Predictors of self-harm and suicide in LGBT youth: The role of gender, socio-economic status, bullying and school experience.

BACKGROUND: Lesbian, gay and bisexual (LGB) young people's increased risk of self-harm, suicidal attempts and suicide compared with heterosexual youth is well established. The current study sought to examine whether these findings also apply to the trans (T) population and which factors act as additional risk or protective factors. METHODS: In a national cross-sectional survey, 3713 LGBT adolescents, aged 11-19 years, reported on their own history of self-harm, suicidal ideation and suicide attempts, as well as their experiences of school and homophobic, biphobic and transphobic bullying. Logistic regressions tested the association between risk and protective factors on self-harm, suicidal ideation and suicide attempts. RESULTS: A high proportion of the sample reported self-harm (65.3%), suicidal ideation (73.8%) and suicide attempts (25.7%). Demographic risk factors included identifying as female, non-binary or trans and being from a low-income background. Bullying and online bullying were associated with an increased risk for each outcome, and positive school experience was associated with a reduced risk for each outcome. CONCLUSIONS: Consistent with minority stress theory, the study found high rates of mental health problems within LGBT youth. Interventions focused on improving young people's experiences in schools appear useful targets to help improve mental health outcomes.

Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

BACKGROUND: Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study. METHODS: We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation. The primary end point was the best overall response rate (i.e., the percentage of patients who had a complete or partial response), as judged by an independent review committee. RESULTS: A total of 93 patients received an infusion and were included in the evaluation of efficacy. The median time from infusion to data cutoff was 14 months (range, 0.1 to 26). The best overall response rate was 52% (95% confidence interval, 41 to 62); 40% of the patients had complete responses, and 12% had partial responses. Response rates were consistent across prognostic subgroups. At 12 months after the initial response, the rate of relapse-free survival was estimated to be 65% (79% among patients with a complete response). The most common grade 3 or 4 adverse events of special interest included cytokine release syndrome (22%), neurologic events (12%), cytopenias lasting more than 28 days (32%), infections (20%), and febrile neutropenia (14%). Three patients died from disease progression within 30 days after infusion. No deaths were attributed to tisagenlecleucel, cytokine release syndrome, or cerebral edema. No differences between response groups in tumor expression of CD19 or immune checkpoint-related proteins were found. CONCLUSIONS: In this international study of CAR T-cell therapy in relapsed or refractory diffuse large B-cell lymphoma in adults, high rates of durable responses were produced with the use of tisagenlecleucel. (Funded by Novartis; JULIET ClinicalTrials.gov number, NCT02445248 .).

Development of a B-cell maturation antigen-specific T-cell antigen coupler receptor for multiple myeloma.

BACKGROUND AIMS: T cells engineered with synthetic receptors have delivered powerful therapeutic results for patients with relapsed/refractory hematologic malignancies. The authors have recently described the T-cell antigen coupler (TAC) receptor, which co-opts the endogenous T-cell receptor (TCR) and activates engineered T cells in an HLA-independent manner. Here the authors describe the evolution of a next-generation TAC receptor with a focus on developing a TAC-engineered T cell for multiple myeloma. METHODS: To optimize the TAC scaffold, the authors employed a bona fide antigen-binding domain derived from the B-cell maturation antigen-specific monoclonal antibody C11D5.3, which has been used successfully in the clinic. The authors first tested humanized versions of the UCHT1 domain, which is used by the TAC to co-opt the TCR. The authors further discovered that the signal peptide affected surface expression of the TAC receptor. Higher density of the TAC receptor enhanced target binding in vitro, which translated into higher levels of Lck at the immunological synapse and stronger proliferation when only receptor-ligand interactions were present. RESULTS: The authors observed that the humanized UCHT1 improved surface expression and in vivo efficacy. Using TAC T cells derived from both healthy donors and multiple myeloma patients, the authors determined that despite the influence of receptor density on early activation events and effector function, receptor density did not impact late effector functions in vitro, nor did the receptor density affect in vivo efficacy. CONCLUSIONS: The modifications to the TAC scaffold described herein represent an important step in the evolution of this technology, which tolerates a range of expression levels without impacting therapeutic efficacy.

Referral guidelines for medical imaging in children: an ESR-EuroSafe Imaging survey on availability, awareness and use in clinical practice among European radiologists.

