Automated Textural Classification of Osteoarthritis Magnetic Resonance Images

Osteoarthritis (OA) is the most common cause of disability in the United Kingdom and United States. Identifying the rate of OA progression remains an important clinical and research challenge for early disease monitoring. Texture analysis of tibial subchondral bone using magnetic resonance imaging (MRI) has demonstrated the ability to discriminate between different stages of OA. This work combines texture analysis with machine learning methods (Lasso, Decision Tree, and Neural Network) to predict radiographic disease progression over 3 years, trained using data from the Osteoarthritis Initiative. We achieved high sensitivity (86%), specificity (64%) and accuracy (74%) for predictions of OA progression.The authors acknowledge research support from the National Institute of Health Research Cambridge Biomedical Research Centre. RT acknowledges the support of the UK Engineering and Physical Sciences Research Council (EPSRC) grant EP/L016516/1 for the University of Cambridge Centre for Doctoral Training, the Cambridge Centre for Analysis. JK and JM acknowledge support by GlaxoSmithKline. AM acknowledges research support from Arthritis Research UK; Tissue Engineering Centre award. FG acknowledges research support from Cancer Research UK

A Recurrent Neural Network Survival Model: Predicting Web User Return Time

The size of a website's active user base directly affects its value. Thus, it is important to monitor and influence a user's likelihood to return to a site. Essential to this is predicting when a user will return. Current state of the art approaches to solve this problem come in two flavors: (1) Recurrent Neural Network (RNN) based solutions and (2) survival analysis methods. We observe that both techniques are severely limited when applied to this problem. Survival models can only incorporate aggregate representations of users instead of automatically learning a representation directly from a raw time series of user actions. RNNs can automatically learn features, but can not be directly trained with examples of non-returning users who have no target value for their return time. We develop a novel RNN survival model that removes the limitations of the state of the art methods. We demonstrate that this model can successfully be applied to return time prediction on a large e-commerce dataset with a superior ability to discriminate between returning and non-returning users than either method applied in isolation.Comment: Accepted into ECML PKDD 2018; 8 figures and 1 tabl

Do gadolinium-based contrast agents alter 23Na T1 relaxivity in glioma?

Incomplete fluid suppression on fluid-attenuated inversion-recovery 23Na-MRI (IR-23Na-MRI) was observed in three patients undergoing IR-23Na-MRI after gadolinium contrast injection, as part of a brain tumour imaging study. To evaluate this, 23Na-MRI T1 maps were acquired before and after injection of a gadolinium-based contrast agent on a grade IV glioma (GBM) patient, which showed a statistically significant change of 23Na-MRI T1 within the peritumoral oedema (p=0.0095). Gadolinium contrast-enhanced 23Na-MRI could potentially add further applications for sodium imaging and probe tumour tissue structure in new ways to investigate proliferation and treatment response

Dynamic contrast-enhanced MRI of synovitis in knee osteoarthritis: repeatability, discrimination and sensitivity to change in a prospective experimental study

OBJECTIVES: Evaluate test-retest repeatability, ability to discriminate between osteoarthritic and healthy participants, and sensitivity to change over 6 months, of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) biomarkers in knee OA. METHODS: Fourteen individuals aged 40-60 with mild-moderate knee OA and 6 age-matched healthy volunteers (HV) underwent DCE-MRI at 3 T at baseline, 1 month and 6 months. Voxelwise pharmacokinetic modelling of dynamic data was used to calculate DCE-MRI biomarkers including Ktrans and IAUC60. Median DCE-MRI biomarker values were extracted for each participant at each study visit. Synovial segmentation was performed using both manual and semiautomatic methods with calculation of an additional biomarker, the volume of enhancing pannus (VEP). Test-retest repeatability was assessed using intraclass correlation coefficients (ICC). Smallest detectable differences (SDDs) were calculated from test-retest data. Discrimination between OA and HV was assessed via calculation of between-group standardised mean differences (SMD). Responsiveness was assessed via the number of OA participants with changes greater than the SDD at 6 months. RESULTS: Ktrans demonstrated the best test-retest repeatability (Ktrans/IAUC60/VEP ICCs 0.90/0.84/0.40, SDDs as % of OA mean 33/71/76%), discrimination between OA and HV (SMDs 0.94/0.54/0.50) and responsiveness (5/1/1 out of 12 OA participants with 6-month change > SDD) when compared to IAUC60 and VEP. Biomarkers derived from semiautomatic segmentation outperformed those derived from manual segmentation across all domains. CONCLUSIONS: Ktrans demonstrated the best repeatability, discrimination and sensitivity to change suggesting that it is the optimal DCE-MRI biomarker for use in experimental medicine studies. KEY POINTS: • Dynamic contrast-enhanced MRI (DCE-MRI) provides quantitative measures of synovitis in knee osteoarthritis which may permit early assessment of efficacy in experimental medicine studies. • This prospective observational study compared DCE-MRI biomarkers across domains relevant to experimental medicine: test-retest repeatability, discriminative validity and sensitivity to change. • The DCE-MRI biomarker Ktrans demonstrated the best performance across all three domains, suggesting that it is the optimal biomarker for use in future interventional studies

