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Disasters and other emergency events have complex effects on human systems, particularly if the events are severe or prolonged. When these types of events happen in rural communities, the resources of the local public health, healthcare, and emergency response organizations can be quickly depleted or overwhelmed. Planning for emergencies can help to mitigate their impact. Model-based systems engineering (MBSE) methods, including computer simulations, can provide insight on how best to prepare for these events and to explore the effects of varying approaches and resource utilization. To best apply these methods for improving disaster management in rural settings, a synthesis of the current body of evidence in this field is needed. The objective of this scoping review was to provide a descriptive overview of the application of computer simulation based on MBSE approaches to disaster preparedness and response for rural healthcare systems. Six studies met inclusion criteria, and varied in terms of MBSE method used, healthcare setting, and disaster type and context considered. We identified a gap in the research regarding the application of MBSE approaches to support rural healthcare disaster preparedness planning efforts. Model-based systems engineering and systems thinking, therefore, represent novel methods for developing tools and computational simulations that could assist rural communities better prepare for disasters.

Background: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS). Method: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS. Results: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30). Conclusion: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome.

OBJECTIVE: We prospectively examined whether subjective intoxication serves as a risk factor for experiencing alcohol-induced blackouts. We then examined whether subjective intoxication and/or blackouts predicted motivation to decrease their drinking, and whether this motivation to change would promote future changes in drinking behavior. METHOD: Participants (N = 1,854, 62.1% female, 53.2% Caucasian, M(age) = 21.8) were recruited the summer prior to matriculating into a large, public university to complete a 6-year longitudinal study. Self-reported motivation to decrease their drinking behavior, their frequency of blackouts, quantity of alcohol consumption, and subjective intoxication (i.e., feeling drunk) were assessed annually during the transition out of college (Years 4–6). RESULTS: In a cross-lagged model, subjective intoxication (i.e., feeling drunk) prospectively predicted experiencing blackouts (p < .001). Controlling for both objective (e.g., quantity) and subjective intoxication, blackouts at Year 4 predicted greater motivation to decrease drinking behavior at Year 5 (p < .01), but this motivation did not predict less quantity of alcohol use by Year 6 (p = .076). CONCLUSIONS: Subjective intoxication is a robust predictor of blackouts across time. Additionally, blackouts are modest, developmentally-limited predictors of motivation to change drinking behavior, but blackouts do not predict future behavior change.

OBJECTIVE: This study examined how freshman year substance use prospectively predicted time to college graduation, and whether delayed graduation predicted postponed adoption of adult roles and future substance use. PARTICIPANTS: Participants were part of a longitudinal study that began in 2004. The first analyses focused on freshman year (N=2,050). The second analyses corresponded to a subset of participants at age 27 (N=575). METHODS: Measures included self-reported substance use, adult role adoption, and university reported graduation dates. RESULTS: Results indicated that frequent binge drinking and marijuana use during freshman year predicted delayed college graduation. Those who took longer to graduate were more likely to have lower incomes and were less likely to obtain a graduate degree. Taking 5–6 years to graduate was associated with greater likelihood of alcohol-related problems. CONCLUSIONS: Findings support the importance of interventions during freshman year of college to decrease substance use and promote timely graduation.

Introduction: Robotic-assisted surgery (RAS) is increasingly used in adulthood but its application in pediatric population is limited. We report our initial experience in pediatric RAS, focusing on...

Gastric duplication cysts (GDCs) represent 4-9% of alimentary tract duplications. Early diagnosis and surgical excision are essential to avoid morbidity or neoplastic degeneration. Roboticassisted excision of GDCs has never been described in childhood. We report an asymptomatic male patient with 2 gastric cystic masses at ultrasonography (US)-study (diameter 25mm and 8mm), increasing in size at follow-up. At 20 months of age, magnetic- resonance-imaging-scan confirmed 2 round gastric masses (44×35mm and 16×12mm, respectively). Two months later, an elective robotic-assisted excision of GDCs was completed without complications. The patient was discharged at day 6 after procedure. Histology confirmed the diagnosis of GDCs. At a 2-year follow- up, US-study did not evidence any issue. In this first reported case of robotic-assisted cystectomy for CGD in childhood, the procedure seems safe, effective, and feasible. This approach improves the movements of the surgical instruments with better 3- D visualization in comparison with the laparoscopic approach.

