Home closure as a weapon in the Dutch war on drugs: Does judicial review function as a safety net?

BACKGROUND: A widespread sense of a failing criminal justice system and increased feelings of insecurity changed the response to crime into a culture of control, which is characterized by policies that punish and exclude. In the Netherlands, these influences can be witnessed in the war on drugs where local authorities use their administrative power to close homes involved in drug-related crime. Citizens can invoke judicial review over these administrative interferences by claiming that such closure results in an unfair balance between purposes, means and consequences. This paper assesses whether judicial review functions as a safety net against losing one's home due to drug-related crime. METHODS: We used doctrinal legal research methods to examine the "law in the books" and empirical legal research methods to analyse the "law in action". We used a survey to investigate how often the drug-related closure power was used in 2015, and we statistically analysed all published case law of Dutch lower courts between 2007 and 2016. RESULTS: The scope of the closure power broadened over the years and our data show that local authorities fiercely make use of this instrument. In 41.4% of the cases, citizens are successful in fighting the closure. While scholarly literature indicates that judicial courts function as safeguards by questioning the proportionality of administrative action, raising a proportionality defence does not necessarily result in a more favourable outcome for citizens. In fact, raising a proportionality defence makes it more likely to result in dismissal of the appeal. CONCLUSION: The stretched scope of the drug-related closure power together with the relatively low success rate of citizens who fight the loss of their home and a seemingly meaningless proportionality check show no sign of a safety net against the loss of one's home at the suit of a local authority.

[Ernst von der Porten : looking for facts before and after forced emigration]. / Ernst von der Porten : Spurensuchen vor und nach der erzwungenen Emigration.

The Ernst von der Porten medal has been awarded for many years to exceptional personalities by the Alliance of German Anesthesiologists to honor the outstanding achievements of the physician Ernst von der Porten from Hamburg in the development of anesthesiology as an autonomous discipline Only recent access to hitherto inaccessible documents enabled the reconstruction of his final years. He was persecuted and excluded by the National Socialist (NS) regime due to his Jewish roots and finally forced to emigrate. Records revealed that even in the so-called safe exile, degrading treatment and humiliation continued for Ernst von der Porten and his family. He eventually evaded this situation by committing suicide.

Aortic elasticity and size are associated with aortic regurgitation and left ventricular dysfunction in tetralogy of Fallot after pulmonary valve replacement.

BACKGROUND: Aortic wall pathology and concomitant aortic dilatation have been described in tetralogy of Fallot (TOF) patients, which may negatively affect aortic valve and left ventricular systolic function. OBJECTIVE: To assess aortic dimensions, aortic elasticity, aortic valve competence and biventricular function in repaired TOF patients after pulmonary valve replacement (PVR) using magnetic resonance imaging (MRI). METHODS: MRI was performed in 16 patients with TOF after PVR (10 male; mean age 31 years (SD 15)) and 16 age and gender-matched healthy subjects. RESULTS: TOF patients showed aortic root dilatation (mean difference 7.8-8.8 mm, p<0.01 at all four predefined levels) and reduced aortic elasticity (pulse wave velocity in aortic arch 5.5 m/s (1.2) vs 4.6 m/s (0.9), p = 0.04; aortic root distensibility 1.4/10(-3) mm Hg (1.7) vs 5.7/10(-3) mm Hg (3.6), p<0.01). Minor degrees of aortic regurgitation (AR) (AR fraction 6% (8) vs 1% (1), p<0.01) and reduced left ventricular ejection fraction (LVEF) were present (51% (8) vs 58% (6), p = 0.01), whereas right ventricular ejection fraction (RVEF) was within normal limits (47% (8) vs 52% (7), p = 0.06). The degree of AR fraction was associated with dilatation of the aortic root (r = 0.39-0.49, p<0.05) and reduced aortic root distensibility (r = 0.44, p = 0.02), whereas reduced LVEF was correlated with degree of AR and RVEF (r = 0.41, p = 0.02 and r = 0.49, p<0.01, respectively). CONCLUSIONS: Aortic root dilatation and reduced aortic elasticity are frequently present in patients with TOF, in addition to minor degrees of AR and reduced left ventricular systolic function. Aortic wall pathology in repaired TOF patients may therefore represent a separate mechanism leading to left ventricular dysfunction, as part of a multifactorial process of left ventricular dysfunction.

Neuroprotective agents for clinical trials in ALS: a systematic assessment.

