Magnetic resonance imaging shows spinal curvature in Chinook salmon (Oncorhynchus tshawytscha) is associated with chronic inflammation of peri-vertebral soft tissues.

Chinook salmon (Oncorhynchus tshawytscha) farmed in New Zealand are known to develop abnormal spinal curvature late in seawater production. Its cause is presently unknown, but there is evidence to suggest a neuromuscular pathology. Using magnetic resonance imaging (MRI), we evaluated the relationship between soft tissue pathology and spinal curvature in farmed Chinook salmon. Regions of interest (ROIs) presenting as pathologic MRI signal hyper-intensity were identified from scans of 24 harvest-sized individuals: 13 with radiographically-detectable spinal curvature and 11 without. ROIs were excised from individuals using anatomical landmarks as reference points and histologically analysed. Pathologic MRI signal was observed more frequently in individuals with radiographic curvature (92%, n = 12) than those without (18%, n = 2), was localized to the peri-vertebral connective tissues and musculature, and presented as three forms: inflammation, fibrosis, or both. These pathologies are consistent with a chronic inflammatory process, such as that observed during recovery from a soft tissue injury, and suggest spinal curvature in farmed Chinook salmon may be associated with damage to and/or compromised integrity of the peri-vertebral soft tissues. Future research to ascertain the contributing factors is required.

Metabolic resilience of the Australasian snapper (Chrysophrys auratus) to marine heatwaves and hypoxia.

Marine organisms are under threat from a simultaneous combination of climate change stressors, including warming sea surface temperatures (SST), marine heatwave (MHW) episodes, and hypoxic events. This study sought to investigate the impacts of these stressors on the Australasian snapper (C. auratus) - a finfish species of high commercial and recreational importance, from the largest snapper fishery in Aotearoa New Zealand (SNA1). A MHW scenario was simulated from 21°C (current February SST average for north-eastern New Zealand) to a future predicted level of 25°C, with the whole-animal and mitochondrial metabolic performance of snapper in response to hypoxia and elevated temperature tested after 1-, 10-, and 30-days of thermal challenge. It was hypothesised that key indicators of snapper metabolic performance would decline after 1-day of MHW stress, but that partial recovery might arise as result of thermal plasticity after chronic (e.g., 30-day) exposures. In contrast to this hypothesis, snapper performance remained high throughout the MHW: 1) Aerobic metabolic scope increased after 1-day of 25°C exposure and remained high. 2) Hypoxia tolerance, measured as the critical O2 pressure and O2 pressure where loss of equilibrium occurred, declined after 1-day of warm-acclimation, but recovered quickly with no observable difference from the 21°C control following 30-days at 25°C. 3) The performance of snapper mitochondria was also maintained, with oxidative phosphorylation respiration and proton leak flux across the inner mitochondrial membrane of the heart remaining mostly unaffected. Collectively, the results suggest that heart mitochondria displayed resilience, or plasticity, in snapper chronically exposed to 25°C. Therefore, contrary to the notion of climate change having adverse metabolic effects, future temperatures approaching 25°C may be tolerated by C. auratus in Northern New Zealand. Even in conjunction with supplementary hypoxia, 25°C appears to represent a metabolically optimal temperature for this species.

Patient engagement with radiation therapists: Patient perspectives, challenges, and opportunities. A systematic review.

