First passage time analysis of spatial mutation patterns reveals sub-clonal evolutionary dynamics in colorectal cancer.

The signature of early cancer dynamics on the spatial arrangement of tumour cells is poorly understood, and yet could encode information about how sub-clones grew within the expanding tumour. Novel methods of quantifying spatial tumour data at the cellular scale are required to link evolutionary dynamics to the resulting spatial architecture of the tumour. Here, we propose a framework using first passage times of random walks to quantify the complex spatial patterns of tumour cell population mixing. First, using a simple model of cell mixing we demonstrate how first passage time statistics can distinguish between different pattern structures. We then apply our method to simulated patterns of mutated and non-mutated tumour cell population mixing, generated using an agent-based model of expanding tumours, to explore how first passage times reflect mutant cell replicative advantage, time of emergence and strength of cell pushing. Finally, we explore applications to experimentally measured human colorectal cancer, and estimate parameters of early sub-clonal dynamics using our spatial computational model. We infer a wide range of sub-clonal dynamics, with mutant cell division rates varying between 1 and 4 times the rate of non-mutated cells across our sample set. Some mutated sub-clones emerged after as few as 100 non-mutant cell divisions, and others only after 50,000 divisions. The majority were consistent with boundary driven growth or short-range cell pushing. By analysing multiple sub-sampled regions in a small number of samples, we explore how the distribution of inferred dynamics could inform about the initial mutational event. Our results demonstrate the efficacy of first passage time analysis as a new methodology in spatial analysis of solid tumour tissue, and suggest that patterns of sub-clonal mixing can provide insights into early cancer dynamics.

Prevalence of major cardiovascular risk factors among oil and gas and energy company workers.

INTRODUCTION: Cardiovascular diseases (CVD) remain the biggest cause of disability and premature death throughout the world. AIM: The aim of this study was to describe and determine the prevalence of major cardiovascular risk factors emerged at the first medical examination carried out by a group of an oil and gas contractor company workers in the observation period 2000-2010. METHODS: An observational cross-sectional study was conducted on 1073 workers (mean age 41 years, SD = 9.5) presenting overweight BMI (body mass index) values, hypertension and cholesterol problems. RESULTS: In particular, we found that workers > 45 years had significant higher risk to have obesity (OR = 3.8, CI 95% = 2.5-5.7), hypertension (OR = 2.7, CI 95% = 2.1-3.6), high blood fasting glucose (OR = 2.6, CI 95% = 1.2-5.5), high cholesterol (OR = 2.7, CI 95% = 2.0-3.6), high triglycerides (OR = 1.8, CI 95% = 1.4-2.4) compared to younger (< 45 years).

Hematuria one-stop clinic: first experience in Italy with 150 cases.

OBJECTIVES: Starting from the UK experience, we decided to test both the feasibility and the advantages of this diagnostic pathway now established in an Italian hospital. We analyzed the outcomes in detecting transitional cell carcinoma (TCC) of the bladder, other malignant and non-malignant conditions. MATERIALS AND METHODS: Between April and December 2010, one hundred and fifty patients presenting with hematuria were referred to the Hematuria One Stop Clinic (HOSC) at our Institution. Each patient underwent a visit, a Urinary Tract Ultrasound, a Cystoscopy and CT IVP in selected cases (evidence of alterations or lesions of the renal parenchyma, presence of stones of the urinary tract, evidence of doubtful or positive urinary cytology). Where a TCC of the bladder was diagnosed, the patient underwent TUR-BT. In other cases (stones, BPH etc.) the appropriate therapeutic pathway was followed. RESULTS: 25.3% of patients with hematuria were found to have a bladder cancer; 21.3% had a urinary stone (2% in the bladder); 1.3% had prostate cancer; 1.3% had a renal cell carcinoma. The mean age was 69.8 yrs. 6% of the patients (23.6% on patients with TCC of the bladder) had a G3 disease. The mean time from admission to the HOSC until the operation day, in case of TCC of the bladder, was 10.61 days. CONCLUSIONS: The Italian experience of the One Stop Clinic confirms a high rate of bladder cancer detection. Furthermore, a high rate of non-malignant conditions was detected, stressing the importance of the HOSC not only as a cancer clinic but as a complete general urological clinic. We report a shorter waiting time to operation, especially for bladder TCC G3 patients.