Differences in Discounting Behavior and Brain Responses for Food and Money Reward.

Most neuroeconomic research seeks to understand how value influences decision-making. The influence of reward type is less well understood. We used functional magnetic resonance imaging (fMRI) to investigate delay discounting of primary (i.e., food) and secondary rewards (i.e., money) in 28 healthy, normal-weighted participants (mean age = 26.77; 18 females). To decipher differences in discounting behavior between reward types, we compared how well-different option-based statistical models (exponential, hyperbolic discounting) and attribute-wise heuristic choice models (intertemporal choice heuristic, dual reasoning and implicit framework theory, trade-off model) captured the reward-specific discounting behavior. Contrary to our hypothesis of different strategies for different rewards, we observed comparable discounting behavior for money and food (i.e., exponential discounting). Higher k values for food discounting suggest that individuals decide more impulsive if confronted with food. The fMRI revealed that money discounting was associated with enhanced activity in the right dorsolateral prefrontal cortex, involved in executive control; the right dorsal striatum, associated with reward processing; and the left hippocampus, involved in memory encoding/retrieval. Food discounting, instead, was associated with higher activity in the left temporoparietal junction suggesting social reinforcement of food decisions. Although our findings do not confirm our hypothesis of different discounting strategies for different reward types, they are in line with the notion that reward types have a significant influence on impulsivity with primary rewards leading to more impulsive choices.

A European-Japanese study on peach allergy: IgE to Pru p 7 associates with severity.

BACKGROUND: Pru p 3 and Pru p 7 have been implicated as risk factors for severe peach allergy. This study aimed to establish sensitization patterns to five peach components across Europe and in Japan, to explore their relation to pollen and foods and to predict symptom severity. METHODS: In twelve European (EuroPrevall project) and one Japanese outpatient clinic, a standardized clinical evaluation was conducted in 1231 patients who reported symptoms to peach and/or were sensitized to peach. Specific IgE against Pru p 1, 2, 3, 4 and 7 and against Cup s 7 was measured in 474 of them. Univariable and multivariable Lasso regression was applied to identify combinations of parameters predicting severity. RESULTS: Sensitization to Pru p 3 dominated in Southern Europe but was also quite common in Northern and Central Europe. Sensitization to Pru p 7 was low and variable in the European centers but very dominant in Japan. Severity could be predicted by a model combining age of onset of peach allergy, probable mugwort, Parietaria pollen and latex allergy, and sensitization to Japanese cedar pollen, Pru p 4 and Pru p 7 which resulted in an AUC of 0.73 (95% CI 0.73-0.74). Pru p 3 tended to be a risk factor in South Europe only. CONCLUSIONS: Pru p 7 was confirmed as a significant risk factor for severe peach allergy in Europe and Japan. Combining outcomes from clinical and demographic background with serology resulted in a model that could better predict severity than CRD alone.

Thermogravimetric substrate analysis for prediction of biogas and methane yields.

Biodegradability of biomass constituents is the reason for the gap between theoretical biogas/methane yield and the maximum yield obtainable in bioconversion. The prediction of biogas/methane yields by applying thermal analysis is a relatively new development in this field. The aim of this study was to develop a bioconversion model based on thermogravimetry. Eleven substrates with a specific biogas yield within the range 104 to 572 mLN per gram of volatile solids were subjected to thermogravimetry and a multi linear regression model was developed to predict biogas and methane yields. The optimum parameters describe biogas and methane yields with a root mean square error of 58.8 and 34.3 mLN per gram of volatile solids respectively. The coefficient of determination for these two datasets was 0.81 and 0.84. A prediction technique based on thermogravimetric analysis appears to be a good alternative to other prediction models.

Cellular responses and microRNA profiling in bovine spermatozoa under heat shock.