OBJECTIVES: Justification of medical exposures from medical imaging is fundamental to radiation protection. Referral guidelines are intended to help physicians decide when an imaging study is justified. For two decades, referral guidelines have been a legally binding requirement for European Union member states. Recently, the European Society of Radiology (ESR) developed iGuide tool, which provides evidence-based referral guidance for imaging inclusive of children. The aim of this survey was to assess the availability, use and familiarity of referral guidelines for medical imaging in children and knowledge about the availability of ESR iGuide among ESR member radiologists. METHODS: Over a 2-month period (15 September-15 November 2019), 33,257 ESR member radiologists were invited to respond to an anonymised web-based questionnaire, which consisted of 12 multiple-choice questions. RESULTS: In total, 2067/33,257 responses (6.3%) were received from 52 countries. A total of 1068 out of 2067 (51.7%) respondents were aware that imaging referral guidelines are a legal requirement. One thousand five (48.6%) of all respondents did not know whether dedicated guidelines for imaging in children were available, and only 653 (31.2%) were aware of the mainstays of the available guidelines. Similarly, just 746 (36.1%) of all respondents were aware of ESR iGuide availability and features. CONCLUSIONS: The information gathered confirms that effective and widespread adoption of imaging referral guidelines is lacking, especially in children. Further work is required to improve uptake and awareness. KEY POINTS: • Justification of medical exposures is fundamental to radiation protection and evidence-based referral guidelines are crucial for practical implementation of this principle. • About half of survey respondents are aware that the availability of imaging referral guidelines is a legal requirement, despite this being mandated since 1997. • The information gathered from this survey confirms that, especially in children, an effective and widespread adoption of imaging referral guidelines is lacking.

CACNA1C risk variant is associated with increased amygdala volume.

Genome-wide association studies suggest that genetic variation within L-type calcium channel subunits confer risk to psychosis. The single nucleotide polymorphism at rs1006737 in CACNA1C has been associated with both schizophrenia and bipolar disorder and with several intermediate phenotypes that may serve as neurobiological antecedents, linking psychosis to genetic aetiology. Amongst others, it has been implicated in alterations in amygdala structure and function. In the present study, we show that the risk allele (A) is associated with increased amygdala volume in healthy individuals (n = 258). This observation reinforces a hypothesis that genetic variation may confer risk to psychosis via alterations in limbic structures. Further study of CACNA1C using intermediate phenotypes for psychosis will determine the mechanisms by which variation in this gene confers risk.

Characterization of antibiotic and disinfectant susceptibility profiles among Pseudomonas aeruginosa veterinary isolates recovered during 1994-2003.

AIMS: To evaluate susceptibility of Pseudomonas aeruginosa veterinary isolates to antibiotics and disinfectants. METHODS AND RESULTS: Pseudomonas aeruginosa isolates collected from dogs (n = 155) and other animals (n = 20) from sixteen states during 1994-2003 were tested for susceptibility. Most isolates were resistant to twenty-one antimicrobials tested, and the highest prevalence of resistance was to ß-lactams (93.8%) and sulphonamides (93.5%). Fluoroquinolone resistance did not increase from 1994 to 2003. Ciprofloxacin and enrofloxacin had a 5 and 16% prevalence of resistance, respectively, while sarafloxacin and nalidixic acid had a prevalence of resistance of 97 and 98%, respectively. Strains were pan-resistant to triclosan and chlorhexidine, were highly resistant to benzalkonium chloride and demonstrated high susceptibility to other disinfectants. Didecyldimethylammonium chloride was the most active ammonium chloride. Inducible resistance was observed to cetyl ammonium halides, chlorhexidine and benzyl ammonium chlorides, which formulate disinfectants used in veterinary clinics and dairies. Organic acid inhibition was associated with the dissociated acid species. CONCLUSIONS: Dissociated organic acids appear able to inhibit Ps. aeruginosa, and rates of fluoroquinolone resistance merit sustained companion animal isolate surveillance. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of Ps. aeruginosa susceptibility to 24 disinfectants and illustrates the high resistance of Ps. aeruginosa to both antibiotics and disinfectants.

Isolation and characterization of chitin-degrading micro-organisms from the faeces of Goeldi's monkey, Callimico goeldii.

