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Deciphering the genesis and evolution of the Martian polar caps can provide crucial understanding of Mars' climate system. The growing scientific interest for the exploration of Mars at high latitudes, and the need of minimizing the resources onboard landers and rovers, motivates the need for adequate navigation support from orbit. We propose a novel concept based on a constellation that can support autonomous navigation of different kind of users devoted to scientific investigations of those regions. We study two constellations, that differ mainly for the semi-major axis, composed of 5 small satellites (based on the SmallSats design being developed in Argotec), offering dedicated coverage of the Mars polar regions. We focus on the architecture of the inter-satellite links (ISL), the key elements providing both ephemerides and time synchronization for the broadcasting of the navigation message. Our concept is based on suitably configured coherent links, able to suppress the adverse effects of on-board clock instabilities and to provide excellent range-rate accuracies between the constellation's nodes. The data quality allows attaining good positioning performance for both constellations with a largely autonomous system. Indeed, we show that ground support can be heavily reduced by employing an ISL communication architecture.

Objective To analyze the pattern of failure in relation to pre-treatment [18F] FDG-PET/CT uptake in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radio-chemotherapy (RT-CHT). Methods and materials From 2012 to 2016, 87 HNSCC patients treated with definitive RT-CHT, with intensity modulated radiation therapy with simultaneous integrated boost, underwent pre-treatment [18F] FDG-PET/CT (PETpre), and MRI/CT for radiotherapy (RT) planning purposes. Patients with local recurrence, received [18F] FDG-PET/CT, (PETrec) at the time of the discovery of recurrence. In these patients, the metabolic target volume (MTV), MTVpre and MTVrec were segmented on PET images by means of an adaptive thresholding algorithm. The overlapping volume between MTVpre and MTVrec (MTVpre&rec) was generated and the dose coverage of MTVrec and MTVpre&rec was checked on the planning CT using the D99 and D95 dose metrics. The recurrent volume was defined as: ‘‘In-Field (IF)’’, “Marginal recurrence” or ‘‘Out-of-Field (OF)’’ if D95 was respectively equal or higher than 95%, D95 was between 95 and 20% or the D95 was less than 20% of prescribed dose. Results We found 10/87 patients (11.5%) who had recurrence at primary site. Mean MTVpre was 12.2 cc (4.6–28.9 cc), while the mean MTVrec was 4.3 cc (1.1–12.7 cc). Two recurrences resulted 100% inside MTVpre, 4 recurrences were mostly inside (61–91%) and 4 recurrences were marginal to MTVpre (1–33%). At dosimetric analysis, five recurrences (50%) were IF, 4 (40%) marginal and one (10%) OF. The mean D99 of the overlapping volumes MTVpre&rec was 68.1 Gy (66.5–69.2 Gy), considering a prescription dose of 70 Gy to the planning target volume (PTV). Conclusion Our study shows that the recurrence may originate from the volume with the highest FDG-signal. Tumor relapse in the high-dose volume support the hypothesis that an intensification of the dose on these volumes could be further assessed to prevent local relapse.

We aim to develop and validate a new adaptive method for prostate cancer radiation therapy (RT), using an offline strategy to improve treatment personalization by modeling the internal target volume on individual basis and account for the residual set-up uncertainties by robust optimization.Twenty patients with intermediate-high prostate cancer treated with radical radiation therapy were enrolled. The first step of the offline adaptive RT strategy is the identification of a patient-specific internal target volume based on the kV cone beam computed tomography (kV-CBCT) data sets acquired during the first 5 fractions. The deformable image registration algorithm ANACONDA was used to propagate the clinical target volumes (CTVs) from the reference-planning computed tomography to the CBCTs; these contours were assessed by a radiation oncologist. In the second step, the internal target volume was used to replan the treatment using a min-max robust algorithm based on the worst scenario optimization. The CTV coverage and organs-at-risk sparing achieved with the robust plan (RP) were analyzed and compared with the original standard plan, calculating the dose distributions on the residual CBCTs.The RP was shown to achieve optimal coverage of the CTV even in the worst scenario, with significantly lower doses to the rectum and bladder. CTV coverage of the RP was statistically better than the standard plan in terms of D99 (P = .008) and D98 (P = .02). Statistically significant mean dose reduction and D2 reduction were noted for the rectum (P.05) and bladder (P.009). Moreover, the RP appeared to be less sensitive to bladder and rectal filling.This adaptive strategy in prostate cancer radiation therapy is feasible and safe; it may be used to adapt the treatment with better target coverage and organs-at-risk sparing than standard planning target volume-based planning.

Additional file 1: Table S1.Antidepressant treatments (n=37). Figure S1. Slope coefficients from univariate linear regression models evaluating the association between levels of PCSK9 and characteristics of subjects.