BACKGROUND: Riluzole is currently the only Food and Drug Administration-approved treatment for ALS, but its effect on survival is modest. OBJECTIVE: To identify potential neuroprotective agents for testing in phase III clinical trials and to outline which data need to be collected for each drug. METHODS: The authors identified 113 compounds by inviting input from academic clinicians and researchers and via literature review to identify agents that have been tested in ALS animal models and in patients with ALS. The list was initially narrowed to 24 agents based on an evaluation of scientific rationale, toxicity, and efficacy in previous animal and human studies. These 24 drugs underwent more detailed pharmacologic evaluation. RESULTS: Twenty drugs were selected as suitable for further development as treatments for patients with ALS. Talampanel and tamoxifen have completed early phase II trials and have demonstrated preliminary efficacy. Other agents (ceftriaxone, minocycline, ONO-2506, and IGF-1 polypeptide) are already in phase III trials involving large numbers of patients with ALS. Remaining agents (AEOL 10150, arimoclomol, celastrol, coenzyme Q10, copaxone, IGF-1-viral delivery, memantine, NAALADase inhibitors, nimesulide, scriptaid, sodium phenylbutyrate, thalidomide, trehalose) require additional preclinical animal data, human toxicity and pharmacokinetic data including CNS penetration prior to proceeding to large scale phase III human testing. Further development of riluzole analogues should be considered. CONCLUSIONS: Several potential neuroprotective compounds, representing a wide range of mechanisms, are available and merit further investigation in ALS.

Evaluation of a method that supports pathology report coding.

OBJECTIVES: The paper focuses on the problem of adequately coding pathology reports using SNOMED. Both the agreement between pathologists in coding and the quality of a system that supports pathologists in coding pathology reports were evaluated. METHODS: Six sets of three pathologists each received a different set of 40 pathology reports. Five different SNOMED code lines accompanied each pathology report. Three pathologists evaluated the correctness of each of these code lines. Kappa values and values for the reliability coefficients were determined to gain insight in the variance observed when coding pathology reports. The system that is evaluated compares a newly entered report, represented as a multi-dimensional word vector, with reports in a library, represented in the same way. The reports in the library are already coded. The system presents the code lines belonging to the five library reports most similar to the newly entered one to the pathologist in this way supporting the pathologist in determining the correct codes. A high similarity between two reports is indicated by a large value of the inproduct of the vector of the newly entered report and the vector of a report in the library. RESULTS: Agreement between pathologists in coding was fair (average kappa of 0.44). The reliability coefficient varied from 0.81 to 0.89 for the six sets of pathology reports. The system gave correct suggestions in 50% of the reports. In another 30% it was helpful for the pathologists. CONCLUSIONS: On the basis of the level of the reliability coefficients it could be concluded that three pathologists are indeed sufficient for obtaining a gold standard for evaluating the system. The method used for comparing reports is not strong enough to allow fully automatic coding. It could be shown that the system induces a more uniform coding by pathologists. An evaluation of the incorrect suggestions of the system indicates that the performance of the system can still be improved.

Supporting the classification of pathology reports: comparing two information retrieval methods.

In this contribution two methods from the domain of information retrieval are compared. The goal of the retrieval is to select from a library of pathology reports those ones that are most similar to a given report. The SNOMED codes that accompany these reports are presented to the pathologist who has to code the given report with the aim to improve the quality of coding. The reports were represented either as a vector of words or as a vector of N-grams. Both 4-, 5- and 6-grams were used. The similarity of the reports was determined by comparing the SNOMED terms that were added to the reports. It could be concluded that the word-based method was consistently better than the N-gram method.

Automatic coding of diagnostic reports.

A method is presented for assigning classification codes to pathology reports by searching similar reports from an archive collection. The key for searching is textual similarity, which estimates the true, semantic similarity. This method does not require explicit modeling, and can be applied to any language or any application domain that uses natural language reporting. A number of simulation experiments was run to assess the accuracy of the method and to indicate the role of size of the archive and the transfer of document collections across laboratories. In at least 63% of the simulation trials, the most similar archive text offered a suitable classification on organ, origin and diagnosis. In 85 to 90% of the trials, the archive's best solution was found within the first five similar reports. The results indicate that the method is suitable for its purpose: suggesting potentially correct classifications to the reporting diagnostician.

Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1.

