µL and/or AIDS-defining disease when starting first-line ART. Proportions of those discontinuing ART were compared using univariate analysis. Virological response was analysed using the Food & Drug Administration (FDA) snapshot analysis (HIV-1 RNA < 50 HIV-1 RNA copies/mL at week 48). RESULTS: Two hundred and eighteen late presenters were included in the study: 13.8% were women and 23.8% were of non-European ethnicity, and the mean baseline CD4 count was 91 cells/µL (standard deviation 112 cells/µL). A total of 131 late presenters started on INI- and 87 on PI-based treatment. It was found that 86.1% of patients treated with INIs and 81.1% of patients treated with PIs had a viral load < 50 copies/mL at week 48; proportions of discontinuation because of adverse events were 6.1% in the INI group and 11.5% in the PI group. No significant differences in discontinuation proportions were observed at week 12 or 48 between INI- and PI-based regimens (P = 0.76 and 0.52, respectively). Virological response was equally good in those receiving INIs and those receiving PIs (86.1% vs. 81.1%, respectively; P = 0.36). CONCLUSIONS: In a European cohort of late presenters starting first-line INI or PI-based ART regimens, there were no significant differences in discontinuation proportions or virological response at week 48.

Inflammation status in HIV-positive individuals correlates with changes in bone tissue quality after initiation of ART.

BACKGROUND: The mechanisms behind ART-induced bone changes in HIV-infected patients are poorly known. We aimed to analyse changes in inflammatory and bone markers in HIV after tenofovir disoproxil fumarate initiation, and the associations with changes in the bone strength parameters. METHODS: HIV-positive participants starting tenofovir disoproxil fumarate-based ART underwent dual-energy X-ray absorptiometry (QDR 4500 SL®, Hologic, Waltham, MA, USA) for bone mineral density (BMD), a microindentation test (OsteoProbe®, Active Life Scientific, Santa Barbara, CA, USA) for bone quality [bone material strength index (BMSi)] and phlebotomy at baseline and 48 weeks after ART. A panel of inflammatory biomarkers and bone turnover markers were measured by ELISA. HIV-negative controls underwent identical procedures once. Values are expressed as medians and IQRs, and non-parametric tests were used to perform the analysis. RESULTS: Twenty HIV-infected individuals and 20 HIV-negative control individuals were matched in terms of age and gender. HIV individuals showed higher levels of inflammatory markers. We found no differences in bone turnover markers. HIV-positive individuals presented lower BMSi values at baseline compared with controls [86 (83-90) versus 89 (88-93), respectively; P = 0.034]. We found no difference in BMD (at either of the sites evaluated). BMSi tended to increase with treatment. IL-1ß at baseline was positively correlated with changes in BMSi after ART (rho = 0.564, P = 0.014). Baseline levels of sclerostin tended to be negatively correlated with changes in BMSi (rho = -0.402, P = 0.097). We found a negative correlation between time since HIV diagnosis and changes in BMSi (rho = -0.466, P = 0.04). CONCLUSIONS: We observed a correlation between changes in bone quality and the inflammatory environment in HIV-positive individuals. Moreover, among the underlying mechanisms we highlight the Wnt pathway as having a potentially significant role in ART bone quality recovery.

Liver-related mortality and hospitalizations attributable to chronic hepatitis C virus coinfection in persons living with HIV.

OBJECTIVES: The aim of this study was to compare liver-related mortality and liver-related hospitalizations for persons living with HIV (PLWH) with and without hepatitis C virus (HCV) exposure, and to estimate the fraction of liver disease attributable to chronic HCV coinfection. METHODS: An ambispective cohort study followed PLWH between 1993 and 2014. PLWH were classified into three groups: those who were HIV-monoinfected, those who cleared HCV spontaneously and those with chronic HCV coinfection. Liver-related mortality was estimated for the three groups and compared with the adjusted standardized mortality ratio. RESULTS: Data for 2379 PLWH were included in the study (1390 monoinfected individuals, 146 spontaneous HCV resolvers and 843 with chronic HCV coinfection). Global mortality was 33.8%, 21.4% of which was liver-related. Patients who died from liver-related causes were mostly on antiretroviral therapy and had an undetectable HIV viral load when they died. The liver-related mortality rate in those with chronic HCV coinfection was 10.01 per 1000 patient-years vs. 3.84 per 1000 patient-years in the HIV-monoinfected group (P < 0.001). The adjusted standardized mortality ratio in the chronically HCV-coinfected group was 4.52 (95% confidence interval 2.98-5.86). The fractions of liver-related mortality and liver-related hospitalizations attributable to chronic HCV coinfection were 0.61 and 0.74, respectively. There were no differences in liver-related events between HIV-monoinfected individuals and those who spontaneously cleared HCV. CONCLUSIONS: Chronic HCV infection increases the risk of liver-related mortality and liver-related hospitalizations in PLWH, despite good control of HIV infection. Sixty per cent of liver-related mortality in chronically HCV-coinfected PLWH could be attributable to chronic HCV infection. The effect of mass HCV eradication with new therapies should be evaluated.