Aim The Italian Society of Occupational Medicine (SIML), the Italian Diabetes Society (SID) and the Association of Diabetologists (AMD) joined a working group that produced a consensus paper aimed to assess the available evidence regarding the interplay between specific working conditions, including shift- and night-time work, working activities at high risk of accidents and work at heights, working tasks requiring high-energy expenditure, working activities at extreme temperatures and diabetes. Data synthesis Diabetes is a group of metabolic disorders caused by defects in insulin secretion and/or action affecting millions of people worldwide, many of whom are or wish to be active members of the workforce. Although diabetes, generally, does not prevent a person from properly performing his/her working tasks, disease complications can significantly compromise a person's ability to work. Therefore, it appears evident the need to understand the relationship between occupational risk factors and diabetes. The working group included in the document some practical recommendations useful to ensure diabetic workers the possibility to safely and effectively undertake their jobs and to adequately manage and treat their disease, also in the workplace. In this perspective concerted action of all the workplace preventive figures, occupational physicians and diabetologists should be strongly encouraged. Conclusions Further studies are necessary to define workplace-based interventions, which should be minimally invasive towards the work organization, allowing diabetic workers to fully realize their work skills while improving their wellbeing at work.

Introduction In Italy about 45% of people aged ≥18 years are overweight/obese and might thus be more susceptible to the adverse health effects of air pollution exposure. Particulate matter ≤10 µm (PM10) represents a common pollutant of living and working environments and has been associated with increased risk of cardiovascular diseases (CVD) and hypercoagulability. Extracellular vesicles (EV) might play an important role in PM-related CVD, as they can travel in body fluids and transfer miRNAs between cells. We investigated whether PM10 exposure is associated with changes in fibrinogen levels, EV release, and EV-miRNA content in a large sample of overweight/obese adults. Methods EV concentrations were quantified by nanoparticle tracking analysis and flow cytometry. To identify altered levels of EV-miRNAs, we profiled miRNAs of 883 subjects by the QuantStudio 12K Flex Real Time PCR System. The top 40 EV-miRNAs were validated through custom miRNA plates. Statistical analyses included multiple linear regressions, mediation analysis and bioinformatics analysis. Results In a sample of 1630 overweight/obese subjects from the SPHERE (Susceptibility to Particle Health Effects, miRNAs and Exosomes) study, short-term exposure to PM10 was associated with increased release of EVs, especially those from monocyte/macrophage components (CD14+) and platelets (CD61+). Nine EV-miRNAs (let-7c-5p; miR-106a-5p; miR-143–3 p; miR-185–5 p; miR-218–5 p; miR-331–3 p; miR-642–5 p; miR-652–3 p; miR-99b-5p) were downregulated in response to PM10 exposure and exhibited putative roles in CVD. Five of these nine EV-miRNAs were mediators in the positive association between PM10 exposure and fibrinogen levels. Conclusions Our study sheds some light on the potential mechanisms underlying the adverse cardiovascular health effects of air pollution exposure. Our results were obtained in a hypersusceptible population and thus strengthen the relevance of health promotion interventions for both the general public and the working population, as they might be particularly feasible in the workplace.

Background The independent prognostic impact of diabetes mellitus ( DM ) and prediabetes mellitus (pre‐ DM ) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐ DM on survival outcomes in the GISSI ‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial. Methods and Results We assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI ‐ HF trial, who were stratified by presence of DM (n=2852), pre‐ DM (n=2013), and non‐ DM (n=2070) at baseline. Compared with non‐ DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐ DM patients and those with pre‐ DM . Cox regression analysis showed that DM , but not pre‐ DM , was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI , 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI , 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI , 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI , 1.01–1.29, respectively). Conclusions Presence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00336336.

PURPOSE The aim of this study was to assess the relationship between administered 99mTc tetrofosmin activity in myocardial gated-SPECT and findings of myocardial perfusion and left ventricular ejection fraction (LVEF) as markers of diagnostic outcome. MATERIALS AND METHODS Fifty-two patients with heterogeneous cardiac diseases and a clinical referral for myocardial perfusion imaging were prospectively studied. A separate-day acquisition protocol was adopted with a low fixed activity of 370 MBq, which corresponds to an average reduction of 31% with respect to the median value of 533 MBq usually administered in our laboratory. A standard acquisition with a time/frame of 25 seconds was performed (ST). Immediately after the conclusion of the first acquisition, a second acquisition was performed with a high time/frame of 33 seconds (HT), which corresponds to an increase of 31% with respect to standard time/frame adopted in our laboratory. The order of ST and HT acquisitions was randomized in individual patients. The summed stress scores (SSS), the summed rest scores (SRS), the LVEF, and the end-diastolic volume (EDV) were automatically calculated. RESULTS The image quality score was significantly higher in HT than in ST. No significant differences were found in SSS, SRS, LVEF, and EDV between HT and ST SPECT. The agreement between HT and ST was 84% (kw=0.88) in the correct classification of stress images. The agreement between HT and ST was 84% (k=0.70) in the detection of ischemia and scar. The limits of agreement between the HT and the ST methods were roughly within ±3 points for SSS and SRS, ±13% for poststress LVEF, and ±18 mL for poststress EDV. CONCLUSIONS Using about half of the activity recommended by the current diagnostic reference levels for separate-day myocardial perfusion imaging, the present study demonstrates that images may be obtained using ST protocol with quantitative results comparable with those from studies performed using the HT protocol, which is equivalent to an administered activity of 530 MBq. The former protocol would allow for a significant reduction of the dose to the patients as well as to the operators. Further studies are needed to confirm that this dose-sparing approach does not hamper sensitivity and specificity for coronary stenoses.