AIMS: The objective of this study was the isolation and characterization of chitin-degrading micro-organisms from the faeces of the insectivorous Goeldi's monkey, Callimico goeldii. METHODS AND RESULTS: Faeces samples were screened for chitin-degrading bacteria using basal medium in which chitin was included as the carbon and energy source. Of fifteen bacterial isolates with chitin-degrading activity, fourteen were also capable of degrading cellulose. All isolates were either aerobes or facultative anaerobes. CONCLUSIONS: Phylogenetic analyses of those isolates exhibiting strongest activity, as determined by the most distinctive zones of clearing in chitin-supplemented medium, were identified as Cellulosimicrobium spp., Arthrobacter spp., Staphylococcus spp. and Enterobacteriaceae. SIGNIFICANCE AND IMPACT OF THE STUDY: This study reports on the isolation of chitin-degrading microflora from nonhuman primates. Considering that chitin and cellulose are the most abundant naturally occurring polymers, it is of interest to note that the majority of isolates are capable of digesting both substrates. This may be of significance given that omnivorous primates live in seasonal environments, where the availability of food items varies with the seasons. Furthermore, given the presence of a chitin-degrading microflora, this may have implications, in terms of the inclusion of fungi and/or insects in the diets of these animals in captivity, whether as part of medical research or conservation programmes.

Kids+ Parent Infant Program (PIP): a community model for supporting partnerships in early developmental follow-up and support.

High-risk infants are discharged home from hospital with increased care needs and the potential for the emergence of developmental disabilities, contributing to high levels of parental stress and anxiety. To enable optimal outcomes for high-risk infants and their families, developmental follow-up programs need to continue following hospital discharge. However, current follow-up care for high-risk infants is variable in terms of type, access and equity, and there seems to be a gap in existing services such as supporting the transition home, parental support, and inclusion of all at-risk infants regardless of causality. Routine follow-up that identifies developmental delays or neuromotor concerns can facilitate timely referral and access to targeted intervention during critical periods of development. The Kids+ Parent Infant Program (PIP) is a unique model of developmental follow-up that shares some characteristics with established programs, but also includes additional key elements for a seamless, wrap-around service for all high-risk infants and their families living in a regional area of Australia. This community-based program provides integrated assessment and intervention of infants, alongside parent support and education, embracing a holistic model that accounts for the complexity and interrelatedness of infant, parent, medical and developmental factors. By prioritising the well-being of high-risk infants and their families, the Kids+ PIP paves the way for improved developmental outcomes and provides an innovative model for developmental follow-up, with the potential for reproduction in other healthcare settings.

Impulsiveness and insula activation during reward anticipation are associated with genetic variants in GABRA2 in a family sample enriched for alcoholism.

Genetic factors, externalizing personality traits such as impulsivity, and brain processing of salient stimuli all can affect individual risk for alcoholism. One of very few confirmed genetic association findings differentiating alcoholics from non-alcoholics is with variants in the inhibitory γ-amino butyric acid α2 receptor subunit (GABRA2) gene. Here we report the association of two of these GABRA2 variants with measures of alcohol symptoms, impulsivity and with insula cortex activation during anticipation of reward or loss using functional magnetic resonance imaging (fMRI). In a sample of 173 families (449 subjects), 129 of whom had at least one member diagnosed with alcohol dependence or abuse, carriers for the G allele in two single-nucleotide polymorphisms (SNPs) and haplotypes were more likely to have alcohol dependence symptoms (rs279858, P=0.01; rs279826, P=0.05; haplotype, P=0.02) and higher NEO Personality Inventory-Revised (NEO-PI-R) Impulsiveness scores (rs279858, P=0.016; rs279826, P=0.012; haplotype, P=0.032) with a stronger effect in women (rs279858, P=0.011; rs279826, P=0.002; haplotype, P=0.006), all P-values are corrected for family history and age. A subset of offspring from these families (n=44, 20 females), genotyped for GABRA2, participated in an fMRI study using a monetary incentive delay task. Increased insula activation during reward (r(2)=0.4; P=0.026) and loss (r(2)=0.38; P=0.039) anticipation was correlated with NEO-PI-R Impulsiveness and further associated with the GG genotype for both SNPs (P's<0.04). Our results suggest that GABRA2 genetic variation is associated with Impulsiveness through variation of insula activity responses, here evidenced during anticipatory responses.