Role of Periostin in Uncontrolled Asthma in Children (DADO study).

BACKGROUND AND OBJECTIVE: Asthma is the most common chronic disease in children. Cases of severe asthma (SA) are underdiagnosed. Periostin is a biomarker for SA in adults, but its role in children is poorly understood. Objectives: The aims of the study were to estimate the percentage of cases of uncontrolled severe asthma (UcSA) in children with poorly controlled asthma and to evaluate the role of periostin as a biomarker. MATERIAL AND METHODS: We performed an observational study in children aged 5 to 14 years with poorly controlled asthma. Demographic and clinical data were collected in addition to the results of the lung function test, the fraction of exhaled nitric oxide, the skin prick test, total IgE, specific IgE, blood eosinophil count, serum periostin, treatment, asthma control, and quality of life. Variables were compared between the group with UcSA and the other children. RESULTS: Fifty children with poorly controlled asthma (72% male) were included. Nineteen children (38%) had UcSA. Most children had limitations in their activities of daily living and had visited the emergency department. In addition, 38% were hospitalized. Quality of life was poor. Only 42% of the children received appropriate treatment. The UcSA group was more likely to have a total IgE >500 kUA/mL (52.6% vs 19%, P=.02) and less likely to have serum periostin >1000 ng/mL (31.2% vs 63%, P=.04). CONCLUSIONS: In our setting, 38% of children with poorly controlled asthma have UcSA, which is associated with higher levels of total serum IgE and lower levels of serum periostin.

Liver toxicity and risk of discontinuation in HIV/hepatitis C virus-coinfected patients receiving an etravirine-containing antiretroviral regimen: influence of liver fibrosis.

OBJECTIVES: The aim of the study was to establish the risk of liver toxicity in HIV/hepatitis C virus (HCV)-coinfected patients receiving etravirine, according to the degree of liver fibrosis. METHODS: A prospective cohort study of 211 HIV-infected patients initiating an etravirine-containing regimen was carried out. HCV coinfection was defined as a positive HCV RNA test, and baseline liver fibrosis was assessed by transient elastography. Hepatotoxicity was defined as clinical symptoms, or an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value > 5-fold higher than the upper limit of normal if baseline values were normal, or 3.5-fold higher if values were altered at baseline. RESULTS: Overall, 145 patients (69%) were HCV coinfected, with a lower nadir (165 versus 220 cells/µL, respectively; p = 0.03) and baseline (374 versus 498 cells/µL, respectively; p = 0.04) CD4 count than monoinfected patients. Etravirine was mainly used with two nucleoside reverse transcriptase inhibitors (129; 61%) or with a boosted protease inhibitor (PI) (28%), with no significant differences according to HCV serostatus. Transient elastography in 117 patients (81%) showed a median (range) stiffness value of 8.25 (3.5-69) kPa, with fibrosis stage 1 in 43 patients (37%) and fibrosis stage 4 in 28 patients (24%). During an accumulated follow-up time of 449.3 patient-years (median 548 days), only one patient with advanced fibrosis (50.8 kPa) had grade 3-4 liver toxicity (0.7%). Transaminases changed slightly, with no significant differences compared with baseline fibrosis, and nine and six patients had grade 1 and 2 transaminase increases, respectively. Also, HCV coinfection was not associated with a higher risk of discontinuation (25% discontinued versus 21% of monoinfected patients; p = 0.39, log-rank test) or virological failure (8% versus 12%, respectively; p = 0.4). CONCLUSIONS: Our data suggest that etravirine is a safe option for HIV/HCV-coinfected patients, including those with significant liver fibrosis.