INTRODUCTION: Radiotherapy is a major component of cancer care and treatment is delivered almost exclusively by therapeutic radiographers/radiation therapists (RTTs). Numerous government and professional guidance publications have recommended a person-centred approach to healthcare through communication and collaboration between professionals, agencies, and users. With approximately half of patients undergoing radical radiotherapy experiencing some degree of anxiety and distress, RTTs are uniquely placed as frontline cancer professionals to engage with patients regarding their experience. This review seeks to map the available evidence of patient reported views of their experience of being treated by RTTs and any impact, this treatment had on the patient's frame of mind or perception of treatment. METHODS: In line with the principles of the Preferred Reporting Items for Systematic and Meta-Analyses (PRISMA) systematic review methodology, a review of relevant literature was conducted. Electronic databases MEDLINE, PROQUEST, EMBASE and CINAHL were searched. RESULTS: Nine hundred and eighty-eight articles were identified. Twelve papers were included in the final review. CONCLUSION: Increased time with, and continuity of RTTs during treatment has a positive influence on patients' perspectives of RTTs. A positive patient perspective of their engagement with RTTs can be a strong predictor of overall satisfaction in radiotherapy. IMPLICATIONS FOR PRACTICE: RTTs should not underestimate the impact of their supportive role in guiding patients through treatment. A standardised method for integrating patients' experience and engagement with RTTs is lacking. Further RTT led research is required in this area.

Patient-reported perspectives of therapeutic radiographers when undergoing radiotherapy: A European multi-centre study.

INTRODUCTION: Radiotherapy is delivered almost exclusively by therapeutic radiographers/radiation therapist (RTTs). Patient's perspectives of RTTs affect levels of trust and confidence in the profession and can have a significant impact on overall radiotherapy experience. The study reports patients' perspectives of RTTs from their experience of undergoing radiotherapy. Four partner sites collaborated in this research and included Malta, Poland, Portugal, and the UK (lead site). METHODS: A survey was developed to gather information from patients receiving radiotherapy or who had had radiotherapy within the previous 24 months. Participants ranked their responses to 23 statements relating to person-centred care on a 5-point scale of 1 (strongly disagree) to 5 (strongly agree). Mann-Whitney or Kruskal Wallis tests were applied to test differences in responses to 5 key statements for patient characteristics including gender, age group, diagnosis, country, time spent with RTTs and number of fractions remaining at survey completion. RESULTS: Three hundred and forty-seven surveys are included. Patients report a positive perception of RTTs (95.4% agree with 'I feel cared for'). Statistically significant differences in responses were found between gender, diagnosis, country, time spent with RTTs and fractions of radiotherapy remaining. Patients who had more time with RTTs and completed their surveys during radiotherapy had a more positive perception of RTTs. CONCLUSION: This study suggests that sufficient time with RTTs is key to ensuring a positive radiotherapy patient experience. RTTs being attentive, understanding, and informative are most predictive of a positive overall patient experience. Timing of survey completion can influence responses. IMPLICATIONS FOR PRACTICE: RTT education programmes should incorporate training on person-centred care at all levels. Further research into patient experience of RTTs is warranted.

Patients' perspectives of the skills and competencies of therapy radiographers/radiation therapists (TRs/RTTs) in the UK, Portugal and Malta; a qualitative study from the SAFE Europe project.

INTRODUCTION: The role of the Therapy Radiographer/Radiation Therapist (TR/RTT) is to provide radiotherapy to patients with a cancer diagnosis. This includes, not only administration of treatment, but also management of side-effects and provision of support/care. Despite this role being consistent throughout Europe, there is currently no standardisation of education for TRs/RTTs. The SAFE EUROPE project aims to standardize TR/RTT education to enable 'safe and free exchange' of TRs/RTTs across Europe. Consequently, this study aims to explore patients' perspectives regarding the current skills and competencies of TRs/RTTs. METHODS: From May 2021 to February 2022, semi-structured interviews were conducted with patients who had recently received radiotherapy in the UK, Malta and Portugal. Ethical approval for this study was granted by the NHS Research Ethics Committee with additional local approvals obtained. RESULTS: Forty-eight participants from the UK (n = 18), Portugal (n = 19), and Malta (n = 11) completed interviews. Participants described high satisfaction with TRs'/RTTs' competence and skills in all three countries. The main theme arising from the analysis was the importance of trust building with TRs/RTTs. Six factors were identified as influencing levels of trust: communication; side-effect management; team consistency; relational skills; patient dignity; and competence. A small number of patients reported feeling rushed and not having their physical and emotional needs met by TRs/RTTs. CONCLUSION: This multicentre study demonstrated that patients perceive TRs/RTTs in the UK, Malta and Portugal as highly competent and skilled. Practical recommendations are provided to address identified deficits in practice, which can be addressed through adaptation of TR/RTT education/training and clinical practice. IMPLICATIONS FOR PRACTICE: Recommendations arising from this study are important to ensure that TRs/RTTs have transferable skills that provide consistently high quality care to patients throughout Europe.