Stored blood transfusion induces transient pulmonary arterial hypertension without impairing coagulation in an ovine model of nontraumatic haemorrhage.

BACKGROUND AND OBJECTIVES: Transfusion of blood products in particular older products is associated with patient morbidity. Previously, we demonstrated a higher incidence of acute lung injury in lipopolysaccharide-treated sheep transfused with stored blood products. As transfusion following haemorrhage is more common, we aimed to determine whether a 'first hit' of isolated haemorrhage would precipitate similar detrimental effects following transfusion and also disrupt haemostasis. MATERIALS AND METHODS: Anaesthetized sheep had 33% of their total blood volume collected into Leukotrap bags (Pall Medical), which were processed into packed red blood cells and cross-matched for transfusion into other sheep. After 30 mins, the sheep were resuscitated with either: fresh (<5 days old) or stored (35-42 days old) ovine blood followed by 4% albumin to replacement volume, albumin alone or normal saline alone and monitored for 4 h. RESULTS: The first hit of haemorrhage precipitated substantial decreases in mean arterial pressure however haemostasis was preserved. Transfusion of stored ovine blood induced (1) transient pulmonary arterial hypertension but no oedema and (2) reduced fibrinogen levels more than fresh blood, but neither induced coagulopathy. Thus, transfusion of stored blood affected pulmonary function even in the absence of overt organ injury. CONCLUSION: The fact that stored blood transfusions: (1) did not induce acute lung injury in contrast to previous lipopolysaccharide-primed animal models identifies the 'first hit' as an important determinant of the severity of transfusion-mediated injury; (2) impaired pulmonary dynamics verifies the sensitivity and vulnerability of the pulmonary system to injury.

Isolation and characterization of soilborne virulent bacteriophages infecting the pathogen Rhodococcus equi.

AIMS: To isolate and characterize a diversity of bacteriophages (phages) that infect the soilborne pathogen Rhodococcus equi. METHODS AND RESULTS: Twenty-seven phages were isolated from soil samples from geographically distinct locations using a range of R. equi bacterial strains, including clinical isolates. On the basis of host range, genomic DNA restriction profiles and virion protein profiles, the diversity of these phages was extensive, with phages being divided into 16 groupings. CONCLUSIONS: Based on a range of criteria, these phages could be divided into 16 distinct groupings. The majority of the phages recovered from soil were Siphoviridae, adding to the limited number of Siphoviridae described to date for R. equi. One grouping consisted of phages belonging to the Myoviridae. SIGNIFICANCE AND IMPACT OF THE STUDY: This represents the first study looking at the diversity of phages infecting the pathogen R. equi, including the first Myoviridae to be isolated and characterized for the genus Rhodococcus and for the nonmycobacterial actinomycetes. Given their diverse host range, including clinical isolates, this collection of phages offers the potential for the development of phage cocktails for use as a therapeutic or alternatively in the biocontrol of this pathogen in reservoirs of infection relating to animal husbandry.

Distinct and overlapping functions of allelic forms of human mannose binding protein.

Human mannose binding protein (MBP) is a C-type serum lectin involved in first-line host defense against a variety of bacterial, fungal and viral pathogens. Recently an association was found between low levels of serum MBP and an increased frequency of recurrent infections in infants. A particular genotype, in which glycine is substituted by aspartic acid at codon 54 of MBP in the fifth collagen repeat, shows apparent concordance with the clinical phenotype. We report, however, that this genotype occurs in 5% of the population and encodes a functional protein. Our results indicate that the Gly54Asp allele does not account for a deficiency state, but instead suggest that MBP may have two predominant allelic forms that have overlapping function and differ only in their ability to activate the classical pathway of complement.

Investigating CT head diagnostic reference levels based on indication-based protocols - a single site study.