Background Consequences of heavy drinking include alcohol-induced blackouts, which are periods of amnesia for all or part of a drinking event. One risk factor for blackouts is family history of problematic alcohol use (FH +); however, research rarely distinguishes maternal from paternal FH +. The objective of this study was to examine whether maternal or paternal FH + better predicts likelihood of experiencing blackouts than a general measure of overall FH +, and whether gender moderates this association. Method Participants (N = 1164; 65.4% are female) were first-time college freshmen (age range = 17–19) who participated in a 6-year, 10-assessment, longitudinal study in the United States. Alcohol-induced blackouts, the dependent measure, were dichotomized (yes/no) based on endorsement of memory problems after drinking using a single item during Years 4–6. FH +, captured at baseline, was coded if participants self-reported that their mother, father, or any of their four grandparents were a possible or definite problem drinker. Results Overall, 773 (66.4%) participants reported experiencing blackouts during Years 4–6. Women were more likely to report blackouts than men; however, compared with women with a maternal FH +, men with a maternal FH + were more than twice as likely to report blackouts. Discussion Men appear to be more susceptible than women to the effects of a maternal FH +. Genetic and environmental explanations for this finding are discussed. In sum, these findings are an important step toward understanding a significant yet understudied negative consequence of heavy alcohol use.

Despite the high prevalence of prescription opioid dependence in the U.S., little is known about the course of this disorder and long-term response to treatment. We therefore examined 18-month post-randomization outcomes of participants in the Prescription Opioid Addiction Treatment Study, a multi-site, randomized controlled trial examining varying durations of buprenorphine-naloxone treatment and different intensities of counseling for prescription opioid dependence. Thus the current follow-up study provides a unique contribution to the field by reporting longer-term outcomes of a well-characterized population of treatment-seeking prescription opioid dependent patients. Participants from the treatment trial (N=252/653) completed an 18-month follow-up telephone assessment. Multivariable analyses examined associations between participant characteristics and key indicators of month-18 status: opioid abstinence, DSM-IV opioid dependence, and opioid agonist treatment. Overall, participants showed improvement from baseline to month 18: 49.6% were abstinent in the previous 30 days, with only 16.3% opioid-dependent. Some participants, however, had initiated past-year heroin use (n=9) or opioid injection (n=17). Most participants (65.9%) engaged in substance use disorder treatment during the past year, most commonly opioid agonist therapy (48.8%). Of particular interest in this population, multivariable analysis showed that greater pain severity at baseline was associated with opioid dependence at 18 months. In conclusion, although opioid use outcomes during the treatment trial were poor immediately following a buprenorphine-naloxone taper compared to those during 12 weeks of buprenorphine-naloxone stabilization, opioid use outcomes at 18-month follow-up showed substantial improvement over baseline and were comparable to the rate of successful outcomes during buprenorphine-naloxone stabilization in the treatment trial.

Opioid analgesics misuse is a significant military health concern recognized as a priority issue by military leadership. Opioids are among those most commonly prescribed medications in the military for pain management. The military has implemented opioid risk mitigation strategies, including the Sole Provider Program and the Controlled Drug Management Analysis and Reporting Tool, which are used to identify and monitor for risk and misuse. However, there are substantial opportunities to build on these existing systems to better ensure safer opioid prescribing and monitor for misuse. Opioid risk mitigation strategies implemented by the civilian sector include establishing clinical guidelines for opioid prescribing and prescription monitoring programs. These strategies may help to inform opioid risk mitigation in the military health system. Reducing the risk of opioid misuse and improving quality of care for our Warfighters is necessary. This must be done through evidence-based approaches with an investment in research to improve patient care and prevent opioid misuse as well as its sequelae.

The INSIDE collaboration aims to build an on-line hadrontherapy monitoring system, based on a dual-head in-beam PET scanner and a secondary charged particles profiler. In this work preliminary experimental results are presented. The validation of the FLUKA-based Monte Carlo simulation tool is shown together with the expected scanner performances.

Summary. A multicentre cross-sectional survey was performed to provide an accurate picture of patients with chronic hepatitis B (CHB) cared for by Italian Infectious Diseases Centers (IDCs). This analysis describes factors associated with access to the treatment of CHB in a country where barriers to treatment are not expected to exist because of comprehensive coverage under the National Health System (NHS). The study was performed in 74 IDCs. The analysis focused on 3305 patients with CHB of 3760 HBsAg-positive patients enrolled from March to September, 2008. To account for missing values, a Multiple Imputation method was used. Treatment was reported in 2091 (63.3%) patients. In the multivariate analysis, an increased chance of getting treatment was independently associated with 10 years increase of age at diagnosis (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.1–1.3, P

Neuroticism is associated with greater susceptibility to the adverse effects of stress and greater exposure to the stressors associated with acculturation in U.S. born Mexican Americans. Neuroticism and acculturation have been associated with injury to crucial stress response systems and are known risk factors for certain mood and anxiety disorders. The purpose of the current study was to examine the effects of neuroticism, and acculturation on the cortisol awakening response (CAR) in healthy Mexican-American adults. Salivary cortisol samples were collected at awakening and 30, 45, and 60 min thereafter, on two consecutive weekdays from 59 healthy Mexican American adult males (26) and females (33), ages 18 to 38 years. Participants were assessed for level of neuroticism and acculturation. Data were analyzed using a mixed effects regression model with repeated measures at four time points. Results showed a significant Neuroticism × Acculturation × Time interaction. The CAR was virtually eliminated in highly acculturated Mexican Americans with greater Anglo orientation and high neuroticism compared with less acculturated Mexican Americans with greater Mexican orientation and lower neuroticism. Findings suggest that some Mexican Americans with high levels of neuroticism may be particularly susceptible to certain challenges and stressors associated with acculturation leading over time to the development of allostatic load, desensitization of the Hypothalamic CRF system and attenuation of the CAR.

