Dancing with the Octopus (summary)

In the Netherlands, the political discussion on administrative burdens is still ongoing. To generate a more scientific background on this topic, in January 2003 a PhD thesis was published, titled 'Dancing with the Octopus; information obligations of enterprises in the social constitutional state from a public administration point of view'. The full text of this thesis is available in Dutch only. You can download an English summary here.

MISTRAL

This report outlines the MISTRAL model (Administrative Compliance Cost Assessment Tool), by emphasising the issues of when a model may be applied, why it will be applied, how the model works and why the model should be used. The report concludes by narrating several results obtained on the basis of MISTRAL.

Accelerometry based detection of epileptic seizures

Epilepsy is one of the most common neurological disorders. Epileptic seizures are the manifestation of abnormal hypersynchronous discharges of cortical neurons that impair brain function. Most of the people affected can be treated successfully with drug therapy or neurosurgical procedures. But there is still a large group of epilepsy patients that continues to have frequent seizures. For these patients automated detection of epileptic seizures can be of great clinical importance. Seizure detection can influence daily care or can be used to evaluate treatment effect. Furthermore automated detection can be used to trigger an alarm system during seizures that might be harmful to the patient. This thesis focusses on accelerometry (ACM) based seizure detection. A detailed overview is provided, on the perspectives for long-term epilepsy monitoring and automated seizure detection. The value of accelerometry for seizure detection is shown by means of a clinical evaluation and the first steps are made towards automatic detection of epileptic seizures based on ACM. With accelerometers movements are recorded. A large group of epileptic seizures manifest in specific movement patterns, so called motor seizures. Chapter 2 of this thesis presents an overview of the published literature on available methods for epileptic seizure detection in a long-term monitoring context. Based on this overview recommendations are formulated that should be used in seizure detection research and development. It is shown that for seizure detection in home environments, other sensor modalities besides EEG become more important. The use of alternative sensor modalities (such as ACM) is relatively new and so is the algorithm development for seizure detection based on these measures. It was also found that for both the adaptation of existing techniques and the development of new algorithms, clinical information should be taken more into account. The value of ACM for seizure detection is shown by means of a clinical evaluation in chapter 3. Here 3-D ACM- and EEG/video-recordings of 18 patients with severe epilepsy are visually analyzed. A striking outcome presented in this chapter is the large number of visually detected seizures versus the number of seizures that was expected on forehand and the number of seizures that was observed by the nurses. These results underscore the need for an automatic seizure detection device even more, since in the current situation many seizures are missed and therefore it is possible that patients do not get the right (medical) treatment. It was also observed that 95% of the ACM-patterns during motor seizures are sequences of three elementary patterns: myoclonic, tonic and clonic patterns. These characteristic patterns are a starting point for the development of methods for automated seizure detection based on ACM. It was decided to use a modular approach for the detection methodology and develop algorithms separately for motor activity in general, myoclonic seizures and tonic seizures. Furthermore, clinical information is incorporated in the detection methodology. Therefore in this thesis features were used that are either based on the shape of the patterns of interest as described in clinical practice (chapter 4 and 7), or the features were based on a physiological model with parameters that are related to seizure duration and intensity (chapter 5 and 6). In chapter 4 an algorithm is developed to distinguish periods with and without movement from ACM-data. Hence, when there is no movement there is no motor seizure. The amount of data that needs further analysis for seizure detection is thus reduced. From 15 ACM-signals (measured on five positions on the body), two features are computed, the variance and the jerk. In the resulting 2-D feature space a linear threshold function is used for classification. For training and testing the algorithm ACM data along with video data are used from nocturnal recordings in mentally retarded patients with severe epilepsy. Using this algorithm the amount of data that needs further analysis is reduced considerably. The results also indicate that the algorithm is robust for fluctuations across patients and thus there is no need for training the algorithm for each new patient. For the remaining data it needs to be established whether the detected movement is seizure related or not. To this purpose a model is developed for the accelerometer pattern measured on the arm during a myoclonic seizure (chapter 5). The model consists of a mechanical and an electrophysiological part. This model is used as a matched wavelet filter to detect myoclonic seizures. In chapter 6 the model based wavelet is compared to three other time frequency measures: the short time Fourier transform, the Wigner distribution and the continuous wavelet transform using a Daubechies wavelet. All four time-frequency methods are evaluated in a linear classification setup. Data from mentally retarded patients with severe epilepsy are used for training and evaluation. The results show that both wavelets are useful for detection of myoclonic seizures. On top of that, our model based wavelet has the advantage that it consists of parameters that are related to seizure duration and intensity that are physiological meaningful. Besides myoclonic seizures, the model is also useful for the detection of clonic seizures; physiologically these are repetitive myoclonic seizures. Finally for the detection of tonic seizures, in chapter 7 a set of features is studied that incorporate the mean characteristics of ACM-patterns associated with tonic seizures. Linear discriminant analysis is used for classification in the multi-dimensional feature space. For training and testing the algorithm, again data are used from recordings in mentally retarded patients with severe epilepsy. The results show that our approach is useful for the automated detection of tonic seizures based on 3-D ACM and that it is a promising contribution in a complete multi-sensor seizure detection setup

Information obligations in the Dutch constitutional state

Administrative compliance obligations incurred by private enterprise entail a vital component of the Dutch democracy. The Netherlands government has to be able to supervise and ensure compliance with laws governing for instance a clean environment and safe labour conditions. Efficient data compilation in this respect is however not always guaranteed, as administrative compliance obligations entail a severe burden for private enterprise. EIM designed the first theoretical framework of this kind to explain the origins, the legal setting and the role of administrative compliance obligations. Amongst others, the study outlines the increasing recognition of (the significance of) administrative compliance obligations.