INTRODUCTION: This study aimed to provide clinically-relevant insights into establishing CT DRLs based on indication-based protocols in Ireland, focusing on CT head examinations performed at a neurology centre of excellence hospital. METHODS: Dose data were collected retrospectively. Typical values for six CT head indication-based protocols were established using a sample size of 50 patients for each protocol. Typical values for each protocol were set as the median of the distribution curve. Dose distributions for each protocol were calculated and compared using non-parametric median test (k-samples) to ascertain significant dose differences between the typical values. RESULTS: Most typical values pairings showed significant differences (p < 0.001) except between stroke/non-vascular brain, stroke/acute brain, and acute brain/non-vascular brain pairings. This was expected due to similar scan parameters. The typical value for stroke (3-phases angiogram) was 52% lower than the typical value for stroke. Dose levels of the male populations recorded were higher than female populations for all protocols. Statistical comparison showed significant differences for dose quantities and/or scan length between both genders in five protocols. CONCLUSION: Proposed values for DLP were up to 63% and 69% lower than the EU and Irish national DRLs respectively. Establishment of CT stroke DRLs should be based on the scan performed instead of number of scan acquisitions. Lastly, gender-based CT DRLs for specific protocols within the head region require further investigation. IMPLICATIONS FOR PRACTICE: With increasing CT examinations worldwide, radiation dose optimisation is key. The value of indication based DRLs is to enhance the required patient protection so image quality can be maintained, however with relevant DRLs for varying protocols. Establishment of CT typical values and site specific DRLs for procedures beyond the national DRLs can drive dose optimisation locally.

Low-cost 3D-printed anthropomorphic cardiac phantom, for computed tomography automatic left ventricle segmentation and volumetry - A pilot study.

INTRODUCTION: Accurate cardiac left ventricle (LV) delineation is essential to CT-derived left ventricular ejection fraction (LVEF). To evaluate dose-reduction potential, an anatomically accurate heart phantom, with realistic X-ray attenuation is required. We demonstrated and tested a custom-made phantom using 3D-printing, and examined the influence of image noise on automatically measured LV volumes METHODS: A single coronary CT angiography (CCTA) dataset was segmented and converted to Standard Tessellation Language (STL) mesh, using open-source software. A 3D-printed model, with hollow left heart chambers, was printed and cavities filled with gelatinized contrast media. This was CT-scanned in an anthropomorphic chest phantom, at different exposure conditions. LV and "myocardium" noise and attenuation was measured. LV volume was automatically measured using two different methods. We calculated Spearmans' correlation of LV volume with noise and contrast-noise ratio respectively om 486 scans of the phantom. Source images were compared to one phantom series with similar parameters. This was done using Dice coefficient on LV short-axis segmentations. RESULTS: Phantom "Myocardium" and LV attenuation was comparable to measurements on source images. Automatic volume measurement succeeded, with mean volume deviation to patient images less than 2 ml. There was a moderate correlation of volume with CNR, and strong correlation of volume with image noise. With papillary muscles included in LV volume, the correlation was positive, but negative when excluded. Variation of volumes was lowest at 90-100 kVp for both methods in the 486 repeat scans. The Dice coefficient was 0.87, indicating high overlap between the single phantom series and source scan. Cost of 3D-printer and materials was 400 and 30 Euro respectively. CONCLUSION: Both anatomically and radiologically the phantom mimicked the source scans closely. LV volumetry was reliably performed with automatic algorithms. IMPLICATIONS FOR PRACTICE: Patient-specific cardiac phantoms may be produced at minimal cost and can potentially be used for other anatomies and pathologies. This enables radiographic phantom studies without need for dedicated 3D-labs or expensive commercial phantoms.

Excess body fat is associated with higher risk of vertebral deformities in older women but not in men: a cross-sectional study.

UNLABELLED: Thinness is a risk factor for fractures, but the effect of obesity on fracture risk is less clear. We found an association between measures of obesity and prevalence and number of vertebral deformities in women but not in men, in a cross-sectional study of 1,011 participants aged 50-80 years. INTRODUCTION: Low body weight is well recognised as a risk factor for fractures, but the association between overweight and fracture risk is less well described. This cross-sectional study describes the association between measures of obesity and vertebral deformities in 1,011 male and female participants in the Tasmanian Older Adult Cohort study. METHODS: Vertebral deformities (anterior wedging) of T4-L4 were determined by morphometric dual-emission X-ray absorptiometry. Body fat was assessed as weight, body mass index (BMI), waist-hip ratio (WHR), waist circumference and DXA measures of trunk fat (in percent) and total fat mass. RESULTS: The mean age of participants was 63 ± 7 years, and mean BMI was 28 ± 5. Prevalent thoracic vertebral deformities were associated with increasing weight [standardised ß (Sß) 0.29, p = 0.003], BMI (Sß 0.33, p < 0.001), trunk fat (Sß 0.20, p = 0.03), waist circumference (Sß 0.19, p = 0.03) and fat mass (Sß 0.23, p = 0.03), but not the WHR in women, and only with decreasing total fat mass in men. In addition, the number of vertebral deformities increased as weight, BMI or fat mass increased in women (all p < 0.05) but decreased with increasing total fat mass in men. Associations between fat mass and vertebral deformities were mainly linear, but there was some evidence of a threshold effect in women with a BMI ≥ 35. CONCLUSIONS: There is a deleterious association between increasing amounts of body fat in women but not in men and the prevalence and number of vertebral deformities, which may reflect loading of the thoracic spine.