BACKGROUND: Early onset drinking is associated with later heavy drinking and related consequences. Early drinking onset and binge drinking are also independently associated with blackouts, which are periods of amnesia for events during a drinking episode. The objective of this study was to examine how early onset drinking relates to changes in the frequency of experiencing blackouts across 3 years controlling for year-specific binge drinking. METHODS: Participants (N = 1,145; 67.9% female) from a 6-year, longitudinal study are included in these analyses. Measures of self-reported age at drinking onset included ages at first drink, first high, and first drunk, which were used to create a latent early onset drinking factor. Frequency of binge drinking and blackouts were assessed annually during Years 4 to 6. RESULTS: Overall, 69.2% of participants reported experiencing blackouts. After controlling for year-specific binge drinking, a growth curve model indicated that early onset drinkers reported more frequent blackouts at Year 4. There were, however, no significant effects of acceleration or deceleration in the frequency of blackouts across the 3 years. Early onset drinkers continued to experience more frequent blackouts compared with those who initiated alcohol use later, despite decreases in binge drinking over time. CONCLUSIONS: Early onset drinkers reported more frequent blackouts across all 3 years, indicating that early alcohol initiation predisposes those individuals to continue to experience more frequent blackouts, despite a decrease in their binge drinking. This may be due to various factors, such as altered hippocampal development and functioning resulting from early alcohol exposure. Language: en

Chronic inflammation contributes to tumorigenesis. The retinoblastoma protein (pRb), in its hyperphosphorylated form, releases E2 promoter binding factor-1 (E2F1), which drives cell proliferation. Here, we show that pRb is hyperphosphorylated in both mouse and human colitis. In turn, pRb hyperphosphorylation is associated with release of E2F1 from pRb, resulting in the activation of E2F1 target molecules involved in proliferation and apoptosis. These observations provide insight into the in vivo mechanisms associated with chronic colon inflammation and increased colon cancer risk.

We present an experimental study of the dynamics of a magneto–optical trap (MOT) loaded from an alkali dispenser current controlled source. In our experimental vacuum conditions and for a low trapping force MOT the trap loading process critically depends on the dispensers working regime. This allows to completely characterize the dispensers–MOT system and to determine the best loading conditions.

This paper presents a novel multichannel time to digital converter (TDC) specifically designed for the digitization of photon time of flight (TOF) and energy in positron emission tomography (PET) scanners. A coarse-fine architecture based on a counter combined with a delay locked loop (DLL) is implemented using a fully synchronous approach exploiting the pipeline principle and dynamic logic. This makes the design particularly compact and suitable for multichannel applications. The converter is also able to reject the events generated by the dark noise of the photodetectors used in the PET modules. This significantly reduces the communication bandwidth required for reading the TDC outputs. The TDC has been designed in a 65 nm CMOS process and features 8 channels that provide the arrival time information of an event with an LSB of 102 ps. The core occupies an active area of $0.3~\hbox{mm}^2$ and consumes 230 mW.

Dosimetry in Hadrontherapy M. Marafini, A. Attili, G. Battistoni, N. Belcari, M.G. Bisogni, N. Camarlinghi, F. Cappucci, M. Cecchetti, P. Cerello, F. Ciciriello , G.A.P. Cirrone, S. Coli, F. Corsi , G. Cuttone, E. De Lucia, S. Ferretti, R. Faccini, E. Fiorina, P.M. Frallicciardi, G. Giraudo, E. Kostara, A. Kraan, F. Licciulli , B. Liu, N. Marino, C. Marzocca , G. Matarrese , C. Morone, M. Morrocchi, S. Muraro, V. Patera, F. Pennazio, C. Peroni, L. Piersanti, M.A. Piliero, G. Pirrone, A. Rivetti, F. Romano, V. Rosso, P. Sala, A. Sarti, A. Sciubba, G. Sportelli, C. Voena, R. Wheadon and A. Del Guerra Museo Storico della Fisica e Centro Studi e Ricerche E. Fermi , Roma, Italy b−f INFN Sezione di: Roma, Roma; Torino, Torino; Milano, Milano; Pisa, Pisa; Bari, Bari; Italy Laboratori Nazionali del Sud dell'INFN, Catania, Italy Laboratori Nazionali di Frascati dell'INFN, Frascati, Italy Dipartimento di Scienze di Base e Applicate per Ingegneria, Sapienza Universita di Roma, Roma, Italy