Analysis of transgenic mice expressing familial amyotrophic lateral sclerosis (ALS)-linked mutations in the enzyme superoxide dismutase (SOD1) have shown that motor neuron death arises from a mutant-mediated toxic property or properties. In testing the disease mechanism, both elimination and elevation of wild-type SOD1 were found to have no effect on mutant-mediated disease, which demonstrates that the use of SOD mimetics is unlikely to be an effective therapy and raises the question of whether toxicity arises from superoxide-mediated oxidative stress. Aggregates containing SOD1 were common to disease caused by different mutants, implying that coaggregation of an unidentified essential component or components or aberrant catalysis by misfolded mutants underlies a portion of mutant-mediated toxicity.

Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutant.

Mutations in superoxide dismutase 1 (SOD1), the only proven cause of amyotrophic lateral sclerosis (ALS), provoke disease through an unidentified toxic property. Neurofilament aggregates are pathologic hallmarks of both sporadic and SOD1-mediated familial ALS. By deleting NF-L, the major neurofilament subunit required for filament assembly, onset and progression of disease caused by familial ALS-linked SOD1 mutant G85R are significantly slowed, while selectivity of mutant-mediated toxicity for motor neurons is reduced. In NF-L-deleted animals, levels of the two remaining neurofilament subunits, NF-M and NF-H, are markedly reduced in axons but are elevated in motor neuron cell bodies. Thus, while neither perikaryal nor axonal neurofilaments are essential for SOD1-mediated disease, the absence of assembled neurofilaments both diminishes selective vulnerability and slows SOD1(G85R) mutant-mediated toxicity to motor neurons.

Automatic SNOMED classification--a corpus-based method.

This paper presents a method of automatic classification of clinical narrative through text comparison. A diagnosis report can be classified by searching archive texts that show a high textual similarity, and the 'nearest neighbor classifies the case. This paper describes the method's theoretical background and gives implementation details. Large scale simulation experiments were run with a wide range of histology reports. Results showed that for 80-84% of the trials, relevant classification lines were included among the first five alternatives. In 5% of the cases, retrieval was unsuccessful due to the absence of relevant archive reports. From the results it is concluded that the method is a versatile approach for finding potentially good classifications.

Elevated free nitrotyrosine levels, but not protein-bound nitrotyrosine or hydroxyl radicals, throughout amyotrophic lateral sclerosis (ALS)-like disease implicate tyrosine nitration as an aberrant in vivo property of one familial ALS-linked superoxide dismutase 1 mutant.

Mutations in superoxide dismutase 1 (SOD1; EC 1.15.1.1) are responsible for a proportion of familial amyotrophic lateral sclerosis (ALS) through acquisition of an as-yet-unidentified toxic property or properties. Two proposed possibilities are that toxicity may arise from imperfectly folded mutant SOD1 catalyzing the nitration of tyrosines [Beckman, J. S., Carson, M., Smith, C. D. & Koppenol, W. H. (1993) Nature (London) 364, 584] through use of peroxynitrite or from peroxidation arising from elevated production of hydroxyl radicals through use of hydrogen peroxide as a substrate [Wiedau-Pazos, M., Goto, J. J., Rabizadeh, S., Gralla, E. D., Roe, J. A., Valentine, J. S. & Bredesen, D. E. (1996) Science 271, 515-518]. To test these possibilities, levels of nitrotyrosine and markers for hydroxyl radical formation were measured in two lines of transgenic mice that develop progressive motor neuron disease from expressing human familial ALS-linked SOD1 mutation G37R. Relative to normal mice or mice expressing high levels of wild-type human SOD1, 3-nitrotyrosine levels were elevated by 2- to 3-fold in spinal cords coincident with the earliest pathological abnormalities and remained elevated in spinal cord throughout progression of disease. However, no increases in protein-bound nitrotyrosine were found during any stage of SOD1-mutant-mediated disease in mice or at end stage of sporadic or SOD1-mediated familial human ALS. When salicylate trapping of hydroxyl radicals and measurement of levels of malondialdehyde were used, there was no evidence throughout disease progression in mice for enhanced production of hydroxyl radicals or lipid peroxidation, respectively. The presence of elevated nitrotyrosine levels beginning at the earliest stages of cellular pathology and continuing throughout progression of disease demonstrates that tyrosine nitration is one in vivo aberrant property of this ALS-linked SOD1 mutant.

ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions.