PET scanners require routine monitoring and quality control (QC) to ensure proper scanner performance. QC helps to ensure that PET equipment performs as specified by the manufacturer and that there have not been significant changes in the system response since acceptance. In this work we describe the maintenance history and we report on the results obtained from the PET system QC testing program over 5 years at two centers, both utilizing a Siemens Biograph 16 HiRez PET/CT system. QC testing programs were based on international standards and included the manufacturer’s daily QC, monthly uniformity and sensitivity, quarterly cross-calibration and annual resolution and image quality. For the Winnipeg and Novara sites, two and one PET detector blocks have been replaced, respectively. Neither system has had other significant PET system related hardware replacements. The manufacturer’s suggested daily QC was sensitive to detecting problems in the function of PET detector elements. The same test was not sensitive for detecting long term drifts in the systems: the Novara system observed a significant deterioration over five years of testing in the sensitivity which exhibited a decrease of 16% as compared to its initial value measured at system installation. The measure of the energy spectrum, showed that the 511 keV photopeak had shifted to a position of 468 keV. This shift was corrected by having service personnel perform a complete system calibration and detector block setup. We recommend including tests of system energy response and of sensitivity as part of a QC program since they can provide useful information on the actual performance of the scanner. A modification of the daily QC test by the manufacturer is suggested to monitor the long term stability of the system. Image quality and spatial resolution tests have proven to be of limited value for monitoring the system over time.

[ 153 Sm]Sm-EDTMP is a radiopharmaceutical used in palliation cares of bone metastases. The purpose of this study is to provide an explicit description of [ 153 Sm]Sm-EDTMP pharmacokinetics, adopting a simple three-compartmental model with the analytical expressions calculating the rate constants and determining biodistribution parameters, like radiopharmaceutical uptake and clearance. This biokinetic model allowed us to calculate on an individual basis the dose to bone surface and to red bone marrow and to assess the degree of variability in dosimetric parameters using a fixed administered activity based only on patient weight. In this study twenty patients were enrolled and were treated with [ 153 Sm]Sm-EDTMP, administering a fixed activity per kilogram (37 MBq/kg); blood and urine samples were collected during 24 h post treatment. The median value of the administered activity was 2.7 GBq. Blood clearance confirmed that an aliquot of [ 153 Sm]Sm-EDTMP rapidly localizes and is retained in bone, while the remainder is rapidly cleared from the blood pool by the urinary system. Our data show a bi-exponential clearance from blood: the rapid component has a half life median value of 6 min (range: 2–24 min), while the slow one has a half life median value of 1.4 h (range: 0.6–5.8 h). Median value of the urinary excretion is 40 (range: 3–75) % of the administered activity. Our model shows the behaviour of a tracer which is distributed in the extracellular space of the body, localized in the skeleton and excreted via glomerular filtration. Half life median values of [ 153 Sm]Sm-EDTMP transferring between compartments, T 1/2 (blood→ECF), T 1/2 (ECF→blood) are 7.4 (range: 1.9–37) and 48 (range: 8–408) min, respectively. Median values of half lives of [ 153 Sm]Sm-EDTMP clearance through the urine and of uptake into bone are 1.0 (range: 0.1–6.0) and 1.6 (range: 0.6–9.0) h, respectively. Median value of red marrow absorbed dose is 2.1 (range: 0.7–3.5) Gy and 0.8 (range: 0.3–2.1) Gy/GBq, while median value of bone surface absorbed dose is 11.5 Gy (range: 5.0–18.4) and 4.4 (range: 2.3–14.3) Gy/GBq. It is remarkable that there is a really great biological variability within patients, especially considering the excreted activity. The cumulated activity in bone and red marrow doses were significantly higher in prostate cancer, where metastatic bone lesions are osteoblastic, than in breast cancer where metastatic bone lesions are osteolytic or mixed (lytic/blastic). The relevant biological variability in biodistribution and metabolism of [ 153 Sm]Sm-EDTMP suggests that the fixed administered activity based on patient weight is not sufficient to optimize the treatment and a better optimization would be reached by using a predictive dosimetry tailored to individual patient characteristics.