Closed-loop optogenetic control of the dynamics of neural activity in non-human primates.

Electrical neurostimulation is effective in the treatment of neurological disorders, but associated recording artefacts generally limit its applications to open-loop stimuli. Real-time and continuous closed-loop control of brain activity can, however, be achieved by pairing concurrent electrical recordings and optogenetics. Here we show that closed-loop optogenetic stimulation with excitatory opsins enables the precise manipulation of neural dynamics in brain slices from transgenic mice and in anaesthetized non-human primates. The approach generates oscillations in quiescent tissue, enhances or suppresses endogenous patterns in active tissue and modulates seizure-like bursts elicited by the convulsant 4-aminopyridine. A nonlinear model of the phase-dependent effects of optical stimulation reproduced the modulation of cycles of local-field potentials associated with seizure oscillations, as evidenced by the systematic changes in the variability and entropy of the phase-space trajectories of seizures, which correlated with changes in their duration and intensity. We also show that closed-loop optogenetic neurostimulation could be delivered using intracortical optrodes incorporating light-emitting diodes. Closed-loop optogenetic approaches may be translatable to therapeutic applications in humans.

The relationships between specific dynamic action, nutrient retention and feed conversion ratio in farmed freshwater Chinook salmon (Oncorhynchus tshawytscha).

Improving the feed conversion ratio (FCR; the amount of feed consumed relative to the amount of weight gain) can reduce both production costs and environmental impacts of farmed fish. The aim of this study was to investigate what drives FCR to understand how nutrients are retained, as well as the amount of oxygen consumed for digestion, absorption and assimilation (a metabolic process known as specific dynamic action, SDA). Feed-efficient and inefficient Chinook salmon (Oncorhynchus tshawytscha) in fresh water were identified using ballotini beads and X-radiography that tracked individual feed intake across three assessment periods under satiated feeding. This allowed a comparison of physiological traits and body composition between the two FCR phenotypes over two time points as Chinook salmon grew from 305 to 620 g. Fish with higher daily feed intake (DFI) had higher daily weight gain (DWG) as expected. Nonetheless, the relationship between FCR and DFI as well as FCR and DWG was variable between time points. FCR and DWG were not correlated at the first time point and were negatively correlated at the second time point. In contrast, FCR and DFI were positively correlated at the first time point but not the second. Despite this, efficient fish ate smaller meals and retained more protein, lipid and energy in their body tissues. There was no detectable difference in metabolism between the two FCR phenotypes with respect to minimal resting metabolic rate, maximum metabolic rate, aerobic scope, or SDA parameters. In conclusion, FCR is not consistently associated with growth and metabolic differences in freshwater Chinook salmon, but FCR-efficient fish retain more nutrients and consume smaller meals.

Short-term PM exposure and social stress cause pulmonary and cardiac dysfunction.

Ambient particulate matter (PM) exposure increases risk for cardiopulmonary health problems which may be exacerbated in a stressful environment. Co-exposure to PM and stress characterizes the experience of many deployed military personnel and first responders but has not been thoroughly investigated. This is especially relevant to military personnel who have been exposed to high PM levels in conjunction with stressful military conflict situations. To understand the mechanisms and time-course of the health consequences following burn pit exposure, we exposed mice to moderate levels of ambient PM less than 2.5 µM in diameter (PM2.5) alone or in combination with psychological stress. We found male mice exposed to PM2.5 alone or in combination with stress had significantly reduced pulmonary function when subjected to methacholine, indicating increased airway hyperreactivity. These mice experienced increased goblet cell hyperplasia in their lungs, with no change in alveolar density. Mice exposed to PM2.5 and/or stress also exhibited reduced cardiac contractility, right ventricular (RV) output, and changes in RV capillary density and cardiac inflammatory markers. Taken together, these data indicate that short-term exposure to PM2.5 with or without stress causes a clear reduction in pulmonary and cardiac function. We believe that this model is well-suited for the study of military and other occupational exposures, and future work will identify potential mechanisms, including the inflammatory progression of these co-exposures.