In brief: Elevated temperatures disturbed sperm physiology. Bovine sperm cells exposed to heat shock led to diminished mitochondrial activity, fertilizing ability, increased oxidative stress and caspase activity concomitant with a delay in embryonic developmental kinetics and modulation of sperm-borne microRNAsmiRNAs. Abstract: Sperm function is susceptible to adverse environmental conditions. It has been demonstrated that in vivo and in vitro exposure of bovine sperm to elevated temperature reduces sperm motility and fertilizing potential. However, the cascade of functional, cellular, and molecular events triggered by elevated temperature in the mature sperm cell remains not fully understood. Therefore, the aim of this study was to determine the effect of heat shock on mature sperm cells. Frozen-thawed Holstein sperm were evaluated immediately after Percoll purification (0 h non-incubation control) or after incubation at 35, 38.5, and 41°C for 4 h. Heat shock reduced sperm motility after 3-4 h at 41°C while mitochondrial activity was reduced by 38.5 and 41°C when compared to the control. Heat shock also increased sperm reactive oxygen species production and caspase activity. Heat-shocked sperm had lower fertilizing ability, which led to diminished cleavage and blastocyst rates. Preimplantation embryo developmental kinetics was also slowed and reduced by sperm heat shock. The microRNA (miR) profiling identified >300 miRs in bovine sperm. Among these, three and seven miRs were exclusively identified in sperm cells exposed to 35 and 41°C, respectively. Moreover, miR-181d was enriched in sperm cells exposed to higher temperatures. Hence, elevated temperature altered the physiology of mature sperm cells by perturbing cellular processes and the miR profile, which collectively led to lower fertilizing ability and preimplantation development.

The Dynamic of PRAMEY Isoforms in Testis and Epididymis Suggests Their Involvement in Spermatozoa Maturation.

The preferentially expressed antigen in melanoma, Y-linked (PRAMEY) is a cancer/testis antigen expressed predominantly in bovine spermatogenic cells, playing an important role in germ cell formation. To better understand PRAMEY's function during spermatogenesis, we studied the dynamics of PRAMEY isoforms by Western blotting (WB) with PRAMEY-specific antibodies. The PRAMEY protein was assessed in the bovine testicular and epididymal spermatozoa, fluid and tissues, and as well as in ejaculated semen. The protein was further examined, at a subcellular level in sperm head and tail, as well as in the subcellular components, including the cytosol, nucleus, membrane, and mitochondria. RNA expression of PRAMEY was also evaluated in testis and epididymal tissues. Our WB results confirmed the previously reported four isoforms of PRAMEY (58, 30, 26, and 13 kDa) in the bovine testis and spermatozoa. We found that testicular spermatozoa expressed the 58 and 30 kDa isoforms. As spermatozoa migrated to the epididymis, they expressed two additional isoforms, 26 and 13 kDa. Similarly, the 58 and 30 kDa isoforms were detected only in the testis fluid, while all four isoforms were detected in fluid from the cauda epididymis. Tissue evaluation indicated a significantly higher expression of the 58 and 13 kDa isoforms in the cauda tissue when compared to both the testis and caput tissue (p < 0.05). These results indicated that testis samples (spermatozoa, fluid, and tissue) expressed predominantly the 58 and 30 kDa PRAMEY isoforms, suggesting their involvement in spermatogenesis. In contrast, the 26 kDa isoform was specific to epididymal sperm and the 13 kDa isoform was marked in samples derived from the cauda epididymis, suggesting their involvement in sperm maturation. Results from the sperm head and tail experiments indicated that the 13 kDa isoform increased 4-fold in sperm tails from caput to cauda, suggesting this isoform may have a significant role in tail function. Additionally, the 13 kDa isoform increased significantly (p < 0.05) in the cytosol during epididymal passage and tended to increase in other subcellular components. The expression of PRAMEY in the sperm subcellular components during epididymal maturation suggests the involvement of PRAMEY, especially the 13 kDa isoform, in sperm motility.

Is benzyl alcohol a significant contact sensitizer?

BACKGROUND: Benzyl alcohol is a widely used preservative, solvent and fragrance material. According to published data, it is a rare sensitizer in humans. OBJECTIVES: To identify characteristics and sensitization patterns of patients with positive patch test reactions to benzyl alcohol and to check the reliability of the patch test preparation benzyl alcohol 1% pet. PATIENTS AND METHODS: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2010-2019. RESULTS: Of 70 867 patients patch tested with benzyl alcohol 1% pet., 146 (0.21%) showed a positive reaction, most of them (89%) only weakly positive. The number of doubtful and irritant reactions significantly exceeded the number of positive reactions. Reproducibility of positive test reactions was low. Among benzyl alcohol-positive patients, compared to benzyl alcohol-negative patients, there were significantly more patients with leg dermatitis (17.8% vs. 8.6%), more patients aged 40 years or more (81.5% vs. 70.5%) and more patients who were tested because of a suspected intolerance reaction to topical medications (34.9% vs. 16.6%). Concomitant positive reactions were mainly seen to fragrances, preservatives and ointment bases. CONCLUSIONS: Sensitization to benzyl alcohol occurs very rarely, mainly in patients with stasis dermatitis. In view of our results, benzyl alcohol cannot be regarded as a significant contact allergen, and therefore marking it as skin sensitizer 1B and labelling it with H 317 is not helpful.