Trends on epidemiological, virological, and clinical features among newly diagnosed HIV-1 persons in Northwest Spain over the last 10 years.

To describe temporal trend and characteristics of newly HIV-diagnosed patients in a medical care area in Northwest Spain over the last 10 years. All newly diagnosed patients for HIV-infection from 2004 to 2013 at a reference medical care area in Northwest of Spain were identified. Epidemiological, virological, immunological, and clinical data, as well as HIV genotype and drug resistance information were recorded. A total of 565 newly HIV-diagnosed patients were identified. The number of new cases increased in the last 5 years (66 cases/year). Overall, 53.1% had a median CD4 counts < 350 cells/µl and 33.6% had an AIDS defining criteria. Non-B variants were found in 34.4% of patients being subtype F (25.8%) the most common non-B subtype. The rate of transmitted drug resistance (TDR) over the study period was 3.7%, but a decreased to 2.6% was observed in the last 5 years. The most prevalent TDR mutations were: T215 revertants (1.5%), K219QENR (1.2%), for NRTIs; K103N (1.9%), for NNRTIs; L90M (0.3%), for PIs. Overall, 73.2% of patients started antiretroviral treatment and 9.9% of patients died during follow-up. The number of newly HIV diagnosed patients increased since year 2009. There is a high prevalence of late diagnosis (53%) and 33% had an AIDS defining criteria. Interestingly, the most prevalent non-B subtype in our population was F (25.8%). These findings support the need to facilitate the access for HIV testing to reduce the rate of late HIV diagnosis, improve the clinical outcome and prevent HIV transmission.

Impact of HIV infection on sustained virological response to treatment against hepatitis C virus with pegylated interferon plus ribavirin.

It is commonly accepted that human immunodeficiency (HIV) coinfection negatively impacts on the rates of sustained virological response (SVR) to therapy with pegylated interferon plus ribavirin (PR). However, this hypothesis is derived from comparing different studies. The aim of this study was to determine the impact of HIV coinfection on SVR to PR in one single population. In a multicentric, prospective study conducted between 2000 and 2013, all previously naïve hepatitis C virus (HCV)-infected patients who started PR in five Spanish hospitals were analyzed. SVR was evaluated 24 weeks after the scheduled end of therapy. Of the 1046 patients included in this study, 413 (39%) were coinfected with HIV. Three hundred and forty-one (54%) HCV-monoinfected versus 174 (42%) HIV/HCV-coinfected patients achieved SVR (p < 0.001). The corresponding figures for undetectable HCV RNA at treatment week 4 were 86/181 (47%) versus 59/197 (30%), p < 0.001. SVR was observed in 149 (69%) HCV genotype 2/3-monoinfected subjects versus 91 (68%) HIV/HCV genotype 2/3-coinfected subjects (p = 0.785). In the HCV genotype 1/4-infected population, 188 (46%) monoinfected patients versus 82 (30%) with HIV coinfection (p < 0.001) achieved SVR. In this subgroup, absence of HIV coinfection was independently associated with higher SVR [adjusted odds ratio (95% confidence interval): 2.127 (1.135-3.988); p = 0.019] in a multivariate analysis adjusted for age, sex, baseline HCV RNA load, IL28B genotype, fibrosis stage, and type of pegylated interferon. HIV coinfection impacts on the rates of SVR to PR only in HCV genotype 1/4-infected patients, while it has no effect on SVR in the HCV genotype 2/3-infected subpopulation.

Are hospitalizations for rotavirus gastroenteritis associated with meteorologic factors?

Local climatic factors might explain seasonal patterns of rotavirus infections, but few models have been proposed to determine the effects of weather conditions on rotavirus activity. Here, we study the association of meteorologic factors with rotavirus activity, as determined by the number of children hospitalized for rotavirus gastroenteritis on the Mediterranean island of Mallorca (Spain). We conducted a retrospective review of the medical records of children aged 0-5 years admitted for rotavirus gastroenteritis between January 2000 and December 2010. The number of rotavirus hospitalizations was correlated to temperature, humidity, rainfall, atmospheric pressure, water vapor pressure, wind speed, and solar radiation using regression and time-series techniques. A total of 311 patients were hospitalized for rotavirus gastroenteritis in the 11-year study period, with a seasonal pattern from December to June, and a peak incidence in February. After multiple regressions, weekly rotavirus activity could be explained in 82 % of cases (p < 0.001) with a one-week lag meteorologic model. Rotavirus activity was negatively associated to temperature and positively associated to atmospheric pressure, solar radiation, and wind speed. Temperature and solar radiation were the factors that contributed most to the model, with a peak rotavirus activity at 9 °C and 800 10KJ/m(2), respectively. In conclusion, hospitalization for rotavirus was strongly associated with mean temperature, but an association of rotavirus activity with solar radiation, atmospheric pressure, and wind speed was also demonstrated. This model predicted more than 80 % of rotavirus hospitalizations.