But: Comparer l'appendicectomie trans-ombilicale (TULAA) et l'appendicectomie conventionnelle (OA) dans les formes non-compliquees d'appendicite aigue. Methodes: 58 TULAA et 65 OA avec un diagnostic pre-operatoire d'appendicite aigue non compliquee sont comparees. Le pneumoperitoine etait obtenu avec un trocart trans-ombilical de 10 mm et un trocart de 5 mm etait introduit dans la fosse iliaque gauche. L'appendicectomie etait realisee en dehors de l'abdomen apres l'exteriorisation de l'appendice a travers l'incision ombilicale. Resultats: Dans le groupe TULAA, le temps operatoire et le sejour hospitalier etaient reduits. La conversion n'a ete necessaire que dans 1 cas (1,7%) et dans 1 cas (1,7%), un trocart supplementaire de 5 mm a ete introduit. Aucune complication per et post-operatoire n'est survenue dans le groupe TULAA avec un excellent resultat cosmetique. Dans le groupe OA, nous avons une infection parietale (1,5%) et dans 8 cas (12,3%) un elargissement de l'incision etait necessaire. Conclusion: TULAA est la meilleure approche de l'appendicite non compliquee, est moins agressif et traumatique. Elle permet une evaluation complete de la cavite peritoneale avec des resultats cosmetiques superieures, particulierement chez les patients obeses et en cas d'appendice ectopique.

But: Decrire un cas pediatrique de syndrome de «Blue Rubber Bleb Nevus» (BRBNS) ou syndrome de Bean, un desordre systemique rare caracterise par des malformations vasculaires, cutanees et gastro-intestinales qui aboutissent souvent a des hemorragies gastro-intestinales majeures ou a des pertes occultes avec anemie et deficit en fer. Observation: Une fille de 6 ans avec de multiples lesions vasculaires, cutanees caracteristiques etait admise pour une hemorragie rectale massive. Quelques mois auparavant, elle avait ete traitee endoscopiquement pour des angiomes gastriques qui entrainaient un melaena. Les investigations pre-operatoires revelent la recidive des lesions gastriques. A la laparotomie, plus de 25 angiomes du tractus gastro-intestinal ont ete trouves, de multiples resections intestinales etaient realisees. Resultats: Aucun probleme per- ou post-operatoire n'est observe et l'enfant est completement saine, sans recidive d'hemorragie apres un suivi de 3 annees. Conclusions: BRBNS appartient au groupe des malformations vasculaires veineuses. Dans la majorite des cas, il survient sporadiquement mais il peut-etre la consequence d'une transmission autosomale dominante. Des analyses recentes ont localise un locus sur le chromosome 9 responsable des malformations veineuses. Les patients avec BRBNS presentent des lesions cutanees typiques avec quelques lesions mamelonnees caoutchouteuses; le nombre de lesions cutanees et du tractus gastro-intestinal et la severite de l'anemie sont en rapport. Le traitement est dependant de l'extension sur le tube digestif et la severite de la presentation clinique. En l'absence d'hemorragie massive, un traitement conservateur peut etre suffisant, autrement, des resections sont necessaires, mais des lesions supplementaires peuvent secondairement se developper. Le management avec electrocoterisation ou photocoagulation par laser est generalement inefficace meme si quelques publications le recommandent. Le traitement pharmacologique est inutile. Le pronostic de BRBNS est inconnu.

Introduction Most patients relapse to opioids within one month of opioid agonist detoxification, making the antecedents and parallel processes of first use critical for investigation. Craving and withdrawal are often studied in relationship to opioid outcomes, and a novel analytic strategy applied to these two phenomena may indicate targeted intervention strategies. Methods Specifically, this secondary data analysis of the Prescription Opioid Addiction Treatment Study used a discrete-time mixture analysis with time-to-first opioid use (survival) simultaneously predicted by craving and withdrawal growth trajectories. This analysis characterized heterogeneity among prescription opioid-dependent individuals (N = 653) into latent classes (i.e., latent class analysis [LCA]) during and after buprenorphine/naloxone stabilization and taper. Results A 4-latent class solution was selected for overall model fit and clinical parsimony. In order of shortest to longest time-to-first use, the 4 classes were characterized as 1) high craving and withdrawal, 2) intermediate craving and withdrawal, 3) high initial craving with low craving and withdrawal trajectories and 4) a low initial craving with low craving and withdrawal trajectories. Odds ratio calculations showed statistically significant differences in time-to-first use across classes. Conclusions Generally, participants with lower baseline levels and greater decreases in craving and withdrawal during stabilization combined with slower craving and withdrawal rebound during buprenorphine taper remained opioid-free longer. This exploratory work expanded on the importance of monitoring craving and withdrawal during buprenorphine induction, stabilization, and taper. Future research may allow individually tailored and timely interventions to be developed to extend time-to-first opioid use.