Radioactive holmium poly(L-lactic acid) microspheres for treatment of liver malignancies

Liver metastases frequently occur during the progression of various solid tumours, especially colorectal cancers, and are the cause of 25-50% of all cancer deaths [1-3]. In particular in patients with colorectal cancer the liver is the main metastatic site. Median survival of patients with liver metastases is approximately 6-12 months, and in the presence of extensive hepatic metastases survival is reported to be less than 6 months with no 5-year survivors [1,4,5]. Systemic chemotherapy results in only limited increase in life span with a median survival of around 1 year. In addition to systemic chemotherapy, local hepatic arterial chemotherapy, chemo-occlusion or combination therapies have resulted in some extension of life span of approximately 12-24 months [5-7]. Although loco-regional chemotherapy showed good palliative properties, a number of side effects such as nausea, vomiting and diarrhoea has been reported. In addition, hepatic toxicity associated with these therapies is often observed [5,8]. Surgery is still the only accepted treatment with curative intention, but only a minority of the patients can be subjected to this treatment [9,10]. Other newly developed surgical modalities like cryo-ablation and radiofrequency ablation have resulted in refinement of the surgical techniques which can be applied to a greater number of patients. Nevertheless, surgical therapies are only possible in approximately 10% of the patients [11,12]. External beam radiotherapy in the treatment of hepatic malignancies is limited by the radiosensitivity of normal liver tissue, which can tolerate doses of only up to 30 Gy for whole liver irradiation [3,13,14]. Therefore, investigators have searched for ways to utilise the arterial vascularization of hepatic metastases in order to inject local radioactive deposits. Yttrium-90 ( 90 Y) labelled microspheres which can be administered intra-arterially, became available in the late 1980s and resulted in the start of a new safe therapy for treatment of liver cancer [2,15]. Livers of patients can receive up to 150 Gy without developing radiation hepatitis; a safety limit of 80 to 100 Gy is used in most studies [16,17]. The median survival in a study of 17 patients with liver metastases from colorectal cancer treated with 90 Y microspheres was 14 months and there were 3 long-term survivors of 4 years [18]. As important as longevity, the treatment has very little morbidity [8]. Although studies with 90 Y labelled microspheres, either based on glass or resin, showed promising results, their high density (3.3 g/ml for glass and 1.6 g/ml for resin), apparent non-emission of 90 Y (Emax=2.28 MeV, t1/2=64.1h) for imaging can be considered as disadvantages. Therefore, Mumper et al. [19] proposed the use of poly(L-lactic acid) (PLLA) microspheres loaded with the ß -emitter holmium-166 ( 166 Ho) as alternative for the glass or resin based systems. 166 Ho-loaded microspheres have favourable characteristics above the 90 Y glass and resin based systems because of their relatively low density and biodegradability. Moreover, 166 Ho also emits ? -photons, which makes image-guided radionuclide therapy possible. However, because of the relatively low contents of holmium, 10% (w/w), Mumper et al. were not able to produce a patient dose with sufficient activity

Effects of high relative humidity and dry purging on VOCs obtained during breath sampling on common sorbent tubes.

BACKGROUND:Offline breath analysis by GC-MS requires the use of sorbent traps to concentrate and store volatile compounds. The selection of which sorbent to use and best practices for managing water retention are important considerations to allow for reproducible, untargeted, biomarker discovery in water saturated breath samples. OBJECTIVE:To assess three commonly used sorbent materials for their use in breath volatile sampling and determine how the high relative humidity inherent in such samples effects the capture of volatile compounds of interest. METHODS:TenaxGR, TenaxTA/Carbograph1TD and TenaxTA/Carbograph5TD tubes were selected as they are the most commonly used sorbents in the breath sampling literature. The recovery of 29 compounds in a standard mix loaded using high humidity gas was tested for each sorbent and compared to loading in dry gas. Water retention and dry purge rates were determined. Finally, breath samples were sampled simultaneously on to each sorbent type using the ReCIVA and analysed by TD-GC-MS. RESULTS:All three sorbents exhibited acceptable reproducibility when loaded with the standard mix in dry gas. Loading the standard mix in humid gas led to reduced recovery of compounds based on their chemical properties. Dry purging performance for each sorbent material was assessed and was shown to be 1.14, 1.13 and 0.89 mg H2O min-1for TenaxGR, TenaxTA/Carbograph1TD and TenaxTA/Carbograph5TD respectively. A comparison of breath profiles on different sorbents showed differences in background artefacts (sulfur dioxide, cyclopenten-1-one and 3-nonene) and endogenous breath compounds (2-methyl-furan and furfural). CONCLUSIONS:High relative humidity during sampling reduces the ability of sorbent tubes to capture volatile compounds and could impact method detection limits during breath sampling. Sufficient water to impair accurate analysis was retained on all tubes. Minimal differences were observed between sorbent materials when used to sample breath, however, suggestions are provided for sorbent selection for future studies