The purpose of this study was to analyze the behavior of a contouring algorithm for PET images based on adaptive thresholding depending on lesions size and target‐to‐background (TB) ratio under different conditions of image reconstruction parameters. Based on this analysis, the image reconstruction scheme able to maximize the goodness of fit of the thresholding algorithm has been selected. A phantom study employing spherical targets was designed to determine slice‐specific threshold (TS) levels which produce accurate cross‐sectional areas. A wide range of TB ratio was investigated. Multiple regression methods were used to fit the data and to construct algorithms depending both on target cross‐sectional area and TB ratio, using various reconstruction schemes employing a wide range of iteration number and amount of postfiltering Gaussian smoothing. Analysis of covariance was used to test the influence of iteration number and smoothing on threshold determination. The degree of convergence of ordered‐subset expectation maximization (OSEM) algorithms does not influence TS determination. Among these approaches, the OSEM at two iterations and eight subsets with a 6–8 mm post‐reconstruction Gaussian three‐dimensional filter provided the best fit with a coefficient of determination R2=0.90 for cross‐sectional areas ≤ 133 mm 2 and R2=0.95 for cross‐sectional areas > 133 mm 2 . The amount of post‐reconstruction smoothing has been directly incorporated in the adaptive thresholding algorithms. The feasibility of the method was tested in two patients with lymph node FDG accumulation and in five patients using the bladder to mimic an anatomical structure of large size and uniform uptake, with satisfactory results. Slice‐specific adaptive thresholding algorithms look promising as a reproducible method for delineating PET target volumes with good accuracy. PACS numbers: 87.57.nm, 87.55.D‐, 87.57.uk

Purpose To investigate the ArcCheck performances for PsQA of SBRT treatments and to find the better gamma analysis criteria. Methods Twelve spherical targets (radii from 4 mm to 15 mm) were simulated in a phantom consisting of the ArcCheck with the MultiPlug™ homogeneous RW3 insert. For each target a SBRT treatment was planned. The delivered doses were simultaneously measured by ArcCheck and gafchromic EBT3 films. The ArcCheck measurements in standard mode (Sm), were repeated in high density mode (HDm). PsQAs were performed using a local gamma index analysis (threshold 20%). Passing Rates (PR) of EBT3 films, ArcCheck Sm and HDm acquisitions were investigated as a function of DD%, DTA criteria and target dimensions. The correlation between ArcCheck and EBT3 film PR was stated and the better gamma criteria for ArcCheck PR was found by means of the maximization of Level Of Agreement with the film. Results The EBT3 films assessed optimal dose delivery accuracy with maximum deviations below the limit of 3%, close to the EBT3 uncertainty budget. For each of the reported methods the PR resulted significantly related to DTA, DD% and target dimension, with DTA criterion resulting the leading effect. Optimal gamma analysis criteria for EBT3 film resulted by combination of DTA = 1 mm and D%⩾3%, a PR threshold of 75% resulted predictive of clinical acceptable agreement in the target and dose falloff regions. The difference between the performances of ArcCheck Sm and HDm acquisition modes was not clinically relevant. The ArcCheck Sm and EBT3 film PR were significantly correlated between them. An optimal LOA Conclusions The ArcCheck resulted suitable for PsQA in SBRT treatments with properly selected local gamma criteria.

Purpose According to the EU directive 2013/59, the equipment used for computed tomography (CT) shall be able to inform the practitioner of relevant parameters for assessing the patient dose. Among them, the radiation output is usually displayed in terms of computed tomography dose index – CTDI [mGy]. The aim of this study was to measure the accuracy of the displayed CTDI100 for different manufacturers or models of CT and to assess the impact of acquisition parameters on CTDI100 accuracy. Methods 10 CT from 4 different manufacturers (16-slices n = 6, 32-slices n = 1, 64-slices n = 3) were included in the study. The accuracy of the displayed CTDI100 was checked with a dosimeter with traceable calibration. Reference values for the displayed CTDI100 were derived from the equipment’s manual. The impact of the CT model (16, 64, 128 slices), phantom size (head or body), kVp (80, 100, 120, 140 kVp) and primary collimation (from 1.25 to 40 mm, grouped in four level ⩽ 3, from 3 to ⩽ 10, from 10 to ⩽ 20, > 20 mm) on the accuracy of the displayed CTDI100, was assessed by a four-way factorial ANOVA. CT model, phantom size, kVp and primary collimation, were considered as independent variables (factors) and CTDI accuracy as the dependent variable. Results All the factors had a statistically significant impact on CTDI100 accuracy (p 0,05). In a head to head comparison, the lower accuracies were found on average for sixteen channels CT (10 ± 5%), for 80 KV (15 ± 11%) and for thick collimations (13 ± 7%), whilst no significant differences were found between head and body phantoms. Conclusions For sixteen channels CT and acquisition protocols involving the use of head phantom with low KV and thick primary collimation, the inaccuracies of the displayed CTDI can be higher than 20%, which is the suspension level indicated in the EC RP N.162 Publication for the accuracy of indicated dose parameters. This suggests the need of individual calibration of CT X-ray tubes by the manufacters and the necessity of including this check in the quality control programs for CT.

The radiopharmaceutical [153Sm]Sm-EDTMP is administered for painful bone metastases with the standard dosage of 37 MBq/kg, without evaluation of patient individual characteristics. For a better dose estimate in vivo stability should be considered, because labelled and unlabelled samarium do not have the same metabolic pathway. We evaluated radiopharmaceutical in vitro stability, measuring the activity by beta and gamma spectrometry. Subsequently we verified in vivo stability on serial blood and urine samples. The percentage of the unlabelled radiopharmaceutical is high and, on the basis of radiochemical data as well as blood clearance and urine excretion, we calculated the main parameters for a preliminary biokinetic model.