Predictive approaches to guide the expression of recombinant vaccine targets in Escherichia coli: a case study presentation utilising Absynth Biologics Ltd. proprietary Clostridium difficile vaccine antigens.

Bacterial expression systems remain a widely used host for recombinant protein production. However, overexpression of recombinant target proteins in bacterial systems such as Escherichia coli can result in poor solubility and the formation of insoluble aggregates. As a consequence, numerous strategies or alternative engineering approaches have been employed to increase recombinant protein production. In this case study, we present the strategies used to increase the recombinant production and solubility of 'difficult-to-express' bacterial antigens, termed Ant2 and Ant3, from Absynth Biologics Ltd.'s Clostridium difficile vaccine programme. Single recombinant antigens (Ant2 and Ant3) and fusion proteins (Ant2-3 and Ant3-2) formed insoluble aggregates (inclusion bodies) when overexpressed in bacterial cells. Further, proteolytic cleavage of Ant2-3 was observed. Optimisation of culture conditions and changes to the construct design to include N-terminal solubility tags did not improve antigen solubility. However, screening of different buffer/additives showed that the addition of 1-15 mM dithiothreitol alone decreased the formation of insoluble aggregates and improved the stability of both Ant2 and Ant3. Structural models were generated for Ant2 and Ant3, and solubility-based prediction tools were employed to determine the role of hydrophobicity and charge on protein production. The results showed that a large non-polar region (containing hydrophobic amino acids) was detected on the surface of Ant2 structures, whereas positively charged regions (containing lysine and arginine amino acids) were observed for Ant3, both of which were associated with poor protein solubility. We present a guide of strategies and predictive approaches that aim to guide the construct design, prior to expression studies, to define and engineer sequences/structures that could lead to increased expression and stability of single and potentially multi-domain (or fusion) antigens in bacterial expression systems.

A catalog of associations between rare coding variants and COVID-19 outcomes.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease-19 (COVID-19), a respiratory illness that can result in hospitalization or death. We investigated associations between rare genetic variants and seven COVID-19 outcomes in 543,213 individuals, including 8,248 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome-wide or when specifically focusing on (i) 14 interferon pathway genes in which rare deleterious variants have been reported in severe COVID-19 patients; (ii) 167 genes located in COVID-19 GWAS risk loci; or (iii) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, with results publicly browsable at https://rgc-covid19.regeneron.com.

Giant ankyrin-G regulates cardiac function.

Cardiovascular disease (CVD) remains the most common cause of adult morbidity and mortality in developed nations. As a result, predisposition for CVD is increasingly important to understand. Ankyrins are intracellular proteins required for the maintenance of membrane domains. Canonical ankyrin-G (AnkG) has been shown to be vital for normal cardiac function, specifically cardiac excitability, via targeting and regulation of the cardiac voltage-gated sodium channel. Noncanonical (giant) AnkG isoforms play a key role in neuronal membrane biogenesis and excitability, with evidence for human neurologic disease when aberrant. However, the role of giant AnkG in cardiovascular tissue has yet to be explored. Here, we identify giant AnkG in the myocardium and identify that it is enriched in 1-week-old mice. Using a new mouse model lacking giant AnkG expression in myocytes, we identify that young mice displayed a dilated cardiomyopathy phenotype with aberrant electrical conduction and enhanced arrhythmogenicity. Structural and electrical dysfunction occurred at 1 week of age, when giant AnkG was highly expressed and did not appreciably change in adulthood until advanced age. At a cellular level, loss of giant AnkG results in delayed and early afterdepolarizations. However, surprisingly, giant AnkG cKO myocytes display normal INa, but abnormal myocyte contractility, suggesting unique roles of the large isoform in the heart. Finally, transcript analysis provided evidence for unique pathways that may contribute to the structural and electrical findings shown in giant AnkG cKO animals. In summary, we identify a critical role for giant AnkG that adds to the diversity of ankyrin function in the heart.

