Exploring management and outcomes of elderly patients with glioblastoma using data from two randomised trials (GEINO1401/EX-TEM).

PURPOSE: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. METHODS: Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. RESULTS: Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0-1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months. CONCLUSION: In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.

Risk characterization of N-nitrosodimethylamine in pharmaceuticals.

Since 2018, N-nitrosodimethylamine (NDMA) has been a reported contaminant in numerous pharmaceutical products. To guide the pharmaceutical industry, FDA identified an acceptable intake (AI) of 96 ng/day NDMA. The approach assumed a linear extrapolation from the Carcinogenic Potency Database (CPDB) harmonic-mean TD50 identified in chronic studies in rats. Although NDMA has been thought to act as a mutagenic carcinogen in experimental animals, it has not been classified as a known human carcinogen by any regulatory agency. Humans are exposed to high daily exogenous and endogenous doses of NDMA. Due to the likelihood of a threshold dose for NDMA-related tumors in animals, we believe that there is ample scientific basis to utilize the threshold-based benchmark dose or point-of-departure (POD) approach when estimating a Permissible Daily Exposure limit (PDE) for NDMA. We estimated that 29,000 ng/kg/day was an appropriate POD for calculating a PDE. Assuming an average bodyweight of 50 kg, we expect that human exposures to NDMA at doses below 5800 ng/day in pharmaceuticals would not result in an increased risk of liver cancer, and that there is little, if any, risk for any other type of cancer, when accounting for the mode-of-action in humans.

Can a mock medication-taking learning activity enable pharmacy students to experience the range of barriers and facilitators to medication adherence? An analysis informed by the Theoretical Domains Framework and COM-B model.

Background: Pharmacy professionals are well-placed to provide medication adherence support to patients. The Capability, Opportunity, Motivation-Behaviour (COM-B) and Theoretical Domains Framework (TDF) are two complementary models previously applied to medication-taking behaviour. Understanding the patient-specific barriers and facilitators to adherence using psychological frameworks from the early stages of pharmacy education enables the design and delivery of effective interventions. Objectives: To examine whether a novel 'mock medicine' learning activity enabled students to experience the range of barriers and facilitators to medication adherence using the COM-B and TDF. Methods: A mock medicine activity was conducted with students at pharmacy schools in three universities in the UK, Norway, and Australia over one week. Percentage adherence was calculated for five dosing regimens; theoretical framework analysis was applied to map reflective statements from student logs to COM-B and TDF. Results: A total of 349 students (52.6%) returned completed logs, with high overall mean adherence (83.5%, range 0-100%). Analysis of the 277 (79.4%) students who provided reflective statements included barriers and facilitators that mapped onto one (9%), two (29%) or all three (62%) of the COM-B components and all fourteen TDF domains (overall mean = 4.04; Uni 1 = 3.72; Uni 2 = 4.50; Uni 3 = 4.38; range 1-8). Most frequently mapped domains were 'Environmental context and resources' (n = 199; 72%), 'Skills' (n = 186; 67%), 'Memory, attention and decision-making' (184; 66%) and 'Beliefs about capabilities' (n = 175; 63%). Conclusions: This is the first study to utilise both COM-B and TDF to analyse a proxy measure of medication adherence in pharmacy education. Data mapping demonstrated that students experienced similar issues to patients when prescribed a short course of medication. Importantly, all the factors influencing medication-taking reported by students were captured by these two psychological frameworks. Future educational strategies will involve students in the mapping exercise to gain hands-on experience of using these psychological constructs in practice.

Hitting the Target: Developing High-quality Evidence for Proton Beam Therapy Through Randomised Controlled Trials.

The National Health Service strategy for the delivery of proton beam therapy (PBT) in the UK provides a unique opportunity to deliver high-quality evidence for PBT through randomised controlled trials (RCTs). We present a summary of three UK PBT RCTs in progress, including consideration of their key design characteristics and outcome assessments, to inform and support future PBT trial development. The first three UK multicentre phase III PBT RCTs (TORPEdO, PARABLE and APPROACH), will compare PBT with photon radiotherapy for oropharyngeal squamous cell carcinoma, breast cancer and oligodendroglioma, respectively. All three studies were designed by multidisciplinary teams, which combined expertise from clinicians, clinical trialists and scientists with strong patient advocacy and guidance from national radiotherapy research networks and international collaborators. Consistent across all three studies is a focus on the reduction of long-term radiotherapy-related toxicities and an evaluation of patient-reported outcomes and health-related quality of life, which will address key uncertainties regarding the clinical benefits of PBT. Innovative translational components will provide insights into mechanisms of toxicity and help to frame the key future research questions regarding PBT. The UK radiotherapy research community is developing and delivering an internationally impactful PBT research portfolio. The combination of data from RCTs with prospectively collected data from a national PBT outcomes registry will provide an innovative, high-quality repository for PBT research and the platform to design and deliver future trials of PBT.