Water-driven microbial nitrogen transformations in biological soil crusts causing atmospheric nitrous acid and nitric oxide emissions.

Biological soil crusts (biocrusts) release the reactive nitrogen gases (Nr) nitrous acid (HONO) and nitric oxide (NO) into the atmosphere, but the underlying microbial process controls have not yet been resolved. In this study, we analyzed the activity of microbial consortia relevant in Nr emissions during desiccation using transcriptome and proteome profiling and fluorescence in situ hybridization. We observed that < 30 min after wetting, genes encoding for all relevant nitrogen (N) cycling processes were expressed. The most abundant transcriptionally active N-transforming microorganisms in the investigated biocrusts were affiliated with Rhodobacteraceae, Enterobacteriaceae, and Pseudomonadaceae within the Alpha- and Gammaproteobacteria. Upon desiccation, the nitrite (NO2-) content of the biocrusts increased significantly, which was not the case when microbial activity was inhibited. Our results confirm that NO2- is the key precursor for biocrust emissions of HONO and NO. This NO2- accumulation likely involves two processes related to the transition from oxygen-limited to oxic conditions in the course of desiccation: (i) a differential regulation of the expression of denitrification genes; and (ii) a physiological response of ammonia-oxidizing organisms to changing oxygen conditions. Thus, our findings suggest that the activity of N-cycling microorganisms determines the process rates and overall quantity of Nr emissions.

Raman spectroscopy reveals collagen and phospholipids as major components of hyalinosis in the arteriolosclerotic ulcer of Martorell.

BACKGROUND: Arteriolosclerotic ulcers of Martorell are histologically characterized by hyaline arteriolosclerosis resulting in concentric occlusion of the arteriolar lumina. Although several authors have previously reported on hyaline changes in hypertensive arteriolopathies, so far, little information is available on the molecular composition of hyaline wall depositions. OBJECTIVES: This study aimed at the molecular characterization of hyaline arteriolar deposits in patients with hypertensive arteriolopathy using confocal Raman spectroscopy. METHODS: Samples of patients diagnosed with arteriolosclerotic ulcers of Martorell were analysed using confocal Raman spectroscopy. The findings were correlated with histological analyses. Skin samples from healthy, non-hypertensive patients served as controls. RESULTS: Confocal Raman spectroscopy analysis revealed that subendothelial hyaline deposits in arteriolosclerotic ulcers are mainly composed of collagen and phospholipids, in particular phosphatidylcholine. The presence of collagen within hyaline deposits was confirmed by Masson's Trichrome and Picrosirius Red staining. Additionally, the presence of collagen could also be shown for hypertensive nephrosclerosis. Actin was markedly decreased in hyalinized compared to control vessels, corresponding to the loss of smooth muscle cells in the process of hyalinization. This was confirmed by immunofluorescence staining for α-smooth muscle actin and desmin. CONCLUSION: The present findings suggest that arteriolar hyaline deposits in hypertensive arteriolopathy are mainly composed of collagen and phospholipids, in particular phosphatidylcholine. Together with the concurrent absence of actin, these findings suggest that potentially critical disease mechanisms involve pressure-induced vascular smooth muscle cell apoptosis with subsequent deposition of collagen.

Autophagy is a pro-survival adaptive response to heat shock in bovine cumulus-oocyte complexes.

Autophagy is a physiological mechanism that can be activated under stress conditions. However, the role of autophagy during oocyte maturation has been poorly investigated. Therefore, this study characterized the role of autophagy on developmental competence and gene expression of bovine oocytes exposed to heat shock (HS). Cumulus-oocyte-complexes (COCs) were matured at Control (38.5 °C) and HS (41 °C) temperatures in the presence of 0 and 10 mM 3-methyladenine (3MA; autophagy inhibitor). Western blotting analysis revealed that HS increased autophagy marker LC3-II/LC3-I ratio in oocytes. However, there was no effect of temperature for oocytes matured with 3MA. On cumulus cells, 3MA reduced LC3-II/LC3-I ratio regardless of temperature. Inhibition of autophagy during IVM of heat-shocked oocytes (3MA-41 °C) reduced cleavage and blastocyst rates compared to standard in vitro matured heat-shocked oocytes (IVM-41 °C). Therefore, the magnitude of HS detrimental effects was greater in the presence of autophagy inhibitor. Oocyte maturation under 3MA-41 °C reduced mRNA abundance for genes related to energy metabolism (MTIF3), heat shock response (HSF1), and oocyte maturation (HAS2 and GREM1). In conclusion, autophagy is a stress response induced on heat shocked oocytes. Inhibition of autophagy modulated key functional processes rendering the oocyte more susceptible to the deleterious effects of heat shock.