Projecting Climate Dependent Coastal Flood Risk With a Hybrid Statistical Dynamical Model.

Numerical models for tides, storm surge, and wave runup have demonstrated ability to accurately define spatially varying flood surfaces. However these models are typically too computationally expensive to dynamically simulate the full parameter space of future oceanographic, atmospheric, and hydrologic conditions that will constructively compound in the nearshore to cause both extreme event and nuisance flooding during the 21st century. A surrogate modeling framework of waves, winds, and tides is developed in this study to efficiently predict spatially varying nearshore and estuarine water levels contingent on any combination of offshore forcing conditions. The surrogate models are coupled with a time-dependent stochastic climate emulator that provides efficient downscaling for hypothetical iterations of offshore conditions. Together, the hybrid statistical-dynamical framework can assess present day and future coastal flood risk, including the chronological characteristics of individual flood and wave-induced dune overtopping events and their changes into the future. The framework is demonstrated at Naval Base Coronado in San Diego, CA, utilizing the regional Coastal Storm Modeling System (CoSMoS; composed of Delft3D and XBeach) as the dynamic simulator and Gaussian process regression as the surrogate modeling tool. Validation of the framework uses both in-situ tide gauge observations within San Diego Bay, and a nearshore cross-shore array deployment of pressure sensors in the open beach surf zone. The framework reveals the relative influence of large-scale climate variability on future coastal flood resilience metrics relevant to the management of an open coast artificial berm, as well as the stochastic nature of future total water levels.

Use of the TELE-ASD-PEDS for Autism Evaluations in Response to COVID-19: Preliminary Outcomes and Clinician Acceptability.

The COVID-19 pandemic has caused unprecedented disruptions to healthcare, including direct impacts on service delivery related to autism spectrum disorder (ASD). Caregiver-mediated tele-assessment offers an opportunity to continue services while adhering to social distancing guidelines. The present study describes a model of tele-assessment for ASD in young children, implemented in direct response to disruptions in care caused by the COVID-19 pandemic. We present preliminary data on the outcomes and provider perceptions of tele-assessments, together with several lessons learned during the period of initial implementation.

Selection of resistance by antimicrobial coatings in the healthcare setting.

Antimicrobial touch surfaces have been introduced in healthcare settings with the aim of supporting existing hygiene procedures, and to help combat the increasing threat of antimicrobial resistance. However, concerns have been raised over the potential selection pressure exerted by such surfaces, which may drive the evolution and spread of antimicrobial resistance. This review highlights studies that indicate risks associated with resistance on antimicrobial surfaces by different processes, including evolution by de-novo mutation and horizontal gene transfer, and species sorting of inherently resistant bacteria dispersed on to antimicrobial surfaces. The review focuses on antimicrobial surfaces made of copper, silver and antimicrobial peptides because of the practical application of copper and silver, and the promising characteristics of antimicrobial peptides. The available data point to a potential for resistance selection and a subsequent increase in resistant strains via cross-resistance and co-resistance conferred by metal and antibiotic resistance traits. However, translational studies describing the development of resistance to antimicrobial touch surfaces in healthcare-related environments are rare, and will be needed to assess whether and how antimicrobial surfaces lead to resistance selection in these settings. Such studies will need to consider numerous variables, including the antimicrobial concentrations present in coatings, the occurrence of biofilms on surfaces, and the humidity relevant to dry-surface environments. On-site tests on the efficacy of antimicrobial coatings should routinely evaluate the risk of selection associated with their use.