Soil, aquatic biota (moss: Brachythecium rivulare; aquatic macrophytes: Juncus effusus, Potamogeton crispus; fish: Salmo trutta fario, Anguilla anguilla, Phoxinus phoxinus, Chelon labrosus) and sediment samples from the Urumea river valley were analysed for metals by acid digestion and atomic absorption spectroscopy. The sediments show the presence of metal pollution (Cd: 2.5–24 mg kg-1; Pb: 125–1,150 mg kg-1; Zn: 125–2,500 mg kg-1) because mining and industrial wastes. A selective retention of dense minerals in dam sediments contributes to the load of metal, but interstitial water analysis (Cd: ), but they are used, indistinctly, for farming and pasture.

The 4D-MPET project aims to design a positron emission tomography detection module capable of working inside a magnetic resonant imaging system. The proposed detector will feature a three-dimensional architecture based on two tiles of silicon photomultipliers coupled to a single LYSO scintillator on both its faces. Silicon photomultipliers are magnetic-field compatible photo-detectors with a very small size enabling novel detector geometries that allow the measurement of the depth of interaction. Furthermore they can be fabricated using standard silicon technology, have a large gain in the order of 106 and are very fast thus allowing evaluating the time of flight. Based on custom integrated circuits, the readout electronics include an innovative current mode front-end coupled to a novel time to digital converter. The former, implemented in AMS 0.35 \(\upmu \)m SiGe-BiCMOS technology, features a very low input impedance (17 \(\Omega \)) current buffer and a large bandwidth (1 GHz), which lead to a time resolution of \(\sim \)100 ps FWHM. The time to digital converter exploits the combination of a submicron technology (UMC 65 nm LLLVT) together with a systolic topology so as to work at a high frequency of 2.5 GHz. This yields to a nominal time resolution of 29 ps (\(\sigma )\) whereas the photon energy is evaluated with a bin size of 400 ps by using a time over threshold technique. Finally, the depth of interaction measurement is performed by an external FPGA with a simulated spatial resolution of 1.3 mm FWHM along the z coordinate.

Generally laser ablation of materials is performed at laser fluences above a definite threshold for which a dense plume of energetic particles is ejected from the irradiated target and considerably high ablation rate is achieved. No particular effort has been devoted to correlate the film quality to the employed laser fluence, also in correlation with different possible ablation mechanisms of ablation. We have performed measurements of ablation rate on silicon carbide single crystal targets by XeCl laser pulses as function of the laser fluence and we have investigated the angular distribution of the emitted material through the measurements of the thickness of the deposited films as well as the morphology of the craters in the irradiated targets as a function of the laser fluence. We have also modelled the melting dynamics and calculated the surface temperature and the consequent ‘pure thermal’ evaporation following each laser pulse by using the well known ‘thermal model’ often used for the laser annealing. In the presented paper we show that SiC ablation behaviour depends on the laser fluence so that three phenomenologically different energy density ranges may be defined.

Positron emission tomography (PET) is a molecular imaging technique that provides images of physiological processes inside the body. In clinical applications, PET image quality benefits from the time of flight (TOF) feature. This is based on measuring the difference in the arrival times of couples of nearly collinear photons generated during the PET exam on a detector ring with a resolution less than 100 ps. In this scenario, a time to digital converter (TDC) can be used for the read out of the detectors to provide the photon arrival time. If matrices of Silicon Photomultipliers are used as photodetectors, multichannel topology and real time noise rejection capability are strongly required in the design of the converter along with good linearity. We present an innovative TDC architecture which is suitable for TOF PET applications.

The importance of a high-quality hybrid imaging, providing morphological and functional information with only one acquisition session, is widely acknowledged by the scientific community. The historical limitations to the quality of PET images are related to the unsatisfactory measurement of the depth of interaction (DOI) in the crystals and of the time of flight (TOF), that cause a parallax error and an unfavorable signal to background condition in the image reconstruction process, respectively. The 4DMPET project is developing a high performance PET block-detector featuring 4D image reconstruction capabilities. The detector module is based on a fast scintillating continuous crystal coupled on both sides to arrays of Silicon PhotoMultipliers (SiPM). The SiPMs collect the scintillation light and provide the trigger signal, the time and the energy released in the crystal at the pixel level. The photon depth of interaction (DOI) is reconstructed by measuring the cluster size asymmetry on the two faces of the crystal, thus obtaining a comparable spatial resolution in the three coordinates and removing the parallax error. The event position along the line of response can be measured with high precision by means of TOF techniques. We discuss the module design concept and the results of the detailed Monte Carlo detector simulation, which inspire the architectural solutions selected for the layout and the front-end The expected resolution for 3D spatial coordinates of the interaction point in the crystal (1 mm) and the TOF (about 110 ps) would provide a substantial improvement of the image quality. 4DMPET aims at building a prototype block detector demonstrating that the proposed layout meets the expected performance and is suitable for designing a detector focused on a specific application.