This paper reports a study on a grid-tied photovoltaic system, using a microinverter based on Cuk converter working in DCM. Since, when the Cuk converter is working in DCM, its output voltage presents a linear behavior in relationship to its duty cycle. Therefore, the duty cycle must have a sinusoidal behavior, in absolute value, in order to generate a rectified sine current waveform, at its output. The connection of a full bridge current source inverter in cascade with the Cuk converter, allows obtaining a sinusoidal current waveform at the microinverter output. One of the most important challenges on microgeneration systems is the island detection. In this sense, if the system is unable to detect the islanding, this may cause power quality degradation, electrical safety threats, especially related to maintenance crews, and damage to third-party devices connected to the same power grid.

This study was undertaken to quantify the cumulative effective dose (CED) of radiation and the dose to relevant organs in endovascular aortic repair (EVAR) patients, to assess radiation risks and to evaluate the clinical usefulness of multi-detector computed tomography (MDCT) follow-up.The radiation exposures were obtained from 71 consecutive EVAR patients with a follow-up duration ≥1 year. Dose calculations were performed on an individual basis and expressed as effective doses and organ doses. Radiation risk was expressed as risk of exposure-induced death (%), using the biological effects of ionising radiation model. Two radiologists independently assessed the images for abdominal aortic aneurysm expansion without endoleaks, thrombotic occlusion, endoleaks and device migration. They first reviewed arterial imaging alone and subsequently added non-contrast and delayed phases to determine the overall performance.The median total CED and annual CED were 224 and 104 mSv per patient-year. The median cumulative organ doses were 191, 205, 230, 269 and 271 mSv for lung, bone marrow, liver, colon and stomach, respectively. The average risk of exposure-induced death was 0.8 % (i.e., odds 1 in 130). All the findings related to EVAR outcome and leading to a change in patient management were visible during the arterial phase of the MDCT angiography. Omission of the unenhanced scan and the venous phase of the MDCT angiography would have led to a significant reduction of about 60 % of the associated MDCT radiation exposure in a single patient.EVAR patients received high radiation doses and the excess cancer risk attributable to radiation exposure is not negligible. The unenhanced scan and the venous phase of the MDCT angiography could have been omitted without compromising the utility of the examination and with a significant reduction of doses and associated risks.

Human DNA polymerase eta (hPol eta) is one of the newly identified Y-family of DNA polymerases. These polymerases synthesize past template lesions that are postulated to block replication fork progression. hPol eta accurately bypasses UV-associated cis-syn cyclobutane thymine dimers in vitro and contributes to normal resistance to sunlight-induced skin cancer. We describe here mutational analysis of motif II, a highly conserved sequence, recently reported to reside in the fingers domain and to form part of the active site in Y-family DNA polymerases. We used a yeast-based complementation system to isolate biologically active mutants created by random sequence mutagenesis, synthesized the mutant proteins in vitro and assessed their ability to bypass thymine dimers. The mutability of motif II in 210 active mutants has parallels with natural evolution and identifies Tyr52 and Ala54 as prime candidates for involvement in catalytic activity or bypass. We describe the ability of hPol eta S62G, a mutant polymerase with enhanced activity, to bypass five other site-specific lesions. Our results may serve as a prototype for studying other members of the Y-family DNA polymerases.

The paper describes 2 years outcome on BMI, smoking habits and physical activity of 2 WHP carried in engineering plants. Three important results were achieved: stationarity of body weight despite ageing of examined population; increase of workers that perform regular physical activity and a slight increase of smoking cessation. NSAS questionnaire showed a marked improvement in life styles compared to the data obtained 2 years before. Our findings suggest that an efficacy on life style modification can be achieved by WHP campaigns with little time and cost consuming. The collaboration between occupational physician, employer and employees but also with external professionals is the key of success.

MHC class I molecules require the assembly of heavy chain with beta2-microglobulin (beta 2m) and peptide in order to present Ag on the cell surface. Endoplasmic reticulum resident proteins associate with class I molecules and aid assembly. Free class I heavy chains associate with calnexin, which may facilitate association with beta 2m. Invariant chain (Ii) also associates with MHC class I molecules, but its role in class I assembly is not clear. We report here that Ii strongly associates with HLA class I/beta 2m heterodimers, but weakly with free class I heavy chains in HLA-B7-transfected T2 cells. Ii/HLA class I complexes persist stably within the endoplasmic reticulum/cis-Golgi compartment in peptide-processing deficient cells, but are much less prominent in normally processing cells. Furthermore, Ii differentially associates with variant HLA-B7 molecules that have peptide-binding groove mutations, and the degree of association correlates with HLA-B7 variant cell surface expression. Ii also shows HLA class I molecule specificity, associating to a greater degree with HLA-B7 than HLA-A2. Together these observations suggest that Ii stabilizes particular HLA class I/beta 2m heterodimers until peptide is loaded, and that this association may enhance class I cell surface expression.