Acute high temperature exposure impairs hypoxia tolerance in an intertidal fish.

Acute heat shock has previously been shown to improve subsequent low O2 (hypoxia) tolerance in an intertidal fish species, a process known as cross-tolerance, but it is not known whether this is a widespread phenomenon. This study examined whether a rock pool specialist, the triplefin fish Bellapiscis medius, exhibits heat shock induced cross-tolerance to hypoxia, i.e., longer time to loss of equilibrium (LOE) and lower critical O2 saturation (Scrit) after recovering from an acute heat challenge. Non-heat shock controls had a median time to loss of equilibrium (LOE50) of 54.4 min under severe hypoxia (7% of air saturation) and a Scrit of 15.8% air saturation. Contrary to expectations, however, treatments that received an 8 or 10°C heat shock showed a significantly shorter LOE50 in hypoxia (+8°C = 41.5 min; +10°C = 28.7 min) and no significant change in Scrit (+8°C = 17.0% air saturation; +10°C = 18.3% of air saturation). Thus, there was no evidence of heat shock induced cross-tolerance to hypoxia in B. medius because exposure to acute heat shock impaired hypoxia tolerance.

Differential Coping Strategies in Response to Salinity Challenge in Olive Flounder.

To examine how different fish coping strategies respond to salinity challenge, olive flounder (Paralichthys olivaceus) with active coping style (AC) and passive coping style (PC) were transferred from seawater (SW) to freshwater (FW) and their behavior and physiology were analyzed. Different behavioral coping strategies, in terms of escape and feeding tendencies, were confirmed in AC and PC fish without FW exposure. Differences in swimming distance between AC and PC flounder were then assessed after 1 and 2 days of FW transfer. Plasma parameters and branchial gene expression were also determined 2, 5, 8, and 14 days after transfer, with comparisons between AC and PC fish and against a SW-acclimated control group. The results showed that: (1) PC flounder exhibited a significant reduction in swimming activity, while AC flounder significantly increased locomotion 2 days after transfer. (2) The plasma osmolality and plasma ionic (Na+ and Cl-) concentration of FW-acclimated PC flounder declined in a continuous fashion over time but this contrasted against the plasma parameters of AC flounder which fluctuated below the baseline level of a SW-acclimated control group. (3) The expression of NKA-α1 and NHE-3-like mRNA in PC flounder gill increased significantly from 5 days, but the expression of these two genes in AC flounder only increased after 8 days of transfer. (4) There were no remarkable differences observed in Rhcg expressions between AC and PC flounder. This study indicates for the first time that PC flounder adopt a "freeze-passive tolerance" strategy while AC flounder adopt a "flight-active resistance" defense strategy in response to salinity challenge.

Intertidal triplefin fishes have a lower critical oxygen tension (Pcrit), higher maximal aerobic capacity, and higher tissue glycogen stores than their subtidal counterparts.

Decreased oxygen (O2) availability (hypoxia) is common in rock pools and challenges the aerobic metabolism of fishes living in these habitats. In this study, the critical O2 tension (Pcrit), a whole animal measure of the aerobic contribution to hypoxia tolerance, was compared between four New Zealand triplefin fishes including an intertidal specialist (Bellapiscis medius), an occasional intertidal inhabitant (Forsterygion lapillum) and two exclusively subtidal species (F. varium and F. malcolmi). The intertidal species had lower Pcrit values than the subtidal species indicating traits to meet resting O2 demands at lower O2 tensions. While resting O2 demand (standard metabolic rate; SMR) did not show a major difference between species, the intertidal species had higher maximal rates of O2 consumption ([Formula: see text]) and higher aerobic metabolic scope (MS). The high O2 extractive capacity of the intertidal species was associated with increased blood O2 carrying capacity (i.e., higher Hb concentration), in addition to higher mass-specific gill surface area and thinner gill secondary lamellae that collectively conveyed a higher capacity for O2 flux across the gills. The specialist intertidal species B. medius also had higher glycogen stores in both white muscle and brain tissues, suggesting a greater potential to generate ATP anaerobically and survive in rock pools with O2 tensions less than Pcrit. Overall, this study shows that the superior Pcrit of intertidal triplefin species is not linked to a minimisation of SMR, but is instead associated with an increased O2 extractive capacity of the cardiorespiratory system (i.e., [Formula: see text], MS, Hb and gill O2 flux).