Background The continuing migration of individuals from geographic areas with high/medium endemicity has determined the arrival of new chronic hepatitis B virus (HBV) carriers in Italy. The magnitude of this phenomenon and clinical/virological features of HBsAg-positive migrants remain not very well defined. Aims To evaluate the proportion of HBsAg-positive immigrants enrolled in this multicenter Societa` Italiana di Malattie Infettive e Tropicali (SIMIT) cross-sectional study and to compare the characteristics of chronic hepatitis B infection in migrants to those of Italian carriers. Methods From February 1 to July 31 2008, anonymous data were obtained from all HBsAg-positive patients aged C18 years observed at 74 Italian centers of infectious diseases. Results Of the 3,760 HBsAg-positive subjects enrolled, 932 (24.8 %) were immigrants, with a prevalent distribution in central to northern Italy. The areas of origin were: Far East (37.1 %), Eastern Europe (35.4 %), Sub- Saharan Africa (17.5 %), North Africa (5.5 %), and 4.5 % from various other sites. Compared to Italian carriers, migrants were significantly younger (median age 34 vs. 52 years), predominantly female (57.5 vs. 31 %), and most often at first observation (incident cases 34.2 vs. 13.3 %). HBeAg-positives were more frequent among migrants (27.5 vs. 14 %). Genotype D, found in 87.8 % of Italian carriers, was present in only 40 % of migrants, who were more frequently inactive HBV carriers, with a lower prevalence of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Only 27.1 % of migrants received antiviral treatment compared to 50.3 % of Italians. Conclusions Twenty-five percent of all HBV carriers examined at Italian centers was composed of immigrants with demographic, serological, and virological characteristics that differed from those of natives and appeared to have an inferior access to treatment

Positron emission tomography (PET) is a clinical and research tool for in vivo metabolic imaging. The demand for better image quality entails continuous research to improve PET instrumentation. In clinical applications, PET image quality benefits from the time of flight (TOF) feature. Indeed, by measuring the photons arrival time on the detectors with a resolution less than 100 ps, the annihilation point can be estimated with centimeter resolution. This leads to better noise level, contrast and clarity of detail in the images either using analytical or iterative reconstruction algorithms. This work discusses a silicon photomultiplier (SiPM)-based magnetic-field compatible TOF-PET module with depth of interaction (DOI) correction. The detector features a 3D architecture with two tiles of SiPMs coupled to a single LYSO scintillator on both its faces. The real-time front-end electronics is based on a current-mode ASIC where a low input impedance, fast current buffer allows achieving the required time resolution. A pipelined time to digital converter (TDC) measures and digitizes the arrival time and the energy of the events with a timestamp of 100 ps and 400 ps, respectively. An FPGA clusters the data and evaluates the DOI, with a simulated z resolution of the PET image of 1.4 mm FWHM.

Summary Introduction The identification of novel reverse-transcriptase (RT) drug-resistance mutations is critical in predicting the probability of success to anti-HBV treatment. Furthermore, due to HBV-RT/HBsAg gene-overlap, they can have an impact on HBsAg-detection and quantification. Methods 356 full-length HBV-RT sequences from 197 drug-naive patients and 159 patients experiencing virological-breakthrough to nucleoside/nucleotide-analogs (NUCs) were analyzed. Mutants and wild-type HBs-antigens were expressed in HuH7-hepatocytes and quantified in cell-supernatants and cell-lysates by Architect HBsAg-assay. Results Ten novel RT-mutations (rtN53T-rtS78T-rtS85F-rtS135T-rtA181I-rtA200V-rtK212Q-rtL229V/F-rtM309K) correlated with specific NUC-treatments and classical drug-resistance mutations on divergent evolutionary pathways. Some of them reduced RT-binding affinity for anti-HBV drugs and altered S-antigen structure. Indeed, rtS78T (prevalence: 1.1% in drug-naive and 12.2% in adefovir-failing patients) decreased the RT-affinity for adefovir more than the classical adefovir-resistance mutations rtA181 T/V (WT:−9.63 kcal/mol, rtA181T:−9.30 kcal/mol, rtA181V:−7.96 kcal/mol, rtS78T:−7.37 kcal/mol). Moreover, rtS78T introduced a stop-codon at HBsAg-position 69, and completely abrogated HBsAg-quantification in both supernatants and cell-lysates, indicating an impaired HBsAg-secretion/production. Furthermore, the HBsAg-mutation sP217L, silent in RT, significantly correlated with M204V/I-related virological-breakthrough and increased HBsAg-quantification in cell-lysate. Conclusions Mutations beyond those classically known can affect drug-binding affinity of mutated HBV-RT, and may have potential effects on HBsAg. Their cumulative effect on resistance and HBV-pathogenicity indicates the importance of preventing therapeutic failures.