To determine the influence of peptide-binding groove residues and MHC-bound peptide on HLA-B7 conformation, we investigated the binding sites of nine locus- or allele-specific mAbs using a panel of 82 HLA-B7 variants. The functional mAb epitopes encircle the HLA-B7 peptide-binding groove. Three mAbs are affected by mutations at solvent-accessible peptide-binding groove mutations. Mutations in peptide-binding groove residues 45, 63, and 150 affect multiple nonoverlapping mAb epitopes, probably by interaction with other MHC residues or bound peptide. However, 18 of 24 peptide-binding groove mutations do not affect mAb binding, indicating that the conformation of solvent-accessible HLA-B7 structures is largely dissociated from changes in the peptide-binding groove. To test whether bound peptides alter HLA-B7 conformation, we loaded HLA-B7 heavy chains on acid-stripped cells with beta2-microglobulin and 20 individual synthetic peptides. Two of eight mAbs are sensitive to HLA-B7-bound peptides. A likely interpretation of these data is that the conformational flexibility of HLA-B7 is due to peptide-induced conformational shifts in MHC side chains, rather than major shifts in the MHC main chain. These results suggest that HLA-B7 conformation is largely maintained in the context of different bound peptides and different peptide-binding grooves.

Introduction Point-spread-function (PSF) modelling seem to be very attractive to obtain superior image quality in [F-18] FDG oncological studies, nonetheless it is known to significantly increase noise variability. Purpose To evaluate the impact of PSF/TF on noise structure of iterative reconstructed (IR) images. Materials and methods An anthropomorphic phantom with [F-18] FDG clinical concentrations was acquired on Biograph-mCT (Siemens) and Discovery690 (General Electric) PET/CT scanners. Overall, 96 datasets were obtained by varying reconstruction modalities (RM = IR, TF, PSF, TF+PSF), frame (128,256), equivalent iterations number (IT = 63,270), and Gaussian filter (GF = 2, 4, 6 mm). To limit noise correlation in PET imaging, 6 groups of concentric ROIs (r = 8;10;13;16;19 mm) were drawn on 3 slices at liver level. Fixing slice and ROI size, the signal variation was defined: SV% = 100∗SD/M, were SD,M are standard deviation, mean among the mean count values found for the ROIs, respectively. Results SV decreases with ROI size and GF, and increases with IT. Moreover, SV depends on RM, but in different ways on the two PET scanners. For Biograph-mCT, highest and lowest SV were observed for PSF and TF and for GF = 2, 4, 6 mm mean(range) values were: 7.8%(5.1–10.6), 5.7%(3.1–8.5), 4.5%(2.5–6.7) and 4.5%(2.7–6.4), 3.8%(2.4–5.4), 3.2(2.2–4.5), respectively. For Discovery690, highest and lowest SV were observed for PSF+TF and IR and for GF = 2, 4, 6 mm the mean(range) values were: 8.3%(6.8–10.5), 8.1%(6.7–10.2), 7.9%(6.6–9.7) and 5.1%(3.5–8.2), 4.5%(3.1–7.0), 4.2%(3.2–6.2), respectively. Same trends are observed for the range of SV values. Conclusions The PET scanners of this study showed different behaviors of SV in relation to RM. Increased SV could lead to degradation of precision in quantitative oncological studies with [F-18] FDG for monitoring treatment response.

Introduction the skin of the hands of the nuclear medicine’s staff involved in preparation and manipulation of unsealed radiopharmaceuticals is the organ at highest risk for irradiation. The dose limit, to be applied to the average of 1 cm 2 of skin regardless the surface of the exposed area, is of difficult assessment. The ORAMED project identified the tip of the index of the non-dominant hand as the point of maximum exposure. Due to the high estimated proportion of workers liable to exceed the extremities annual dose limit (15–20%), the fingers dose monitoring is highly recommended especially in busy labs. Purpose To evaluate under routine operating conditions, in 3 nuclear medicine departments, the irradiation dose to the extremities of workers involved in the preparation of 99m Tc-radiopharmaceuticals. Materials and methods Two operators for each centre were monitored by using 4 TLD (LiF: Mg, Cu, P) for 2 weeks. For each single task the operational time and the manipulated activities were recorded. Results The mean daily 99m Tc activity manipulated was 56 GBq resulting in a mean dose equivalent values of: 38.5, 18.9, 5.4 and 63.7 microSv/GBq for the monitored hand positions: index tip of non-dominant, index base of non-dominant, wrist of non-dominant and index tip of dominant hand respectively. Conclusion Conversely to the ORAMED findings, the index fingertip of the dominant hand receives the highest dose. Based on the daily handled activities, the dose limit could be exceeded in 138 working days, thus confirming the concerns raised by many authors.