Mix methods approach to explore patients' perspectives on the acceptability of a urinary biomarker test in replacement of cystoscopy in bladder cancer surveillance

OBJECTIVE: To determine the minimal accepted sensitivity (MAS) of a urine biomarker that patients are willing to accept to replace cystoscopy and to qualitatively assess their views and reasons. PATIENT AND METHODS: Patients were part of a prospective multi-center observational study recruiting patients with bladder cancer for a urine biomarker study (DETECT II; ClinicalTrials.gov: NCT02781428). A mix methods approach comprising of 1) Questionnaire to assess patients' experience with cystoscopy and patients' preference for cystoscopy vs urinary biomarker and 2). Semi-structured interviews to understand patient views, choice and reasons for their preference. RESULTS: A urine biomarker with MAS of 90% would be accepted by 75.8% of patients. This is despite a high self-reported prevalence of hematuria (51.0%), dysuria/ lower urinary tract symptoms (69.1%) and urinary tract infection requiring antibiotics (25.8%). There was no association between MAS with patient demographics, adverse events experienced, cancer characteristics and distance of patients' home to hospital. Qualitative analysis suggest that patients acknowledge that cystoscopy is invasive, embarrassing and associated with adverse events but are willing to tolerate the procedure due to a high sensitivity. Patients have confidence in cystoscopy and appreciate the visual diagnosis of cancer. Both low and high-risk patients would consider a biomarker with a reported sensitivity similar to cystoscopy. CONCLUSION: Patients value the high sensitivity cystoscopy accords despite the reported discomfort and adverse events experienced following cystoscopy. The sensitivity of a urinary biomarker must be close to cystoscopy before patients' acceptance

Exploring patients’ experience and perception of being diagnosed with bladder cancer: A mixed methods approach

OBJECTIVE: To determine patient experience and perception following a diagnosis of non-muscle invasive bladder cancer (NMIBC). PATIENT AND METHODS: Patients were part of a prospective multi-centre observational study recruiting patients with NMIBC for a urine biomarker study (DETECT II; ClinicalTrials.gov: NCT02781428). A mix methods approach comprising 1) the Brief Illness Perception Questionnaire (Brief IPQ) and 2) semi-structured interviews to explore patients' experience of experiencing haematuria, initial and subsequent experience with NMIBC diagnosis. Both assessments were completed at 6 months following NMIBC diagnosis. RESULTS: A total of 213 patients completed the Brief IPQ. Patients felt that they had minimal symptoms (median [IQR: 2 [0-5]) and were not particularly affected emotionally (3 [1-6]) with a minimal effect to their daily life (2 [0-5]). However, they remained concern about their cancer diagnosis (5 [3-8]) and felt that they had no personal control over the cancer (2 [2-5]) and believed that their illness would affect them for some time (6 [3-10]). A significant association with a lower personal control of the disease (p70 years of age. A high number of patients were uncertain about the cause of their bladder cancer diagnosis. Qualitative analysis found that at initial presentation of haematuria, most patients were not aware of the risk of bladder cancer. Patients were most anxious and psychologically affected between the interval of cystoscopy diagnosis and transurethral resection of bladder tumour (TURBT). Following TURBT, most patients were positive about their cancer prognosis. CONCLUSION: NMIBC patients have a poor perception of disease control and believe that their disease will continue over a prolonged period of time. This is particularly more pertinent in the elderly. Patients are most psychologically affected during the interval between cancer diagnosis following cystoscopy and tumour resection at TURBT. Further, health awareness about the causes of bladder cancer remained poor with a significant number of patients unaware of the cause of bladder cancer. Psychological support and prompt TURBT following bladder cancer diagnosis would help improve the mental health of patients with NMIBC

Using an e-Health Intervention to Reduce Prolonged Sitting in UK Office Workers: A Randomised Acceptability and Feasibility Study