Ion beam therapy is a valuable method for the treatment of deep-seated and radio-resistant tumors thanks to the favorable depth-dose distribution characterized by the Bragg peak. Hadrontherapy facilities take advantage of the specific ion range, resulting in a highly conformal dose in the target volume, while the dose in critical organs is reduced as compared to photon therapy. The necessity to monitor the delivery precision, i.e. the ion range, is unquestionable, thus different approaches have been investigated, such as the detection of prompt photons or annihilation photons of positron emitter nuclei created during the therapeutic treatment. Based on the measurement of the induced β+ activity, our group has developed various in-beam PET prototypes: the one under test is composed by two planar detector heads, each one consisting of four modules with a total active area of 10 × 10 cm2. A single detector module is made of a LYSO crystal matrix coupled to a position sensitive photomultiplier and is read-out by dedicated frontend electronics. A preliminary data taking was performed at the Italian National Centre for Oncological Hadron Therapy (CNAO, Pavia), using proton beams in the energy range of 93–112 MeV impinging on a plastic phantom. The measured activity profiles are presented and compared with the simulated ones based on the Monte Carlo FLUKA package.

The pixel identification capability is a common problem of detector systems consisting of scintillating matrices coupled to photodetectors. In positron emission tomography (PET) systems, a better pixel identification leads directly to an improvement of the spatial resolution of the system. To gain pixel identification efficiency especially at the peripheral active area, ultra-transmitting (UT) glasses can be inserted between the crystal and PMT array in order to promote light spread and avoid overlap of responses due to the enhanced light spread. Measurements with three different UT glass thicknesses ( d = 0.7 , 1.0 and 1.35 mm) have been performed in order to study their impact on pixel identification properties compared to direct coupling.

Some interesting features of laser ablation of fused silica at 308 nm wavelength are reported. In particular it is shown that the major ablation mechanism does not involve a phase transition of the irradiated target but leads to the emission of fragments instead of vapour. Only a few percent of the amount of ablated material is in the gaseous or plasma phase. We present the features (thickness, morphology, particle density, composition) of the film produced for different laser fluences and as a function of the angle subtended by the substrate and the normal to the target. Also we provide evidence that an electrical field does affect the spatial distribution of the emitted material.

Impulsivity and sensation seeking have been associated with substance use disorders, including opioid use disorders. This pilot study sought to examine whether impulsivity and sensation seeking, as measured by the Barratt Impulsiveness Scale (BIS) and Sensation Seeking Scale (SSS), were associated with opioid analgesic misuse risk in chronic, low-back pain patients prescribed opioid analgesics. Participants were 42 chronic, low-back pain patients enrolled in a larger study examining problematic opioid analgesic use. Impulsivity was assessed using the BIS, sensation seeking was measured using the SSS, and opioid analgesic misuse risk was assessed using the Current Opioid Misuse Measure (COMM). Significant bivariate associations were found between the COMM and the following predictor variables: age and the three BIS subscales: Attentional Impulsiveness, Non-planning Impulsiveness, and Motor Impulsiveness. Using a multivariate linear regression, after controlling for age, the BIS subscales accounted for 29.0% of the variance in the COMM. Attentional Impulsiveness was the only significant BIS subscale. These results suggest a potential relationship between impulsivity, but not sensation seeking, and risk for opioid analgesic misuse. Impulsivity is not a prominent trait observed in chronic pain patients; however, it may be an important risk factor for opioid analgesic misuse for a subset of individuals with chronic pain. As such, these findings suggest that additional exploration of this potential risk factor is warranted.

Silicon Photomultipliers are used in many new generation PET block detectors. High granularity pixel SiPMs allow a high precision measurement of the photon interaction coordinates along the crystal surface. In order to further improve the resolution it is necessary to measure the photon Depth of Interaction (DOl), so as to reduce the parallax error in the Line of Response reconstruction. An innovative technique for DOl determination is proposed and tested. Measurements are made with a 2 cm × 2 cm × 1 cm LYSO slab with readout on the front and back large sides by means of two 4 × 4 square SiPM pixel matrices of 5 mm pitch. The data acquisition is based on the new BASIC32 chip read out with an FPGA-based system.

