Clinically occult metastases in patients with cutaneous melanoma. Detection with sentinel lymph node biopsy and whole body positron emission tomography

Objective: The aim of this study was to investigate the use of sentinel lymph node biopsy (SLNB) and whole body positron emission tomography (PET), with emphasis on surgical treatment and prognosis, in the detection of clinically occult metastases in patients with clinically localized cutaneous melanoma. Patients and methods: The study population consisted of 1255 patients with clinical stage I–II cutaneous melanoma, operated at Turku University Hospital between 1983 and 2007. 334 patients underwent SLNB and they were compared to 921 retrospective patients. A subgroup of 30 symptom-free patients with high risk melanoma underwent prospectively whole body PET 6–24 months postoperatively. Results: Overall, the disease-specific survival rate was 84.4 % at five years. Sex, Breslow thickness, age and nodal status were independent prognostic factors for survival. SLNB revealed occult nodal metastases in 17 % of the patients. There was no significant difference in disease-specific overall survival between SLNB patients and controls, but the nodal disease-free time was significantly longer suggesting better local control after SLNB and subsequent completion lymph node dissection. The followup time was different between the study cohorts and initial surgery was performed during different time periods. SLNB detected micrometastases in seven of 155 patients (4.5 %) with thin T1 primary melanoma and in four of 25 patients (16 %) with head and neck melanoma. In six of 30 asymptomatic patients with high risk melanoma (20 %), whole body PET detected occult distant metastases. Conclusion: Both SLNB and whole body PET were reliable methods to detect clinically occult metastases in patients with cutaneous melanoma. This upstaging altered the treatment in each case.

Early Detection of Alzheimer's Disease Beta-amyloid Pathology -Applicability of Positron Emission Tomography with the Amyloid Radioligand 11C-PIB

Early Detection of Alzheimer's Disease Beta-amyloid Pathology -Applicability of Positron Emission Tomography with the Amyloid Radioligand ¹¹C-PIB Accumulation of beta amyloid (Abeta) in the brain is characteristic for Alzheimer’s disease (AD). Carbon-11 labeled 2-(4’-methylaminophenyl)-6-hydroxybenzothiazole (¹¹C-PIB) is a novel positron emission tomography (PET) amyloid imaging agent that appears to be applicable for in vivo Abeta plaque detection and quantitation. The biodistribution and radiation dosimetry of ¹¹C-PIB were investigated in 16 healthy subjects. The reproducibility of a simplified ¹¹C-PIB quantitation method was evaluated with a test-retest study on 6 AD patients and 4 healthy control subjects. Brain ¹¹C-PIB uptake and its possible association with brain atrophy rates were studied over a two-year follow-up in 14 AD patients and 13 healthy controls. Nine monozygotic and 8 dizygotic twin pairs discordant for cognitive impairment and 9 unrelated controls were examined to determine whether brain Abeta accumulation could be detected with ¹¹C-PIB PET in cognitively intact persons who are at increased genetic risk for AD. The highest absorbed radiation dose was received by the gallbladder wall (41.5 mjuGy/MBq). About 20 % of the injected radioactivity was excreted into urine, and the effective whole-body radiation dose was 4.7 mjuSv/MBq. Such a dose allows repeated scans of individual subjects. The reproducibility of the simplified ¹¹C-PIB quantitation was good or excellent both at the regional level (VAR 0.9-5.5 %) and at the voxel level (VAR 4.2-6.4 %). ¹¹C-PIB uptake did not increase during 24 months’ follow-up of subjects with mild or moderate AD, even though brain atrophy and cognitive decline progressed. Baseline neocortical ¹¹C-PIB uptake predicted subsequent volumetric brain changes in healthy control subjects (r = 0.725, p = 0.005). Cognitively intact monozygotic co-twins – but not dizygotic co-twins – of memory-impaired subjects exhibited increased ¹¹C-PIB uptake (117-121 % of control mean) in their temporal and parietal cortices and the posterior cingulate (p<0.05), when compared with unrelated controls. This increased uptake may be representative of an early AD process, and genetic factors seem to play an important role in the development of AD-like Abeta plaque pathology. ¹¹C-PIB PET may be a useful method for patient selection and follow-up for early-phase intervention trials of novel therapeutic agents. AD might be detectable in high-risk individuals in its presymptomatic stage with ¹¹C-PIB PET, which would have important consequences both for future diagnostics and for research on disease-modifying treatments.

Fraud detection in the banking sector : a multi-agent approach

Fraud is an increasing phenomenon as shown in many surveys carried out by leading international consulting companies in the last years. Despite the evolution of electronic payments and hacking techniques there is still a strong human component in fraud schemes. Conflict of interest in particular is the main contributing factor to the success of internal fraud. In such cases anomaly detection tools are not always the best instruments, since the fraud schemes are based on faking documents in a context dominated by lack of controls, and the perpetrators are those ones who should control possible irregularities. In the banking sector audit team experts can count only on their experience, whistle blowing and the reports sent by their inspectors. The Fraud Interactive Decision Expert System (FIDES), which is the core of this research, is a multi-agent system built to support auditors in evaluating suspicious behaviours and to speed up the evaluation process in order to detect or prevent fraud schemes. The system combines Think-map, Delphi method and Attack trees and it has been built around audit team experts and their needs. The output of FIDES is an attack tree, a tree-based diagram to ”systematically categorize the different ways in which a system can be attacked”. Once the attack tree is built, auditors can choose the path they perceive as more suitable and decide whether or not to start the investigation. The system is meant for use in the future to retrieve old cases in order to match them with new ones and find similarities. The retrieving features of the system will be useful to simplify the risk management phase, since similar countermeasures adopted for past cases might be useful for present ones. Even though FIDES has been built with the banking sector in mind, it can be applied in all those organisations, like insurance companies or public organizations, where anti-fraud activity is based on a central anti-fraud unit and a reporting system.

Risk Assessment of a Supplier in the Pharmaceutical Industry

The topic of this Master’s Thesis is risk assessment in the supply chain, and the work was done for a company operating in the pharmaceutical industry. The unique features of the industry bring additional challenges to risk management, due to high regulatory, docu-mentation and traceability requirements. The objective of the thesis was to generate a template for assessing the risks in the supply chain of current and potential suppliers of the case company. Risks pertaining to the case setting were sought mainly from in-house expertise of this specific product and supply chain as well as academic research papers and theory on risk management. A questionnaire was set up to assess the found risks on impact, occurrence and possibility of detection. Through this classification of the severity of the risks, the supplier assessment template was formed. A questionnaire template, comprised of the top 10 risks affecting the flow of information and materials in this setting, was formulated to serve as a generic tool for assessing risks in the supply chain of a pharmaceutical company. The template was tested on another supplier for usability and accuracy of found risks, and it demonstrated functioning in a differing supply chain and product setting.