Assessment of pain relief after four botulinum toxin A injection cycles in patients with post-stroke lower limb spasticity: A prospective, observational study.

INTRODUCTION: Spasticity is common after a stroke and is an independent risk factor for developing pain. BotulinumtoxinA injection is the treatment of choice for focal spasticity. We examined the effect of intramuscular botulinumtoxinA on pain relief in patients in routine clinical practice who were experiencing pain as a primary complaint associated with post-stroke lower limb spasticity. METHODS: Prospective, multicentre, post-marketing observational study. The study period was 16 months. The primary effectiveness variable was the mean change from baseline on the pain 0-10 Numerical Rating Scale after four botulinumtoxinA injection cycles. Secondary endpoints included changes from baseline on the pain 0-100 Visual Analogue Scale, Goal Attainment Scale, modified Ashworth Scale, 10-Meter Walk Test, Penn Spasm Frequency Scale, and 36-item Short-Form Health Survey. RESULTS: Of 186 enrolled patients, 180 (96.8%) received botulinumtoxinA at least once. The mean (standard deviation) pain 0-10 Numerical Rating Scale score decreased significantly (p<0.0001) from 4.9 (2.2) at baseline to 2.5 (2.1) at study end, representing a 50% decrease in pain severity. Relief of pain due to spasticity was supported by improvement from baseline in all secondary variables except the 10-Meter Walk Test. Two adverse events (erysipelas and phlebitis) in one patient were considered likely to be related to botulinumtoxinA injection. CONCLUSION: BotulinumtoxinA appears to provide pain relief as an additional benefit of local treatment in patients with post-stroke lower limb spasticity for whom pain relief is a primary therapeutic goal (a Lay Abstract has been provided as Appendix A).

Depressive symptoms and suicide attempts among farmers exposed to pesticides.

Pesticides safeguard crop health but may diminish cholinesterase activity in farmers, potentially leading to psychiatric disorders like depression and suicide attempts. This study, with 453 participants (225 pesticide-exposed farmers, 228 non-farmers) in Almería, Spain, aimed to investigate the presence of depressive symptoms and suicide attempts, the decrease acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity, and their relationship with pesticide exposure in farmers. Depressive symptoms were evaluated using the Spanish adaptation of the Beck Depression Inventory, and blood samples were analyzed for AChE and BChE activity. Farmers showed significantly increased risk of moderate/severe depression and suicide attempts compared to non-farmers (OR = 2.18; p = 0.001), with highest risks observed among mancozeb users (OR = 2.76; p = 0.001 for depression) and malathion users (OR = 3.50; p = 0.001 for suicide attempts). Findings emphasize elevated depression and suicide risks among pesticide-exposed farmers, particularly associated with chlorpyrifos, mancozeb, and malathion exposure.

[Outbreaks of acute gastroenteritis in Antofagasta Region, Chile 2010]. / Brote de gastroenteritis aguda en la Región de Antofagasta,Chile: 2010.

Outbreaks of acute gastroenteritis are a public health problem. Norovirus is known as the most common cause (50%). In Chile, immediate notification allows surveillance of these events. We describe an acute gastroenteritis outbreak that occurred in Antofagasta region, between March and April 2010. An observational study was conducted to perform the outbreak investigation. Local residents who met case definition were included. Stool samples, epidemiological surveys and environmental samples were requested. The outbreak began approximately on March 8, 2010 and lasted until April 28 with 31,036 reported cases (rate 54 per 1000 inhabitants). The most affected age group was between 25 and 44 years, and diarrhea was the main symptom (97% of cases). We determined the presence of norovirus genogroup II in clinical and environmental samples. This outbreak was caused by consumption of raw vegetables from La Chimba, which were watered and contaminated with treated sewage containing low concentration of free residual chlorine. Subsequently, the outbreak spread from person to person in a poor sanitary environment.