The design of a Positron Emission Tomography detection module capable of working inside a Magnetic Resonant Imaging system is the main objective of the 4D-MPET project. Combining the two imaging technologies offers better soft tissue contrast and lower radiation doses by providing both functional and morphological information at the same time. The proposed detector will feature a three-dimensional architecture based on two tiles of Silicon Photomultipliers coupled to a single LYSO scintillator on both its faces. Silicon Photomultipliers are magnetic-field compatible photo-detectors with a very small size enabling novel detector geometries that allow the measurement of the Depth of Interaction as well as a high detector packing fraction to maximize system sensitivity. Furthermore they can be fabricated using standard silicon technology, have a large gain in the order of 106 and are very fast thus allowing evaluating the Time of Flight. Among the other features of the proposed detection system, the architecture of the innovative readout electronics will be also described which plays a relevant role for the achievement of the desired performance and is based on custom integrated circuits. Simulation results of the whole system show good performance in terms of time and spatial resolution: a timestamp of 100 ps is the ultimate performance achievable with the use of a double threshold technique along with fast electronics. Time over threshold is exploited to provide the energy information with a bin size of 400 ps. Moreover, a z resolution of 1.4 mm Full Width at Half Maximum can be achieved. The proposed detector can also be exploited in other tracking applications, such as High Energy Physics and Astrophysics.

Objectives: The reactor produced low-energy beta emitter Lu (T1⁄2 = 6.7 d) is used on a routine basis in the clinical targeted radiotherapy in nuclear oncology. Currently the radionuclide is commercially available in its c.a. and n.c.a form. Here an efficient use of Lu for radiolabeling can be limited by several factors such as quality of the radionuclide and the chemicals or suboptimal parameters of the radiolabeling reaction. Identification of critical factors as well as an interpretation of the results is, however, complicated and limited by the analytical techniques applied. Methods: C.a. and n.c.a. Lu preparations were obtained from different commercial suppliers. The radionuclide has been employed for the systematical preparation of Lu-DOTA-octreotate. Radiolabeling yields and achievable specific activity of the compound have been analyzed using conventional HPLC. For the characterization and better understanding of critical parameters of the process, species identification in the final product (e.g. radiolabeled compound) has been performed by means of LC-ESI-TOF. Isotope and specific activity analysis of the Lu of different origin have been additionally done by means of SF-ICP-MS. Results: We were able to obtain straightforward information about the radiolabeled compound and isotope such as structure, quality and even origin and isotopic composition of the radionuclide used for the reaction. LC-ESI-TOF allows an efficient identification of the different species in the final product such as unlabeled or contaminated precursors, giving worthwhile information about the quality and limiting parameters. N.c.a. Lu was confirmed to be superior for the preparation of radiolabeled compounds of high specific activity. Conclusions: For the first time we demonstrate that LCESI-TOF is a suitable tool for a direct species identification of Lu-radiolabeled peptides. Using a combination of different analytical approaches we could confirm that Lu is available with a high quality and can be used for an efficient preparation of therapeutic agents. Acknowledgements: We thank the team of Isotope and Elemental Analysis of Paul Scherrer Institute (Hot Laboratory Division/ Nuclear Energy and Safety Department) for the performance of SF-ICP-MS measurements.

We describe a case of an elderly man known for coronary artery disease (previous bypass surgery) hospitalized for ischemia in inferior wall. Since the operation, the patient underwent coronary angiographies. Due to the impossibility of selective engagement of left subclavian artery from femoral access, LIMA was always visualized through a right radial approach. Despite the suspicious of abnormal origin of left subclavian artery, aortic angiography was never performed. During the third angiography, the double aortic arch was coincidentally visualized by using a left Amplatz catheter. The diagnosis was confirmed by 64-slice computed tomography scan.

While childhood trauma appears to be a risk factor for the onset of depression and subclinical depressive symptomatology in Mexican Americans, the specific physiological mechanisms contributing to this relationship remain to be clarified. Stress-induced dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis is associated with depressive symptomatology in non-Hispanics. The current study assessed the extent to which the cortisol awakening response (CAR) predicts subclinical depressive symptomatology beyond the influence of childhood trauma in a sample of 55 Mexican American males and females ages 18–38 years, without a diagnosis of clinical depression. Participants were assessed for exposure to early trauma and current depressive symptomatology. Salivary cortisol samples were collected on two consecutive days at awakening, 30, 45, and 60 minutes thereafter, and again at 3pm, 6pm and 9pm. Data were analyzed using general linear models with repeated measures at four morning time points, and again, at three afternoon and evening time points. Results indicated a significant Symptoms × Time interaction for the CAR (p

Results Three out of four HBV patients with occult infection, showed reactivation phases of HBV viremia. Different mutations were observed, with differences between preand post-reactivation sera. HBV-DNA remained at low levels during the entire study period also in absence of specific anti-HBV therapy. The phylogenetic analysis showed that, for each patient with HBV reactivation, all the isolates were originated from a unique parental virus. Specific mutations of PreS/S, Core and X regions were observed. Discussion Mutations in the “a” determinant of the S protein could be responsible for the absence of HBsAg detection. The presence of stop codon in the pre-core region and of mutations in the X region could, in part, explain the reactivation of HBV viremia.