A Repurposing Programme Evaluating Transdermal Oestradiol Patches for the Treatment of Prostate Cancer Within the PATCH and STAMPEDE Trials: Current Results and Adapting Trial Design.

AIMS: Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer. MATERIALS AND METHODS: The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately. RESULTS: Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of -3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3-13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80-1.53; P = 0.54). Oncological outcomes are awaited. FUTURE: Efficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure - overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway.

Enzootic calcinosis in Toggenburg goats in New Zealand.

CASE HISTORY: Necropsies on Toggenburg goats culled from a small farm in the Manawatu district of New Zealand, performed at Massey University (Palmerston North, NZ) over a period of 29 years (1991-2019), revealed soft tissue mineralisation, particularly of cardiovascular tissues. The farm spans 10 acres and runs between 15 and 30 Toggenburg goats. The goats are predominantly on pasture comprising a variety of types. PATHOLOGICAL FINDINGS: Necropsies were performed on all adult goats (n = 45) that died or were euthanised. Histopathology was performed on 42 goats (93%), of which 33 (73%) included sufficient tissues diagnostically relevant to soft tissue mineralisation. The most significant gross findings were in various arteries, with the aorta most commonly affected, followed by the heart and lungs. The aortic intima showed prominent, multifocal to coalescing, raised, wrinkled, white plaques. Microscopically there were multiphasic lesions of mineralisation, chondroid, and osseous metaplasia in the elastic arteries, aorta, heart and lungs. A lumbar vertebra from one goat had prominent, basophilic, fibrillar, tangled matrix lining Haversian canals and lamellae. LABORATORY FINDINGS: Blood samples were collected from 15 adult goats in the affected herd and from 10 adult Toggenburg goats from an unaffected herd. Samples were collected by jugular venipuncture at 2-month intervals for 12 months (April 2018-March 2019). Concentrations of calcium, phosphorus, 25-hydroxyvitamin D2 and D3 (25OHD2, 25OHD3) in serum were analysed. The concentration of total 25OHD in serum was 34.2 (95% CI = 18.9-49.4) nmol/L (p < 0.001) higher in goats from the affected herd than in goats from the unaffected herd. Serum 25OHD2 concentration was 46.2 (95% CI = 39.2-53.2) nmol/L higher (p < 0.001) in goats from the affected herd compared to the unaffected herd. Serum Ca concentrations in affected goats were 0.101 (95% CI = 0.005-0.196) mmol/L higher (p = 0.039) than unaffected goats, but remained within the reference range. There was no evidence of a difference in serum 25OHD3 and P concentration between the herds. VEGETATION SURVEY: All paddocks on the property were surveyed every 2 months along evenly spaced line transects, and then further traversed perpendicularly to form a grid. No known calcinogenic species were identified. Known plant sources of vitamin D identified on the farm included mushrooms (species not defined), Dactylis glomerata, lichen, pine pollen, and algae. DIAGNOSIS: Soft tissue mineralisation and enzootic calcinosis. CLINICAL RELEVANCE: Veterinarians are alerted to the possibility of either enzootic calcinosis in goats and the potential occurrence of calcinogenic plants in New Zealand; or chronic vitamin D toxicosis of non-plant origin.

A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma.

PURPOSE: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. METHODS: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. RESULTS: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. CONCLUSION: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.

Correlation between carotid intima-media thickness and patient outcomes in coronary artery disease in central South Africa.