Introduction Nowadays interventional cardiac procedures are of concern for the relatively high doses delivered to patients. Purpose To estimate the effective dose (E), the organ doses (H t ) and the related risk for cancer induction in terms of radiation exposure-induced death (REID) in patients undergoing coronary angiography (CA) and percutaneous transluminal coronary angioplasty (PTCA) procedures with radial access. Materials and methods 65 patients underwent CA and PTCA interventions on a Philips Allura XPer FD10 angiographic equipment. For each patient, Xray tube voltage, projection, filtration, field dimensions and DAP were obtained by filming the monitor of the workstation during the entire procedure. E and H t were evaluated by means of the MonteCarlo code PCXMC that models radiation beam and transport in an anthropomorphic phantom, allowing also the evaluation of REID. Results Mean fluoroscopy time, DAP and E were: 3.1 min, 29.9 Gyxcm 2 , 9.1 mSv and 8.9 min, 60.9 Gyxcm 2 , 20.3 mSv for CA and PTCA, respectively; the correlation with DAP was very good in CA (r = 0.99) and in PTCA (r = 0.93). For both CA and PTCA, the most irradiated organs were lungs, oesophagus and red marrow, whose mean H t were 32.5 mSv, 30.7 mSv, 11.6 mSv for CA and 58.5 mSv, 66.7 mSv, 24.9 mSv for PTCA; the highest REIDs were for induction of leukemia (0.04% and 0.08%) and lung cancer (0.14% and 0.20%). Conclusions Cardiac interventional procedures with radial access improves patient compliance, reduces haemorrhagic complications compared to femoral access with comparable E and Ht values.

Purpose End Stage Kidney Disease patients are exposed to ionizing radiation during imaging studies. The variability in diagnostic imaging policies and the accompanying risk across Renal Units are unknown. We studied this variability at centre level and quantified the associated risks at patient level, by estimating the organ doses (H T ) and the Risk of exposure-induced cancer death (%) (REID). Materials and methods Fourteen nephrology departments enrolled 739 patients on hemodialysis (HD) and 486 kidney transplant patients (KTP), recording the details of the radiological procedures performed over one year. H T were derived using Montecarlo based simulation software for conventional diagnostic radiology procedures and for Computed Tomography. H T were derived using tabulated conversion factors for cardiac interventional radiology and nuclear medicine procedures. Results The average REID was 0.047 ± 0.12 % and the corresponding 5-years cancer risk attributable to ionizing radiation exposure was 1 every 424 patients. The median REID was 0.009% and the 3 rd quartile was 0.03%. The average REID was significantly higher in HD than in KTP (0.06 ± 0.13 i.e. 1:333 patients for 5-years vs 0.03 ± 0.09 i.e. 1:666 patients for 5-years; p F = 3.23; p Conclusion The excess cancer risk attributable to medical exposure is highly variable among centres (a tenfold variation), suggesting that protocols of individual patient’s follow up with medical imaging are not standardized. On average, KTP have a lower exposure than HD patients (a twofold variation). Disclosure None to declare.

The activity of the hypothalamic-pituitary-adrenal axis in hemodialyzed (HD) patients has been investigated, with conflicting results. Different results are reported concerning both basal ACTH and cortisol concentration and the responses to different stimulating agents, in chronic hemodialyzed patients. The present study was performed in order to asses whether the length of the hemodialytic treatment may affect the pituitary and adrenocortical response to stimulation with ovine CRH (oCRH) and with exogenous ACTH in a group of patients on chronic HD for more than 10 years. Ten uremic patients (aged 38-71, 6 males and 4 females) on chronic hemodialysis for at least 10 years and 7 healthy subjects matched for age and sex were studied. The patients were tested on the day preceding dialysis session. Each subject received on different non-consecutive days oCRH (100 micrograms i.v. in bolus) and ACTH (Synacthen 0.25 mg i.v. in bolus), and blood samples were obtained at appropriate intervals. Basal ACTH and cortisol levels of HD patients were in the upper limit of normal range (ACTH 39.21 +/- 11.11 pg/mL in HD patients vs. 26.88 +/- 14.12 pg/mL in controls; cortisol 19.96 +/- 5.07 in HD patients vs. 12.66 +/- 4.44 in controls); however, the means were not significantly different compared with controls. Following oCRH administration a net increase of ACTH and cortisol was observed in every patient tested (ACTH peak 83.81 +/- 28.49 in HD vs. 78.73 +/- 22.87 pg/mL in controls; cortisol peak 30.73 +/- 19.31 in HD vs. 20.05 +/- 3.19 micrograms/dL in controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Dipartimento di Scienze eTecnologie Alimentari e Microbiologiche (DISTAM), International Center for the Assessment of Nutritional Status(ICANS), Universita` degli Studi di Milano, via Botticelli 21, 20133 Milano, ItalySubmitted 26 March 2010: Accepted 9 January 2011: First published online 22 February 2011AbstractObjective: To evaluate the awareness and knowledge about weight status and itsmanagement.Design: A 1d cross-sectional survey. Basic anthropometric assessments (weight,height, BMI and waist circumference) and a self-administered questionnaire wereconsidered.Setting: Nineteen Clinical Nutrition or Endocrinology and Metabolic DisordersUnits or Dietetics Services in the Italian region of Lombardy.Subjects: All adults attending the ‘Obesity Day’ initiative.Results: A total of 914 participants (605 female and 309 male) were recruited.Although most of the participants (83?5%) considered obesity to be a disease,38?5% were likely to misperceive their weight status. In particular, 38?8% ofnormal-weight adults believed themselves to be overweight, whereas 71?1% and37?5% of classes I and II/III obese adults classified themselves as being over-weight and mildly obese, respectively. However, most of the overweight (90?2%),mildly(96?8%)andmoderately/severelyobeseadults(99?1%)recognizedtheneedto lose weight. In all, 37?8% of the sample underestimated the role of physicalactivity in weight management. Interestingly, only 17?2% of dieters (previous orcurrent) declared being advised by their doctor to lose weight. Multivariate modelsrevealed that higher age, low education and higher BMI were important determi-nants of poor weight control and management. In addition, previous dietingappeared not to provide better knowledge, whereas the role of physical activitywas recognized mainly by those practising it.Conclusions: The present study suggests that in Italy knowledge about weightmanagement should be improved not only in the general population but alsoamong health-care professionals. To confirm thisfinding, there isnow the rationalefor a nationally representative survey. New educational programmes can bedesigned on the basis of the information collected.KeywordsBMIWeight statusWeight perceptionWeight managementGiven the time trends of the obesity epidemic, publichealth systems are clearly involved in more effectivemanagement and prevention policies. Weight excess isresponsible for several chronic degenerative disorders,which in turn negatively affect the patient’s outcome.Accumulation of total and abdominal fat has been inde-pendently associated with overall-cause and disease-specific mortality, thus making body weight reduction andlong-term maintenance of weight loss a clinical impera-tive