Mean glandular dose in the mammary gland and dose of radiation in the thyroid gland and lens in women with and without breast implants during different modalities of mammography.

There have always been concerns about the secondary effects of diagnostic methods that use ionizing radiation. During mammography, the parameters to be concerned about are the mean glandular dose and the scatter dose. We evaluated the dose of radiation to the breast, thyroid gland, and lens in digital mammography in women with and without implants, in tomosynthesis in women with and without implants, and in contrast-enhanced mammography. MATERIALS AND METHODS: The study included 212 women with and without disease who were attended at the Centro Clínico de Estereotaxia, CECLINES, in Caracas, Venezuela, between June 2017 and August 2017; the women were classified into five groups according to the mammographic modality used to evaluate them and whether or not they had implants. The statistical analysis included descriptive statistics for the study population. We used the Mann-Whitney U to compare the mean glandular dose and dose in the thyroid gland and lens between groups. RESULTS: The mean glandular dose and the dose of radiation received in the thyroid and lens were within the acceptable range. In a few exceptions, the mean glandular dose per view was slightly higher than 3 mGy. The scatter dose to the thyroid gland and the lens during mammography has a very small contribution to the annual dose equivalent. CONCLUSION: The mean glandular dose and the scatter dose to the thyroid gland and lens delivered during tomosynthesis and 2D mammography in women with implants were higher than those delivered during other mammographic techniques in women without implants.

Meropenem penetration into epithelial lining fluid in mice and humans and delineation of exposure targets.

Pseudomonas aeruginosa pneumonia remains a most-difficult-to-treat nosocomial bacterial infection. We used mathematical modeling to identify drug exposure targets for meropenem in the epithelial lining fluid (ELF) of mice with Pseudomonas pneumonia driving substantial [2 to 3 log(10) (CFU/g)] killing and which suppressed resistant subpopulation amplification. We bridged to humans to estimate the frequency with which the largest licensed meropenem dose would achieve these exposure targets. Cell kills of 2 and 3 log(10) (CFU/g) and resistant subpopulation suppression were mediated by achieving time > MIC in ELF of 32%, 50%, and 50%. Substantial variability in meropenem's ability to penetrate into ELF of both mice and humans was observed. Penetration variability and high exposure targets combined to prevent even the largest licensed meropenem dose from achieving the targets at an acceptable frequency. Even a highly potent agent such as meropenem does not adequately suppress resistant subpopulation amplification as single-agent therapy administered at maximal dose and optimal schedule. Combination chemotherapy is likely required in humans if we are to minimize resistance emergence in Pseudomonas aeruginosa pneumonia. This combination needs evaluation both in the murine pneumonia model and in humans.

FSI Analysis of a healthy and a stenotic human trachea under impedance-based boundary conditions.

In this work, a fluid-solid interaction (FSI) analysis of a healthy and a stenotic human trachea was studied to evaluate flow patterns, wall stresses, and deformations under physiological and pathological conditions. The two analyzed tracheal geometries, which include the first bifurcation after the carina, were obtained from computed tomography images of healthy and diseased patients, respectively. A finite element-based commercial software code was used to perform the simulations. The tracheal wall was modeled as a fiber reinforced hyperelastic solid material in which the anisotropy due to the orientation of the fibers was introduced. Impedance-based pressure waveforms were computed using a method developed for the cardiovascular system, where the resistance of the respiratory system was calculated taking into account the entire bronchial tree, modeled as binary fractal network. Intratracheal flow patterns and tracheal wall deformation were analyzed under different scenarios. The simulations show the possibility of predicting, with FSI computations, flow and wall behavior for healthy and pathological tracheas. The computational modeling procedure presented herein can be a useful tool capable of evaluating quantities that cannot be assessed in vivo, such as wall stresses, pressure drop, and flow patterns, and to derive parameters that could help clinical decisions and improve surgical outcomes.