Low-cost workplace interventions are required to reduce prolonged sitting in office workers as this may improve employees’ health and well-being. This study aimed to assess the acceptability and feasibility of an e-health intervention to reduce prolonged sitting among sedentary UK-based office workers. Secondary aims were to describe preliminary changes in employee health, mood and work productivity after using an e-health intervention. Healthy, university office workers (n = 14) completed this study. An 8 week randomised crossover design was used, consisting of two trials: Intervention (computer-based prompts) and Control. Eligibility and retention rates were recorded to assess the feasibility of the trial and interviews were conducted following the intervention to explore its acceptability. Sitting, standing and stepping were objectively assessed prior to and during week 8 of each trial. Before and after each trial, measurements of vascular function, cerebrovascular function, mood and work productivity were obtained. This study had eligibility and retention rates of 54.5% and 77.8%, respectively. Participants expressed a lack of autonomy and disruption to their workflow when using the e-health intervention, raising concerns over its acceptability and long-term implementation. Preliminary data indicate that the intervention may improve the patterning of activity accrued during work hours, with increases in the number of standing and stepping bouts completed, in addition to improving vascular function. This e-health intervention is feasible to deliver in a cohort of university office workers. However, adaptations to its implementation, such as personalised settings, are needed to increase acceptability before larger trials can be conducted

Can renal and bladder ultrasound replace CT urogram in patients investigated for microscopic hematuria?

PURPOSE: Computed tomography urogram (CTU) is recommended when investigating patients with hematuria. We determine the incidence of urinary tract cancer and compare the diagnostic accuracy of CTU and renal and bladder ultrasound (RBUS) at identifying urinary tract cancer. METHODS: The DETECT I study (clinicaltrials.gov NCT02676180) is a prospective observational study recruiting patients ≥18 years following a presentation of macroscopic or microscopic haematuria at 40 hospitals. All patients had cystoscopy and upper tract imaging (CTU, RBUS or both). RESULTS: 3,556 patients with a median age of 68 years were recruited, of which 2166 had RBUS and 1692 had CTU in addition to cystoscopy. The incidence of bladder, renal and upper tract urothelial cancer (UTUC) were 11.0%, 1.4% and 0.8% respectively in macroscopic hematuria patients. Patients with microscopic hematuria had a 2.7%, 0.4% and 0% incidence of bladder, renal and UTUC respectively. The sensitivity and negative predictive value (NPV) of RBUS for the detection of renal cancer was 85.7% and 99.9% respectively but 14.3% and 99.7% for the detection of UTUC. RBUS was poor at identifying renal calculi. Sensitivity of RBUS was lower than CTU for the detection of bladder cancer (both <85%). Cystoscopy has a specificity and PPV of 98.3% and 83.9% respectively. CONCLUSION: CTU can be safely replaced with RBUS in patients with microscopic hematuria. The incidence of UTUC is 0.8% in patients with macroscopic hematuria and CTU is recommended. Patients with suspected renal calculi will require non-contrast renal tract CT. Imaging cannot replace cystoscopy to diagnose bladder cancer

Epidermolysa bullosa in Danish Hereford calves is caused by a deletion in LAMC2 gene

BACKGROUND Heritable forms of epidermolysis bullosa (EB) constitute a heterogeneous group of skin disorders of genetic aetiology that are characterised by skin and mucous membrane blistering and ulceration in response to even minor trauma. Here we report the occurrence of EB in three Danish Hereford cattle from one herd. RESULTS Two of the animals were necropsied and showed oral mucosal blistering, skin ulcerations and partly loss of horn on the claws. Lesions were histologically characterized by subepidermal blisters and ulcers. Analysis of the family tree indicated that inbreeding and the transmission of a single recessive mutation from a common ancestor could be causative. We performed whole genome sequencing of one affected calf and searched all coding DNA variants. Thereby, we detected a homozygous 2.4 kb deletion encompassing the first exon of the LAMC2 gene, encoding for laminin gamma 2 protein. This loss of function mutation completely removes the start codon of this gene and is therefore predicted to be completely disruptive. The deletion co-segregates with the EB phenotype in the family and absent in normal cattle of various breeds. Verifying the homozygous private variants present in candidate genes allowed us to quickly identify the causative mutation and contribute to the final diagnosis of junctional EB in Hereford cattle. CONCLUSIONS Our investigation confirms the known role of laminin gamma 2 in EB aetiology and shows the importance of whole genome sequencing in the analysis of rare diseases in livestock