The prevalence of major mental illness, substance misuse and homelessness in Irish prisoners: systematic review and meta-analyses.

AimsTo systematically review studies from Irish prisons that estimate the prevalence of major mental illness, alcohol and substance misuse, and homelessness at the time of committal. METHODS: Healthcare databases were searched for studies quantifying the point prevalence for each outcome of interest. Searches were augmented by scanning of bibliographies and searches of governmental and non-governmental websites. Proportional meta-analyses were completed for each outcome. RESULTS: We found eight, six and five studies quantifying the point prevalence of major mental illness, substance misuse, and homelessness respectively. Considerable heterogeneity was found for each subgroup (except psychosis where substantial heterogeneity was observed) and random effects models were used to calculate pooled percentages. The pooled percentage for psychotic disorder was 3.6% [95% confidence interval (CI) 3.0-4.2%], for affective disorder 4.3% (95% CI 2.1-7.1%), for alcohol use disorder 28.3% (95% CI 19.9-37.4%), for substance use disorder 50.9% (95% CI 37.6-64.2%) and for those who were homeless on committal 17.4% (95% CI 8.7-28.4%). CONCLUSIONS: Estimates for the prevalence of psychotic illness and substance abuse amongst Irish prisoners are in keeping with international estimates of morbidity in prisons, whilst those for affective disorders are lower. The prevalence of homelessness in committal to Irish prisons is higher than some international estimates. Rates for psychoses, alcohol and substance misuse as well as homelessness in Irish prisons are significantly higher than the general population prevalence of these vulnerabilities. A need for service development is discussed.

Observed high incidence of prostatic calculi with the potential to act as natural fiducials for prostate image guided radiotherapy.

PURPOSE: This study aims to quantify the incidence and distribution of prostatic calculi in a population of prostate radiotherapy patients and assess their potential role in prostate image guided radiotherapy (IGRT). METHODS & MATERIALS: A retrospective analysis of trans-rectal ultrasound (TRUS), computed tomography (CT) planning and treatment verification cone beam CT (CBCT) scans from radical prostate radiotherapy patients (external beam and brachytherapy) between 2012 and 2014 was undertaken by a single experienced observer. An internationally validated schema from the Prostate Imaging Reporting and Data system (PIRADS) was used to map the location of calculi. The association of calculi with patient and disease characteristics was explored. Data was analysed using SPSS (IBM version 22.0) using descriptive statistical methods and logistic binary regression analysis. RESULTS: 389 scan sets from 254 patients were included in the analysis. The overall incidence of calculi was 85% (n = 218) of which 79% (n = 201) were intra-prostatic calculi. The mean number of intra-prostatic calculi was 2 (range 1-10) and the mean size of calculi was 3.7 mm (range 0.5-15 mm). Calculi were most frequently observed in the posterior of the mid-gland (PI-RADs 3p, 9p) and posterior of the apex (PI-RADs 5p, 11p). 99% (n = 135) of CT planning scans with a corresponding CBCT had calculi in the same PIRADs location and all calculi were visible at the last fraction. There was no statistically significant association of calculi and N stage, M stage or Gleason score. CONCLUSIONS: A significant proportion of prostate radiotherapy patients have prostatic calculi detectable on pre radiotherapy imaging. Calculi observed on CT were also detectable on CBCT in 99% of cases and remain visible at the end of treatment. These findings add to the growing evidence base supporting the potential of calculi as an alternative to fiducial markers to aid prostate IGRT.