Stereotactic Body Radiotherapy for Large Unresectable Hepatocellular Carcinomas - A Single Institution Phase II Study.

AIMS: To evaluate the safety and efficacy of liver stereotactic body radiotherapy (SBRT) in the treatment of unresectable hepatocellular carcinomas (HCC) measuring >5 cm. MATERIALS AND METHODS: Between November 2013 and February 2016, 13 patients with unresectable HCC (>5 cm), ineligible for other local treatments, with a Child-Pugh score (CPS) ≤ B7, were enrolled into a single-institution phase II study. SBRT was delivered by volumetric-modulated arc radiotherapy. Radiological response was reported using modified Response Evaluation Criteria in Solid Tumours criteria and toxicities graded by Common Terminology Criteria for Adverse Events v4 criteria. RESULTS: Sixteen hepatomas (median size 7.5 cm, range 5.1-9.7 cm) were treated in 13 patients. The baseline CPS was A5/6 in nine patients (69%) and B7 in four patients (31%). Five patients (38%) received previous liver-directed treatment. The median prescribed dose was 45 Gy (range 40-45 Gy) in five fractions. The median follow-up was 17.7 months. The 1-year local control rate was 92%. The median overall survival was 17.7 months and the 1-year overall survival was 62%. The median time to local progression was not reached. Five patients (39%) had an increase in CPS by two or more points at 3 months. Overall, there were 10 grade 3 acute toxicities occurring in seven patients, of which six were haematological. Quality of life remained clinically stable or improved at 3 months in 61.5% and 53.8% of patients based on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 Global Health Score and Functional Assessment of Cancer Therapy - Hepatobiliary version 4 score, respectively. CONCLUSIONS: In our cohort, SBRT to unresectable large HCC tumours provided excellent local control with acceptable toxicities. Regional recurrence remained the major cause of failure. Further studies are warranted to examine the role for SBRT in combination with other modalities to maximise disease control in the liver.

Ageing of Polymer Frictional Interfaces: The Role of Quantity and Quality of Contact.

When two objects are in contact, the force necessary for one to start sliding over the other is larger than the force necessary to keep the sliding motion going. This difference between static and dynamic friction is thought to result from a reduction in the area of real contact upon the onset of slip. Here, we resolve the structure in the area of contact on the molecular scale by means of environment-sensitive molecular rotors using (super-resolution) fluorescence microscopy and fluorescence lifetime imaging. We demonstrate that the macroscopic friction force is not only controlled by the area of real contact but also controlled by the "quality" of that area of real contact, which determines the friction per unit contact area. We show that the latter is affected by the local density of the contacting surfaces, a parameter that can be expected to change in time at any interface that involves glassy, amorphous materials.

Deletion of the mouse X-linked Prame gene causes germ cell reduction in spermatogenesis.

Preferentially expressed antigen in melanoma (PRAME) is cancer/testis antigen and a transcriptional repressor, inhibiting the signaling of retinoic acid through the retinoic acid receptor (RAR) for promoting cell proliferation and preventing cell apoptosis in cancer cells. The role of PRAME in testis and germline is unknown. We report here the generation and characterization of an X-linked Prame conditional knockout (cKO) mouse. Although fertile, the testis size (p < .01) and sperm count (p < .05) of the Prame cKO mice were significantly reduced by 12% at 4 months of age compared with the Prame floxed mice. Histological, immunofluorescence with germ cell-specific markers and terminal deoxynucleotidyl transferase dUTP nick end labeling analyses of testis cross-sections at postnatal day 7 (P7), P14, P21, P35, P120, and P365 indicated a significant increase in apoptotic germ cells at P7 and P14 and an increase in abnormal seminiferous tubules at P21 and P35. Germ cells were gradually lost resulting in two different phenotypes in the Prame cKO testes: Sertoli-cell-only for some of the affected tubules in young mice (at P35) and germ cell arrest at spermatogonia stage for other affected tubules in mature mice. Both phenotypes were a consequence of disruption in RAR signaling pathway by the depletion of Prame at a different time point during the first and subsequent rounds of spermatogenesis. The results suggest that Prame plays a minor, but important role in spermatogenesis and different paralogs in the Prame gene family may be functionally and partially redundant.