Developing µSpherePlatform Using a Commercial Hairbrush: An Agarose 3D Culture Platform for Deep-Tissue Imaging of Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is a viable diagnostic biomarker for the detection and treatment of prostate cancer. Although numerous imaging techniques and fluorescent probes have been developed, targeted imaging and intraoperative surgery continue to remain as a proof-of-concept with a severe lack of tools having high affinity and penetrative capacity. In vitro three-dimensional cell culture has gained immense interest in cancer research and drug discovery programs as it yields important physiological information and serves an excellent model for bioimaging and penetration analysis studies. Current techniques employed in spheroid formation include liquid overlay and hanging drop methods, both of which are low-yielding and technically demanding. We describe for the first time a simple-to-use platform, µSpherePlatform, an inexpensive, high-throughput method yielding morphologically homogeneous spheroids in bulk for analyzing penetrative capacity and imaging ability of PCa diagnostics. Microwell arrays made of agarose have been fabricated using a commercial hairbrush as a master template. This procedure has been described in detail, and arrays of spheroids (100-120 spheroids/6-well plate) with >95% success rates have been produced from PCa cell lines (LNCaP and DU-145). A PSMA-targeted fluorescent conjugate was synthesized and evaluated in the spheroids developed using µSpherePlatform by multiphoton imaging. A synthetic 3D scaffold strategy is reported herein, which (1) correlates perfectly with the in vivo model, (2) is amenable for automated analysis, (3) shows a negligible lot to lot variation, (4) is simplistic, (5) is useful for high-throughput assays, (6) is extremely compatible with imaging techniques, (7) generates PCa spheroids within 48 h, and (8) forms large size-controllable spheroids of diameter 500-1300 µm. The µSpherePlatform thus provides a significant contribution to multimodal analyses of cancer diagnostics and deep-tissue imaging studies.

Mean glandular dose in the mammary gland and dose of radiation in the thyroid gland and lens in women with and without breast implants during different modalities of mammography. / Dosis glandular promedio en glándula mamaria y dosis de radiación en glándula tiroides y cristalino en mujeres con y sin implantes mamarios durante diferentes modalidades mamográficas.

There have always been concerns about the secondary effects of diagnostic methods that use ionizing radiation. During mammography, the parameters to be concerned about are the mean glandular dose and the scatter dose. We evaluated the dose of radiation to the breast, thyroid gland, and lens in digital mammography in women with and without implants, in tomosynthesis in women with and without implants, and in contrast-enhanced mammography. MATERIALS AND METHODS: The study included 212 women with and without disease who were attended at the Centro Clínico de Estereotaxia, CECLINES, in Caracas, Venezuela, between June 2017 and August 2017; the women were classified into five groups according to the mammographic modality used to evaluate them and whether or not they had implants. The statistical analysis included descriptive statistics for the study population. We used the Mann-Whitney U to compare the mean glandular dose and dose in the thyroid gland and lens between groups. RESULTS: The mean glandular dose and the dose of radiation received in the thyroid and lens were within the acceptable range. In a few exceptions, the mean glandular dose per view was slightly higher than 3mGy. The scatter dose to the thyroid gland and the lens during mammography has a very small contribution to the annual dose equivalent. CONCLUSION: The mean glandular dose and the scatter dose to the thyroid gland and lens delivered during tomosynthesis and 2D mammography in women with implants were higher than those delivered during other mammographic techniques in women without implants.

Statistical control of processes applied to geometric uncertainties for CTV expansion margins determination in prostate cancer patients treated with VMAT: a prospective study in 57 patients.

PURPOSE: To study the control graphs applicability for the geometric uncertainties of VMAT treatments in prostate cancer patients, and their use to verify the hypothesis of the data obtained randomness, to apply the margins of Van Herk expression. MATERIAL AND METHODS: During the first 5 days of treatment, and then once a week, a Kv CBCT was performed, compared with the simulation CT and adjusted the displacements, to determine the inter-fraction errors. Immediately after radiation therapy, another CBCT was performed (for intra-fraction errors). With these data, the X, R position control charts have been made. The patients, not maintained the deviations within the charts control limits, were called "anomalies". Then, we compared the deviations and margins calculated with the van Herk expression for all patients and for those without anomalies. RESULTS: The margins determined show appreciable differences if there were calculated for the total set of patients or for the set of them without anomalies in the control charts. For the overall set of patients, the lateral, longitudinal, and vertical margins were 0.45 cm, 0.52 cm, 0.56 cm, while for the set of patients without anomalies were 0.29 cm, 0.35 cm, and 0.38 cm. CONCLUSIONS: The use of control charts allows tracking geometric deviations both inter and intra-fraction, variability real-time control and to detect situations in which it can change for non-random reasons, and require immediate investigation. Maintaining geometric deviations in the control state decreases the margins needed to administer a high dose to CTV in a high percentage of cancer prostate patients.