OBJECTIVES: Carotid intima-medial thickness (CIMT) is a non-invasive tool used to detect atherosclerosis and diagnose cardiovascular disease. This study aimed to determine whether pre-operative CIMT measurements correlated with intra- and postoperative outcomes in patients with acute coronary syndrome (ACS) undergoing coronary artery bypass graft (CABG) surgery. METHODS: This retrospective, analytical cohort included 89 patients diagnosed with ACS who received CABG surgery. Patients were divided into two cohorts: group 1: normal CIMT < 0.07 cm and group 2: abnormal CIMT ≥ 0.07 cm. B-mode ultrasound was used to measure the CIMT in all patients. Pre-, intra- and postoperative data and complications were recorded for each patient. RESULTS: The study included 77 (86.5%) males and 12 (13.5%) females. Pre-operative mean body mass index was significantly higher (p = 0.03) in group 2 than in group 1. Group 2 had a significantly increased incidence of diabetes (p = 0.008) and hypertension (p = 0.009), and increased NT-proBNP levels (p = 0.02). Intra- and postoperative outcomes between the groups were comparable, with no significant differences. CONCLUSION: The study showed no correlation between abnormal CIMT and increased adverse intra- and postoperative patient outcomes. Therefore, the results of this study show CIMT should not be considered a tool to predict adverse events in patients undergoing CABG surgery.

Phylogenomics illuminates the phylogeny of flower weevils (Curculioninae) and reveals ten independent origins of brood-site pollination mutualism in true weevils.

Weevils are an unusually species-rich group of phytophagous insects for which there is increasing evidence of frequent involvement in brood-site pollination. This study examines phylogenetic patterns in the emergence of brood-site pollination mutualism among one of the most speciose beetle groups, the flower weevils (subfamily Curculioninae). We analysed a novel phylogenomic dataset consisting of 214 nuclear loci for 202 weevil species, with a sampling that mainly includes flower weevils as well as representatives of all major lineages of true weevils (Curculionidae). Our phylogenomic analyses establish a uniquely comprehensive phylogenetic framework for Curculioninae and provide new insights into the relationships among lineages of true weevils. Based on this phylogeny, statistical reconstruction of ancestral character states revealed at least 10 independent origins of brood-site pollination in higher weevils through transitions from ancestral associations with reproductive structures in the larval stage. Broadly, our results illuminate the unexpected frequency with which true weevils-typically specialized phytophages and hence antagonists of plants-have evolved mutualistic interactions of ecological significance that are key to both weevil and plant evolutionary fitness and thus a component of their deeply intertwined macroevolutionary success.

Outcomes of single-ventricle physiology in central South Africa.

INTRODUCTION: Single-ventricle physiology is a critical cardiac condition requiring early diagnosis and intervention. The objectives of this study were to report on the management and outcomes of patients diagnosed with single-ventricle physiology in central South Africa. METHODS: This study was a retrospective, observational analysis of patients presenting with single-ventricle physiology at the Universitas Academic Hospital in central South Africa between November 1997 and June 2021. RESULTS: Patients were referred from the Free State (54%) and Northern Cape (29%) provinces and Lesotho. One hundred and fifty-four patients presented with single-ventricle physiology: 114 received interventions and 40 were not eligible for intervention. Patients presented for the first time at a median age of 34.5 days, with patients from nearby districts presenting within a few days of birth. However, patients from outlying areas presented much later. Eighty-seven patients received systemic-to-pulmonary artery shunting or pulmonary artery banding. Sixty-three patients proceeded to bidirectional Glenn procedures, and 30 patients (26%) had full palliation to Fontan. Twenty-one patients died after stage 1, six after the Glenn procedure and two after the Fontan procedure. Overall, 34 (29.8%) patients were lost to follow up. CONCLUSION: Patients in our study presented late and follow up of these patients was a challenge. The highest mortality rate occurs during the first stage of palliation. Outcomes from this study are comparable to other sub-Saharan studies.

Protothecosis in four dogs in New Zealand.