The frequency of photosensitizing drug dispensings in Austria and Germany: a correlation with their photosensitizing potential based on published literature.

BACKGROUND: Drug-induced photosensitivity refers to the development of cutaneous adverse events due to interaction between a pharmaceutical compound and sunlight. Although photosensitivity is a very commonly listed side-effect of systemic drugs, reliable data on its actual incidence are lacking so far. OBJECTIVES: A possible approach to evaluate the real-life extent of drug-induced photosensitivity would be an analysis of the frequency of exposure to a given photosensitizing drug combined with an indicator of its photosensitizing potential. This could serve as a basis for developing a pharmaceutical 'heatmap' of photosensitivity. METHODS: The present study investigated the number of reimbursed dispensed packages of potentially photosensitizing drugs in Germany (DE) and Austria (AT) between 2010 and 2017 based on nationwide health insurance-based databases. In addition, an indicator for the photosensitizing potential was established for each drug based on the number of reports on photosensitivity in the literature. RESULTS: This analysis includes means of 632 826 944 (+/-14 894 918) drug dispensings per year in DE and 113 270 754 (+/-1 964 690) in AT. Out of these, the mean percentage of drugs that enlist photosensitivity as a potential side-effect was 49.5% (±0.7) in DE and 48.2% (±1.2) in AT. When plotting the number of reimbursed dispensed packages vs. the number of reports on photosensitivity, two categories of drugs show high numbers for both parameters, that is diuretics and non-steroidal anti-inflammatory drugs (NSAIDs). CONCLUSIONS: Diuretics and NSAIDs appear to be responsible for the greatest part of exposure to photosensitizing drugs with potential implication on public health.

Serum levels of folate, 25-hydroxyvitamin D3 and cobalamin during UVB phototherapy: findings in a large prospective trial.

BACKGROUND: Narrowband UVB phototherapy (NB-UVB) is a mainstay in the treatment of numerous inflammatory dermatoses. Whereas, a wealth of studies has shown that NB-UVB treatment increases 25-hydroxyvitamin D3 (25(OH)D) levels, only sparse and controversial data exist on its effect on serum folate and cobalamin. OBJECTIVES: To determine whether exposure to NB-UVB alters serum folate or cobalamin levels. METHODS: A single-centre, prospective, open observational study on 101 patients subjected to NB-UVB phototherapy between late fall and early spring. Serum folate, 25(OH)D and cobalamin levels were measured after 0, 12, 24 and 36 NB-UVB exposures. RESULTS: After 12 NB-UVB exposures a significant decrease of mean serum folate (-1.0 nmol/L; P = 0.03) and cobalamin (-14.5 pmol/L, P = 0.03) levels was observed whereas serum levels of 25(OH)D showed a significant increase (35.4 nmol/L, P < 0.0001). CONCLUSIONS: A standard course of NB-UVB induces a small but significant decrease of serum folate and cobalamin levels.

Volumetry of Mesiotemporal Structures Reflects Serostatus in Patients with Limbic Encephalitis.

BACKGROUND AND PURPOSE: Limbic encephalitis is an autoimmune disease. A variety of autoantibodies have been associated with different subtypes of limbic encephalitis, whereas its MR imaging signature is uniformly characterized by mesiotemporal abnormalities across subtypes. Here, we hypothesized that patients with limbic encephalitis would show subtype-specific mesiotemporal structural correlates, which could be classified by supervised machine learning on an individual level. MATERIALS AND METHODS: T1WI MPRAGE scans from 46 patients with antibodies against glutamic acid decarboxylase and 34 patients with antibodies against the voltage-gated potassium channel complex (including 10 patients with leucine-rich glioma-inactivated 1 autoantibodies) and 48 healthy controls were retrospectively ascertained. Parcellation of the amygdala, hippocampus, and hippocampal subfields was performed using FreeSurfer. Volumes were extracted and compared between groups using unpaired, 2-tailed t tests. The volumes of hippocampal subfields were analyzed using a multivariate linear model and a binary decision tree classifier. RESULTS: Temporomesial volume alterations were most pronounced in an early stage and in the affected hemispheric side of patients. Statistical analysis revealed antibody-specific hippocampal fingerprints with a higher volume of CA1 in patients with glutamic acid decarboxylase-associated limbic encephalitis (P = .02), compared with controls, whereas CA1 did not differ from that in controls in patients with voltage-gated potassium channel complex autoantibodies. The classifier could successfully distinguish between patients with autoantibodies against leucine-rich glioma-inactivated 1 and glutamic acid decarboxylase with a specificity of 87% and a sensitivity of 80%. CONCLUSIONS: Our results suggest stage-, side- and antibody-specific structural correlates of limbic encephalitis; thus, they create a perspective toward an MR imaging-based diagnosis.