Characterization of antimicrobial resistance of Pseudomonas aeruginosa isolated from canine infections.

AIMS: To determine the prevalence of Pseudomonas aeruginosa among dogs with suspected soft tissue infections and to characterize these isolates. METHODS AND RESULTS: Swabs were taken from infected soft tissues of 402 dogs. Pseudomonas aeruginosa strains were confirmed phenotypically and tested for susceptibility to 11 antimicrobial agents and genotyped by SpeI pulsed-field gel electrophoresis (PFGE). The genetic basis of fluoroquinolone (FQ) resistance and the presence of integrons were also characterized. A total of 27 (6·7%) dogs tested positive for Ps. aeruginosa. Fourteen different SpeI patterns were observed in 25 typeable strains. Among the ß-lactams, three isolates presented resistance to ticarcillin and carbenicillin, while only one isolate exhibited resistance to ceftazidime. Among the aminoglycosides (AGs), three strains showed resistance to amikacin, and four strains exhibited resistance to gentamicin and tobramycin. Four strains with mutations that led to the substitution of Thr at position 83 with Ile in GyrA and the exchange of Ser at position 87 with Leu in ParC displayed resistance to all tested FQs. These strains also carried class 1 integrons and showed resistance to between 6 and 10 antimicrobials. These integrons included four different gene cassettes (aacA4-aadA1, bla(OXA-31) -aadA2, aadA1-arr-3-catB3 and cmlA5-cmlA-aadA1). CONCLUSIONS: A small proportion of infected dogs treated in two animal hospitals in Beijing, China carried Ps. aeruginosa isolates. Low levels of resistance to anti-pseudomonal agents were observed in these strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first report on the antimicrobial resistance profiles of Ps. aeruginosa isolated from infected canine origin in China. Additionally, this is the first report of the oxacillin resistance gene bla(OXA-31) in a canine Ps. aeruginosa isolate.

Large differences in education and training of radiographers in Europe and Central Asia: Results from an IAEA coordinated study.

INTRODUCTION: Education and training of radiographers is known to be diverse between countries and regions. Under an IAEA project, this work collected data on radiographer education for the Europe and Central Asia region with a particular focus on radiation protection gaps and potential actions. METHODS: Following piloting, an electronic questionnaire was distributed to all national counterparts for the IAEA Technial Coopearation (TC) Europe region (n = 33 countries) and nominated national representatives. Contacts were additionally invited to a virtual workshop to discuss and rank common problems in education and training of radiographers and to propose potential solutions. RESULTS: Responses were received from 31 countries, including 14 from the European Union. Just over half of countries reported radiographer education being in higher education with 71% having program durations more than 3 years (range: 1 month-4 years). Programs included a spectrum of both clinical training and radiation protection hours with ten-fold variations noted across the region. Inclusion of core radiation protection topics within curricula varied similarly, as did radiographers' clinical involvement in both justification and optimisation between countries. Workshop participants identified five common training problems, namely education availability, lack of standardisation, radiation protection course quality, teamwork problems and lack of equipment. CONCLUSION: Radiographer education in the IAEA Europe region is heterogeneous with substantial differences in duration and quality of training programs between countries, which likely impact on quality of patient care delivered. Common problems have been identified and potential solutions proposed to focus quality improvement initiatives. IMPLICATIONS FOR PRACTICE: Radiographer education and training is diverse throughout the IAEA TC Europe region, with likely impacts on radiation protection practices applied. Clinical involvement of radiographers in justification and optimisation differs, potentially limiting adherence to radiation protection principles.