High levels of familial Amyotrophic Lateral Sclerosis (ALS)-linked SOD1 mutants G93A and G37R were previously shown to mediate disease in mice through an acquired toxic property. We report here that even low levels of another mutant, G85R, cause motor neuron disease characterized by an extremely rapid clinical progression, without changes in SOD1 activity. Initial indicators of disease are astrocytic inclusions that stain intensely with SOD1 antibodies and ubiquitin and SOD1-containing aggregates in motor neurons, features common with some cases of SOD1 mutant-mediated ALS. Astrocytic inclusions escalate markedly as disease progresses, concomitant with a decrease in the glial glutamate transporter (GLT-1). Thus, the G85R SOD1 mutant mediates direct damage to astrocytes, which may promote the nearly synchronous degeneration of motor neurons.

Mechanisms of selective motor neuron death in transgenic mouse models of motor neuron disease.

To examine the mechanism(s) of disease underlying ALS, transgenic mouse models have been constructed that express aberrant neurofilaments or mutations in the abundant, cytoplasmic enzyme superoxide dismutase 1 (SOD1). In addition to progressive weakness arising from selective motor neuron death, mice expressing a modest level of a point mutant in neurofilament subunit NF-L show most of the pathologic hallmarks observed in familial and sporadic ALS, including perikaryal proximal axonal swellings, axonal degeneration, and severe skeletal muscle atrophy. Additional mice expressing familial ALS-linked mutations in the cytoplasmic enzyme SOD1, the only proven cause of ALS and which accounts for approximately 20% of familial disease, have demonstrated that at least one mutation causes disease through acquisition of an adverse property by the mutant enzyme, rather than elevation or loss of SOD1 activity. These animals not only provide a detailed look at the pathogenic progression of disease, but also represent a tool for testing hypotheses concerning the specific mechanism(s) of neuronal death and for testing therapeutic strategies.

Sequence variants in human neurofilament proteins: absence of linkage to familial amyotrophic lateral sclerosis.

Neurofilaments, assembled from NF-L (68 kd), NF-M (95 kd), and NF-H (115 kd), are the most abundant structural components in large myelinated axons, particularly those of motor neurons. Aberrant neurofilament accumulation in cell bodies and axons of motor neurons is a prominent pathological feature of several motor neuron diseases, including sporadic and familial amyotrophic lateral sclerosis (ALS). Transgenic methods have proved in mice that mutation in or increased expression of neurofilament subunits can be primary causes of motor neuron disease that mimics the neurofilamentous pathology often reported in human disease. To examine whether mutation in neurofilament subunits causes or predisposes to ALS, we used single-strand conformation polymorphism coupled with DNA sequencing to search for mutations in the entirety of the human NF-L, NF-M, and NF-H genes from 100 familial ALS patients known not to carry mutations in superoxide dismutase 1 (SOD1), as well as from 75 sporadic ALS patients. Six polypeptide sequence variants were identified in rod and tail domains of NF-L, NF-M, or NF-H. However, all were found at comparable frequency in DNAs from normal individuals and no variant cosegregated with familial disease. Two deletions found previously in NF-H genes of sporadic ALS patients were not seen in this group of familial or sporadic ALS patients.

Mechanisms of selective motor neuron death in ALS: insights from transgenic mouse models of motor neuron disease.

Concerning the mechanism(s) of disease underlying amyotrophic lateral sclerosis (ALS), transgenic mouse models have provided (i) a detailed look at the pathogenic progression of disease, (ii) a tool for testing hypotheses concerning the mechanism of neuronal death, and (iii) a host appropriate for testing therapeutic strategies. Thus far, these efforts have proved that mutation in a neurofilament subunit can cause progressive disease displaying both selective motor neuron death and aberrant neurofilament accumulation similar to that reported in human disease. Additional mice expressing point mutations in the cytoplasmic enzyme superoxide dismutase (SOD1), the only known cause of ALS, have proved that disease arises from a toxic property of the mutant enzyme rather than loss of enzymatic activity.

Speech interfacing for diagnosis reporting systems: an overview.

Automatic speech recognition has since long been seen as an ideal method for innovation in diagnosis reporting. Speech technology now seems on the verge of introducing (commercially) attractive systems. The selection of a good speech recogniser is only one consideration in system design. Interface aspects, error handling, reporting method and implementation in the daily working routine are interwoven with the selection of an appropriate speech recognition technique, and should therefore be determined first.