CASE HISTORIES: Medical records of four dogs diagnosed with protothecosis in New Zealand were reviewed. The dogs were aged between 4 and 9 years and three of the four dogs were female. Breeds were one Labrador, one Miniature Schnauzer and two crossbreeds. The reasons for initial veterinary evaluation were a cough and opaque appearance of the right eye (Case 1), diarrhoea (Cases 2 and 3), and cutaneous disease (Case 4). CLINICAL FINDINGS: The ocular signs were characterised by panuveitis, retinal detachment and secondary glaucoma. Gastrointestinal signs included chronic haemorrhagic diarrhoea due to colitis. Three cases had disseminated infection and developed both bilateral, blinding, ocular disease and chronic gastrointestinal disease. Cutaneous signs consisted of draining fistulae over the olecranon, multifocal cutaneous nodules, and ulceration and tracts of the foot pads. Disseminated protothecosis was confirmed by histopathology of biopsied ocular tissues in Cases 1 and 2 and by gastrointestinal biopsies in Case 3. Prototheca spp. were also identified in cytological specimens from Cases 1 and 4 and recovered by culture in Cases 2 and 4. Cutaneous protothecosis was diagnosed in Case 4 initially by cytology and histopathology of skin lesions, and Prototheca zopfii was confirmed by PCR of cultured organisms. TREATMENT AND OUTCOME: Prior to diagnosis of protothecosis, a variety of treatments were prescribed to treat the gastrointestinal and ocular signs. After diagnosis, only Cases 2 and 4 received medication aimed at treating the protothecal infection, which was itraconazole in both cases. Following the progression of clinical signs and concerns about quality of life, all four dogs were euthanised. DIAGNOSIS: Disseminated protothecosis in three dogs, cutaneous protothecosis in one dog. CLINICAL RELEVANCE: Canine protothecosis is rarely reported, despite the ubiquity of the causal algae, and the disease usually carries an extremely grave prognosis when infection is generalised. In New Zealand, protothecosis should be considered as a differential diagnosis in dogs with panuveitis, chorioretinitis or retinal detachment, colitis, or nodular, ulcerative or fistulating cutaneous lesions.

Development and initial psychometric properties of the Warwick-Edinburgh Mental Wellbeing Scale-Intellectual Disability version.

BACKGROUND: The Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS; Tennant et al., 2007) is yet to be validated in the intellectual disability (ID) population. The aim of this study was to report the development process and assess the psychometric properties of a newly adapted version of the WEMWBS and the Short WEMWBS for individuals with mild to moderate IDs (WEMWBS-ID/SWEMWBS-ID). METHOD: The WEMWBS item wordings and response options were revised by clinicians and researchers expert in the field of ID, and a visual aid was added to the scale. The adapted version was reviewed by 10 individuals with IDs. The measure was administered by researchers online using screenshare, to individuals aged 16+ years with mild to moderate IDs. Data from three UK samples were collated to evaluate the WEMWBS-ID (n = 96). A subsample (n = 22) completed the measure again 1 to 2 weeks later to assess test-retest reliability, and 95 participants additionally completed an adapted version of the adapted Rosenberg Self-Esteem Scale to examine convergent validity. Additional data from a Canadian sample (n = 27) were used to evaluate the SWEMWBS-ID (n = 123). RESULTS: The WEMWBS-ID demonstrated good internal consistency (ω = 0.77-0.87), excellent test-retest reliability [intraclass correlation coefficient (ICC) = .88] and good convergent validity with the self-esteem scale (r = .48-.60) across samples. A confirmatory factor analysis for a single factor model demonstrated an adequate fit. The SWEMWBS-ID showed poor to good internal consistency (ω = 0.36-0.74), moderate test-retest reliability (ICC = .67) and good convergent validity (r = .48-.60) across samples, and a confirmatory factor analysis indicated good model fit for a single factor structure. CONCLUSIONS: The WEMWBS-ID and short version demonstrated promising psychometric properties, when administered virtually by a researcher. Further exploration of the scales with larger, representative samples is warranted.

CT-derived measures of muscle quantity and quality predict poorer outcomes from elective colorectal surgery: a UK multicentre retrospective cohort study.

PURPOSE: To assess whether preoperative radiologically defined lean muscle measures are associated with adverse clinical outcomes in patients undergoing elective surgery for colorectal cancer. METHODS: This retrospective UK-based multicentre data collection study identified patients having had colorectal cancer resection with curative intent between January 2013 to December 2016. Preoperative computed-tomography (CT) scans were used to measure psoas muscle characteristics. Clinical records provided postoperative morbidity and mortality data. RESULTS: This study included 1122 patients. The cohort was separated into a combined group (patients with both sarcopenia and myosteatosis) and others group (either sarcopenia or myosteatosis, or neither). For the combined group, anastomotic leak was predicted on univariate (OR 4.1, 95% CI 1.43-11.79; p = 0.009) and multivariate analysis (OR 4.37, 95% CI 1.41-13.53; p = 0.01). Also for the combined group, mortality (up to 5 years postoperatively) was predicted on univariate (HR 2.41, 95% CI 1.64-3.52; p < 0.001) and multivariate analysis (HR 1.93, 95% CI 1.28-2.89; p = 0.002). A strong correlation exists between freehand-drawn region of interest-derived psoas density measurement and using the ellipse tool (R2 = 81%; p < 0.001). CONCLUSION: Measures of lean muscle quality and quantity, which predict important clinical outcomes, can be quickly and easily taken from routine preoperative imaging in patients being considered for colorectal cancer surgery. As poor muscle mass and quality are again shown to predict poorer clinical outcomes, these should be proactively targeted within prehabilitation, perioperative and rehabilitation phases to minimise negative impact of these pathological states.