Design of a 3D printed coronary artery model for CT optimization.

INTRODUCTION: To design a custom phantom of the coronary arteries to optimize CT coronary angiography (CCTA) protocols. METHODS: Characteristics of the left and right coronary arteries (mean Hounsfield Unit (HU) values and diameters) were collected from consecutive CCTA examinations (n = 43). Four different materials (two mixtures of glycerine, gelatine and water, pig hearts, Ecoflex™ silicone) were scanned inside a Lungman phantom using the CCTA protocol to find the closest model to in vivo data. A 3D printed model of the coronary artery tree was created using CCTA data by exporting a CT volume rendering into Autodesk Meshmixer™ software. The model was placed in an acid bath for 5 h, then covered in Ecoflex™, which was removed after drying. Both the Ecoflex™ and pig heart were later filled with a mixture of contrast (Visipaque 320 mg I/ml), NaCl and gelatin and scanned with different levels of tube current and iterative reconstruction (ASiR-V). Objective (HU, noise and size (vessel diameter) and subjective analysis were performed on all scans. RESULTS: The gelatine mixtures had HU values of 130 and 129, Ecoflex™ 65 and the pig heart 56. At the different mA/ASiR-V levels the contrast filled Ecoflex™ had a mean HU 318 ± 4, noise 47±7HU and diameter of 4.4 mm. The pig heart had a mean HU of 209 ± 5, noise 38±4HU and a diameter of 4.4 mm. With increasing iterative reconstruction level the visualisation of the pig heart arteries decreased so no measurements could be performed. CONCLUSION: The use of a 3D printed model of the arteries and casting with the Ecoflex™ silicone is the most suitable solution for a custom-designed phantom. IMPLICATIONS FOR PRACTICE: Custom designed phantoms using 3D printing technology enable cost effective optimisation of CT protocols.

THE EFFECTS OF CONE-BEAM COMPUTED TOMOGRAPHY IMAGING GUIDANCE ON PATIENT RADIATION EXPOSURES IN TRANS-ARTERIAL CHEMOEMBOLISATION FOR HEPATOCELLULAR CARCINOMA.

This study investigated the effects of cone-beam computed tomography (CBCT) guidance in trans-arterial chemoembolisation (TACE) procedures on the number of digital subtraction angiography (DSA) runs acquired and total patient radiation exposure in patients with hepatocellular carcinoma (HCC). A retrospective, analytical cross-sectional, single institution, study was conducted. Dose data were compared across the control (DSA guidance alone) and study (DSA and CBCT guidance) groups. A total of 122 procedures were included within the study. There was a significant reduction in the number of DSA runs (3 vs 5, p < 0.001) and DSA air kerma-area product (PKA) (3077.3 vs 4276.6 µGym2, p = 0.042) for the study group when compared to the control group. Total procedural PKA and total procedural reference air kerma (Ka,r) were shown to be 50 and 73% higher, respectively, for the study group when compared to the control group. CBCT imaging guidance does reduce the number of DSA runs and DSA PKA required to complete the TACE procedure for patients diagnosed with HCC; however, a substantial increase in total procedural PKA is to be expected and it is thus important that this increased dose is carefully considered and justified.

Autologous, lentivirus-modified, T-rapa cell "micropharmacies" for lysosomal storage disorders.

T cells are the current choice for many cell therapy applications. They are relatively easy to access, expand in culture, and genetically modify. Rapamycin-conditioning ex vivo reprograms T cells, increasing their memory properties and capacity for survival, while reducing inflammatory potential and the amount of preparative conditioning required for engraftment. Rapamycin-conditioned T cells have been tested in patients and deemed to be safe to administer in numerous settings, with reduced occurrence of infusion-related adverse events. We demonstrate that ex vivo lentivirus-modified, rapamycin-conditioned CD4+ T cells can also act as next-generation cellular delivery vehicles-that is, "micropharmacies"-to disseminate corrective enzymes for multiple lysosomal storage disorders. We evaluated the therapeutic potential of this treatment platform for Fabry, Gaucher, Farber, and Pompe diseases in vitro and in vivo. For example, such micropharmacies expressing α-galactosidase A for treatment of Fabry disease were transplanted in mice where they provided functional enzyme in key affected tissues such as kidney and heart, facilitating clearance of pathogenic substrate after a single administration.