Egyptian stones are of primary importance among all the natural stones used for monumental works in various historical epochs, from the Ancient Egyptians through the Romans and until today. Recently, a straightforward project aimed at investigating the stony handcrafts preserved in the Egyptian Museum of Turin, Italy, has been undertaken, with the specific purpose of obtaining a systematic petrographic classification of these objects and determining their possible geological source.

SPECT studies are sensitive but inaccurate means through which to analyze small volumes such as, for instance, remnant tissues after thyroidectomy. We studied the relation between known volumes (0.1–10 cm3) and volumes measured with SPECT studies and using solutions of four different isotopes: 99mTc, 117mSn, 111In, 131I. The curves we determined were tested on SPECT images of two patients treated with 131I. Our work suggests the possibility to evaluate the small remnant mass using calibration curves specific to the system of image acquisition. However, it is necessary to extend the study to a larger number of patients.

This study was designed to assess the response of growth hormone (GH) to growth hormone releasing hormone (GHRH) and the possible interaction of acutely administered recombinant human erythropoietin (rhEPO) on GH response to GHRH in a group of uraemic patients. Eight patients on maintenance haemodialysis, not previously treated with rhEPO, and six healthy controls were tested with GHRH (100 micrograms i.v. in bolus), and with GHRH (100 micrograms i.v. in bolus) plus rhEPO (40 U/kg in constant infusion for 30 min) on different days. GHRH injection provoked a GH release in five out of eight uraemic patients; the overall mean response did not differ significantly from the GH response obtained in controls (P = 0.30). Erythropoietin infusion significantly increased GH release after GHRH (P less than 0.01 at 15, 30, 45, 60 min after GHRH injection) in uraemic patients; in controls, on the contrary, stimulation with GHRH plus rhEPO did not induce a greater increase of GH release compared with that observed after GHRH alone (mean GH peak 37.66 +/- 7.68 mU/l after GHRH; and 38.0 +/- 9.18 mU/l after GHRH plus rhEPO; P greater than 0.5). In this study acutely administered rhEPO significantly potentiated the GH response to GHRH in uraemic patients whereas the same effect was not demonstrable in subjects with normal renal function.

Objective:Recent studies have shown a strong predictive value of Neutrophil-Lymphocyte Ratio (NLR) for the risk of coronary heart disease. Higher values of NLR are useful to reclassify arteriosclerotic risk in subjects at low CV risk. On the other hand, high-sensitivity C-Reactive Protein (hsCRP) ha

DNA polymerase eta (Pol eta) is a member of a new class of DNA polymerases that is able to copy DNA containing damaged nucleotides. These polymerases are highly error-prone during copying of unaltered DNA templates. We analyzed the relationship between bypass efficiency and fidelity of DNA synthesis by introducing substitutions for Tyr-52, a highly conserved amino acid, within the human DNA polymerase eta (hPol eta) finger domain. Most substitutions for Tyr-52 caused reduction in bypass of UV-associated damage, measured by the ability to rescue the viability of UV-sensitive yeast cells at a high UV dose. For most mutants, the reduction in bypass ability paralleled the reduction in polymerization activity. Interestingly, the hPol eta Y52E mutant exhibited a greater reduction in bypass efficiency than polymerization activity. The reduction in bypass efficiency was accompanied by an up to 11-fold increase in the incorporation of complementary nucleotides relative to non-complementary nucleotides. The fidelity of DNA synthesis, measured by copying a gapped M13 DNA template in vitro, was also enhanced as much as 15-fold; the enhancement resulted from a decrease in transitions, which were relatively frequent, and a large decrease in transversions. Our demonstration that an amino acid substitution within the active site enhances the fidelity of DNA synthesis by hPol eta, one of the most inaccurate of DNA polymerases, supports the hypothesis that even error-prone DNA polymerases function in base selection.