Technique for inferring angle change as a function of time for high-current electron beams using a dose-rate monitor array.

Intense electron beams striking a high-atomic number target produce high-output pulsed photon fluxes for flash x-ray experiments. Without an external guide field, such beams are subject to the dynamics of high-current electron beam propagation, including changes to electron trajectories either from self-fields or from development of beam instabilities. The bremsstrahlung output (dose-rate) scales approximately as IVx, where I is the beam current, V the electron energy, and x is in the range 2.0-2.65 and depends upon the electron angle on the converter. Using experimental beam data (dose-rate, I and V), this equation can be solved for x, a process known as "inverting the radiographer's equation." Inversion methods that rely on thermoluminescent dosimeters, which are time-integrated, yield no information about evolution of the electron beam angle in time. We propose here an inversion method that uses several dose-rate monitors at different angles with respect to the beam axis. By measuring dose-rates at different angles, one can infer the time-dependent beam voltage and angle. This method compares well with estimates of corrected voltage and results in a self-consistent picture of beam dynamics. Techniques are demonstrated using data from self-magnetic pinch experiments at the RITS-6 facility at Sandia National Laboratories.

Frictional weakening of slip interfaces.

When two objects are in contact, the force necessary to overcome friction is larger than the force necessary to keep sliding motion going. This difference between static and dynamic friction is usually attributed to the growth of the area of real contact between rough surfaces in time when the system is at rest. We directly measure the area of real contact and show that it actually increases during macroscopic slip, despite the fact that dynamic friction is smaller than static friction. This signals a decrease in the interfacial shear strength, the friction per unit contact area, which is due to a mechanical weakening of the asperities. This provides a novel explanation for stick-slip phenomena in, e.g., earthquakes.

Stereotactic Body Radiotherapy for Small Unresectable Hepatocellular Carcinomas.

AIMS: Stereotactic body radiotherapy (SBRT) is an option for the treatment of hepatocellular carcinoma (HCC) in patients ineligible for standard local therapies. This study reports on the safety and efficacy of SBRT in small HCC tumours (≤5 cm) in the province of British Columbia. MATERIALS AND METHODS: Between March 2011 and July 2015, 31 patients with Child-Pugh Class A or B, with small HCCs measuring ≤5 cm were treated with SBRT at our institution. Primary end points were local control, progression-free survival, overall survival and toxicity. RESULTS: Thirty-four hepatomas (median size 3.3 cm, range 1.3-5.0 cm) were treated. The median follow-up was 18.3 months. Twenty-six patients (84%) had received previous liver-directed treatments. Most patients (88%) were treated with 45 Gy in three or five fractions. Six patients (19%) had worsened Child-Pugh score by two or more points during follow-up; overall 32% of patients experienced ≥ grade 3 + toxicities. One-year local control and overall survival were 94 and 84%, respectively. One-year progression-free survival was 49%; 81% of patients with disease progression received further HCC therapy. On univariate analysis, small tumour size predicted for improved overall survival (P = 0.01) whereas prescription biological equivalent dose (BED10) ≥100Gy10 approached significance (P = 0.06). CONCLUSION: SBRT provides high local control to small inoperable HCC. SBRT can be delivered safely even after previous liver-directed therapies and further liver therapies can follow treatment with SBRT. Although overall 32% of patients experienced ≥ grade 3 + toxicities, and 19% had a deterioration in Child-Pugh score of two or more points, these changes were mainly transient with minimal clinical impact. Despite excellent local control, disease progression outside of the irradiated site remains prominent. Further studies are warranted to examine combined therapy approaches to maximise disease control.