Short-term outcomes of uterine artery embolization for urgent or emergent abnormal uterine bleeding.

PURPOSE: To evaluate the outcomes of uterine artery embolization (UAE) for patients with urgent or emergent abnormal uterine bleeding (AUB). MATERIALS AND METHODS: Retrospective review of all patients from 1/2009-12/2020 who were treated urgently or emergently with UAE for AUB. Urgent and emergent cases were defined as those requiring inpatient admissions. Demographic data were collected for each patient including hospitalizations related to bleeding and length of stay (LOS) for each hospitalization. Hemostatic interventions other than UAE were collected. Hematologic data were collected before and after UAE including hemoglobin, hematocrit, and transfusion products. Data specific to the UAE procedure included complication rates, 30-day readmission, 30-day mortality, embolic agent, site of embolization, radiation dose, and procedure time. RESULTS: 52 patients (median age: 39) underwent 54 urgent or emergent UAE procedures. The most common indications for UAE were malignancy (28.8%), post-partum hemorrhage (21.2%), fibroids (15.4%), vascular anomalies (15.4%), and post-operative bleeding (9.6%). There were no procedure-related complications. Following UAE, 44 patients (84.6%) achieved clinical success and required no additional intervention. Packed red blood cell transfusion decreased from a mean of 5.7 to 1.7 units (p < 0.0001). Fresh frozen plasma transfusion decreased from a mean of 1.8 to 0.48 units (p = 0.012). 50% of patients received a transfusion prior to UAE, while only 15.4% were transfused post-procedure (p = 0.0001). CONCLUSIONS: Emergent or urgent UAE is a safe and effective procedure to control AUB hemorrhage secondary to a variety of etiologies.

A survey of patient informational preferences when choosing between medical and surgical therapy for ulcerative colitis: a sub-study from the DISCUSS project.

AIM: People living with ulcerative colitis (UC) have two broad treatment avenues, namely medical or surgical therapy. The choice between these can depend on patient preference as well as the receipt of relevant information. The aim of this study was to define the informational needs of patients with UC. METHOD: A postal survey was designed to capture respondent demographics, treatment experienced within the previous 12 months and informational preferences by rating a long list of items. It was delivered through two hospitals that provide tertiary inflammatory bowel disease services. Descriptive analyses were performed to describe demographics and experiences. Principal component analysis was carried out using a varimax rotation to investigate informational needs. RESULTS: A total of 101 responses were returned (20.1% response rate). The median age of respondents was 45 years and the median time since diagnosis was 10 years. Control preferences skewed towards shared (42.6%) or patient-led but clinician-informed (35.6%). Decision regret was low for the population (median 12.5/100, range 0-100). Key informational needs related to medical therapy were benefits and risks of long-term therapy, burden of hospital attendance, reproductive health, need for steroid treatment and impact on personal life. For surgery, these were stoma information, effect on daily life, effect on sexual and reproductive health, risks and benefits and disruption of life due to surgery. CONCLUSION: This study has identified key areas for discussion when counselling patients about treatment decisions around medical therapy and surgery for UC.

Reservoir computing using networks of memristors: effects of topology and heterogeneity.

Reservoir computing (RC) has attracted significant interest as a framework for the implementation of novel neuromorphic computing architectures. Previously attention has been focussed on software-based reservoirs, where it has been demonstrated that reservoir topology plays a role in task performance, and functional advantage has been attributed to small-world and scale-free connectivity. However in hardware systems, such as electronic memristor networks, the mechanisms responsible for the reservoir dynamics are very different and the role of reservoir topology is largely unknown. Here we compare the performance of a range of memristive reservoirs in several RC tasks that are chosen to highlight different system requirements. We focus on percolating networks of nanoparticles (PNNs) which are novel self-assembled nanoscale systems that exhibit scale-free and small-world properties. We find that the performance of regular arrays of uniform memristive elements is limited by their symmetry but that this symmetry can be broken either by a heterogeneous distribution of memristor properties or a scale-free topology. The best perfomance across all tasks is observed for a scale-free network with uniform memistor properties. These results provide insight into the role of topology in neuromorphic reservoirs as well as an overview of the computational performance of scale-free networks of memristors in a range of benchmark tasks.